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Convenção Latinoamericana de Hérnia

19 a 21 abril de 2018 Foz do Iguaçu - Brasil Realização

www.cbhernia.com.br Apoio

Save the date! Patrocinadores

Federación Latinoamericana de Hernia Federação Latinoamericana de Hernia

Organização e Viagens

GROUP

ANÚNCIO MAIO 2017.indd 1

31/05/2017 18:36:42


SUMÁRIO / CONTENTS Rev Col Bras Cir 2017; 44(2)

E DITORI AL Rastreamento do câncer de pâncreas Pancreatic cancer screening Mônica Soldan....................................................................................................................................................................................... 109

O R IGINAL ARTIC L ES Inguinodinia em pacientes submetidos à hernioplastia inguinal convencional Inguinodynia in patients submitted to conventional inguinal hernioplasty Bruno Garcia Dias; Marcelo Protásio dos Santos; Ana Barbara de Jesus Chaves; Mariana Willis; Marcio Couto Gomes; Fernandes Tavares Andrade; Valdinaldo Aragão de Melo; Paulo Vicente dos Santos Filho....................................................................................................... 112 Impacto do curativo de espuma não aderente com Ibuprofeno na vida dos pacientes com úlcera venosa Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers Geraldo Magela Salomé; Lydia Masako Ferreira........................................................................................................................................ 116 Paratireoidectomia subtotal transaxilar single-port: estudo de viabilidade em cadáver Transaxillary single-port subtotal parathyroidectomy: feasibility study in cadavers Alexandre Elmães de Marsillac; Rossano Kepler Alvim Fiorelli; Henrique Neubarth Phillips; Pietro Novellino; André Lacerda Oliveira; Ricardo Paiva A. Scheiba Zorron.......................................................................................................................................................................... 125 Avaliação da expressão de Telomerase (hTert), Ki67 e p16ink4a em lesões intraepiteliais cervicais de baixo e alto graus Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions Ana Paula Szezepaniak Goulart; Manoel Afonso Guimarães Gonçalves; Vinicius Duval da-Silva................................................................... 131 O Transtorno de Déficit de Atenção e Hiperatividade interfere nos resultados da cirurgia bariátrica? Does the Attention Deficit Hyperactivity Disorder interfere with bariatric surgery results? Doglas Gobbi Marchesi; Jovana Gobbi Marchesi Ciriaco; Gustavo Peixoto Soares Miguel; Gustavo Adolfo Pavan Batista; Camila Pereira Cabral; Larissa Carvalho Fraga............................................................................................................................................................................. 140 Gênero bacteriano é fator de risco para amputação maior em pacientes com pé diabético Bacterial genus is a risk factor for major amputation in patients with diabetic foot Natália Anício Cardoso; Lígia de Loiola Cisneiros; Carla Jorge Machado; Juliana Merlin Cenedezi; Ricardo Jayme Procópio; Túlio Pinho Navarro....... 147 Implantes de acrílico customizados para a reconstrução de defeitos extensos da calota craniana: uma abordagem de exceção para pacientes selecionados Customized acrylic implants for reconstruction of extensive skull defects: an exception approach for selected patients Rafael Denadai Pigozzi da Silva; Cesar Augusto Raposo-Amaral; Marcelo Campos Guidi; Cassio Eduardo Raposo-Amaral; Celso Luiz Buzzo....... 154 Carcinoma ductal invasor: relação de características anatomopatológicas com a presença de metástases axilares em 220 casos Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases Ranniere Gurgel Furtado de Aquino; Paulo Henrique Diógenes Vasques; Diane Isabelle Magno Cavalcante; Ayane Layne de Sousa Oliveira; Bruno Masato Kitagawa de Oliveira; Luiz Gonzaga Porto Pinheiro............................................................................................................. 163 Análise das condições clínicas de pessoas obesas em período pré e pós-operatório de cirurgia bariátrica Analysis of obese patients’ medical conditions in the pre and postoperative periods of bariatric surgery Anderson da Silva Rêgo; Aline Zulin; Sandro Scolari; Sônia Silva Marcon; Cremilde Aparecida Trindade Radovanovic.................................... 171 Reconstrução imediata com enxerto autólogo de gordura: influência na recorrência local de câncer de mama Immediate reconstruction with autologous fat grafting: influence inbreast cancerregional recurrence Camile Cesa Stumpf; Jorge Villanova Biazus; Fernando Schuh Ângela Erguy Zucatto; Rodrigo Cericatto; José Antônio Crespo Cavalheiro; Andrea Pires Souto Damin; Márcia Portela Melo....................................................................................................................................... 179 Panorama do câncer da pele em comunidades de imigrantes Pomeranos do Estado do Espírito Santo Profile of skin cancer in Pomeranian communities of the State of Espírito Santo Patrícia Henriques Lyra Frasson; Danilo Schwab Duque; Estanrley Barcelos Pinto; Giulia Cerutti Dalvi; Sammy Zogheib Madalon; Tarcizo Afonso Nunes; Paulo Roberto Merçon de-Vargas.................................................................................................................................................. 187

Rev. Col. Bras. Cir.

