Page 1

ENGLISH

Setembro / Outubro

5


CONTENTS / SUMÁRIO Rev Col Bras Cir 2017; 44(5)

E D I TORI AL Challenges in high technology surgery Cirurgia de alta tecnologia: desafios a enfrentar Mauro Pinho ......................................................................................................................................................................................... 426

O R IG I NAL ARTIC LES Thoraco-laparoscopic esophagectomy: thoracic stage in prone position Esofagectomia vídeo-tóraco-laparoscópica com tempo torácico em posição pronada Carlos Bernardo Cola; Flávio Duarte Sabino; Carlos Eduardo Pinto; Maria Ribeiro Morard; Pedro Portari Filho; Tereza Guedes ..................... 428 Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study Fatores prognósticos do câncer de mama e sobrevida global em cinco e dez anos na cidade de Goiânia, Brasil: estudo de base populacional Ruffo de Freitas Júnior; Rodrigo Disconzi Nunes; Edesio Martins; Maria Paula Curado; Nilceana Maya Aires Freitas; Leonardo Ribeiro Soares; José Carlos Oliveira .................................................................................................................................................................... 435 Epidemiological profile and treatment of substance losses by trauma to the lower limbs Perfil epidemiológico e tratamento de perdas de substância por trauma em membros inferiores Ricardo Barros Martins Rezende; Jefferson Lessa Soares de Macedo; Simone Corrêa Rosa; Fernando Soares Galli ....................................... 444 Use of transfer factor in immunosuppressed surgical patients Avaliação do uso de fator de transferência na resposta imunológica de pacientes cirúrgicos imunodeprimidos Celia Regina Oliveira Garritano; Francesco di Nubila; Renata M. Couto; Rossano Kepler Alvim Fiorelli; Luciana Berti Aun ............................. 452 Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats Efeitos do dimetilsulfóxido e da pentoxifilina na vitalidade de retalhos cutâneos em ratos Stephanie Luzia da Costa Pedretti; Cícero de Lima Rena; Maria Christina Marques Nogueira Castãnon; Ana Paula do Nascimento Duque; Fernando Henrique Pereira; Tarcizo Afonso Nunes ...................................................................................................................... 457 Colon cancer surgery in patients operated on an emergency basis Cirurgia do câncer de cólon em pacientes operados de emergência Rodrigo Felippe Ramos; Lucas Carvalho Santos dos-Reis; Beatriz Esteves Borgeth Teixeira; Igor Maroso Andrade; Jaqueline Suelen Sulzbach; Ricardo Ary Leal ............................................................................................................................................................ 465 Development of a laparoscopic training model using a smartphone Desenvolvimento de modelo treinamento em cirurgia laparoscópica com utilização de smartphone André Takashi Oti; Lucas Nascimento Galvão; Thyago Cezar Prado Pessoa; Camylla Rodrigues de Oliveira Rocha; Andrew Moraes Monteiro; Mauro José Pantoja Fonteles; Marcus Vinicius Henriques Brito; Edson Yuzur Yasojima ......................................... 471 Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy Influência do cólon na regeneração do fígado de ratos submetidos à hepatectomia e colectomia Marília Carvalho Moreira; Ítalo Medeiros Azevedo; Cláudia Nunes Oliveira; Aldo da Cunha Medeiros ........................................................ 476 Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy Métodos de avaliação nutricional preditores de mortalidade pós-operatória em pacientes submetidos à gastrectomia por câncer gástrico Aline Kirjner Poziomyck; Leandro Totti Cavazzola; Luisa Jussara Coelho; Edson Braga Lameu; Antonio Carlos Weston; Luis Fernando Moreira ........................................................................................................................................................................... 482 Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil Levantamento epidemiológico das fraturas de face do Serviço de Cirurgia e Traumatologia Bucomaxilofacial da Santa Casa de Misericórdia de Porto Alegre – RS Rodrigo Andrighetti Zamboni; João Carlos Birnfeld Wagner; Maurício Roth Volkweis; Eduardo Luis Gerhardt; Elissa Muller Buchmann; Caren Serra Bavaresco ...................................................................................................................................... 491

Rev Col Bras Cir

Rio de Janeiro

Vol 44

Nº 5

p 426 / 548

set/out

2017


O R IGINAL ARTIC L ES Effects of local pressure on cutaneous blood flow in pigs Efeitos da pressão local no fluxo sanguíneo cutâneo de porcos Michel Luciano Holger Toledano Vaena; João Paulo Sinnecker; Bruno Benedetti Pinto; Mario Fritsch Toros Neves; Fernando Serra-Guimarães; Ruy Garcia Marques ..................................................................................................................................... 498 Observation time and spontaneous resolution of primary phimosis in children Tempo de observação e resolução espontânea de fimose primária em crianças Pedro Luiz Toledo de Arruda Lourenção; Dênis Silva Queiroz; Wilson Elias de-Oliveira Junior; Giovana Tuccille Comes; Rozemeire Garcia Marques; Débora Rodrigues Jozala; Erika Veruska Paiva Ortolan .................................................................................... 505

R E V I EW ARTI CLES Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency Escleroterapia ecoguiada com espuma para tratamento da insuficiência venosa crônica grave Guilherme Camargo Gonçalves de-Abreu; Otacílio de Camargo Júnior; Márcia Fayad Marcondes de-Abreu; José Luís Braga de-Aquino........ 511 Management of infected pancreatic necrosis: state of the art Necrose pancreática com infecção: estado atual do tratamento Roberto Rasslan; Fernando da Costa Ferreira Novo; Alberto Bitran; Edivaldo Massazo Utiyama; Samir Rasslan .............................................. 521 A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma Proposta de padronização da Sociedade Brasileira de Cirurgia Oncológica para procedimentos de citorredução cirúrgica e quimioterapia intraperitoneal hipertérmica no Brasil: pseudomixoma peritoneal, tumores do apêndice cecal e mesotelioma peritoneal maligno Thales Paulo Batista; Bruno José Queiroz Sarmento; Janina Ferreira Loureiro; Andrea Petruzziello; Ademar Lopes; Cassio Cortez Santos; Cláudio de Almeida Quadros; Eduardo Hiroshi Akaishi; Eduardo Zanella Cordeiro; Felipe José Fernández Coimbra; Gustavo Andreazza Laporte; Leonaldson Santos Castro; Ranyell Matheus Spencer Sobreira Batista; Samuel Aguiar Júnior; Wilson Luiz Costa Júnior; Fábio Oliveira Ferreira ........................................................................................................................................... 530

T E A CHI NG Educational project: low cost porcine model for venous cutdown training Projeto de ensino: modelo porcino de baixo custo para treinamento de dissecção venosa Fernando Antônio Campelo Spencer Netto; Mariana Thalyta Bertolin Silva; Michael de Mello Constantino; Raphael Flávio Fachini Cipriani; Michel Cardoso ........................................................................................................................................... 545

Rev Col Bras Cir

Rio de Janeiro

Vol 44

Nº 5

p 426 / 548

set/out

2017


VOCÊ CONHECE A NOVA SOLUÇÃO PARA HÉRNIA?

TELA COMPOSTA SYMBOTEX™ Indicada para reparo ventral convencional ou laparoscópico.

DESIGN Estrutura 3D da tela oferece resistência reforçada1 esuportesignificativonocrescimentotecidual2.

MANIPULAÇÃO Desenvolvidaparafacilitaraimplantaçãodatela3. Tela transparente3commarcaçãocentral¥,3,4 eefeitoadesivonaparedeabdominal3,5.

REPARO Desenvolvidaparaofereceraospacientesum reparodehérniaideal,commenorprobabilidade de aderência visceral6. ¥ Se a tela não for cortada (Consulte as Instruções de Uso) Referências: 1. Com base no relatório de teste interno n° TEX043, Comparação das propriedades físicas e mecânicas da tela composta Symbotex™ com as da tela composta otimizada Parietex. Julho de 2013. 2. Weyhe D, Cobb W, Lomanto D, et al. Comparative analysis of the performance of a series of meshes based on weight and pore size in a novel mini-pig hernia model. EHS. 2013;SC130037. Termo de verificação de projeto n° 0901CR247b. Julho de 2013. 3. Demonstrado em um estudo pré-clinico interno report # 0901CR252, efetuado em suínos em Maio de 2013 com 6 cirurgiões com o objetivo de validar o design da tela composta Symbotex™ vs. Parietex™ composite mesh. Junho 2013. 4. Baseado em resultados de um estudo pré-clinico interno de validação de design report #0901CR249a, realizado em modelo porcino para validação do design da tela composta™. Junho de 2013. 5.Com base no memorando interno n° 0901CR261a, Definição do efeito pegajoso da tela composta Symbotex™ observado durante a validação interna de projeto realizada em um modelo suíno. Julho de 2013. 6. Avaliada em um estudo pré-clínico patrocinado iniciado em abril de 2013 usando um modelo de abrasão cecal em rato para avaliar os efeitos no tecido local, integração tecidual e para reduzir o desempenho de fixação tecidual da tela composta Symbotex™ vs. tela composta otimizada Parietex™ Relatório Namsa n° 162750. Maio de 2013.

3 Jornada Norte/Nordeste de Hérnia

Agende esta data na sua agenda! 18 de novembro de 2017 Salvador – BA

Sócio(a) quite (SBH e SOBRACIL)

Gratuito

Não sócio(a) e sócio(a) não quite

100,00

Residente / Pós graduando(a)

50,00

Acadêmicos de medicina

50,00

9/11/17 3:48 PM

to ites ui at qu IL! gr os C to ad RA en oci OB Ev ss e S a ra SBH da

a

pa

11092017 - Anúncio CBC.indd 1

Reg. nº10349000526 - © 2017 Medtronic. Todos os direitos reservados. Medtronic, o logo da Medtronic e Outros são, em conjunto, marcas registradas da Medtronic. ™* Marcas de terceiros são marcas registradas de seus respectivos proprietários. Todas as outras marcas são marcas registradas de uma empresa da Medtronic. M. Luz 08/2017.

Mais informações e inscrições no site: www.sbhernia.com.br Realização

Patrocinadores

Apoio

Organização e Viagens

GROUP


em pauta! Informativo o cial da SOBRACIL o SOBRANEWS vem trazendo a seus leitores noticias e novidades da área da medicina, além de antecipar e descrever congressos, cursos de educação continuada, projetos da Sociedade e entrevistas com cirurgiões de diferentes especialidades sobre suas pesquisas e trabalhos na área da cirurgia minimamente invasiva e robótica. Lançado em 2013 e publicado todos os meses, o boletim ca disponível on-line e é enviado a todos os sócios. Para uma Sociedade que desde o início propaga o uso de tecnologias de ponta na medicina, um boletim do nível do SOBRANEWS é cada vez mais importante.

M

100 95 75

25 5 0

www.sobracil.org.br


Órgão Oficial do Colégio Brasileiro de Cirurgiões EDITOR

ASSOCIATE EDITORS

Guilherme Pinto Bravo Neto TCBC-RJ Associate Professor, Department of Surgery, Faculdade de Medicina, Universidade Federal do Rio de Janeiro-UFRJ-Rio de Janeiro-RJ-Brasil.

FELIPE CARVALHO VICTER TCBC - RJ - UNIVERSIDADE DO ESTADO DO RIO DE JANEIRO - UERJ – RIO DE JANEIRO – RJ, BRASIL RODRIGO MARTINEZ TCBC-RJ - UNIVERSIDADE FEDERAL DO RIO DE JANEIRO – UFRJ - RIO DE JANEIRO – RJ – BRASIL FERNANDO PONCE DE LEON ACBC- RJ – UNIVERSIDADE FEDERAL DO RIO DE JANEIRO – UFRJ – RIO DE JANEIRO – RJ-BRASIL

LIBRARIAN

Lenita Penido Xavier

WRITING ASSISTANT David S. Ferreira Júnior

GRAPHIC DESIGN HG Design Digital Ltda.

RESPONSIBLE JOURNALIST João Maurício Carneiro Rodrigues

ADVISORY BOARD ABRÃO RAPOPORT - ECBC-SP - Hospital Heliópolis - São Paulo - SP - BR ALDO DA CUNHA MEDEIROS - ECBC-RN - Universidade Federal do Rio Grande do Norte – Natal – RN - BR ALEXANDRE FERREIRA OLIVEIRA - TCBC-PE - Universidade Federal de Pernambuco – Recife – PE - BR ÁLVARO ANTONIO BANDEIRA FERRAZ - TCBC-PE - Universidade Federal de Pernambuco – Recife – PE - BR ANA CRISTINA GOUVEIA MAGALHÃES - Universidade Federal do Rio de Janeiro- Rio de Janeiro- RJ – BR ANDY PETROIANU - TCBC-MG – Universidade Federal de Minas Gerais – Belo Horizonte – MG - BR ANTONIO CARLOS VALEZI - TCBC-PR – Universidade Estadual de Londrina - Londrina - PR – BR ANTONIO JOSÉ GONÇALVES - TCBC-SP – Faculdade de Ciências Médicas da Santa Casa de São Paulo- São Paulo - SP - BR ARLINDO MONTEIRO DE CARVALHO JR. - TCBC-PB - Universidade Federal da Paraíba João Pessoa - PB - BR CARLOS ALBERTO PORCHAT - TCBC-RJ - Hospital Clementino Fraga Filho da Universidade Federal do Rio de Janeiro - RJ - BR CARLOS ANSELMO LIMA - TCBC-SE- Universidade Federal de Sergipe – Aracaju - SE - BR CARLOS DELROY - Universidade Federal de São Paulo - São Paulo - SP - BR DAYSE COUTINHO VALENTE - TCBC-RJ- Instituto Fernando Luiz Barroso – Rio de Janeiro - RJ - BR DIOGO FRANCO - TCBC-RJ - Universidade Federal do Rio de Janeiro- Rio de Janeiro – RJ - BR DJALMA JOSE FAGUNDES - ECBC-SP - Universidade Federal de São Paulo – São Paulo – SP – BR EDMUND CHADA BARACAT - TCBC – SP - Universidade Federal de São Paulo – São Paulo – SP – BR EDNA FRASSON DE SOUZA MONTERO - TCBC-SP- Universidade Federal de São Paulo – São Paulo – SP – BR EDUARDO CREMA - TCBC-MG - Universidade Federal do Triângulo Mineiro - Uberaba MG - BR EDUARDO HARUO SAITO - TCBC-RJ- Universidade do Estado do Rio de Janeiro – Rio de Janeiro - RJ - BR ELIZABETH GOMES DOS SANTOS - TCBC-RJ - Universidade Federal do Rio de Janeiro – Rio de Janeiro – RJ - BR FÁTIMA CARNEIRO FERNANDES - Universidade Federal do Rio de Janeiro - Rio de Janeiro - RJ - BR FLÁVIO DANIEL SAAVEDRA TOMASICH - TCBC-PR – Hospital de Clínicas da Universidade Federal do Paraná – Curitiba –PR- BR FLÁVIO MALCHER M. DE OLIVEIRA - TCBC-RJ - Hospital Universitário Gaffrée e Guinle - Rio de Janeiro - RJ - BR FREDERICO AVELLAR SILVEIRA LUCAS - TCBC-RJ - Instituto Nacional do Câncer – Rio de Janeiro - RJ - BR GIULIANO ANCELMO BENTO - ACBC- RJ – Universidade do Estado do Rio de Janeiro – Rio de Janeiro – RJ – BR GUSTAVO PEREIRA FRAGA - TCBC-SP - Universidade Estadual de Campinas – Campinas - SP – BR HAMILTON PETRY DE SOUZA - ECBC-RS - Pontifícia Universidade Católica do Rio Grande do Sul – Porto Alegre - RS – BR HAROLDO VIEIRA DE MORAES Jr. - Universidade Federal do Rio de Janeiro - Rio de Janeiro - RJ - BR HENRI CHAPLIN RIVOIRE - TCBC-RS -Universidade Federal do Rio Grande do Sul - Porto Alegre - RS - BR HENRIQUE MURAD - ECBC-RJ - Universidade Federal do Rio de Janeiro - Rio de Janeiro - RJ - BR JOSÉ ANACLETO DUTRA RESENDE Jr. - Hospital Universitário Pedro Ernesto-UERJ - Rio de Janeiro - RJ - BR JOSÉ EDUARDO DE AGUILAR NASCIMENTO - TCBC-MT-Universidade Federal de Mato Grosso – Cuiabá – MT –BR JOSÉ EDUARDO FERREIRA MANSO - TCBC-RJ – Universidade Federal do Rio de Janeiro – Rio de Janeiro – RJ – BR JOSÉ LUIZ BRAGA DE AQUINO - TCBC-SP - Faculdade de Ciências Médicas - PUC Campinas - SP - BR JOSÉ MARCUS RASO EULÁLIO - TCBC-RJ – Universidade Federal do Rio de Janeiro – Rio de Janeiro – RJ – BR JOSÉ MAURO DA SILVA RODRIGUES - TCBC-SP - Pontifícia Universidade Católica de São

Paulo - São Paulo - SP - BRA JOSÉ WILSON NOLETO - Universidade Federal da Paraíba - João Pessoa - PB - BR JULIO CESAR BEITLER - TCBC-RJ – Universidade Estácio de Sá – Rio de Janeiro - RJ - BR JÚLIO CEZAR UILI COELHO - TCBC-PR – Universidade Federal do Paraná – Curitiba - PR – BR KATIA SHEYLA MALTA PURIM - Universidade Positivo - Curitiba - PR - BR LEONEL DOS SANTOS PEREIRA - Universidade Federal do Rio de Janeiro - Rio de Janeiro - RJ - BR LISIEUX EYER DE JESUS - TCBC-RJ- Universidade Federal Fluminense – Niterói – RJ – BR LUIZ CARLOS DUARTE DE MIRANDA - ACBC-RJ - Universidade Federal do Rio de Janeiro - Rio de Janeiro - RJ - BR LUIZ CARLOS VON BAHTEN - TCBC-PR- Universidade Federal do Paraná – Curitiba - PR – BR LUIZ GUSTAVO DE OLIVEIRA E SILVA - TCBC-RJ- Hospital Federal de Ipanema/Ministério da Saúde- Rio de Janeiro - RJ - BR LUIZ RONALDO ALBERTI - Universidade Federal de Minas Gerais – Belo Horizonte – MG –BR MANOEL XIMENES NETO - ECBC-DF –Universidade de Brasília – Brasília - DF - BR MANUEL DOMINGOS DA CRUZ GONÇALVES - ECBC-RJ- Universidade Federal do Rio de Janeiro- Rio de Janeiro –RJ – BR MARCOS ALPOIN FREIRE - TCBC-RJ- Universidade Federal do Rio de Janeiro- Rio de Janeiro – RJ – BR MARIA APARECIDA DE ALBUQUERQUE CAVALCANTE - Universidade Federal do Rio de Janeiro - Rio de Janeiro - RJ - BR MARIA DE LOURDES P. BIONDO SIMÕES - TCBC-PR – Pontifícia Universidade Católica do Paraná – Curitiba – PR - BR MARCELO AUGUSTO F. RIBEIRO JR. - TCBC-SP - Universidade de Santo Amaro- UNISA - São Paulo - SP - BR MAURÍCIO AUGUSTO S. MAGALHÃES COSTA - TCBC-RJ - Sociedade Brasileira de Mastologia - Rio de Janeiro - RJ - BR MAURO ANTÔNIO C. GUIMARÃES FILHO - Hospital Moinho dos Ventos - Porto Alegre - RS- BR MAURO DE SOUZA LEITE PINHO - TCBC-SC – Universidade da Região de Joinville – Joinville - SC - BR NELSON ADAMI ANDREOLLO - TCBC-SP – Universidade Estadual de Campinas Campinas - SP - BR NELSON ALFRED SMITH - Universidade Federal do Rio de Janeiro- Rio de Janeiro – RJ – BR NELSON FONTANA MARGARIDO – TCBC-SP – Universidade de São Paulo – São Paulo – SP – BR ORLANDO JORGE MARTINS TORRES - TCBC-MA - Universidade Federal do Maranhão - São Luís - MA - BR OSVALDO MALAFAIA - ECBC-PR- Universidade Federal do Paraná – Curitiba –PR- BR PAULO FRANCISCO GUERREIRO CARDOSO - ACBC-RS- Fundação Faculdade Federal de Ciências Médicas de Porto Alegre – Porto Alegre – RS - BR PAULO GONÇALVES DE OLIVEIRA - TCBC-DF - Universidade de Brasília – Brasília - DF - BR RENATO ABRANTES LUNA - TCBC-RJ - Hospital Federal dos Servidores do Estado do Rio de Janeiro - Rio de Janeiro - RJ - BR RICARDO ANTONIO CORREIA LIMA - TCBC-RJ – Universidade Federal do Estado do Rio de Janeiro- Rio de Janeiro – RJ – BR RICARDO VITOR COHEN - TCBC-SP - Hospital Alemão Oswaldo Cruz - São Paulo - SP - BR ROBERTO CAMPOS MEIRELLES - TCBC-RJ - Universidade do Estado do Rio de Janeiro - Rio de Janeiro - RJ - BR RODRIGO ALTENFELDER SILVA - TCBC-SP - Faculdade de Ciências Médicas da Santa Casa de São Paulo - São Paulo - SP-BR RODRIGO FELIPPE RAMOS - TCBC - RJ - Universidade Federal Fluminense - Niterói - RJ - BR ROGERIO APARECIDO DEDIVITIS - TCBC-SP - Universidade de São Paulo - São Paulo SP - BR RUFFO DE FREITAS JÚNIOR - TCBC-GO - Universidade Federal de Goiás - Goiânia – GO – BR SILVIA CRISTINE SOLDÁ - TCBC-SP- Faculdade de Ciências Médicas da Santa Casa de São Paulo- São Paulo - SP - BR SILVIO HENRIQUES DA CUNHA NETO – TCBC- RJ - Universidade Federal do Rio de Janeiro- Rio de Janeiro – RJ – BR SIZENANDO VIEIRA STARLING - TCBC-MG - Hospital João XXIII - Belo Horizonte - MG - BR THALES PAULO BATISTA - TCBC-PE- Faculdade Pernambucana de Saúde/ Instituto de Medicina Integral Professor Fernando Figueira - Recife - PE - BR VIVIAN RESENDE - TCBC-MG - Universidade Federal de Minas Gerais - Belo Horizonte MG - BR WILSON CINTRA JR. - TCBC-SP-Universidade de São Paulo- São Paulo- SP - BR


NATIONAL CONSULTANTS ALCINO LÁZARO DA SILVA, ECBC-MG - Universidade Federal de Minas Gerais - MG ALUIZIO SOARES DE SOUZA RODRIGUES, ECBC-RJ - Universidade Federal do Rio de Janeiro - UFRJ - RJ ANTONIO PELOSI DE MOURA LEITE, ECBC-SP - Instituto de Moléstias Cardiovasculares de São José do Rio Preto - SP DARIO BIROLINI, ECBC-SP - Faculdade de Medicina da Universidade de São Paulo - SP EUGÊNIO AMÉRICO BUENO FERREIRA, ECBC-SP - Faculdade de Medicina de Jundiaí - SP FERNANDO LUIZ BARROSO, ECBC-RJ - Hospital Municipal de Ipanema - RJ. FERNANDO MANOEL PAES LEME, ECBC-RJ - Faculdade de Medicina de Campos - RJ GASPAR DE JESUS LOPES FILHO, TCBC-SP - Universidade Federal de São Paulo - SP GUILHERME EURICO BASTOS DA CUNHA, ECBC-RJ - Universidade Federal Fluminense - RJ HELÁDIO FEITOSA DE CASTRO FILHO, TCBC-CE Universidade Federal do Ceará - CE ISAC JORGE FILHO, TCBC-SP - Universidade de Ribeirão Preto - SP. JOSÉ REINAN RAMOS, TCBC-RJ - Hospital Vitória-RJ LUIZ GUILHERME BARROSO ROMANO, ECBC-RJ MARCOS F. MORAES, ECBC-RJ - Universidade Gama Filho-RJ

ORLANDO MARQUES VIEIRA, ECBC-RJ - Universidade Federal do Rio de Janeiro-RJ ROBERTO SAAD JR., TCBC-SP - Faculdade de Ciências Médicas da Santa Casa de São Paulo-SP SAMIR RASSLAN, ECBC-SP - Faculdade de Medicina da Universidade de São Paulo-SP SAUL GOLDENBERG, ECBC-SP - Universidade Federal de São Paulo- Escola Paulista de Medicina - SP

INTERNATIONAL CONSULTANTS ARNULF THIEDE - Department of Surgery, University of Würzburg Hospital, Oberdürrbacher Str. 6, D-97080 Würzburg, Germany CLAUDE DESCHAMPS - M.D - The Mayo Clinic, MN,USA EDUARDO PARRA-DAVILA - Florida Hospital Celebration Health - 400 Celebration Pl, Kissimmee, FL 34747, USA. EMILIO DE VICENTE LÓPEZ – Sanchinarro Hospital, Madrid, Spain KARL H. FUCHS - Markus-Krankenhaus Frankfurter Diakonie-Kliniken, Wilhelm- Epstein-Straße 4, 60435 Frankfurt am Main MURRAY BRENNAN - HeCBC Department of Surgery, Memorial SloanKettering Cancer Center, New York NY, USA ULRICH ANDREAS DIETZ - Department of Surgery I, University of Würzburg, Medical School, Würzburg, Germany W. WEDER - Klinikdirektor-UniversitätsSpital Zürich, Switzerland

FORMER EDITORS 1967 - 1969 JÚLIO SANDERSON

1969 - 1971 JOSÉ HILÁRIO

1973 - 1979 HUMBERTO BARRETO

1980 - 1982 EVANDRO FREIRE

1980 - 1982 EVANDRO FREIRE

1983 - 1985 JOSÉ LUIZ XAVIER PACHECO

1986 - 1991 MARCOS MORAES

1992 - 1999 MERISA GARRIDO

2000 - 2002 2002 - 2005 JOSÉ ANTÔNIO GOMES DE SOUZA GUILHERME PINTO BRAVO NETO

2006 - 2015 JOSÉ EDUARDO FERREIRA MANSO

THE JOURNAL OF THE BRAZILIAN COLLEGE OF SURGEONS is indexed in Latindex, Lilacs and Scielo, Scopus, Medline / PubMed, DOAJ, Free Medical Journals, and sent every two months to all members of the CBC, to its subscribers, to medical institutions, libraries, hospitals and study centers, to publications with which it keeps exchange and to its advertisers.

PUBLISHING, SUBSCRIPTIONS and ADMINISTRATION Rua Visconde de Silva, 52 - 3º andar - Botafogo - 22271-092 - Rio de Janeiro - RJ - Brasil Tel.: + 55 21 2138-0659; Fax: + 55 21 2286-2595; E-mail: revistacbc@cbc.org.br http//www.cbc.org.br PRINTING AND FINISHING Gráfica e Editora Prensa Ltda Rua João Alvares, 27 Saúde - Rio de Janeiro - RJ Tel.: (21) 2253-8343

International Standard Serial Number ISSN 0100-6991

GRAPHIC DESIGN Artur Farias

GRAPHIC DESIGN – COVER Libertta Comunicação JOURNAL OF THE BRAZILIAN COLLEGE OF SURGEONS

Indexed in Latindex, Lilacs and Scielo, Scopus, Medline/PubMed, DOAJ and Free Medical Journals


- CONVIDA -

Mais informações:

www.congressobariatrica.com.br


Editorial

DOI: 10.1590/0100-69912017005001

Challenges in high technology surgery Cirurgia de alta tecnologia: desafios a enfrentar

MAURO PINHO, TCBC-RJ1.

W

e are experiencing exciting times of surgical procedures. Thirty years ago, in 1987, Phillipe Mouret performed the first cholecystectomy by video-laparoscopy with electronic resources, beginning a historical revolution that completely changed the surgical practice … and surgeons. Legitimate successors of barber-surgeons, and always associated to incisions, blood and suffering, we have been transmuted in cold professionals acting through bright screens sophisticated equipment performing meticulous risky and precise procedures. As a result, we have the power of reducing suffering and pain. However, it is essential to put it in correct perspective, considering major impact of changes of technological revolution in virtually all areas of human knowledge. It is important to understand that this revolution, as most others, is associated with both benefits and severe consequences, requiring an accurate evaluation of this new reality. Thomas Friedman, author of several best-sellers such as “The World is plane”, presents an excellent analysis in his most recent book “Thank you for being late”. He highlights the main characteristic of modern time as an increased rhythm of changes stressing the low human adaptation to that speed, with consequent increase of exclusion from the job market. Similarly, in January 2017, the renowned magazine “The Economist” stated, in a very interesting article about technological changes, that “when education does not follow the rhythm of technology, the result is inequality”. Teaching, inequality, exclusion. Should we extrapolate these aspects to high tech surgery? No doubt, the answer is yes.

Minimally invasive surgery is increasingly replacing the use of traditional forceps, scissors and retractors. Whether endoscopic, laparoscopic or robotic, it has emerged a new teaching concept: the Training Centers. Let’s get back to the early decades of last century. Before the advances of anesthesia, antibiotics and ventilatory support, young surgeons were trained in minor surgical procedures, such as herniorrhaphys and amputations by personal observation during daily surgical practice, with no deadlines or pre-defined programs. After 1940, the increasing complexity and volume of surgical procedures have led to creation of formal and rigid Programs of Surgical Residency, so called due to deep personal commitment during a few years, when surgical training occurred under strict supervision of experienced surgeons, aware of quality and safety of patients. Returning to present days, modern Training Centers aim to present complex operations such as laparoscopic rectosigmoidectomy or gastrectomy, usually in a two-day course, including some animal models. In the audience, experienced or recently qualified surgeons share their frustration by the drawbacks to reproduce them in their daily practice due to unavailability of resources at severely restraining conditions at public hospitals, besides the lack of preceptorship support during their learning curve. Even in developed countries, high technology surgery is performed mainly in private hospitals, where mostly high cost disposable instruments are available. University teaching hospitals still play an important roleproviding the basics for a conventional surgical training, but not enough time or funding are available to minimally invasive surgery training.

1 - Medical Doctor, Birmingham University, U.K.; Professor of Surgery, University of Joinville Region (UNIVILLE), Joinvile, SC, Brazil; Lubeck Institute of Teaching and Research Director, Itu, SP, Brazil.


Pinho Challenges in High Technology Surgery

427

Therefore, it is important to recognize that the present model of surgical training must be carefully reevaluated, since the increasing rhythm of high tech surgery evolution is incompatible to a single training period at the beginning of medical career. On the other hand, short courses in Training Centers, despite useful and informative, are not enough to provide conditions for an adequate learning curve. So, surgical societies, such as the Brazilian College of Surgeons must play an important role in regulating the system, similarly to other countries. Considering that high tech procedures are mostly stimulated by the medical devices industry, it is essential a critical effort for defining priorities and the real value of each technique, reducing “pioneer� actions with no scientific supportand reducing the pressure fora permanent surgical learning

curves. On the other hand, it is essential the recognition of the importance of industry as the only funding force in high technology surgical training, since traditional teaching programs are mostly unable to play that role. Therefore, it must be recommended an regulatory action by medical societies for a rational and scientific assessment of new techniques, so that funding efforts are dedicated to an adequate high technology surgical training or a planned regional support for low volume centers. We believe that the increasing adoption of high tech procedures will not occur automatically; conversely, the current scenario will lead to a crescent inequality and imbalance of modern surgical practice, with consequentreduction of its benefits to our population.

Rev Col Bras Cir 2017; 44(5): 426-427


Original Article

DOI: 10.1590/0100-69912017005002

Thoraco-laparoscopic esophagectomy: thoracic stage in prone position Esofagectomia vídeo-tóraco-laparoscópica com tempo torácico em posição pronada CARLOS BERNARDO COLA, TCBC-RJ1,2, FLÁVIO DUARTE SABINO, TCBC-RJ1, CARLOS EDUARDO PINTO, TCBC-RJ1, MARIA RIBEIRO MORARD, TCBC-RJ2, PEDRO PORTARI FILHO, TCBC-RJ2, TEREZA GUEDES1. A B S T R A C T Objective: to analyze the National Cancer Institute Abdominopelvic Division (INCA / MS/HC I) initial experience with thoraco-laparoscopic esophagectomy with thoracic stage in prone position. Methods: we studied 19 consecutive thoraco-laparoscopic esophagectomies from may 2012 to august 2014, including ten patients with squamous cells carcinoma (five of the middle third and five of the lower third) and nine cases of gastroesophageal junction adenocarcinoma (six Siewert I and three Siewert II). All procedures were initiated by the prone thoracic stage. Results: There were minimal blood loss, optimal mediastinal visualization, oncological radicality and no conversions. Surgical morbidity was 42 %, most being minor complications (58% Clavien I or II), with few related to the technique. The most common complication was cervical anastomotic leak (37%), with a low anastomotic stricture rate (two stenosis: 10.53%). We had one (5.3%) surgical related death, due to a gastric tube`s mediastinal leak, treated by open reoperation and neck diversion. The median Intensive Care Unit stay and hospital stay were two and 12 days, respectively. The mean thoracoscopic stage duration was 77 min. Thirteen patients received neoadjuvant treatment (five squamous cells carcinoma and eight gastroesophageal adenocarcinomas). The average lymph node sample had 16.4 lymph nodes per patient and 22.67 when separately analyzing patients without neoadjuvant treatment. Conclusion: the thoraco-laparoscopic approach was a safe technique in the surgical treatment of esophageal cancer, with a good lymph node sampling. Keywords: Esophagectomy. Prone Position. Thoracoscopy. Esophageal Neoplasms.

INTRODUCTION

E

sophageal cancer is currently the sixth most common malignant tumor in men and the thirteenth most common in women in Brazil (INCA/MS 2014)1, the squamous cell carcinoma being the most prevalent subtype (60% of new cases), followed by adenocarcinoma (35%), the remaining 5% composed of sarcomas, carcinosarcomas and Gastrointestinal Stromal Tumors (GISTs). Treatment of this condition includes esophagectomy whose morbidity is high, especially when associated with thoracotomy. Due to the prohibitive complication rates, the trans-hiatal technique (without thoracotomy) was developed as a tactic to enable surgery in patients with pneumopathies and/or with a high surgical risk2,3. Data from the literature on the thoraco-laparoscopic technique show advantages when compared with esophagectomy with thoracotomy and laparo-

tomy, such as shorter operative time, lower blood loss, less postoperative pain, lower percentage of pleuropulmonary complications and reduction of hospitalization time, with faster postoperative recovery4-7. Based on these data, we started the systematic thoraco-laparoscopic technique in the abdomino-pelvic surgery section of the National Cancer Institute (INCA HC I / MS-RJ) in May 2012. Our objective is to evaluate morbidity and lymph node sampling of thoracoscopic technique in prone position in a Brazilian public institution specializing in the treatment of cancer.

METHODS We conducted a prospective, non-randomized, observational study from May 2012 to August 2014. We included nineteen patients with esophageal cancer, whose staging by helical tomography and/or echoendoscopy was less than or equal to T3N2M0 (sta-

1 - National Cancer Institute (INCA/MS), Abdomino-pelvic Surgery Section - Rio de Janeiro, RJ, Brazil. 2 - Federal University of the State of Rio de Janeiro (Unirio), Department of General Surgery, Postgraduate Program in Medicine (PPGMED) / Professional Master’s Degree, Rio de Janeiro, RJ, Brazil. Rev Col Bras Cir 2017; 44(5): 428-434


Cola Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

ge III)8. Ten had squamous cell carcinoma (five of medium 1/3 and five of lower 1/3) and nine had adenocarcinoma of the gastro-esophageal junction (Six Siewert I – 2 to 5 cm above the Z line – and three Siewert II – 2 cm above or below the Z line). In patients with squamous cell carcinoma of the middle 1/3, we performed a radical lymph node dissection at the aorto-pulmonary window, left recurrent and upper mediastinum chains. Of the 19 patients, 13 (68.4%) received neoadjuvant treatment, and five (50%) of the 10 cases of squamous cell carcinoma received 50.4 Gy of radiotherapy and two cycles of chemotherapy with cisplatin or carboplatin associated with 5-fluorouracil (5FU). Eight (88.9%) of the nine cases of adenocarcinoma of the cardia received neoadjuvant treatment, five of which received exclusive chemotherapy with four cycles of 5Fu, oxaliplatin and leucovorin (Folfox), and three received 50.4 Gy of radiotherapy and four cycles of Folfox. We excluded patients who were not found to be apt from the cardiovascular or respiratory point of view, or with performance status greater than or equal to two (presence of incapacitating symptoms by the European Clinical Oncology Group classification) or with oncologic stage IV. As a comparison, we used data from our previous retrospective study on conventional esophagectomy3. Despite the impossibility of statistical comparison, given the differences in design and sampling of the studies, the variables analyzed comparing the two studies were length of stay in the ICU, time of postoperative hospitalization and number of dissected lymph nodes. In the group submitted to thoraco-laparoscopy, we also evaluated surgical morbidity, cervical anastomosis fistula, postoperative pneumonia and anastomotic stenosis. We also analyzed the use of neoadjuvant treatment and the difference in lymph node sampling in this group.

429

ce in the medial axillary line (endoscope), the second of 5mm in the seventh intercostal space in the posterior axillary line (surgeon’s left hand) and the third of 12mm in the fourth intercostal space in the posterior axillary line (surgeon’s right hand). We performed the thoracic procedure with the patient in ventral decubitus (prone position), orotracheal intubation with a Robert Shawtype double lumen tube, right lung exclusion, pneumothorax with carbon dioxide, and cavitary pressure of 12 mmHg. We carried out the dissection with atraumatic forceps for manipulation of the esophagus, monopolar electrocautery and a bipolar sealer, dissecting the mediastinum, to achieve an en bloc mobilization of the esophagus with its periaesophageal lymphatic drainage chains and thoracic duct, ligating and sectioning the azygos vein (with a vascular endostapler or ligation with cotton sutures and metal clips). During mediastinal lymphadenectomy, we performed an en bloc resection of the right and left paratracheal lymph nodes, as well as the upper and lower tracheobronchial, infracarinal and periaesophageal chains, and the thoracic duct. In the cases of squamous cell carcinoma of the middle third of the esophagus, we performed the meticulous and complete dissection of the lymph nodes of the aortopulmonary window and the recurrent chains. At the end of the thoracic time, we irrigated the cavity with warm saline solution and positioned a 30 or 32-Fr thoracic drain parallel to the esophageal resection bed (Figure 4), checking for pulmonary re-expansion under thoracoscopic control.

Surgical technique The technique used was thoracoscopy in prone position in all cases (Figures 1 and 2), followed by laparoscopy in the abdominal time. We initiated all procedures by the thoracic time on the right with a 30-degree endoscope and three trocars (Figure 3). The first 10mm trocar was positioned in the fifth intercostal spa-

Figure 1. Prone position with cushions and restraint bands.

Rev Col Bras Cir 2017; 44(5): 428-434


Cola Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

430

Figure 2. Placement of sterile fields.

Figure 3. The three trocars in position.

Figure 4. Thoracic drainage positioned through the endoscope port.

We then positioned the patient in dorsal decubitus, and replaced the double lumen orotracheal tube by a conventional, ventilating both lungs. We initiated the abdominal time by pneumoperitoneum through a 10mm umbilical trocar (open technique), and positioned three additional trocars, two for the surgeon, one 12mm on the left mammillary line above the umbilical line and one 5mm on the right nipple line in the same level). The third trocar, of 5mm for the first auxiliary, was introduced into the right anterior axillary line below the surgeon’s trocars, thus totaling four trocars. We mobilized the stomach by the gastrocolic ligament with bipolar sealer, preserving the gastroepiploic arcade, with ligation of the left gastroepiploic, short gastric, left gastric and posterior gastric vessels. Radical lymphadenectomy included stations 8 (common hepatic artery), 9 (celiac trunk), 7 (left gastric artery) and 11p (proximal splenic artery), as well as stations 1, 2 and 3. At the end of the en bloc lymphadenectomy, we broadly opened the esophageal hiatus by partially sectioning the left pillar to allow passage of the gastric tube into the mediastinum and to communicate abdominal and thoracic dissections. The stomach remained vascularized by the right gastric and gastroepiploic vessels. At the end of abdominal time, we performed a left anterolateral cervicotomy, following the anterior border of the sternocleidomastoid muscle, opening the lining and pre-tracheal layers of the cervical fascia, isolating the cervical esophagus, with careful preservation of both recurrent laryngeal nerves. The esophagus was sectioned, its proximal end repaired by surgical sutures, and the distal one ligated with polyglactin 1 sutures, at the end of which a 24Fr Foley catheter was sutured to aid in the rise of the gastric tube. After the esophageal release, we widened the 12mm abdominal trocar wound (right hand of the surgeon) to 5cm, protecting the abdominal wall with a plastic cover, and removing the surgical specimen with the en bloc mediastinal and abdominal lymphadenectomies. We prepared the gastric tube outside the abdominal cavity through this minilaparotomy, using a linear 80mm shear stapler with five to six blue loads, resulting in a narrow gastric tube, 3cm to 3.5cm wide, with reinforcement of the entire Clipping line with continuous suture of polypropylene 3.0 and addition of a piloromiotomy

Rev Col Bras Cir 2017; 44(5): 428-434


Cola Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

431

RESULTS

(optional). We transposed the prepared gastric tube to the neck with aid of the Foley catheter, and made a lateral-lateral esophagogastric anastomosis with a 45mm endostapler. The lower 2/3 of the cervical wound remained open to evaluate the viability of the gastric tube and to facilitate drainage in case of cervical fistulas.

Table 1 shows the epidemiologic characteristics of the 19 operated patients. Surgical morbidity was 42% (eight patients), the most common complication being cervical fistula (37%), followed by pneumonia (10.5%), with overlapping complications (Table 2).

Table 1. Epidemiological characteristics.

Gender

Male: 15 (79%)

Female: 4 (21%)

Mean age (years)

59.3

58.5

Histology

Squamous cell carcinoma:

Adenocarcinoma:

10 (52,6%)

9 (47,4%)

IA: 1 (5.3%) IIA: 5 (26.3%) IIB: 1 (5.3%) Stage

IIIA: 7 (36.7%) IIIB: 2 (10.6%) IIIC: 3 (15.8%) Upper 1/3:0 Medium 1/3: 5 (26.3%)

Location

Lower 1/3: 14 (73.7%)

Table 2. Morbidity and mortality.

Complications

Patients (%)

Cervical Fistula

7 (36.8%)

Anastomotic stenosis

2 (10.5%)

Pneumonia/Tracheostomy

2 (10.5%)

Reoperation

2 (10.5%)

Organic Failure/Sepsis

1 (5.25%) *

Mediastinal Linfocele

1 (5.25%)

Death

1 (5.25%) *

* complications superimposed on a same case.

Two patients were reoperated: one for acute hiatal hernia (left colon) on the fifth postoperative day,

treated by laparoscopic hiatoplasty, with discharge on the eighth postoperative day; and one due to a mediastinal fistula of the tip of the gastric tube, on the seventh postoperative day, treated by right thoracotomy and cervical shunt of the tip of the gastric tube. The patient died of multiple organ failure on the ninth postoperative day, despite intensive care, and was the only death in our series (5.3%). The mean lymph node sampling was 16.4 lymph nodes, with neoadjuvant treatment in 63.16% of the patients (Table 3). When we analyzed the cases operated without neoadjuvant treatment, we observed a mean of 22.67 lymph nodes (Table 4). The mean of metastatic lymph nodes was 1.95 per patient, 4.8 per patient in the group without neoadjuvant treatment and 0.6 in the group receiving it.

Rev Col Bras Cir 2017; 44(5): 428-434


Cola Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

432 Table 3. Neoadjuvant Treatment.

No

6 (31.58%) 13 (68.42%) QT: 5 (26.32%)

Yes

RT-QT: 8 (42.1%)

Table 4. Neoadjuvant Treatment versus average lymph node sampling.

Yes (QT *)

N=5

14 LNs***

Yes (QT-RT **)

N=8

9.2 LNs

No

N=6

22.7 LNs

* QT: chemotherapy; ** RT: radiotherapy; *** LNs: lymph nodes.

There was no conversion to open technique in any of the 19 cases. The mean duration of the thoracic time was 77 minutes. There was no significant blood loss. The median length of stay in the Intensive Care Center (ICU) and in the hospital were, respectively, two and twelve days. We started the enteral diet on the first postoperative day in all 19 cases.

of pulmonary complications (10.5%) was lower when compared with our previous database of conventional surgeries (20.4%)3. In the specialized literature we found a wide variation in the incidence of postoperative complications, ranging from 0% (Yatabe et al.7) to 50% (Fabian et al.9). This demonstrates heterogeneity between the specialized services and the complexity of the surgical treatment of esophageal cancer. However, despite the adversities it is possible to obtain good results, superior to those of conventional surgery3,5.

Table 5. complications according to Clavien’s classification.

Grade I

1

Grade II

6 (cervical fistulas treated conservatively)

Grade IIIa 1 (mediastinal linfocele: percutaneous drainage) Grade IIIb

2 (reoperations, including death) *

Grade IVa

0

Grade IVb

01 (FMOS: multiple organic failure) *

Grade IVc

1 (death) *

* complications superimposed on the same case.

DISCUSSION Transthoracic esophagectomy is traditionally associated with thoracotomy morbidity and its complications, although it undeniably provides adequate exposure for mediastinal lymphadenectomy2,3,5,6. Video-surgery has been employed to reduce this morbidity, using small intercostal incisions, with a magnified view of the mediastinal structures and better hemostasis, thanks both to the pneumothorax and to the greater delicacy in the dissection and use of modern vascular sealers. It minimizes morbidity of the thoracic time and provides a suitable pathway for complete mediastinal lymphadenectomy, reducing postoperative pain and providing a surgical specimen containing all periesophageal lymphoadiposal tissue and thoracic duct4,9,10. In the present study, there were few complications directly related to the video-surgical technique, demonstrating the safety of the method. Overall morbidity was 42%, comparable to that of other reference centers, the majority of complications being smaller, as shown in table 5 (Clavien’s classification11). The rate

There was one death (mortality of 5.3%), secondary to a mediastinal fistula at the end of the gastric tube. In the literature, we found death rates between 0%9 and 2.9%6, in larger series than ours, making it impossible to compare directly, but showing that it is possible to significantly reduce mortality with the minimally invasive approach. Despite the high rate of cervical fistulas (37%), the evolution was benign in most cases, with spontaneous closure in all cases between two and seven days. Of the seven fistulas, only two evolved with stenosis and were successfully treated with endoscopic dilatation. We believe that conventional cervical time with diamond-shaped anastomosis using the linear stapler helps to reduce the incidence of anastomotic stenosis, agreeing with the literature12,13. Regarding lymph node sampling, it is important to remember that neoadjuvant treatment considerably reduces the number of lymph nodes in the surgical specimen, especially when we associate radiotherapy and che-

Rev Col Bras Cir 2017; 44(5): 428-434


Cola Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

motherapy6,14. In the present study, 68.42% of patients received neoadjuvant treatment (which became the gold standard worldwide after publication of the Cross trial long-term results14), yet our mean lymph node sampling was 16.4 lymph nodes per patient versus 19.55 of our historical series6, in which no patient received neoadjuvant treatment. In the researched literature, only four authors4,5,9,12 reported their average lymph node sampling, the largest being of 18 lymph nodes per patient4, varying between 11.6 and 18, the majority of patients being operated without neoadjuvant treatment4,5,9,12, suggesting that our mean sample size was adequate. When we analyzed only the six cases operated without neoadjuvant treatment, the mean lymph node per patient was 22.67, demonstrating the ability to replicate or even improve lymphadenectomy through thoraco-laparoscopy, perhaps due to better visualization and magnification of mediastinal structures and lymphatic drainage chains4,6,9,10. The median times of ICU and hospital stay were respectively two and 12 days, with a median hospital admission considerably lower than that of our conventional historical series (20 days), suggesting a clear advantage of the thoraco-laparoscopic technique, despite of the im-

433

possibility of direct comparison due to the sample and methodological differences3. We believe that the thoraco-laparoscopic esophagectomy should become the standard technique for the surgical treatment of esophageal and cardia cancer. We believe that with adequate patient selection, accurate oncological staging, trained surgical staff, optimized postoperative support and a larger surgical series, we can improve our results, similar to those obtained in high-volume centers that specialize in the minimally invasive treatment of esophageal cancer2,4-6,8,9,11-14. Despite our small sample, we found that thoraco-laparoscopic esophagectomy is a safe, feasible and reproducible procedure in any large institution specialized in the treatment of cancer. We observed that the oncological radicality is similar or even superior to that of conventional surgery by thoracotomy and laparotomy, probably due to the better visualization and magnification of the anatomical structures. Data analysis allowed us to conclude that thoraco-laparoscopic esophagectomy with the thoracic time in prone position had acceptable morbidity and provided an oncologically adequate lymph node sampling.

R E S U M O Objetivo: analisar a experiência inicial do Serviço de Cirurgia Abdomino-Pélvica do Instituto Nacional de Câncer (INCA/MS/HC I) na esofagectomia vídeo-tóraco-laparoscópica com tempo torácico pronado. Métodos: estudo de 19 esofagectomias vídeo-tóraco-laparoscópicas realizadas de maio de 2012 a agosto de 2014, em dez pacientes portadores de carcinoma epidermoide esofágico (cinco do 1/3 médio e cinco do 1/3 inferior) e em nove portadores de adenocarcinoma da cárdia (seis Siewert I e três Siewert II). Todas as cirurgias foram iniciadas pelo tempo torácico em posição pronada, com mínima perda sanguínea, adequada visualização das estruturas mediastinais, radicalidade oncológica e sem conversões. Resultados: a morbidade cirúrgica foi de 42%, sendo a maioria complicações menores (58% Clavien I ou II). A complicação mais comum foi a fístula cervical em sete casos (37%), com baixa incidência de estenose anastomótica (duas estenoses: 10,53%). Houve um óbito (5,3%), relacionado a uma fístula mediastinal do tubo gástrico, tratada com reoperação e exteriorização cervical. As medianas de permanência em Centro de Terapia Intensiva e hospitalar foram respectivamente dois e 12 dias. A mediana do tempo vídeo-toracoscópico foi de 77min. Treze pacientes (68.4%) receberam tratamento neoadjuvante (cinco portadores de carcinomas epidermoides e oito de adenocarcinomas cárdia). A amostragem linfonodal média foi de 16,4 linfonodos por paciente e 22,67 quando analisados isoladamente os casos que não receberam tratamento neoadjuvante. Conclusão: a técnica vídeo-tóraco-laparoscópica se mostrou método seguro no tratamento cirúrgico do câncer do esôfago e proporcionou boa amostragem linfonodal em nossa casuística inicial. Descritores: Esofagectomia. Decúbito Ventral. Toracoscopia. Neoplasias Esofágicas.

REFERENCES 1.

2.

Câncer de esôfago. In: Instituto Nacional do Câncer José Alencar Gomes da Silva. Coordenação de Prevenção e Vigilância. Estimativa 2014: incidência de câncer no Brasil. Rio de Janeiro: INCA, 2014. p. 42-3.

3.

Smithers BM, Gotley DC, Martin I, Thomas JM. Comparison of the outcomes between open and minimally invasive esophagectomy. Ann Surg. 2007;245(2): 232-40 . Pinto CE, Dias JA, Sá EA, Tsunoda AT, Pinheiro RN. Tratamento cirúrgico do câncer de esôfago. Rev Bras Cancerol. 2007;53(4) 425-30.

Rev Col Bras Cir 2017; 44(5): 428-434


Cola Thoraco-laparoscopic esophagectomy: thoracic stage in prone position

434

4.

Palanivelu C, Prakash A, Senthilkumar R, Senthilnathan P, Parthasarathi R, Rajan PS, et al. Minimally invasive esophagectomy: thoracoscopic mobilization of the esophagus and mediastinal lymphadenectomy in prone position- experience of 130 patients. J Am Coll Surg. 2006;203(1):7-16. 5. Feng M, Shen Y, Wang H, Tan L, Zhang Y, Khan MA, et al. Thoracolaparoscopic esophagectomy: is the prone position a safe alternative to the decubitus position? J Am Coll Surg. 2012;14(5):838-44. 6. Pennathur A, Awais O, Luketich D. Technique of minimally invasive Ivor Lewis esophagectomy. Ann Thorac Surg. 2010;89(6):S2159-62. 7. Yatabe T, Kitagawa H, Yamashita K, Akimori T, Hanazaki K, Yokoyama M. Better postoperative oxygenation in thoracoscopic esophagectomy in prone positioning. J Anesth. 2010;24(5):803-6. 8. NCCN Clinical Practice Guidelines in Oncology. Esophageal and esophagogastric junction cancers (Excluding the proximal 5 cm of the stomach). Fort Washington: NCCN; 2013. 9. Fabian T, McKelvey AA, Kent MS Frederico JA. Prone thoracoscopic esophageal mobilization for minimally invasive esophagectomy. Surg Endosc 2007;21(9):1667-70. 10. Gossot D, Fourquier P, Celerier M. Thoracoscopic esophagectomy: technique and initial results. Ann Thorac Surg. 1993;56(3):667-70. 11. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-13.

12. Nguyen N, Hinojosa M, Smith BR, Chang KJ, Gray J, Hoyt D. Minimally invasive esophagectomy: lessons learned from 104 operations. Ann Surg. 2008;248(6):1081-91. 13. Kanaji S, Nakamura T, Otowa Y, Yamamoto M, Yamashita K, Imanishi T, et al. Thoracoscopic esophagectomy in the prone position for esophageal cancer with right aortic arch: case report. Anticancer Res. 2013;33(10):4515-9. 14. Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, Ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090-8.

Received in: 20/03/2017 Accepted for publication: 18/05/2017 Conflict of interest: none. Source of funding: none. Mailing address: Carlos Bernardo Cola E-mail: bernardocola@yahoo.com.br

Rev Col Bras Cir 2017; 44(5): 428-434


Original Article

DOI: 10.1590/0100-69912017005003

Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study Fatores prognósticos do câncer de mama e sobrevida global em cinco e dez anos na cidade de Goiânia, Brasil: estudo de base populacional RUFFO DE FREITAS JÚNIOR, TCBC-GO1,2; RODRIGO DISCONZI NUNES1; EDESIO MARTINS3; MARIA PAULA CURADO4,5; NILCEANA MAYA AIRES FREITAS2; LEONARDO RIBEIRO SOARES1; JOSÉ CARLOS OLIVEIRA3. A B S T R A C T Objective: to analyze the overall survival and prognostic factors of women with breast cancer in the city of Goiânia. Methods: this is a retrospective, cross-sectional, observational study that included women with malignant neoplasms of the breast identified by the Goiânia Population-based Cancer Registry. The variables studied were age at diagnosis, tumor size, staging, axillary lymph node involvement, tumor grade, disease extent, hormone receptors, and c-erb-B2 oncoprotein. We performed overall survival analyzes of five and ten years. Results: we included 2,273 patients in the study, with an overall survival of 72.1% in five years and 57.8% in ten years. In the multivariate analysis adjusted for tumor size, the factors that influenced the prognosis were axillary lymph nodes, histological grade, progesterone receptor, c erb B2, T staging and disease extension. Conclusion: overall survival in ten years is below that observed in other countries, and possibly reflects what happens with the majority of the Brazilian population. The prognostic factors found in this population follow the same international patterns. Keywords: Breast Neoplasms. Epidemiology. Survival. Prognosis.