Rio de Janeiro

Vol 44

Nº 2

p 109 / 219

mar/abr

2017


O R IG I NAL ARTIC LES Lesões traqueobrônquicas no trauma torácico: experiência de 17 anos Tracheobronchial injuries in chest trauma: a 17-year experience Roberto Saad Jr; Roberto Gonçalves; Vicente Dorgan Neto; Jacqueline Arantes G. Perlingeiro; Jorge Henrique Rivaben; Márcio Botter; José César Assef..................................................................................................................................................................................... 194 Cirurgia no Sistema Brasileiro de Saúde: financiamento e distribuição de médicos Surgery in Brazilian Health Care: funding and physician distribution Nivaldo Alonso; Benjamin B. Massenburg; Rafael Galli; Lucas Sobrado; Dario Birolini.................................................................................. 202

R E VIEW ARTICLE Incidência de câncer colorretal em pacientes jovens Incidence of colorectal cancer in young patients Fábio Guilherme C. M. de Campos; Marleny Novaes Figueiredo; Mariane Monteiro; Sérgio Carlos Nahas; Ivan Cecconello............................ 208

T E CHNICAL NOTE Transversus Abdominis Release (TAR) Robótico: é possível oferecer cirurgia minimamente invasiva para os defeitos complexos da parede abdominal? Robotic Transversus Abdominis Release (TAR): is it possible to offer minimally invasive surgery for abdominal wall complex defects? Maria Vitória França do Amaral; José Ricardo Guimarães; Paula Volpe; Flávio Malcher Martins de Oliveira; Carlos Eduardo Domene; Sérgio Roll; Leandro Totti Cavazzola.............................................................................................................................................................. 216

Rev. Col. Bras. Cir.

Rio de Janeiro

Vol 44

Nº 2

p 109 / 219

mar/abr

2017


Seja Membro Acadêmico da maior associação cirúrgica da América Latina

O Colégio Brasileiro de Cirurgiões cria categoria especial para acadêmicos de medicina VISITE O SITE DO CBC: www.cbc.org.br

• Confira as inúmeras atividades e serviços para sua formação e desenvolvimento. • Pré-requisitos para ser Membro Acadêmico do CBC Informe-se também na Secretaria Geral do CBC Tel.: (21) 2138-0653/0654 Sede: Rua Visconde de Silva, 52 - 3º andar Botafogo - Rio de Janeiro - CEP: 22271-092


A SOBRACIL lança mais uma edição do Programa Jovem Cirurgião, focado no treinamento para residentes e cirurgiões iniciantes em videocirurgia, com programação completa em conhecimentos e habilidades básicas para iniciação no método minimamente invasivo.

Inscrições abertas COORDENADORES

Dr. Cláudio Moura Dr. Thiers Soares

Patrocinador

www.programajovemcirurgiao.com.br O objetivo do programa é dar o treinamento necessário para o aprendizado e disseminação da técnica minimamente invasiva (videocirurgia básica), com conteúdo teórico-prático (prática em simuladores), para que um número cada vez maior de cirurgiões possa usá-la em benefício dos seus pacientes.

100 95 75

25 5 0

01.06.2017.ANÚNCIO JOVEM CIRURGIÃO quinta-feira, 1 de junho de 2017 17:31:30


Cirurgiões

Revista do Colégio Brasileiro de

EDITOR

Órgão Oficial do Colégio Brasileiro Brasileiro de Cirurgiões Cirurgiões ASSOCIATE EDITORS

CONSELHO DE REVISORES - NOVA GESTÃO - 2016

Guilherme Pinto Bravo Neto Associate Professor, EDITOR Department of Surgery, Faculty of Medicine, Federal Guilherme Pinto Bravo Neto University of Rio de JaneiroTCBC - Rio de Janeiro UFRJ - Rio de Janeiro RJ - Brazil.

Felipe Carvalho Victer TCBC-RJ –EDITORES Physician, University Hospital Pedro ASSOCIADOS Ernesto, State University of Rio de Janeiro – UERJ, Rio de JFaneiro , ARVALHO RJ, Brazil ELIPE C V.ICTER Rodrigo M artinez TCBC-RJ TCBC-RJ - Associate Professor, Department of ODRIGO ARTINEZ Surgery, Faculty of MRedicine , FM ederal University of TCBC-RJ Rio de Janeiro – UFRJ, Rio de Janeiro, RJ, Brazil. Fernando eon BRAULIOPonce PONCEdeLLEON PEREIRA DE CASTRO FERNANDO ACBC- RJ – Physician , U niversity Hospital AsCBC-RJ Clementino Fraga Filho, Federal University of Rio de Janeiro – UFRJ, Rio de Janeiro, RJ, Brazil

LIBRARIAN

Lenita Penido Xavier CRB-RJ 4808

ASSISTENTE DE PUBLICAÇÕES MARIA RUTH MONTEIRO WRITING ASSISTANT David da Silva Ferreira Júnior