INTRODUCTION

B

reast cancer is the most frequent malignant neoplasm in the female population, representing a public health problem on a global scale1-3. For the year 2016, the National Cancer Institute (INCA) estimated 57,960 new cases of breast cancer among Brazilian women, with a gross rate of 56.2/100,000; for the state of Goiás, 1,680 new cases, and gross rate of 52.09/100,000; and for the city of Goiânia, 250 new cases, and gross rate of 76.07/100.0004. Although the mortality rate has decreased in some European countries5, in Brazil it remains stable, representing the main cause of cancer death among Brazilian women6,7, as well as in the city of Goiânia6,8. Survival is the most used parameter to evaluate the results of the diagnosis and treatment of a malignant tumor with observations obtained in health

records9-11. The age of the patient at diagnosis, tumor size, number of lymph nodes involved, degree of tumor differentiation, molecular subtype and clinical staging are the main parameters used to evaluate survival and play a fundamental role in the therapeutic planning of this neoplasia10-12. Survival studies are important in the evaluation of the distribution of resources and in the identification of the main prognostic factors in a given region and population. However, few data are available on population-based breast cancer survival. This study aimed to evaluate the overall survival of women with breast cancer residing in Goiânia.

METHODS This is a retrospective, population-based, overall survival study that included women living in the city

1 - Federal University of Goiás (HC/UFG), Mastology Program, Clinics Hospital, Goiânia, GO, Brazil. 2 - Goiás Association to Cancer Combat (ACCG), Araújo Jorge Hospital, Goiânia, GO, Brazil. 3 - Goiás Association to Cancer Combat (ACCG), Goiânia Population-based Cancer Registry, Goiânia, GO, Brazil. 4 - International Prevention Research Institute (iPRI), Senior Research, Lyon, Auvergne-Rhône-Alpes, France. 5 - AC Camargo Cancer Center, AC Camargo Hospital, São Paulo, SP, Brazil. Rev Col Bras Cir 2017; 44(5): 435-443


436

Freitas Júnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

of Goiânia, Goiás state, Brazil, with malignant neoplasms of the breast, with a primary diagnosis from 1995 to 2003.

or addresses of relatives and/or neighbors, and the Regional Electoral Court of Goiás (TRE-GO) for cases that attended or not the 2008 elections.

Goiânia Population-Based Cancer Registry (RCBPGO)

Study variables

The RCBPGO, created in 1986, represents one of the most important cancer registries in Brazil and has worked continuously since its creation until the present day13. Incident cases are collected from general hospitals, cancer hospitals, specialized clinics and diagnostic centers. Periodically, the service coordinator evaluates these sources, taking into account the provision of complete data or the difficulty of attending13. For case inclusion criteria, the registry classifies and codes cases according to ICD-O (International Classification of Diseases for Oncology) and the recommendations of the International Association of Cancer Registries. Confirmation of the diagnosis by histopathological examination in 90% of cases is enough to guarantee the quality of data and information generated by a Population-Based Cancer Registry13. In the period from 1989 to 2003, the confirmation of the diagnoses performed by this means in the RCBPGO was 94.7%14.

Study population We selected the sample through the RCBPGO database, including all the cases of breast cancer in the period from January 1, 1995 to December 31, 2003. We excluded the cases of in situ breast cancer in the same period. For the analysis of survival, the time of follow-up or of the active search for the women had a cut-off date of December 31, 2010.

Data collection We modified the questionnaire used to collect the variables based on a previous study carried out by Abreu et al.10, in 2002, in the population of Goiânia, for the period 1988 to 1990. We obtained additional information on each case in hospital records and in the archives of pathological anatomy laboratories. To identify the vital status of the patients in the analyzed period, we collected data from the Goiás Mortality Information System (SIM), the TELELISTA system (www. telelistas.net), to obtain the current telephone number

We considered the following variables for the study: age at diagnosis (0-49 years, 50-59 and over 60); tumor size in centimeters (2cm, greater than 2cm and less than 5cm and greater than 5cm); clinical staging, according to the TNM system of the American Joint Committee of Cancers (AJCC); axillary lymph nodes (uncommitted, one to three committed, four to nine committed and more than ten committed); histological grade, according to the classification of Bloom and Richardson (1957), grade I being the most differentiated tumors, grade II, the moderately differentiated, and grade III, the anaplastic (G1, G2 and G3, respectively); disease extent (localized, regionalized and metastasis); estrogen (ER) and progesterone (PR) receptor by immunohistochemical reaction, being considered positive or negative, as reported by each laboratory tending to consider the positivity when there was more than 1% of cells marked in the tumor invasion area; presence of c-erb-B2 oncoprotein, classified from zero to three crosses, only those reported as three crosses being considered positive.

Data analysis We divided overall survival into groups of five and ten years of follow-up. We counted time from the date of diagnosis to the occurrence of the event of interest (death) or until censorship (loss due to observation time when the participant completed the previously stipulated follow-up period without dying). Women who remained alive until the end of the follow-up date (maximum follow-up time of 60 or 120 months) were considered as censored in the study. After completing the variables collection and active search of the women, we used the SPSS® for Windows version 18.0 software to construct the database and to compute the Kaplan-Meier method of survival and the log rank test, with a 95% confidence interval. For the multivariate analysis, we used the Cox regression model, in which we adjusted the variables for tumor size.

Rev Col Bras Cir 2017; 44(5): 435-443


Freitas Júnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

Ethical aspects The present study was approved by the Ethics in Research Committee of the Araújo Jorge Hospital of the Goiás Association to Cancer Combat (ACCG). All recommendations of good clinical practice were followed according to resolution CNS 466/2012 and the Helsinki Convention.

RESULTS We included 2,273 women residing in Goiâ-

437

nia, with a confirmed diagnosis of malignant neoplasm of the breast between the period of 1995 and 2003. We obtained access to medical records of 1,579 (69.4%) of them, with adequate collection of the variables. In 694 (30.5%) cases, the medical records were not available (Table 1). At the time of diagnosis of breast cancer, 616 (53.8%) women had a tumor between 2cm and 5cm, 595 (52.9%) had no axillary lymph node involvement, and the predominant histological grade was G2, with 841 (70.6%) cases. In table 1 shows the complete distribution of variables by included women.

Table 1. Distribution of the study variables by the included women (n = 2,273).

Variable

Cases

%

0-49

963

42.4

50-59

609

26.8

> 60

699

30.8

Total with information *

2271

100.0

= 2 cm

311

27.1

> 2 = 5 cm

616

53.8

> 5 cm

218

19.1

Total with information *

1145

100.0

G1

115

9.7

G2

841

70.6

G3

235

19.7

Total with information *

1191

100.0

None

595

52.9

1 to 3

240

21.3

4 to 9

160

14.2

10 or more

131

11.6

Total with information *

1126

100.0

Positive

505

67.3

Negative

246

32.7

Total with information *

751

100.0

Age at diagnosis

Tumor size

Histological Grade

Lymph Nodes Committed

Estrogen receptor

Rev Col Bras Cir 2017; 44(5): 435-443


438

Freitas JĂşnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

Progesterone receptor Positive

441

60.0

Negative

294

40.0

Total with information *

735

100.0

Positive

88

12.1

Negative

637

87.9

Total with information *

725

100.0

T1

215

21.9

T2

441

45.1

T3

140

14.3

T4

183

18.7

Total with information *

979

100.0

N0

588

57.5

N1

322

31.4

N2

113

11.1

Total with information *

1023

100.0

Localized

1172

59.8

Regional

622

31.8

Metastasis

166

8.4

Total with information *

1960

100.0

c-erb-B2

Staging – T

Staging – N

Disease extent

*Total of patients with information for this particular variable.

Overall survival at five years was 72.1%, and for women with tumors smaller than 2cm, 85.5%. For women who presented G1 tumors, survival was 87.6%, and for women without axillary lymph node involvement, 90.2%. As for estrogen, progesterone and c-erb-B2 oncoprotein receptors, the highest five-year survival rates were ER positive (83.0%), PR positive (84.9%) and c-erb-B2 negative (79.6%). With regard to staging, the best prognoses were for women with T1 (90.8%) and N0 (86.0%). As for disease extent, wo-

men with tumors with localized disease and confined to the breast had a five-year overall survival of 84.1%. Overall survival in ten years, on its turn, was 57.8%. In patients with tumors smaller than 2cm the survival was 68.5%, being 62.5% among those with tumors of 2 to 5cm. Patients with lymph node involvement had survival at ten years of 58%, while for those with free axilla, it was 77% (p<0.001). We observed the same in patients with G1 tumors (80.2%) and G3 tumors (55.1%). Women with positive estro-

Rev Col Bras Cir 2017; 44(5): 435-443


Freitas JĂşnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

gen (64.5%) and progesterone (66.6%) receptors had better prognoses, as well as those with c-erb-B2 negative tumors (63.7%). Patients with tumors detected in the early stages had the highest overall survival rates at ten years. In the univariate analysis of the five-year overall survival, the following variables were significant: age at diagnosis (p<0.002); tumor size (p<0.001), histological grade (p<0.001); number of committed lymph nodes (p<0.001); ER (p<0.001); PR (p<0.001); T staging (p<0.001); N staging (p<0.001); and the presence of metastatic disease (p<0.001). The c-erb-B2 variable

439

was not significant (p<0.06). In the univariate analysis of the ten-year overall survival, similar values were found in all variables except ER (p<0.005), c-erb-B2 (p=0.005) and age at diagnosis (p<0.001). In the five-year multivariate analysis adjusted for tumor size, the cumulative risk of death from breast cancer was higher among women with histological grade G3, with lymph node involvement, negative PR, more advanced staging (T3 / T4) and metastatic disease (Table 2). For the ten-year analysis, in addition to the factors found in the five-year one, the c-erb-B2 variable was also significant (Table 3).

Table 2. Multivariate analysis of overall survival in 60 months (five years) of women with breast cancer in the city of Goiânia (1995-2003).

Study variables

HR (95% CI)

Histological grade

p value 0.004

G1/G2

1.00

G3

2.39 (1.31-4.33)

Committed lymph nodes

0.002

No

1.00

Yes

2.73 (1.43-5.20)

Estrogen receptor

0.64

Positive

1.00

Negative

1.15 (0.62-2.13)

Progesterone receptor

0.01

Positive

1.00

Negative

2.27 (1.21-4.24)

c-erb-B2

0.30

Negative

1.00

Positive

1.38 (0.74-2.57)

T Staging

<0.001

T1/T2

1.00

T3/T4

2.79 (1.63-4.75)

Disease extent

0.014

Localized/Regional

1.00

Metastasis

2.78 (1.23-6.31)

* Adjusted by the size of the tumor; HR: Hazard Ratios. Rev Col Bras Cir 2017; 44(5): 435-443


Freitas Júnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

440

Table 3. Multivariate analysis of overall survival in 120 months (ten years) of women with breast cancer in the city of Goiânia (1995-2003).

Study variables

HR (95% CI)

Histological grade

p value 0.008

G1/G2

1.00

G3

2.01 (1.20-3.40)

Committed lymph nodes

0.004

No

1.00

Yes

2.18 (1.28-3.68)

Estrogen receptor

0.24

Positive

1.00

Negative

1.36 (0.80-2.30)

Progesterone receptor

0.02

Positive

1.00

Negative

1.81 (-3.01 1.09)

c-erb-B2

0.034

Negative

1.00

Positive

1.73 (1.04-2.87)

T Staging

<0.001

T1/T2

1.00

T3/T4

2.48 (1.59-3.85)

Disease extent

0.036

Localized/Regional

1.00

Metastasis

2.24 (1.05-4.76)

* Adjusted by the size of the tumor; HR: Hazard Ratios.

DISCUSSION The epidemiological data on breast cancer in Goiânia6,8,14, as well as the variation in incidence in recent years15, have been described periodically. However, few survival studies were performed using data from population-based registries. In this scenario, stands out the RCBPGO, whose data were the source of three previous survival studies that included women between 1988 and 199010, 1990-19949 and 19952003 (present series). Despite the methodological differences, we observed an increase in survival from one series to the other, corresponding to 57%, 65.4% and 72.1%, respectively. This increase was possibly related to improvements in local screening and diagnosis of

breast cancer16-18, which led to a reduction in advanced cases and an increase in initial cases14,19. The inclusion of new targeted drugs and therapies should also have contributed to this outcome improvement20,21. Recently the CONCORD-2 study was published, which evaluated more than 25,000,000 people diagnosed with malignant neoplasms between 1995 and 2009, followed in 279 population-based registries from 67 countries. In South and Central America, breast cancer survival rates increased between 1995-1999 and 2005-2009, mainly in Brazil, from 78% to 87%3. We should note that the difference in variation between the five-year survival found in the CONCORD-2 analysis (87.0%) and that found in the present study (72.1%) is justified because these are different outco-

Rev Col Bras Cir 2017; 44(5): 435-443


Freitas Júnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

mes. The CONCORD-2 study evaluated net survival, in which the outcome for survival analysis is only death related to breast cancer, with deaths related to other causes considered as censorship3. We evaluated overall survival, for which all patient deaths were considered as outcome. Thus, the difference found relates to the methodological question and not to information divergence22. Other studies conducted in Brazil, using data from hospital-based cancer registries, also found overall survival at five years similar to the present one, including the Barretos Cancer Hospital series (74.8%) and the Santa Catarina Breast Cancer Research Group (76.2%)23,24. On the other hand, a study conducted by the Brazilian Breast Cancer Research Group (GBECAM), using different hospital-based records, showed that overall survival was influenced by the type of health insurance, with patients in the public system presenting lower survival (p<0.001) compared with the patients in the private system. In the subgroup evaluation, there was no difference between patients with clinical stage 0-II (p=0.176), but patients with stage III-IV in the public health system had significantly lower overall survival compared with the private system subgroup (p=0.008). These data reinforce the importance of clinical staging to the diagnosis of breast cancer, whose early detection may minimize the differences in survival observed between the public and the private care systems. Regarding the overall survival in ten years in Brazil, only the study by Abreu et al.10 evaluated information collected in population-based registries, showing a general survival of 41.5% between 1998 and 2000 in the city of Goiânia. In the present series, overall survival after ten years of follow-up was 57.8%, which maintains the pattern of increase in overall survival rates in the city of Goiânia. However, it still differs considerably from other studies, which showed a relative survival rate of 86.0% in Sweden and 85.7% in Finland1,26, possibly due to the absence of adequate mammographic screening in the Brazilian population. In Europe, the ONCOPOOL study evaluated 16,944 women treated at ten reference centers for breast cancer between 1990 and 1999. Overall survi-

441

val at ten years was 80%. In this study, we highlight the difference in survival between the patients who received the diagnosis through screening programs (84%) and those diagnosed on physical examination (76%)1. The divergences found between the European study and this series are possibly due to the absence of a population screening program for breast cancer and inadequate mammography coverage in Brazil18,19. These data reinforce the current recommendations of the Brazilian Mastology Society, which warrants the screening of breast cancer from age 40 onwards27. In the five-year multivariate analysis, adjusted for tumor size, factors influencing the prognosis were axillary lymph nodes, histological grade, progesterone receptor expression, T staging, and disease extent (Table 2). These data are in agreement with other hospital-based studies that evaluated women with breast cancer at reference centers for the diagnosis and treatment of breast cancer12,23,24. The c-erb-B2 variable was only significant in the ten-year multivariate analysis (Table 3). The high number of “no information” for this variable (Table 2) may have impaired the results in the five-year evaluation. The first immunohistochemistry analyzes only began to be performed at the Araújo Jorge Hospital (reference center in cancer of the state of Goiás), where most of the patients in the study (51.6%) were enrolled in March 1996 and were only included in the routine after a few years. Among the limitations of the current study, we highlight the difficulties of standardization in the filling of charts and records and in the identification of variables. These limitations are inherent to studies based on secondary data24, and do not interfere with the credibility and relevance of the studies in question. Still, considering the survival studies after trackable tumors, the possibility of anticipation and duration biases stands out. However, overall survival remains a clinical outcome of practical relevance10, which may be associated with other variables of interest and translate a broader evaluation of the strategies aimed at the control of such tumors. The robustness of the present study rests on the number of cases and on the reliability of the follow-up, since the active search on the patients’ vital status allowed us to infer high

Rev Col Bras Cir 2017; 44(5): 435-443


Freitas Júnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

442

quality, with a low possibility of bias in relation to the overall survival outcome. It is possible that the results found should reflect what happens to the majority of the Brazilian population. We should also note that the

overall survival in ten years is below that observed in other countries1,26 and therefore, that resources related to early diagnosis and treatment should be better provided to the Brazilian population.

R E S U M O Objetivo: analisar a sobrevida global e os fatores prognósticos de mulheres com câncer de mama na cidade de Goiânia. Métodos: estudo observacional, retrospectivo, transversal, que incluiu mulheres portadoras de neoplasias malignas da mama identificadas pelo Registro de Câncer de Base Populacional de Goiânia. As variáveis estudadas foram: idade ao diagnóstico, tamanho do tumor, estadiamento, comprometimento dos linfonodos axilares, grau tumoral, extensão da doença, receptores hormonais e oncoproteína c-erb-B2. Foram realizadas análises de sobrevida global, de cinco e de dez anos. Resultados: foram incluídas no estudo 2273 pacientes, com sobrevida global em cinco anos de 72,1% e de 57,8% em dez anos. Na análise multivariada ajustada pelo tamanho do tumor, os fatores que influenciaram o prognóstico foram: linfonodos axilares, grau histológico, receptor de progesterona, c-erb-B2, estadiamento T e extensão da doença. Conclusão: a sobrevida global em dez anos está abaixo da observada em outros países, e possivelmente reflete o que acontece com a maioria da população brasileira. Os fatores prognósticos encontrados nesta população seguem o mesmo padrão internacional. Descritores: Neoplasias da mama. Epidemiologia. Sobrevida. Prognóstico.

REFERENCES 1.

2.

3.

4.

Blamey RW, Hornmark-Stenstam B, Ball G, BlichertToft M, Cataliotti L, Fourquet A, et al. ONCOPOOL - a European database for 16,944 cases of breast cancer. Eur J Cancer. 2010;46(1):56-71. Gonzaga CM, Freitas-Junior R, Curado MP, Sousa ALL, Souza-Neto JA, Souza MR. Temporal trends in female breast cancer mortality in Brazil and correlations with social inequalities: ecological time-series study. BMC Public Health. 2015;15:96. Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, Marcos-Gragera R, Stiller C, Azevedo e Silva G, Chen WQ, Ogunbiyi OJ, Rachet B, Soeberg MJ, You H, Matsuda T, Bielska-Lasota M, Storm H, Tucker TC, Coleman MP; CONCORD Working Group. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015; 385(9972):977-1010. Erratum in: Lancet. 2015;385(9972):946. Instituto Nacional do Câncer José Alencar Gomes da Silva. Coordenação de Prevenção e Vigilância. Estimativa 2016: incidência de câncer no Brasil [Internet]. Rio de Janeiro: INCA, 2016 [citado em 2016 Jul 09]. Disponível em: http://www.inca.gov.br/

estimativa/2016/estimativa-2016-v11.pdf 5. Malvezzi M, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2014. Ann Oncol. 2014;25(8):1650-6. 6. 6. Freitas-Junior R, Gonzaga CMR, Freitas NM, Martins E, Dardes RC. Disparities in female breast cancer mortality rates in Brazil between 1980 and 2009. Clinics (São Paulo). 2012;67(7):731-7. 7. Kluthcovsky AC, Faria TN, Carneiro FH, Strona R. Female breast cancer mortality in Brazil and its regions. Rev Assoc Med Bras (1992). 2014;60(4):387-93. 8. Gonzaga CM, Freitas-Junior R, Souza MR, Curado MP, Freitas NM. Disparities in female breast cancer mortality rates between urban centers and rural areas of Brazil: ecological time-series study. Breast. 2014;23(2):180-7. 9. Coleman MP, Quaresma M, Berrino F, Lutz JM, De Angelis R, Capocaccia R, Baili P, Rachet B, Gatta G, Hakulinen T, Micheli A, Sant M, Weir HK, Elwood JM, Tsukuma H, Koifman S, E Silva GA, Francisci S, Santaquilani M, Verdecchia A, Storm HH, Young JL; CONCORD Working Group. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol. 2008;9(8):730-56. 10. Abreu E, Koifman RJ, Fanqueiro AG, Land MGP, Koifman S. Sobrevida de dez anos de câncer de mama feminino em coorte populacional em Goiânia (GO), Brasil, 19881990. Cad Saúde Colet. 2012;20(3):305-13.

Rev Col Bras Cir 2017; 44(5): 435-443


Freitas Júnior Prognostic factors and overall survival of breast cancer in the city of Goiania, Brazil: a population-based study

11. Xing Y, Meng Q, Sun L, Chen X, Cai L. Survival analysis of patients with unilateral and bilateral primary breast cancer in Northeast China. Breast Cancer. 2015;22(5):536-43. 12. Balabram D, Turra CM, Gobbi H. Survival of patients with operable breast cancer (Stages I-III) at a Brazilian public hospital--a closer look into cause-specific mortality. BMC Cancer. 2013;13:434. 13. Moura L, Curado MP, Simões EJ, Cezário AC, Urdaneta M. Avaliação do registro de câncer de base populacional do município de Goiânia, estado de Goiás, Brasil. Epidemiol Serv Saúde. 2006;15(4):717. 14. Nunes RD, Martins E, Freitas-Júnior R, Curado MP, Freitas NM, Oliveira JC. Descriptive study of breast cancer cases in Goiânia between 1989 and 2003. Rev Col Bras Cir. 2011;38(4):212-6. 15. Freitas-Junior R, Freitas NMA, Curado MP, Martins E, Silva CMB, Rahal RMS, et al. Incidence trend for breast cancer among young women in Goiânia, Brazil. Sao Paulo Med J. 2010;128(2):81-4. 16. Unger-Saldaña K. Challenges to the early diagnosis and treatment of breast cancer in developing countries. World J Clin Oncol. 2014;5(3):465-77. 17. Corrêa RS, Freitas-Junior R, Peixoto JE, Rodrigues DC, Lemos ME, Marins LA, et al. [Estimated mammogram coverage in Goiás State, Brazil]. Cad Saúde Pública. 2011;27(9):1757-67. Portuguese. 18. Freitas-Junior R, Rodrigues DC, Corrêa RD, Peixoto JE, de Oliveira HV, Rahal RM. Contribution of the Unified Health Care System to mammography screening in Brazil, 2013. Radiol Bras. 2016;49(5):305-10. 19. Martins E, Freitas-Junior R, Curado MP, Freitas NM, Oliveira JC, Silva CM. [Temporal evolution of breast cancer stages in a population-based cancer registry in the Brazilian central region]. Rev Bras Ginecol Obstet. 2009;31(5):219-23. Portuguese. 20. Hamy-Petit AS, Belin L, Bonsang-Kitzis H, Paquet C, Pierga JY, Lerebours F, et al. Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort. Br J Cancer. 2016;114(1):44-52. 21. Kümler I, Knoop AS, Jessing CA, Ejlertsen B, Nielsen DL. Review of hormone-based treatments

22.

23.

24.

25.

26.

27.

443

in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant. ESMO Open. 2016;1(4):e000062. 22. Freitas-Junior R, Soares LR, Barrios CH. Cancer survival: the CONCORD-2 study. Lancet. 2015;386(9992):428-9. 23. Carneseca EC, Mauad EC, Araujo MA, Dalbó RM, Longatto-Filho A, Vazquez VL. The Hospital de Câncer de Barretos Registry: an analysis of cancer survival at a single institution in Brazil over a 10-year period. BMC Research Notes. 2013;6:141-51. Schneider IJC, d`Orsi E. [Five-year survival and prognostic factors in women with breast cancer in Santa Catarina State, Brazil]. Cad Saúde Pública. 2009; 25(6):1285-96. Portuguese. Liedke PE, Finkelstein DM, Szymonifka J, Barrios CH, Chavarri-Guerra Y, Bines J, et al. Outcomes of breast cancer in Brazil related to health care coverage: a retrospective cohort study. Cancer Epidemiol Biomarkers Prev. 2014;23(1):126-33. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, Trama A, Visser O, Brenner H, Ardanaz E, Bielska-Lasota M, Engholm G, Nennecke A, Siesling S, Berrino F, Capocaccia R; EUROCARE-5 Working Group. Cancer survival in Europe 19992007 by country and age: results of EUROCARE 5 - a population-based study. Lancet Oncol. 2014;15(1):23-34. Urban LABD, Peixoto JE, Ferreira CAP, Canella EO, Kefalasb AL, Maranhão NMA, et al. Recommendations of Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, Sociedade Brasileira de Mastologia, and Federação Brasileira das Associações de Ginecologia e Obstetrícia for imaging screening for breast cancer. Radiol Bras. 2012;45(6):334-9.

Received in: 16/03/2017 Accepted for publication: 11/05/2017 Conflict of interest: none. Source of funding: none. Mailing address: Ruffo de Freitas Júnior E-mail: ruffojr@terra.com.br / ribeiroufg@hotmail.com

Rev Col Bras Cir 2017; 44(5): 435-443


Original Article

DOI: 10.1590/0100-69912017005004

Epidemiological profile and treatment of substance losses by trauma to the lower limbs Perfil epidemiológico e tratamento de perdas de substância por trauma em membros inferiores RICARDO BARROS MARTINS REZENDE1; JEFFERSON LESSA SOARES DE MACEDO, TCBC-DF1; SIMONE CORRÊA ROSA1; FERNANDO SOARES GALLI1. A B S T R A C T Objectives: to evaluate the epidemiological profile, the surgical treatment and the postoperative results of patients with complex traumatic injuries to the lower limbs. Methods: we conducted a retrospective study of patients with traumatic complex injuries treated by the Plastic Surgery Service of a regional hospital in Brasília. We analyzed clinical-epidemiological data, type of surgical procedure and functional recovery of the limb after six months of treatment. Results: 119 patients were treated, with a mean age of 29 years, predominantly men (76.4%). Motorcycle accident was responsible for most of the injuries, in 37.8% of cases. The most frequent surgical treatment was skin grafting (62.1%), followed by the fasciocutaneous flap (21.9%), muscular flap (12.6%) and microsurgical flap (3.4%). Six months after completion of the surgical treatment, 35.3% of the patients needed crutches to move, characterizing a delay in limb functional recovery that, however, was significantly related to the presence of fractures, external fixation or bone exposure in the preoperative period. Conclusion: the profile of the patient with complex traumatic lower limb injury was a male, motorcycle accident victim, and grafting was the most used treatment. Orthopedic trauma with bone fracture, bone exposure and the presence of external fixator were significantly associated with a higher risk of limb functional impairment, requiring locomotion crutches after six months of treatment. Keywords: Lower Extremity. Wounds and Injuries. Surgical Flaps. Surgery, Plastic. Health Profile.

INTRODUCTION

H

igh-energy trauma has increased significantly in the last decades, mainly due to auto and motorcycles accidents. Trauma victims may have lesions of varying severity and location, the lower limbs being an important site of injury. These can vary from simple skin solutions of continuity to great tissue losses and exposure of noble structures1,2. Lesions severity and treatment difficulties require professional knowledge and familiarity with repair techniques, making reconstructions of the lower limbs a challenge for the surgeon. The scarcity of adjacent tissues is one of the difficulties in the search for reconstruction1,2. The lower limbs have peculiar anatomical features that make their reconstruction a complex theme. These include the need to support body weight, a greater propensity to develop deep venous thrombosis, problems with venous stasis and chronic edema,

frequent occurrence of atherosclerosis and difficult nervous regeneration3,4. It is essential to know in detail the anatomical structures, the etiopathology of the lesion and to have a multidisciplinary team throughout the process of reconstruction and rehabilitation. Functional recovery should always be sought, regardless of the proposed treatment, be it reconstruction or amputation3-6. The objective of this study is to evaluate the epidemiological profile, the treatment offered and the postoperative results of victims of trauma to the lower limbs admitted to the Plastic Surgery Service of the North Wing Regional Hospital, Brasília - DF.

METHODS This is a retrospective study of patients admitted to the Plastic Surgery Service of a regional public hospital, who had wounds with loss of substance

1 - North Wing Regional Hospital, Plastic Surgery Service, Brasília, DF, Brazil. Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

in the lower limbs due to trauma, from January 2011 to December 2015. Patients were admitted after clinical and surgical control of their wounds by other specialties, such as orthopedics and general surgery. Exclusion criteria were: patients with chronic ulcers or loss of substance in the lower limbs whose etiology was vascular, lymphatic or oncologic. The demographic data studied were gender, age, origin, trauma mechanism and the most affected region of the lower limb. In addition, we also evaluated the characteristics of the wound, such as presence of preoperative fracture, bone exposure and presence of external fixator. We analyzed the type of reconstructive surgical treatment and counted only the main procedure of each patient for data analysis. For example, in the case of a sural flap, the graft donor area is covered with skin graft. In these cases, we counted only the fasciocutaneous flap, since the graft would be a complementary treatment of the sural flap. In some patients, surgical debridements were isolated or associated with negative pressure therapy (vacuum system). After wound preparation, the patients underwent reconstructive surgical procedures, such as skin grafts, fasciocutaneous flaps, muscle flaps, or microsurgical flaps. We classified tissue integration as complete when the graft or flap had no ischemia or necrosis, as partial when there was partial loss, and as necrosis when there was complete loss of the treatment applied. Finally, we analyzed the functional recovery of the limb and the need for crutches six months after the surgical treatment, information obtained by the medical record or by direct contact with the patient. We used the Epiinfo 7.15 software for statistical analysis. The study was approved by the Ethics in Research Committee of the State Department of Health of the Federal District (CAAE number: 47391715.6.0000.5553, opinion number: 1,167,841).

RESULTS The sample consisted of 119 patients, with a predominance of the male gender (76.4% of cases) and age ranging from two to 70 years (mean 29). The patients’ origin was mainly from the Federal District

445

(65.5%), followed by the cities around it, mainly from the state of Goiás. The hospitalization time ranged from one to 160 days, with average 21.2 (Table 1).

Table 1. Demographic data of victims of lower limbs trauma with loss of substance admitted to the North Wing Regional Hospital, Brasília/DF, in the period of 2011 to 2015.

Gender

N

%

Male

91

76.4

Female

28

23.6

Federal District

78

65.5

Goiás

32

26.9

Other

9

7.6

0-19

26

21.8

20-29

40

33.6

30-39

20

27.8

≥ 40

33

27.8

Total

119

100

Origin

Age group

N = number of cases; % = percentage of total cases.

The most frequent etiology of the injuries was motorcycle accident (37.8% of cases), followed by trampling (30.3%) and auto accident (11.8%). The lower third of the leg was the most affected area, in 50.4% of patients, followed by the middle third of the leg, in 32% (Table 2). Regarding the preparation of traumatic lesions for the reconstructive surgical procedure (graft or flap), 25 (21.0%) patients required isolated debridements, and 15 (12.6%), debridement associated with vacuum therapy. Tibial fracture was present in 44 (37.0%) patients, external fixator in 32 (26.9%) and there was bone exposure in 37 (31.1%). Many individuals required more than one surgical procedure for complete reconstruction of the affected limb. The number of reconstructive procedures per patient ranged from one to seven. The total

Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

446

number of reconstructive procedures was 224 and the mean reconstructive procedures per patient were 1.88.

Table 2. Etiology and localization of victims of trauma to the lower limbs with loss of substance admitted to the North Wing Regional Hospital, BrasĂ­lia/DF, in the period of 2011 to 2015.

Etiology of Trauma

N

%

Motorcycle accident

45

37.8

Run-over

36

30.3

Automobile accident

14

11.8

Fall from height

7

5.9

Firearm

6

5.0

Other *

11

9.2

Lower 1/3

60

50.4

Middle 1/3

38

32.0

Upper 1/3

21

17.6

Total

119

100

Location of lesions

* Working machine accident, stab wound, injury during run. N = number of cases; % = percentage of total cases.

The most frequent surgical procedure was skin grafting (62.1% of cases) (Table 3). The fasciocutaneous flap was the second most frequent procedure and was done in 21.9% of cases, the reverse sural flap and the neighborhood flaps standing out. Cross-legged flaps were required in 3.4% of hospitalized patients. Muscle flaps were performed in 12.6% of the patients, with prominence of the medial head gastrocnemius muscle flap. The microsurgical flap was performed in four patients, representing 3.4% of the sample (Figures 1 to 3). Patients submitted to cutaneous grafts had a complete integration rate of 86.4%, 10.8% of partial integration, and 2.7% evolved with necrosis and total graft loss. Fasciocutaneous flaps had a rate of 88.4% complete integration and 11.5% partial integration, with no case of total necrosis. Muscle flaps had a 73.3% complete integration rate and 26.6% partial integration, also without total necrosis cases. The microsurgical flap was performed in four patients, presenting total loss in one case. The others had complete integration.

Table 3. Relationship of location of the lesions in the leg with the surgical treatment of victims of lower limbs trauma with loss of substance admitted to the North Wing Regional Hospital, BrasĂ­lia/DF, in the period of 2011 to 2015.

Location

Lower 1/3

Middle 1/3

Upper 1/3

Total

N/%

N/%

N/%

N/%

45/37.8

17/14.3

12/10.1

74/62.1

Sural2

8/6.7

4/3.4

0

12/10.1

Neighborhood3

2/1.7

5/4.2

3/2.5

10/8.4

Cross-leg 4

2/1.7

2/1.7

0

4/3.4

Gastrocnemius 5

0

6/5.1

6/5.1

12/10.1

Soleus6

0

3/2.5

0

3/2.5

Microsurgical7

3/2.5

1/0.8

0

4/3.4

60/50.4

38/32.0

21/17.6

119/100

Type of treatment Graft 1 Fasciocutaneous Flap

Muscle flap

Total

N = number of cases; % = percentage of total cases; 1. Sole skin grafting; 2. Reverse sural fasciocutaneous Flap; 3. Neighborhood fasciocutaneous Flap; 4. Fasciocutaneous Flap of the opposite leg (cross-leg); 5. Medial head gastrocnemius muscle flap; 6. Reverse hemisolear muscle flap; 7. Microsurgical anterolateral thigh flap.

Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

Figure 1. Loss of substance on the back of the foot: A. Preoperative; B. Partial skin graft.

447

Figure 2. Reverse sural fasciocutaneous flap: A. Marking; B. Muscle preservation; C. Postoperative.

patients. The factors significantly associated with the need to use crutches to walk after six months of surgical treatment for closure of lower limb substance losses were the presence of preoperative tibial fracture (73.8% x 16.9%, p<0.01, OR: 13.8), the use of external fixator (57.1% x 10.4%, p<0.01, OR: 11.5) and presence of preoperative bone exposure (52.4% x 19.5%, p<0.01, OR: 4.5) (Table 4).

DISCUSSION

Figure 3. Medial head gastrocnemius muscle flap: A. Tissue loss; B. Dissection; C. Mobilization.

Six months after surgical treatment, we evaluated the use of crutches to ambulate in 42 (35.3%)

After the 1970s, repair of loss of lower limb substance evolved with new surgical techniques, with the advent of vacuum therapy and the inclusion of multidisciplinary teams for treatment. Thus, the extremities are now more likely to be recovered3. In cases where the extremity cannot be recovered, the amputation stump can be covered with soft tissues to support the prosthesis, allowing functional gait and maximum functional capacity4. Therefore, besides the need to cover the wound, there is also a need to allow mobility of the

Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

448

Table 4. Factors associated with the use of crutches after surgical treatment of victims of lower limbs trauma with loss of substance admitted to the North Wing Regional Hospital, BrasĂ­lia/DF, in the period of 2011 to 2015.

Use of crutches** Yes

No

N=42

N=77

Fracture of tibia

31 (73.8%)

Use of external fixator Bone exposure

Associated factors*

Or

95% CI

p

13 (16.9%)

13.8

5.5 -34.4

< 0.01

24 (57.1%)

8 (10.4%)

11.5

4.4 -29.8

< 0.01

22 (52.4%)

15 (19.5%)

4.5

1.9 -10.4

< 0.01

* Evaluated during the period of stay in the North Wing Hospital Regional. ** Use of crutches six months after treatment of injuries.

joints, normal ambulation and return of the individual to normal activities3,5. The main victims of this type of trauma that are hospitalized in regional hospitals are young adults. The mean age of this study was 29 years, being that part of the society that is economically active, bringing great socioeconomic impact. The main etiologies of this trauma are motorcycle accidents and road accidents. Tibia fracture occurred in 37% of the patients participating in this study, demonstrating the severity of the lesions. Increasingly complex lower-limb trauma in large cities is likely to occur, probably due to the increase in vehicular and motorcycle traffic, due to the difficulty of adapting the cities to the high demand of public transport. This type of trauma has a high socioeconomic cost, leading to long-term withdrawal from work, as has been observed in other studies7. Surgical treatment of loss of lower limb substance involves several techniques and, as a basic principle, one should opt, where possible, for the simplest procedures, provided that they are effective and safe, such as skin grafts. These are used in superficial lesions where there is no need for bony filling or covering. They can also be applied in patients whose clinical status does not allow for larger procedures5,6. Studies of angiosomes, a unit composed of the skin and underlying tissue supplied by the same vessel (analogous to the sensitive dermatomes), described by Taylor8 in 2003, revolutionized flap surgery. Knowledge of the vascular pedicles of

subcutaneous tissue and skin, muscle and fascia areas, as well as of the stratigraphic and segmental distribution of this vascularization, paved the way for the use of each of these structures as independent units transformed into flaps8. Perforating vessels cross the deep fascia and are responsible for the vascular supply of a particular cutaneous or fasciocutaneous region. These vessels allow the creation of flaps that spare the muscles. With a Doppler, the local perforating vessels that can serve as a vascular pedicle are mapped, allowing free flaps to be manufactured9,10. The recent advances in microsurgical techniques, associated with modern orthopedic bone repair techniques and fixation methods, have allowed the recovery of many limbs that were doomed to amputation a long time ago8-10. The fasciocutaneous flaps have their vascularization enriched by the presence of the fascia and are less morbid than the muscular ones. On the other hand, the muscular flaps have more robust vascularization, fill larger spaces and allow a greater fight against infection11. Microsurgical flaps may be alternative options, especially in lesions of the distal third of the leg, ankle or foot12. The vascular conditions of the limb should be evaluated both pre- and postoperatively. Circulatory diseases may make apparently well-planned flaps unfeasible. In addition, postoperative immobilization, which is fundamental in most cases, is also a predisposing factor for thromboembolic complications.

Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

When the patient presents loss of lower limb substance without conditions to perform the reconstructive surgical procedure (graft or flap), the area of substance loss should be prepared for reconstruction. At that moment, surgical debridement alone or associated with vacuum therapy is fundamental3. Negative pressure therapy on the lower limb loss bed controls edema, reduces exudate, decreases bacterial population, stimulates the formation of granulation tissue, and increases vascularization in the wound bed13-17. It has become an important adjuvant method in the treatment of complex wounds and should integrate the surgeonsâ&#x20AC;&#x2122; therapeutic arsenal3,18. The application of negative pressure therapy should be done in a clean wound, without devitalized tissue or after adequate debridement, being useful in the treatment of acute traumatic wounds, acting as a bridge between the emergency treatment and the definitive skin cover19. The contraindications of negative pressure therapy are untreated osteomyelitis, presence of tissue with malignancy, presence of necrosis, exposure of vessels, nerves, organs or sites of anastomoses16,18. In the present study, grafting was the most accomplished treatment (62.1%), corresponding to the principle of choosing the simplest procedures when possible. The percentage of complete integration of the grafts was 86.4%, a proportion attributed to patientsâ&#x20AC;&#x2122; profile, which was mostly young, with recent wounds and without circulatory problems. The skin grafts were used in the substance-loss injuries that presented good granulation tissue, but without bone, tendon or vascular-nervous pedicles exposure20. The formation of wound granulation tissue was stimulated with surgical debridements of the devitalized tissues, dressings based on alginate or zinc oxide, and with the use of vacuum therapy. Isolated surgical debridement was required in 21% of individuals of the sample and in 12.6% it was necessary to associate debridement with vacuum therapy. Among the flaps, fasciocutaneous ones were the most used (21.9%), being the main surgical option of flap for the lesions of the middle and lower thirds of the leg, with emphasis on the reverse sural flap and the neighborhood flaps. As for the muscular flaps, they were mostly used to cover lesions of the upper and mi-

449

ddle third of the leg, especially the medial head gastrocnemius muscle flap. Similar data were presented by Franco et al.21,22. The medial head gastrocnemius muscle flap is a good option to cover bone exposures of the upper and middle third of the leg and does not leave motor sequelae. It was performed in 12 patients (10.1%) of this sample. Similar results have been seen in other studies, including concomitant use of the soleus muscle or in combination with a fasciocutaneous flap. In addition, sectioning the origin of the medial head of the gastrocnemius in the medial condyle of the femur and / or the tendons of the goose leg (tendon of the sartorius, gracilis and semitendinosus muscles) is a way of increasing the arc of rotation of this muscular flap23, 24. Distal reverse pedicle flaps, such as the reverse sural, have proved to be very useful and versatile, especially for lesions of the distal third of the leg25,26. This flap was used in 12 (10.1%) patients, similar to another study. Another useful flap in the reconstruction of the distal regions of the lower limb, mainly in the calcaneus and on the Achilles tendon, is the medial plantar flap. The study pointed to a significant association between the presence of tibia fracture at the beginning of treatment and the need for crutches to ambulate after six months of limb reconstruction (OR=13.8; p<0.01). We observed the same significant association with the presence of the external fixator and with the bone exposure (OR=11.5, p<0.01, OR=4.5, p<0.01, respectively). Patients who presented severe trauma with bone fracture, bone exposure or need for external fixators are significantly more likely to present functional impairment of the limb after six months of coverage of the lower limb substance loss27. This study demonstrated that the epidemiological profile of the patient admitted to a regional public hospital for treatment of loss of substance in the lower limb was a young adult, male, motorcycle accident victim. The graft was the most used treatment, followed by fasciocutaneous flaps of the reverse sural type or of the neighborhood. Among the muscular flaps, the flap of the medial head of the gastrocnemius is prominent. Orthopedic trauma with bone fracture, bone exposure or the presence of external fixator were associated with an increased risk of limb functional impairment requiring crutches for walking six months after treatment.

Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

450

R E S U M O Objetivo: avaliar o perfil epidemiológico, o tratamento cirúrgico e os resultados pós-operatórios de pacientes com feridas complexas traumáticas de membros inferiores. Método: estudo retrospectivo dos pacientes com ferimentos complexos traumáticos tratados pelo Serviço de Cirurgia Plástica de um hospital regional de Brasília. Foram analisados os dados clínico-epidemiológicos, o tipo de procedimento cirúrgico e a recuperação funcional do membro após seis meses do tratamento. Resultados: foram tratados 119 pacientes, com média de idade de 29 anos, predominantemente homens (76,4%). O acidente moto ciclístico foi responsável pela maioria das lesões, em 37,8% dos casos. O tratamento cirúrgico mais realizado foi o enxerto de pele (62,1% dos casos), seguido pelo retalho fasciocutâneo (21,9%), o retalho muscular (12,6%) e o retalho microcirúrgico (3,4%). Seis meses após a conclusão do tratamento cirúrgico, 35,3% dos pacientes necessitavam de muletas para se locomover, caracterizando um atraso na recuperação funcional do membro que, no entanto, estava relacionado significativamente à presença de fratura, de fixador externo ou de exposição óssea no pré-operatório. Conclusão: o perfil do paciente com ferida complexa traumática de membros inferiores foi homem, vítima de acidente motociclístico e o enxerto foi o tratamento mais utilizado. O trauma ortopédico com fratura óssea, exposição óssea e a presença de fixador externo estiveram associados significativamente a um maior risco de prejuízo funcional do membro com necessidade de muletas para locomoção após seis meses de tratamento. Descritores: Extremidade Inferior. Ferimentos e Lesões. Retalhos Cirúrgicos. Cirurgia Plástica. Perfil de Saúde.

REFERENCES 1. 2.

3.

4.

5.

6.

7.

8. 9.

Ong YS, Levin LS. Lower limb salvage in trauma. Plast Reconstr Surg. 2010;125(2):582-8. Pelissier P, Boireau P, Martin D, Baudet J. Bone reconstruction of the lower extremity: complications and outcomes. Plast Reconstr Surg. 2003; 11(7)1:22239. Coltro PS, Ferreira MC, Batista BPS, Nakamoto HA, Milcheski DA, Tuma Júnior P. Atuação da cirurgia plástica no tratamento de feridas complexas. Rev Col Bras Cir. 2011;38(6):381-6. Fairbanks GA, Murphy RX Jr, Wasser TE, Morrissey WM. Patterns and implications of lower extremity injuries in a community level I trauma center. Ann Plast Surg. 2004;53(4):373-7. Whitaker IS, Rozen WM, Shokrollahi K. The management of open lower limb fractures: the journey form amputation to evidence-based reconstruction and harpsichords. Ann Plast Surg. 2011;66(1):3-5. Reddy V, Stevenson TR. MOC-PS(SM) CME article: lower extremity reconstruction. Plast Reconstr Surg. 2008;121(4 Suppl):1-7. MacKenzie EJ, Morris JA Jr, Jurkovich GJ, Yasui Y, Cushing BM, Burgess AR, et al. Return to work following injury: the role of economic, social, and jobrelated factors. Am J Public Health. 1998;88(11):16307. Taylor GI. The angiosomes of the body and their supply to perforator flaps. Clin Plast Surg. 2003;30(3):331-42. Attinger CE, Evans, KK, Bulan E, Blume P, Cooper

10.

11.

12.

13.

14.

15.

16.

17.

P. Angiosomes of the foot and ankle and clinical implications for limb salvage: reconstruction, incisions, and revascularization. Plast Reconstr Surg. 2006;117(7 Suppl): 261S-93S. Sgarbi MWM, Gotfryd AO. Amputação ou reconstrução da extremidade esmagada: utilização do Índice da Síndrome da Extremidade Esmagada. Acta Ortop Bras. 2006;14(5):264-7. Chan JK, Harry L, Williams G, Nanchahal J. Soft-tissue reconstruction of open fractures of the lower limb: muscle versus fasciocutaneous flaps. Plast Reconstr Surg. 2012;130(2):284e-295e. Godina M. Early microsurgical reconstruction of complex trauma of the extremities. Plast Reconstr Surg. 1986;78(3):285-92. Argenta LC, Morykwas MJ. Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. Ann Plast Surg. 1997; 38(6):56376; discussion 577. Argenta LC, Morykwas MJ, Marks MW, DeFranzo AJ, Molnar JA, David LR. Vacuum-assisted closure: state of clinic art. Plast Reconstr Surg. 2006;117(7 Suppl):127S42S. Wada A, Ferreira MC, Tuma P Jr, Arrunátegui G. Experience with local negative pressure (vacuum method) in the treatment of complex wounds. São Paulo Med J. 2006;124(3):150-3. Lima RVKS, Coltro PS, Farina JA Jr. Terapia por pressão negativa no tratamento de feridas complexas. Rev Col Bras Cir. 2017;44(1):81-93. Ferreira MC, Paggiaro AO. Terapia por pressão negativa-

Rev Col Bras Cir 2017; 44(5): 444-451


Rezende Epidemiological profile and treatment of substance losses by trauma to the lower limbs

18.

19.

20.

21.

22.

23.

24.

vácuo. Rev Med (São Paulo). 2010;89(3/4):142-6. Anghel EL, Kim PJ. Negative-pressure wound therapy: a comprehensive review of the evidence. Plast Reconstr Surg. 2016;138(3 Suppl):129S-37S. Milcheski DA, Ferreira MC, Nakamoto HA, Pereira DD, Batista BN, Tuma P Jr. Uso da terapia por pressão negativa subatmosférica em feridas traumáticas agudas. Rev Col Bras Cir. 2013;40(5):392-7. Macedo JLS, Rosa SC, Botelho DL, Santos CP, Queiroz MN, Gomes TGACB. Reconstrução de membros inferiores: perfil, manejo e evolução dos pacientes do Hospital Regional da Asa Norte do Distrito Federal. Rev Col Bras Cir. 2017;44(1):9-16. Franco D, D’Ávila F, Arnaud M Jr, D’Ávila B, Franco T. Tratamento das áreas cruentas de perna com retalhos locais. Rev Bras Cir Plast. 2015;30(2):264-72. Parrett BM, Matros E, Pribaz JJ, Orgill DP. Lower extremity trauma: trends in the management of softtissue reconstruction of open tibia-fibula fractures. Plast Reconstr Surg. 2006;117(4):1315-22. D’Avila F, Franco D, D’Avila B, Arnaut M Jr. Uso de retalhos musculares locais para cobertura de exposições ósseas na perna. Rev Col Bras Cir. 2014;41(6):434-9. Macedo JLS, Rosa SC, Silva AA, Rezende Filho Neto AVF, Ruguê PHS, Scartazzini C. Versatilidade do

451

uso do retalho do músculo gastrocnêmio medial na reconstrução de lesões de partes moles de membros inferiores. Rev Bras Cir Plast. 2016;31(4):527-33. 25. Kenser U, Bach AD, Polykandriotis E, Kopp J, Horch RE. Delayed reverse sural flap for staged reconstruction of the foot and lower leg. Plast Reconstr Surg. 2005;116(7):1910-7. 26. Follmar KE, Baccarani A, Baumeister SP, Levin LS, Erdmann D. The distally based sural flap. Plast Reconstr Surg. 2007;119(6):138e-48e. 27. Yazar S, Lin CH, Wei FC. One-stage reconstruction of composite bone and soft-tissue defects in traumatic lower extremities. Plast Reconstr Surg. 2004;114(6):1457-66.

Received in: 30/03/2017 Accepted for publication: 20/05/2017 Conflict of interest: none. Source of funding: none. Mailing address: Ricardo Barros Martins Rezende E-mail: ricardobmr@yahoo.com.br / jlsmacedo@yahoo. com.br

Rev Col Bras Cir 2017; 44(5): 444-451


Original Article

DOI: 10.1590/0100-69912017005005

Use of transfer factor in immunosuppressed surgical patients Avaliação do uso de fator de transferência na resposta imunológica de pacientes cirúrgicos imunodeprimidos

CELIA REGINA OLIVEIRA GARRITANO, TCBCRJ1; FRANCESCO LUCIANA BERTI AUN1.

DI

NUBILA1; RENATA M. COUTO1; ROSSANO KEPLER ALVIM FIORELLI, TCBC-RJ1;

A B S T R A C T Objective : to evaluate the action of Transfer Factor on the immune response of patients with malignant neoplasm submitted to surgery, chemotherapy and radiotherapy. Method: we analyzed the variations of leukocytes, total lymphocytes, T-lymphocytes and CD4 counts in 60 patients submitted to immunostimulation with a single, daily dose of 0.5mg sublingual Transfer Factor, started simultaneously with chemotherapy and/or radiotherapy. Results: there were statistically significant increases in the counts of all cell lines studied, more pronounced after 12 months of use of the medication. Conclusion: the Transfer Factor restored immune response and showed no side effects. Keywords: Transfer Factor. Immunity, Cellular. Neoplasm Invasiveness.

INTRODUCTION

D

iscovered by Henry Sherwood Lawrence in 1955, the Transfer Factor (TF) is an extract obtained from calf splenic cells, consisting of a conjugated polypeptide with molecular weight around 6,000 Daltons and structure similar to the RNA1-3. TF has an important immune stimulatory function, promoting the maturation and differentiation of thymocytes in T lymphocytes, the restoration of function of malfunctioning peripheral lymphocytes, the recovery of humoral immunity through differentiation of B lymphocytes, forming plasmocytes and synthesizing specific humoral antibodies, the increase in allogeneic graft rejection capacity, the in vitro activation of T lymphocytes through cytotoxic action, lymphokine production and increased activity of the mononuclear phagocytic system. When administered orally, it establishes direct contact with the Peyer’s plaques and lymph nodes, where it exerts a selective action on lymphocytes and antigen-presenting cells. Digestive enzymes and hydrochloric acid do not

influence its stability2-4. The first evidence that cancer arises due to somatic genetic changes came from studies on Burkitt’s lymphoma4. Since then, several malignancies have been associated with oncogens, with the possibility of using immunomodulators as a complementary treatment to surgery, chemotherapy and radiotherapy5-10. The best results of neoplastic disease treatment are achieved when surgery accomplishes the reduction of tumor load, complemented by chemotherapy and radiotherapy. However, these procedures affect the immune system, and even temporarily, influence the respective therapeutic regimens, which sometimes have to be interrupted due to the low number of leukocytes, lymphocytes and the important side effects resulting from impaired immune response. Immunostimulatory agents have contributed to avoid or minimize these collateral damages, among them the Transfer Factor, which was first used in the treatment of cancer by Fudenberg et al.11 in 1976, and which has also been used in the treatment of non neoplastic diseases2,3,11.

1 - Federal University of the State of Rio de Janeiro (UNIRIO), Department of General and Specialized Surgery / Master’s Degree in Medicine, Rio de Janeiro, RJ, Brazil. Rev Col Bras Cir 2017; 44(5): 452-456


Garritano Use of transfer factor in immunosuppressed surgical patients

453

METHODS We carried out this study at the Gaffrée and Guinle University Hospital of the Federal University of the State of Rio de Janeiro – UNIRIO. We included 60 patients, both men and women, aged over 30 years, with malignant neoplasms, confirmed by histopathological examination of the surgical specimen, submitted to Chemotherapy (QT) and/or radiotherapy (RT) after surgery, and followed as outpatients for 12 months. We applied the immunostimulation with TF provided by the Laboratório de Extratos Alergênicos Ltda., registered with the Ministry of Health with the number 1729.0011.001-4. We administered the substance as a single dose of 0.5 mg sublingually daily and started concurrently with chemotherapy and/or radiotherapy. All patients underwent immunological evaluation prior to initiation of treatment by laboratory tests (leukocyte count, total lymphocytes, T lymphocytes, and CD4 lymphocyte subpopulation), which were repeated six and 12 months after initiation of therapy. We then compared those with the exams results

before the beginning of treatment. We present results as mean and standard deviation. We performed the data analysis using tables and graphs using the Microsft Office Excell7® software. For statistical analysis, we used Graph Pad Instat software version 3.0, San Diego California® and, for the purpose of interpretation, the type I error limit was up to 5% (p <0.05). We tested the variables through the Kolmogorov-Smirnov (KS) method, inference through the Wilcoxon’s test for non-parametric samples and the Student’s t-test for parametric samples. The study was evaluated and approved by the Ethics in Research Committee, in accordance with Resolution 196/96.

RESULTS In the statistical analysis, all the samples evaluated had a normal distribution by the Kolmogorov and Smirnov (KS) method. The characteristics of the patients analyzed are contained in table 1.

Table 1. Characteristics of the analyzed group.

Gender Male 14 (23.3%)

Age group – cases (%)

Tumor location – cases (%)

Female

30-39 years

96.7%) 4

Breast

20 (33.3%)

60 (76.7%)

40-49 years

15 (25%)

Intestine

18 (30%)

50-59 years

8 (13.3%)

Stomach

11 (18.3%)

60-69 years

20 (33.3%)

Pancreas

5 (8.3%)

+ 70 years

13 (21.7%)

Uterus

3 (5%)

Lung

1 (1.7%)

Liposarcoma

1 (1.7%)

Kidney

1 (1.7%)

Regarding the total leukocyte count, 39 (65%) patients presented a 6-month increase in values and 50 (83.3%) in 12 months compared with the counts before the beginning of therapy. This increase ranged from 1.9% to 103% in six months, and from 2.1% to 170% in 12 months. We observed that of the 21 cases (35%) that had a reduction of the leukocyte values in six months, 18 (85.7%) were able to recover them in 12 months, and 12 (57.1%) achieved rates higher than before

treatment. The total lymphocyte count increased in six months in 40 (66.7%) patients and in 48 (80%) cases in 12 months. This increase ranged from 1.5% to 85% in six months and from 0.2% to 137.7% in 12 months. Of the 20 cases (33.3%) that had a reduction in lymphocyte values at six months, 16 (80%) were able to recover them in 12 months, 13 (65%) presenting higher values than those found at the beginning of treatment.

Rev Col Bras Cir 2017; 44(5): 452-456


Garritano Use of transfer factor in immunosuppressed surgical patients

454

When analyzing the means of the leukocyte counts, we observed an increase of 5.6% when comparing the rates before treatment with those after six months, of 20.1% between pre-treatment and 12 months,

and of 12.4% between six and 12 months of treatment. Regarding total lymphocyte means, this increase was 5%, 24.8% and 14.9%, respectively. Statistical analysis of these variations was very significant (Table 2).

Table 2. Changes in the counts of leukocytes and lymphocytes.

Leukocytes

Count

Lymphocytes

Average

Count

Average

Before

5,073 (± 1281)

Before

1,642 (± 537)

6 months

5,356 (± 1522)

6 months

1,742 (± 580)

12 months

6,019 (± 1341)

12 months

1,980 (± 594)

T test

p < 0.0001

T test

p < 0.0001

Values expressed as mean ± standard deviation.

Table 3. Changes in the counts of T and CD4 lymphocytes.

T-Lymphocytes

Count

CD4-Lymphocytes

Average

Count

Average

Before

1,174 (± 486)

Before

732 (± 279)

6 months

1,278 (± 463)

6 months

772 (± 311)

12 months

1,477 (± 541)

12 months

919 (316 ±)

T test

p < 0.0001

T test

p < 0.0001

Values expressed as mean ± standard deviation.

The analysis of T lymphocytes revealed that 38 (63.3%) patients presented an increase in counts at six months and 46 (76.7%) at 12 months in comparison with the result before the start of therapy. This increase ranged from 0.4% to 320% in six months and from 0.5% to 160% in 12 months. We observed that of the 22 cases (36.7%) that had a reduction in the T lymphocyte counts in six months, 17 (77.3%) were able to recover them in 12 months, and 11 (64.7%) achieved rates higher than before treatment. As for the subpopulation of CD4 lymphocytes, there were also increases, in 35 (58.3%) cases when comparing the time treatment with six months, and in 51 (85%) between the time before treatment and 12 months. This increase ranged from 0.6% to 162.1% in six months and from 0.5% to 337.1% in 12 months. We observed that of the 25 cases (41.7%)

that had CD4 subpopulation reduction in six months, 19 (76%) were able to recover them in 12 months, and 16 (84.2%) were able to obtain rates higher than before treatment. When we evaluated the T-lymphocyte averages of the sample, we observed an increase of 8.8% when comparing the values before the start of treatment with those after six months, of 33.4% between pre-treatment and 12 months, and 15.6% between six and 12 months of treatment. The same was true for the CD4 subpopulation, with an increase of 5.5%, 20.6% and 19%, respectively. Statistical analysis of these variations was very significant (Table 3). When we evaluated the means of the results in the studied period, we observed that in all of them there was an increase in values, which was more expressive after 12 months of treatment, as shown in figure 1.

Rev Col Bras Cir 2017; 44(5): 452-456


Garritano Use of transfer factor in immunosuppressed surgical patients

455

Figure 1. Comparison of the results of the exams performed.

DISCUSSION A deficient immune response favors the appearance of several diseases of viral, bacterial and neoplastic origin. When it comes to cancer, this becomes more serious because the tumor itself, as well as the use of QT, RT and corticosteroids, also affects the immune system, further accentuating immunosuppression. Several immunomodulators have been used to reverse this situation with the aim not only of improving the immune response, minimizing the side effects of QT and RT, but of preventing

the schedules used to be interrupted, which compromises treatment results10-20. The lymphocytes and their T subclasses are fundamental for the immune response, especially regarding solid tumors. Therefore, the combats to this type of tumor have the objective of making T-lymphocytes active and competent16,17,19,20. In this study, we observed that the total lymphocytes and their subclasses showed an increase in counts, which was more pronounced with TF use for 12 months, and even when counts fell in the first six months of treatment, these were recovered after 12 months. The best response was evidenced by the subpopulation of CD4-lymphocytes, with an increase of 80% at the end of the study, and among those who had an initial decrease, 76% of presented an increase with 12 months of treatment. We also sought to analyze the effect of TF on total leukocytes, and we also observed an increase in counts in 83.3% of the cases with 12 months of therapy and, similar to lymphocytes, the 85.7% that had an initial reduction displayed higher rates after 12 months of TF use. We conclude that TF promoted the activation of leukocytes, total lymphocytes and their subclasses, resulting in a stimulation of the immune response, specially when used for a period of 12 months.

R E S U M O Objetivo: avaliar a ação do Fator de Transferência na resposta imunológica de pacientes portadores de neoplasia maligna submetidos à cirurgia, quimioterapia e radioterapia. Método: análise das variações dos valores dos leucócitos, linfócitos totais, linfócitos T e CD4 em 60 pacientes submetidos à imunoestimulação com Fator de Transferência administrado em dose única de 0,5mg por via sublingual, diariamente e iniciada simultaneamente à quimioterapia e/ou radioterapia. Resultados: houve um aumento no número de todas as linhagens celulares estudadas que foi mais acentuada após 12 meses de uso da medicação. A análise estatística realizada com o software Graph Pad Instat, testadas pelo método Kolmogorov and Smirnov, mostrou que os resultados foram significativos. Conclusão: o Fator de Transferência restabeleceu a resposta imune e não apresentou efeitos colaterais. Descritores: Fator de Transferência. Imunidade Celular. Invasividade Neoplásica.

REFERENCES 1.

2.

3.

Al-Askari S. Henry Sherwood Lawrence. In: Biographical Memoirs. Washington, D.C.: National Academy of Sciences; 2009. p. 237-55. Gibson J, Basten A, Van Der Brink C. Clinical use of transfer factor 25 years. Immunol Allergy Clin N A. 1983;3(2):331-57.

4.

5.

Kirkpatrick CH. Therapeutic potential of transfer factor. N Engl J Med. 1980;303(7):390-1. Cosme K, González M, Gorovaya L, Soria Y, Barcelona S, Quintana M, et al. Determinación de la actividad biológica in vivo del Factor de Transferencia. Técnica alternativa. Biotecnol Apl. 2001;18( Espec.):E16. Croce CM. Oncogenes and cancer. N Engl J Med. 2008;358(5):502-11.

Rev Col Bras Cir 2017; 44(5): 452-456


Garritano Use of transfer factor in immunosuppressed surgical patients

456

6.

7.

8.

9.

10.

11.

12.

13.

14.

Cook JA, Taylor D, Cohen C, Hoffmann EO, Rodrigue J, Malshet V, et al. Evaluation of effector cells mediating the antitumor action of glucan. J Reticuloendothel Soc. 1977;22(1):21-34. Diluzio NR. Macrophage glucan-activated macrophages and neoplasia. In: Altura BM, Saba TM, editors. Pathophysiology of the reticuloendothelial system. New York: Raven Press; 1981. p. 209-24. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096-100. Mantovani A, Allavena P, Sica A, Balkwill F. Cancerrelated inflammation. Nature. 2008;454(7203):43644. Garritano CRO, Gomes JCG, Pimenteira CAP. ß1-3 Glucan no tratamento do câncer de intestino. J Bras Med. 2010;98(4):22-4. Levine PH, Pizza G, Ajmera K, De Vinci C, Viza D. Transfer factor in virus-associated malignancies: an underestimated weapon in prevention and treatment of cancer. Adv Tumor Virol. 2002;2:7-20. Souza CA, Vigorito AC, Aranha FJP, Oliveira GB, Eid KAB, Ruiz MA. Terapêutica citoprotetora em pacientes tratados com quimio e/ou radioterapia anti neoplásica. Rev Bras Hematol.Hemoter. 2000;22(2):123-8. Patchen ML, MacVittie TJ, Souza LM. Postirradiation treatment with granulocyte colony-stimulating factor and preirradiation WR-2721 administration synergize to enhance hemopoietic reconstitution and increase survival. Int J Radiat Oncol Biol Phys. 1992;22(4):773-9. De Souza CA, Santini G, Marino G, Nati S, Congiu AM, Vigorito AC, et al. Amifostine (WR2712), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin’s

15.

16.

17.

18.

19.

20.

lymphomas: a phase II study. Braz J Med Biol Res. 2000;33(7):791-8. Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol. 2006;6(5):383-93. Rosenberg SA, Restifo NP, Yang JC, Morgan RA, Dudley ME. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8(4)299-308. Guinn BA, Kasahara N, Farzaneh F, Habib NA, Norris JS, Deisseroth, AB. Recent advances and current challenges in tumor immunology and immunotherapy. Mol Ther. 2007;15(6):1065-71. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006;314(5796):126-9. Ribeiro-Santos G. Quimioterapia do câncer: imunossupressão x imunoestimulação. Rev Inter Toxicol Risco Ambiental Soc. 2009;2(3):51-4. Yoon TJ, Kim TJ, Lee H, Shin KS, Yun YP, Moon WK, et al. Anti-tumor metastatic activity of beta-glucan purified from mutated Saccharomyces cereviase. Int Immunoparmacol. 2008;8(1):36-42.

Received in: 16/03/2017 Accepted for publication: 01/06/2017 Conflict of interest: none. Source of funding: none. Mailing address: Rossano Kepler Alvim Fiorelli E-mail: fiorellirossano@hotmail.com / cgarritano@gmail. com

Rev Col Bras Cir 2017; 44(5): 452-456


Original Article

DOI: 10.1590/0100-69912017005006

Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats Efeitos do dimetilsulfóxido e da pentoxifilina na vitalidade de retalhos cutâneos em ratos STEPHANIE LUZIA DA COSTA PEDRETTI1; CÍCERO DE LIMA RENA, ECBC-MG2; MARIA CHRISTINA MARQUES NOGUEIRA CASTÃNON2; ANA PAULA DO NASCIMENTO DUQUE2; FERNANDO HENRIQUE PEREIRA1; TARCIZO AFONSO NUNES1. A B S T R A C T Objectives: to verify the influence of dimethylsulfoxide and pentoxifylline on the vitality of cutaneous flaps in rats and the tissue repair process. Methods: were studied 30 Wistar rats, submitting them to a 2cm wide by 8cm long dorsal cutaneous flap, of caudal base. We distributed the animals in three groups: Control Group (n=10) with application gauze moistened with 0.9% Saline in the flap bed for 30 seconds; Dimethylsulfoxide group (n=10), with administration of 1ml of 5% dimethylsulfoxide divided into five injections of 0.2ml in the transition of the flap segments; Pentoxifylline group (n=10), with administration of pentoxifylline 20mg/kg, diluted to 1ml and divided into five injections of 0.2ml in the transition of the flap segments. Drugs were administered intraoperatively, in a single dose and subcutaneously. We observed the skin flaps for changes in color and texture. On the 10th postoperative day, we checked the dimensions of viable and necrotic tissues, followed by excision of the specimen for histological analysis. Results: the measurements of length of the viable and necrotic tissues between groups showed no differences. Histological analysis showed that the Dimethylsulfoxide group presented neovascularization, inflammatory infiltrate with leukocytes and more structured conjunctival stroma. The Pentoxifylline group showed neovascularization and inflammatory infiltrate, with moderate to intense granulation. The control group evolved with a higher rate of necrosis in the distal segment. Conclusion: dimethylsulfoxide and pentoxifylline influenced the vitality of the flap and the tissue repair process. However, they did not prevent necrosis macroscopically. Keywords: Wound Healing. Dimethyl Sulfoxide. Pentoxifylline. Rats. Surgical flaps.

INTRODUCTION

C

utaneous flaps are one of the pillars of reconstructions in the specialty of Plastic Surgery. A surgical resource widely used in situations of tissue loss of the integumentary system due to trauma, tumor resection and ischemia, it can present several complications, among them, hematoma, infection, dehiscence and necrosis. The cutaneous flap consists of elevation, detachment and repositioning in the bed, a procedure that can induce a series of events, among which vascular deficit, with reduced perfusion, for a variable and transient period1. In addition to partial interruption of blood flow, the venous return in the dermal and subdermal plexus is impaired. Venous occlusion or congestion can be damaging to the vitality of the flap. Lym-

phatic vessels are also injured, resulting in interstitial edema, contributing to the reduction of capillary perfusion. The sensory and sympathetic nerves are injured with the flap elevation, which causes the release of catecholamines, inducing vasoconstriction and reduction of the local blood supply. It is important to note that the skin flap has to survive the events that occur during the period of reduced perfusion1. The ischemia of the cutaneous flap on the more distal area of vascular supply, especially in the distal segment, even if fleeting and for a short period, can generate reactive oxygen species. The mechanism involved in reperfusion, with the restoration of vascular supply and oxygen influx in the ischemic tissue, can culminate in cellular, inflammatory and metabolic changes mediated by free radicals, with structural and

1 - Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. 2 - Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil. Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

458

functional modifications in the cell, which may contribute to tissue necrosis2-7. This event requires organic adaptations and, where possible, the use of antioxidant drugs may reduce the toxic metabolites responsible for tissue damage. Simultaneously with the events described with surgical trauma and elevation of the flap, an inflammatory process mediated by kinins, serotonin and histamine occurs, resulting in increased microcirculation permeability, with tissue edema, which impairs perfusion and contributes to decrease vascularization in the distal segment of the flap7. Post-trauma tissue edema may last from four to 24 hours8-10. Partial or total skin flap necrosis may require other surgical interventions, which is a challenging situation for the surgeon. Several experimental studies have used drugs to attenuate the formation of reactive oxygen species and tissue edema, and to stimulate tissue repair7, such as hyaluronidase8, dimethylsulfoxide9,11-13, sildenafil10, pentoxifylline6,14-16, streptokinase and allopurinol17, L-arginine18, Kaurenoic acid19 and latex sap of Hevea brasiliensi20. Dimethylsulfoxide has an analgesic and anti-inflammatory effect, acts on coagulation, mainly in the cascade of arachidonic acid, is an inhibitor of platelet aggregation and acts as a subdermal vasodilator, antioxidant, free radical scavenger, protecting from the ischemia-reperfusion phenomenon2,5,9,11-13,19. Pentoxifylline has hemorheological properties, increases erythrocyte deformability and acts on the coagulation cascade, with thromboxane release and increased prostacyclin synthesis. As an important vasodilator, it acts on the morphological and biochemical immunomodulation mechanism and contributes to decrease reactive oxygen species4,6,14-16,19. The present study aims to evaluate the effects of dimethylsulfoxide (DMSO) and pentoxifylline (PTFL) on the vitality of skin flaps in rats.

METHODS We studied 30 male, non-isogenic Wistar rats (Rattus norvegicus, Rodentia Mammalia), with a mean age of three months and a mean weight of 302 grams,

acquired by the Reproduction Biology Center (CBR) of the Federal University of Juiz de Fora - MG (UFJF-MG). We followed the ethical principles in animal experimentation according to the Brazilian College of Animal Experimentation (COBEA). All protocols and procedures are in accordance with Federal Law No. 11.734 of 10/08/200821-23 and the project was approved by the Ethics in Research Committee of the Federal University of Minas Gerais, according to protocol 251/2013. We divided the sample into three groups, distributed as follows: Control group (n=10): gauze moistened with 0.9% saline solution in the flap bed for 30 seconds; DMSO group (n=10): injection of 1ml of 5% dimethylsulfoxide divided into five injections of 0.2ml in the transition of the flap segments; PTFL group (n=10): injection of pentoxifylline 20mg/kg, diluted with bidistilled water to complete the volume of 1ml and divided into five injections of 0.2ml in the transition of the flap segments. We anesthetized the animals with 90 mg/kg of 5% ketamine hydrochloride, associated with 10mg/ kg of 2% xylazine intraperitoneally20. We marked the flap on the back of the animals with a blue pilot overhead and a millimeter ruler, of 2cm x 8cm (16 cm2), according to the McFarlaneâ&#x20AC;&#x2122;s rectangular flap, with caudal base vascular supply3,8,11. We divided the flaps in every 2.6cm into proximal, intermediate and distal segments, and performed flap dissection up to the fleshy pannicus, including it. We submitted all the animals to the procedure with the same technique and, after elevation of the flap, we administered the drugs. We intraoperatively injected the flap borders in a single, subcutaneous dose, with 1-ml syringe, 3-mm needle, as follows: two injections of 0.2ml on the right side and two injections on the left side, at the transition of the proximal and intermediate segment and at the transition of the intermediate and distal segment, and one injection of 0.2ml at the center of the distal segment (Figure 1). Then, we repositioned the flap in the bed and sutured it with single, separated stitches of 4.0 monofilament nylon, 0.5cm distant from each other. We used no antibiotic and made no dressings. We observed the animals daily, evaluating the behavior, weight and aspect of the flap. We measured the total and viable tissue lengths with the anes-

Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

thetized animal prior to the procedure. Total size and necrotic tissue size were measured with the anesthetized animal on the day of euthanasia. The same observer performed all the measurements, with a millimeter ruler. We considered a macroscopic aspect of viable tissue to be one with normal coloration and texture or with few changes in the superficial skin layer, and necrosis, when the skin had a hard texture, dark color and crust24.

Figure 1. Drug Administration Scheme.

On the 10th postoperative day, we euthanized the animals under anesthesia with 180mg/kg 5% ketamine and 20mg/kg 2% xylazine23. We resected the flap specimen, which was adhered in a filter paper mold and placed in 10% neutral buffered formaldehyde solution for 48 hours for fixation. The specimen was duly identified and sent for histological analysis, which was performed in 4-Âľm thickness sections stained with hematoxylin and eosin. The steps were carried out at the Pathology Laboratory of the Holy Home of Mercy of Juiz de Fora, MG, and in the Department of Morphology of the Biological Sciences Institute of the Federal University of Juiz de Fora, MG, by an observer unknown to the group of the sample studied. An Olympus BX 51 microscope was used. The histological study of the flap was done in order to evaluate the evolution of the tissue repair process and the effect of dimethylsulfoxide and pentoxifylline on their vitality7,10,25,26. In the qualitative analysis of each sample of proximal, intermediate and distal segment, we observed the epidermis, layers of the dermis and the layers of the fleshy paniculus. The presence of neoformed vessels and leukocyte inflammatory infiltrate was considered granulation, and necrosis was the presence of devitalised elements.

459

The categorical variables were: granulation, granulation with leukocytes, granulation and/or necrosis, analyzed in the central portion of the proximal, intermediate and distal segments, respectively10,25,26. We divided the variables into six categories, assigning the respective scores and descriptions of each, according to the histological findings: a) ABSENT (score= 0) - absence of vessels and cellular elements of granulation; b) DISCRETE (score= 1) - granulation with few vessels, collagen fibers and sparse leucocytes in the optical field; c) MODERATE (score= 2) - granulation with greater frequency of dispersed vessels in the field and of collagen fibers, and leukocytes forming aggregates, with areas free of infiltration; d) INTENSE (score= 3) - granulation with vessels arranged in the whole field, collagen fibers and leucocytes with dense aggregate, without areas free of infiltrate; e) INTENSE + NECROSIS (score= 4) - granulation with vessels arranged throughout the field, collagen fibers and leukocytes forming a dense aggregate, without an area free of infiltrate, with areas of necrosis, intercalated or close to the granulation tissue, called granulation and necrosis foci; f) NECROSIS (score= 5) - fields full of devitalized elements, frequently evidenced, called necrosis. The image capture of the slides was performed at the Genetics Laboratory of UFJF-MG, with the CyberneticsÂŽ Image-Pro Plus 4.5 software, coupled to the Olympus BX 51 microscope, in 25x, 40x and 100x magnifications. The photographic documentation of the animals was performed in all stages of the experiment on the same days, D1, D3, D5, D7 and D10, in all groups, by the same observer, with a professional digital camera Cannon EF 100 mm, 1:2:8 USM - Tokyo - Japan. We calculated the sample size with significance level between 0.01 and 0.05, coefficient of variation of 15 to 20% for differences between the treated and control groups17. We performed the statistical study of the variables of the three groups with the software Statistical Package for Social Sciences (SPSS)18, and analyzed the categorical variables of the histological analysis with the software R Core version 3.0.1 (2013: 05.16), both with the contribution of the Biostatistical Support Nucleus of the Faculty of Medicine of UFMG. We analyzed the pairs of means different from the categorical

Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

460

variables studied with the ANOVA and Fisher’s exact tests. The associations between the control, DMSO and PTFL groups were interpreted and clarified. The adjusted residue was equal to or greater than 1.96, when there was a significant association between the group variable and the category and p value <0.05.

RESULTS Four animals died in the immediate postoperative period, three in the PTFL group and one in the control group. On the 10th postoperative day, one animal of the DMSO group had clear fluid and trabeculae in the flap bed, suggestive of infection. We replaced these five animals. At

clinical observation until the 10th day, the animals in the experiment showed no signs of suffering, such as bent posture, behavioral changes, ocular or nasal secretion, hair bruising and diarrhea. They accepted food and water routinely. The aspect of the cutaneous flap varied from pallor, cyanosis to necrosis. The texture in the distal segment was gradually modified in all groups, becoming hardened, with crusts, with subtle differences between the DMSO and PTFL groups. We observed the delimitation of tissue necrosis on the seventh postoperative day. We submitted the measurements of the total flap size, viable tissue size and necrotic tissue size of each animal, as well as the equivalent percentages among the three groups, to the ANOVA test, which did not significant differences, with (p>0.05 - Table 1).

Table 1. Means and standard deviations (SD) of the flap dimensions and p-value.

Dimension of the skin flap

p

Control

DMSO

PTFL

Mean (SD)

Mean (SD)

Mean (SD)

Overall dimension (cm)

7.16 (±0.00)

(6.98±0.36)

6.87 (±0.30)

0.240

Viable tissue (cm)

3.81 (±0.53)

3.85 (±0.75)

(3.69±0.51)

0.831

Necrotic tissue (cm)

3.35 (±0.47)

(3.13±0.63)

3.18 (±0.47)

0.630

Viable tissue (%)

53.17 (±6.40)

53.98 (±10.03)

53.69 (±6.87)

0.973

Necrotic tissue (%)

46.37 (±6.40)

45.37 (±9.24)

45.41 (±6.96)

0.888

The frequency in absolute numbers of the variables granulation and granulation/leukocytes in the proximal and intermediate segments was not significant (p>0.05. The control group presented the variable granulation/necrosis, with three cases of intense granulation (score= 3), one with intense granulation and necrotic foci (score= 4) and six with necrosis alone (score= 5). The DMSO group presented, in the variable granulation/necrosis, three cases of intense granulation (score= 3) and seven with intense granulation and necrotic foci (score= 4). The PTFL group presented, in the variable granulation/ necrosis, three cases with moderate granulation (score= 2), five with intense granulation (score= 3) and only two with intense granulation with necrotic foci (score= 4). The frequency in absolute numbers of the variable granulation/necrosis in the distal segment in the control, DMSO and PTFL groups were significant (p=0.0004791). No spe-

cimen from the DMSO or PTFL groups displayed necrosis (score= 5) when compared with the control group, which had six cases of necrosis (p=0.0004791). These results suggest effects of the drugs on tissue repair (Table 2). Figure 2 shows photomicrographs of the histological section of the distal segment of the control group, where there is inflammatory infiltrate and predominance of vacuoles, edema and necrosis. Figure 3 shows a histological section photomicrograph of the distal segment of the DMSO group with elements with intense inflammatory infiltrate with necrotic foci and neovascularization, structured connective tissue stroma. Figure 4 depicts a histological section photomicrograph of the distal segment of a PTFL group specimen, showing moderate inflammatory infiltrate, neovascularization and absence of necrosis. All specimens were analyzed with a 100x magnification and hematoxylin and eosin staining.

Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

461

Table 2. Scores assigned in histological evaluation.

Variable/Group

Score (category)

Control

DMSO

PTFL

p

Granulation

Absent (0)

5

9

5

0.124

Discreet

5

1

5

Discrete (1)

5

7

4

Moderate (2)

5

3

5

Intense (3)

0

0

1

Moderate (2)

0

0

3*

Intense (3)

3

3

5*

Intense/necrosis (4)

1

7*

2

Necrosis (5)

6*

0

0

Granulation/ Leukocytes

Granulation/ Necrosis*

0.643

0.0004791

* statistical significance

DISCUSSION

Figure 2. Photomicrography of control group specimen: (i) inflammatory infiltrate, edema, necrosis, HE-100x.

Figure 3. Photomicrography of DMSO group specimen: neoformed vessels, inflammatory infiltrate, H.E-100x.

Figure 4. Photomicrography of PTFL group specimen: neoformed vessels, inflammatory infiltrate, H.E-100x.

The choice of the rat for the experiment in this research was due to the ease of animal acquisition, simple handling, low cost and feasible conditions for research. Moreover, this animal is widely used as a model in research1,4,8,9,11,14,16. The McFarlane skin flap was standardized with a caudal base vascular supply and we created a difficult condition of venous return, favoring tissue edema, increased capillary pressure and consequent increase in necrosis, thus allowing investigation of the influence of the possible effects of DMSO and PTFL on tissue repair and on the vitality of the flap in face of such conditions3,8,11,24,27-29. Studies indicate that the tissue dimensions with cutaneous necrosis get delimited on the seventh postoperative day24. In the present work we decided to maintain the clinical observation of the animals for ten days, considering that Almeida et al.9, in 2004, reported that the period required for the reorganization of the vascular supply of the flap was nine days. Drug administration was performed with a 3-mm needle to reduce local trauma, and the volume of 1ml, not to cause edema and to avoid the reduction of perfusion. We chose the subcutaneous route because of the better dispersion of the substance, since it is easily accessible, capable of obtaining an adequate level of concentration in the tissues adjacent to the flap, with little systemic absorption, thus increasing admi-

Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

462

nistration safety9. We did not find in the literature a study with PTFL administration, but only the Almeida9 study, with subcutaneous DMSO. The reperfusion of the ischemic area can lead to the formation of reactive oxygen species that cause tissue damage and culminate with necrosis4. Oxidative stress, a result of this process, starts from the first minutes after trauma and can be one of the factors responsible for cell death, with tissue loss, mainly in the flap’s distal segment. We believe that surgical trauma, such as the flap confection, causes an endogenous imbalance in the formation of reactive oxygen species from the first postoperative minutes. We rely on the premise that oxidative stress occurs early in the surgical trauma, and has repercussions throughout the flap healing, which is why we decided to perform the injections of drugs intraoperatively in a single dose1,2,4,9,10. In previous research, it was found that antioxidant substances21, as well as DMSO and PTFL, can act favorably and early in the operative wound1,4,5,6,9,11-16,19. The intermediate segments of the flap are those called the “transition zone”, since they are between the proximal portion, where the survival of the flaps is expected due to the proximity of the vascular supply, and the distal portion, where necrosis can occur due to the distance from the blood supply. These areas submitted to a period of ischemia and subsequent reperfusion are those in which the pharmacological intervention can modify the flap’s evolution. The purpose is to improve the vitality of the flap through

the vasodilation in the microcirculation and increase the perfusion pressure with consequent benefit to the tissues10. Since DMSO and PTFL have antioxidant properties, the research proposal was to administer them subcutaneously and to evaluate the effects on the flap’s tissue repair. We observed histological features of granulation, such as exuberant neovascularization, inflammatory infiltrate with leukocytes in the PTFL group, and more structured conjunctival stroma with neovascularization in the DMSO group, in addition to the absence of necrotic specimens in the group treated with PTFL25,26. We observed necrosis in 60% of the specimens in the distal segment of the control group animals. This research envisaged a horizon for the use of DMSO and PTFL to expand effective strategies to improve the vitality of cutaneous flaps, reducing or even avoiding necrosis. These drugs are affordable and available for therapeutic use in skin flaps. It is necessary to dedicate new researches to promoting knowledge about the safety and the tissue modifications under the influence of these drugs and, thus, to extrapolate their use for medical practice. Our study demonstrated that DMSO and PTFL influenced the vitality of the skin flap and the tissue repair process in rats. The animals treated with these drugs had neovascularization and infiltrate with leukocytes statistically superior to those observed in the control group animals, which expressed devitalized tissues. However, they did not prevent macroscopic necrosis.

R E S U M O Objetivos: verificar a influência do dimetilsulfóxido e da pentoxifilina na vitalidade e no processo de reparo tecidual de retalhos cutâneos em ratos. Método: foram estudados 30 ratos Wistar, nos quais foi confeccionado retalho cutâneo dorsal de 2cm de largura por 8cm de comprimento, de base caudal, e distribuídos em três grupos: Grupo Controle (n=10) com aplicação de gaze umedecida com solução salina a 0,9%, no leito do retalho, por 30 segundos; Grupo dimetilsulfóxido (n=10) com injeção de 1ml de dimetilsulfóxido a 5% divididos em cinco injeções de 0,2ml na transição dos segmentos do retalho; Grupo pentoxifilina (n=10) com injeção de 1ml pentoxifilina 20mg/kg, divididos em cinco injeções de 0,2ml na transição dos segmentos do retalho. Os fármacos foram administrados no transoperatório, em dose única e por via subcutânea. Os retalhos cutâneos foram observados quanto às alterações de cor e textura. No décimo dia de pós-operatório aferiu-se a dimensão do tecido viável e de necrose, seguido da exérese da peça para análise histológica. Resultados: a medida da dimensão de tecido viável e de necrose dos grupos não apresentou diferenças. A análise histológica mostrou que o grupo dimetilsulfóxido apresentou neovascularização, infiltrado inflamatório com leucócitos e estroma conjuntivo mais estruturado. O grupo pentoxifilina, mostrou neovascularização e infiltrado inflamatório com granulação moderada e intensa. O grupo controle evoluiu com maior índice de necrose no segmento distal. Conclusão: dimetilsulfóxido e pentoxifilina influenciaram na vitalidade do retalho e no processo de reparo tecidual. Entretanto, não evitaram a necrose macroscopicamente. Descritores: Cicatrização. Dimetil Sulfóxido. Pentoxifilina. Ratos. Retalhos Cirúrgicos.

Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

463

REFERENCES 13. 1.

Cymrot M, Percário S, Ferreira LM. Comportamento do estresse oxidativo e da capacidade antioxidante total em ratos submetidos a retalhos cutâneos isquêmicos. Acta Cir Bras. 2004;19(1):18-26. 2. Barreiros ALBS, David JM, David JP. Estresse oxidativo: relação entre geração de espécies reativas e defesa do organismo. Quím Nova. 2006;29(1):113-23. 3. Camargo CP, Margarido NF, Guandelini E, Vieira GA, Jacomo AL, Gemperli R. Description of a new experimental model skin flap for studying skin viability in rats. Acta Cir Bras. 2014;29(3):166-70. 4. Campos EBP, Yoshida WB. O papel dos radicais livres na fisiopatologia da isquemia e reperfusão em retalhos cutâneos: modelos experimentais e estratégias de tratamento. J Vasc Br. 2004;3(4):357-66. 5. Guimarães SB, Kimura OS, Vasconcelos PRL. Dimetilsulfóxido atenua a lesão de isquemia-reperfusão em testículo de ratos. Acta Cir Bras. 2010:25(4):35761. 6. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med. 2011;32(46):234-46. 7. Balbino CA, Pereira LM, Curi R. Mecanismos envolvidos na cicatrização: uma revisão. Rev Bras Cienc Farm. 2005;41(1):27-51. 8. Acevedo-Bogado CE, Bins-Ely J, D’Acampora AJ, Neves RE. Efeito da hialuronidase na sobrevida de retalhos cutâneos em ratas. Acta Cir Bras. 2002;17(Suppl. 1):14-6. 9. Almeida KG, Fagundes DJ, Manna MCB, Montero EFS. Ação do dimetil-sulfóxido na isquemia de retalhos randômicos de pele em ratos. Acta Cir Bras. 2004;19(6):649-57. 10. Barral SM, Araújo ID, Vidigal PV, Mayrink CA, Araujo AD, Costa PR. Effects of sildenafil on the viability of random skin flaps. Acta Cir Bras. 2011; 26(4):314-9. 11. Adamson JE, Horton CE, Crawford HH, Ayers WT Jr. The effects of dimethyl sulfoxide on the experimental pedicle flap: a preliminary report. Plast Reconstr Surg. 1966;37(2):105-10. 12. Celen O, Yildirim E, Berberoglu U. Prevention of wound edge necrosis by local application of dimethylsulfoxide.

14.

15.

16.

17.

18.

19.

20.

21.

22.

Acta Chir Belg. 2005;105(3):287-90. Melo JUDS, Vasconcelos PRLD, Santos JMV, Campos Júnior MM, Barreto MVA, Kimura ODS. Efeitos do dimetilsulfóxido no estresse oxidativo e na regeneração hepática pós-hepatectomia em ratos. Rev Col Bras Cir. 2008;35(2):103-8. Babaei S, Bayat M, Nouruzian M, Bayat M. Pentoxifylline improves cutaneous wound healing in streptozotocininduced diabetic rats. Eur J Pharmacol. 2013;700(13):165-72. Brasileiro JL, Fagundes DJ, Miiji LON, Oshima CTF, Teruya R, Marks G, et al. Isquemia e reperfusão de músculo sóleo de ratos sob ação da pentoxifilina. J Vasc Bras. 2007;6(1):50-63. Leal PR, Cammarota MC, Sbalchiero J, Marques MM, Moreira M. Efeitos da pentoxifilina e o cloridrato de buflomedil em retalhos randomizados em ratos sob influência da nicotina. Rev Soc Bras Cir Plast. 2004;19(3):31-42. Moura T, Marques AA, Bernal SO, Gagliocca GD, Gemperli R, Ferreira MC. Estudo da ação da estreptoquinase e do alopurinol em retalhos cutâneos em ilha submetidos à isquemia prolongada: estudo experimental em ratos. Rev Assoc Med Bras. 2009;55(5):601-5. Guimarães MVTN, Moreira GHG, Rocha LP, Nicoluzzi JEL, Souza CJF, Repka JCD. Ação da l-arginina na evolução de retalhos cutâneos de ratos sob exposição à nicotina. Rev Col Bras Cir. 2013;40(1):49-54. Silva JJ, Pompeu DG, Ximenes NC, Duarte AS, Gramosa NV, Carvalho KM, et al. Effects of kaurenoic acid and arginine on random skin flap oxidative stress, inflammation, and cytokines in rats. Aesthetic Plast Surg. 2015;39(6):971-7. Penhavel MVC, Tavares VH, Carneiro FP, Sousa JBD. Effect of Hevea brasiliensis latex sap gel on healing of acute skin wounds induced on the back of rats. Rev Col Bras Cir. 2016;43(1):48-53. Eckelman WC, Kilbourn MR, Joyal JL, Labiris R, Valliant JF. Justifying the number of animals for each experiment. Nucl Med Biol. 2007;34(3):229-32. Damy SB, Camargo RS, Chammas R, Figueiredo LFPD. Aspectos fundamentais da experimentação animal: aplicações em cirurgia experimental. Rev Assoc Med Bras. 2010;56(1):103-11.

Rev Col Bras Cir 2017; 44(5): 457-464


Pedretti Effects of dimethylsulfoxide and pentoxifylline in the vitality of cutaneous flaps in rats

464

23. Universidade Federal de Minas Gerais. Comitê de Ética em Experimentação Animal. Protocolos anestésicos comumente utilizados em animais de pequeno porte. Belo Horizonte: CETEA-UFMG; 2012. 24. Pace D, Campos AC, Graf R. Efeito de substâncias antioxidantes (vitamina C, vitamina E e gingko biloba) na viabilidade de retalho cutâneo dorsal em ratos. Rev Soc Bras Cir Plast. 2006;21(2):77-81. 25. Garros IC, Campos ACL, Tâmbara EM, Tenório SB, Torres OJM, Agulham MA, et al. Extrato de Passiflora edulis na cicatrização de feridas cutâneas abertas em ratos: estudo morfológico e histológico. Acta Cir Bras. 2006;21(Supll. 3):55-65. 26. Martins NLP, Malafaia O, Ribas-Filho JM, Heibel M, Baldez RN, Vasconcelos PRL, et al. Análise comparativa da cicatrização da pele com o uso intraperitoneal de extrato aquoso de Orbignya phalerata (babaçu). Estudo controlado em ratos. Acta Cir Bras. 2006;21(Suppl 3):66-75. 27. Costa W, Silva AL, Costa GR, Nunes TA. Histology

of the rectus abdominis muscle in rats subjected to cranial and caudal devascularization. Acta Cir Bras. 2012;27(2):162-7. 28. Ohara H, Kishi K, Nakajima T. Rat dorsal paired island skin flaps: a precise model for flap survival evaluation. Keio J Med. 2008:57(4):211-6. 29. Kelly CP, Gupta A, Keskin M, Jackson IT. A new design of a dorsal flap in the rat to study skin necrosis and its prevention. J Plast Reconstr Aesthet Surg. 2010;63(9):1553-6. Received in: 06/04/2017 Accepted for publication: 25/05/2017 Conflict of interest: none. Source of funding: none. Mailing address: Stephanie Luzia da Costa Pedretti E-mail: stephanielcpedretti@yahoo.com.br / tan@medicina.ufmg.br

Rev Col Bras Cir 2017; 44(5): 457-464


Original Article

DOI: 10.1590/0100-69912017005007

Colon cancer surgery in patients operated on an emergency basis Cirurgia do câncer de cólon em pacientes operados de emergência RODRIGO FELIPPE RAMOS, TCBC-RJ1; LUCAS CARVALHO SANTOS JAQUELINE SUELEN SULZBACH2; RICARDO ARY LEAL, TCBC-RJ1.

DOS-REIS2;

BEATRIZ ESTEVES BORGETH TEIXEIRA2; IGOR MAROSO ANDRADE2;

A B S T R A C T Objective: to study the epidemiological profile of patients with colorectal cancer operated on an emergency basis at the Bonsucesso Federal Hospital. Methods: this is a retrospective study of patients operated between January 1999 and December 2012. We analyzed the following variables: age, gender, clinical data, TMN staging, tumor location, survival and types of surgery. Results: we evaluated 130 patients in the study period. The most frequent clinical picture was intestinal obstruction, in 78% of cases. Intestinal perforation was the surgical indication in 15%. The majority (39%) of the patients had advanced TNM staging, compared with 27% in the initial stage. There were 39 deaths (30%) documented in the period. The most common tumor site was the sigmoid colon (51%), followed by the ascending colon (16%). The curative intent was performed in most cases, with adjuvant treatment being performed in 40% of the patients. Distant metastases were found in 42% of the patients and 10% had documented disease recurrence. Disease-free survival at two and five years was 69% and 41%, respectively. Conclusion: there was a high mortality rate and a low survival rate in colorectal cancer patients operated on urgently. Keywords: Colorectal Neoplasms. Intestinal Obstruction. Intestinal Perforation. Colorectal Surgery. Emergencies.

INTRODUCTION

C

tion, but also by the advanced stage of the tumor found in such situations6. Perforation can occur in 3% to 8%

olorectal cancer (CRC) is the third most common type of cancer among men and the second among women1. It has a good prognosis when diagnosed in the early stages, with an overall mortality of 8.5%1. Mortality and morbidity are relatively low in electively operated patients, but in those operated in an emergency, there is a significant increase in these rates, as well as a reduction in survival over five years2-4. The most common clinical presentation in patients with CRC admitted to the emergency room is obstruction, followed by colon perforation5. It is estimated that approximately 10 to 19% of CRC patients will present obstruction at some point in the natural course of the disease6. This condition presents as a risk factor for a worse prognosis, with a mortality in the immediate postoperative period between 15 and 30% when compared with elective patients (1% to 5%)7. This fact is explained not only by the patients’ deterioration of the clinical status due to the obstructive emergency condi-

of cases8, and although it is a more serious condition and presents greater postoperative morbidity and mortality than colonic obstruction5, survival rates are similar in both situations9. The most commonly used surgical technique in patients with urgently operated CRC is the Hartmann’s procedure, because it is a safe technique, especially in patients with a high surgical risk9. However, this technique causes several problems of both psychosocial and colostomy-related care. Furthermore, it demands another surgical procedure for the reconstruction of intestinal transit, which also presents considerable morbidity10. Although it is a cancer type with a relatively good prognosis, mainly due to the natural history, its overall mortality remains high in Brazil11, especially in those patients operated on as an emergency8. This reflects the failure of CRC screening policies, with the diagnosis often made in advanced stages, with complications such as obstruction and perforation.

1 - Bonsucesso Federal Hospital, Rio de Janeiro, RJ, Brazil. 2 - Estácio de Sá University, Rio de Janeiro, RJ, Brazil. Rev Col Bras Cir 2017; 44(5): 465-470


Ramos Colon cancer surgery in patients operated on an emergency basis

466

The purpose of this paper is to demonstrate the reality of a reference hospital of to contribute both from the epidemiological point of view and in the promotion of protocols for tracking CRC.

METHODS We conducted an observational, retrospective, descriptive study at the II Surgery Clinic of the Bonsucesso Federal Hospital, with medical records of patients treated between January 1999 and December 2012. We included only the patients with CRC diagnosis operated on an emergency basis. We excluded patients operated due to colon obstruction or perforation by other diseases or by tumors not confirmed by anatomopathological examination. We also excluded patients with medium and low rectum tumors because of the different treatment modalities between the colon and rectum tumors. The variables analyzed were age, gender, clinical data, tumor location, type of surgery, whether curative or palliative, TNM staging, adjuvant treatment, presence of metastases, relapse, and type of intestinal reconstruction. The main outcomes were death and disease-free survival at two and five years. All data were collected and inserted in a specific data collection form and in MS Excel® spreadsheet and later analyzed with the Bioestat® software. We present quantitative variables as mean ± standard deviation, and qualitative ones, as frequency and percentage. This study was approved by the Ethics in Research Committee of the Bonsucesso Federal Hospital (opinion number 1,183,590).

stage IV (Figure 2). In 42% of cases, it was not possible to establish adequate staging. More than half (51%) of the tumors were located in the sigmoid colon, 16% in the ascending colon, 10% in the descending colon, 9% in the transverse colon, 8% in the cecum and 6% in the rectum (Figure 3).

Figure 1. Clinical presentation at admission.

Figure 2. TNM Staging.

RESULTS We evaluated a total of 130 patients in the study period, 55% female and 45% male. The mean age was 59.5 years. The most frequent clinical presentation on admission was intestinal obstruction (78%), followed by pain (72%) and weight loss (41%). Anemia (25%), perforation (15%), bleeding (11%), fistula (2%) and intussusception (1%) were also observed (Figure 1). As for TNM staging, 3% had stage I, 13% stage IIA, 3% stage IIB, 11% stage IIIB, 6% stage IIIC and 22%

Surgery had curative intent in 52% of the cases, whereas in 37% it was only palliative. In 11% it was not possible to determine the intention of treatment, if curative or palliative. Retrosigmoidectomy was the most performed surgery (39%), followed by right hemicolectomy (29%), left hemicolectomy (14%), derivative colostomy (8%), total colectomy (4%), transversectomy (3%) and derivative ileostomy (3%) (Figure 4). As for the method chosen for reconstruction/maintenance of intestinal transit, terminal stoma was preferred, with 34%

Rev Col Bras Cir 2017; 44(5): 465-470


Ramos Colon cancer surgery in patients operated on an emergency basis

followed by simple primary anastomosis (26%), mucosal fistula (16%), derivative stoma (10%) and anastomosis with stoma protection (7%). In 7% of the cases, a procedure for reconstruction or maintenance of the intestinal transit was not required or possible (Figure 5). Adjuvant treatment was performed in 40% of cases. Individuals representing 25% of the series received no adjuvant treatment, and in 35% it was not possible to obtain information regarding this type of treatment.

467

period, even during hospital admission, totaling 39 deaths (30% of the total). We could not assess deaths due to reasons not related to CRC in the postoperative outpatient follow-up. There was a documented disease recurrence in 10% of patients, whereas in 29% of cases it was not possible to document disease recurrence. The presence of distant metastasis was documented in 42% of patients, either at the time of diagnosis or during follow-up. The most common site of distant metastases was the liver (20%), followed by peritoneum (11%), uterus and attachments (4%), abdominal wall (2%) and lung (1%). Other sites with less than 1% frequency accounted for 4% of metastases occurrences, whereas in 21% of cases it was not possible to determine the presence or absence of distant metastases. We could assess the disease-free survival at two years in 72 patients, being 69%. The five-year disease-free survival was 41%.

Figure 3. Tumor location.

Figure 5. Type of intestinal reconstruction.

DISCUSSION

Figure 4. Type of procedure.

There were twenty-six deaths (20% of the total sample) directly related to CRC during the postoperative follow-up. Thirteen deaths occurred for reasons not directly related to CRC in the postoperative

The estimate for 2016 is 16,660 new cases of colon and rectum cancer in men and 17,620 in women in Brazil11. Because of its high incidence in our country, CRC is one of the three malignant tumors that have screening policies advocated by the Ministry of Health, along with neoplasms of the breast and cervix. Despite this, screening for colon cancer is not routinely applied, due to the lack of access to health services by the general population. Some studies have already demonstrated the relationship between the effectiveness of screening po-

Rev Col Bras Cir 2017; 44(5): 465-470


Ramos Colon cancer surgery in patients operated on an emergency basis

468

licies with staging of the colorectal tumor at the time of diagnosis, and consequently the impact on complications such as obstruction, perforation, and on mortality12,13. According to the literature, 7% to 40% of CRCs will undergo emergency surgery, mainly due to obstruction or perforation14. Mortality is high in these patients, ranging from 16% to 38%14, being two to four times greater than in electively managed individuals15. However, there is controversy in these data, since most of these studies do not define the degree of obstruction, whether partial or total, reflecting the discrepancy in the percentage of mortality in the various articles. The high mortality in emergency surgeries is multifactorial6. A multivariate analysis revealed, as independent risk factors for mortality, besides surgical urgency, advanced CRC, age greater than 70 years, presence of important comorbidities, presence of sepsis and blood transfusion in the perioperative period5. However, among these factors, undoubtedly the one that has the greatest impact on mortality is staging. Biondo et al.16 observed that in patients submitted to elective surgery with curative intent, about 13% had stage I, 58% stage II and 29% stage III. In patients submitted to emergency surgery, 5% had stage I, 44% stage II and 51% stage III. For stage II patients, there was no statistically significant difference in survival between elective and urgent procedures. In patients with stage III, there was a higher mortality in the emergency surgery subgroup. In our study, perioperative mortality was 10% (13 patients). In agreement with literature data, we believe that this high mortality is more related to the disease advanced staging than to the clinical conditions related to the urgency of the surgery, since all had advanced disease (stage III or IV). In the postoperative follow-up, there were 26 deaths (20%) related to CRC, with a two-year survival of 69%, and 17% survival in five years. These results, however, should be viewed with great caution due to the great loss of follow-up of the patients, inherent in studies of this nature, and to the small sample of those who completed the follow-up periods. Likewise, there was loss of access to patients who died for reasons other than CRC, since many seek other medical care units other than the Oncology Surgery Outpatient Clinic or our Hospital’s Emergency Room. Another study with longer follow-up may provide better scientific evidence on these variables.

Regarding treatment, resection, for curative or palliative purposes, was the most adopted option (89%). In those patients in whom derivative stoma was performed (11%), the reason was tumor unresectability or lack of clinical conditions for resection. The achievement of a temporary derivative stoma for subsequent elective tumor resection (two-stage surgery) is not adopted in our service, nor is it recommended by most authors in the literature. When the tumor is resected at the first moment, there is lower postoperative mortality, shorter hospitalization time and greater disease-free survival in five years, demonstrating that the main factor related to tumor recurrence is the adoption of the basic oncological principles, not the emergency situation itself, when compared with two-time surgery17. While in the right colon tumors the primary anastomosis was the procedure of choice for reconstruction of the intestinal transit, in the tumors of the left colon and high rectum, the Hartmann’s procedure was the most adopted. In fact, it is well established in the literature that the primary ileo-transverse anastomosis is safe, even under conditions of fecal peritonitis18, with low dehiscence rates, ranging from 0.5% to 4.6%19. In the tumors of the left colon, there is still some controversy about the best surgical procedure to be adopted. While it is common sense that the Hartmann’s surgery is the procedure of choice in critically ill patients or patients with generalized fecal peritonitis, this is not the case in stable, low-risk patients. Some authors20 advocate that, in these patients, primary anastomosis with or without stoma protection is the procedure of choice, in view of the need for a second surgery for reconstruction of the transit and that about 40 to 60% of patients will not have the possibility of performing it, for several reasons, thus affecting quality of life21,22. Others, however, share the idea that Hartmann’s surgery is the safest in emergency surgery for CRC, since as well as providing R0 resections, does not have the potential for anastomotic dehiscence9. Like a third group of authors23, we believe that primary anastomosis resection and Hartmann’s surgery are not competing procedures, but two proposals that should be used according to the clinical situation. We understand that in our country, where a great part of such surgeries is performed by surgeons still in formation

Rev Col Bras Cir 2017; 44(5): 465-470


Ramos Colon cancer surgery in patients operated on an emergency basis

and in places with few resources, the Hartmann’s surgery should be the option in the great majority of cases, the resection with primary anastomosis being restricted to very specific situations. The placement of transtumoral endoscopic prostheses as a measure of palliation or temporary colonic clearance has the advantage of being a less morbid procedure than the Hartmann’s surgery or a derivative

469

colostomy6,16, but we do not have such resources in our Service. Our study allowed us to verify that the mortality in patients with CRC operated on an emergency basis is still quite high, with the disease presenting in advanced stages. These data reflect flaws in CRC screening policies that would make early diagnosis and treatment of this disease possible.

R E S U M O Objetivos: estudar o perfil epidemiológico de pacientes com câncer colorretal operados em caráter de urgência no Hospital Federal de Bonsucesso. Métodos: estudo retrospectivo de pacientes operados entre janeiro de 1999 e dezembro de 2012. Foram analisadas as seguintes variáveis: idade, sexo, dados clínicos, estadiamento TMN, localização do tumor, sobrevida e tipos de cirurgia. Resultados: foram avaliados 130 pacientes no período do estudo. O quadro clínico mais observado foi a obstrução intestinal, em 78% dos casos. Perfuração intestinal foi a indicação cirúrgica em 15%. A maior parte (39%) dos pacientes apresentava estadiamento TNM avançado da doença, contra 27% em estágio inicial. Houve 39 óbitos (30%) documentados no período. A localização mais comum da doença foi no cólon sigmoide (51%), seguido do cólon ascendente (16%). A intenção curativa foi realizada na maioria dos casos, sendo o tratamento adjuvante realizado em 40% dos pacientes. Metástases à distância foram encontradas em 42% dos pacientes e 10% apresentaram recidiva documentada da doença. A sobrevida livre de doença em dois e cinco anos foi de 69% e 41% respectivamente. Conclusão: houve alta mortalidade e baixa sobrevida em pacientes com câncer colorretal operados de urgência. Descritores: Neoplasias Colorretais. Obstrução Intestinal. Perfuração Intestinal. Cirurgia Colorretal. Emergências.

REFERENCES 1.

2.

3.

4.

5.

6. 7.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-86. Sjo OH, Larsen S, Lunde OC, Nesbakken A. Short term outcome after emergency and elective surgery for colon cancer. Colorectal Dis. 2009;11(7):733-9. Alves A, Panis Y, Mathieu P, Mantion G, Kwiatkowski F, Slim K; Association Française de Chirurgie. Postoperative mortality and morbidity in French patients undergoing colorectal surgery: results of a prospective multicenter study. Arch Surg. 2005;140(3):278-83. McArdle CS, Hole DJ. Emergency presentation of colorectal cancer is associated with poor 5-year survival. Br J Surg. 2004;91(5):605-9. Alvarez JA, Baldonedo RF, Bear IG, Truán N, Pire G, Alvarez P. Presentation, treatment, and multivariate analysis of risk factors for obstructive and perforative colorectal carcinoma. Am J Surg. 2005;190(3):376-82. Gainant A. Emergency management of acute colonic cancer obstruction. J Visc Surg. 2012;149(1):e3-e10. Rault A, Collet D, Sa Cunha A, Larroude D, Ndobo’epoy

F, Masson B. [Surgical management of obstructed colonic cancer]. Ann Chir. 2005;130(5):331-5. French. 8. Santos AC, Martins LLT, Brasil AMS, Pinto AS, Neto SG, Oliveira EC. Emergency surgery for complicated colorectal cancer in central Brazil. J Coloproctol. (Rio J.) 2014;34(2):104-8. 9. Charbonnet P, Gervaz P, Andres A, Bucher P, Konrad B, Morel P. Results of emergency Hartmann’s operation for obstructive or perforated left-sided colorectal cancer. World J Surg Oncol. 2008;6:90. 10. Banerjee S, Leather AJ, Rennie JA, Samano M, Gonzalez JG, Papagrigoriadis S. Feasibility and morbidity of reversal of Hartmann’s. Colorectal Dis. 2005;7(5):4549. 11. Instituto Nacional do Câncer José Alencar Gomes da Silva. Coordenação de Prevenção e Vigilância. Estimativa 2016: incidência de câncer no Brasil [Internet]. Rio de Janeiro: INCA, 2016 [citado em 2016 Out 27]. Disponível em: http://www.inca.gov.br/ estimativa/2016/estimativa-2016-v11.pdf 12. Mastalier B, Tihon C, Ghiţă B, Botezatu C, Deaconescu V, Mandisodza P, et al. Surgical treatment of colon cancer: Colentina surgical clinic experience. J Med Life. 2012;5(3):348-53.

Rev Col Bras Cir 2017; 44(5): 465-470


Ramos Colon cancer surgery in patients operated on an emergency basis

470

13. Altobelli E, D’Aloisio F, Angeletti PM. Colorectal cancer screening in countries of European Council outside of the EU-28. World J Gastroenterol. 2016;22(20):494657. 14. Chen HS, Sheen-Chen SM. Obstruction and perforation in colorectal adenocarcinoma: an analysis of prognosis and current trends. Surgery. 2000;127(4):370-6. 15. Kelley WE Jr, Brown PW, Lawrence W Jr, Terz JJ. Penetrating, obstructing, and perforating carcinoma of the colon and rectum. Arch Surg. 1981;116(4):381-4. 16. Biondo S, Martí-Ragué J, Kreisler E, Parés D, Martín A, Navarro M, et al. A prospective study of outcomes of emergency and elective surgeries for complicated colonic cancer. Am J Surg. 2005;189(4):377-83. 17. Cuffy M, Abir F, Audisio RA, Longo WE. Colorectal cancer presenting as surgical emergencies. Surg Oncol. 2004;13(2-3):149-57. 18. Bokey EL, Chapuis PH, Fung C , Hughes WJ, Koorey SG, Brewer D, et al. Postoperative morbidity and mortality following resection of the colon and rectum for cancer. Dis Colon Rectum. 1995;38(5):480-6. 19. Trompetas V. Emergency management of malignant acute left-sided colonic obstruction. Ann R Coll Surg Engl. 2008;90(3):181-6. 20. Villar JM, Martinez AP, Villegas MT, Muffak K, Mansilla

A, Garrote D, et al. Surgical options for malignant leftsided colonic obstruction. Surg Today. 2005;35(4):27581. 21. Zorcolo L, Covotta L, Carlomagno N, Bartolo DC. Safety of primary anastomosis in emergency colorectal surgery. Colorectal Dis. 2003;5(3):262-9. 22. Durán Giménez-Rico H, Abril Vega C, Herreros Rodríguez J, Concejo Cútoli P, Paseiro Crespo G, Sabater Maroto C, et al. Hartmann’s procedure for obstructive carcinoma of the left colon and rectum: a comparative study with one-stage surgery. Clin Transl Oncol. 2005;7(7):306-13. 23. Armbruster C, Kriwanek S, Roka R. [Spontaneous perforation of the large intestine. Resection with primary anastomosis or staged (Hartmann) procedure?]. Chirurg. 2001;72(8):910-3. German. Received in: 07/04/2017 Accepted for publication: 08/06/2017 Conflict of interest: none. Source of funding: none. Mailing address: Rodrigo Felippe Ramos E-mail: rofelippe@terra.com.br / rfelippe76@gmail.com

Rev Col Bras Cir 2017; 44(5): 465-470


Original Article

DOI: 10.1590/0100-69912017005008

Development of a laparoscopic training model using a smartphone Desenvolvimento de modelo treinamento em cirurgia laparoscópica com utilização de smartphone ANDRÉ TAKASHI OTI1; LUCAS NASCIMENTO GALVÃO, ACCBC-PA2; THYAGO CEZAR PRADO PESSOA2; CAMYLLA RODRIGUES DE OLIVEIRA ROCHA2; ANDREW MORAES MONTEIRO1; MAURO JOSÉ PANTOJA FONTELES1; MARCUS VINICIUS HENRIQUES BRITO, TCBC-PA1; EDSON YUZUR YASOJIMA, TCBC-PA1. A B S T R A C T Objective: to develop a model of training in video-surgery, of low cost and that uses a smartphone as an image-generating source. Methods: We developed a 38cm high, 40cm wide, 40cm long hexagonal-shaped training box, with a front opening of 12x8 cm for coupling the smartphone. The internal illumination is made with LED lamps and for the support of the smartphone, we used a selfie stick, fixed in the upper part of the box, that allows control of height, distance, angulation, and the coupling of devices with different formats. We selected 20 undergraduate students without previous training in video-surgery, who performed four exercises in the box, with assessment of the time and amount of errors in the execution of the tasks. Each student completed the training for three consecutive weeks. We collected the data in spreadsheets for later analysis. Results: Nineteen students completed the training program, with significant improvement in the times and in the number of errors. Conclusion: the developed model was feasible and promoted the acquisition of skills in this group of students. In addition, it presents low cost, is portable and uses common equipment, such as smartphones. Keywords: Surgery. Training. Education, Medical.