ASSISTENTE DE REDAÇÃO DAVID

DA

SILVA FERREIRA JÚNIOR

GRAPHIC DESIGN

João Maurício Carneiro Rodrigues

JORNALISTA RESPONSÁVEL Mtb 18.552 JOÃO MAURÍCIO CARNEIRO RODRIGUES Mtb 18.552

COPYHOLDERS COUNCIL ADVISORY BOARD ABRÃO RAPOPORT - ECBC- SP - HELIOPOLIS HOSPITAL - SÃO PAULO - SP - BR JOSÉ LUIZ BRAGA DE AQUINO - TCBC-SP - FACULTY OF MEDICAL SCIENCES - PUCMAURICIO GONÇALVES RUBINSTEIN, TCBC-RJ ABRAO RAPOPORT – ECBC-SP- HOSPHEL- SP-BR EDMUND CHADA BARACAT – TCBC – SP- UNIFESP-BR ALDO DA CUNHA MEDEIROS - ECBC- RN - FEDERAL UNIVERSITY OF RIO GRANDE DO CAMPINAS - SP - BR NORTE - NATAL - RN - BR JOSÉ MARCUSUNIFESP-BR RASO EULÁLIOMAURO - TCBC-RJ - FEDERAL OF RIO DE JANEIRO DE SOUZA LEITE UNIVERSITY PINHO – TCBC-SC - HOSPITAL ALBERTO SCHANAIDER – TCBC-RJ - UFRJ-BR EDNA FRASSON DE SOUZA MONTERO – TCBC-SPALEXANDRE FERREIRA OLIVEIRA - TCBC- MG - FEDERAL UNIVERSITY OF JUIZ DE - RIO DE JANEIRO - RJ - BR MUNICIPAL SÃO SC-BR ALDO -DA CUNHA MEDEIROSTCBC-RN-UFRN-BR EDUARDO HARUO SAITO, TCBC-RJ JULIO CESAR BEITLER - TCBC-RJ FORA JUIZ DE FORA - MG - BR - ESTÁCIO DEJOSÉSÁ UNIVERSITY - RIO DE JANEIRO - RJ - BR ALVARO ANTONIO BANDEIRA FERRAZ - TCBC-PE - FEDERAL UNIVERSITY OF JÚLIO CEZAR UILI COELHO - TCBC-PR - FEDERAL UNIVERSITY OF PARANÁ - CURITIBA - BR LUIZ ANTONIO MODOLIN, ECBC-SP ALESSANDRO BERSCH FABIO XERFAN NAHAS – TCBC-SP –UNIFESP-BR PERNAMBUCO - RECIFEOSVALDT - PE - BR– TCBC-RS- UFRGS-BR KATIA SHEYLA MALTA PURIMMIGUEL - POSITIVO UNIVERSITY - CURITIBA - PR - BR ANA CRISTINA GOUVEIA MAGALHÃES FEDERAL UNIVERSITY OF RIO DE JANEIRO EYER DE JESUS - TCBC-RJ NELSON ADAMI ANDREOLLO – TCBC-SP - UNICAMP-SP-BR ALEXANDRE FERREIRA OLIVEIRA, TCBC-MG FERNANDO QUINTANILHA RIBEIROLISIEUX – SP- FCMSC-SP-BR RIO DE JANEIRO - RJ - BR FLUMINENSE FEDERAL UNIVERSITY - NITERÓI - RJ - BR ANDY PETROIANU - TCBC-MG - FEDERAL UNIVERSITY OFFLAVIO MINASDANIEL GERAIS - BELOTOMASICH,TCBC-PR LUIZ CARLOS VON BAHTEN - TCBC-PR FEDERAL UNIVERSITY OF PARANÁ - CURITIBA - BR NELSON -ALFRED SMITH ALEXANDRE PIASSI PASSOS, TCBC-MG SAAVEDRA HORIZONTE - MG - BR LUIZ GUSTAVO DE OLIVEIRA E SILVA - TCBC-RJ - IPANEMA FEDERAL HOSPITAL / NELSON -FONTANA ÁLVARO ANTONIO – TCBC-PE - UFPE-BR FREDERICO SILVEIRA TCBC-RJ ANGELITA HABR BANDEIRA - GAMA - FERRAZ TCBC-SP - UNIVERSITY OF SÃO PAULO - SÃO AVELLAR PAULO - SP - BR LUCAS, MINISTRY OF HEALTH - RIO DE JANEIRO RJ - BR MARGARIDO – TCBC-SP - USP-BR ANTONIO CARLOS VALEZI - TCBC-PR - STATE UNIVERSITY OF LONDRINA LUIZ GUSTAVO PERISSÉ - FEDERAL UNIVERSITY OF RIO DE JANEIRO - RIO DE JANEIRO - RJ - BR OSVALDO MALAFAIA – TCBC-PR- UFPR-BR ANA CRISTINA GOUVEIA MAGALHÃES, UFRJ-RJ GASPAR DE JESUS LOPES FILHO –TCBC-SP – UNIFESP LONDRINA - PR - BR LUIZ RONALDO ALBERTI - FEDERAL UNIVERSITY OF MINAS GERAIS - BELO HORIZONTE ANTONIO CLAUDIO JAMEL COELHO UNIVERSITY /MINISTRY - MG - BR PAULO FRANCISCO GUERREIRO CARDOSO – ACBC-RS- FFFCMPA-BR ANDY PETROIANUTCBC-MG - UFMG-BR- TCBC-RJ - GAMA FILHO GIOVANNI ANTONIO MARSICO, TCBC-RJ OF HEALTH - RIO DE JANEIRO - RJ - BR MANOEL XIMENES NETO - ECBC-DF - UNIVERSITY OF BRASÍLIA - BRASÍLIA - DF - BR PAULO GONÇALVES DE OLIVEIRA – TCBC-DFUNB-DF-BR ANGELITA HABR-GAMA – TCBC-SPUSP-BR - FACULTY OF MEDICAL GIULIANO ANCELMO- BENTO,ACBC-RJ ANTONIO JOSÉ GONÇALVES - TCBC-SP SCIENCES SÃO MANUEL DOMINGOS DA CRUZ GONÇALVES - ECBCRJ - FEDERAL UNIVERSITY OF RIO PAULO HOLY HOME - SÃO PAULO - SP - BR DE JANEIRO - RIO DE JANEIRO - RJ - BR RICARDO ANTONIO CORREIA LIMA, TCBC-RJ ANTONIO CARLOS VALEZI, TCBC-PR GUSTAVO PEREIRA FRAGA – TCBC-SPUNICAMP BR ANTONIO NOCCHI KALIL - TCBC-RS - FEDERAL UNIVERSITY OF