INTRODUCTION

S

ince the first laparoscopic cholecystectomy in 1987, video-surgery has spread rapidly because of the advantages over the conventional technique, such as reduction in hospitalization time and postoperative pain, as well as better aesthetic results1,2. Their increasing presence in the surgical routine, however, did not accompany the greater access to the method in the teaching centers. The main obstacles are the difficulty of access to materials and the high cost of equipment3,4. In addition, the method requires specific training to be performed safely5-8. Several models have been developed to meet this need. Despite the significant increase in the gain of abilities with such models, all used high-cost image sources, such as camcorders, webcams, tablets and laparoscopic optics9 11. Image capture equipment is usually expensive because it needs to be compact, lightweight, and produce images with quality and sharpness. An

appliance that has these characteristics is the smartphone, besides being present in everyday life, without the need of extra expenses with its acquisition. Its adaptation to a training box would represent an imaging source available at any time, which would allow recording and playback of training sessions. Thus, the objective of this work was to develop a model of a training box in video-surgery using a smartphone.

METHODS The study was approved by the Ethics in Research Committee on Human Subjects (CAAE: 48743115.0.0000.5174). We summoned students from the 1st to 5th year of medical schools in Belém (PA), of both genders, aged 16 to 25 years, through an online call. All signed the free and informed consent form and filled the questionnaire with basic personal information and academic background. We excluded students who participated in previous video-surgery training and those

1 - University of the State of Pará (UEPA), Belém, PA, Brazil. 2 - Cesupa, Belém, PA, Brazil. Rev Col Bras Cir 2017; 44(5): 471-475


Oti Development of a laparoscopic training model using a smartphone

472

who did not finish the training program.

Training box Made of recycled wood, which provides lightness and cost reduction, we developed a training box in hexagonal format to facilitate the entry angle of the tweezers and better ergonomics, measuring 38cm in height, 40cm in width and 40cm in length, with an opening of 12x8cm in the frontal region. We made the internal lighting with rechargeable LED lamps attached to the upper portion. As support for the Smartphone, we used a selfie stick, which allows control of height, distance, angulation, and enables the coupling of devices with different formats. We attached the selfie stick to the top of the box, allowing the capture of different angles of the interior of the prototype (Figure 1). We standardized, as an imaging source, an equipment with an eight-megapixel camera and a 4.6-inch screen.

right support with the ipsilateral hand clamp, pass to the left hand clamp and deposit on the pin on the contralateral side. After the transfer of all rings, the student carried out the exercise in the opposite direction.

Figure 2. Training platforms.

Wire path: The ring must travel through a wire path without touching it or being dropped. String passing: series of rings of the same size, fixed on a platform and queued in different positions. The student must take the string with the right tweezers, cross the string through the ring and capture it with the left tweezers, following a pre-established sequential course, in the shortest time possible. Knot making: the student must make a knot in three strings attached to a sponge in the shortest possible time.

Course Dynamics Figure 1. Training box in hexagonal format.

Exercises We adapted to the boxes four work platforms of well-established programs, such as the Fundamentals of Laparoscopic Surgery (FLS)12 and McGuil Inanimated System for Training and Evaluation of Laparoscopic Skills (MISTELS)13 (Figure 2). Objects transfer: consists of a platform with five pins on each side, with a ring inserted in one of the pins. The student must remove the ring from the

The students received initial guidance through video lessons with notions about the management of the instruments and demonstration of the exercises. Then they performed the first training, rested two minutes and started the second exercise, and so on. At the end of the fourth and last practices, there was a five-minute break to start the new cycle. The training was conducted during weekly sessions, for three consecutive weeks, with no time restrictions. In each week, three cycles of the same exercise were performed, and at the end of the course, each student performed nine times the same exercise. We measured the times in se-

Rev Col Bras Cir 2017; 44(5): 471-475


Oti Development of a laparoscopic training model using a smartphone

473

conds and the errors noted during the completion of each task by individual monitors.

Statistical analysis We compiled the data in Microsoft Excel® and submitted them to statistical analysis with the software Bioestat® 5.3. We used the ANOVA test for analysis of variance and the Student t test for analysis of significance between the times. We considered significant results those with p<0.05.

RESULTS

Figure 4 . Mean errors during the exercises. P1: practice 1, P2: practice 2,…, P9: practice 9.

We enrolled 62 students and selected 20, of whom 19 completed the training. Regarding the mean of the times in each exercise, we observed a significant improvement at the end of the course in relation to the initial time (Figure 3). There was a decrease in the number of errors in relation to the beginning of the program, besides stabilization in the acquisition of skills during the fourth practice, and significant improvement from that point on (Figure 4). The use of recycled wood, simple labor and the use of materials present in the daily life reduced the manufacturing costs of the boxes, which had a unit value of R$ 167.66 (about US$ 53.35).

Figure 3. Average execution times of the exercises. P1: practice 1, P2: practice 2,…, P9: practice 9.

DISCUSSION The training of the surgeon in video-surgery requires the acquisition of skills such as adaptation to

two-dimensional vision, due to loss of depth perception, limitation of movements and adequacy to the long instruments, characteristic of the method. The learning curve is also higher when compared with the conventional technique and the development of these skills can be done through simulator practices14-16. In the search for the ideal training model, several authors developed boxes with different characteristics, aiming at improvements such as portability, lower cost, availability and greater realism. At the same time, programs such as FLS12 and MISTELS13 have been created, based on tests of theoretical and practical knowledge, in order to enable professionals in the area. We based the present study on these programs, adapting them to the local reality, with the intention of developing a new, more accessible training model. The high cost of materials and equipment is still the main obstacle to the installation of laparoscopic training laboratories17, whether in colleges or medical residency programs. Several models in the literature have attempted to reduce costs through cheaper materials18,19, more accessible imaging sources17,20 and simpler open models21. There are publications of models similar to the one developed in this work, which use a smartphone as image source, but using another box format and made with other materials3,18,22. This equipment is designed with simple, low cost, portable material, and accessible at any time. Despite the simple model, there was a statistically significant improvement in all exercises, confirming

Rev Col Bras Cir 2017; 44(5): 471-475


Oti Development of a laparoscopic training model using a smartphone

474

the results of other studies with similar low cost and more accessible technology15,23. Willaert14, in a systematic review, found no difference in the acquisition of basic skills between simpler models compared with virtual reality simulators. In our study, the students achieved stabilization in the acquisition of skills in the fourth practice, without the need for several repetitions in each exercise, allowing training to be performed in a shorter period in the future24. Recent articles have demonstrated a higher frequency of training when there is greater flexibility of time and place, hence the importance of this model’s portability. Training centers where the si-

mulators are fixed prevent the displacement and, consequently, there is less adherence to training25,26. In the state of Pará, there are no routine courses in video-surgery training, which leads the student to move to other states in search of immersion courses, with very high costs. The development of an accessible training model and the creation of a local course could change this context. The training box with a smartphone promoted the acquisition of video-surgical skills in the group of students studied, thus providing an accessible and affordable alternative in undergraduate education and training, which can be applied to postgraduate surgery.

R E S U M O Objetivo: desenvolver modelo de treinamento em vídeo-cirurgia, de baixo custo e que utiliza smartphone como fonte geradora de imagem. Métodos: foi desenvolvida uma caixa de treinamento em formato hexagonal de 38cm de altura, 40cm de largura e 40cm de comprimento e com abertura na região frontal de 12x8 cm para acoplamento do smartphone. A iluminação interna é feita com lâmpadas de LED e para o suporte do smartphone foi utilizado um selfiestick, fixado na parte superior da caixa, que permite controle de altura, distância, angulação, e possibilita acoplamento de aparelhos com diferentes formatos. Foram selecionados 20 alunos de graduação, sem treinamento prévio em vídeo-cirurgia, que realizaram quatro exercícios na caixa com aferição do tempo e quantidade de erros na execução das tarefas. Cada aluno realizou o treinamento durante três semanas consecutivas. Os dados foram coletados em planilhas e analisados posteriormente. Resultados: dezenove alunos concluíram o treinamento, com melhora significante nos tempos e na quantidade de erros. Conclusão: o modelo desenvolvido mostrou-se viável e promoveu a aquisição de habilidades neste grupo de alunos. Além disso, apresenta baixo custo, é portátil e utiliza equipamento comum, como smartphones. Descritores: Cirurgia. Treinamento. Educação Médica.

REFERENCES 1.

2.

3.

4.

5.

Castro PM, Akelman D, Munhoz CB, Sacramento ID, Mazzurana M, Alvarez GA. Laparoscopic cholecystectomy versus minilaparotomy in cholelithiasis: systematic review and meta-analysis. Arq Bras Cir Dig. 2014;27(2):148-53. Cagir B, Rangraj M, Maffuci L, Herz BL. The learning curve for laparoscopic cholecystectomy. J Laparoendosc Surg. 1994;4(6):419-27. Couto RS, Veloso AC, Antunes FG, Ferrari R, Carneiro RGF. Device model for training of laparoscopic surgical skills. Rev Col Bras Cir. 2015;42(6):418-20. Moura Júnior LG. Modelo acadêmico de ensino teórico-prático em vídeo cirurgia por meio de novo simulador real de cavidade abdominal [dissertação]. Universidade Federal do Ceará: Fortaleza; 2015. Gardner AK, Willis RE, Dunkin BJ, van Sickle KR, Brown KM, Truitt MS, et al. What do residents need to be competent laparoscopic and endoscopic surgeons?

Surg Endosc. 2016;30 (7):3050-9. 6. Glassman D, Yiasemidou M, Ishii H, Somani BK, Ahmed K, Biyani CS. Effect of playing vídeo games on laparoscopic skills performance: a systematic review. J Endourol. 2016;30(2):146-52. 7. Marlow N, Altree M, Babidge W, Field J, Hewett P, Maddern GJ. Laparoscopic skills acquisition: a study of simulation and traditional training. ANZ J Surg. 2014;84(12):976-80. 8. Agha R, Fowler AJ. The role and validity of surgical simulation. Int Surg. 2015;100(2):350-7. 9. Kalvach J, Ryska O, Ryska M. [Existing laparoscopic simulators and their benefit for the surgeon]. Rozhl Chir. 2016;95(1):4-12. Czech. 10. Harenberg S, McCaffrey R, Butz M, Post D, Howlett J, Dorsch KD, et al. Can multiple object tracking predict laparoscopic surgical skills? J Surg Educ. 2016;73(3):386-90. 11. Stunt JJ, Wulms PH, Kerkhoffs GM, Dankelman J, van Dijk CN, Tuijthof G. How valid are commercially

Rev Col Bras Cir 2017; 44(5): 471-475


Oti Development of a laparoscopic training model using a smartphone

12.

13.

14.

15.

16.

17.

18.

19.

20.

available medical simulators? Adv Med Educ Pract. 2014;5:385-95. Soper NJ, Fried GM. The fundamentals of laparoscopic surgery: its time has come. Bull Am Coll Surg. 2008;93(9):30-2. Vassiliou MC, Ghitulescu GA, Feldman LS, Stanbridge D, Leffondré K, Sigman HH, et al. The MISTELS program to measure technical skill in laparoscopic surgery: evidence for reliability. Surg Endosc. 2006;20(5):7447. Willaert W, van de Putte D, van Renterghen K, van Nieuwenhove Y, Ceelen W, Pattyn P. Training models in laparoscopy: systematic review comparing their effectiveness in learning surgical skills. Acta Chir Belg. 2013;113(2):77-95. Vitish-Sharma P, Knowles J, Patel B. Acquisition of fundamental laparoscopic skills: is a box really as good as a virtual reality trainer? Int J Surg. 2011;9(8):65961. Newmark J, Dandolu V, Milner R, Grewal H, Harbison S, Hernandez E. Correlating virtual reality and box trainer tasks in the assessment of laparoscopic surgical skills. Am J Obstet Gynecol. 2007;197(5):546.e1-4. Martins JMP, Ribeiro RVP, Cavazzola LT. White box: caixa para treinamento laparoscópico de baixo custo. ABCD Arq Bras Cir Dig. 2015;28(3):204-6. Lee M, Savage J, Dias M, Bergersen P, Winter M. Box, cable and smartphone: a simple laparoscopic trainer. Clinical Teach. 2015;12(6):384-8. Aslan A, Nason GJ, Giri SK. Homemade laparoscopic surgical simulator: a cost-effective solution to the challenge of acquiring laparoscopic skills? Ir J Med Sci. 2015;185(4):791-6. Chen X, Pan J, Chen J, Huang H, Wang J, Zou L, et al. A novel portable foldable laparoscopic trainer for surgical education. J Surg Educ. 2016;73(2):185-9.

475

21. Yoon R, Del Junco M, Kaplan A, Okhunov Z, Bucur P, Hofmann M, et al. Development of a novel iPadbased laparoscopic trainer and comparison with a standard laparoscopic trainer for basic laparoscopic skills testing. J Surg Educ. 2015;72(1):41-6. 22. Pérez Escamirosa F, Ordorica Flores R, Minor Martínez A. Construction and validation of a low-cost surgical trainer based on iPhone technology for training laparoscopic skills. Surg Laparosc Endosc Percutan Tech. 2015;25(2):e78-82. 23. Madan AK, Frantzides CT. Substituting virtual reality trainers for inanimate box trainers does not decrease laparoscopic skills acquisition. JSLS. 2007;11(1):87-9. 24. Duarte RJ, Cury J, Oliveira LCN, Srougi M. Establishing the minimal number of virtual reality simulator training sessions necessary to develop basic laparoscopic skills competence: evaluation of the learning curve. Int Braz J Urol. 2013;39(5):712-9. 25. Thinggaard E, Kleif J, Flemming B, Strandbygard J, Gögenur I, Ritter EM, et al. Off-site training of laparoscopic skills, a scoping review using a thematic analysis. Surg Endosc. 2016;11(11):32-41. 26. van der Aa JE, Schreuder HW. Training laparoscopic skills at home: residents’ opinion of a new portable tablet box trainer. Surg Innov. 2015; 23(2):196-200.

Received in: 17/04/2017 Accepted for publication: 01/06/2017 Conflict of interest: none. Source of funding: none. Mailing address: Lucas Nascimento Galvão E-mail: lucasgalvao24988@gmail.com / and.oti@hotmail. com

Rev Col Bras Cir 2017; 44(5): 471-475


Original Article

DOI: 10.1590/0100-69912017005009

Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy Influência do cólon na regeneração do fígado de ratos submetidos à hepatectomia e colectomia MARÍLIA CARVALHO MOREIRA1; ÍTALO MEDEIROS AZEVEDO1; CLÁUDIA NUNES OLIVEIRA1; ALDO DA CUNHA MEDEIROS, ECBC-RN1. A B S T R A C T Objective: to evaluate whether colectomy, associated with 70% hepatectomy, influences liver regeneration in rats. Methods: we distributed 18 Wistar rats in three groups of six animals each. In group I (sham), we performed laparotomy; In group II, colectomy + 70% hepatectomy; In group III, only 70% hepatectomy. On the 6th postoperative day, we collected blood by cardiac puncture under anesthesia, followed by euthanasia. We performed serum dosages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and alkaline phosphatase (AF), hepatocyte growth factor (HGF) and transforming growth factor-α (TGF-α). We calculated liver regeneration by the formula: liver weight ratio per 100g body weight at the time of euthanasia / liver weight preoperatively projected for 100g body weight × 100. Results: ALT and AST levels were significantly lower in group II when compared with group III (p<0.001). Albuminemia showed significantly higher levels in group II. Levels of HGF and TGF-α in group II were significantly higher than in group III. The percentage of hepatic regeneration was significantly higher in group II than in group III. Conclusion: Colectomy performed simultaneously with 70% hepatectomy had a positive influence on liver regeneration in rats. Further research is needed to reveal the molecular mechanisms of this effect and to characterize the colon influence in liver physiology. Keywords: Liver Regeneration. Colectomy. Hepatectomy. Rats.

INTRODUCTION

T

he liver is one of the most complex organs in the human body. Its mass is measured in proportion to the individuals’ body weight1, and this ratio is restored after hepatic resection2. Half of all patients with colorectal cancer develop hepatic metastases in the course of this disease3. Patients with metastases may benefit from hepatic resection, as it provides an opportunity for healing4, with isolated segmentectomy and lobectomy being the most common surgical interventions. The results have been relatively good if the resection safety margins and the liver functional reserve are adequate5. Long-term survival after liver resection for colorectal metastases has improved significantly in recent years6. These facts justify the study of hepatic regeneration in the presence of simultaneous colectomy, due to the high incidence of colorectal disease with metastases and to the frequency with which these procedures are performed at the same operative time. Liver regeneration has been the subject of

studies over the years. However, the mechanisms by which the organ is stimulated to replicate and the relationship between cells and cytokines have not yet been fully elucidated. Nutritional and other factors have been evaluated, all demonstrating some influence on the regeneration process7-9. New knowledge has emerged on liver regeneration, emphasizing the performance of growth factors and other cytokines10,11. In animal models, hepatic regeneration mechanisms have been investigated in detail. Hepatocytes early express tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), mainly produced by Kupffer cells, and the proliferation and growth of hepatocytes are induced primarily in response to the transforming growth factor-α (TGF-α) and hepatocyte growth factor (HGF), among others10. One of the first studies to investigate the colon role in hepatic regeneration examined the effect of ileocolectomy associated with 50% hepatectomy on the regenerative response, evaluating thymidine kinase activity and mitotic figures as regeneration markers.

1 - Federal University of Rio Grande do Norte, Post-graduation Program in Health Sciences, Natal, RN, Brazil. Rev Col Bras Cir 2017; 44(5): 476-481


Moreira Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy

When compared, this surgical procedure generated a significantly greater regenerative response than sole hepatectomy or hepatectomy with ileum resection12. Moser et al.13 studied the participation of genetic factors in hepatic regeneration after colectomy in 2006. However, a study by Hachiya et al.14 in 2008 concluded that the process of liver regeneration after synchronous resection of the liver and colon in rats was reduced. Faced with the controversy, we seek to contribute to the theme. The objective of the present study was to examine the influence of extensive colon resection on liver function and regeneration in an experimental rat model.

METHODS The Institutional Committee on Ethics in the Use of Animals approved the research project under protocol number 054-10. The animal care followed the standards of the Brazilian legislation for the scientific use of animals (Law 11.794/2008, CONCEA). We used 18 male, adult Wistar rats (Rattus norvegicus), weighing 294 ± 13g, supplied by the Health Center of the Federal University of Rio Grande do Norte (UFRN). The animals were housed in individual polypropylene cages with 12-hour light-dark cycles, controlled humidity and temperature, with ad libitum access to water and chow for rodents. For seven days prior to the experiment, they remained in the laboratory for acclimatization. One day before the surgical interventions, they took only water, and were then randomly divided into three groups with six rats each: in group I (sham), we performed laparotomy; in group II, colectomy + 70% hepatectomy; in group III, only 70% hepatectomy. All animals were anesthetized with intraperitoneal injection of ketamine (70mg/kg) and xylazine (10mg/kg), and operated with aseptic technique after abdominal wall trichotomy and antisepsis with 70% ethyl alcohol. The animals of group II, 70% hepatectomy + colectomy, underwent median laparotomy, through which we resected the whole cecum and 5cm of the proximal colon, proceeding with an end-to-end, sin-

477

gle-plane ileocolic anastomosis, with simple, separated stitches of 6 0 polypropylene, with the aid of a DFV surgical microscope (São Paulo, Brazil), 10x magnification. Concomitantly, we resected the left and middle lobes of the liver (70% hepatectomy). In group III, hepatectomy, the animals were submitted to resection of the left and middle lobes of the liver (70% hepatectomy). In the sham group, we carried out a median laparotomy and mild manipulation of the cecum and liver under the same conditions of anesthesia and antisepsis. In all animals, after checking hemostasis, we sutured the abdominal incision in two planes with 4-0 nylon sutures. After the intervention, postoperative pain control was done with intramuscular meperidine at a dose of 10mg/kg once daily for the first three days. We kept the animals under observation for six days, during which we observed weight loss parameters through digital weighing, with sensitivity to variation of one gram. The animals received only water in the first 24 postoperative hours, followed by a solid diet until euthanasia and, in the observation period, were kept in a postoperative control room. On the sixth postoperative day, we weighed and anesthetized the animals with the same technique described above, and collected 5ml blood samples by cardiac puncture for laboratory tests. We then submitted them to euthanasia with an anesthetic overdose (100mg/Kg intraperitoneal thiopental sodium). We resected the remaining liver (right lobe), washed it with 0.9% saline solution and weighed it on a precision scale. In the sham group, we weighed the whole liver.

Serum dosages We processed the whole blood serum collected from the animals on the sixth postoperative day by centrifugation at 3,000 rpm for ten minutes, and stored it at 40°C until dosed. We measured serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and alkaline phosphatase (AF) in all animals with Wiener kits, Konelab Autoanalyzer, Finland. We used Enzyme-linked immunosorbent assays (ELISA) for the determination of hepatocyte growth factor (HGF) and transforming growth factor-α (TGF-α), using ABCAM kits (Massachusetts, USA) and a microplate reader (BioTek, Vermont USA).

Rev Col Bras Cir 2017; 44(5): 476-481


Moreira Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy

478

Calculation of hepatic regeneration Initially, we calculated the hepatic mass / body mass ratio of sham animals (HMBMR). After the observation period, we weighed the rats (B) in a precision scale, removed the entire liver and weighed it too (A). We expressed the acquired data as a percentage of the ratio of A to B, multiplied by 100, calculated by the formula: HMBMR= (Liver mass / Body mass) x 100. This ratio established the percentage that the liver represents over the body mass of each animal. We evaluated the changes in the HMBMR of the animals of the studied groups as degree of hepatic regeneration. Hepatic Regeneration (HR) was defined as: HR=([HMBMReuta - HMBMRpos] / HMBMRpos) x 100. Where: HR is the percentage of hepatic regeneration; HMBMReuta is the Hepatic Mass-Body Mass Ratio in euthanasia (after the observation period); HMBMRpos is the Hepatic Mass-Body Mass Ratio in the immediate postoperative period (shortly after hepatectomy).

Statistical analysis We used the ANOVA test followed by the Tukey test to compare the laboratory parameters be-

tween groups. To evaluate the difference between the means of liver regeneration between groups, we applied the Student’s t-test. For all tests, we set the significance level at 5%, using the statistical package SPSS®21.

RESULTS All animals survived the experiments and there was no significant difference in the evolution of their body weights between groups. On the 6th postoperative day, biochemical measurements showed significantly higher levels of ALT in animals submitted to 70% hepatectomy + colectomy when compared with the sham group (p<0.01). However, ALT, AST and AF levels in the group of animals submitted solely to hepatectomy were significantly higher than in the hepatectomy + colectomy group (p<0.01). Albuminemia was significantly higher in the rats of the sham and hepatectomy + colectomy groups than in the hepatectomy group (p<0.01). There was no significant difference of albuminlevels between the sham and the hepatectomy + colectomy groups (p>0.05). Table 1 summarized the values of the biochemical data.

Table 1. Values of biochemical data and their statistical interpretation.

Sham

70% Hepatectomy + colectomy

70% Hepatectomy

ALT (IU/l)

46.6 ± 3.01a

128.7 ± 5.1a

208.4 ± 19.3a

AST (IU/l)

50.05 ± 2.17a

49.1 ± 2.04b

69.7 ± 2.7ab

AF (IU/l)

154.6 ± 15.3a

161.5 ± 6.1b

211.6 ± 13.7ab

4.6 ± 0.4a

4.1 ± 0.2b

3.4 ± 0.3ab

Albumin (g/l)

Tukey test: mean ± SD values followed by the same letter are statistically significant, with p < 0.01. AST, Aspartate aminotransferase; ALT, Alanine aminotransferase; AF, Alkaline Phosphatase.

Table 2 shows that the values of the HGF and TGF α of the animals submitted to hepatectomy + colectomy were significantly higher than in the sham and hepatectomy groups (p<0.01). The calculation of the percentage of hepa-

tic regeneration revealed that in the animals of the hepatectomy + colectomygroup, regeneration occurred significantly higher than in the animals submitted to isolated hepatectomy (p=0.003). These data are summarized in table 3.

Rev Col Bras Cir 2017; 44(5): 476-481


Moreira Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy

479

Table 2. Values of growth factors and their statistical interpretation.

Sham

70% Hepatectomy + colectomy

70% Hepatectomy

HGF (pg/ml)

282.8 ± 13.3a

408 ± 18.2a

360 ± 58.6a

TGF-α(ng/ml)

0.93 ± 0.1a

3.8 ± 0.3a

2.3 ± 0.4a

Tukey test: mean ± SD values followed by the same letter are statistically significant, with p < 0.01.

Table 3. Descriptive data and inferential test of liver regeneration.

Groups

Regeneration (%)

70% Hepatectomy

70% Hepatectomy + colectomy

p-value

18.8 ± 8.90

52.7 ± 16.32

0.003

Mean ± standard deviation (Student’s t test).

DISCUSSION Hepatic regeneration is a very complex topic that arouses great interest due to the way it happens through cellular interactions, humoral and molecular mechanisms, and influence of portal system organs, which have not yet been fully elucidated. In a previous study, we demonstrated that the ileus acts positively on the parameters of hepatic regeneration in rats15. The present study showed that animals submitted to 70% hepatectomy simultaneous to a resection of the cecum and part of the colon had significantly better hepatic regeneration during the observation period than animals submitted to 70% hepatectomy alone. The hepatic resection simultaneous to colectomy did not increase the risk of postoperative complications and all rats survived until the end of the experiments. Our results suggest that simultaneous colon and liver resection contributed to improve hepatic regeneration parameters assessed on the sixth postoperative day and, at the same time, liver function and injury tests had more favorable levels than in animals with isolated hepatectomy. Hachiya et al.14 performed an ileocolectomy simultaneously with hepatectomy in rats and concluded that there was a reduction in regeneration and impairment of endothelial cell function in the remaining liver. One criticism to their model is that they added ileus resection to the animals.

It is known that ileus is essential to the process of liver regeneration15. A study in rats submitted to hepatectomy and simultaneous resection of a segment of only 1cm of the colon concluded that there was a higher degree of liver regeneration than in the animals submitted to isolated hepatectomy16. The theme is controversial, the studies are scarce in the literature and the methodology is much varied. We indirectly analyzed the degree of hepatic impairment due to injury caused by interventions in the liver and colon, through ALT, AST, AF and albumin. Being a cytoplasmic and mitochondrial enzyme, AST is found in many organs besides the liver, including heart, skeletal muscle, kidneys and brain tissues. However, ALT is cytoplasmic, is mainly found in the liver and is more specific than AST17. Serum transaminases are sensitive in the demonstration of hepatocyte damage and, independent of etiological factors, their values remain high while hepatic lesions persist17. Table 1 show that ALT levels were higher in the hepatectomy + colectomy group compared with sham, and this serum level was significantly lower than in the isolated hepatectomy group. As regards to AST, AF and albumin, their serum levels did not differ significantly between the hepatectomy + colectomy and sham groups. These data are relevant because they may mean that the absence of the colon should have exerted a protective effect on the liver and had a positive influence on

Rev Col Bras Cir 2017; 44(5): 476-481


Moreira Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy

480

liver regeneration. In order to calculate the percentage of hepatic regeneration, we chose to compare only the two groups with hepatectomy, since in the sham group, there was no intervention in the liver and we considered liver regeneration null. There are many growth factors produced by hepatocytes during regeneration18. TGF-α has been shown to be mitogenic for hepatocytes in cultures, being more active than other growth factors, which are mitogenic for various types of non-parenchymal cells, especially endothelial cells. TGF-α-deficient mice have a normal hepatic regeneration after hepatectomy19. HGF is a potent hepa-

tocyte proliferation factor10. In the present study, the association of colectomy with hepatectomy had a positive relationship with serum levels of HGF and TGF-α on the sixth postoperative day, coinciding with a higher percentage of hepatic regeneration than in the group of animals submitted to isolated hepatectomy. These findings are consistent with findings of other authors20. Our study demonstrated that colectomy positively influenced liver regeneration after 70% hepatectomy in rats. Further research is needed to reveal the molecular mechanisms of this effect and to characterize the influence of the colon on other parameters of liver physiology.

R E S U M O Objetivo: avaliar se a colectomia, associada à hepatectomia 70%, influencia a regeneração do fígado em ratos. Métodos: foram utilizados 18 ratos Wistar distribuídos em três grupos de seis animais cada. No grupo I (sham) foi realizada laparotomia; no grupo II colectomia + hepatectomia 70%; no grupo III apenas hepatectomia 70%. No sexto dia pós-operatório foi colhido sangue por punção cardíaca, sob anestesia, seguido de eutanásia. Foram realizadas dosagens séricas de aspartato aminotransferase (AST), alanina aminotransferase (ALT), albumina e fosfatase alcalina (FA), fator de crescimento de hepatócitos (HGF) e fator de crescimento transformador-α (TGF-α). A regeneração do fígado foi calculada pela fórmula: razão peso do fígado por 100g do peso corporal no momento da eutanásia/peso do fígado no pré-operatório projetado por 100g de peso corporal ×100. Resultados: Os níveis de ALT e AST foram significativamente menores no grupo II quando comparados com o grupo III (p<0,001). A albuminemia mostrou níveis significativamente mais elevados no grupo II. Os níveis de HGF e TGF-α no grupo II foram significativamente mais elevados que no grupo III. O percentual de regeneração hepática foi significativamente mais elevado no grupo II do que no grupo III. Conclusão: o estudo demonstrou que a colectomia realizada simultaneamente à hepatectomia 70% influenciou positivamente na regeneração do fígado em ratos. Pesquisas adicionais são necessárias para revelar os mecanismos moleculares deste efeito e para caracterizar a influência do cólon na fisiologia do fígado. Descritores: Regeneração Hepática. Colectomia. Hepatectomia. Ratos.

REFERENCES 1.

2. 3.

4.

5.

Tarlás MR, Ramalho FS, Ramalho LNZ, Castro-e-Silva T, Brandão DF, Ferreira J, et al. Cellular aspects of liver regeneration. Acta Cir Bras. 2006;21(Suppl. 1):63-6. Fausto N. Liver regeneration. J Hepatol. 2000;32(Suppl. 1):19-31. Faivre J, Manfredi S, Bouvier AM. [Epidemiology of colorectal cancer liver metastases]. Bull Acad Natl Med. 2003;187(5):815-22. French. Wicherts DA, Miller R, de Haas RJ, Bitsakou G, Vibert E, Veilhan LA, et al. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg. 2008;248(6):994-1005. Inoue Y, Hayashi M, Komeda K, Masubuchi S, Yamamoto M, Yamana H, et al. Resection margin with anatomic or nonanatomic hepatectomy for

6.

7.

8.

9.

liver metastasis from colorectal cancer. J Gastrointest Surg. 2012;16(6):1171-80. Tomlinson JS, Jarnajin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575-80. Silva RM, Malafaia O, Torres OJ, Czeczko NG, Marinho Jr CH, Kozlowski RK. Evaluation of liver regeneration diet supplemented with omega-3 fatty acids: experimental study in rats. Rev Col Bras Cir. 2015;42(6):393-7. Toderke EL, Baretta GAP, Gama Filho OP, Matias JEF. Sirolimus influence on hepatectomy-induced liver regeneration in rats. Rev Col Bras Cir. 2014;41(3):203-7. Salomão LS, Young SB, Galhardo MA, Pereira LA, Pires AR, Boaventura GT, et al. Evaluation of liver regeneration by modulation with ischemic

Rev Col Bras Cir 2017; 44(5): 476-481


Moreira Influence of the colon in liver regeneration of rats submitted to hepatectomy and colectomy

10. 11.

12.

13.

14.

15.

16.

preconditioning after ischemia and reperfusion and partial hepatectomy. Rev Col Bras Cir. 2012;39(3):211-5. Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology. 2006;43(2 Suppl 1):S45-53. Jesus RP, Waitzberg DL, Campos FG. Regeneração hepática: papel dos fatores de crescimento e nutrientes. Rev Assoc Med Bras. 2000;46(3):242-54. Kahn D, Von Sommoggy S, Hickman R, Terblanche J. Ileocolectomy enhances the regenerative response after partial hepatectomy in the pig. S Afr J Surg. 1990;28(1):11-3. Moser MJ, Gong Y, Zhang MN, Lipschitz J, Cohen A, Minuk GY. The effects of colectomy on immediateearly proto-oncogene expression and hepatic regeneration in the rat. Dig Dis Sci. 2006;51(7):117982. Hachiya Y, Chijiiwa K, Noshiro H, Tanaka M. Impaired liver regeneration after synchronous liver and colon resection in rats. Hepatogastroenterology. 2008;55(82-83):641-6. Medeiros AC, Azevedo AC, Oséas JM, Gomes MD, Oliveira FG, Rocha KB, et al. The ileum positively regulates hepatic regeneration in rats. Acta Cir Bras. 2014;29(2):93-8. Sasanuma H, Mortensen FV, Knudsen AR, FunchJensen P, Okada M, Nagai H, et al. Increased liver regeneration rate and decreased liver function after synchronous liver and colon resection in rats. Ann

17.

18.

19.

20.

481

Surg Innov Res. 2009;3(1):1-7. McGill MR. The past and present of serum aminotransferases and the future of liver injury biomarkers. EXCLI J. 2016;15(6):817-28. Matsumoto K, Miyake Y, Umeda Y, Matsushita H, Matsuda H, Takaki A, et al. Serial changes of serum growth fator levels and liver regeneration after partial hepatectomy in healthy humans. Int J Mol Sci. 2013;14(10):20877-89. Russell WE, Kaufmann WK, Sitaric S, Luetteke NC, Lee DC. Liver regeneration and hepatocarcinogenesis in transforming growth factor-alpha-targeted mice. Mol Carcinog. 1996;15(3):183-9. Efimova EA, Glanemann M, Nussler AK, Schumacher G, Settmacher U, Jonas S, et al. Changes in serum levels of growth factors in healthy individuals after living related liver donation. Transplant Proc. 2005;37(2):1074-5.

Received in: 24/04/2017 Accepted for publication: 01/06/2017 Conflict of interest: none. Source of funding: National Council for Scientific and Technological Development, Protocol No. 4449083 / 20144. Mailing address: Marília Carvalho Moreira E-mail: mariliarn@gmail.com / cirurgex.ufrn@gmail.com

Rev Col Bras Cir 2017; 44(5): 476-481


Original Article

DOI: 10.1590/0100-69912017005010

Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy Métodos de avaliação nutricional preditores de mortalidade pós-operatória em pacientes submetidos à gastrectomia por câncer gástrico

ALINE KIRJNER POZIOMYCK1; LEANDRO TOTTI CAVAZZOLA, TCBC-RS1; LUISA JUSSARA COELHO1; EDSON BRAGA LAMEU1; ANTONIO CARLOS WESTON, TCBC-RS1; LUIS FERNANDO MOREIRA, TCBC-RS1. A B S T R A C T Objectives: to determine the nutritional evaluation method that best predicts mortality in 90 days of patients submitted to gastrectomy for gastric cancer. Methods: we conducted a prospective study with 44 patients with gastric cancer, stages II to IIIa, of whom nine were submitted to partial gastrectomy, 34 to total gastrectomy, and one to esophago-gastrectomy. All patients were nutritionally evaluated through the same protocol, up to 72h after hospital admission. The parameters used were Patient-Generated Subjective Global Assessment (PGSGA), classical anthropometry, current weight and height, percentage of weight loss (%WL) and body mass index (BMI). We also measured the thickness of the thumb adductor muscle (TAM) in both hands, dominant hand (TAMD) and non-dominant hand (TAMND), as well as the calculated the prognostic nutritional index (PNI). The laboratory profile included serum levels of albumin, erythrocytes, hemoglobin, hematocrit, leukocytes, and total lymphocytes count (TLC). Results: of the 44 patients studied, 29 (66%) were malnourished by the subjective method, 15 being grade A, 18 grade B and 11 grade C. Cases with PGSGA grade B and TAMD 10.2±2.9 mm were significantly associated with higher mortality. The ROC curves (95% confidence interval) of both PGSGA and TAMD thickness reliably predicted mortality at 30 and 90 days. No laboratory method allowed predicting mortality at 90 days. Conclusion: PGSGA and the TAMD thickness can be used as preoperative parameters for risk of death in patients undergoing gastrectomy for gastric cancer. Keywords: Nutrition Assessment. Stomach Neoplasms. Mortality. Prognosis.

INTRODUCTION

A

ce preoperative nutritional interventions can restore nutritional status and improve surgical outcomes8-11.

lthough with decreasing incidence and mortality in many countries in the last decades, gastric cancer is still common worldwide and its prognosis is poor1-4. Gastrectomy is the only potentially curative treatment, but it is associated with increased postoperative catabolism and metabolic, endocrine, neuroendocrine and immune changes that contribute to high postoperative morbidity rates5-6. Patients with gastric cancer have a high risk of malnutrition, with a weight loss greater than 10% in the last six months reported in 30% to 38% of cases5. Malnutrition, defined as a state of deficiency of energy, protein and other specific nutrients, has a negative impact on clinical outcome, with a longer hospital stay and increased mortality7. A thorough screening for malnutrition is very important, sin-

However, nutritional assessment is known to be particularly difficult, since none of the currently used methods or instruments alone or in combination have proven to be adequate to increase its sensitivity and specificity11-13. Regarding evaluation of therapy, no quality measure is as precise, easily quantifiable and important as postoperative mortality1. Thirty-day mortality (30DM) is the commonly used parameter, but 90-day mortality (90DM) has been increasingly recognized as a more reliable indicator in many surgical procedures, since 30DM is believed to underestimate total mortality in cases of debilitating, aggressive and advanced tumors of the upper gastrointestinal tract14. The objective of this study was to prospectively evaluate the method of nutritional evaluation

1 - Federal University of Rio Grande do Sul, Post-Graduation Program in Surgical Sciences, Porto Alegre, RS, Brazil. Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

that best predicts mortality in 90 days of patients undergoing gastrectomy for gastric cancer.

METHODS We carried out a prospective study based on a convenience sample that included 44 patients, 29 males and 15 females, mean age 63 (±10.2) years (range 34-83), who underwent gastrectomy at the Santa Rita Hospital of Santa Casa de Misericórdia, Porto Alegre, RS, Brazil, from March 2009 to March 2011. All were aware of the study and agreed to participate. We obtained a signed informed consent form from all participants. This study is part of the research line of the Southern Surgical Oncology Research Group (SSORG) and was approved by the Ethics in Research Committee under number 2,041/08 of the Holy Home of Mercy of Porto Alegre. We evaluated the nutrition status of all patients through the same protocol, up to 72 hours after hospital admission. The parameters used were the Patient-Generated Subjective Global Assessment (PGSGA), classical anthropometry, current weight and height, percentage of weight loss (%WL) and body mass index (BMI). We also measured the thickness of the thumb adductor muscle (TAM) in both hands, dominant hand (TAMD) and non-dominant one (TAMND). The laboratory profile included serum levels of albumin, erythrocytes, hemoglobin, hematocrit, leukocytes, and total lymphocytes count (TLC). We calculated the prognostic nutritional index (PNI) using the following formula: 10x serum albumin value (g/dl) + 0.005 x total lymphocytes count in the peripheral blood (per mm3)6. We used Portuguese-validated versions of the PGSGA, adapted by Ottery15, specific for cancer patients, to evaluate the nutritional status. These results were categorically classified as A, B or C, for well nourished, moderately or severely malnourished, respectively. We used the sum of the scores to determine specific nutritional approaches16. We routinely checked the current weight and height with a pre-calibrated platform-type digital scale and a measuring rod. We used the tables proposed by Lipschitz et al.16 and by the World Health Organization (WHO)17 to classify

483

the body mass index (BMI) of elderly and adult patients, respectively. We considered the usual weight as reported by the patients to determine the percentage of weight loss. We measured TAM thickness with an adipometer, by compressing the thumb adductor muscle at the apex of an imaginary triangle formed by the extension of the thumb and index finger18. A single trained nutritionist evaluated all of these anthropometric measures, attempting to reduce bias. All measurements were performed in triplicate and the results presented as the average of three measurements. Statistical analysis included relative counts and frequencies, as well as measures of central tendency (mean and median) and variability (standard deviation and interquartile range), which we used whenever necessary. We used the Kolmogorov-Smirnov test to evaluate the symmetry of the distribution, and performed the comparison of categorical data with the Fisher’s exact test or Monte Carlo simulation for alternative outcomes, when necessary. In the bivariate analysis, we compared continuous variables between the two independent groups with the Student’s t or the Mann-Whitney tests. We determined the linear relationship between parametric and non-parametric continuous variables with the Pearson or Spearman correlation, respectively. We used the Receiver Operating Characteristic (ROC) curve to determine if subjective, anthropometric and laboratory variables correlated with mortality. We used the SPSS program (Statistical Package Social Sciences for Windows) 17.0 to analyze the data, considering a 95% confidence interval and significance level of p<0.05.

RESULTS Of the 44 patients evaluated, nine (20.4%) underwent partial gastrectomy, 34 (77.3%) total gastrectomy and one (2.3%) esophago-gastrectomy. Stages ranged from II to IIIa, with a predominance of stage III, according to the AJCC 2010 classification, which, in a univariate analysis, did not reveal a significant difference in relation to mortality. Patient characteristics and mortality are shown in table 1.

Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

484

Table 1. Description of the sample according to mortality (n=44).

Death Variables

Alive (n = 31)

p

Death within 30 days (n = 6) %

Death within 90 days (n Death Death within = 13) within 90 A 30 days daysB n %

n

%

n

Male

21

67.7

4

66.7

8

61.5

Female

10

32.3

2

33.3

5

38.5

Gender >0.999+

0.098+

Age (Mean ± Sd)

60.4 ± 11.2

62.7 ± 9.5

64.1 ± 9.4

0.7813*

0.375*

BMI

23.7 ± 3.6

18.4 ± 3.4

22.2 ± 5.2

0.003*

0.463*

(elderly)

25.0 ± 3.7

19.8 ± 0.1

24.9 ± 4.1

0.043*

0.980*

(adults)

22.8 ± 3.2

17.7 ± 4.2

19.1 ± 4.8

0.013*

0.035*

% WL/6 m

12.1 ± 11.2

26.8 ± 17.4

18.5 ± 14.5

0.092+

0.102+

TAMD

14.9 ± 3.1

8.5 ± 1.9

10.2 ± 2.9

<0.001*

<0.001*

TAMND

13.6 ± 3.3

7.3 ± 1.7

9.4 ± 3.5

<0.001*

0.002*

Albumin

3.9 ± 0.4

3.4 ± 0.8

3.7 ± 0.7

0.265*

0.257*

Hemoglobin

12.8 ± 2.2

12.8 ± 2.4

12.2 ± 1.8

0.900*

0.102*

Hematocrit

38.0 ± 5.4

37.2 ± 6.3

36.1 ± 4.9

0.577*

0.058*

TLC

1587.6 ± 608.1

1414.8 ± 553.1

1578.7 ± 623.6

0.482+

0.945+

PNI

47.9 ± 6.1

41.4 ± 10.4

44.7 ± 8.5

0.209*

0.398*

A: minimum level of significance in the comparison between the groups “alive vs. death within 30 days”; B: minimum level of significance in the comparison between the groups “alive vs. death within 90 days”; BMI: body mass index; % WL/6 m: percentage of weight loss in the last six months; TAMD: Thumb Adductor Muscle of the dominant hand; TAMND: Thumb Adductor Muscle of the non-dominant hand; TLC: total lymphocytes count; PNI: prognostic nutritional Index; * Fisher’s exact test (by Monte Carlo simulation); + Kruskal Wallys and one-way analysis of variance Post Hoc Sheffé, where means followed by letters point out significant difference of 5%.

One third of the patients had some degree of malnutrition and 11 (25%) of them were severely malnourished. The length of hospital stay was on average 24 (± 21) days. Thirteen (29.5%) patients died within the first three postoperative months, and the most frequent causes were anastomosis and sepsis dehiscence in six (46.1%) and acute respiratory failure in four (30.8%). Differences in the PGSGA were not statistically significant (c2calc=1.682, p=0.431). However, the proportion of patients with weight loss over 10%

at six months (n=26; 59.1%) was significant in this sample (c2calc=46.7; p<0.001). Of the 13 patients who died, 12 (92.3%) were diagnosed as grade B or C by the PGSGA, while 14 (45.2%) of those who survived were diagnosed as grade A and 12 (38.7%) as grade B (p=0.025). Regarding the TAM thickness, there was no statistically significant difference observed between the dominant and non-dominant hands (p<0.02). The TAM thickness in the dominant hand (TAMD) was the best parameter capable of predicting death (Table 2).

Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

All patients who died within the first three postoperative months were significantly more malnourished as demonstrated by the TAMD (Table 2). Although albu-

485

min was decreased in the malnourished patients who died, no laboratory method predicted 90-day mortality with statistical strength (Table 3).

Table 2. Anthropometric parameters and 90-days postoperative mortality.

Mortality at 90 days (n = 44) Death (n = 13)

Anthropometric Method

No death (n = 31)

p

Mean

SD

Median

P25

P 75

Mean

SD

Median

P25

P 75

BMI (kg/m²)

22.2

5.2

22.7

18.4

26.6

23.7

3.6

23.4

21.5

26.5

0.463*

%WL/6 m

18.5

14.5

16.4

11.4

18.8

12.1

11.2

11.0

3.1

16.7

0.102+

TAMD

10.2

2.9

9.7

8.5

12.8

14.9

3.1

15.3

13.0

16.7

< 0.001*

TAMND

9.4

3.5

8.3

7.7

12.0

13.6

3.3

13.7

11.7

16.0

0.002*

BMI: Body mass index; %WL/6 m: percentage of weight loss in the last six months; TAMD: Thumb adductor muscle of the dominant hand; * Student’s t test for independent groups; + Mann Whitney test.

Table 3. Laboratory Parameters and 90-days postoperative mortality.

Mortality at 90 days Laboratory Method

Death (n=13)

p

No death (n=31)

Mean

SD

Median

P25

P 75

Mean

SD

Median

P25

P 75

Albumin (g/dl)

3.7

0.7

3.8

3.3

4.2

3.9

0.4

3.9

3.6

4.3 0.257*

Hemoglobin (g/ dl)

12.2

1.8

12.3

11.2

13.1

12.8

2.2

13.2

12.3 14.3 0.102*

Hematocrit (%)

36.2

5.0

35.9

32.8

38.5

38.0

5.4

38.5

36.3 41.1 0.058*

1578.7

623.6

1387

1093 2048 0.945*

44.7

8.5

47.6

43.1 51.8 0.398*

TLC (g/dl) PNI

1655.1 852.1 2125.7 1587.6 608.1 46.8

40.3

51.2

47.9

6.1

TLC : total lymphocytes count; PNI: prognostic nutritional Index; * Student’s t test for independent groups.

Table 4 presents data on laboratory parameters and postoperative mortality, in which the PGSGA (p<0.001), TAMD (p<0.001) and albumin (p=0.026) predicted mortality at 30 days. However, only the PGSGA showed significance in predicting 90-day mortality (p=0.047). It is worth noting that there was no statistically significant difference in TAM values in relation to gender, either in the dominant hand (Female: 12.6 ± 3.4 vs. Male: 14.2 ± 3.9, p=0.157) or in the non-do-

minant one (Female: 11.6 ± 3.6 vs. Male: 12.9 ± 3.9, p=0.265). The predictive power calculated by the area below the ROC curve was statistically significant for PGSGA (0.833), BMI (0.857), TAMD (0.874) and TAMND (0.755), with the highest prediction powers concentrated on TAMD (p=0.006) and PGSGA (p=0.008), as shown in table 5. Significant estimates for areas under the curve of variables as predictors of mortality are shown around 0.70.

Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

486

Table 4. Nutritional Parameters and postoperative mortality.

Death within 30 days (n = 6-13.6%) Yes (n = 6) No (n = 38)

Variables

p

Death within 90 days (n = 13-29.5%) Yes (n = 13) No (n = 31)

BMI

18.4 ± 3.4

24.1 ± 3.7

0.001*

22.4 ± 5.2

23.7 ± 3.6

TAMD*

8.5 ± 1.9

14.3 ± 3.3

< 0.001*

10.1 ± 2.9

14.9 ± 3.1

TAMND Albumin

7.3 ± 1.7 3.4 ± 0.8

< 0.001* 0.026*

1414.8 ± 553.1

PNI PGSGA (A) (B)

41.4 ± 10.4

0.035*

9.4 ± 3.5 3.7 ± 0.7 1578.7 ± 623.6 44.7 ± 8.5

13.6 ± 3.3 3.9 ± 0.4

TLC

13.2 ± 3.4 4.0 ± 0.4 1613.9 ± 616.4 47.9 ± 6.0

0 (0.0%) 0 (0.0%)

15 (39.5%) 18 (47.4%)

< 0.001+

(C)

6 (100.0%)

5 (13.2%)

0.463

p

0.463 < 0.001* 0.002* 0.257*

1587.6 ± 608.1 0.945+ 47.9 ± 6.1

0.398*

1 (7.7%) 6 (46.6%)

14 (45.4%) 12 (38.7%)

0.025+

6 (46.2%)

5 16.1%)

TAMD : Thumb adductor muscle of the dominant hand; TAMND: Thumb adductor muscle of the non-dominant hand; TLC: total lymphocytes count; PNI: prognostic nutritional Index; PGSGA: Patient-Generated Subjective Global Assessment; * Student’s t test for independent groups; + Mann Whitney test + Fisher exact test (Monte Carlo simulation).

Table 5. Area under the ROC curve of cutoff for predictors of mortality parameters within 30 and 90 days post gastrectomy.

ROC Curve-Mortality Parameters

Area under the curve (95% CI)

p

Cut-off point

0.833 (0.763 -0.956)

0.008

(B)

BMI

0.857 (0.722-0.992)

0.021

> 22.6

TAMD

0.874 (0.763 -0.948)

0.006

= 11.2

TAMND

0.755 (0.617 -0.822)

0.037

= 8.4

Albumin

0.652 (0.368 -0.877)

0.238

= 3.3

PNI

0.667 (0.410 -0.923)

0.197

< 43.6

0.739 (0.653 -0.845)

0.036

(B)

TAMD

0.866 (0.774 -0.992)

0.024

= 10.7

TAMND

0.805 (0.688 -0.922)

0.041

= 9.7

Death within 30 days Subjective PGSGA Anthropometrical

Laboratory

Death within 90 days Subjective PGSGA Anthropometrical

PGSGA: Patient-Generated Subjective Global Assessment; BMI: body mass index; TAMD: Thumb adductor muscle thickness of the dominant hand; TAMND: Thumb adductor muscle thickness of the non-dominant hand; PNI: prognostic nutritional Index. Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

DISCUSSION The consumptive process occurs according to a cascade of events and is independent of the size of the surgical procedure, which explains the most expressive and evidenced mortality in the most malnourished patients10. Anastomosis dehiscence in patients with poorer nutritional status and with more advanced age is an independent factor of worse prognosis19, considerably worsening the incidence of postoperative death in patients with gastric tumor. Significant weight loss is generally seen in patients with incurable solid tumors8,20, as observed in our results. Gavazzi et al.21 found weight loss over 5% in the previous three months in 35% of patients recently diagnosed with gastric carcinoma. Rey-Ferro et al.22 found an average of 10% weight loss, and in those who died postoperatively, weight loss had been significantly higher than in those who survived (p=0.06). These results were also confirmed in the study by Shim et al.6, in which preoperative weight loss (p=0.008) and gastric cancer (p<0.001) were independent risk factors for severe malnutrition. Recently, Gonzalez et al.23 reported that TAM thickness was significantly associated with nutritional status in a sample of surgical patients in southern Brazil. We found similar results, the lowest TAM thickness being related to higher mortality, as also demonstrated by Melo and Silva24 in 151 elective procedures and Bragagnolo25 in 87 large procedures of the upper gastrointestinal tract, all in Brazil. In the present study, almost two-thirds (67%) of the patients were malnourished by PGSGA, similar to other studies, showing malnutrition rates of 66% and 57%26,27, but lower than the 86% and 88% described in other works24-25. Paceli et al.28 found a preoperative weight loss greater than 10% in 42% of gastric cancer patients, similar to those of other Asian studies, of 13% and 31%6,7, respectively. However, this incidence may increase to 81% in the postoperative period, which confirms that gastrectomy significantly affects nutrition20,29. Probably, these differences between South American and Asian studies are due to differences in the higher prevalence of early stage disease in Asian countries, when nutrition is not yet significantly impaired. Nutritional status has long been associated

487

with immunocompetence, complications, and infections. Yamanaka et al.30, in 1980, demonstrated that serum albumin and prealbumin predicted better preoperative nutritional status than standard anthropometry in 413 patients with gastric cancer (40% of stage IV cases). In their study, Rey-Ferro et al.22 argue that hypoalbuminemia and weight loss have a positive predictive value for mortality in patients with gastric cancer. In a multicenter US Gastric Cancer Collaborative study involving 775 patients undergoing gastrectomy, Ejaz et al.31 observed that BMI < 18.5kg/m2 and low levels of albumin were related to a significant decrease in overall survival after gastrectomy. However, in our study, it was not possible to significantly associate these parameters with mortality, suggesting that albumin and serum protein parameters may not be as sensitive as anthropometric measures for nutritional status. The Glasgow prognostic score (GPS) is a significant predictor of long-term survival in patients with curable gastric cancer, but not for short-term evaluations32,33. A Brazilian group found a relationship between PGSGA and GPS, and both measures were associated with postoperative complications and survival in patients with esophageal and stomach cancer29. An ongoing study in our research group is evaluating the role of GPS as a short-term predictor of worsening nutritional status and postoperative complications. The prognostic nutritional index (PNI) has been advocated as a good predictor of postoperative morbidity, prognosis and recurrence patterns in patients in Asian studies5,34. In a recent update of nutrition in patients with gastric cancer, PNI, or a combination of preoperative BMI<18.5kg/m2 and low albumin levels, appear as predictors of decreased overall survival after gastrectomy9. In the present study we did not find statistical significance capable of proving the prediction of mortality. In our study, 30-day mortality was highly correlated with TAM thickness (p <0.001), PGSGA (p<0.001) and albumin (p=0.026), these parameters not being related to outcomes in 90 days, except for PGSGA (p=0.047). These results were confirmed by the ROC curve, with the area under the curve (AUC) better correlated with TAM thickness (p=0.003) than PGSGA (p=0.013) and much better than albumin (p=0.097).

Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

488

The failure to demonstrate the significance of these parameters as for the risk of death in 90 days is probably due to the patients having been submitted to pre and postoperative nutritional support. However, these 90-day mortality results require confirmation in larger series. According to Tegels et al.4, the evidence for the value of nutritional screening tools in the prediction of gastric cancer surgery postoperative outcomes is scarce. Considering PGSGA as a gold standard and comparing it with other methods of nutritional assessment in patients with gastric and colorectal cancer, Abe Vicente et al.26 found a better association with the MUST tool (p<0.001) and suggested Combination of both methods as a good assessment of nutritional status. However, these assessments based on questionnaires may be more difficult to perform in our country, since the vast majority of patients have low educational level. In a study of 751 patients diagnosed with gastrointestinal cancer (51% of gastric cancer), Wu et al.35 found a higher incidence of complications and longer hospital stay according to the increase in PGSGA levels in patients undergoing surgery or who received chemotherapy/radiotherapy, also observed in our study. Although similar rates of postoperative complications were observed in patients with different degrees of weight loss, albumin and BMI, there was no difference in the incidence of anastomosis dehiscence (greater in

patients with weight loss greater than 10%, serum albumin <3.0g/dl, or BMI<18.5kg/m2). Similarly, in other articles6,23-26 on nutritional assessment in gastric cancer patients that also include patients with colorectal cancer, the results may not reliably demonstrate changes in nutritional status, since tumor development and nutritional status are quite distinct between tumors of the lower and upper gastrointestinal tract. In addition, a wide variety of methods have been used to assess nutritional status in each study, which challenges subsequent comparison5,23,29,30,35. We believe in the need of a more specific nutritional evaluation for these surgical oncology patients with tumors of the gastrointestinal tract, which allows the early identification of nutritional changes, is necessary. With it, a nutritional intervention could be established early to improve postoperative results and decrease mortality rates. There is an ongoing nutritional risk assessment by a combination of weight loss, gastrointestinal signs and symptoms, pain score, GPS, performance status, and implications of oncological treatments measured in a larger sample. The methods evaluated in our study showed a greater prediction of mortality in 30 days. Further studies to determine the best predictors of mortality in 90 days should be performed. On the other hand, the present study indicates that the dominant hand TAM thickness and the PGSGA are reliable prediction parameters of mortality both in 30 and in 90 days in patients submitted to gastrectomy due to stomach cancer.

R E S U M O Objetivos: determinar o método de avaliação nutricional que melhor prediz a mortalidade em 90 dias de pacientes submetidos à gastrectomia por câncer gástrico. Métodos: estudo prospectivo de 44 pacientes portadores de câncer gástrico, estágios II a IIIa, dos quais nove foram submetidos à gastrectomia parcial, 34 à gastrectomia total e um à esôfago-gastrectomia. Todos os pacientes foram avaliados nutricionalmente através do mesmo protocolo, até 72h da admissão hospitalar. Os parâmetros utilizados foram a Avaliação Subjetiva Global Produzida Pelo Paciente (ASG-PPP), antropometria clássica, incluindo peso e altura atuais, porcentagem de perda ponderal (%PP) e índice de massa corporal (IMC). A espessura do músculo adutor do polegar (MAP) em ambas mãos, mão dominante (MAPD) e mão não-dominante (MAPND) também foram realizadas, assim como o cálculo do índice nutricional prognóstico (IPN). O perfil laboratorial incluiu níveis séricos de albumina, eritrócitos, hemoglobina, hematócrito, leucócitos e contagem total de linfócitos (CTL). Resultados: dos 44 pacientes estudados, 29 (66%) eram desnutridos pelo método subjetivo, sendo 15 grau A, 18 grau B e 11 grau C. Os casos com ASG-PPP grau B e com MAPD 10,2±2,9 mm foram significativamente associados à maior mortalidade. As curvas ROC (intervalo de confiança de 95%) de ambas ASG-PPP e espessura da MAPD fidedignamente predisseram mortalidade em 30 e 90 dias. Nenhum método laboratorial permitiu prever a mortalidade em 90 dias. Conclusão: a ASG-PPP e a espessura da MAPD podem ser utilizados como parâmetros pré-operatórios para risco de morte em pacientes submetidos à gastrectomia por câncer gástrico. Descritores: Avaliação Nutricional. Neoplasias Gástricas. Mortalidade. Prognóstico.

Rev Col Bras Cir 2017; 44(5): 482-490


Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

REFERENCES 1.

Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, et al. Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype. Eur J Cancer. 2014;50(7):133044. 2. Piazuelo MB, Correa P. Gastric cancer: overview. Colomb Med (Cali). 2013;44(3):192-201. 3. Bertuccio P, Chatenoud L, Levi F, Praud D, Ferlay J, Negri E, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125(3):666-73. 4. Tegels JJ, De Maat MF, Hulsewé KW, Hoofwijk AG, Stoot JH. Improving the outcomes in gastric cancer surgery. World J Gastroenterol. 2014;20(38):13692704. 5. Jiang N, Deng JY, Ding XW, Ke B, Liu N, Zhang RP, et al. Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer. World J Gastroenterol. 2014;20(30):1053744. 6. Shim H, Cheong JH, Lee KY, Lee H, Lee JG, Noh SH. Perioperative nutritional status changes in gastrointestinal cancer patients. Yonsei Med J. 2013;54(6):1370-6. 7. Ryu SW, Kim IH. Comparison of different nutritional assessments in detecting malnutrition among gastric cancer patients. World J Gastroenterol. 2010;16(26):3310-7. 8. Andreoli A, De Lorenzo A, Cadeddu F, Iacopino L, Grande M. New trends in nutritional status assessment of cancer patients. Eur Rev Med Pharmacol Sci. 2011;15(5):469-80. 9. Rosania R, Chiapponi C, Malfertheiner P, Venerito M. Nutrition in patients with gastric cancer: an update. Gastrointest Tumors. 2016;2(4):178-87. 10. Poziomyck AK, Fruchtenicht AV, Kabke GB, Volkweis BS, Antoniazzi JL, Moreira LF. Reliability of nutritional assessment in patients with gastrointestinal tumors. Rev Col Bras Cir. 2016;43(3):189-97. 11. Sungurtekin H, Sungurtekin U, Balci C, Zencir M, Erdem E. The influence of nutritional status on complications after major intraabdominal surgery. J Am Coll Nutr. 2004;23(3):227-32. 12. Pablo AM, Izaga MA, Alday LA. Assessment of

13.

14.

15.

16. 17.

18.

19.

20.

21.

22.

23.

489

nutritional status on hospital admission: nutritional scores. Eur J Clin Nutr. 2003;57(7):824-31. Damhuis RA, Wijnhoven BP, Plaisier PW, Kirkels WJ, Kranse R, van Lanschot JJ. Comparison of 30-day, 90day and in-hospital postoperative mortality for eight different cancer types. Br J Surg. 2012;99(8):114954. Gonzalez MC, Borges LR, Silveira DH, Assunção MCF, Orlandi SP. Validação da versão em português da avaliação subjetiva global produzida pelo paciente. . Rev Bras Nutr Clin. 2010;25(2):102-8. Ottery FD. Definition of standardized nutritional assessment and interventional pathways in oncology. Nutrition. 1996;12(1 Suppl):S15-9. Lipschitz DA. Screening for nutritional status in the elderly. Prim Care. 1994;21(1):55-67. 17. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253. Lameu EB, Gerude MF, Campos AC, Luiz RR. The thickness of the adductor pollicis muscle reflects the muscle compartment and may be used as a new anthropometric parameter for nutritional assessment. Curr Opin Clin Nutr Metab Care. 2004;7(3):293-301. Toneto MG, Moreira LF, Jeckel Neto E, Souza HP. Gastrectomia em pacientes idosos: análise dos fatores relacionados a complicações e mortalidade. Rev Col Bras Cir. 2004;31(6):373-9. Mariette C, De Botton ML, Piessen G. Surgery in esophageal and gastric cancer patients: what is the role for nutrition support in your daily practice? Ann Surg Oncol. 2012;19(7):2128-34. Gavazzi C, Colatruglio S, Sironi A, Mazzaferro V, Miceli R. Importance of early nutritional screening in patients with gastric cancer. Br J Nutr. 2011;106(12):1773-8. Rey-Ferro M, Castaño R, Orozco O, Serna A, Moreno A. Nutritional and immunologic evaluation of patients with gastric cancer before and after surgery. Nutrition. 1997;13(10):878-81. Gonzalez MC, Pureza Duarte RR, Orlandi SP, Bielemann RM, Barbosa-Silva TG. Adductor pollicis muscle: a study about its use as a nutritional parameter in surgical patients. Clin Nutr. 2015;34(5):1025-9.

Rev Col Bras Cir 2017; 44(5): 482-490


490

Poziomyck Nutritional assessment methods as predictors of postoperative mortality in gastric cancer patients submitted to gastrectomy

24. Melo CY, Silva SA. Adductor pollicis muscle as predictor of malnutrition in surgical patients. Arq Bras Cir Dig. 2014;27(1):13-7. 25. Bragagnolo R, Caporossi FS, Dock-Nascimento DB, de Aguilar-Nascimento JE. [Adductor pollicis muscle thickness: a fast and reliable method for nutritional assessment in surgical patients]. Rev Col Bras Cir. 2009;36(5):371-6. Portuguese. 26. Abe Vicente M, BarĂŁo K, Silva TD, Forones NM. What are the most effective methods for assessment of nutritional status in outpatients with gastric and colorectal cancer? Nutr Hosp. 2013;28(3):585-91. 27. Dias Rodrigues V, Barroso de Pinho N, Abdelhay E, Viola JP, Correia MI, Brum Martucci R. Nutrition and immune-modulatory intervention in surgical patients with gastric cancer. Nutr Clin Pract. 2017;32(1):1229. Epub 2016 Jul 9. 28. Pacelli F, Bossola M, Rosa F, Tortorelli AP, Papa V, Doglietto GB. Is malnutrition still a risk factor of postoperative complications in gastric cancer surgery? Clin Nutr. 2008;27(3):398-407. 29. da Silva JB, Mauricio SF, Bering T, Correia MI. The relationship between nutritional status and the Glasgow prognostic score in patients with cancer of the esophagus and stomach. Nutr Cancer. 2013;65(1):25-33. 30. Yamanaka H, Nishi M, Kanemaki T, Hosoda N, Hioki K, Yamamoto M. Preoperative nutritional assessment to predict postoperative complication in gastric cancer patients. JPEN J Parenter Enteral Nutr. 1989;13(3):286-91. 31. Ejaz A, Spolverato G, Kim Y, Poultsides GA, Fields RC, Bloomston M, et al. Impact of body mass index on

32.

33.

34.

35.

perioperative outcomes and survival after resection for gastric cancer. J Surg Res. 2015;195(1):74-82. Kubota T, Hiki N, Nunobe S, Kumagai K, Aikou S, Watanabe R, et al. Significance of the inflammationbased Glasgow prognostic score for short- and longterm outcomes after curative resection of gastric cancer. J Gastrointest Surg. 2012;16(11):2037-44. Fukuda Y, Yamamoto K, Hirao M, Nishikawa K, Maeda S, Haraguchi N, et al. Prevalence of malnutrition among gastric cancer patients undergoing gastrectomy and optimal preoperative nutritional support for preventing surgical site infections. Ann Surg Oncol. 2015;22 Suppl 3:77885. 3Kanda M, Mizuno A, Tanaka C, Kobayashi D, Fujiwara M, Iwata N, et al. Nutritional predictors for postoperative short-term and long-term outcomes of patients with gastric cancer. Medicine (Baltimore). 2016;95(24):e3781. Wu BW, Yin T, Cao WX, Gu ZD, Wang XJ, Yan M, et al. Clinical application of subjective global assessment in Chinese patients with gastrointestinal cancer. World J Gastroenterol. 2009;15(28):3542-9.

Received in: 25/04/2017 Accepted for publication: 01/06/2017 Conflict of interest: none. Source of funding: none. Mailing address: Aline Kirjner Poziomyck E-mail: akirjner@yahoo.com.br / akirjner@gmail.com

Rev Col Bras Cir 2017; 44(5): 482-490


Original Article

DOI: 10.1590/0100-69912017005011

Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil Levantamento epidemiológico das fraturas de face do Serviço de Cirurgia e Traumatologia Bucomaxilofacial da Santa Casa de Misericórdia de Porto Alegre – RS RODRIGO ANDRIGHETTI ZAMBONI1,2; JOÃO CARLOS BIRNFELD WAGNER1; MAURÍCIO ROTH VOLKWEIS1; EDUARDO LUIS GERHARDT1; ELISSA MULLER BUCHMANN2; CAREN SERRA BAVARESCO2. A B S T R A C T Objectives: to investigate the incidence and etiology of face trauma with diagnosis of facial fracture treated at the Buccomaxillofacial Surgery and Traumatology Service of the Santa Casa de Misericórdia Hospital Complex in Porto Alegre. Methods: we conducted a cross-sectional, retrospective epidemiological study of 134 trauma victims with 153 facial fractures. Results: the male gender was the most affected (86.6%) and the incidence was higher in the age group from 21 to 30 years. The main etiology was assault (38.8%), followed by motor vehicle accidents (14.2%), motorcycle accidents (13.4%), falls (9%), road accidents (6.7%), sports accidents (5.2%), work accidents (5.2%), firearm injuries (4.5%) and cycling accidents (3%). The most frequent fractures were those of the zygomatic complex (44.5%), followed by fractures of the mandible (42.5%), maxillary bone (5.2%), nasal bones (4.5%) and zygomatic arch (3.3%). Conclusion: the fractures of the zygomatic complex and the mandible were the ones with the highest incidence in the facial traumas, having physical assaults as their main cause. Keywords: Epidemiology. Facial Injuries. Oral and Maxillofacial Surgeons.

INTRODUCTION

T

rauma is the public health problem with the greatest potential to be prevented and treated. Thus, understanding the cause and severity of maxillofacial lesions may contribute to the establishment of clinical and research priorities for the effective treatment and prevention of these injuries1. Trauma is among the leading causes of death and morbidity in the world, accounting for 7.4% to 8.7% of emergency care2. The increase in the level of life expectancy, urban growth and its forms of locomotion, unemployment crises and the consumption of alcohol and drugs in the different regions, alter the age, gender, etiology and frequency of facial lesions3. Studies aimed at investigating the treatments and complications of facial trauma allow quantification and qualification of such lesions’ sequelae4. The main causes of facial fractures include auto accidents and assaults. Other causes are falls, sports accidents and accidents at work5-7. In some countries, the reduction of

motor vehicle accidents by the introduction of safety measures and legislation to punish vehicle-driving irregularities has increased physical assaults and sports accidents to the condition of main agents causing traumatic buccomaxillofacial injuries8. Thus, it is evident the need for campaigns to prevent the main etiological agents of facial trauma, to contribute to the reduction of this type of occurrence. The objective of this study is to determine the incidence and etiology of facial traumas with diagnosis of facial fractures seen at the Buccomaxillofacial Surgery and Traumatology Service (CTBMF) of the Holy Home of Mercy Hospital Complex of Porto Alegre, RS, Brazil.

METHODS This work was accomplished after approval by the Ethics in Research Committee of the Holy Home of Mercy of Porto Alegre, under the protocol n° 460/09.

1 - Santa Casa de Misericórdia Complex of Porto Alegre, Bucomaxillofacial Surgery Service, Porto Alegre, RS, Brazil. 2 - Lutheran University of Brazil, Post-Graduation Program in Dentistry, Canoas, RS, Brazil. Rev Col Bras Cir 2017; 44(5): 491-497


492

Zamboni Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil

This is a retrospective, cross-sectional, epidemiological study of 134 patients with 153 facial fractures treated from January 2004 to December 2008. The data evaluated considered the etiological agent of the lesion, age and gender, as well as the fractures’ locations. We divided the etiological agents into nine groups: aggression, fall, automobile accidents, cycling accidents, motorcycle accidents, sports accidents, work accidents, firearm injuries and run-overs. We classified fractures of the facial skeleton into mandibular bone, zygomatic complex, maxillary bones, nasal bones and zygomatic arches9,10. We included orbital fractures in the subgroup of fractures of the zygomatic complex, as it participates in the orbit floor, as well as in its lateral wall11. We included dento-alveolar fractures in the group of fractures of the bone corresponding to the fractured arch, and we excluded the exclusively dental fractures from the statistics. We analyzed the data collected in the medical charts and transposed them to specific records, being one record for each chart. We extracted the following data: patient identification, age group, gender, etiological agent of facial fracture and facial fracture classification. We performed a descriptive analysis of the data, calculating frequency and percentage for categorical variables, and mean and standard deviation for quantitative variables. To identify the factors associated with the trauma site, we used the ANOVA test with Tukey’s multiple comparisons for the quantitative variables and the chi-square or Fisher’s exact test for categorical variables. We analyzed data in the SPSS 12.0 software and the minimum level of significance was 5%.

RESULTS Regarding the profile of the patients treated, the male gender was the most affected, representing 86.6% of face fractures, when compared with the female one (13.4%), establishing a ratio of approximately 6:1. Regarding the distribution of frequencies and percentages referring to the age groups, we verified that the most affected age group was from 21 to 30 years old, with 41 cases (30.6%), followed by the age

group from 31 to 40 years, with 38 patients (28.4%). Regarding the etiological agents, we recorded 52 cases (38.8%) of assault, 19 cases of auto accident (14.2%), 18 motorcycle accidents (13.4%), 12 cases of fall (9%), nine run-overs (6.7%), seven sports accidents (5.2%), seven work accidents (5.2%), six cases of firearm injury (4.5%) and four cases of cycling accident (3%) (Table 1). Table 1. Frequency and percentage of facial fractures according to etiological agent.

Etiologic Agent

Frequency

%

Automobile accident

19

14.2

Bicycle accident

4

3.0

Sports accident

7

5.2

Motorcycle accident

18

13.4

Work accident

7

5.2

Assault

52

38.8

Run-over

9

6.7

Firearm

6

4.5

Fall

12

9.0

Total

134

100

Fonte: dados obtidos nos prontuários do Serviço de CTBMF Santa Casa - POA, 2009.

In the distribution of patients with facial fractures according to the etiological agent and in relation to the mean age, we verified, through the Analysis of Variance complemented by the Tukey’s Multiple Comparison Test, that patients with face fractures due to sports accidents were younger (24.86 years) than patients who had face fractures due to work accidents (47 years) or fall. The other etiologies did not differ as for the age (Table 2). We grouped automobile accidents, motorcycle accidents, cycling accidents and run-overs in the item traffic accidents. Of the 153 facial fractures, 68 (44.5%) occurred in the zygomatic complex, 65 (42.5%) in the mandible, eight (5.2%) in the maxillary bone, seven (4.5%) in the nasal bones and in the zygomatic arch we recorded five fractures (3.3%) (Table 3). Regarding the number of facial fractures in both males and females, the mandibular

Rev Col Bras Cir 2017; 44(5): 491-497


Zamboni Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil

493

bone was the most affected. None of the types of facial fractures assessed in this study showed gender preference, according to the chi-square and Fisher’s exact tests.

Table 4 shows the distribution of facial fractures according to age group. We found no significant difference in this assessment.

Table 2. Distribution of patients with facial fractures according to etiological agents and mean age.

Table 3. Distribution of frequencies and percentages of facial fractures.

Frequency

%

Zygomatic Complex

68

44.5

Mandible

65

42.5

Maxilla

8

5.2

Nasal Bones

7

4.5

Zygomatic Arch

5

3.3

Type of fracture

Age group (years) Etiologic Agent

N

Average

Standard Deviation

Traffic accident

50

32.08

14.042

Sports accident

7

24.86

5.872

Work accident

7

47.00

11.240

Assault

52

34.56

11.823

Firearm

6

29.00

5.831

Fall

12

42.33

13.547

Total

134

34.22

13.119

Fonte: dados obtidos nos prontuários do Serviço de CTBMF Santa Casa - POA, 2009.

Fonte: dados obtidos nos prontuários do Serviço de CTBMF Santa Casa - POA, 2009.

Table 4. Distribution of facial fractures according to age group.

Type of fracture

Age (in years) 11-20

21-30

31-40

41-50

51-60

61-70

Total

Zygomatic Complex

9

16

19

11

9

4

68

Mandible

8

23

21

8

2

3

65

Maxilla

0

1

3

1

2

1

8

Nasal Bones

3

2

1

1

0

0

7

Zygomatic Arch

0

1

3

0

1

0

5

Fonte: dados obtidos nos prontuários do Serviço de CTBMF Santa Casa - POA, 2009.

With respect to the frequency and percentage of the etiological agent related to the facial fracture region, the Fisher’s exact test showed no significant difference in fracture type according to etiology. Regarding gender and etiological agent, we observed that men presented more fractures due to assaults (42.2%), while women had more fractures due to run-overs (22.2%) and falls (27.8%).

DISCUSSION The results of an epidemiological survey of face traumas of a population should be evaluated accor-

ding to a series of variables related to individuals and the region studied. Ellis et al.12 point out that the cause of the lesion and the geographical area where it occurred, the socioeconomic level of the population, the study period and the population mobility can alter results and show the most varied trauma presentations. Data obtained in this study revealed that the two main etiological factors of facial fractures are assaults and traffic accidents. Three decades ago, the studies pointed to motor vehicle accidents as the main cause of facial trauma9,10. However, current research in Brazil shows an increasing participation of physical assault as an etiological factor of facial trauma due to the increase in urban violence,

Rev Col Bras Cir 2017; 44(5): 491-497


494

Zamboni Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre â&#x20AC;&#x201C; RS â&#x20AC;&#x201C; Brazil

which, among other problems, is associated with the socioeconomic and emotional conflicts to which many individuals are subjected, especially the youngest6,11. Public actions such as speeding control and severe punishment for drunk drivers, as well as the introduction of safety devices such as seat belts and helmets, air bags, side protection bars and the evolution of the automobile industry as a whole are responsible for decreasing the number of facial traumas due to motor vehicle accidents10,13. Our results are in agreement with other evidence in the literature reporting that assaults were the main cause of facial fractures3,11,14-19. In the present study, assaults resulted in 38.8% of the cases, excluding gunshot wounds. The second most involved etiological agent was automobile accidents, accounting for 14.2% of facial fractures, being in accordance with the literature. When studied in conjunction with run-overs, motorcycle accidents and cycling accidents, that percentage rises to 37.3%. These data show a worrying reality, since even when all types of traffic accidents were present, the facial trauma index was still lower than that of assaults16. Other studies, however, still point car accidents as the most frequent etiological agent3,20-23. This may be due to the inclusion of patients who were victims of facial trauma in the eighties and nineties, when the use of protective equipment in vehicles was not mandatory, especially in Brazil10,13. According to Adebayo et al.5, the etiologies of face traumas vary with the socioeconomic conditions of each region. Studies carried out in different regions report divergences regarding the main etiological factor. Thus, Thomson et al.23 verified that most facial fractures were caused by falls and Subhashraj, Ramkumar and Ravindran24 concluded that the motorcycle accident was the main etiological factor. In our study, these agents represented the fourth and third causes of facial fracture, respectively. Accidents at work were the etiological agent with the highest mean age (47 years), while sports accidents had the lowest one (24.86 years). Fall is the main mechanism of trauma in the age group over 40 years, and is usually related to the presence of multiple diseases9,19,25. However, Macedo et al.11 stated that the fall proved to be an important trauma mechanism

at the extremes of age. Karyouti26 reported that children are constantly engaged in sports activities and risky exercise, without the use of appropriate protective equipment and away from the supervision of those responsible, contributing to the increase in the number of facial fractures. Since the care for children in the facility where we conducted this study is restricted, we could not confront these data6,27. Regarding age, the studied sample revealed that the highest prevalence of facial fractures occurs in the age group of 21 to 30 years and from 31 to 40 years, unlike other studies in which the predominant age group was from 61 to 70 years old5,9,15,17,20-23,28-34. For Reis et al.14, the most affected age group was 11 to 30 years. This is due to the fact that in this age group individuals are more exposed to the risk factors, since they are in full physical and professional activity7. Evidence in the literature reveals a high number of fractures and facial trauma caused by sports, among them soccer, hockey, rugby and wrestling, which brings into question the incentive to use personal protective equipment7. Fractures of the zygomatic complex were responsible for 44.5% of the total fractures in this study, followed by mandible fractures, with 42.5%, both in agreement with the reviewed literature5,20,21-23,26,28,30,31,34. However, there is great disagreement with the researched authors, the nose bone fractures being more prevalent in several studies17,29,32. As for Alvi, Doherty and Lewen16, orbital fractures were the most prevalent. The relationship between the type of fracture and the etiology of trauma showed no difference in this study. Some works have found that most mandible fractures are the result of physical assault, traffic accidents, gunshot wounds, accidents with industrial workers and sports accidents7,19. According to Greenberg and Haug25, assaults cause more fractures of the mandible, zygomatic complex and nose bones, whereas motor vehicle accidents promote more fractures in the maxillary bones. As in most studies, our work showed a predominance of facial fractures in men5,9,11,15,20,34. Thomson et al.23, however, identified the female gender as more prevalent. We observed a difference in etiology according to gender, in which men have more fractu-

Rev Col Bras Cir 2017; 44(5): 491-497


Zamboni Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil

res due to assaults (42.2%), while women have more fractures due to run-overs (22.2%) and falls (27.8%). Silva34 emphasizes that trauma should not be seen only as a medical problem, but also a social and economic one. Costs incurred in providing care to victims by health workers, damage to property involved at the time of trauma, loss of wages and permanent or transient disabilities often lead to difficulties in the social reintegration of victims and their return to the job market. All these factors, added to the familiar incon-

495

veniences and psychological wear and tear on patient care reveal a much greater repercussion of this disease, which deserves constant attention by health institutions that provide assistance to traumatized patients. This research provides data for a better understanding of the facial fractures’ main etiological agents and the most affected bones in the studied population, being of fundamental importance for the planning, organization and improvement of care of such patients.

R E S U M O Objetivos: pesquisar a incidência e etiologia dos traumas de face com diagnóstico de fratura facial atendidos no Serviço de Cirurgia e Traumatologia Bucomaxilofacial do Complexo Hospitalar Santa Casa de Misericórdia de Porto Alegre. Métodos: estudo epidemiológico, transversal, retrospectivo de 134 pacientes vítimas de trauma com 153 fraturas faciais. Resultados: o gênero mais acometido foi o masculino (86,6%) e sua incidência foi maior na faixa etária dos 21 aos 30 anos. A principal etiologia foi a agressão (38,8%), seguida de acidentes automobilísticos (14,2%), acidentes motociclísticos (13,4%), quedas (9%), atropelamentos (6,7%), acidentes esportivos (5,2%), acidentes de trabalho (5,2%), ferimentos por arma de fogo (4,5%) e acidentes ciclísticos (3%). As fraturas mais frequentes foram as do complexo zigomático (44,5%), seguidas das fraturas da mandíbula (42,5%), osso maxilar (5,2%), ossos próprios nasais (4,5%) e arco zigomático (3,3%). Conclusões: as fraturas do complexo zigomático e da mandíbula foram as de maior incidência nos traumas de face, e tiveram como principal causa as agressões físicas. Descritores: Epidemiologia. Traumatismos Faciais. Cirurgiões Bucomaxilofaciais.

REFERENCES 1.

2.

3. 4.

5.

6.

7.

Gassner R, Tuli T, Hächl O, Moreira R, Ulmer H. Craniomaxillofacial trauma in children: a review of 3,385 cases with 6,060 injuries in 10 years. J Oral Maxillofac Surg. 2004;62(4):399-407. Barker R, Hockey R, Spinks D, Miles E. Facial Injury. Injury Bulletin Queensland Injury Surveillance Unit. 2003;79:1-6 Banks P. Killey’s fraturas da mandíbula. 4ª ed. São Paulo: Santos; 1994. Moreira RWF. Análise epidemiológica de casos de traumatismo crâniomaxilo-facial atendidos no Estado da Pensilvânia - EUA, no período entre 1994 e 2002 [dissertação]. Piracicaba (SP): UNICAMP/ FOP; 2004. Adebayo ET, Ajike OS, Adekeye EO. Analysis of the pattern of maxillofacial fractures in Kaduna, Nigeria. Br. J. Oral Maxillofac. Surg. 2003;41(6):396-400. Owusu JA, Bellile E, Moyer JS, Sidman JD. Patterns of Pediatric Mandible Fractures in the United States. JAMA Facial Plast Surg. 2016;18(1):37-41.

Bobian MR, Hanba CJ, Svider PF, Hojjat H, Folbe AJ, Eloy JA, et al. Soccer-related facial trauma. A nationwide perspective. Ann Otol Rhinol Laryngol. 2016;125(12):992-6. 8. Holderbaum MA. Levantamento epidemiológico das fraturas de face na comunidade atendida junto ao Grupo Hospitalar Conceição - Porto Alegre, 1997 [dissertação]. Porto Alegre (RS): Pontifícia Universidade Católica do Rio Grande do Sul; 1997. 9. Wulkan M, Parreira Júnior JG, Botter DA. Epidemiologia do trauma facial. Rev Assoc Med Bras. 2005;51(5):290-5. 10. Montovani JC, Campos LMP, Gomes MA, Moraes VRS, Ferreira FD, Nogueira EA. Etiologia e incidência das fraturas faciais em adultos e crianças: experiência em 513 casos. Rev Bras Otorrinolaringol. 2006; 72(2):235-41. 11. Macedo JLS, Camargo LM, Almeida PF, Rosa SC. Perfil epidemiológico do trauma de face dos pacientes atendidos no pronto socorro de um hospital público. Rev Col Bras Cir. 2008;35(1):913.

Rev Col Bras Cir 2017; 44(5): 491-497


496

Zamboni Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil

12. Ellis E 3rd, el-Attar A, Moos KF. An analysis of 2,067 cases of zygomatico-orbital fractures. J Oral Maxillofac Surg. 1985;43(6):417-28. 13. Shapiro AJ, Johnson RM, Miller SF, McCarthy MC. Facial fractures in a level I trauma centre: the importance of protective devices and alcohol abuse. Injury. 2001;32(5):353-6. 14. Reis LF, Marzola C, Toledo Filho JL. Prevalência das fraturas faciais, na região de Bauru, no período de janeiro de 1991 a dezembro de 1995. Rev Odonto Ciênc. 2001;16(34):231-40. 15. Valente ROH, Souza LCM, Antonini SV, Glock L, Castro Neto WN. Epidemiologia das fraturas mandibulares atendidas no Hospital da Santa Casa de Misericórdia de São Paulo (HSCSP) entre 1996 e 1998. Rev Bras Cir Period. 2003;1(2):141-6. 16. Alvi A, Doherty T, Lewen G. Facial fractures and concomitant injuries in trauma patients. Laryngoscope. 2003;113(1):102-6. 17. Portolan M, Torriani MA. Estudo de prevalência das fraturas bucomaxilofaciais na região de Pelotas. Revista Odonto Ciênc. 2005; 20(47):63-8. 18. Falcão MFL, Segundo AVL, Silveira MMF. Estudo epidemiológico de 1758 fraturas faciais tratadas no Hospital da Restauração, Recife/PE. Rev Cir Traumatol Buco-Maxilo-Fac. 2005;5(3):65-72. 19. Moore BK, Smit R, Colquhoun A, Thompson WM. Maxillofacial fractures at Waikato Hospital, New Zealand: 2004 to 2013. N Z Med J. 2015;128(1426):96-102. 20. Brasileiro BF. Prevalência, tratamento e complicações dos casos de trauma facial atendidos pela FOP - UNICAMP de abril de 1999 a março de 2004 [dissertação]. Piracicaba (SP): UNICAMP; 2005. 21. Patrocínio LG, Patrocínio JA, Borba BHC, Bonatti BS, Pinto LF, Vieira JV, et al. Fratura de mandíbula: análise de 293 pacientes tratados no Hospital de Clínicas da Universidade Federal de Uberlândia. Rev Bras Otorrinolaringol. 2005;71(5):560-5. 22. Paes JV. Estudo retrospectivo da prevalência de fraturas de faciais no planalto serrano Catarinense. [dissertação] Porto Alegre (RS): Pontifícia Universidade Católica do Rio Grande do Sul; 2008. 23. Thomson WM, Stephenson S, Kieser JA, Langley

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

JD. Dental and maxillofacial injuries among older New Zealanders during the 1990s. Int J Oral Maxillofac Surg. 2003;32(2):201-5. Subhashraj K, Ramkumar S, Ravindran C. Pattern of mandibular fractures in Chennai, India. Br J Oral Maxillofac Surg. 2008;46(2):126-7. Greenberg AM, Haug RH, editors. Craniomaxillofacial fractures: principles of internal fixation using the AO/ASIF technique. New York: Springer-Verlag; 1993. Karyouti SM. Maxillofacial injuries at Jordan University Hospital. Int J Oral Maxillofacial Surg. 1987;16(3):262-5. Almahdi HM, Higzi MA. Maxillofacial fractures among Sudanese children at Khartoum Dental Teaching Hospital. BMC Res Notes. 2016;9:120. Camarini ET, Pavan AJ, Iwaki Filho L, Barbosa CEB. Estudo epidemiológico dos traumatismos bucomaxilofaciais na região metropolitana de Maringá-PR entre os anos de 1997 e 2003. Rev Cir Traumatol Buco-Maxilo-Fac. 2004;4(2):125-9. Mourouzis C, Koumoura F. Sports-related maxillofacial fractures: a retrospective study of 125 patients. Int J Oral Maxillofac Surg. 2005;34(6): 635-8. Bezerra MF. Estudo epidemiológico dos pacientes hospitalizados e atendidos pelo Serviço de Cirurgia e Traumatologia Bucomaxilofacial do Hospital São Lucas, Porto Alegre, 2000 a 2005 [dissertação]. Porto Alegre (RS): Pontifícia Universidade Católica do Rio Grande do Sul; 2006. Menezes MM, Yui KCK, Araujo MAM, Valera MC. Prevalência de traumatismos maxilo-faciais e dentais em pacientes atendidos no Pronto-Socorro Municipal de São José dos Campos/SP. Revista Odonto Ciênc. 2007;22(57):210-6. Sarmento DJS, Santos JA, Cavalcanti AL. Características e distribuição das fraturas mandibulares por causas externas: estudo retrospectivo. Pesq Bras Odontoped Clin Integr. 2007;7(2):139-44. Claro FA. Prevalência de fraturas maxilo-faciais na cidade de Taubaté: revisão de 125 casos. Rev Biociênc Taubaté. 2003;9(4):31-7. Silva AC. Análise epidemiológica e avaliação do

Rev Col Bras Cir 2017; 44(5): 491-497


Zamboni Epidemiological study of facial fractures at the Oral and Maxillofacial Surgery Service, Santa Casa de Misericordia Hospital Complex, Porto Alegre – RS – Brazil

tratamento e das complicações dos casos de trauma facial atendidos na FOP - Unicamp, no período de abril de 1999 a março de 2000 [dissertação]. Piracicaba (SP): UNICAMP; 2001. Received in: 28/04/2017 Accepted for publication: 22/06/2017

497

Conflict of interest: none. Source of funding: none. Mailing address: Caren Serra Bavaresco E-mail: c_bavaresco@yahoo.com.br / tutoracarensb@ gmail.com

Rev Col Bras Cir 2017; 44(5): 491-497


Original Article

DOI: 10.1590/0100-69912017005012

Effects of local pressure on cutaneous blood flow in pigs Efeitos da pressão local no fluxo sanguíneo cutâneo de porcos

MICHEL LUCIANO HOLGER TOLEDANO VAENA, TCBC-RJ1; JOÃO PAULO SINNECKER2; BRUNO BENEDETTI PINTO1; MARIO FRITSCH TOROS NEVES1; FERNANDO SERRA-GUIMARÃES1; RUY GARCIA MARQUES, TCBC-RJ1. A B S T R A C T Objective: to evaluate the effects of increasing pressures on the cutaneous blood flow in the skin of pigs. Methods: we conducted an experimental study in pigs submitted to subcutaneous magnetic implants (n=30). After healing, were applied external magnets with varying magnetic forces to the skin, generating compression. We evaluated the cutaneous circulation of the skin under compression by the Laser Speckle Contrast Imaging (LSCI) technique. We measured the depth of the implants by ultrasonography, and applied computational simulations to the calculation of the different pressure values, considering the different distances between implants and external magnets. Results: nineteen implants presented complications. The remaining 11 were submitted to different magnetic compression forces and perfusion analysis. Two linear regression models showed an inverse correlation between exerted pressure and cutaneous perfusion, with significant variation, mainly in the initial pressure increases, of up to 20mmHg. Conclusion: The main reduction in cutaneous blood flow resulted from initial increases of up to 20 mmHg. The results suggest that tissue ischemia can occur even in low-pressure regimes, which could contribute to the appearance of skin lesions, particularly ulcers related to medical devices. Keywords: Pressure Ulcer. Skin. Microcirculation. Regional Blood Flow. Models, Animal. Swine.

INTRODUCTION

P

ressure ulcers are usually defined as localized lesions on the skin, and may or may not include the underlying tissue. They usually occur on a prominent bone or arise related to a medical device or others. The lesion is the result of intense and/or prolonged pressure, or of shear pressure. Certain factors such as advanced age, the presence of multiple comorbidities, among others, may increase the risk of developing pressure ulcers during hospitalization1. The prevalence of pressure ulcers (grades 1-4) in hospitalized patients in Europe is 18.1%2, and 13.5% in the United States3, and their incidence when related to medical devices is 34.5%4. Considering that the prevalence in developing countries is equal that or greater, the overall economic impact is enormous. Pressure relief is the most important aspect in the prevention of pressure ulcers, either by mobilization of the patient or by the use of specific mat-

tresses that increase the contact area, reducing the interface pressure5. The effects of increasing pressures exerted on the surface of the skin in the microcirculatory blood flow have been studied before, but without a more detailed quantitative analysis6. Understanding these effects may help in the prevention of pressure ulcers by establishing more adequate parameters for the safety of support surfaces and medical devices that come in contact with the skin. The aim of our study is to evaluate the effects of increasing pressures on the microcirculatory blood flow of the skin of pigs.

METHODS We used a system consisting of a subcutaneous magnetic implant and external magnets of different intensities to generate an in vivo increasing compression of the skin. We introduced thirty magne-

1 - University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. 2 - Brazilian Center for Physical Research, Department of Experimental Physics of Low Energies, Rio de Janeiro, RJ, Brazil. Rev Col Bras Cir 2017; 44(5): 498-504


Vaena Effects of local pressure on cutaneous blood flow in pigs

499

tic implants (n=30) into two male pigs (Sus domesticus) weighing 17.2kg (pig #1) and 19kg (pig #2), with prior approval of the institution’s ethics committee for animal testing. After complete healing of the wound, we applied external magnets of four different intensities to the skin, generating compression. We evaluated the cutaneous circulation of compressed skin with the Laser Speckle contrast Imaging (LSCI) technique, with the PeriCam PSI device. Each magnetic implant consisted of a silicone capsule containing two N40 grade neodymium magnets (Nd2Fe14B). The capsule was made of silicone elastomer (medical grade) with shore 30A hardness, manufactured in an ellipsoid shape (50mm long and 22mm wide), with a flattened profile (4mm height), without edges or tips, to avoid tissue trauma. The two internal neodymium magnets were identical, disk-shaped, 6mm in diameter and 1.5mm thick, with field-strength intensities of 48 mT and axially magnetized, with nominal magnetic remanence of 1.25 T (Figure 1A). We sedated the animals with intramuscular injection (acepromazine acetate 0.2mg/kg) and transported them to the surgical center. After venous catheterization, we administered additional anesthetics (propofol and thiopental sodium) in dose-effect mode and performed tracheal intubation. Each pig was kept under general anesthesia during the introduction of the implants. The dorsal skin was trichotomized and prepared with antiseptic solution (chlorhexidine 2%). We marked the cutaneous incision sites with a dermographic pen. We made all 2cm incisions over the dorsal skin, and introduced a straight cannula through each incision (Figure 1B). The cannula promoted blunt dissection and detachment of the sub-dermal plane, making a narrow tunnel parallel to the skin surface. We introduced each implant through the cutaneous incision (Figure 1C) and placed it in its final position under the dermis, and sutured the incisions. We used topical antibiotic spray on the sutured wounds. At the end of the procedure, each pig received a total of 15 implants under the dorsal skin, totaling 30 implants (Figure 1D). After the post-anesthetic recovery, the animals were released to feed and move freely during the wounds’ healing period.

Figure 1. A- Implant; B- Dissection; C- Insertion; D- final aspect.

Forty days after the procedure, were sedated the pigs again, transported them to the surgical center and anesthetized them. We kept the ambient temperature constant to avoid changes in the cutaneous circulation. We evaluated the perfusion on the pigs’ dorsal skin over the implants using the LSCI technique. Skin sites that had apparent clinical changes (such as erythema, continuity solutions or fluctuation) were excluded from the analysis. The LSCI technique uses the “mottling” phenomenon to obtain a perfusion map of the tissues, capturing the changes in the “mottled” pattern, which correspond to the reflexes of erythrocytes in movement, with a camera located inside the projector of the Pericam PSI device when illuminated by the Laser beam (Figure 2). We analyzed these changes mathematically and generated a tissue perfusion map.

Figure 2. Evaluation of the cutaneous circulation by the LSCI technique.

Rev Col Bras Cir 2017; 44(5): 498-504


Vaena Effects of local pressure on cutaneous blood flow in pigs

500

After this initial evaluation, we placed magnets of different forces on the dorsal skin on the same sites, above the implants. These external magnets consisted of a synthesized N48 grade rectangular magnetic neodymium block (25mm x 12mm x 3mm) with a 4mm center hole to allow penetration of the laser beam into the skin (Figure 3A). On this rectangular magnet, we added up to three pairs of cylindrical magnets (9mm X 3mm) of grade N42 neodymium. For each added pair, the total magnetization of the system increased, thereby increasing the magnetic attraction force between the implant under the skin and the external magnetic block, thus increasing the mechanical pressure on the skin surface (Figures 3B, 3C and 3D).

the pulling force exerted by the system. Thus, given the surface area (already known) of the outer magnetic block and defining the intensity of the magnetic force exerted by the system, it was possible to calculate the exact pressure the skin surface was submitted to. To calculate the pressure values exerted by the outer block on the skin surface, we performed computational simulations using the COMSOL Multiphysics® simulations software under license n. 2072699. We tabulated the data obtained from the PeriCam cutaneous perfusion readings and compared them with the estimated blood pressure levels. We performed statistical analysis with the R software (The R Foundation for Statistical Computing, Vienna, Austria). After applying the Shapiro-Wilk test to the variables, we computed the Pearson correlation coefficient. We calculated the linear regression models and the applied F test (p<0.05) for statistical significance.

RESULTS

Figure 3. A- External block + implant; B, C, D- Magnets added.

After the procedure, we removed the outer magnets and subjected the dorsal skin to ultrasonographic examination. Again, any implant sites containing subclinical collections not previously identified, such as seromas or abscesses, were excluded from the study. The depth of the implants relative to the skin surface was measured at 0.1mm intervals using a linear high frequency (12Mhz) transducer. This precise measurement of the implants’ depth allowed to establish the exact distance (shown as the distance “x” in Figure 3A) between the magnetic components and, therefore, to determine

Seventeen implants (57%) presented complications: implant extrusion (12), partial wound dehiscence (1) and infection abscess (4). We detected two collections of peri-implant fluids during ultrasonographic examination. We performed PeriCam cutaneous perfusion readings of the dorsal skin on the remaining eleven implant sites in both pigs (five on pig #1 and six on pig #2). Ultrasonographic examination results showed that the depth of the implants relative to the skin surface (the distance “x” in Figure 3A) ranged from 0.83 mm to 1.73mm (1.31mm ± 0.28mm). The estimated pressure levels exerted by the rectangular magnetic block on the skin ranged from 5.36mmHg to 37.47mmHg (19.5mmHg ± 7.52mmHg). A scatter plot of cutaneous perfusion readings by the PeriCam apparatus and exerted pressures is shown in figure 4A. We applied two different linear regression models to the dispersion diagram, as shown in figure 4B. The Pearson coefficient of -0.4299 showed an inverse correlation, with statistical significance. The F test applied in Models 1 and 2 showed statistical significance (p=0.0036 and p=0.0004). The properties of the two linear regression models are summarized in table 1. As seen below, Model 2 (a second order polynomial) showed a higher fit (higher R2) when compared with Model 1 (linear).

Rev Col Bras Cir 2017; 44(5): 498-504


Vaena Effects of local pressure on cutaneous blood flow in pigs

501 Table 1. Properties of the linear regression models applied to the scatter plot.

Variables

Estimated F test T test value (p-value) (p-value)

1 model Intercept (α)

40.8021

Pressure (β1)

-1.3084

0.0036

0.0000

0.1654

0.0036

2 model

Figura 4. A) Gráfico de dispersão; B) Regressões lineares.

DISCUSSION Recent studies have questioned the safety of the standard limit of 32mmHg pressure used as a parameter for interface pressure on support surfaces7. In hospitalized patients, a source of pressure on the skin surface may be the medical devices themselves employed to patient monitoring or treatment4. Ulcers related to medical devices can be caused by nasal cannulas, endotracheal tube attachments, pulse oximetry sensors, anti-embolism stockings, orthopedic splints etc. Whereas all of these devices are specially designed not to damage skin integrity, the high prevalence of ulcers related to medical devices suggests that current safety parameters should be questioned. Over time, different animal models have been proposed in the literature to study the local circulatory effects of mechanical pressure exerted on the skin. Due to practical limitations, most studies are performed on rats. Although mouse skin circulation is provided by direct cutaneous arteries of the panniculus carnosus, which is absent in humans, several publications of different authors have employed and validated animal models of rats8. However, considering the anatomical and histological similarities with the human skin, the pig is considered the best animal model for cutaneous healing9. Pioneering studies on pressure ulcers developed by Groth10, Kosiak11 and Dinsdale12, using rabbits, dogs and pigs, respectively, evaluated the effects of applying pressure to the skin of live animals, basi-

Intercept (α)

84.3855

0.0004

0.0000

Pressure (β1)

-6.0037

0.0012

[Pressure]² (β2) 0.1102

0.0076

0.2830

cally by macroscopically inspecting the skin changes and subsequent histopathological analysis. This type of study was also employed by Daniel13, who in turn demonstrated the greater vulnerability of deep tissues to pressure ischemia, while the dermis could withstand longer ischemic intervals without necrosis. These studies, if taken as a whole, have not yet contemplated real-time dynamic changes in the dermal circulation due to increased pressure on the skin. Of course, the collection of information in live animals adds technical difficulties and ethical implications that do not occur in postmortem specimens14,15. Branemark16, however, drew attention to this issue by using a vital microscopy camera study, demonstrating the influence of higher pressures on the skin and the ischemic changes in the microcirculation. In the last two decades, in vivo cutaneous microcirculation research has been based more on non-invasive methods, such as optical microscopy and laser-Doppler techniques. Techniques derived from optical microscopy basically depend on transillumination, which tends to restrict anatomical areas that can be studied (such as video-capillaroscopy of the nail bed in humans), or may require vital microscopy camera techniques17. The limitation of such techniques is that they basically provide morphological information about the microcirculation. Laser-Doppler techniques, on the other hand, provide quantitative information related to the skin blood flow. This latter method was validated by Salcido et al.18 in the research on the development of pressure ulcers, but there are many technical issues

Rev Col Bras Cir 2017; 44(5): 498-504


Vaena Effects of local pressure on cutaneous blood flow in pigs

502

that must be taken into account to guarantee the fidelity and reproducibility of Laser-Doppler techniques19. The LSCI technique has been used more recently and provides real-time, non-invasive skin circulation monitoring. It has been shown that the flow measurements between Laser Doppler and LSCI display a linear relationship20, but one of the main advantages of LSCI is its high reproducibility21. In addition, the LSCI measurement depth is more superficial than the Laser Doppler techniques22. In our study, the central orifice in the rectangular external magnetic block allowed the laser beam to penetrate the Region of Interest (ROI) while the pressure on the skin was gradually increased with the additional magnets. The LSCI technique allowed non-contact, non-invasive monitoring of skin blood flow. The magnetic system avoided the influence of external factors that could affect perfusion readings by the LSCI technique, such as variations in the animal position, variations in lighting conditions or changes in the ROI. The magnetic system also ensured that the ROI remained within the tissue under compression. In addition, the long interval between the introduction of the implants and the evaluation of the dermal circulation allowed the complete healing of the surgical wounds, thus avoiding the influence of inflammatory changes and the phenomenon of autonomization on the evaluated skin segments. Few studies have also used magnetic force to induce mechanical compression in animal models. Peirce23 developed an animal model of ischemia-reperfusion injury by implanting a steel plate under the dorsal skin of rats. An external magnet was applied to the skin 24 hours after the implantation procedure, generating compression and local ischemia. Peirce’s experimental model advocates the initiation of compression cycles 24 hours after the surgical procedure. This model does not take into account the inflammatory changes inherent in the surgical procedure, nor the local circulatory changes in the skin flap due to subcutaneous tissue dissection. Despite these conceptual limitations, the Pierce study demonstrated that ischemia-reperfusion cycles were more damaging to the skin when compared with ischemia alone. These results were also demonstrated using non-magnetic compression models17. Nguyen-Tu24 used Peirce’s animal model to

study the microvascular response of skin to pressure in obese rats. The results of that study suggest that obesity could play a protective role by reducing skin lesions induced by compression through changes in skin structure. A clear limitation of the study, which the authors recognize, is related to the possible changes in the pressures applied to the skin due to the different skin thicknesses between groups. It is known that the magnetic attraction force is inversely proportional to the distance applied. In fact, because of the non-linearity of the magnetic force, small variations in the implant’s depth under the skin can cause large variations in the pressure exerted on the surface of the skin. Although it should be noted that in the Nguyen-Tu study the same magnets were used in both groups of rats (obese and non-obese), different skin thicknesses may have generated different pressures in each group. In our study, such thickness variations were not neglected, and computational simulations (using COMSOL Multiphysics® modeling software and ultrasound measurements) allowed the calculation of different pressure values, taking into account the different distances due to the different skin thicknesses. Perfusion Units (PUs) are arbitrary units used by the LSCI technique and should be interpreted as real-time flow measurements, without absolute values. They serve to be compared to each other in real-time dynamic analysis. The results in our study suggest that dermal blood flow is extremely sensitive to the pressure exerted on the surface of the skin. Basically, the Model 2 curve shows a drop in blood flow to about half at pressures up to 10mmHg. Between 10 and 20 mmHg, the flow falls to one-fourth of normal physiological levels and continues to drop at 25mmHg. These results are in accordance with what would be expected within the knowledge of the mean value of cutaneous capillary pressure since the pioneering study of Landis25 and also of more recent publications26. However, readings of the LSCI technique also demonstrated blood flow measurements under higher pressure regimes. In fact, Shibata et al.6, using capillaroscopy based on a video probe, observed that a vertical tension level similar to blood pressure was necessary to interrupt the capillary flow. However, as we have previously emphasized, techniques derived from optical microscopy do

Rev Col Bras Cir 2017; 44(5): 498-504


Vaena Effects of local pressure on cutaneous blood flow in pigs

503

not allow the quantification of changes in the flow due to increases in pressure. Based on the results of our study, it is likely that under pressures greater than 2530mmHg, blood continues to circulate, but well below physiological levels in terms of flow. These results corroborate the questioning about the safety of the standard pressure limit of 32mmHg used in the supportive surface definitions26. In addition, they may help explain the onset of certain ulcers, particularly pressure ulcers related to medical devices. In clinical practice, mechanical pressure exerted on the skin surface generates locally increased interstitial pressures that may exceed capillary pressure. According to the anatomical topography of the compressed region, these pressures are transmitted hete-

rogeneously, resulting in partial blockage or complete collapse of the capillaries, generating tissue ischemia. When certain pathological conditions outweigh compensatory mechanisms (self-regulation of capillary circulation), pressure ulcers can arise even in the context of slight pressures exerted on the skin. Our results suggest that the main reduction in cutaneous blood flow originates from the initial increases of pressure up to 20mmHg, reinforcing the importance of surveillance and early relief of the pressure exerted in the prevention of pressure ulcers. Even under mild pressure conditions, health professionals should be aware of pressure ulcers related to medical devices, in particular due to the specificities of the contact interface and to the frequent presence of comorbidities.

R E S U M O Objetivo: avaliar os efeitos de pressões crescentes exercidas sobre a pele de porcos no fluxo sanguíneo cutâneo. Métodos: estudo experimental em porcos submetidos a implantes magnéticos subcutâneos (n=30). Após a cicatrização, foram aplicados sobre a pele, ímãs externos com forças magnéticas variadas, gerando compressão. A circulação cutânea da pele submetida à compressão foi avaliada pela técnica Laser Speckle Contrast Imaging (LSCI). A profundidade dos implantes foi medida por ultrassonografia, e simulações computacionais foram aplicadas para o cálculo dos diferentes valores de pressão, considerando-se as variadas distâncias entre implantes e ímãs externos. Resultados: dezenove implantes apresentaram complicações. Os 11 restantes foram submetidos à diferentes compressões magnéticas e análise de perfusão. Dois modelos de regressão linear mostraram uma correlação inversa entre pressão exercida e perfusão cutânea com variação significativa principalmente nos acréscimos iniciais de pressão até 20mmHg. Conclusão: a principal redução do fluxo sanguíneo cutâneo resulta dos acréscimos iniciais de pressão de até 20mmHg. Os resultados sugerem que a isquemia tecidual pode ocorrer mesmo em regimes de baixa pressão, o que poderia contribuir para surgimento de lesões de pele, particularmente as úlceras relacionadas a dispositivos médicos. Descritores: Lesão por Pressão. Pele. Microcirculação. Fluxo Sanguíneo Regional. Modelos Animais. Suínos.

REFERENCES 1.

2.

3.

4.

5.

Gardiner JC, Reed PL, Bonner JD, Haggerty DK, Hale DG. Incidence of hospital-acquired pressure ulcers - a population-based cohort study. Int Wound J. 2016;13(5):809-20. Vanderwee K, Clark M, Dealey C, Gunningberg L, Defloor T. Pressure ulcer prevalence in Europe: a pilot study. J Eval Clin Pract. 2007;13(2):227-35. VanGilder C, Amlung S, Harrison P, Meyer S. Results of the 2008-2009 International Pressure Ulcer Prevalence Survey and a 3-year, acute care, unit-specific analysis. Ostomy Wound Manage. 2009;55(11):39-45. Black JM, Cuddigan JE, Walko MA, Didier LA, Lander MJ, Kelpe MR. Medical device related pressure ulcers in hospitalized patients. Int Wound J. 2010;7(5):35865.

6.

7.

8.

9.

Moysidis T, Niebel W, Bartsch K, Maier I, Lehmann N, Nonnemacher M, et al. Prevention of pressure ulcer: interaction of body characteristics and different mattresses. Int Wound J. 2011;8(6):578-84. Shibata M, Yamakoshi T, Yamakoshi K, Komeda T. Observation of capillary flow in human skin during tissue compression using CCD video-microscopy. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:51614. Gefen A. The biomechanics of sitting-acquired pressure ulcers in patients with spinal cord injury or lesions. Int Wound J. 2007;4(3):222-31. Salcido R, Popescu A, Ahn C. Animal models in pressure ulcer research. The J Spinal Cord Med. 2007;30(2):107-16. Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound repair

Rev Col Bras Cir 2017; 44(5): 498-504


Vaena Effects of local pressure on cutaneous blood flow in pigs

504

10.

11. 12.

13.

14.

15. 16.

17.

18.

19.

20.

Regen. 2001;9(2):66-76. Groth KE. Klinische Beobachtungen und experimentelle Studien über die Entstehung des Dekubitus. Acta Chir Scand. 1942; Suppl 76:209. Kosiak M. Etiology of decubitus ulcers. Arch Phys Med Rehabil. 1961;42:19-29. Dinsdale SM. Decubitus ulcers: role of pressure and friction in causation. Arch Phys Med Rehabil. 1974;55(4):147-52. Daniel RK, Priest DL, Wheatley DC. Etiologic factors in pressure sores: an experimental model. Arch Phys Med Rehabil. 1981;62(10):492-8. Marques RG, Morales MM, Petroianu A. Brazilian law for scientific use of animals. Acta Cir Bras. 2009;24(1):69-74. Schanaider A, Silva PC. Uso de animais em cirurgia experimental. Acta Cir Bras. 2004;19(4):441-7. Branemark PI. Microvascular function at reduced flow rates. In: Kenedi RM, Coeden JM, editors. Bed sore biomechanics. London (UK): Macmillan Education; 1976. p. 63-8. Tsuji S, Ichioka S, Sekiya N, Nakatsuka T. Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers. Wound Repair Regen. 2005;13(2):209-15. Salcido R, Fisher SB, Donofrio JC, Bieschke M, Knapp C, Liang R, et al. An animal model and computercontrolled surface pressure delivery system for the production of pressure ulcers. J Rehabil Res Dev. 1995;32(2):149-61. Roustit M, Cracowski JL. Non-invasive assessment of skin microvascular function in humans: an insight into methods. Microcirculation. 2012;19(1):47-64. Millet C, Roustit M, Blaise S, Cracowski JL. Comparison between laser speckle contrast imaging and laser Doppler imaging to assess skin blood flow

21.

22.

23.

24.

25. 26.

in humans. Microvasc Res. 2011;82(2):147-51. Mahé G, Humeau-Heurtier A, Durand S, Leftheriotis G, Abraham P. Assessment of skin microvascular function and dysfunction with laser speckle contrast imaging. Cir Cardiovasc Imaging. 2012;5(1):155-63. O’Doherty J, McNamara P, Clancy NT, Enfield JG, Leahy MJ. Comparison of instruments for investigation of microcirculatory blood flow and red blood cell concentration. J Biomed Opt. 2009;14(3):034025-. Peirce SM, Skalak TC, Rodeheaver GT. Ischemiareperfusion injury in chronic pressure ulcer formation: a skin model in the rat. Wound Repair Regen. 2000;8(1):68-76. Nguyen-Tu MS, Begey AL, Decorps J, Boizot J, Sommer P, Fromy B, et al. Skin microvascular response to pressure load in obese mice. Microvasc Res. 2013;90:138-43. Landis EM. Micro-injection studies of capillary blood pressure in human skin. Heart. 1930;15(15):209-28. de Graaff JC, Ubbink DT, Lagarde SM, Jacobs MJ. The feasibility and reliability of capillary blood pressure measurements in the fingernail fold. Microvasc Res. 2002;63(3):270-8.

Received in: 28/04/2017 Accepted for publication: 01/06/2017 Conflict of interest: none. Source of funding: FAPERJ – Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro. Mailing address: Michel Luciano Holger Toledano Vaena E-mail: michel.vaena@hotmail.com / gmail.com

Rev Col Bras Cir 2017; 44(5): 498-504

michel.vaena@


Original Article

DOI: 10.1590/0100-69912017005013

Observation time and spontaneous resolution of primary phimosis in children Tempo de observação e resolução espontânea de fimose primária em crianças PEDRO LUIZ TOLEDO DE ARRUDA LOURENÇÃO1; DÊNIS SILVA QUEIROZ1; WILSON ELIAS DE-OLIVEIRA JUNIOR1; GIOVANA TUCCILLE COMES1; ROZEMEIRE GARCIA MARQUES1; DÉBORA RODRIGUES JOZALA1; ERIKA VERUSKA PAIVA ORTOLAN1. A B S T R A C T Objective: to investigate spontaneous resolution rate of a series of patients with physiologic phimosis in relation to observation time and presence of symptoms. Methods: retrospective and longitudinal follow-up study of patients with physiologic phimosis, that did not apply topic treatment. These patients were invited for a new visit for reevaluation, or recent data were obtained by chart analysis. Spontaneous resolution rate was determined and statistically compared to age, presence of symptoms at first medical visit and time until reevaluation. Results: seventy one patients were included. Medium time of observation from first visit to reevaluation was 37.4 months. There was spontaneous resolution of phimosis in 32 (45%) patients. Children with spontaneous resolution were younger at initial diagnosis and were observed during a longer period of time. Most asymptomatic patients at first visit presented spontaneous resolution. However, it was not possible to stablish a significant relationship between presence of symptoms and evolution of physiologic phimosis. Conclusions: time of observation was the main determinant of spontaneous resolution of patients with physiologic phimosis, reinforcing the current more conservative approach regarding circumcision of those patients. Keywords: Phimosis. Circumcision, Male. Child.

INTRODUCTION

P

himosis is a clinical condition where prepuce does not allow the exposure of glans1,2. Primary physiologic phimosis is considered when prepuce is normal (also histologically) but does not allow glans exposure and usually spontaneously resolves until adolescence3,4. On the other hand, secondary or pathologic phimosis is defined as the absence of glans exposure due to the presence of a fibrous ring at prepuce, due to repeated balanoposthitis, ammoniacal dermatitis, or sclerous-atrophic liquen of unknown origin5-8. Up to 96% of boys are born with phimosis, being one of the most common diagnosis in Pediatrics9. However, although with high prevalence and, usually, with a benign evolution, treatment is controversial10. Circumcision is the surgical removal of prepuce and is one of the most ancient described surgical procedures and one of the most performed nowadays11. In the last years, medical indication of

circumcision is being limited, due to encouraging results of the use of topic corticoids, and natural evolution with spontaneous resolution of patients with physiologic phimosis12-14. At the present, it is being advocated to limit and postpone surgical procedure, reserving it to patients with recurrent balanoposthitis, recurrent urinary infections, to adolescents that cannot completely expose their glans and to patients with pathologic phimosis. However, one every six boys in the World will be submitted to circumcision4. Aside from ethnic and religious factors (responsible for neonatal circumcision in some cultures), familial pressure is responsible for a large number of surgeries. In clinical practice, in many occasions it is very hard to convince family of conservative expectant treatment. Parents hardly believe that phimosis will spontaneously resolve and desire to anticipate surgery, even of asymptomatic patients17. Therefore, it is very important to perform studies to verify the natural evolution of physiologic

1 - Botucatu School of Medicine (UNESP), Pediatric Surgery Division, Department of Surgery and Orthopedics, Botucatu, São Paulo, Brazil. Rev Col Bras Cir 2017; 44(5): 505-510


Lourenção Observation time and spontaneous resolution of primary phimosis in children

506

phimosis and spontaneous resolution. We decided to investigate spontaneous resolution rate of a series of patients with physiologic phimosis, and to verify which factors influence this evolution.

METHODS Retrospective study, with longitudinal observational follow-up, of patients up to 15 years old, attended at Pediatric Surgery Ambulatory at Clinical Hospital of Botucatu Medical School – UNESP, from 2006 to 2013, with diagnosis of phimosis; patients were in a waiting list to perform elective circumcision. Until 2013, we performed circumcision in all patients older than two years old, with physiologic phimosis, that were not using diapers. Former data were obtained by chart analysis; age at first medical appointment (phimosis diagnosis), symptoms (micturition difficulties (“ballooning”), balanoposthitis, paraphimosis, urinary tract infections) were recorded, as well as physical exam observations and use (or not) of topical corticosteroids. Patients were contacted by phone to attend a new consultation for reevaluation. In that moment, it was determined the time between first consultation and reevaluation, age, presence of symptoms and physical exam findings, previous use of topic treatment, and phimosis spontaneous resolution or not. For patients that could not be contacted by phone, or that did not attend consultation, reevaluation data were obtained by analysis of medical charts at the most recent ambulatory visit, if it occurred in the last six months. For patients already submitted to circumcision, reevaluation data were collected at the medical evaluation at surgery that was considered the reevaluation date. In all moments of the study, phimosis diagnosis was made by non- retractile prepuces, represented by types 3, 4 and 5 of Kikiros et al.12 scale of retractility of prepuce. Prepuces type 0, 1 and 2 were considered normal. In the study it was included all patients at waiting list with physiologic phimosis. Patients with secondary phimosis that were submitted to any topic treatment and those who did not attend reevaluation medical appointments or without recent information (last six months) were excluded.

Descriptive statistical analysis was made by determination of frequencies and percentages of categorized variables and medium, median and standard deviations of continuous variables. Comparison of patients with spontaneous resolution or not, related to age at diagnosis, age at reevaluation and time from first medical appointment to reevaluation, was made by variance analysis (ANOVA), followed by Tukey test. To verify the association between spontaneous resolution rate of phimosis and age groups, interval between first and reevaluation medical appointment, and presence of symptoms at first visit, it was performed Chi-square test. Comparison between symptoms at different moments of evaluation was made by Proportion Analysis Test. Comparison between median time until reevaluation of operated patients and with spontaneous resolution was made by Student t test. Significance level was 5% and it was used the SAS program for Windows version 9.2. This study was approved by the Ethical Committee in Research of Botucatu Medical School (CAAE nº 27102714.7.0000.5411). All patients’ parents and/ or guardians that attended medical visits signed a free consent form, and patients older than 11 years old also signed the consent form.

RESULTS Ninety nine children were followed from 2006 to 2013 and were included in the waiting list for circumcision. Twenty eight patients were excluded due to topic treatment, pathological phimosis or absence at the reevaluation medical appointment or lack of recent information regarding phimosis. In the end, 71 patients were included in the study. Medium time of observation (between first and reevaluation medical appointments) was 37.4 months. Spontaneous resolution of physiologic phimosis was observed in 32 patients (45%). Among those 39 without resolution, 32 (82%) had already been submitted to circumcision. For these patients, data of surgery was considered reevaluation data. Comparison between patients with and without spontaneous resolution, related to median age at diagnosis and at reevaluation, and medium time between both moments of evaluation is shown in table 1. When those 32 circumcised patients were specifically

Rev Col Bras Cir 2017; 44(5): 505-510


Lourenção Observation time and spontaneous resolution of primary phimosis in children

analyzed, medium time of observation was significantly lower than of patients with spontaneous resolution (26.3 months versus 48.5 months; p=0.002, t-Student test). On the other hand, children without spontaneous resolution were significantly older than those with spontaneous resolution (60.2x44.2 months; p=0.004, ANOVA, Tukey).

507

common symptom in both was micturition alteration (“ballooning”). Proportion of asymptomatic patients was significantly higher at reevaluation than at first medical appointment (p=0.01). There were three times more patients that already had paraphimosis at reevaluation.

Table 1. Comparison of ages of patients at first and reevaluation medical appointments and time between these two moments, in relation to phimosis evolution.

Spontaneous resolution (n=32) Medium (±standard deviation)

Without spontaneous resolution (n=35) Medium (±standard deviation)

p*

Age at first medical appointment (months)

44.2 (± 30.3)

60.3 (± 35.4)

0.04

Age at reevaluation (months)

92.7(± 37.9)

Figure 1. Spontaneous resolution x observation time.

Time between first medical appointment 48.5 (± 30.6) and reevaluation (months)

88.6(± 42.8)

0.67

28.2 (± 25.5) 0.003

* ANOVA, Tukey.

Stratification in intervals of time of observation, between first and reevaluation medical appointments, in relation to spontaneous resolution of phimosis, is shown in figure 1. Most patients with interval of observation lower than five years did not present spontaneous resolution (32x19), while most with at least five years of interval (13x7) showed spontaneous resolution (p=0.03; Chi-square test). There were no statistical significant differences between stratified spontaneous resolution rates of different age groups (lower than 5 years, 5 to 7 years, 7 to 10 years, older than 10 years) at clinical reevaluation (p=0.91; Chi-square test). Clinical symptoms present in both moments of evaluation are resumed at table 2. Most patients were asymptomatic in both moments, and the most

Spontaneous resolution of phimosis in relation to presence of symptoms at first medical appointment was also investigated. Among 34 patients with symptoms at first medical appointment, 13 (38.2%) showed spontaneous resolution and 37 that were asymptomatic at first medical appointment, 19 (51%) presented spontaneous resolution, with higher rate of spontaneous resolution of patients initially asymptomatic (p=0.2672; Chi-square test).

Table 2. Clinical symptoms at first and reevaluation medical appointments.

Symptoms

First medical Difference of Reevaluation appointment proportions*

Micturition 32.4% (23/71) “ballooning”

19.7% (14/71)

z=1.720645; p=0.08

Previous urinary 15.5% (11/71) tract infection

9.86% (7/71)

z=1.008921; p=0.3283

4.2% (3/71)

z=-1.014389; p=0.3697

Previous episode of 23.9% (17/71) balanoposthitis

11.2% (8/71)

z=1.983005; p=0.0474

Asymptomatic 52.1% (37/71)

73.2% (52/71)

z=-2.60257; p=0.01

Previous episode of paraphimosis

1.4% (1/71)

* Proportion Difference Test (Z test).

Rev Col Bras Cir 2017; 44(5): 505-510


Lourenção Observation time and spontaneous resolution of primary phimosis in children

508

DISCUSSION Although circumcision is one of the most ancient procedures in history of surgical interventions, and one of the most commonly in childhood, its indication is still very controversial2,18. Surgical intervention is not necessary to correct phimosis of all children with non-retractile prepuce16. This resolution will occur physiologically in most of these children19. Gairdner20 observed resolution in 90% of patients until three years old and in 99% until 17 years old. Kaplan21 showed that only 4% of children had a totally retractile prepuce at birth, and that 50% presented it completely closed without visualization of urethral orifice. On the other hand, at six months of age, it was observed retractile prepuce in 20% of boys. Similar results were also obtained by Kayaba et al.22 among 603 Japanese boys. Incidence of totally retractile foreskin gradually increased from 0% at six months old to 62.9% in age group of 11 to 15 years old. Routine circumcision for all boys, with different ages, although performed in many centers, is not considered a necessary treatment by most guidelines, although some evidences show potential benefits like diminishing risk of sexually transmitted diseases, urinary infections prophylaxis and cancer of penis17,18. Absolute indications for circumcision include xerotic balanitis and recurrent balanoposthitis, that affect approximately 2% of children4,14,16. Balanoprepucial adhesions, esmegma cysts, micturition “ballooning”, and non-retractile prepuce are physiologic conditions, and parents must be tranquilized, without the need of specialist evaluation4. Adolescents that did not present spontaneous resolution also have surgical indication16. Relative indications include recurrent urinary infections, long foreskin and resolved episodes of paraphimosis4,23. Also, recent results with topic treatment with corticosteroids are promising and limit routine circumcision12,13,19. Our study included a series of children with physiologic phimosis, initially evaluated between 2006 and 2013, observed for a medium period of 37.4 months. There was spontaneous resolution in 45% of patients. Children with spontaneous resolution were younger at initial diagnosis (44.2x60.3 months; p=0.04) and were followed-up for longer period of time (48.5x28.2

months; p=0.003). Although medium age at first medical appointment was higher for those without spontaneous resolution, spontaneous resolution rates showed little variation among different age groups (p=0.91), showing that this physiologic evolution may occur in different age groups, from five years until adolescence, with more than ten years. It was not possible to stablish a “cut-off” age for spontaneous resolution. Most children followed-up for a minimum of five years showed spontaneous resolution (p=0.03). On the other hand, in our series, most patients were followed-up for less than five years. Among 39 children without spontaneous resolution, 32 had already been submitted to circumcision. Medium time of observation of those patients was lower than of patients with spontaneous resolution (26.3x48.5 months; p=0.002). Among those 32 operated, 19 (59.3%) had initial symptoms of balanoposthitis, paraphimosis or urinary infections, that justified surgery4. The 13 other patients (40.7%) remained asymptomatic, but were operated after a short period of time, for they were the first in the waiting list. It is our belief that many of these patients did not present spontaneous resolution due to the fact of insufficient time for its occurrence. Most children were asymptomatic, at first and at reevaluation medical appointments. Also, among asymptomatic children, the most common clinical complaint in both moments of evaluation was micturition “ballooning”, a very common symptom that provokes anxiety of parents, but that must be considered physiologic and without absolute indication for surgery4. It is important to stress the significant higher number of patients with balanoposthitis at first consultation than at reevaluation. During initial visit, orientations about local hygiene and care may explain diminishing of these symptoms during follow-up. All symptoms were more commonly present at first consultation than at reevaluation, except paraphimosis episodes. This may be explained by the fact that this complication increases with time, being more common in older children4,23. Although most asymptomatic patients presented spontaneous resolution, it was not possible to stablish a significant relationship between presence of symptoms and physiologic phimosis evolution (p=0.2672). This is highlighted by the fact that 13 of

Rev Col Bras Cir 2017; 44(5): 505-510


Lourenção Observation time and spontaneous resolution of primary phimosis in children

34 symptomatic patients at first medical appointment presented spontaneous resolution. In our series of patients, the main factor that determined spontaneous resolution of physiologic phimosis was the time of observation, preferably with more than five years intervals. Presence of symptoms such as balanoposthitis, paraphimosis episodes or urinary tract infections may influence evolution, determining an earlier surgical intervention. In spite of all controversial data about medical indication of circumcision, and the potential benefits of routine neonatal circumcision, our data reinforce current tendency for more conservative approach of circumcision indication in patients with

509

physiologic phimosis. More important is “enough time” for spontaneous resolution. For that, it is important to explain the parents the reasons for this conservative approach and the real chance of spontaneous resolutions. Risks related to surgical and anesthetic procedure, health care costs, high rate of spontaneous resolution of physiologic phimosis and high rate of success of topic treatment, are important to limit indication of routine circumcision. At present, in our service, we limit indications of postectomy to secondary phimosis, for those with balanoposthitis episodes, or urinary tract infections, and for adolescents with physiologic phimosis without result with topic treatment.

R E S U M O Objetivo: investigar a taxa de resolução espontânea de uma série de pacientes com diagnóstico de fimose fisiológica e sua relação com o tempo de observação e com a presença de sintomas. Métodos: estudo retrospectivo e de seguimento longitudinal e observacional de pacientes em acompanhamento por fimose fisiológica, que não haviam realizado tratamento tópico. Estes pacientes foram convocados para uma consulta médica de reavaliação ou tiveram dados recentes obtidos a partir da análise dos prontuários. A taxa de resolução espontânea foi determinada e comparada estatisticamente de acordo com a idade, com a presença de sintomas no momento da primeira consulta e com o tempo transcorrido entre a primeira consulta e a reavaliação. Resultados: setenta e um pacientes foram incluídos no estudo. O tempo médio de observação, entre a primeira consulta e a reavaliação foi de 37,4 meses. Houve resolução espontânea da fimose em 32 (45%) pacientes. As crianças que apresentaram resolução espontânea eram mais jovens no momento do diagnóstico inicial e foram observadas por um maior intervalo de tempo. A maior parte dos pacientes assintomáticos na primeira consulta apresentou resolução espontânea. No entanto, não foi possível estabelecer uma relação significativa entre a presença de sintomas e a evolução da fimose fisiológica. Conclusões: o tempo de observação foi o maior determinante para a resolução espontânea de pacientes com fimose fisiológica, o que reforça a tendência atual mais conservadora em relação às indicações de circuncisão para estes pacientes. Descritores: Fimose. Circuncisão Masculina. Criança.

REFERENCES

of childhood. London: Butterworths; 1951. Robarts FH. Penis and prepuce. In: Mason Brown JJ, editor. Surgery of childhood. London: Edward Arnold; 1962. p. 1159-81. 8. Catterall RD, Oates JK. Treatment of balanitis xerotica obliterans with hydrocortisone injections. Br J Vener Dis. 1962;38:75-7. 9. Shahid SK. Phimosis in children. ISRN Urol. 2012; 2012:707329. 10. Ng WT, Fan N, Wong CK, Leung SL, Yuen KS, Sze YS, et al. Treatment of childhood phimosis with a moderately potent topical steroid. ANZ J Surg. 2001; 71(9):541-3. 11. Marzaro M, Carmignola G, Zoppellaro F, Schiavon G, Ferro M, Fusaro F, et al. [Phimosis: when does it require surgical intervention?]. Minerva Pediatr. 1997;49(6):245-8. Italian. 7.

1.

2. 3.

4. 5.

6.

Braz A. Fimose. Curso de patologias cirúrgicas do pênis e escroto na criança. Pediatr Atual. 1998;11:54-66. Hodges FM. Phimosis in antiquity. World J Urol. 1999;17(3):133-6. Ashfield JE, Nickel KR, Siemens DR, MacNeily AE, Nickel JC. Treatment of phimosis with topical steroids in 194 children. J Urol. 2003;169(3):1106-8. Malone P, Steinbrecher H. Medical aspects of male circumcision. BMJ. 2007; 335(7631):1206-90. Spilsbury K, Semmens JB, Wisniewski ZS, Holman CD. Circumcision for phimosis and other medical indications in Western Australian boys. Med J Aust. 2003;178(4):155-8. Higgins TT, Williams DI, Ellison Nash DF. The urology

Rev Col Bras Cir 2017; 44(5): 505-510


Lourenção Observation time and spontaneous resolution of primary phimosis in children

510

12. Kikiros CS, Beasley SW, Woodward AA. The response of phimosis to local steroid application. Ped Surg Int. 1993;8(4):329-32. 13. Pileggi F de O, Vicente YA. Phimotic ring topical corticoid cream (0.1% mometasone furoate) treatment in children. J Pediatr Surg. 2007;42(10):1749-52. 14. Tekgül S, Riedmiller H, Gerharz E, Hoebeke P, Kocvara R, Nijman R, et al; Guidelines on Paediatric Urology. European Society for Paediatric Urology: Nice (FR); 2008. 15. Fergusson DM, Lawton JM, Shannon FT. Neonatal circumcision and penile problems: an 8-year longitudinal study. Pediatrics. 1988;81(4):537-41. 16. Koff WJ, Damião R, Correrette FB; Sociedade Brasileira de Urologia. Reuniões de consensos e diretrizes. Sociedade Brasileira de Urologia - SBU. Rio de Janeiro: SBU; 2005. 17. Morris BJ, Waskett JH, Banerjee J, Wamai RG, Tobian AA, Gray RH, et al. A ‘snip’ in time: what is the best age to circumcise? BMC Pediatr. 2012;12:20. 18. Simpson E, Carstensen J, Murphy P. Neonatal circumcision: new recommendations & implications for practice. Mo Med. 2014;111(3):222-30.

19. Sneppen I, Thorup J. Foreskin morbidity in uncircumcised males. Pediatrics. 2016;137(5): pii: e20154340. 20. Gairdner D. The fate of foreskein: a study of circumcision. Br Med J. 1949; 2(4642):1433-7. 21. Kaplan GW. Complications of circumcision. Urol Clin North Am. 1983;10(3): 543-9. 22. Kayaba H, Tamura H, Kitajima S, Fujiwara Y, Kato T, Kato T. Analysis of shape and retractability of the prepuce in 603 Japanese boys. J Urol. 1996; 156(5):1813-5. 23. Pohlman GD, Phillips JM, Wilcox DT. Simple method of paraphimosis reduction revisited: point of technique and review of the literature. J Pediatr Urol. 2013;9(1):104-7. Received in: 15/05/2017 Accepted for publication: 22/06/2017 Conflict of interest: none. Source of funding: none. Mailing address: Pedro Luiz Toledo de Arruda Lourenção E-mail: plourencao@gmail.com / lourencao@fmb.unesp.br

Rev Col Bras Cir 2017; 44(5): 505-510


Review Article

DOI: 10.1590/0100-69912017005014

Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency Escleroterapia ecoguiada com espuma para tratamento da insuficiência venosa crônica grave GUILHERME CAMARGO GONÇALVES DE-AQUINO, TCBC-SP1.

DE-ABREU1;

OTACÍLIO

DE

CAMARGO JÚNIOR1; MÁRCIA FAYAD MARCONDES

DE-ABREU1;

JOSÉ LUÍS BRAGA

A B S T R A C T Chronic venous insufficiency is characterized by cutaneous alterations caused by venous hypertension; in severe forms, it progresses to lower limb ulcers. Lower limb varicose veins are the main cause of chronic venous insufficiency, and the classic treatment includes surgery and compressive therapy. Minimally invasive alternative treatments for varicose veins include new techniques such as venous thermal ablation using laser or radiofrequency. The use of different methods depends on clinical and anatomical factors. Ultrasound-guided foam sclerotherapy is the venous injection of sclerosing foam controlled by Doppler ultrasound. Sclerotherapy is very useful to treat varicose veins, and probably, is cheaper than other methods. However, until the present, it is the less studied method. Keywords: Varicose Ulcer. Varicose Veins. Venous Insufficiency. Sclerotherapy. Ultrasonography, Doppler, Duplex.

INTRODUCTION

Importance of great saphenous vein (GSV)

C

hronic venous insufficiency (CVI) is characterized by cutaneous alterations caused by venous hypertension1-3. Lower limb varicose veins are the most frequent cause of CVI4 and the most severe form of the disease is venous ulcer5. It is estimated that 30 to 40% of adult population presents varicose veins6,7 and up to 6% of patients with varicose veins will develop ulcers at some time in their lives8. Up to 30% of varicose veins can progress to more severe forms of CVI9,10. CVI causes pain, functional impairment and worsening of quality of life11-14. Almost 1% of general population may present venous ulcer in some moment and prevalence of open venous ulcer is around 0.1% to 0.3%8,15. In Brazil, from 2009 to 2013, 420,000 hospitalizations were caused by varicose veins and it was spent more than U$ 90 million16. In the same period, more than 220,000 temporary social security assistant were granted, with an expense with venous disease of more than US$ 60 million. From 2008 to 2012, there were 5,5 thousand retirements due to incapacity and lower limb varicose veins17.

In a study of 3072 patients followed and examined for more than six years, varicose vein prevalence increased from 22.7% to 25.1% and prevalence of CVI from 14.5% to 16. Among patients with GSV reflux, 31.8% showed worsening of CVI and only 19.8% of those without reflux progressed9,15. Reflux to great saphenous vein is the most frequent event associated to CVI and ulcer formation4,18. In the presence of venous reflux, a long liquid column is formed, increasing hydrostatic pressure and venous hypertension19. GSV reflux is identified in up to 80% of patients with CVI20-23.

Chronic venous insufficiency evaluation Guidelines based on evidences recommend evaluation of patients with interview and physical exam, Doppler vascular ultrasound exam (DUS) and categorization of patients using CEAP classification1,4. CEAP classification describes systematically CVI according to clinical presentation, etiology (primary or secondary), anatomy (superficial, deep and perforating veins) and physiopathology (obstruction, reflux, or both). It guides treatment24-26, but with low sensitivity to slight alterations

1 - Pontifical Catholic University of Campinas, Campinas, SP, Brazil. Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

512

of the severity of the disease27. Follow-up of treatment results must include evaluation of quality of life, severity score and anatomic and physiologic data obtained by DUS. Clinical score of severity of disease proposed by the American Venous Forum is based on signals and symptoms identified by the examiner and allows follow-up of CVI evolution28. The score does not measure quality of life, but is sensitive to clinical presentation and is considered the best method nowadays to follow up the results of treatment4,29. Recently, it is becoming popular the evaluation of quality of life (QL) to quantify the impact of CVI on patients30. QL of patients with CVI is altered by physical aspect, pain, functional impairment and mobility deficit31,32. Specific questionnaires for CVI QL evaluation are validated in English and are difficult to use in other languages, since they must be translated and validated33-35. Charing Cross and Aberdeen question forms are translated and validated in Portuguese36,37. Evolution of disease is best assessed when multiple instruments are used, avoiding systematic errors of single question forms37-39. Anatomic and functional evaluation of venous system must be made by Doppler ultrasound (DUS), the ideal method, since is reproducible and non-invasive, allowing the access to venous patency or occlusion, identification and quantification of venous reflux, measure of caliber of veins and differentiation of primary and secondary venous disease40-42. DUS does not identify venous hypertension. Venous pressure measure is invasive and in the present is not often performed43.

Treatment Clinical treatment is based in rest with elevation of lower limbs and use of compressive socks. Most patients may benefit of compressive treatment that is recommended to open or healed varicose ulcer and is not indicated to patients with arterial obstruction. Compressive treatment improves symptoms and is efficient for ulcer healing, but with low adherence. Clinical treatment does not eliminate varicose veins and does not alter anatomic basis of venous hypertension. Rate of recurrence of ulcer in one year reaches 70%, and 35% of patients have four or more episodes of ulcer44,45. Obese and older patients have difficulty to wear elastic stockings, 15% are not capable to use them and 26% need help to wear them46,47. Low adherence to treatment is

responsible for ulcer recurrence48. Single compressive therapy is not efficient for patients with varicose veins and CVI49-52. In our country, the most common treatment for varicose veins and GSV reflux is surgical (proximal ligature and flebo-extraction of great saphenous vein)1,2,53. In patients with GSV reflux and intact deep venous system, surgery is efficient and indicated to avoid recurrence of varicose ulcer5,54. In the ESCHAR randomized study, surgery and clinical treatments were equivalent: 65% of ulcer healed in 24 weeks. Surgery was not able to heal ulcers more rapidly, but, after 12 months, recurrence was 28% in the group without surgery and 12% in the surgical group55,56. Surgery improves quality of life12, but cannot be performed in a considerable amount of patients. In randomized trials, up to 25% of patients refuses surgery45,56. Surgical patients present more pain and post-operatory discomfort and delay resuming work activities57. In five years, recurrence, with new indication of surgery, is 6%58. Complications such as deep venous thrombosis (DVT) may occur in 5% of patients, saphenous nerve lesion in 7% and hematoma in 33%59. Worse surgical results are related to pre-operatory factors such as body mass index superior to 29kg/ m2, previous pregnancies, recurrent varicose veins, CVI with eczema and healed ulcers60-62. Among minimally invasive techniques for the treatment of varicose veins and reflux of GSV it is included ultra-sound guided foam sclerotherapy (UFS) and thermal ablation using radiofrequency or laser. Thermal ablation is performed by inserting a thermal element catheter in the distal part of GSV by puncture. The procedure is performed with femoral blockage or with local anesthesia. Catheter must progress proximally inside the vein, in all extension to be treated. Thermal energy released by the catheter destroys venous endothelium. Veins with excess tortuosity, occluded segments, stenotic, or with parietal irregularities may impair progression of catheter. Big diameter veins are challenging for thermal ablation, since they distance thermal element from endothelium. Excessively superficial veins increase the risk of thermal lesion of skin. Finally, costs of catheters and generators limit their use. Minimally invasive treatments present advantages such as rapid recovery of patients and possibility of ambulatory treatment. These modali-

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

ties have good relation cost/efficiency and complication rate similar to conventional surgical treatment. According to recommendations of the British National Institute for Health and Clinical Excellence, these treatments must by primarily used in relation to conventional surgery49. Patients with worse quality of life had better benefits when submitted to minimally invasive techniques, regardless the one used38,63. Ultrasound guided foam sclerotherapy is less expensive than other methods, but cost analysis in Brazil is lacking.

513

Foam sclerotherapy results In 2000, Cabrera et al.74 published a retrospective study of 500 patients with GSV reflux treated by UFS and reported occlusion of 81% of treated veins. They did not report any severe complication75. Wright et al.76, in 2006, treated 437 patients, 70.9% with GSV reflux. They reported elimination of reflux in 83.9% of treated veins with UFS in one year. Foam sclerotherapy was inferior to surgery to eliminate venous reflux, but patients returned to daily activities more rapidly. Rasmussen et al.77, in 2011, studied 580 limbs with GSV reflux,

History Elsholz (1623-1688) was the first to perform injection in humans and Zollikofer (1682) was the first to perform sclerotherapy64. Since XVII Century, several sclerosing agents were used, and many of them were toxic. Varicose veins sclerotherapy was used and favored until XIX Century. In the XX Century, surgical technique developed and became the treatment with better results; therefore, sclerotherapy for trunk veins was abandoned65. Also, during XX Century, many reports of the use of detergent sclerosing agents were published, with higher sclerosing power, forming foam when mixed with gas. In 1937, Biegeleisen used etanolamine; in 1946, Reiner used tetradecyl sodium sulfate and, in 1963, Henschel described sclerotherapy with polidocanol66. The first description of foam sclerotherapy was in 193967. In 1944, Orbach described the technique of blood displacement with air bubble to treat varicose veins with diameter of up to 4mm, and, in 1956, Fluckiger described that foam reached distant places from the point of injection by manual massage orientation67-69. In 1989, Knight70 described the ultrasound-guided venous puncture and, in 1993, Schadeck71 described that foam was visible at ultrasound, allowing observation of its progress. In 1995, Cabrera72 described good results for ultrasound guided sclerotherapy using foam, that was patented for use in saphenous vein. In 2000, Tessari73 described the reproducible low cost technique to produce foam using syringes connected to three-way stopcock, mixing liquid and air at a 1:4 proportion, displacing the mix from one syringe to another at least for ten times. Tessari method produces an homogenous and stable foam that popularized foam sclerotherapy68,72,73.

randomized for surgical treatment, thermal ablation or UFS. 1443 were submitted to foam sclerotherapy and, after one year of treatment, 16.3% maintained reflux, an index superior to other groups. Patients had faster recovery with less pain than those treated by surgery. There was no statistical difference among complications of studied groups77. Brittenden et al.78, in a randomized trial, compared foam, surgery and thermal ablation in 785 patients. 280 patients were submitted to foam sclerotherapy. In six months, 63% of veins eliminated reflux. UFS result was inferior to surgical and thermal ablation groups. Wright, Rasmussen and Brittenden studies, as well as most studies on foam sclerotherapy, are characterized by the small proportion of patients with open or healed ulcer76-78. Rate of occlusion of treated veins in several studies varied from 53 to 85%75,78-83. Myers84 studied 1189 sclerotherapies in 489 patients; 454 GSV were treated and 53.1% of veins occluded after one single session of sclerotherapy. Occlusion rate of tributary veins was higher than of GSV. Veins with diameter higher than 6mm had worse results than those with five or lower diameter. Best results were observed with foam sclerotherapy, with more than 12ml of volume and with sclerosing agents with higher concentration84. Interest of foam sclerotherapy of varicose veins in patients with severe CVI is justified since frequently these patients are older and less prone to surgical treatment. Few randomized studies compared UFS to clinical treatment for ulcer healing and casuistic is small. There are evidences of favoring it in detriment to surgical treatment. In a meta-analysis Mauck85 identified less recurrence of varicose ulcers when venous reflux was

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

514

surgically removed. Mauck results were similar to those of ESCHAR study. Several authors that study healing of varicose ulcers following UFS report healing rates higher than those of ESCHAR study, however, there is a predominance of non-comparative studies. O’Hare86 reported 91.2% rate of healing in 24 weeks, Kulkarni87 71.1% in 24 weeks, Campos88 91.3% after one year and Cabrera89 83% in six months. Campos90, in 2014, randomized 49 patients with ulcer and GSV reflux for surgery or UFS. Twenty three limbs were submitted to UFS and healing occurred in 91.3% after one year of treatment. There were no severe complications or differences in relation to surgical group. Ulcer healing rate, clinical improvement and of QL were similar88,90. Silva91 identified healing of 84.2% of ulcers. Randomized studies report similar healing of ulcers with surgery, thermal ablation or UFS, with numerous casuistic77,92,93. Brittenden94 showed improvement of QL, however, less intense in patients treated by UFS when compared to surgery.

Safety Wright76 reported an incidence of deep venous thrombosis (DVT) in 5.3% of patients after injection of 60ml of foam, and the author decided to reduce maximum volume to 30ml. After reduction, 95 patients were treated without new episodes of DVT76. According to European consensus, foam volume should be limited to 10ml per session95,96. Yamaki97 affirms that equivalent volumes injected fractioned caused less progression of foam to deep venous system evaluated by Doppler. When foam volume used is reduced, the procedure is safer, but requires a higher number of treatment sessions to eliminate numerous and bulky varicose veins. Some authors use the maneuver of elevation the limb to reduce venous volume and allow contact of lesser volume with endothelium96,97. More frequent side effects following UFS are phlebitis and cutaneous pigmentation. There are a few reports of severe complications such as DVT, pulmonary thromboembolism, stroke and cerebral embolization in patients with permeate oval foramen. Severe complications are rare (<0.1%)82,98. Thomasset99 states that women have more side effect reactions than men, specifically cutaneous pigmentation. Cavezzi and Parsi100 estimates the occurrence of pigmentation in 10%

to 30% of patients, with resolution in 12 months. Jia82 in a systematic review of more than 9000 sclerotherapies describes the most frequent complications: 4.7% of phlebitis, 17.8% of cutaneous pigmentation and 25.6% of local pain. He also observed less than 1% of deep venous thrombosis and pulmonary embolism, and 1.4% of visual disturbances.

Current Recommendations Laser or radiofrequency ablation is recommended by guidelines of “American Venus Forum” (AVF) and British National Institute for Health and Clinical Excellence (NICE) as first choice of treatment of saphenous veins with reflux. There are evidences that treatment avoids ulcer recurrence and speeds recovery with less pain than conventional surgery. AVF states that evidences on UFS are insufficient4,5. According to NICE, evidences on safety and efficacy of UFS are adequate and recommends that foam sclerotherapy must be offered primarily than surgical treatment49. European guidelines published in 2014 considered UFS evidences adequate and recommend the method to treat saphenous veins and varicose collateral veins96. Patients submitted to UFS present better QL than surgical patients after four weeks of treatment due to less pain. After one year of treatment, surgical patients show better QL, but with higher rate of recurrence of varicose veins than those submitted to UDS77,101. UFS has lower cost and the procedure is faster, without the need of anesthesia88,102. It is reported higher recurrence rate of varicose veins and lower occlusion rate of treated veins with UDS, when compared to thermal ablation and surgical treatment. However, meta-analysis have identified similar efficacy of minimally invasive methods and surgical treatment83,103. According to guidelines of Brazilian Society of Vascular Surgery, UDS may be used as an alternative to surgery in patients with primary CVI1.

Critical Opinion CVI is prevalent and causes important economic and social burden. Most studies primarily access patients with less severe disease and, rarely, results are categorized according to clinical class. Patients with severe CVI are usually older and less prone to surgical procedure. Sclerotherapy may replace surgical treatment

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

of varicose veins in many patients. Main limitations of method include cutaneous pigmentation (frequent and usually compromise esthetical result), and the need of repeat treatment until total elimination of varicose veins. Patients must be warranted that esthetical result of foam sclerotherapy is less predictable than surgical resection. Low efficacy of a single session of sclerotherapy may be solved by subsequent sessions. Those enhance costs, but have no additional technical difficulty. After surgery of

515

varicose veins, in case of necessity of reoperation, the presence of scars and adhesions may difficult technically the procedure or cause iatrogenic lesions. The main interests of UFS are its low cost, the easy application and low limitation in relation to other therapeutic methods. In literature, most studies show reduced evidence due to bias of selection and randomization49 and long term results are still lacking and must be checked by controlled randomized trials.

R E S U M O A insuficiência venosa crônica é caracterizada por alterações cutâneas decorrentes da hipertensão venosa que, nas formas graves, evoluem com úlceras nos membros inferiores. As varizes dos membros inferiores são a causa mais frequente de insuficiência venosa crônica, que tem como tratamentos clássicos a cirurgia de varizes e a terapia compressiva. Novas técnicas de termo-ablação venosa por laser e radiofrequência são alternativas minimamente invasivas para o tratamento de varizes. A aplicabilidade dos diferentes métodos é limitada por requisitos anatômicos e clínicos. A escleroterapia ecoguiada com espuma consiste na injeção endovenosa da espuma esclerosante monitorada pelo Ultrassom Doppler. A escleroterapia tem grande aplicabilidade para tratamento das varizes e, provavelmente, é mais barato que outros métodos. Entretanto é, até o momento, o método menos estudado. Descritores: Varizes. Insuficiência Venosa. Úlcera da Perna. Escleroterapia. Ultrassom.

REFERENCES 1.

2.

3.

4.

Castro e Silva M, Cabral ALS, Barros Jr N, Castro AA, Santos MERC. Diretrizes sobre Diagnóstico, Prevenção e Tratamento da SBACV. Diagnóstico e tratamento da doença venosa. J Vasc Bras. 2005;4(3 Suppl 2): S185-94. de Aguiar ET , Pinto LJ, Figueiredo MA, Savino Neto S. Diretrizes sobre Diagnóstico, Prevenção e Tratamento da SBACV. Úlcera de insuficiência venosa crônica. J Vasc Bras. 2005; 4(3 Supl 2):S195200. Luccas GC, Menezes FH, Barel EV, Medeiros CAF. Varizes dos membros inferiores. In: Brito JC, editor. Cirurgia vascular e endovascular. 2nd ed. Revinter; 2002. p. 1509-26. Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, Gloviczki ML, Lohr JM, McLafferty RB, Meissner MH, Murad MH, Padberg FT, Pappas PJ, Passman MA, Raffetto JD, Vasquez MA, Wakefield TW; Society for Vascular Surgery; American Venous Forum. The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum J Vasc Surg. 2011;53:(5

Suppl):2S-48S. 5. O’Donnell TF, Passman MA, Marston WA, Ennis WJ, Dalsing M, Kistner RL, Lurie F, Henke PK, Gloviczki ML, Eklöf BG, Stoughton J, Raju S, Shortell CK, Raffetto JD, Partsch H, Pounds LC, Cummings ME, Gillespie DL, McLafferty RB, Murad MH, Wakefield TW, Gloviczki P; Society for Vascular Surgery; American Venous Forum. Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum. J Vasc Surg. 2014;60(2 Suppl):3S-59S. 6. Scott TE, LaMorte WW, Gorin DR, Menzoian JO. Risk factors for chronic venous insufficiency: a dual casecontrol study. J Vasc Surg. 1995;22(5):622-8. 7. Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic venous insufficiency in men and women in the general population: Edinburgh Vein Study. J Epidemiol Community Health. 1999;53(3):149-53. 8. Nelzen O. Prevalence of venous leg ulcer: the importance of the data collection method. Phlebolymphology. 2008;15(4):143-150. 9. Rabe E. Epidemiology of varicose veins. Phlebolymphology. 2010;17(1):21. 10. Tatsioni A, Balk E, O’Donnell T, Lau J. Usual care in

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

516

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

the management of chronic wounds: a review of the recent literature. J Am Coll Surg. 2007;205(4):617624e57. Garratt AM, Macdonald LM, Ruta DA, Russell IT, Buckingham JK, Krukowski ZH. Towards measurement of outcome for patients with varicose veins. Qual Health Care. 1993;2(1):5-10. Garratt AM, Ruta DA, Abdalla MI, Russell IT. Responsiveness of the SF-36 and a condition-specific measure of health for patients with varicose veins. Qual Life Res. 1996;5(2):223-34. Lopes CR, Figueiredo M, Ávila AM, Soares LMBM, Dionísio VC. Avaliação das limitações de úlcera venosa em membros inferiores. J Vasc Bras. 2013;12(1):5-9. Vlajinac HD, Radak DJ, Marinkovic JM, Maksimovic MZ. Risk factors for chronic venous disease. Phlebology. 2012;27(8):416-22. Pannier F, Rabe E. Progression of chronic venous disorders: results from the Bonn Vein Study. J Vasc Surg. 2011;53(1):254-55. Brasil. Ministério da Saúde. DATASUS [Internet]. [acesso 2016 Ago 29]. Disponível em: http://datasus. saude.gov.br/informacoes-de-saude/tabnet Brasil. Ministério da Previdência Social. DATAPREV [Internet]. [acesso em 2016 Ago 19]. Disponível em: http://portal.dataprev.gov.br/ Pang AS. Location of valves and competence of the great saphenous vein above the knee. Ann Acad Med Singapore. 1991;20(2):248-50. Bradbury A, Ruckley CV. Clinical presentation and assessment of patients with venous disease. In: Gloviczki P, editor. Handbook of venous disorders: guidelines of the American Venous Forum. 3rd ed. London: Hodder Arnold; 2009. p. 331-41. Kistner RL, Eklof B, Masuda EM. Diagnosis of chronic venous disease of the lower extremities: the “CEAP” classification. Mayo Clin Proc. 1996;71(4):338-45. 21. Hanrahan LM, Araki CT, Rodriguez AA, Kechejian GJ, LaMorte WW, Menzoian JO. Distribution of valvular incompetence in patients with venous stasis ulceration. J Vasc Surg. 1991;13(6):805-11. Labropoulos N, Leon M, Geroulakos G, Volteas N, Chan P, Nicolaides AN. Venous hemodynamic abnormalities in patient with leg ulceration. Am J Surg. 1995;169(6):572-4.

23. Obermayer A, Garzonk. Identifying the source of superficial reflux in venuos leg ulcers usin duplex ultrasound. J Vasc Surg. 2010;52(5):1255-61. 24. Leal JAR. Como avaliar o impacto da doença venosa crônica na qualidade de vida [dissertação]. Porto: Universidade do Porto; 2010. 25. Eklöf B, Rutherford RB, Bergan JJ, Carpentier PH, Gloviczki P, Kistner RL, Meissner MH, Moneta GL, Myers K, Padberg FT, Perrin M, Ruckley CV, Smith PC, Wakefield TW; American Venous Forum International Ad Hoc Committee for Revision of the CEAP Classification. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg. 2004;40(6):1248-52. 26. Porter JM, Moneta GL. Reporting standards in venous disease: an update. International Consensus Committee on Chronic Venous Disease. J Vasc Surg. 1995;21(4):635-45. 27. Beebe HG, Bergan JJ, Bergqvist D, Eklof B, Eriksson I, Goldman MP, et al. Classification and grading of chronic venous disease in the lower limbs-a consensus statement. Organized by Straub Foundation with the cooperation of the American Venous Forum at the 6th annual meeting, February 22-25, 1994, Maui, Hawaii. Vasa. 1995;24(4):313-8. 28. Rutherford RB, Padberg FT Jr, Comerota AJ, Kistner RL, Meissner MH, Moneta GL. Venous severity scoring: an adjunct to venous outcome assessment. J Vasc Surg. 2000;31(6):1307-12. 29. Vasquez MA, Rabe E, McLafferty RB, Shortell CK, Marston WA, Gillespie D, Meissner MH, Rutherford RB; American Venous Forum Ad Hoc Outcomes Working Group. Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg. 2010;52(5):1387-96. 30. Murray CJ, Salomon JA, Mathers CD, Lopez AD. Summary measures of population health: conclusions and recommendations. In: Murray CJ, Salomon JA, Mathers CD, Lopez AD, editors. Summary Measures of Population Health: Concepts, Ethics, Measurement and Applications. Geneva, Switzerland: World Health Organization; 2002. p. 731-56. 31. van Kolaar I, Vossen C, Rosendaal F, Cameron L,

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

32.

33.

34.

35.

36.

37.

38.

39.

40.

Bovill E, Kaptein A. Quality of life in venous disease. Thromb Haemost. 2003;90(1):27-35. Vasquez MA, Munschauer CE. Venous Clinical Severity Score and quality-of-life assessment tools: application to vein practice. Phlebology. 2008;23(6):259-75. McDaniel MD, Nehler MR, Santilli SM, Hiatt WR, Regensteiner JG, Goldstone J, et al. Extended outcome assessment in the care of vascular diseases: revising the paradigm for the 21st century. Ad Hoc Committee to Study Outcomes Assessment, Society for Vascular Surgery/International Society for Cardiovascular Surgery, North American Chapter. J Vasc Surg. 2000;32(6):1239-50. Leal FJ, Couto RC, Pitta GBB, Leite PTF, Costa LM, Higino WJF, et al. Tradução e adaptação cultural do Questionário Aberdeen para Veias Varicosas. J Vasc Bras. 2012;11(1):34-42. Leal FJ, Couto RC, Pitta GBB. Validação no Brasil de Questionário de Qualidade de Vida na Doença Venosa Crônica (Questionário Aberdeen para Veias Varicosas no Brasil/AVVQ-Brasil). J Vasc Bras. 2015;14(3):241-7. Couto RC, Leal FJ, Pitta GBB, Bezerra RC B, Segundo Walmir SS, Porto TM. Tradução e adaptação cultural do Charing Cross Venous Ulcer Questionnaire Brasil. J Vasc Bras. 2012;11(2):102-7. Couto RC, Leal FJ, Pitta GBB. Validação do questionário de qualidade de vida na úlcera venosa crônica em língua portuguesa (Charing Cross Venous Ulcer Questionnaire - CCVUQ-Brasil). J Vasc Bras. 2016;15(1):4-10. Lattimer CR, Kalodiki E, Azzam M, Geroulakos G. The Aberdeen varicose vein questionnaire may be the preferred method of rationing patients for varicose vein surgery. Angiology. 2014;65(3):205-9. Staniszewska A, Tambyraja A, Afolabi E, Bachoo P, Brittenden J. The Aberdeen varicose vein questionnaire, patient factors and referral for treatment. Eur J Vasc Endovasc Surg. 2013;46(6):715-8. Nicolaides AN; Cardiovascular Disease Educational and Research Trust; European Society of Vascular Surgery; The International Angiology Scientific Activity Congress Organization; International Union

517

41.

42.

43.

44.

45.

46.

47.

48.

49.

of Angiology; Union Internationale de Phlebologie at the Abbaye des Vaux de Cernay. Investigation of chronic venous insufficiency: a consensus statement (France, March 5-9, 1997). Circulation. 2000;102(20):E126-63. Coleridge-Smith P, Labropoulos N, Partsch H, Myers K, Nicolaides A, Cavezzi A. Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles. Eur J VascEndovasc Surg. 2006 Jan;31(1):83-92. Neumann M, Cornu-Thénard A , Jünger M , Mosti G, Munte K, Partsch H, et al. Evidence based (S3) Guideline for Diagnostics and Treatment of Venous Leg Ulcers. In: EDF guidelines leg ulcers / version 4.0. [cited 2016. Jul 07]. Available from: http:// www.euroderm.org/edf/index.php/edf-guidelines/ category/5-guidelines-miscellaneous?download=22: guideline-diagnostics-and-treatment-of-venous-legulcers-update-2014 Nicolaides AN, Miles C. Photoplethysmography in the assessment of venous insufficiency. J Vasc Surg. 1987;5(3):405-12. Callam MJ, Harper DR, Dale JJ, Ruckley CV. Chronic ulcer of the leg: clinical history. Br Med J (Clin Res Ed). 1987;294(6584):1389-91. Samuel N, Carradice D, Wallace T, Smith GE, Chetter IC. Endovenous thermal ablation for healing venous ulcers and preventing recurrence. Cochrane Database Syst Rev. 2013;(10):CD009494. Reich-Schupke S, Murmann F, Altmeyer P, Stücker M. Compression therapy in elderly and overweight patients. Vasa. 2012;41(2):125-31. Franks PJ, Oldroyd MI, Dickson D, Sharp EJ, Moffatt CJ. Risk factors for leg ulcer recurrence: a randomized trial of two types of compression stocking. Age Ageing. 1995;24(6):490-4. Harper D, Nelson E, Gibson B, Prescott R, Ruckley CV. A prospective randomised trial of class 2 and class 3 elastic compression in the prevention of venous ulceration. Phlebology. 1995;(Suppl 1):872-3. National Clinical Guideline Centre (UK). Varicose veins in the legs. The diagnosis and management of varicose veins. London (UK): National Institute for Health and Care Excellence; 2013.

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

518

50. Raju S, Hollis K, Neglen P. Use of compression stockings in chronic venous disease: patient compliance and efficacy. Ann Vasc Surg. 2007;21(6):790-5. 51. Pannier F, Hoffmann B, Stang A, Jöckel KH, Rabe E. Prevalence and acceptance of therapy with medical compression stockings: results of the Bonn vein study. Phlebologie. 2007;36(5):245-9. 52. Mayberry JC, Moneta GL, Taylor LM Jr, Porter JM. Fifteen-year results of ambulatory compression therapy for chronic venous ulcers. Surgery. 1991;109(5):575-81. 53. Coleridge-Smith PD. Leg ulcer treatment. J Vasc Surg. 2009;49(3):804-8. 54. Lurie F, Creton D, Eklof B, Kabnick LS, Kistner RL, Pichot O, et al. Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected patient population (EVOLVeS Study). J Vasc Surg. 2003;38(2):207-14. 55. Barwell JR, Davies CE, Deacon J, Harvey K, Minor J, Sassano A, et al. Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial. Lancet. 2004;363(9424):1854-9. 56. Gohel MS, Barwell JR, Taylor M, Chant T, Foy C, Earnshaw JJ, et al. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial. BMJ. 2007;335(7610):83. 57. Nesbitt C, Eifell RK, Coyne P, Badri H, Bhattacharya V, Stansby G. Endovenous ablation (radiofrequency and laser) and foam sclerotherapy versus conventional surgery for great saphenous vein varices. Cochrane Database Syst Rev. 2011;(10):CD005624. 58. Dwerryhouse S, Davies B, Harradine K, Earnshaw JJ. Stripping the long saphenous vein reduces the rate of reoperation for recurrent varicose veins: fiveyear results of a randomized trial. J Vasc Surg. 1999 Apr;29(4):589-92. 59. van Rij AM, Chai J, Hill GB, Christie RA. Incidence of deep vein thrombosis after varicose vein surgery. Br J Surg. 2004;91(12):1582-5. 60. Fischer R, Chandler JG, Stenger D, Puhan MA, De Maeseneer MG, Schimmelpfennig L. Patient characteristics and physician-determined variables

61.

62.

63.

64.

65.

66. 67.

68.

69.

70.

71.

72.

73.

affecting saphenofemoral reflux recurrence after ligation and stripping of the great saphenous vein. J Vasc Surg. 2006;43(1):81-7. Mackenzie RK, Lee AJ, Paisley A, Burns P, Allan PL, Ruckley CV et al. Patient, operative, and surgeon factors that influence the effect of superficial venous surgery on disease-specific quality of life. J Vasc Surg. 2002;36(5):896-902. Islamoglu F. A alternative treatment for varicose veins: ligation plus foam sclerotherapy. Dermatol Surg. 2011;37(4):470-9. Ghauri AS, Nyamekye I, Grabs AJ, Farndon JR, Whyman MR, Poskitt KR. Influence of a specialised leg ulcer service and venous surgery on the outcome of venous leg ulcers. Eur J Vasc Endovasc Surg. 1998;16(3):238-44. Goldman MP. Sclerotherapy: treatment of varicose and telangiectatic leg vein. 2nd ed. Mosby-Year Book: St Louis; 1995. Coppleson VM. The treatment of varicose veins by injection. 2nd ed. Sydney : Cornstalk Publ. Co.; 1929. Bergan JJ. Foam sclerotherapy: a textbook. London: Royal Society of Medicine Press; 2008. Wollmann JC. The history of sclerosing foams. Dermatol Surg. 2004;30(5):694-703. Erratum in: Dermatol Surg. 2005;31(2):249. Geroulakos G. Foam sclerotherapy for the management of varicose veins: a critical reappraisal. Phlebolymfology. 2006;13(4):202-6. vanCleef JF. [The history of endovenous techniques for treating varices]. Phlebologie. 2013;66(2):15-27. French. Knight RM, Vin F, Zygmunt JA. Ultrasonic guidance of injection into the superficial venous system. In: Davy A. Stemmer R, editors. Phelobologie 89. Paris: John Libbey Eurotext; 1989. p. 339-41. Schadeck M, Allaert FA. Duplex scanning in the mechanism of the scleroterapy: importance of the spasm. Phlebologie. 1995;Suppl 1:574-6. Cabrera J, Cabrera J Jr, García-Olmedo MA. Nuevo método de esclerosis em las varices tronculares. Patol Vasc. 1995;4:55-73. Tessari L, Cavezzi A, Frullini A. Preliminary experience with a new sclerosing foam in the treatment of

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

74.

75.

76.

77.

78.

79.

80.

81.