HEALTH SCIENCES OF MARCOS ALPOIN FREIRE - TCBC-RJ - FEDERAL UNIVERSITY OF RIO DE JANEIRO - RIO DE PORTO ALEGRE - PORTO ALEGRE - RSTCBC-RJ - BR JANEIRO - RJ - BR RENATO ABRANTES LUNA, TCBC-RJ ANTONIO CLAUDIO JAMEL COELHO. HAMILTON PETRY DE SOUZA – TCBC-RSPUCRS-BR ARLINDO MONTEIRO DE CARVALHO JR. - TCBC-PB - FEDERAL UNIVERSITY OF PARAÍBA MARIA DE LOURDES P. BIONDO SIMÕES - TCBC-PR - PONTIFICAL CATHOLIC UNIVERSITY -ANTONIO JOÃO PESSOA - PB - BR OF PARANÁ JOSÉ GONÇALVES – TCBC-SP - FCMSCSP-BR JOÃO GILBERTO MAKSOUD- ECBC-SPUSP-BR - CURITIBA - PR - BRRENATO MIRANDA DE MELO, TCBC-GO ARTHUR BELARMINO GARRIDO JUNIOR - TCBC-SP - UNIVERSITY OF SÃO PAULO - SÃO MAURICIO GONÇALVES RUBINSTEIN - TCBC-RJ - FEDERAL UNIVERSITY OF RIO DE RICACHENEVSKY GURSKI – TCBC-RS- UFRGS-BR ANTONIO NOCCHI KALIL – TCBC-RS - UFCSPA-BR JOSÉ EDUARDO DE AGUILAR-NASCIMENTO – TCBC–MTPAULO - BR. JANEIRO - RIO DE UFMT-BR JANEIRO - RJRICHARD - BR CARLOS ANSELMO LIMA - TCBC - FEDERAL UNIVERSITY OF SERGIPE - ARACAJU - SE - BR MAURO DE SOUZA LEITE PINHO - TCBC-SC- UNIVERSITY OF THE JOINVILLE REGION ROBERTO SAAD JR., TCBC-SP ARLINDO MONTEIRO DE CARVALHO JR., TCBC-PB JÚLIO CEZAR UILI COELHO- TCBC-PR - UFPR-BR DANILO NAGIB SOLOMON PAUL - ECBC-ES - SUPERIOR SCHOOL OF SCIENCES - JOINVILLE - SC- BR VITÓRIA HOMEGARRIDO OF MERCY - VITÓRIA - ES --BRAZIL MIGUEL LUIZ ANTONIO MODOLIN - ECBC-SP - FACULTY OF MEDICINE RODOLFO ACATAUASSU NUNES, TCBC-RJ - UNIVERSITY OF ARTHUR HOLY BELARMINO JUNIOR – TCBC-SP USP-BR LISIEUX EYER DE JESUS- TCBC-RJ- UFF-BR DAYSE COUTINHO VALENTE - TCBC-RJ - FERNANDO LUIZ BARROSO INSTITUTE - RIO SAO PAULO - SP - BR RODRIGO ALTENFELDER SILVA – TCBC-SP-OFFCMSC-SP-BR AUGUSTO – TCBC-MG- UFU-BR LUIZ CARLOS VON BAHTEN- TCBC-PRUFPR-BR DE JANEIRODIOGO - RJ - FILHO BR NELSON ADAMI ANDREOLLO - TCBC-SP - STATE UNIVERSITY CAMPINAS DIOGO FRANCO - TCBC-RJ - FEDERAL UNIVERSITY OF RIO DE JANEIRO - RIO DE CAMPINAS - SP - BR ROGERIO APARECIDO DEDIVITIS, TCBC-SP CARLOS ANSELMO LIMA, TCBC-RJ LUIZ GUSTAVO DE OLIVEIRA E SILVA, TCBC-RJ JANEIRO - RJ - BR NELSON ALFRED SMITH - FEDERAL UNIVERSITY OF RIO DE JANEIRO - RIO DE JANEIRO - RJ - BR DJALMA JOSE FAGUNDES - SANTOS, ECBC-SPTCBC-RJ - FEDERAL UNIVERSITY SÃO PAULO - SÃO OSVALDO MALAFAIA - ECBC-PR - FEDERAL UNIVERSITY PARANÁUFGO-BR - CURITIBA - PR - BR RUFFO DE FREITAS JÚNIOR-OF TCBC-GOCARLOS EDUARDO RODRIGUES LUIZOF GUSTAVO PERISSÉ PAULO - SP - BR PAULO FRANCISCO GUERREIRO CARDOSO - ACBC-RS - FEDERAL FACULTTY OF MEDICAL EDMUND CHADA BARACAT SÃO PAULO - SÃO SCIENCES FOUNDATION OF PORTO - PORTO ALEGRE - RS - BR RUIALEGRE HADDAD – TCBC-RJUFRJ-BR CLEBER DARIO KRUEL – TCBC-RS- - TCBC-SP UFRGS-B - FEDERAL UNIVERSITY LUIZ OF RONALDO ALBERTI PAULO - SP - BR PAULO GONÇALVES DE OLIVEIRA - TCBC-DF - UNIVERSITY OF BRASÍLIA - BRASÍLIA SILVIA CRISTINE SOLDÁ- TCBC-SP- FCMSC-SP-BR DANILOFRASSON NAGIB SALOMÃO PAULO – TCBC-ESEMESCAM-BR. LUIZ EDNA DE SOUZA MONTERO - TCBC-SP - FEDERAL MANOEL UNIVERSITY OFFERREIRA SÃO PAULO - DF - BR - SÃO PAULO - SP - BR RICARDO ANTONIO CORREIA LIMA - TCBC-RJ - FEDERAL UNIVERSITY OF THE STATE SIZENANDO VIEIRA STARLING, TCBC-MG DAYSE COUTINHO VALENTE, TCBC-RJ MANOEL XIMENES NETO- ECBC-DF - UNB-DF-BR EDUARDO HARUO SAITO - TCBC-RJ - STATE UNIVERSITY OF RIO DE JANEIRO - RIO DE OF RIO DE JANEIRO - RIO DE JANEIRO - RJ - BR JANEIRO - RJ - BR– TCBC-RJ- UFRJ-BR RENATO– TCBC-RJABRANTES LUNA - TALITA TCBC-RJ - RIO DE JANEIRO STATE UFRJ-BR EMPLOYEES FEDERAL ROMERO FRANCOECBC-RJDIOGO FRANCO MANUEL DOMINGOS DA CRUZ GONÇALVES UFRJ-BR ELIZABETH GOMES DOS SANTOS - TCBC-RJ - FEDERAL UNIVERSITY OF RIO DE JANEIRO HOSPITAL - RIO DE JANEIRO - RJ - BR ERNESTO COELHO MARCELO DE PAULA LOUREIRO, TCBC-PR -DJALMA RIO DE JANEIRO - RJ - BR NETO,ACBC-RJ RENATO MIRANDA DE MELO THALES - TCBC-PAULO GO - BATISTA, FEDERALTCBC-PE UNIVERSITY OF GOIÁS - GOIÂNIA FABIO XERFAN NAHAS - TCBC-SP - FEDERAL UNIVERSITY OF SÃO PAULO - SÃO PAULO - GO - BR WILSON CINTRA TCBC-SP MARIA DE LOURDES P. BIONDO SIMOES – TCBC-PR – PUCPR-BR -DJALMA SP - BR JOSE FAGUNDES – TCBC-SP- UNIFESP-BR ROBERTO SAAD JR. - TCBC-SP - FACULTY OFJR., MEDICAL SCIENCES OF THE SÃO PAULO FLAVIO DANIEL SAAVEDRA TOMASICH - TCBC-PR - CLINICS HOSPITAL - FEDERAL HOLY HOME - SÃO PAULO - SP WILLIAM - BR ABRÃO SAAD- ECBC-SP- USP -BR UNIVERSITY OF PARANÁ - CURITIBA - PR - BR RODRIGO ALTENFELDER SILVA - TCBC-SP - FACULTY OF MEDICAL SCIENCES OF THE FREDERICO AVELLAR SILVEIRA LUCAS - TCBC-RJ - NATIONAL CANCER INSTITUTE - RIO SÃO PAULO HOLY HOME - SÃO PAULO - SP - BR DE JANEIRO - RJ - BR ROGERIO APARECIDO DEDIVITIS - TCBC-SP - UNIVERSITY OF SÃO PAULO - SÃO FERNANDO ATHAYDE VELOSO MADUREIRA - TCBC-RJ - FEDERAL UNIVERSITY OF THE PAULO - BR ARNULF THIEDE DIETZOF GOIÁS - GOIÂNIA CONSULTANTS STATE OF RIO DE JANEIRO - RIOEDITORS DE JANEIRO - RJ - BR. RUFFO DE FREITAS JÚNIOR - ULRICH TCBC-GO - ANDREAS FEDERAL UNIVERSITY GASPAR DE JESUS LOPES FILHO - TCBC-SP - FEDERAL UNIVERSITY OF SÃO - University - GO - BRof Würzburg Department of PAULO Surgery, Department of Surgery I, University of Würzburg, SÃO PAULO - SP - BR SOLDÁ - TCBC-SP - FACULTY OF MEDICAL SCIENCES OF THE SÃO Hospital, OberdürrbacherSILVIA Str. CRISTINE 6, D-97080 Medical School, Würzburg, Germany GIOVANNI ANTONIODA MARSICO TCBC-RJ - ANDARAÍ FEDERAL HOSPITAL /MINISTRY PAULO HOLY HOME - SÃO PAULO - SP - BR ALCINO LÁZARO SILVA, -ECBC-MG Würzburg, Germany OF HEALTH - RIO DE JANEIRO - RJ - BR SILVIO HENRIQUES DA CUNHA NETO - FEDERAL UNIVERSITY OF RIO DE JANEIRO - RIO ANTONIOANCELMO PELOSI DE MOURA LEITE, ECBC-SP GIULIANO BENTO - ACBC-RJ - UNIVERSITY OF THE STATE OF RIO DE DE JANEIRO - RJ - BR WEDER JANEIRO - RIO DE JANEIRO - RJ - BR IZENANDO VIEIRA STARLING W. - TCBC-MG - JOHN XXIII HOSPITAL - BELO HORIZONTE DARIO BIROLINI, ECBC-SP MURRAY BRENNAN - MG - BR GUSTAVO PEREIRA FRAGA - TCBC-SP - STATE UNIVERSITY OF CAMPINAS - CAMPINAS Klinikdirektor- UniversitätsSpital Zürich, HeCBC Department of Surgery, Memorial -FARES SP - BR RAHAL, ECBC-SP TALITA ROMEROSloanFRANCO - ECBC-RJ - FEDERAL UNIVERSITY OF RIO DE JANEIRO - RIO Switzerland HAMILTON PETRY DE SOUZA - ECBC-RS - PONTIFICAL CATHOLIC UNIVERSITY RIO DE JANEIRO - RJUSA - BR Kettering CancerOFCenter, New York NY, FERNANDO LUIZ BARROSO, GRANDE DO SUL - PORTO ALEGRE ECBC-RJ - RS - BR TÉRCIO DE CAMPOS - TCBC- SP - FACULTY OF MEDICAL SCIENCES OF THE SÃO PAULO JOÃO MAKSOUD - ECBC-SP - UNIVERSITY OF SÃO PAULO - SÃO PAULO - BR. HOLY HOME - SÃO PAULO - SP - BR ISAC GILBERTO JORGE FILHO, TCBC-SP CLAUDE DESCHAMPS H.UNIVERSITY FUCHS OF JOSÉ EDUARDO DE AGUILAR NASCIMENTO - TCBC- MT KARL - FEDERAL THALES PAULO BATISTA - TCBCPE - PERNAMBUCO HEALTH FACULTY / PROFESSOR IVO H.GROSSO J. CAMPOS PITANGUY, TCBC-RJ MATO - CUIABÁ - MT - BR FERNANDO FIGUEIRA INSTITUTE OF INTEGRAL MEDICINE - RECIFE - PE - BR M.D The Mayo Clinic, MN,USA Markus-Krankenhaus Frankfurter DiakonieJOSÉ EDUARDO FERREIRA MANSO - TCBC-RJ - FEDERAL UNIVERSITY OF RIO DE JANEIRO WILSON CINTRA JR. - TCBC-SP - UNIVERSITY OF PAULO - SÃO PAULO - SP - BR MARCOS F. MORAES, ECBC-RJ Kliniken, Wilhelm-Epstein-Straße 4, 60435 - RIO DE JANEIRO - RJ - BR WILLIAM ABRÃO SAAD - ECBC-SP - UNIVERSITY OF SÃO PAULO - SÃO PAULO - SP - BR