82.

varicose veins. Dermatol Surg. 2001;27(1):58-60. Cabrera J, Cabrera J Jr, García-Olmedo MA. Treatment of varicose long saphenous veins with sclerosant in microfoam form: long-term outcomes. Phlebology. 2000;15(1):19-23. Cabrera J, Cabrera J Jr, García-Olmedo MA. Sclerosants in microfoam. A new approach in angiology. Int Angiol. 2001;20(4):322-9. Wright D, Gobin JP, Bradbury AW, Coleridge-Smith P, Spoelstra H, Berridge D, Wittens CHA, Sommer A, Nelzen O, Chanter D; The Varisolve® European Phase III Investigators Group. Varisolve® polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: European randomized controlled trial. Phlebology. 2006;21(4):180-90. Rasmussen LH, Lawaetz M, Bjoern L, Vennits B, Blemings A, Eklof B. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. Br J Surg. 2011;98(8):1079-87. Brittenden J, Cotton SC, Elders A, Tassie E, Scotland G, Ramsay CR, et al. Clinical effectiveness and costeffectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial. Health Technol Assess. 2015;19(27):1-342. Rabe E, Otto J, Schliephake D, Pannier F. Efficacy and safety of great saphenous vein sclerotherapy using standardized polidocanol foam (ESAF): a randomised controlled multicentre clinical trial. Eur J Vasc Endovasc Surg. 2008;35(2):238-45. Yamaki T, Nozaki M, Iwasaka S. Comparative study of duplex-guided foam sclerotherapy and duplexguided liquid sclerotherapy for the treatment of superficial venous insufficiency. Dermatol Surg. 2004;30(5):718-22; discussion 722. Figueiredo M, Araújo SP, Penha-Silva N. Ecoescleroterapia com microespuma em varizes tronculares primárias. J Vasc Bras. 2006;5(3):177-83. Jia X, Mowatt G, Burr JM, Cassar K, Cook J, Fraser C. Systematic review of foam sclerotherapy for varicose veins. Br J Surg. 2007;94(8):925-36.

519

83. van den Bos R, Arends L, Kockaert M, Neumann M, Nijsten T. Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 2009;49(1):230-9. 84. Myers KA, Jolley D, Clough A, Kirwan J. Outcome of ultrasound-guided sclerotherapy for varicose veins: medium-term results assessed by ultrasound surveillance. Eur J Vasc Endovasc Surg. 2007;33(1):116-21. 85. Mauck KF, Asi N, Elraiyah TA, Undavalli C, Nabhan M, Altayar O, et al. Comparative systematic review and meta-analysis of compression modalities for the promotion of venous ulcer healing and reducing ulcer recurrence. J Vasc Surg. 2014;60(2 Suppl):73S92S. 86. O’Hare JL, Earnshaw JJ. Randomised clinical trial of foam sclerotherapy for patients with a venous leg ulcer. Eur J Vasc Endovasc Surg. 2010;39(4):495-9. 87. Kulkarni SR, Slim FJ, Emerson LG, Davies C, Bulbulia RA, Whyman MR, et al. Effect of foam sclerotherapy on healing and long-term recurrence in chronic venous leg ulcers. Phlebology. 2013;28(3):140-6. 88. Campos W Jr, Torres IO, da Silva ES, Casella IB, Puech-Leão P. A prospective randomized study comparing polidocanol foam sclerotherapy with surgical treatment of patients with primary chronic venous insufficiency and ulcer. Ann Vasc Surg. 2015;29(6):1128-35. 89. Cabrera J, Redondo P, Becerra A, Garrido C, Cabrera J Jr, García-Olmedo MA, et al. Ultrasoundguided injection of polidocanol microfoam in the management of venous leg ulcers. Arch Dermatol. 2004;140(6):667-73. 90. Campos W Jr. Estudo comparativo entre escleroterapia com espuma de polidocanol e cirurgia convencional para tratamento de varizes primárias dos membros inferiores em portadores de úlcera venosa [dissertação]. 2014. São Paulo (SP): Universidade de São Paulo; 2014. 91. Silva MAM, Burihan MC, Barros OC, Nasser F, Ingrund JC, Neser A. Resultados do tratamento da Insuficiência Venosa Crônica grave com espuma de polidocanol guiada por ultrassom. J Vasc Bras. 2012;11(3):207-11. 92. Biemans AA, Kockaert M, Akkersdijk GP, van den Bos

Rev Col Bras Cir 2017; 44(5): 511-520


de-Abreu Ultrasound-guided foam sclerotherapy for severe chronic venous insufficiency

520

93.

94.

95.

96.

97.

98. 99.

RR, de Maeseneer MG, Cuypers P, et al. Comparing endovenous laser ablation, foam sclerotherapy, and conventional surgery for great saphenous varicose veins. J Vasc Surg. 2013;58(3):727-34. Shadid N, Ceulen R, Nelemans P, Dirksen C, Veraart J, Schurink GW, et al. Randomized clinical trial of ultrasound-guided foam sclerotherapy versus surgery for the incompetent great saphenous vein. Br J Surg. 2012;99(8):1062-70. Brittenden J, Cotton SC, Elders A, Ramsay CR, Norrie J, Burr J, et al. A randomized trial comparing treatments for varicose veins. N Engl J Med. 2014;371(13):1218-27. Breu FX, Guggenbichler S. European Consensus Meeting on Foam Sclerotherapy, April, 4-6, 2003, Tegernsee, Germany. Dermatol Surg. 2004;30(5):709-17; discussion 717. Rabe E, Breu FX, Cavezzi A, Coleridge Smith P, Frullini A, Gillet JL, Guex JJ, Hamel-Desnos C, Kern P, Partsch B, Ramelet AA, Tessari L, Pannier F; Guideline Group. European guidelines for sclerotherapy in chronic venous disorders. Phlebology. 2014;29(6):338-54. Yamaki T, Nozaki M, Sakurai H, Takeuchi M, Soejima K, Kono T. Multiple small-dose injections can reduce the passage of sclerosant foam into deep veins during foam sclerotherapy for varicose veins. Eur J Vasc Endovasc Surg. 2009;37(3):343-8. Guex JJ. Complications and side-effects of foam sclerotherapy. Phlebology. 2009;24(6):270-4. Thomasset SC, Butt Z, Liptrot S, Fairbrother BJ, Makhdoomi KR. Ultrasound guided foam sclerotherapy: Factors associated with outcomes and complications. Eur J Vasc Endovasc Surg.

2010;40(3):389-92. 100. Cavezzi A, Parsi K. Complications of foam sclerotherapy. Phlebology. 2012;27 Suppl 1:46-51. 101. Figueiredo M, Araújo S, Barros N Jr, Miranda F Jr. Results of surgical treatment compared with ultrasound-guided foam sclerotherapy in patients with varicose veins: a prospective randomised study. Eur J Vasc Endovasc Surg. 2009; 38(6):758-76. 102. Bountouroglou DG, Azzam M, Kakkos SK, Pathmarajah M, Young P, Geroulakos G. Ultrasoundguided foam sclerotherapy combined with saphenofemoral ligation compared to surgical treatment of varicose veins: early results of a randomized controlled trial. Eur J Vasc Endovasc Surg. 2006;31(1):93-100. 103. Luebke T, Brunkwall J. Systematic review and metaanalysis of endovenous radiofrequency obliteration, endovenous laser therapy, and foam sclerotherapy for primary varicosis .J Cardiovasc Surg (Torino). 2008;49(2):213-33. Received in: 02/03/2017 Accepted for publication: 22/06/2017 Conflict of interest: none. Source of funding: none. Mailing address: Guilherme Camargo Gonçalves de Abreu E-mail: gcgabreu@gmail.com / guilherme.cga@puccampinas.edu.br

Rev Col Bras Cir 2017; 44(5): 511-520


Review Article

DOI: 10.1590/0100-69912017005015

Management of infected pancreatic necrosis: state of the art Necrose pancreática com infecção: estado atual do tratamento ROBERTO RASSLAN, TCBC-SP1; FERNANDO -SP1; SAMIR RASSLAN, TCBC-SP1.

DA

COSTA FERREIRA NOVO1; ALBERTO BITRAN, TCBC-SP1; EDIVALDO MASSAZO UTIYAMA, TCBC-

A B S T R A C T Pancreatic necrosis occurs in 15% of acute pancreatitis. The presence of infection is the most important factor in the evolution of pancreatitis. The diagnosis of infection is still challenging. Mortality in infected necrosis is 20%; in the presence of organic dysfunction, mortality reaches 60%. In the last three decades, there has been a real revolution in the treatment of infected pancreatic necrosis. However, the challenges persist and there are many unsolved questions: antibiotic treatment alone, tomography-guided percutaneous drainage, endoscopic drainage, video-assisted extraperitoneal debridement, extraperitoneal access, open necrosectomy? A step up approach has been proposed, beginning with less invasive procedures and reserving the operative intervention for patients in which the previous procedure did not solve the problem definitively. Indication and timing of the intervention should be determined by the clinical course. Ideally, the intervention should be done only after the fourth week of evolution, when it is observed a better delimitation of necrosis. Treatment should be individualized. There is no procedure that should be the first and best option for all patients. The objective of this work is to critically review the current state of the art of the treatment of infected pancreatic necrosis. Keywords: Pancreatitis. Pancreatitis, Acute Necrotizing. Infection. Drainage.

INTRODUCTION

A

cute pancreatitis is one of the main causes of hospitalization among benign diseases of digestive system, with an annual cost of two billion dollars in the US1,2. In the last ten years, it has been observed an increase of incidence and 20% of hospitalization. Severity of disease is associated to pancreatic or peri-pancreatic tissue necrosis, and the presence of infection is the most important factor for pancreatitis evolution3. Twenty per cent of patients present pancreatic necrosis and one third of this group have infection. In spite of modern intensive care treatments, mortality of infected pancreatic necrosis is almost 30% (12% to 39%), and, in the presence of multiple organ failure, may reach 70%3-5. Therefore, infected pancreatic necrosis should not be considered a benign disease. Infected pancreatic necrosis treatment experienced a great revolution in the past two decades6. At first, all patients with infected necrosis will need an invasive procedure that may be performed by endosco-

py, percutaneous access or surgery. In the past, surgery was the first or only option, but recent studies advocate the step up approach, a stepwise treatment, beginning with minimally invasive measures and surgical intervention when initial procedure fails7-10. Indication and moment of intervention, choice of procedure and step up approach modified considerably the treatment of severe acute pancreatitis. Infection of pancreatic necrosis generates a series of doubts, such as etiology, diagnosis, clinical presentation, role of tomography and use of fine needle puncture, and prophylactic use of antibiotics. The objective of the present work is to critically analyze the current status of treatment of infected acute pancreatitis.

How to diagnose infection? Pancreatic necrosis infection usually occurs in the second or third weeks of evolution. Systemic and laboratory alterations before that period usually are caused by the inflammatory response or infection elsewhere. If these manifestations persist after the first seven

1 - University of São Paulo School of Medicine, Division of General Surgery and Trauma, Department of Surgery, São Paulo, SP, Brazil. Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

522

or ten days, maybe infection is present5,11. One of the great challenges of the treatment of a patient with severe acute pancreatitis is the definition of the presence of infection of pancreatic necrosis. Occasionally, severity of the disease is only local, without severe systemic manifestations, even in the presence of infection. On the other hand, critical patient at intensive care unit, under mechanic ventilation, with deep vein access and catheters, may have other sources of infection. Many times, definition of infection etiology is difficult. It is fundamental to stress that collection of blood and urine cultures must always be performed in the presence of suspected infection before administration of antibiotics. Finding the agent in the blood culture is valuable, since it may guide which local is infected according to identified agent, and which antibiotics to use. Abdominal tomography is an indispensable resource for evaluation of a patient with worsening of clinical and infectious status. Presence of gas in the pancreatic collection suggests necrosis infection, observed in 40% of patients, and there is also alteration of the tomographic image when compared to the initial exam4,12-14. Fine needle puncture was very used and widespread in the past. Its use nowadays is restrict and controversial12. One of the reasons for this change is the modern conservative treatment of infected pancreatic necrosis. The presence of a microorganism in the aspirate of fine needle puncture does not mean immediate change of treatment. On the other hand, definition of etiologic agent helps choosing the correct antibiotics, in special in patients at intensive unit care for more than two weeks; in that scenario, it is not rare the presence of resistant germs to antibiotics. In this context, the advocated treatment is the use of carbapenemic drugs that usually are efficient to control infection. Rodriguez et al.13 reported 25% of false negative results of fine needle puncture and that this could be explained by previous use of antibiotics. A recent study evaluated the opinion of specialists about the use of fine needle puncture and showed that among 118 interviewees, none use routinely the method and 85% only use it in selected patients14. This current approach is based on the fact that invasive procedures must be performed usually after four weeks. In the presence of suspicion of infection or

image of infected pancreatic necrosis, initial treatment is the use of antibiotics. In the nineties, infection diagnosis after fine needle puncture lead to immediate surgical procedure, what is not done nowadays. Van Baal et al.12 retrospectively evaluated 208 patients submitted to drainage of pancreatic necrosis and divided them into three groups: those with presence of clinical signs of infection, with gas in the collection at tomography, and those with positive fine needle puncture. Result of culture of pancreatic necrosis, obtained by necrosectomy or external drainage, showed the presence of microorganisms in 80% of patients with clinical signs of infection, in 94% of patients with gas at tomography, and in 88% of patients with positive fine needle puncture. The authors suggested that infection diagnosis may be based on clinical evolution and image exam, and that fine needle puncture should be reserved to situations when the procedure will change treatment. This is observed in patients with multiple organ failure and signs of infection, which origin is not safely determined.

Prophylactic antibiotics: are they still used? The use of antibiotic prophylaxis is being studied and discussed in literature. The first studies in the nineties suggested that prophylactic use of antibiotics lowered the incidence of pancreatic necrosis infection and mortality. However, the methodology quality of those studies are questionable15,16. More recent randomized studies did not confirm the initial data. Dellinger et al.17 conducted a multicenter study and evaluated 100 patients with severe acute pancreatitis that were divided into two groups: placebo and use of meropenem. Infection was observed in 18% of patients of treated group, and in 12% of patients that received placebo. Surgery was necessary in 26% of those treated with antibiotics and in 20% of those treated with placebo. There was no difference of mortality. Garcia-Barrasa et al.18 evaluated the use of ciprofloxacin for infection prophylaxis of pancreatic necrosis and also did not observe difference of mortality or of necrosis infection. Therefore, the use of antibiotics in pancreatic necrosis must be restricted to patients with diagnosed infection, that usually occurs after the third week. Most used antibiotics are those with good penetration in the

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

523

pancreatic tissue, such as carbapenemic, quinolones and metronidazol.

Percutaneous Drainage Open pancreatic necrosectomy is a significant surgical trauma for many critically ill patients. Since morbidity (34% to 95%), mortality (13% to 39%) and pancreatic insufficiency due to the procedure are high, in the last two decades some authors proposed a less invasive treatment13,19,20. Freeny et al.21 advocated in the end of the nineties the percutaneous drainage of infected pancreatic necrosis. They evaluated 34 patients: in 47% drainage was the only intervention. In 74% of patients infection was controlled, allowing postponement of surgical treatment. In the beginning of this century, other authors also observed that minimally invasive access is associated to lower activation of inflammatory response, when compared to surgical treatment. These initial studies encouraged the PANTER trial (Pancreatitis, Necrosectomy versus step up approach), a multicenter randomized study performed at the Netherlands8. Open necrosectomy was compared to step up approach, that consists in a stepwise treatment with initial percutaneous drainage, and, in the persistence of infection, open necrosectomy by laparotomy or via retroperitoneal. From that moment on, the concept of set up approach widespread, being the first option percutaneous drainage, and necrosectomy only performed in failed treatment. Van Santvoort et al.10 evaluated 88 patients, 45 submitted to surgery and 43 to step up approach. There was no difference of mortality between both groups (19% of step up group vs. 16% of surgery group), but only 12% of patients of the minimally invasive group progressed to multiple organ failure versus 40% of the other group. Percutaneous drainage was the only necessary treatment in 35% of patients. It is important to highlight the necessity of more than one percutaneous puncture in 44% of patients submitted to the step up approach. On the other hand, the group submitted to open necrosectomy needed a new surgery in 42%. Incidence of diabetes was also lower in the group treated by the step up approach (16% versus 38%). The first step, percutaneous drainage, is performed to control infection, postpone surgery, and, in

some cases, to avoid surgery. In literature, success of percutaneous drainage to avoid necrosectomy is variable, from 30% to 100%9,19,21. The objective of the drainage is to remove the liquid that surrounds pancreatic necrosis. Drains do not remove pancreatic necrosis, but the removal of liquid under pressure may control infection. Therefore, drainage must be indicated for patients with evidence of pancreatic necrosis infection and performed usually at third or fourth weeks of evolution11,22. A recent study observed that 88% of surgeons perform drainage before fourth week14. It is discussed the role of rinsing after percutaneous drainage, the size of the drain and the possible advantage to change to progressively larger drains. Percutaneous drainage modified the evolution of pancreatitis, due to its capacity to resolve infection and multiple organ failure.

Predictive factors of success of percutaneous drainage Success of percutaneous drainage is directly related to volume, local and distribution of the liquid collection and peri-pancreatic necrosis, aside from the clinical condition of the patient9,23,24. The presence of debris is one of the most important factors related to the success of drainage. Literature does not characterize subgroups of patients with predictive factors that should be exclusively treated by percutaneous drainage. This information is important, since when drainage is insufficient, necrosectomy must be performed right after control of sepsis and improvement of organic dysfunction, if possible. Babu et al.23 showed that percutaneous drainage reverted sepsis in 62% of patients and 48% did not need necrosectomy. These authors described a high rate of success with only drainage, in relation to others in literature. They believe that the reason is the extensive rinsing of abdominal cavity with saline to remove debris. They indicate as predictive factors for success of drainage: sepsis resolution, APACHE II levels at the procedure and multiple organ failure in the first week of pancreatitis. Hollemans et al.24 evaluated 113 patients and showed that male sex, presence of multiple organ failure, extension of pancreatitis necrosis and heterogeneity

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

524

of collection are predictive of failure of drainage, indicating the necessity of necrosectomy. These authors proposed a nomogram. When all factors are present, success of exclusive drainage is 2%. However, it must be pointed out that regardless the chance of success of percutaneous drainage, treatment of infected pancreatic necrosis must be initiated with drainage. The change for a higher caliber drain must be encouraged to postpone and avoid necrosectomy, but there are no studies showing this treatment as definitive to avoid surgery24.

When endoscopic treatment must be indicated? Endoscopy may be used in two procedures for infected pancreatic necrosis: drainage and necrosectomy. Some authors advocate endoscopic necrosectomy when endoscopic drainage fails7,11,25,26. Studies that analyze endoscopic necrosectomy efficiency are still rare. A systematic review of literature evaluated 14 series with 455 patients. It was necessary an average of four procedures per patient, and exclusive endoscopic treatment was observed in 81%. Mortality was 6% and morbidity 36%, and bleeding was the main complication. The quality of these studies is questionable, since most do not indicate the severity of disease and only 57% involved infected pancreatic necrosis25. Indication for this type of treatment must be restricted to delimited pancreatic necrosis. Bakker et al.27 performed the first randomized study comparing transgastric endoscopic necrosectomy with video-assisted retroperitoneal necrosectomy (PENGUIN trial - Pancreatitis, Endoscopy Transgastric vs Primary Necrosectomy in Patients with Infected Necrosis). They evaluated 20 patients, ten in each group: in the group treated endoscopically, interleukin-6 levels following the procedure were lower, patients did no present multiple organ failure and pancreatic fistula was observed in only 10% of patients, versus 70% in patients submitted to video-assisted procedure. It was necessary an average of three endoscopic procedures and two patients needed surgery. However, in spite of promising results with endoscopy, it must be stressed the low number of patients, and that, in the surgical group, necrosectomy was the first procedure, while in the endoscopic group endoscopic drainage preceded

necrosectomy. After the promising results of PENGUIN trial, it was proposed the TENSION trial that introduced stepwise treatment for endoscopy and surgery. The study will compare the surgical step up approach (initial percutaneous drainage and eventually surgical procedure in cases of failure) with endoscopic step up approach (endoscopic drainage followed by endoscopic necrosectomy in case of initial treatment failure)28.

Which is the best moment for drainage or necrosectomy? The timing of surgical intervention in pancreatic necrosis has changed over the last two decades. Gรถtzinger et al.29 showed mortality of 46% of patients submitted to surgery during the first three weeks of the beginning of the disease, versus 25% after this period. Rodriguez et al.13 also stated that postponing surgical treatment is associated to lowering of mortality. This study evaluated 167 patients submitted to necrosectomy. The group operated with less than four weeks of evolution had a mortality rate of 20.3%, while the group when the procedure was performed after four weeks, mortality was 5.3%. Present consensus advocate that any invasive procedure must be postponed until pancreatic necrosis is delimited, that usually is observed after four weeks of symptoms5,11,30,31. A Dutch group proposed a clinical randomized study in 2015 (POINTER trial) with the objective to compare the results of early drainage versus late drainage in infected pancreatic necrosis22. Grinsven et al.14 proposed a question form about the best moment for drainage in infected pancreatic necrosis. They observed that 55% of interviewees postpone drainage after the diagnosis of infection, but 45% adopt immediate drainage. In this study, 87% of interviewees advocate the use of step up approach. Percutaneous drainage was indicated by 12% of interviewees only in the presence of delimited pancreatic necrosis, by 44% in some situations before delimitation, and other 44% performed drainage in any possible moment. This work showed that the presence of gas at abdominal tomography and signs of infection are associated to earlier drainage in relation to only clinical signs. The higher discrepancy of opinion of specialists is

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

525

observed in the first three weeks of disease. After this period, when pancreatic necrosis is delimited, most indicate drainage.

Open or minimally invasive necrosectomy Open necrosectomy was considered the main treatment for decades, but with therapeutic minimally invasive improvements, it was observed a change of concepts. The reason was the need to reduce morbidity of procedure, that is performed in already frail patients6,32,33. Blunt dissection must be performed, avoiding resection to prevent bleeding, enteric fistula and removal of viable pancreatic tissue10,34. After debridement, in the past, abdominal cavity was maintained open for scheduled reoperations, what was abandoned. Nowadays, it is advocated abdominal closure with extensive drainage of retroperitoneum and reintervention on demand13,30. Open necrosectomy usually is associated to higher mortality, that varies from 20% to 60%, although some studies report mortality lower than 10%34,35. Madenci et al.34 reported mortality of 8.8% in 68 patients submitted to open necrosectomy. In spite of low mortality, 41% of patients needed drainage of abdominal collections during post-operatory and 15% were reoperated. Doctor et al.35 evaluated 59 patients submitted to necrosectomy, with promising results, mortality of 10% and reoperation in only 8%. In that study, incidence of pancreatic fistula was 50.8%. Minimally invasive retroperitoneal access is been widespread and becoming popular in the last 20 years. Main options are percutaneous necrosectomy and video-assisted debridement of pancreatic necrosis (VARD)36. These techniques are variations of retroperitoneal access via subcostal incision, proposed by Fagniez et al.37 in the eighties. This access is accompanied by a high morbidity rate: enteric fistula in 45%, bleeding in 40% and colon necrosis in 15% of patients. Percutaneous necrosectomy was widespread by the group of Liverpool38. Technique includes passage of a 12Fr drain by interventionist radiology guided by image, and, posteriorly the path is dilated to allow placement of a nephroscope, and, with the aid of forceps, removal and irrigation of necrosis. In general, several approaches are needed. This access is not adequate to patients with necrosis of head and uncinate process

of pancreas38-41. Rarity et al.41 analyzed retrospectively patients submitted to open necrosectomy in relation to this access. Authors followed up 394 patients. 69.5% were treated by percutaneous necrosectomy. Mortality was 15.3% in 274 patients that used minimally invasive access versus 23.3% in 120 patients submitted to open necrosectomy. It was also observed less organ dysfunction and less complication following the minimally invasive procedure. VARD retroperitoneal access is performed by a 5cm incision of left flank, and the percutaneous drain path is used to access the pancreatic necrosis. Laparoscopic optics is introduced and CO2 is inflated by the percutaneous drain. Necrosis is removed by forceps that are used in open surgery. In case of necrosis of head or central region of pancreas, percutaneous necrosectomy and VARD have technical limitations and these methods should not be used as first option. Some authors propose laparoscopic debridement, but experience is still limited30. Paresh42 published in 2006 the largest casuistic in literature of video-assisted transperitoneal access. Eighteen patients were treated, and only half had pancreatic necrosis infection. Mortality was 2% and 11% needed reintervention.

Is there a role for non-surgical treatment? Exclusive clinical treatment or with minimally invasive procedures avoids surgical complications, such as worsening of multiple organ failure, pancreatic insufficiency and incisional hernia34. Runzi et al.43 published the first big series of non-surgical treatment of infected pancreatic necrosis. They evaluated 28 patients, and, among these, 16 were not operated. The others presented multiple organ failure. Mortality was 12.5%. it must be pointed out that in that work, only three patients were submitted to percutaneous drainage, although ten presented worsening of clinical condition. Lee et al.44 also described non- surgical treatment. They treated eight patients exclusively with antibiotics. Rasslan et al.45 presented a series of six patients with necrosis and gas in the retroperitoneum treated exclusively with antibiotics. We believe that, in the beginning of disease, treatment must be made only with antibiotics, but in the presence of worsening of clinical conditions, some intervention must be made.

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

526

CONCLUSIONS Infected pancreatic necrosis treatment must be made by a multidisciplinary team including surgeon, intensive care specialist, radiologist and endoscopic surgeon. Only referral centers have conditions to treat this disease. When we review the treatment of infected acute pancreatitis in the last two decades, it is observed an extraordinary evolution. We do not operate as many times as before, scheduled reoperations are no longer used, new resources are available, as those here described, and a significant reduction of morbidity and mortality rates

was achieved. There is no mandatory procedure to be made initially or as best option. The use of the step-up approach and postponing the drainage must be adopted in all patients. In those with infection, even with gas in retroperitoneum, it is possible to use only antibiotics with good results, in patients without multiple organ failure. Minimally invasive treatment with drainage may be the first alternative, but evolution, clinical condition and pancreatic necrosis characteristics will define the best technique to be used. Literature presents high rates of success with minimally invasive drainage, but, when infection is not reverted, open necrosectomy must be considered.

R E S U M O A necrose pancreática ocorre em 15% das pancreatites agudas. A presença de infecção é o fator mais importante na evolução da pancreatite. Confirmar o diagnóstico de infecção ainda é um desafio. A mortalidade na necrose infectada é de 30% e na vigência de disfunção orgânica, chega a 70%. Nas últimas décadas, ocorreu uma verdadeira revolução no tratamento da necrose pancreática infectada. Mesmo assim, persiste o desafio e há múltiplas questões ainda não resolvidas: tratamento exclusivo com antibiótico, drenagem percutânea guiada por tomografia, drenagem por via endoscópica, desbridamento extra-peritoneal vídeo-assistido, acesso extra-peritoneal, necrosectomia por via aberta? Foi proposto o tratamento por etapas, “step up approach”, iniciando-se com as medidas menos invasivas e reservando-se a intervenção operatória para os casos em que o procedimento anterior não resolver definitivamente o problema. A indicação e o momento da intervenção devem ser determinados pela evolução clínica. O ideal é que a intervenção seja feita apenas depois da quarta semana de evolução, quando já existe melhor delimitação da necrose. O tratamento deve ser individualizado. Não existe um procedimento que deva ser o primeiro e a melhor opção para todos os doentes. O objetivo deste trabalho é fazer uma análise crítica do estado atual do tratamento da necrose pancreática infectada. Descritores: Pancreatite. Pancreatite Necrosante Aguda. Infecção. Drenagem.

REFERENCES 1.

2.

3.

4.

5.

6.

Fagenholz PJ, Fernández-del Castillo C, Harris NS, Pelletier AJ, Camargo CA, Jr. National study of United States emergency department visits for acute pancreatitis, 1993-2003. BMC Emerg Med. 2007;7:1. Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas. 2006;33(4):323-30. Werge M, Novovic S, Schmidt PN, Gluud LL. Infection increases mortality in necrotizing pancreatitis: a systematic review and meta-analysis. Pancreatology. 2016;16(5):698-707. Ball CG, Hameed SM, Dixon E, Lillemoe KD. Severe acute pancreatitis for the acute care surgeon. J Trauma Acute Care Surg. 2016;80(6):1015-22. Forsmark CE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med. 2016;375(20):1972-81.

7.

8.

Bradley EL 3rd, Dexter ND. Management of severe acute pancreatitis: a surgical odyssey. Ann Surg. 2010;251(1):6-17. Bruno MJ; Dutch Pancreatitis Study Group. Improving the outcome of acute pancreatitis. Dig Dis. 2016;34(5):540-5. Besselink MG, van Santvoort HC, Nieuwenhuijs VB, Boermeester MA, Bollen TL, Buskens E, Dejong CH, van Eijck CH, van Goor H, Hofker SS, Lameris JS, van Leeuwen MS, Ploeg RJ, van Ramshorst B, Schaapherder AF, Cuesta MA, Consten EC, Gouma DJ, van der Harst E, Hesselink EJ, Houdijk LP, Karsten TM, van Laarhoven CJ, Pierie JP, Rosman C, Bilgen EJ, Timmer R, van der Tweel I, de Wit RJ, Witteman BJ, Gooszen HG; Dutch Acute Pancreatitis Study Group. Minimally invasive ‘step-up approach’ versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

9.

10.

11.

12.

13.

14.

15.

527

[ISRCTN13975868]. BMC Surg. 2006;6:6. Tong Z, Li W, Yu W, Geng Y, Ke L, Nie Y, et al. Percutaneous catheter drainage for infective pancreatic necrosis: is it always the first choice for all patients? Pancreas. 2012;41(2):302-5. van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, LamĂŠris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG; Dutch Pancreatitis Study Group. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362(16):1491-502. da Costa DW, Boerma D, van Santvoort HC, Horvath KD, Werner J, Carter CR, et al. Staged multidisciplinary step-up management for necrotizing pancreatitis. Br J Surg. 2014;101(1):e65-79. van Baal MC, Bollen TL, Bakker OJ, van Goor H, Boermeester MA, Dejong CH, Gooszen HG, van der Harst E, van Eijck CH, van Santvoort HC, Besselink MG; Dutch Pancreatitis Study Group. The role of routine fine-needle aspiration in the diagnosis of infected necrotizing pancreatitis. Surgery. 2014;155(3):442-8. Rodriguez JR, Razo AO, Targarona J, Thayer SP, Rattner DW, Warshaw AL, et al. Debridement and closed packing for sterile or infected necrotizing pancreatitis: insights into indications and outcomes in 167 patients. Ann Surg. 2008;247(2):294-9. an Grinsven J, van Brunschot S, Bakker OJ, Bollen TL, Boermeester MA, Bruno MJ, Dejong CH, Dijkgraaf MG, van Eijck CH, Fockens P, van Goor H, Gooszen HG, Horvath KD, van Lienden KP, van Santvoort HC, Besselink MG; Dutch Pancreatitis Study Group. Diagnostic strategy and timing of intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study. HPB (Oxford). 2016;18(1):49-56 Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, Kivisaari L, Valtonen V, et al. Early antibiotic treatment in acute necrotising pancreatitis. Lancet. 1995;346(8976):663-7.

16. Pederzoli P, Bassi C, Vesentini S, Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993;176(5):480-3. 17. Dellinger EP, Tellado JM, Soto NE, Ashley SW, Barie PS, Dugernier T, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann Surg. 2007;245(5):674-83. 18. GarcĂ­a-Barrasa A, Borobia FG, Pallares R, Jorba R, Poves I, Busquets J, et al. A double-blind, placebocontrolled trial of ciprofloxacin prophylaxis in patients with acute necrotizing pancreatitis. J Gastrointest Surg. 2009;13(4):768-74. 19. Rasch S, Phillip V, Reichel S, Rau B, Zapf C, Rosendahl J, et al. Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas-A Retrospective Multicenter Analysis of the German Pancreatitis Study Group. PLoS One. 2016;11(9):e0163651. 20. Howard TJ, Patel JB, Zyromski N, Sandrasegaran K, Yu J, Nakeeb A, et al. Declining morbidity and mortality rates in the surgical management of pancreatic necrosis. J Gastrointest Surg. 2007;11(1):43-9. 21. Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M. Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: techniques and results. AJR Am J Roentgenol. 1998;170(4):969-75. 22. van Grinsven J, van Santvoort HC, Boermeester MA, Dejong CH, van Eijck CH, Fockens P, Besselink MG; Dutch Pancreatitis Study Group. Timing of catheter drainage in infected necrotizing pancreatitis. Nat Rev Gastroenterol Hepatol. 2016;13(5):306-12. 23. Babu RY, Gupta R, Kang M, Bhasin DK, Rana SS, Singh R. Predictors of surgery in patients with severe acute pancreatitis managed by the step-up approach. Ann Surg. 2013;257(4):737-50. 24. Hollemans RA, Bollen TL, van Brunschot S, Bakker OJ, Ahmed Ali U, van Goor H, Boermeester MA, Gooszen HG, Besselink MG, van Santvoort HC; Dutch Pancreatitis Study Group. Predicting success of catheter drainage in infected necrotizing pancreatitis. Ann Surg. 2016;263(4):787-92 25. van Brunschot S, Fockens P, Bakker OJ, Besselink

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

528

26.

27.

28.

29.

30.

31.

MG, Voermans RP, Poley JW, et al. Endoscopic transluminal necrosectomy in necrotising pancreatitis: a systematic review. Surg Endosc. 2014;28(5):142538. Erratum in: Surg Endosc. 2014;28(6):2003. Voermans RP, Besselink MG, Fockens P. Endoscopic management of walled-off pancreatic necrosis. J Hepatobiliary Pancreat Sci. 2015;22(1):20-6. Bakker OJ, van Santvoort HC, van Brunschot S, Geskus RB, Besselink MG, Bollen TL, van Eijck CH, Fockens P, Hazebroek EJ, Nijmeijer RM, Poley JW, van Ramshorst B, Vleggaar FP, Boermeester MA, Gooszen HG, Weusten BL, Timmer R; Dutch Pancreatitis Study Group. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA. 2012;307(10):1053-61. van Brunschot S, van Grinsven J, Voermans RP, Bakker OJ, Besselink MG, Boermeester MA, et al. Transluminal endoscopic step-up approach versus minimally invasive surgical step-up approach in patients with infected necrotising pancreatitis (TENSION trial): design and rationale of a randomised controlled multicenter trial [ISRCTN09186711]. BMC Gastroenterol. 2013;13:161. Gรถtzinger P, Wamser P, Exner R, Schwanzer E, Jakesz R, Fugger R, et al. Surgical treatment of severe acute pancreatitis: timing of operation is crucial for survival. Surg Infect (Larchmt). 2003;4(2):205-11. Freeman ML, Werner J, van Santvoort HC, Baron TH, Besselink MG, Windsor JA, Horvath KD, vanSonnenberg E, Bollen TL, Vege SS; International Multidisciplinary Panel of Speakers and Moderators. Interventions for necrotizing pancreatitis: summary of a multidisciplinary consensus conference. Pancreas. 2012;41(8):1176-94. van Santvoort HC, Bakker OJ, Bollen TL, Besselink MG, Ahmed Ali U, Schrijver AM, Boermeester MA, van Goor H, Dejong CH, van Eijck CH, van Ramshorst B, Schaapherder AF, van der Harst E, Hofker S, Nieuwenhuijs VB, Brink MA, Kruyt PM, Manusama ER, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, Cuesta MA, Wahab PJ, Gooszen HG; Dutch Pancreatitis Study Group. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

2011;141(4):1254-63. Cirocchi R, Trastulli S, Desiderio J, Boselli C, Parisi A, Noya G, et al. Minimally invasive necrosectomy versus conventional surgery in the treatment of infected pancreatic necrosis: a systematic review and a meta-analysis of comparative studies. Surg Laparosc Endosc Percutan Tech. 2013;23(1):8-20. Chang YC. Is necrosectomy obsolete for infected necrotizing pancreatitis? Is a paradigm shift needed? World J Gastroenterol. 2014;20(45):16925-34. Madenci AL, Michailidou M, Chiou G, Thabet A, Fernandez-del Castillo C, Fagenholz PJ. A contemporary series of patients undergoing open debridement for necrotizing pancreatitis. Am J Surg. 2014;208(3):324-31. Doctor N, Philip S, Gandhi V, Hussain M, Barreto SG. Analysis of the delayed approach to the management of infected pancreatic necrosis. World J Gastroenterol. 2011;17(3):366-71. Logue JA, Carter CR. Minimally invasive necrosectomy techniques in severe acute pancreatitis: role of percutaneous necrosectomy and video-assisted retroperitoneal debridement. Gastroenterol Res Pract. 2015;2015:693040. 37. Fagniez PL, Rotman N, Kracht M. Direct retroperitoneal approach to necrosis in severe acute pancreatitis. Br J Surg. 1989;76(3):264-7. Connor S, Ghaneh P, Raraty M, Sutton R, Rosso E, Garvey CJ, et al. Minimally invasive retroperitoneal pancreatic necrosectomy. Dig Surg. 2003;20(4):2707. Carter CR, McKay CJ, Imrie CW. Percutaneous necrosectomy and sinus tract endoscopy in the management of infected pancreatic necrosis: an initial experience. Ann Surg. 2000;232(2):175-80. Gomatos IP, Halloran CM, Ghaneh P, Raraty MG, Polydoros F, Evans JC, et al. Outcomes from minimal access retroperitoneal and open pancreatic necrosectomy in 394 patients with necrotizing pancreatitis. Ann Surg. 2016;263(5):992-1001. Raraty MG, Halloran CM, Dodd S, Ghaneh P, Connor S, Evans J, et al. Minimal access retroperitoneal pancreatic necrosectomy: improvement in morbidity and mortality with a less invasive approach. Ann Surg. 2010;251(5):787-93.

Rev Col Bras Cir 2017; 44(5): 521-529


Rasslan Management of infected pancreatic necrosis: state of the art

529

42. Parekh D. Laparoscopic-assisted pancreatic necrosectomy: a new surgical option for treatment of severe necrotizing pancreatitis. Arch Surg. 2006;141(9):895-902. 43. Runzi M, Niebel W, Goebell H, Gerken G, Layer P. Severe acute pancreatitis: nonsurgical treatment of infected necroses. Pancreas. 2005;30(3):195-9. 44. Lee JK, Kwak KK, Park JK, Yoon WJ, Lee SH, Ryu JK, et al. The efficacy of nonsurgical treatment of infected pancreatic necrosis. Pancreas. 2007;34(4):399-404. 45. Rasslan R, da Costa Ferreira Novo F, Rocha MC, Bitran A, de Souza Rocha M, de Oliveira Bernini C, et al. Pancreatic necrosis and gas in the retroperitoneum:

treatment with antibiotics alone. Clinics (Sao Paulo). 2017;72(2):87-94.

Received in: 25/04/2017 Accepted for publication: 01/06/2017 Conflict of interest: none. Source of funding: none. Endereço para correspondência: Roberto Rasslan E-mail: robertorasslan@uol.com.br / roberto.rasslan@hc. fm.usp.r

Rev Col Bras Cir 2017; 44(5): 521-529


Review Article

DOI: 10.1590/0100-69912017005016

A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma Proposta de padronização da Sociedade Brasileira de Cirurgia Oncológica para procedimentos de citorredução cirúrgica e quimioterapia intraperitoneal hipertérmica no Brasil: pseudomixoma peritoneal, tumores do apêndice cecal e mesotelioma peritoneal maligno THALES PAULO BATISTA, TCBC-PE1,2; BRUNO JOSÉ QUEIROZ SARMENTO3; JANINA FERREIRA LOUREIRO4; ANDREA PETRUZZIELLO5,11; ADEMAR LOPES, ECBC-SP6; CASSIO CORTEZ SANTOS7; CLÁUDIO DE ALMEIDA QUADROS, TCBC-BA8; EDUARDO HIROSHI AKAISHI, TCBC-SP9; EDUARDO ZANELLA CORDEIRO10; FELIPE JOSÉ FERNÁNDEZ COIMBRA, TCBC-SP11; GUSTAVO ANDREAZZA LAPORTE12; LEONALDSON SANTOS CASTRO, TCBC-RJ4,13; RANYELL MATHEUS SPENCER SOBREIRA BATISTA6; SAMUEL AGUIAR JÚNIOR, TCBC-SP6; WILSON LUIZ COSTA JÚNIOR11; FÁBIO OLIVEIRA FERREIRA, TCBC-SP6; COMITÊ DE NEOPLASIAS PERITONEAIS E QUIMIOTERAPIA INTRAPERITONEAL HIPERTÉRMICA DA SOCIEDADE BRASILEIRA DE CIRURGIA ONCOLÓGICA.

A B S T R A C T Cytoreductive surgery plus hypertermic intraperitoneal chemotherapy has emerged as a major comprehensive treatment of peritoneal malignancies and is currently the standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome as well as malignant peritoneal mesothelioma. Unfortunately, there are some worldwide variations of the cytoreductive surgery and hypertermic intraperitoneal chemotherapy techniques since no single technique has so far demonstrated its superiority over the others. Therefore, standardization of practices might enhance better comparisons between outcomes. In these settings, the Brazilian Society of Surgical Oncology considered it important to present a proposal for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil, with a special focus on producing homogeneous data for the developing Brazilian register for peritoneal surface malignancies. Keywords: Injections. Intraperitoneal. Hyperthermia, Induced. Drug Therapy. Peritoneal Neoplasms.

INTRODUCTION

C

ytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a major comprehensive treatment of peritoneal surface malignancies, especially for malignancies that remain confined to the abdominopelvic cavity with litt-

le invasion of the underlying organs and no metastatic spread1. This multimodal approach has proved to be an effective curative treatment or a salvage therapy for a number of patients suffering from peritoneal surface malignancies2,3 and is currently the standard of care for appendiceal epithelial neoplasms and Pseudomyxoma peritonei (PMP) syndrome4,5 as well as diffuse malignant

1 - Medicina Integral Professor Fernando Figueira Institute, Department of Surgery / Oncology, Recife, PE, Brazil. 2 - University of Pernambuco, Department of Surgery, Recife, PE, Brazil. 3 - Hospital de Base of the Federal District, Service of Surgical Oncology, Brasília, DF, Brazil. 4 - Complexo Hospitalar de Niterói, Service of Surgical Oncology, Niterói, RJ, Brazil. 5 - Marcelino Champagnat Hospital, Department of Surgical Oncology, Curitiba, PR, Brazil. 6 - AC Camargo Cancer Center, Department of Pelvic Surgery, São Paulo, SP, Brazil. 7 - Hospital Geral de Fortaleza, Department of Surgery, Fortaleza, CE, Brazil. 8 - São Rafael Hospital, Service of Surgical Oncology, Salvador, BA, Brazil. 9 - Hospital das Clínicas, University of São Paulo, Department of Surgical Oncology, São Paulo, SP, Brazil. 10 - Hospital de Caridade, Department of Surgery, Florianópolis, SC, Brazil. 11 - AC Camargo Cancer Center, Department of Abdominal Surgery, São Paulo, SP, Brazil. 12 - Santa Casa de Misericórdia de Porto Alegre, Department of Surgical Oncology, Porto Alegre, RS, Brazil. 13 - Nacional Cancer Institute, Service of Abdomino-Pelvic Surgery, Rio de Janeiro, RJ, Brazil. Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

peritoneal mesothelioma (DMPM)6,7. The rationale of combining heat with intraperitoneal chemotherapy is the added benefit of the synergistic effect of heat and cytotoxic drugs8. This approach allows full peritoneal chemotherapy perfusion and exposure of poorly vascularized tumoral tissue in the abdomen with high concentrations of cytotoxic agents before the formation of adhesions that might limit peritoneal fluid circulation. The blood-peritoneal barrier limits the passage of these high doses into the plasma and reduces the risk of systemic toxicity. Heat itself has a direct cytotoxic effect; it also enhances the effect of certain antimitotic agents (i.e.: mitomycin C, cisplatin, oxaliplatin) as well as increases their penetration into tumor tissue8,9. Some studies also reveal that hyperthermia can reduce the mechanisms of cellular resistance to cisplatin10 and induce an efficient anticancer immune response via exposure of cell surface heat shock proteins11,12. Furthermore, this technique is delivered intraoperatively, avoiding the need for implantation of peritoneal access devices, hence reducing catheter-related morbidity13,14. In Brazil, the management strategies by peritoneal surface malignancies with CRS/HIPEC have increased by efforts of the Brazilian Society of Surgical Oncology (BSSO) and its members. Following some pioneering initiatives, CRS/HIPEC continued to gain interest throughout the country and several reports of initial or consolidated experiences have shown the efficacy of this treatment in Brazil15-29. In summary, these data are heterogeneous in terms of technical particularities and antimitotic agents, but this combined therapeutic approach has been performed with acceptable morbimorbidity and mortality and appears to provide a survival benefit over conventional treatments in many of our centers. In these settings, the BSSO points out that no single technique has so far demonstrated its superiority, and several variations in techniques have produced heterogeneous and no comparable results, which require some standardization of practices that might permit systematic comparisons30. Thus, we considered it important to present a statement produced by BSSO in order to guide the current clinical practice concerning CRS/HIPEC procedures in Brazil, with a special focus

531

on producing homogeneous data for the developing Brazilian register for peritoneal surface malignancies.

METHODS Development Process This proposal for standardizing HIPEC procedures addresses the following clinical points: 1) common technical aspects; 2) patients selection; 3) intraperitoneal chemotherapy schedules; and 4) perioperative oncological management. The BSSO Committee on Peritoneal Surface Malignancies and HIPEC were asked to consider the available evidence, contribute to the development of recommendations, provide a critical review, and finalize this proposal. Initially, few members (i.e.: the first four listed authors) of this committee were responsible for performing a non-systematic review of the most relevant scientific literature and writing a core proposal of standardization. Thereafter, all members reviewed the former version for discussion and improvements, and approved an ultimate version. An external review was also required from three invited experts in CRS/HIPEC procedures from outside Brazil (i.e.: Sugarbaker PH, Verwall VJ and Deraco M), just before submission for editorial review and consideration for publication. Due to the lack of high-level evidence for all specific points to be addressed, recommendations were made based on large clinical experience and expert options. For technical aspects, proposals of standardization also considered results from a recent survey undertaken by the BSSO concerning the development of CRS/HIPEC procedures throughout our country. Accordingly, the use of words like “must” (or “must not”) and “should” (or “should not”) indicates that a course of action is proposed based on proportional levels of agreement amongst large clinical experiences and expert options, whereas the words “recommend” and “suggest” were also applied in a similar manner.

Disclaimers The information herein provided by the BSSO should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. The information addresses only the

Rev Col Bras Cir 2017; 44(5): 530-544


532

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases, and is not intended to substitute for the independent professional judgment of the treatment provider, as the information does not account for individual variation among patients. Thus, the use of this information is voluntary and BSSO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information, or for any errors or omissions.

Conflicts of Interest All members of the committee were asked to list any conflicts of interest and to complete the journalâ&#x20AC;&#x2122;s disclosure form, which requires disclosure of financial and other interests, including relationships with commercial entities that are reasonably likely to experience direct regulatory or commercial impact as a result of promulgation of this proposal for standardization. In accordance with this policy, all members of this BSSO committee did not disclose any relationships constituting a conflict under the policy.

PROPOSAL FOR STANDARDIZING PROCEDURES Patients Selection Careful patient selection is the cornerstone for the management of peritoneal surface malignancies and must involve a comprehensive evaluation considering clinical, radiological, laboratory and histological findings. The suggested minimal preoperative investigations include: 1) physical examination; 2) cardiopulmonary investigation with cardiac echography and functional pulmonary exploration; 3) renal function investigation by creatininemia and clearance of creatinine; 4) biological evaluation of the hepatic function; 5) evaluation of nutritional state by body mass index and albuminemia; and 6) extent of disease and staging by contrast-enhanced multisliced computed tomography and, if necessary, FDG-PET, magnetic resonance imaging or laparoscopic exploration31,32. Tumor

markers are also helpful and should be considered on the workup33. There is also an overall consensus that patients fit for a major comprehensive oncological approach such as CRS/HIPEC are those ASA I-II, performance status of 0-2, with no limiting comorbidities and aged lower than 65-70 years31,34,35. Preferentially, an experienced pathological team should review the preoperative clinical and histological findings for a proper diagnostic confirmation. Reports of pathological findings for PMP should be in line with the Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia by the Peritoneal Surface Oncology Group International (PSOGI)36 and standards of the 7th edition of the AJCC staging classification, as appropriated37. Due to its rarity, review by an expert pathologist using a panel of at least two positive and two negative immunohistochemical stains is required to make a definitive diagnosis of DMPM. The specific panel depends on the differential diagnosis, but common positive markers include calretinin, D240, CK 5/6, and WT-1, and some frequently used negative markers include MOC-31, PAX8, BG8, Ber-EP4, B72.3, CEA, and CDX-238,39. Accordingly, these peritoneal tumors should be staged by the tumor-node-metastasis (TNM) system proposed by the PSOGI based on analysis of a multi-institutional database40, whereas two distinct pathologic subtypes of borderline malignant potential named well-differentiated papillary mesothelioma (WDPM) and benign multicystic mesothelioma (BMM) that are much more common in the peritoneum than in the pleura should also be well recognized before treatment planning because of their better outcomes38. Patients with DMPM of histological biphasic or sarcomatoid subtype must not be considered for treatment with CRS/HIPEC6 as well as those tumors with high expression of Ki67 (i.e.: =25% by immunohistochemical evaluation)41 that are usually

Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

diagnosed under a high tumor load. Similarly, patients with both Ki-67 > 10 % and PCI > 17-20 are also unlikely to benefit from the procedure and should be considered for other treatment protocols41-43. The extent of peritoneal spreading represents one of the most important prognostic factors and the tumor burden as estimated by PCI (peritoneal cancer index) provides a good probability of achieving a complete cytoreduction during CRS for peritoneal malignancies. However, more than the tumor burden, the distribution of peritoneal spreading in the abdomen constitutes the principal limitation for performing CRS31. In these settings, the most frequent contraindications for CRS/HIPEC are extra-abdominal metastasis, massive involvement of the small bowel and its mesentery, hepatic pedicle and gastro-hepatic ligament, gross retroperitoneal lymph node involvement, and ureteral or biliary obstruction, whereas a restrictive cut-off value for PCI (i.e.: PCI >20) also should not be applied as an absolute exclusion criterion for CRS/HIPEC suffering of PMP31,44,45. Common Technical Aspects Techniques of advanced CRS were previously standardized and described by Sugarbaker and must be followed accordingly with minimal variations of procedures46-48. On the other hand, several techniques of HIPEC have been described since its first use in the 80’s49. Variable particularities of HIPEC include installation circuit, timing of visceral anastomoses (i.e.: before or after HIPEC), length of perfusion, target temperatures, type and volume of perfusate, and others. Herein, a started point of discussion is performing HIPEC as a closed or open abdominal (coliseum) technique. Whilst there are no convincing data favoring any technique50-52, we have chosen for the use of a closed technique based on the simplicity of this method and decreased contamination risk53, as well as because most of the

533

centers perform closed HIPEC procedures in Brazil. In these settings, we also propose a minimum of 4L (ranging from 4-6L) of perfusate into the abdominal cavity in order to counterbalance the theoretical drawbacks of closed techniques in comparison to the open approach since a maximal distention of the abdomen enhances the thermal homogeneity throughout the peritoneal cavity54 and facilitates drug distribution into the whole abdomen, ensuring that every site of the diffuse peritoneal disease receives the optimal treatment. At this point, we also suggest an inflow temperature of 44°C in order to maintain a critical threshold for potentiating cytotoxic chemotherapy of above 40°C into the peritoneal cavity55, with an optimal range of 41-43°C as average between in- and out-drains. In regards of flow rate parameters, our purpose is that 300500mL/min should be applied during the “patientfilling phase” and thus increased to 700mL/min during the “circulation” and “HIPEC” phases56-58. Similarly, as carrier solutions, we suggest the use of 1.5% dextrose isotonic peritoneal dialysis solutions for any drug protocol proposed53 here, even for those oxaliplatin-based schedules59,60. Because the main risk of HIPEC is related to direct or indirect skin exposure to antiblastic drugs, the use of two pairs of gloves should be mandatory to protect the surgical team during abdomen manipulation after the “emptying phase”61-63. In the light of reducing morbidity related to CRS, we point out that right hemicolectomy is not routinely required in PMP resulting from mucinous appendiceal neoplasms at low risk of relapse or lymph node involvement64,65, and that a more conservative approach confining the peritonectomy to where there is evidence of more solid disease is also a suitable approach for PMP/ Appendiceal Tumors66. On the contrary, we suggest a complete parietal peritonectomy in patients with DMPM based on a controlled study conducted by Baratti et al.67 demonstrating improved sur-

Rev Col Bras Cir 2017; 44(5): 530-544


534

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

vival outcomes after the radical approach. Another main controversial issue concerning the technical aspects of CRS is the timing of bowel anastomoses. Recently, the BSSO developed an online survey involving the technical aspects of CRS/HIPEC and achieved no consensus in regards to this issue applying a simplified two-round-based Delphi method, in spite of the fact that previous reports from the 5th International Consensus Metting on Peritoneal Surface Malignancies Treatment had favored the “after HIPEC” approach (54%) for the closed abdomen technique66. Due to the lack of evidence to support a strong recommendation, we propose that intestinal anastomoses should be performed before HIPEC based on no reports of recurrence involving the anastomotic area as an isolated or first site of relapse and because of the lower time of chemotherapeutic exposure for the surgical team. Further, in cases requiring an esophago-jejunal anastomosis after total gastrectomy, this approach may also reduce the exposure of mediastinum to cardiotoxic drugs as cisplatin. In a similar manner, a diverting ileostomy is not routinely recommended and may be avoided at the surgeon’s discretion after colorectal stapled anastomoses68, especially because restoration of bowel continuity is often related to high rate of temporary stomas that will not be subsequently reversed69 as well as to postoperative complication70. Perioperative care practices for CRS/HIPEC are widely variable nationally and internationally and standardization of such practices offers an opportunity to incorporate experience from high-volume centers and may enhance patient outcomes30. In these settings, one of the most recent reviews involving several aspects related to peri, intra and postoperative management of patients undergoing CRS/HIPEC have just been published by Raspé et al.53 and summarizes the main understanding of this committee to improve periopertive care standards for the procedures. Following these

review of evidences, we highlight that a goal-directed fluid therapy using noninvasive monitoring tool of hemodynamic parameters improves outcome in terms of major abdominal and systemic postoperative complication incidences or length of hospital stay compared with the standard approach71,72. We also maintain that implementation of fast-track protocols are feasible in order to accelerate recovery, reduce morbidity and shorten convalescence to ultimately improve outcomes and reduce costs, especially for those patients with low PCI not requiring digestive anastomosis53,73-75. Our proposal is also along the line that ICU stay directly following CRS/HIPEC should be preferably based on the extent or resections performed and individual patient characteristics and risk factors76. Similarly, patients with peritoneal carcinomatosis should be considered as a complex oncological group at high risk of infectious complication - the most important cause of peri-operative morbidity and death in CRS/HIPEC77. Thus, we recommend ampicillin/sulbactan78 or cefoxitin over 24-72hs as antibiotic for infection prophylaxis, preferably as short-course regimens of 24h78, while the use of antibiotic for therapeutic purpose should be guided by culture and sensitivities. On the other hand, the association of antimycotics should be indicated only when a fungal infection was presumed in the presence of neutropenia/fever or normal leukocytosis and neutropenia in patients with fever73,78,79. We also recommend vaccinations to reduce the risk of sepsis for patients in which splenectomy is presumable during CRS/HIPEC. These patients should receive pneumococcal and influenza immunization; patients not previously immunized should also receive Haemophilus influenza type B and meningococcal group C conjugate vaccines80,81. As much as possible, especially because splenectomy increases major complication rate in patients undergoing CRS/HIPEC, we suggest this vaccine should be given at least two weeks before or 14 or more days after procedures82.

Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

Regarding the classification systems to be used for reporting complications related to CRS/HIPEC, we follow the statement from the 5th International Consensus Metting on Peritoneal Surface Malignancies Treatment to adopt the joint NCI/NIH Common Terminology Criteria for Adverse Events (CTCAE), last version83. However, because of different interpretations of severity grades of complications after CRS/HIPEC between this system and the therapy-oriented Clavien-Dindo classification84 - a universally-accepted classification in many surgical fields - we suggest that complications should be reported in both of these systems in order to permit comparison amongst different studies as well as with other comprehensive oncological and surgical procedures. As previously reported in the Milan consensus, the peritoneal cancer index (PCI) and the completeness of cytoreduction (CC) score described by Sugarbaker have been the recommended systems for intraoperative staging and classification for residual disease size, respectively since these experienced surgeonsâ&#x20AC;&#x2122; naked-eye estimations were considered the ideal methods of assessment by the large majority of experts85,86. Intraperitoneal Chemotherapy Schedules (Table 1) Even though several regimens of drugs for HIPEC procedures are available, we suggest the following options for treatment of DMPM: (1) cisplatin 100mg/m2 plus doxorubicin 15mg/m2 or (2) carboplatin 800mg/m2, both for 60min at 4L of perfusate56,87. For PMP and appendiceal tumors, the suggested protocols are (1) oxaliplatin 360mg/m2 for 30min or (2) cisplatin 100mg/m2 plus doxorubicin 15mg/m2 for 60min, both at 4L of perfusate56. These drug dosages should be reduced by about 30% for patients over the age of 60-70 years, patients previously exposed to multiple lines of systemic chemotherapy, patients who needed GM-CSF rescue for febrile neutropenia while on systemic chemothe-

535

rapy, patients who have received radiation therapy to bone-marrow bearing regions, and those who underwent extensive surgical cytoreduction due to high PCI scores88,89. Accordingly, special attention is required for dose reduction of oxaliplatin to 200250mg/m2 in these cases because of the increased risk of postoperative hemorrhagic complications compared with HIPEC and other drugs90. For safety reasons, we point the dose limiting of 1000mg/ m2 (or 200mg/m2/L of perfusate) for carboplatin, total dose of 240mg (or 45mg/L of perfusate) for cisplatin, 15mg/L of perfusate for doxorubicin, and 460mg/m2 for oxaliplatin56,87. A major point concerning the proposed intraperitoneal chemotherapy schedules for CRS/ HIPEC procedures in Brazil is the current unavailability of mitomycin (MMC) in our country due to commercial matters. However, even though some data suggest that MMC might be a better agent for HIPEC delivery than oxaliplatin in patients suffering of peritoneal carcinomatosis of colorectal origins with favorable histologies and low burden of disease (i.e.: PSDSS I/II)91, contrary data also suggests that oxaliplatin offers a survival advantage over MMC in similar settings92, while a trend of better overall survival may also be noted in patients with unfavorable histologies and high burden of disease (i.e., PSDSS III/IV) treated with oxaliplatin91. In fact, the largest published data involving more than two thousand patients with PMP/appendiceal tumors treated by strategies of CRS/HIPEC in 16 specialized centers had demonstrated no significant benefit in terms of overall survival for HIPEC with Oxaliplatin vs. MMC (10y survival of 78% vs. 66%, respectively; differences not statistically significant)4. But other wide data suggests that the use of oxaliplatin does not significantly increase the overall perioperative morbidity and/or mortality rates compared to a mitomycin- and doxorubicin-based protocols93. In these settings, we alternatively suggest the use of oxaliplatin for HIPEC delivery in PMP and apendicecal

Rev Col Bras Cir 2017; 44(5): 530-544


536

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

tumors especially because of the need for a lower perfusion time and the cisplatin plus doxorubicin protocol as an alternative lower-cost option. Similarly, due to the potential of increasing morbidity and complexity of procedures, we do not advoca-

te the routine use of bidirectional oxaliplatin-based HIPEC regimens unless more convincing data could be available, or any intensification of the HIPEC protocol by adding irinotecan to the oxaliplatin-alone regimen94.

Table 1. Proposed chemotherapy schedules of HIPEC (closed abdomen technique) for treatment of Pseudomixoma peritonei (PMP) / Appendiceal Tumors and Diffuse Malignant Peritoneal Mesothelioma (DMPM).

Disease

Intraperitoneal Chemotherapy Schedules

PMP*

Oxaliplatin 360mg/m2, 30min at 4L of perfusate; or CDDP 100mg/m2 plus doxorubicin 15mg/m2, 60min at 4L of perfusate.

DMPM

CDDP 100mg/m2 plus doxorubicin 15mg/m2, 60min at 4L of perfusate; or Carboplatin 800mg/m, 60min at 4L of perfusate.

* Pseudomixoma peritonei (PMP) and appendiceal epithelial neoplasms.

Perioperative Oncological Management Perioperative oncological management involving systemic therapies for both of these conditions is not clearly supported by randomized controlled trials, but a review of data from experienced centers has provided some evidence to this issue. For DMPM, neoadjuvant chemotherapy was not associated with increased completeness of cytoreduction95 and may impact negatively the survival for patients who underwent CRS-HIPEC with curative intent, whereas adjuvant chemotherapy may delay recurrence and improve survival96. Thus, we suggest that upfront CRS plus platin-based HIPEC should be considered the standard approach for DMPM, while waiting for a stronger level of scientific evidence6,67,96. Systemic chemotherapy should be administered principally in patients with recurrent disease or at a high risk for recurrence, and in those who are not appropriate candidates for aggressive surgery or were not optimally debulked97. For PMP from appendiceal origin, prior chemotherapy treatment was also found as independent predictors for a poorer progression-free survival and overall survival according to the largest international registry study

exploring the strategy of CRS/HIPEC4. However, subset analysis of this same data had confirmed the peritoneal mucinous carcinomatosis histopathologic subtype as an independent predictor of a poorer overall and disease-free survival4, in line with other reports that adenocarcinoma with signet ring cell and adenocarcinoid histomorphology contributes to the poor prognosis associated with peritoneal metastasis from appendiceal adenocarcinoma98. Herein, even though the possible benefit of neoadjuvant chemotherapy for high-grade tumors in general remains controversial99,100, preoperative systemic chemotherapy appears to improve the prognosis of patients with signet ring cell histology37, which suggests the need for some discussion in a multidisciplinary tumor board in order to decide about the best approach to each specific case. At this point, our recommendation is to consider the use of preoperative fluoropirimidine-based systemic chemotherapy for high-grade peritoneal metastasis from appendiceal adenocarcinoma with signet ring cell histology and moderate to high PCI scores37,99. In the adjuvant settings, the use systemic therapies should be guided by stands for other advanced colorectal cancers,

Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

as appropriated. Finally, regarding the use of early postoperative intraperitoneal chemotherapy (EPIC) in combination with CRS/HIPEC, our proposal of standardized procedures is not to routinely deliver EPIC for either PMP/appendiceal tumors or DMPM, since this additional procedure is associated with an increased rate of complications and no clear benefit in terms of survival7,13,14, whereas HIPEC-alone protocols are much simpler for patient, surgeon, and nursing care13. As previously reported, the use of EPIC did not translate to better survival outcomes in the largest surgical series exploring CRS/HIPEC for the treatment of PMP/appendiceal tumors4 or DMPM6, which support the proposal being presented. Thus, this BSSO committee suggests the use of EPIC as an alternative treatment option for treatment of these both malignancies only when HIPEC is not available.

CONCLUSION Practices of CRS/HIPEC are widely variable and standardization of such practices may enhance patient

537

outcomes and improve care standards across all centers that offer this procedure in Brazil. Herein, we have reviewed the main worldwide variations for the treatment of PMP/appendiceal tumors and DMPM with CRS/HIPEC and thus proposed standards for common technical aspects, patient selection, intraperitoneal chemotherapy schedules and perioperative oncological managements. The effort of producing a nationally acceptable proposal to guide clinical practice concerning CRS/HIPEC procedures may contribute to producing homogeneous data that permits pooled analysis from the developing Brazilian register for peritoneal surface malignancies.

ACKNOWLEDGMENTS The BSSO committee on peritoneal surface malignancies and HIPEC would like to thank Paul H. Sugarbaker, M.D., Ph.D., from the Peritoneal Surface Oncology Program, MedStar Washington Hospital Center, Washington DC, USA; Vic J. Verwaal, M.D., Ph.D., from Department of Surgery, Aarhus University Hospital, Aarhus, Denmark; and Marcello Deraco, M.D., Ph.D., from Peritoneal Surface Malignancy Program, National Cancer Institute, Milan, Italy, for the external reviews of this paper as described in methods.

R E S U M O A cirurgia citorredutora com quimioterapia intraperitoneal hipertérmica emergiu como um importante tratamento das neoplasias peritoneais e é, atualmente, o padrão de atendimento para neoplasias epiteliais do apêndice associadas à síndrome de pseudomixoma peritoneal, bem como para o mesotelioma peritoneal maligno difuso. No mundo, existem algumas variações reconhecidas das técnicas de cirurgia citorredutora e quimioterapia intraperitoneal hipertérmica, entretanto nenhuma técnica até agora demonstrou sua superioridade sobre o outra. Portanto, a padronização destes procedimentos poderia melhorar a prática clínica e permitir a comparação adequada entre os resultados. Neste cenário, a Sociedade Brasileira de Cirurgia Oncológica considera importante a apresentação de uma proposta de padronização de procedimentos de cirurgia citorredutora com quimioterapia intraperitoneal hipertérmica no Brasil, com um foco especial na produção de dados homogêneos para o desenvolvimento do registro brasileiro das neoplasias peritoneais. Descritores: Injeções Intraperitoneais. Hipertermia Induzida. Quimioterapia. Neoplasias Peritoneais.

REFERÊNCIAS 1.

2.

Lambert LA. Looking up: recent advances in understanding and treating peritoneal carcinomatosis. CA Cancer J Clin. 2015;65(4):28498. Passot G, Vaudoyer D, Villeneuve L, Kepenekian

3.

V, Beaujard AC, Bakrin N, et al. What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: a 25-year experience with 1,125 procedures. J Surg Oncol. 2016;113(7):796-803. Levine EA, Stewart JH 4th, Shen P, Russell GB, Loggie BL, Votanopoulos KI. Intraperitoneal chemotherapy

Rev Col Bras Cir 2017; 44(5): 530-544


538

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

for peritoneal surface malignancy: experience with 1,000 patients. J Am Coll Surg. 2014;218(4):57385 4. Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449-56. 5. PH, Sugarbaker. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol 2006;7(1):69-76. 6. Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237-42. 7. Helm JH, Miura JT, Glenn JA, Marcus RK, Larrieux G, Jayakrishnan TT, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis. Ann Surg Oncol. 2015;22(5):1686-93. 8. Witkamp AJ, de Bree E, Van Goethem R, Zoetmulder FA. Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy. Cancer Treat Rev. 2001;27(6):365-74. 9. Sugarbaker PH. Laboratory and clinical basis for hyperthermia as a component of intracavitary chemotherapy. Int J Hyperthermia. 2007;23(5):43142. 10. Hettinga JV, Konings AW, Kampinga HH. Reduction of cellular cisplatin resistance by hyperthermia - a review. Int J Hyperthermia. 1997;13(5):439-57. 11. Zunino B, Rubio-Patiño C, Villa E, Meynet O, Proics E, Cornille A, et al. Hyperthermic intraperitoneal chemotherapy leads to an anticancer immune response via exposure of cell surface heat shock protein 90. Oncogene. 2016;35(2):261-8. 12. Pelz JO, Vetterlein M, Grimmig T, Kerscher AG, Moll E, Lazariotou M, et al. Hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis: role of heat shock proteins and

13.

14.

15.

16.

17.

18.

19.

20.

dissecting effects of hyperthermia. Ann Surg Oncol. 2013;20(4):1105-13. McConnell YJ, Mack LA, Francis WP, Ho T, Temple WJ. HIPEC + EPIC versus HIPEC-alone: differences in major complications following cytoreduction surgery for peritoneal malignancy. J Surg Oncol. 2013;107(6):591-6. Lam JY, McConnell YJ, Rivard JD, Temple WJ, Mack LA. Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis. Am J Surg. 2015;210(3):424-30. Baiocchi G, Ferreira FO, Mantoan H, da Costa AA, Faloppa CC, Kumagai LY, et al. Hyperthermic intraperitoneal chemotherapy after secondary cytoreduction in epithelial ovarian cancer: a singlecenter comparative analysis. Ann Surg Oncol. 2016;23(4):1294-301. Akaishi E, Teixeira F, Katayama M, Mizumoto N, Costa FP, Buzaid AC, et al. Peritonectomy for peritoneal carcinomatosis: long-term outcomes from a single Brazilian institution. World J Surg. 2009;33(4):835-9; discussion 840. Costa WL Jr, Coimbra FJ, Ribeiro HS, Diniz AL, de Godoy AL, Begnami M, et al. Safety and preliminary results of perioperative chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for high-risk gastric cancer patients. World J Surg Oncol. 2012;10:195. Albuquerque TLC, Von Sohsten AKA, Rodas AKF, Weinstein L, Reis TJCC. Anesthesia in patients undergoing cytoreductive surgery (CS) and intraoperative hyperthermic chemotherapy (HIPEC) [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S199. Velasquez ARE, Quadros CA, Vieira LV, Prisco E, Cangussú HC, Silva RGM, et al. Morbidity and mortality of patients undergoing cytoreductive surgery and intraperitoneal chemotherapy (HIPEC) at São Rafael Hospital between 2011 and 2015 [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S201-S202. Vieira HC, Viana RFR, Lopes PVA, Moreira RCL, Rausch M, Salles PGO. Malignant peritoneal

Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

21.

22.

23.

24.

25.

26.

27.

28.

29.

mesothelioma: a case report [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S199. Firmino NLJ, Soares MC, Miranda E, Azevedo LW, Gomes GES, Diniz AF, et al. A succesful case of HIPEC in a peritoneal mesothelioma patient [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S199-200. Oliveira DNA, Batista TP, Carneiro VCG, Tancredi R, Badiglian-Filho L, Leão CS. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of advanced ovarian cancer: the first two cases of a pioneering clinical trial in Brazil [abstract]. Eur J Surg Oncol 2015 Oct 15;41(Suppl 1):S200. Reis TJCC, Ramalho WC, Barreto CL, Rodas AKF, Albuquerque TCL, Weinstein L, et al. Cytoreductive surgery and HIPEC: experience of the first patients operated in a public hospital [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S200. Cordeiro EZ, Baretta R, Silva CS, Bordinhao RW. Cytoreductive surgery and HIPEC for peritoneal metastasis by colon and appendix carcinoma [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S200201. Reis TJCC, Ramalho WC, Rodas AKF, Albuquerque TCL, Weinstein L, Gomes GES, et al. Economical feasibility of cytoreductive surgery and HIPEC by SUS [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S201. Brito FPB, Vieira SC, Morais Júnior MA, Silva MCA, Lopes AS, Ribeiro MMM. Intraperitoneal hyperthermic chemotherapy with high PCI and disease-free survival after 5 years: a case report [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S201. Cereser Junior CH, Giordani DSN, Weston AC, Pessini SA, Sugarbaker PH, Meinhardt Junior JG. Ovarian cancer with carcinomatosis: a case report [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S202. Reis TJCC, Ramalho WC, Miranda ACG, Pereira CGS, Weinstein L, Lima MBA, et al. Positive impact of nutritional, anti-inflammatory and antihistamine therapy preoperatively in patients undergoing cytoreductive surgery and HIPEC [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S202. Takahashi RM, Aguiar-Junior S, Lopes A, Nakagawa WT, Calsavara VF, Ferreira FO. White-blood-cell

30.

31.

32.

33.

34.

35.

539

count, lactate and C-reactive protein postoperative measures are associated with major complications following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [abstract]. Eur J Surg Oncol. 2015;41(Suppl 1):S203. Maciver AH, Al-Sukhni E, Esquivel J, Skitzki JJ, Kane JM 3rd, Francescutti VA. Current delivery of Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery (CS/HIPEC) and perioperative practices: an international survey of high-volume surgeons. Ann Surg Oncol. 2017;24(4):923-30. Cotte E, Passot G, Gilly FN, Glehen O. Selection of patients and staging of peritoneal surface malignancies. World J Gastrointest Oncol. 2010;2(1):31-5. Yan TD, Morris DL, Shigeki K, Dario B, Marcello D. Preoperative investigations in the management of peritoneal surface malignancy with cytoreductive surgery and perioperative intraperitoneal chemotherapy: expert consensus statement. J Surg Oncol. 2008;98(4):224-7. Taflampas P, Dayal S, Chandrakumaran K, Mohamed F, Cecil TD, Moran BJ. Pre-operative tumour marker status predicts recurrence and survival after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal Pseudomyxoma Peritonei: analysis of 519 patients. Eur J Surg Oncol. 2014;40(5):515-20. López-López V, Cascales-Campos PA, Schneider MA, Gil J, Gil E, Gomez-Hidalgo NR, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients. A systematic literature review. Surg Oncol. 2016;25(4):378-384. Alyami M, Lundberg P, Kepenekian V, Goéré D, Bereder JM, Msika S, Lorimier G, Quenet F, Ferron G, Thibaudeau E, Abboud K, Lo Dico R, Delroeux D, Brigand C, Arvieux C, Marchal F, Tuech JJ, Guilloit JM, Guyon F, Peyrat P, Pezet D, Ortega-Deballon P, Zinzindohoue F, de Chaisemartin C, Kianmanesh R, Glehen O, Passot G; BIG-RENAPE and RENAPE Working Groups. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis in the elderly: a casecontrolled, multicenter study. Ann Surg Oncol.

Rev Col Bras Cir 2017; 44(5): 530-544


540

36.

37.

38.

39.

40.

41.

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

2016;23(Suppl 5):737-45. Carr NJ, Cecil TD, Mohamed F, Sobin LH, Sugarbaker PH, Gonzรกlez-Moreno S, Taflampas P, Chapman S, Moran BJ; Peritoneal Surface Oncology Group International. A consensus for classification and pathologic reporting of Pseudomyxoma Peritonei and associated appendiceal neoplasia: the results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process. Am J Surg Pathol. 2016;40(1):14-26. Milovanov V, Sardi A, Studeman K, Nieroda C, Sittig M, Gushchin V. The 7th Edition of the AJCC Staging Classification Correlates with Biologic Behavior of Mucinous Appendiceal Tumor with Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/ HIPEC). Ann Surg Oncol. 2016;23(6):1928-33. Husain AN, Colby T, Ordonez N, Krausz T, Attanoos R, Beasley MB, Borczuk AC, Butnor K, Cagle PT, Chirieac LR, Churg A, Dacic S, Fraire A, GalateauSalle F, Gibbs A, Gown A, Hammar S, Litzky L, Marchevsky AM, Nicholson AG, Roggli V, Travis WD, Wick M; International Mesothelioma Interest Group. Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2013;137(5):647-67. Hjerpe A, Ascoli V, Bedrossian C, Boon M, Creaney J, Davidson B, et al. Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology. Cytojournal. 2015;12:26. Yan TD, Deraco M, Elias D, Glehen O, Levine EA, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH; Peritoneal Surface Oncology Group. A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database. Cancer. 2011;117(9):1855-63. Pillai K, Pourgholami MH, Chua TC, Morris DL. Prognostic significance of Ki67 expression in

42.

43.

44.

45.

46. 47.

48.

49.

50.

51.

malignant peritoneal mesothelioma. Am J Clin Oncol. 2015;38(4):388-94. Kusamura S, Torres Mesa PA, Cabras A, Baratti D, Deraco M. The Role of Ki-67 and pre-cytoreduction parameters in selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Ann Surg Oncol. 2016;23(5):1468-73. Baratti D, Kusamura S, Cabras AD, Bertulli R, Hutanu I, Deraco M. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Cancer. 2013;49(15):3140-8. Verwaal VJ, Kusamura S, Baratti D, Deraco M. The eligibility for local-regional treatment of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):2203. Esquivel J, Elias D, Baratti D, Kusamura S, Deraco M. Consensus statement on the loco regional treatment of colorectal cancer with peritoneal dissemination. J Surg Oncol. 2008;98(4):263-7. Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221(1):29-42. Sugarbaker PH. Cytoreductive surgery using peritonectomy and visceral resections for peritoneal surface malignancy. Transl Gastrointest Cancer 2013;2(2):54-74. Deraco M, Baratti D, Kusamura S, Laterza B, Balestra MR. Surgical technique of parietal and visceral peritonectomy for peritoneal surface malignancies. J Surg Oncol. 2009;100(4):321-8. Spratt JS, Adcock RA, Muskovin M, Sherrill W, McKeown J. Clinical delivery system for intraperitoneal hyperthermic chemotherapy. Cancer Res. 1980;40(2):256-60. Facy O, Combier C, Poussier M, Magnin G, Ladoire S, Ghiringhelli F, et al. High pressure does not counterbalance the advantages of open techniques over closed techniques during heated intraperitoneal chemotherapy with oxaliplatin. Surgery. 2015;157(1):72-8. Halkia E, Tsochrinis A, Vassiliadou DT, Pavlakou A, Vaxevanidou A, Datsis A, et al. Peritoneal

Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

52.

53.

54.

55.

56.

57.

58.

59.

60.

carcinomatosis: intraoperative parameters in open (coliseum) versus closed abdomen HIPEC. Int J Surg Oncol. 2015;2015:610597. Rodríguez Silva C, Moreno Ruiz FJ, Bellido Estévez I, Carrasco Campos J, Titos García A, Ruiz López M, et al. Are there intra-operative hemodynamic differences between the Coliseum and closed HIPEC techniques in the treatment of peritoneal metastasis? A retrospective cohort study. World J Surg Oncol. 2017;15(1):51. Raspé C, Flöther L, Schneider R, Bucher M, Piso P. Best practice for perioperative management of patients with cytoreductive surgery and HIPEC. Eur J Surg Oncol. 2017;43(6):1013-27. Epub 2016 Sep 28. Rettenmaier MA, Mendivil AA, Gray CM, Chapman AP, Stone MK, Tinnerman EJ, et al. Intra-abdominal temperature distribution during consolidation hyperthermic intraperitoneal chemotherapy with carboplatin in the treatment of advanced stage ovarian carcinoma. Int J Hyperthermia. 2015;31(4):396-402. Schaaf L, van der Kuip H, Zopf W, Winter S, Münch M, Mürdter TE, et al. A Temperature of 40 °C Appears to be a Critical Threshold for Potentiating Cytotoxic Chemotherapy In Vitro and in Peritoneal Carcinomatosis Patients Undergoing HIPEC. Ann Surg Oncol. 2015;22 Suppl 3:S758-65. Kusamura S, Dominique E, Baratti D, Younan R, Deraco M. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008 Sep 15;98(4):247-52. Glehen O, Cotte E, Kusamura S, Deraco M, Baratti D, Passot G, et al. Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol. 2008;98(4):242-6. Batista TP, Badiglian-Filho L, Leão CS. Exploring flow rate selection in HIPEC procedures. Rev Col Bras Cir. 2016;43(6):476-79. Mehta AM, Van den Hoven JM, Rosing H, Hillebrand MJ, Nuijen B, Huitema AD, et al. Stability of oxaliplatin in chloride-containing carrier solutions used in hyperthermic intraperitoneal chemotherapy. Int J Pharm. 2015;479(1):23-7. Mehta AM, Huitema AD, Burger JW, Brandt-Kerkhof

61.

62.

63.

64.

65.

66.

67.

68.

69.

541

AR, van den Heuvel SF, Verwaal VJ. Standard Clinical Protocol for Bidirectional Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Systemic Leucovorin, 5-Fluorouracil, and Heated Intraperitoneal Oxaliplatin in a Chloride-Containing Carrier Solution. Ann Surg Oncol. 2017;24(4):990997. Epub 2016 Nov 28. Caneparo A, Massucco P, Vaira M, Maina G, Giovale E, Coggiola M, et al. Contamination risk for operators performing semi-closed HIPEC procedure using cisplatin. Eur J Surg Oncol. 2014;40(8):925-9. Villa AF, El Balkhi S, Aboura R, Sageot H, HasniPichard H, Pocard M, et al. Evaluation of oxaliplatin exposure of healthcare workers during Heated Intraperitoneal Perioperative Chemotherapy (HIPEC). Ind Health. 2015;53(1):28-37. Konate A, Poupon J, Villa A, Garnier R, Hasni-Pichard H, Mezzaroba D, et al. Evaluation of environmental contamination by platinum and exposure risks for healthcare workers during a Heated Intraperitoneal Perioperative Chemotherapy (HIPEC) procedure. J Surg Oncol. 2011;103(1):6-9. Foster JM, Gupta PK, Carreau JH, Grotz TE, Blas JV, Gatalica Z, et al. Right hemicolectomy is not routinely indicated in pseudomyxoma peritonei. Am Surg. 2012;78(2):171-7. Sugarbaker PH. When and when not to perform a right colon resection with mucinous appendiceal neoplasms. Ann Surg Oncol. 2017;24(3):729-732. Epub 2016 Oct 21. Kusamura S, O’Dwyer ST, Baratti D, Younan R, Deraco M. Technical aspects of cytoreductive surgery. J Surg Oncol. 2008;98(4):232-6. Baratti D, Kusamura S, Cabras AD, Deraco M. Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study. Ann Surg Oncol. 2012;19(5):141624. Sugarbaker PH. Avoiding diverting ileostomy in patients requiring complete pelvic peritonectomy. Ann Surg Oncol. 2016;23(5):1481-5. Riss S, Chandrakumaran K, Dayal S, Cecil TD, Mohamed F, Moran BJ. Risk of definitive stoma after

Rev Col Bras Cir 2017; 44(5): 530-544


542

70.

71.

72.

73.

74.

75.

76.

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

surgery for peritoneal malignancy in 958 patients: comparative study between complete cytoreductive surgery and maximal tumor debulking. Eur J Surg Oncol. 2015;41(3):392-5. de Cuba EM, Verwaal VJ, de Hingh IH, van Mens LJ, Nienhuijs SW, Aalbers AG, et al. Morbidity associated with colostomy reversal after cytoreductive surgery and HIPEC. Ann Surg Oncol. 2014;21(3):883-90. Colantonio L, Claroni C, Fabrizi L, Marcelli ME, Sofra M, Giannarelli D, et al. A randomized trial of goal directed vs. standard fluid therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. J Gastrointest Surg. 2015;19(4):722-9. Mavroudis C, Alevizos L, Stamou KM, Vogiatzaki T, Eleftheriadis S, Korakianitis O, et al. Hemodynamic monitoring during heated intraoperative intraperitoneal chemotherapy using the FloTrac/ Vigileo system. Int Surg. 2015;100(6):1033-9. Cascales Campos PA, Gil Martínez J, Galindo Fernández PJ, Gil Gómez E, Martínez Frutos IM, Parrilla Paricio P. Perioperative fast track program in intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery in advanced ovarian cancer. Eur J Surg Oncol. 2011;37(6):543-8. Cascales-Campos PA, Sánchez-Fuentes PA, Gil J, Gil E, López-López V, Rodriguez Gomez-Hidalgo N, et al. Effectiveness and failures of a fast track protocol after cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal surface malignancies. Surg Oncol. 2016;25(4):349-354. Glehen O, Osinsky D, Cotte E, Kwiatkowski F, Freyer G, Isaac S, et al. Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol. 2003;10(8):863-9. López-Basave HN, Morales-Vasquez F, MendezHerrera C, Namendys-Silva SA, Luna-Ortiz K, Calderillo-Ruiz G, et al. Intensive care unit admission after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Is it necessary? J

77.

78.

79.

80.

81.

82.

83.

84.

Oncol. 2014;2014:307317. Arslan NC, Sokmen S, Avkan-Oguz V, Obuz F, Canda AE, Terzi C, et al. Infectious complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Surg Infect (Larchmt). 2017;18(2):157-63. Valle M, Federici O, Carboni F, Toma L, Gallo MT, Prignano G, et al. Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment. Eur J Surg Oncol. 2014;40(8):950-6. Gaspar GG, Menegueti MG, Auxiliadora-Martins M, Basile-Filho A, Martinez R. Evaluation of the predictive indices for candidemia in an adult intensive care unit. Rev Soc Bras Med Trop. 2015;48(1):77-82. Davies JM, Barnes R, Milligan D and Force; British Committee for Standards in Haematology. Working Party of the Haematology/Oncology Task. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin Med (Lond). 2002;2(5):440-3. Moulis G, Lapeyre-Mestre M, Mahévas M, Montastruc JL, Sailler L. Need for an improved vaccination rate in primary immune thrombocytopenia patients exposed to rituximab or splenectomy. A nationwide population-based study in France. Am J Hematol. 2015;90(4):301-5. Dagbert F, Thievenaz R, Decullier E, Bakrin N, Cotte E, Rousset P, et al. Splenectomy increases postoperative complications following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2016;23(6):1980-5. Younan R, Kusamura S, Baratti D, Cloutier AS, Deraco M. Morbidity, toxicity, and mortality classification systems in the local regional treatment of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):253-7 Lehmann K, Eshmuminov D, Slankamenac K, Kranzbühler B, Clavien PA, Vonlanthen R, et al. Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC. World J Surg. 2016;40(5):1075-81.

Rev Col Bras Cir 2017; 44(5): 530-544


Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

85. Portilla AG, Shigeki K, Dario B, Marcello D. The intraoperative staging systems in the management of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):228-31. 86. González-Moreno S, Kusamura S, Baratti D, Deraco M. Postoperative residual disease evaluation in the locoregional treatment of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):237-41. 87. Shetty SJ, Bathla L, Govindarajan V, Thomas P, Loggie BW. Comparison of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with mitomycin or carboplatin for diffuse malignant peritoneal mesothelioma. Am Surg. 2014;80(4):348-52. 88. Baratti D, Kusamura S, Laterza B, Balestra MR, Deraco M. Early and long-term postoperative management following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Gastrointest Oncol. 2010;2(1):36-43. 89. González-Moreno S, González-Bayón LA, Ortega-Pérez G. Hyperthermic intraperitoneal chemotherapy: Rationale and technique. World J Gastrointest Oncol. 2010;2(2):68-75. 90. Charrier T, Passot G, Peron J, Maurice C, Gocevska S, Quénet F, et al. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy with oxaliplatin increases the risk of postoperative hemorrhagic complications: analysis of predictive factors. Ann Surg Oncol. 2016;23(7):2315-22. 91. Prada-Villaverde A, Esquivel J, Lowy AM, Markman M, Chua T, Pelz J, et al. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014;110(7):779-85. 92. Leung V, Huo YR, Liauw W, Morris DL. Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43(1):144-9. 93. Glockzin G, von Breitenbuch P, Schlitt HJ, Piso P. Treatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicin-based HIPEC protocol in patients with peritoneal carcinomatosis: a

94.

95.

96.

97.

98.

99.

543

matched-pair analysisTreatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicinbased HIPEC protocol in patients with peritoneal carcinomatosis: a matched-pair analysis. J Surg Oncol. 2013;107(6):574-8. Quenet F, Goéré D, Mehta SS, Roca L, Dumont F, Hessissen M, et al. Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg. 2011;254(2):294-301. Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20(4):1093-100. Kepenekian V, Elias D, Passot G, Mery E, Goere D, Delroeux D, Quenet F, Ferron G, Pezet D, Guilloit JM, Meeus P, Pocard M, Bereder JM, Abboud K, Arvieux C, Brigand C, Marchal F, Classe JM, Lorimier G, De Chaisemartin C, Guyon F, Mariani P, Ortega-Deballon P, Isaac S, Maurice C, Gilly FN, Glehen O; French Network for Rare Peritoneal Malignancies (RENAPE). Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study. Eur J Cancer. 2016;65:69-79. Kindler HL. Peritoneal mesothelioma: the site of origin matters. Am Soc Clin Oncol Educ Book. 2013:182-8. hemelandu C, Sugarbaker PH. Clinicopathologic and prognostic features in patients with peritoneal metastasis from mucinous adenocarcinoma, adenocarcinoma with signet ring cells, and adenocarcinoid of the appendix treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2016;23(5):1474-80. Turner KM, Hanna NN, Zhu Y, Jain A, Kesmodel SB, Switzer RA, et al. Assessment of neoadjuvant chemotherapy on operative parameters and outcome in patients with peritoneal dissemination

Rev Col Bras Cir 2017; 44(5): 530-544


544

Batista A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

from high-grade appendiceal cancer. Ann Surg Oncol. 2013;20(4):1068-73. 100. Cummins KA, Russell GB, Votanopoulos KI, Shen P, Stewart JH, Levine EA. Peritoneal dissemination from high-grade appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). J Gastrointest Oncol. 2016;7(1):3-9.

Recebido em: 26/05/2017 Aceito para publicação em: 08/06/2017 Conflito de interesse: nenhum. Fonte de financiamento: nenhuma. Endereço para correspondência: Thales Paulo Batista E-mail: t.paulo@outlook.com / t.paulo@bol.com.br

Rev Col Bras Cir 2017; 44(5): 530-544


Teaching

DOI: 10.1590/0100-69912017005017

Educational project: low cost porcine model for venous cutdown training Projeto de ensino: modelo porcino de baixo custo para treinamento de dissecção venosa FERNANDO ANTÔNIO CAMPELO SPENCER NETTO, TCBC-PR1; MARIANA THALYTA BERTOLIN SILVA1; MICHAEL DE MELLO CONSTANTINO1; RAPHAEL FLÁVIO FACHINI CIPRIANI1; MICHEL CARDOSO1. A B S T R A C T Objective: to describe and evaluate the acceptance of a porcine experimental model in venous cutdown on a medical education project in Southwest of Brazil. Method: a porcine experimental model was developed for training in venous cutdown as a teaching project. Medical students and resident physicians received theoretical training in this surgical technique and then practiced it on the model. After performing the procedure, participants completed a questionnaire on the proposed model. This study presents the model and analyzes the questionnaire responses. Results: the study included 69 participants who used and evaluated the model. The overall quality of the porcine model was estimated at 9.16 while the anatomical correlation between this and human anatomy received a mean score of 8.07. The model was approved and considered useful in the teaching of venous cutdown. Conclusions: venous dissection training in porcine model showed good acceptance among medical students and residents of this institution. This simple and easy to assemble model has potential as an educational tool for its resemblance to the human anatomy and low cost. Keywords: Simulation. Dissection. Educational models. Models, Animal. Swine. Education, Medical.

INTRODUCTION

S

cutdown training and analyzes its acceptance among medical students and residents of the institution.

imulation based teaching has become popular in training of professional skills in several areas and a powerful learning tool in the medical area1-3. Simulation allows the practice of procedures in a controlled environment, where the error is seen as an opportunity to improve learning, giving autonomy to the student, reducing the risk to patients, as well as being attractive to students2-5. Venous cutdown is a relatively simple medical procedure that may be required in a trauma victim as a venous access option. According to the Advanced Trauma Life Support - ATLS®6, along with central venous access and intraosseous access, venous cutdown appears as second option of venous access if peripheral venous access is not possible. The choice of the method should be related to the performer’s experience and patient characteristics. This article reports a low-cost and low-technology experimental porcine model used for venous

METHODS The study was conducted at Universidade Estadual do Oeste do Paraná – Unioeste, from June 2013 to June 2014, as part of a registered education project (Prograd CR 40119/2013)7,8. It attended 61 Medicine students (last year) and eight resident physicians of Internal Medicine Program. Participants used porcine models for resuscitation procedures training and evaluated them through a questionnaire.

Teaching Project Steps Each training session comprised groups of about ten students or residents and was divided into the following steps: 1) discussion of the indication and complications of venous dissection, as well as the description of the technique according to ATLS6; 2) practice of the procedure by the participant under tutor supervision with

1 - Universidade Estadual do Oeste do Paraná (Unioeste), Laboratory of Medical Abilities, Emergency Room Internship Discipline, Cascavel, PR, Brazil Rev Col Bras Cir 2017; 44(5): 545-548


Spencer Netto Educational project: low cost porcine model for venous cutdown training

546

critical and corrective analysis technique; 3) assessment questionnaire completing the model by participant.

Porcine Model of Venous Cutdown In each training session, two models containing a porcine piece composed of skin, subcutaneous tissue and muscle each were made. The porcine pieces were previously purchased in licensed local market and adequate for human consumption, according to the sanitary surveillance rules. For these models, leftovers from other skills laboratory models (chest drainage) were used, with no specific cost falling on them. Each piece was used to training five to nine students. Each porcine piece was fixed by stitches, in a rigid wood surface (Figure 1). A nasogastric tube # 14 was passed between the muscle layer and subcutaneous tissue with the aid of a Kelly clamp, becoming palpable to perform the technique. The nasogastric tube was connected to an artificially colored IV solution system to simulate blood. The remaining materials were used in the Medical Skills Laboratory, obtained by donation at no cost. Details about the building of this model can be found in this site: https://www.youtube.com/watch?v=oLAQ1e61Bdc.

del for training medical students and residents. Some of the answers of the questionnaire were not object of this study, but used in order to improve the model and its application to graduation. Specifically, evaluations were requested of the overall quality of the model (robustness criteria, ease of handling and tissue similarity) and anatomical correlation (similarity to the expected anatomy in humans), both with scores ranging from 0 to 10. The questionnaire was prepared by the lead author and was not previously validated. All information obtained by the questionnaire were grouped into tables using Microsoft ExcelÂŽ and analyzed with averages and percentages.

RESULTS This project included 69 participants. Of these, 61 were graduate students of medicine (88.4%) and eight were medical residents (11.6%). Among the participants, the mean age was 25.8 (23 to 33). None of the study participants had performed a venous cutdown before. As for quantifying the quality of the model, the average grade was 9.16 (7 to 10). The anatomical correlation between the model and the human anatomy was considered 8.07 (5 to 10). All participants judged the simulated training in experimental model useful before performing venous cutdown procedure in patients, as well as other procedures for obtaining venous access for fluid resuscitation. This model was accepted by most of the participants (68/69 â&#x20AC;&#x201C; 98,6%) as an adjunct in the training of venous dissection.

DISCUSSION Figure 1. Materials and porcine model ready for use.

Questionnaire The evaluation questionnaire included epidemiological aspects of the trainees, previous training in managing hypovolemic shock with emphasis on fluid resuscitation (including peripheral venous puncture, deep venous and venous cutdown), and adequacy of the mo-

The use of simulators in several fields - medicine, nursing, engineering, aviation - have gained supporters, but it is still not universally used, since many factors are involved with its implementation as cost, teachers training, physical space, integration and critical evaluation of what is taught, in order to incorporate the simulation in curriculum repertoire of undergrads9-12.

Rev Col Bras Cir 2017; 44(5): 545-548


Spencer Netto Educational project: low cost porcine model for venous cutdown training

This experimental model was considered by all participants of the study as useful in the teaching of venous cutdown at graduation level. They also considered important to conduct training on the model before performing this procedure in a real situation. Thus, the model was approved as an adjunct, in teaching venous cutdown by the participants. Venous cutdown is an alternative to venous access in situations where it is not possible to obtain intravenous percutaneous access. It is especially required in urgent care and emergency. Facing a multiple trauma patient with a hypovolemic shock, venous dissection is a procedure that may save lives by allowing quick access to infusion volume and drugs. Due to the relatively low incidence of the need for phlebotomy, performing this procedure by undergraduate students of medicine and residents is minimal. Therefore, the proper training of venous cutdown by simulators, combining theoretical knowledge (technique, indications, contraindications and complications) with the execution of the procedure in a controlled environment and supervised way, offering no risk to patients, was considered important by all trainees, providing opportunities for learning and preparing for the execution of this procedure. This study confirms the importance of the use of simulation as a methodology in medical education, to make the student an active part in learning, encouraging the commitment to learn what is proposed and making the experience pleasurable to the trainee10. As in other studies1,10,13-15, the participants recognized the need to practice the procedure on models, with this well accepted model for training in venous dissection in our institution. In regard to the assessment of the model

547

anatomical correlation with the human anatomy, the participants attributed average to high similarity. It is cited by participants, as options for model improvement over the use of malleable material to simulate the vessel than the nasogastric tube used, providing greater tactile similarity to the venous consistency. In spite of different consistency of the nasogastric tube, this model allowed the trainee to execute all steps of a venous cutdown. Despite the importance of venous dissection training in simulators, we found no other work in the literature showing models for this purpose. Because of its simplicity and low cost, this model is attractive in the early stages of medical training, particularly in centers where resources are limited. This study was realized in a simple porcine model not recreating the anatomical issues present in real situations, like the difficulty to palpate the vessel, anatomical alterations, obesity, etc. Because the experiment was realized in a controlled environment, it did not generate the stress that the executor is submitted when does the procedure in urgency situation, which is a negative factor in teaching. Regarding the cutdown technique, it was not required to do a counter incision. The reason for this is based on the fact that the dissection realized by the study is oriented to the trauma environment, being recommended by ATLS course, to fluid reposition at the first moment. This venous access should be substituted as soon as possible. The study was composed by inexperienced participants in the procedure of venous cutdown, being necessary the evaluation by experienced professionals to improve the model.

R E S U M O Objetivo: descrever e avaliar a aceitação de um modelo experimental porcino no aprendizado de dissecção venosa em projeto de educação médica no sudoeste do Brasil. Método: um modelo experimental porcino foi desenvolvido para treinamento em dissecção venosa como projeto de ensino. Estudantes de medicina e médicos residentes receberam treinamento teórico sobre esta técnica cirúrgica e em seguida a praticaram no modelo. Após realizar o procedimento, os participantes preencheram um questionário sobre o modelo proposto. Este estudo apresenta o modelo e analisa as respostas ao questionário. Resultados: o estudo contou com 69 participantes que utilizaram e avaliaram o modelo. A qualidade geral do modelo porcino foi estimada em 9,16 enquanto a correlação anatômica entre este e a anatomia humana recebeu o escore médio de 8,07. O modelo foi aprovado e considerado útil no ensino da dissecção venosa. Conclusão: o treinamento de dissecção venosa em modelo porcino apresentou boa aceitação entre estudantes e residentes de medicina desta Instituição. Este modelo simples e de fácil confecção, tem potencial como instrumento de aprendizado por sua semelhança com a anatomia humana, e baixo custo. Descritores: Simulação. Dissecação. Modelos Educacionais. Modelos Animais. Suínos. Educação Médica.

Rev Col Bras Cir 2017; 44(5): 545-548


Spencer Netto Educational project: low cost porcine model for venous cutdown training

548

REFERENCES

torácica. Rev Col Bras Cir. 2016;43(1):60-3. 9.

1.

2.

3.

4.

5.

6.

7.

8.

Huang GC, Sacks H, Devita M, Reynolds R, Gammon W, Saleh M, et al. Characteristics of simulation activities at North American medical schools and teaching hospitals: an AAMC-SSH-ASPE-AACN collaboration. Simul Healthc. 2012;7(6):329-33. Beaubien J, Baker D. The use of simulation for training teamwork skills in health care: how low can you go? Qual Saf Health Care. 2004;13 Suppl 1:i51-6. Heitz C, Eyck RT, Smith M, Fitch M. Simulation in medical student education: survey of clerkship directors in emergency medicine. West J Emerg Med. 2011;12(4):455-60. Gomez MV, Vieira JE, Scalabrini Neto A. Análise do perfil de professores da área da saúde que usam a simulação como estratégia didática. Rev Bras Educ Med. 2011;35(2):157-62. Dourado A, Giannella T. Ensino baseado em simulação na formação continuada de médicos: análise das percepções de alunos e professores de um Hospital do Rio de Janeiro. Rev Bras Educ Med. 2014;38(4):460-9. American College of Surgeons. Suporte avançado de vida no trauma para médicos: ATLS: manual do curso de alunos. 9th ed. Chicago (IL): American College of Surgeons; 2012. Spencer-Netto FAC, Zacharias P, Cipriani RFF, Constantino MM, Cardoso M, Pereira RA. Modelo porcino no ensino da cricotiroidotomia cirúrgica. Rev Col Bras Cir. 2015:42(3):193-6. Spencer-Netto FAC, Sommers CG, Constantino MM, Cardoso M, Cipriani RFF, Pereira RA. Projeto de ensino: modelo suíno para treinamento de drenagem

10.

11. 12.

13.

14.

15.

Fanning RM, Gaba DM. The role of debriefing in simulation-based learning. Simul Healthc. 2007;2(2):115-25. 10. Wang EE, Beaumont J, Kharasch M, Vozenilek J. Resident response to integration of simulation-based education into emergency medicine conference. Acad Emerg Med. 2008;15(11):1207-10. Gaba D. The future vision of simulation in health care. Qual Saf Health Care. 2004;13 Suppl 1:i2-i10. Aggarwal R, Mytton O, Derbrew M, Hananel D, Heydenburg M, Issenberg B, et al. Training and simulation for patient safety. Qual Saf Health Care. 2010;19 Suppl 2:i34-i43. Robertson B, Kaplan B, Atallah H, Higgins M, Lewitt M, Ander D. The use of simulation and a modified Team STEPPS curriculum for medical and nursing student team training. Simul Healthc. 2010;5(6):332-7. Takayesu J, Farrell S, Evans A, Sullivan J, Pawlowski J, Gordon J. How do clinical clerkship students experience simulator-based teaching? A qualitative analysis. Simul Healthc. 2006;1(4):215-9. Bradley P. The history of simulation in medical education and possible future directions. Med Educ. 2006;40(3):254-62.

Received in: 16/03/2017 Accepted for publication: 20/05/2017 Conflict of interest: none. Source of funding: none. Endereço para correspondência: Fernando Antônio Campelo Spencer Netto E-mail: fspencernetto@gmail.com / kummerspencer@ yahoo.com.br

Rev Col Bras Cir 2017; 44(5): 545-548


INSTRUCTIONS FOR AUTHORS SCOPE AND POLITICS The Journal of the Brazilian College of Surgeons (CBC), an official division of the CBC, is published bimonthly in one annual volume, and proposes the dissemination of articles of all surgical specialties, contributing to its teaching, development and national integration. Articles published in the Journal of the Brazilian College of Surgeons follow the uniform requirements recommended by the International Committee of Medical Journals Editors (ICMJE – www.icmje.org), and are submitted to a double blind peer review. The journal of the Brazilian College of surgeons supports the policies for registration of clinical trials of the World Health Organization (WHO) and the ICMJE, recognizing the importance of these initiatives for the record and international dissemination of information on clinical studies in open access. Thus, it will only accept for publication the clinical research articles that have received an identification number on a clinical trial registry validated by the criteria established by WHO and ICMJE. The identification number must be registered at the end of the abstract. Between three and five members of the Editorial Board, anonymous to the authors, receive the texts, also anonymously, and decide for their publication. In the event of conflict of opinions, the Director of publications will evaluate the need for a new appraisal. Rejected articles are returned to authors. Only the works within the journal’s publication standards will be submitted to evaluation. Approved articles may sustain editorial-type alterations, provided that they do not alter the merit of the work. GENERAL INFORMATION The Journal of the Brazilian College of Surgeons evaluates articles for publication in Portuguese (Brazilian authors) and English (foreign authors) that follow the rules for manuscripts submitted to biomedical journals prepared and published by the International Committee of Medical Journal Editors (ICMJE – www.icmje.org) [CIERM Rev Col Bras Cir. 2008; 35 (6): 425-41, or article on the website of the journal (www.revistadocbc.org.br)] with the following characteristics: • Editorial: Is the initial article of an issue, generally about a current subject, requested by the Editor to the author of recognized technical and scientific capacity. • Original Article: Is the full account of clinical or experimental research, with positive or negative results. It must consist of Abstract, Introduction, Methods, Results, Discussion and References, the latter limited to a maximum of 35, aiming to the inclusion, whenever possible, of articles from national authors and national journals. The title should be written in Portuguese and English, and should contain the maximum of information with the minimum of words, without abbreviations. It must be accompanied by the complete name(s) of author(s) followed by the name(s) of the institution(s) where the work was performed. If multicenter, Arabic numerals must indicate the provenance of each of the authors in relation to the listed institutions. Authors should send along with their names only one title and one that best represents their academic activity. The Abstract should have a maximum of 250 words and be structured as follows: objective, methods, results, conclusions and keywords in the form referred to by DeCS (http://decs.bvs.br ). • Review article: The Editorial Board encourages the publication of matters of great interest to the surgical specialties containing synthetic analysis and relevant criticism and not merely a chronological description of literature. I must contain an introduction with description of the reasons that led to the writing of the article, the search criteria, followed by text ordered in titles and subheadings according to the complexity of the subject, and unstructured abstract. When applicable, at the end there may be conclusions and opinions of authors summarizing the review contents. • Letters to the Editor: Scientific Comments or controversy regarding articles published in the journal of the CBC. In general, such letters are sent to the principal author of the article to response and both letters are published in the same journal issue, no replica being allowed. • Scientific Communication: Content that deals with the form of presentation of scientific communication, investigating the problems and proposing solutions. Due to its features, this section can be multidisciplinary, receiving contributions from doctors, surgeons and non-surgeons and other professionals from various areas. It must have an unstructured Abstract, Keywords and free text. • Technical Note: Information about a particular operation or procedure of importance in surgical practice. The original must not exceed six pages including pictures and references if necessary. It must have an unstructured Abstract, Keywords and free text. • Education: Freeform content that addresses the teaching of surgery, both in graduate and post-graduate levels. Unstructured abstract. • Bioethics in surgery: Discussion of bioethical aspects in surgery. The content should address bioethical dilemmas in the performance of surgical activity. Freeform. Unstructured abstract. • Case reports: May be submitted for evaluation and the approved reports will be published, mainly in electronic journal of case reports, the Journal of Case Reports of the Brazilian College of Surgeons which can be accessed through the Brazilian College of Surgeons’ website (www.cbc.org.br) or directly at www.relatosdocbc.org.br. ARTICLE SUBMISSION Sending articles for the Journal of the Brazilian College of Surgeons can only be done through the online platform for submission of scientific papers, which can be accessed through the Brazilian College of Surgeons’ website (www.cbc.org.br) or directly at www.rcbc.gnpapers.com.br.

FORM AND STYLE • Text: Manuscripts submitted for review by the Journal of the Brazilian College of Surgeons must be unpublished and should not be evaluated in whole or in part by another scientific journal. Images should be forwarded separately from the text, and in accordance with the instructions on the online submission platform. Articles should be concise, not exceeding 2500 words. The abbreviations should be as few as possible, limited to the terms mentioned repetitively, as long as they do not hinder the understanding of the text, and should be defined from the first use. • References: Must be predominantly of works published in the last five years, restricted to those cited in the text, in order of citation, numbered consecutively and presented according to the Vancouver format (rules for manuscripts submitted to Biomedical Journals ICMJE- www.icmje.org – CIERM Rev Col Bras Cir. 2008; 35 (6): 425-41-www. revistadocbc.org.br). Annals of congresses and personal communications will not be accepted as references. Citations of books and theses should be discouraged. The authors of the article are responsible for the accuracy of the references. • Acknowledgements: Should be made to people who importantly contributed to the work’s realization. TABLES (maximum of six) Tables should be numbered with Arabic numerals, with captions on the top containing one or two sentences, and explanations of symbols at the bottom. Cite the tables in the text in numerical order including only information necessary for understanding of important points of the text. The data presented should not be repeated in graphs. Tables should follow the above-mentioned Vancouver standards. Tables must be typed in the body of the text, and never sent as figures. FIGURES (maximum of six) Figures are all the photos, graphics, paintings and drawings. All figures must be referred to in the text, being numbered consecutively by Arabic numbers and accompanied by descriptive captions. Histological images should contain in the legends the histological technique used and the degree of magnification. All figures should be submitted separately at the end of the manuscript.

MANDATORY CONDITIONS (READ CAREFULLY) It is expressed that, with the electronic submission, the author (s) agree (s) with the following assumptions: 1) that there is no conflict of interests, compliant with the Brazilian Federal Council of Medicine (CFM) resolution No. 1595/2000 that prevents the publication of works and materials with promotional purposes of products and/or medical devices; 2) that one must cite the funding source, if any; 3) that the work was submitted to the respective Ethics in Research Committee which approved it, providing the aproval number in the text; 4) that all authors authorize that the article suffer changes in the submitted text to be standardized in the language format of the Journal, which can result in removal of redundancies, as well as tables and/ or figures that are deemed unnecessary to understanding the text, provided that it does not change its meaning. If there are disagreements of the authors about these assumptions, they should write a letter leaving explicit the point at which they disagree, which will be appraised by the Editor, who will decide whether the article can be forwarded for publication or returned to the authors. 5) that the authors are allowed to hold the copyright of their published work without restrictions. 6) that if there is conflict of interest, it should be quoted with the text: “the author (s) (provide names) received financial support of the private company (provide name) for this study”. When there is a research foment funding source, it must also be cited. 7) that the responsibility for concepts or statements issued on articles and announcements published in the Journal of the Brazilian College of Surgeons is entirely up to the author (s) and advertisers. 8) that works already published or simultaneously submitted for evaluation in other periodicals will not be accepted. 9) that each approved article will have a cost of R$ 1,000.00 (one thousand reais) for the authors. If the lead author is a member of the Brazilian College of Surgeons, there will be a 50% discount on the article’s fee. Case Reports, approved for publication in the Journal of Case Reports of the Brazilian College of Surgeons are exempt from charges.

CONTACT: 2016-Brazilian College of Surgeons Rua Visconde de Silva, 52-3the floor 22271-090-Rio de Janeiro-RJ-Brazil Tel: + 55 21 2138-0659 Fax: + 55 21-2286 2595 Address for submission of manuscripts: E-mail: revistacbc@cbc.org.br


ABOUT THE JOURNAL Basic information Objectives: To disseminate scientific works of the surgical area of medicine that contribute to its teaching and development. History: The publication and dissemination of scientific activities of its members is one of the aims of medical societies. The Brazilian College of Surgeons (Colégio Brasileiro de Cirurgiões – CBC), founded in 1929, already in its first statute provided for the issuance of the “Bulletin of the Brazilian College of Surgeons” as its official division, whose starting number was published in January 1930. In 1967, the National Directory of CBC changed its name to “Journal of the Brazilian College of Surgeons”. From 1974 on, the journal began to be published bi-monthly, on a regular basis, to the present day. The abbreviation for its title is Rev Col Bras Cir, which should be used in bibliographies, footnotes and in references and bibliographic legends.

Creative Commons The journal of the Brazilian College of Surgeons is licensed with a 4.0 International , non-commercial, Creative Commons Attribution. This license lets others remix, adapt and create from your work, for non-commercial purposes. Although the new works have to assign proper credit and may not be used for commercial purposes, users do not have to license these derivative works under the same terms.

Free access policy This journal provides free and immediate access to its content, following the principle that providing free scientific knowledge to the public provides greater democratization of world knowledge.

About APC (Article Processing Charges) In view of the high costs for publication of the journal, from the issue 1/2017 on, every approved article started to have a cost of R$ 1000.00 (1000 reais) for the authors. Articles in which the lead author is a member of the CBC will have a discount of 50% of the publication fee.

Anti-Plagiarism Policy The Journal of the Brazilian College of Surgeons uses the iThenticate program to identify plagiarism in articles submitted for publication.

Indexing sources • Latindex • LILACS • Scopus • DOAJ • Free Medical Journals • MEDLINE/PUBMED • SciELO

Intellectual property All journal content, except where otherwise stated, is licensed under a Creative Commons License of type CC-BY attribution.

Sponsors The Journal of the Brazilian College of Surgeons is sponsored by CBC through: • Annuity of its associated members • Money from advertisers • Article publication fee


Rcbc v44n5 ingles reduzida