SAUL GOLDENBERG, ECBC-SP

Frankfurt am Main


NATIONAL CONSULTANTS

INTERNATIONAL CONSULTANTS

EDITORES DA REVISTA DO CBC

ALCINO LÁZARO DA SILVA, ECBC-MG - Federal University of Minas Gerais.

ARNULF THIEDE - Department of Surgery, University of Würzburg

ALUIZIO SOARES DE SOUZA RODRIGUES, ECBC-RJ - Federal University of

Hospital, Oberdürrbacher Str. 6, D-97080 Würzburg, Germany

1967 - 1969 JÚLIO SANDERSON

1973 - 1979 HUMBERTO BARRETO

1983 - 1985 1992 - 1999 CLAUDE DESCHAMPS - M.D - The Mayo Clinic, MN,USA JOSÉ LUIZ XAVIER PACHECO MERISA GARRIDO

Rio de Janeiro-UFRJ-Rio de Janeiro-RJ.

ANTONIO PELOSI DE MOURA LEITE, ECBC-SP - Cardiovascular Diseases Institute of São José do Rio Preto-SP

EDUARDO PARRA-DAVILA - Florida Hospital Celebration Health - 400

Celebration Pl, Kissimmee, FL 34747, USA. 1986 - 1991 2000 - 2001 Sanchinarro Madrid MARCOS EMILIO MORAESDE VICENTE LÓPEZ – Hospital JOSÉ ANTÓNIO GOMES DE SOUZA

1969 - 1971 JOSÉ HILÁRIO

1980 - 1982 EVANDRO FREIRE

FERNANDO LUIZ BARROSO, ECBC-RIO DE JANEIRO - Ipanema County

KARL H. FUCHS - Markus-Krankenhaus Frankfurter Diakonie-Kliniken,

Hospital-RJ.

2006-2015

Wilhelm- Epstein-Straße 4, 60435 Frankfurt am Main

DARIO BIROLINI, ECBC-SP - Faculty of Medicine, University of Paulo.

2002 - 2005

FERNANDO PAES LEME, ECBC-RIO DE JANEIRO - Faculty of INTO BRAVO NETO JOSÉ E DUARDO FERREIRA MANSO GUILHERME PMANOEL

MURRAY BRENNAN - HeCBC Department of Surgery, Memorial Sloan-

Medicine of Campos-RJ.

Kettering Cancer Center, New York NY, USA

ISAC JORGE I, TCBC-SP - Ribeirão Preto University (UNAERP)

ULRICH ANDREAS DIETZ - Department of Surgery I, University of

MARCOS F. MORAES, ECBC-RJ - Gama Filho University-RJ.

Würzburg, Medical School, Würzburg, Germany

SAUL GOLDENBERG, ECBC-SP - Federal University of São Paulo- Paulista

W. WEDER - Klinikdirektor-UniversitätsSpital Zürich, Switzerland

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DOI: 10.1590/0100-69912017002015

Editorial

Pancreatic cancer screening Rastreamento do câncer de pâncreas Mônica Soldan1,2.

W

hen it comes to the world population, the incidence of pancreatic cancer is low, with a cumulative risk of 1% throughout life, not rendering in screening recommendations by the World Health Organization1. Pancreatic cancer is the 4th leading cause of death by Cancer in the US, with the prospect of becoming the second in 20301. In Brazil it accounts for 2% of all types of neoplasias and for 4% of all cancer deaths. Although not among the top ten cancers in Brazil, it is the eighth leading cause of cancer death, since most patients are diagnosed in locally advanced or metastatic disease stages. Nevertheless, it holds the 13th position in incidence by type of cancer in the rankings made by the National Cancer Institute of the Brazilian Ministry of Health2. The pancreatic ductal adenocarcinoma (PDA) originates in the exocrine pancreas and accounts for 95% of pancreatic tumors. The risk of developing PDA throughout life is 1.49%, or one in 67, and its incidence increases with age3. Most diagnoses occur after the age of 50, with a peak incidence around 70 to 75 years, being more common in men. Other risk factors related to pancreatic cancer are smoking, chronic pancreatitis, cirrhosis, obesity, sedentary lifestyle, high fat and cholesterol diet, diabetes mellitus, occupational exposure to carcinogens, Jewish ancestry (Ashkenazi) and low socioeconomic status. The main family syndromes related to the disease are hereditary pancreatitis, hereditary non-polypoid colorectal cancer, hereditary breast and ovary cancer, familial atypical multiple melanoma, Peutz-Jeghers and ataxia-telangectasia4. PDA is a disease with high lethality, with a 5% five-year survival rate. Mortality has not changed much in spite of advances in surgical techniques in the last 80 years, after the introduction of pancreatoduodenectomy3. Surgical resection is the only potential cure for PDA, but

in 80% of patients with symptoms the tumor is already unresectable at the time of diagnosis. Candidates for surgical resection survive on average 12 months, this time being reduced to 3.5 months in those not candidates for surgery3. Increased resectability requires the detection of PDA at an early stage, and the selective screening of patients at high risk for its development can be a good way to achieve this goal. Both genetic and modifiable factors contribute to the development of PDA, and the hereditary component can be identified in 10% of cases, with a specific mutation implicated in 20% of such individuals3. Through the identification and screening of patients at increased risk of PDA, the detection of precursor and early lesions (secondary prevention) would come and, as a consequence, there would be an increase in survival among patients undergoing surgical resection. In 2010, 50 specialists of different specialties from different countries gathered in a consortium to generate guidelines for PDA screening, the CAPS consortium, and this meeting drew some conclusions5: screening in the general population is not recommended, as the the disease’s cumulative risk is low (1.3%) throughout life; individuals considered to be at high risk for the development of PDA (>5% cumulative lifetime risk or relative risk increased by 5x) should be screened; the main tool used to quantify this risk is family history, the risk stratification being determined by the number of relatives affected and their relationship to the individuals under risk assessment; several genetic tests may identify familial susceptibility, but their role is limited because the genetic basis of PDA is not fully understood and additional genetic testing may be discovered in the near future. A screening program should aim to identify and treat T1N0M0 lesions with negative margins,

1 - Federal University of Rio de Janeiro, Clementino Fraga Filho University Hospital, Gastroenterology Service, Rio de Janeiro, RJ, Brazil. 2 - São Vicente de Paulo Hospital, Endoscopy Service, Rio de Janeiro, RJ, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 109-111


Soldan Pancreatic cancer screening

110

as well as high-grade dysplastic precursor lesions (intraepithelial pancreatic neoplasia and papillary mucinous intraductal neoplasia). Who should be screened? First-degree relatives of PDA patients belonging to family groups where at least two firstdegree relatives are identified with the disease. Patients with Peutz-Jeghers syndrome (carrying mutations of the STK11 gene) and bearing patients mutation in the p16, BRCA2 and HNPCC genes, with at least one first-degree relative with PDA. When to screen? There is no consensus as to when to start or stop screening, but a slight tendency to recommend its start at age 50. The interval between examinations and the time limit for completing the screening process are also undefined, the currently proposed range being on an annual basis. How to screen? There is consensus that the imaging method to be used is echoendoscopy and/or magnetic resonance cholangiopancreatography. Screening should not be performed with computed tomography or endoscopic retrograde cholangiopancreatography5. Studies evaluating the capabilities of echoendoscopy in the screening of patients at risk showed results with great variability (2% to 46%), and when compared with magnetic resonance imaging (MRI), few data are available. Echoendoscopy appears to be superior in the detection of small solid lesions, whereas MRI seems to be better for detection of cystic lesions1. Carbohydrate antigen (CA) 19.9 is the most commonly used marker for PDA and its use is recommended to monitor treatment in patients who had high levels prior to treatment. The dosage of CA 19.9 is not recommended, however, for screening of asymptomatic individuals. With a cutoff value > 37U/ml, its positive predictive value is extremely low (around 1%) in the general population, even with high sensitivity and specificity (100% and 92%, respectively)1. For the screening of symptomatic

patients, for whom the PDA prevalence is around 50%, the predictive value is higher (70%), using a cutoff value of 40U/ml1. As a tool for evaluating a good tracking strategy, we could use the following questions: 1 - Does it reach the correct target? 2 - Is it applicable, ie, is the technology involved available and affordable? 3 - Does it increase survival? The first question’s answer is the number of precursor and initial stage lesions submitted to surgical resection. As an example, we can cite the article published by Vasen et al., in 20166. In that study, a cohort with prolonged follow-up time, they detected PDA in 13 of 178 individuals (7.3%) with mutation of the CDKN2A gene (responsible for the production of p16), with resection rate of 75%. Two patients (1%) of the same mutation group underwent resection of low-risk precursor lesions, and patients screened for familial PDA accounted for the resection of 6.1% of the precursor lesions and 1.9% of the high-risk precursor lesions. An American study analyzing costs per year of added life and national average expenditures based on Medicare7 found: for Peutz-Jehgers syndrome, US$ 638.62 per year of life added and US$ 2,542.37 national average expenditure; for hereditary pancreatitis, US$ 945.33 and US$ 3,763.44; for familial pancreatic cancer syndrome and p16-Leiden mutations, US$ 1,141.77 and US$ 4,545.45; and for patients with newly onset diabetes over 50 years with weight loss or smoking, US$ 356.42 and US$ 1,418.92. In response to the third question, we can cite the same article by Vasen et al6, which evaluated a long-term prognosis (>50 months) in a large series of patients (>400). In that study, the five-year survival rate in patients under surveillance who had CDKN2A/p16 mutation and PDA was 24%, a much better result when compared with the typically found PDA 5% survival rate. The answers to these questions in our midst may take a long time. Multicentric screening protocols observing the aforementioned CAPS Consortium selection criteria, in reference centers, with multidisciplinary teams containing experienced and engaged surgeons would be a good start.

Rev. Col. Bras. Cir. 2017; 44(2): 109-111


Soldan Pancreatic cancer screening

111

Finally, it is important to emphasize the primary prevention, with health policies that aim to reduce the rates of smoking and obesity, two controllable factors of great impact in the pathophysiology of PDA.

REFERENCES 1. Capurso G, Signoretti M, Valente R, Arnelo U, Lohr M, Poley JW, et al. Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals. World J Gastrointest Endosc. 2015;7(9):833-42. 2. Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva. Tipo de câncer: Pâncreas. INCa: Rio de Janeiro. Disponível em: http:// www2.inca.gov.br/wps/wcm/connect/tiposdecancer/site/home/pancreas 3. Becker AE, Hernandez YG, Frucht H, Lucas AL. Pancreatic ductal adenocarcinoma: risk factors, screen-

ing, and early detection. World J Gastroenterol. 2014;20(32):11182-98. 4. Grupo COI. Câncer de pâncreas [Internet]. Rio de Janeiro. Disponível em: www.grupocoi.com.br/cancer-de-pancreas 5. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013;62(3):339-47. 6. Vasen H, Ibrahim I, Ponce CG, Slater EP, Matthäi E, Carrato A, et al. Benect of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European Expert Centers. J Clin Oncol. 2016;34(17):2010-9. 7. Bruenderman E, Martin RC 2nd. A cost analysis of a pancreatic cancer screening protocol in high-risk populations. Am J Surg. 2015;210(3):409-16.

Rev. Col. Bras. Cir. 2017; 44(2): 109-111


DOI: 10.1590/0100-69912017002001

Original Article

Inguinodynia in patients submitted to conventional inguinal hernioplasty Inguinodinia em pacientes submetidos à hernioplastia inguinal convencional Bruno Garcia Dias1; Marcelo Protásio dos Santos1; Ana Barbara de Jesus Chaves1; Mariana Willis1; Marcio Couto Gomes1; Fernandes Tavares Andrade1; Valdinaldo Aragão de Melo1; Paulo Vicente dos Santos Filho1. A B S T R A C T Objective: to evaluate the incidence of chronic pain and its impact on the quality of life of patients submitted to inguinal hernioplasty using the Lichtenstein technique. Methods: this was a descriptive, cross-sectional study of patients operated under spinal anesthesia from February 2013 to February 2015 and who had already completed six postoperative months. We questioned patients about the presence of chronic inguinal pain and, if confirmed, invited them to a consultation in which we assessed the pain and its impact on quality of life. Results: out of 158 patients submitted to the procedure, we identified 7.6% as having inguinodynia. Of these, there was an impact on the quality of life in 25%. Conclusion: the incidence of inguinodynia after hernioplasty with repercussion in quality of life was similar to the one of found in the world literature. Keywords: Hernia, Inguinal. Chronic Pain. Herniorrhaphy. General Surgery.

INTRODUCTION

T

he development of tension-free repair techniques allowed the reduction of recurrence rates in inguinal hernioplasties, previously considered the main postoperative complication of these procedures1. In contrast, there was an increase in the incidence and chronic inguinal pain –also called inguinodynia–, now the most important complication in the postoperative period of inguinal hernioplasties2. Chronic pain is usually defined as pain for a period of more than three months. However, due to the post-operative inflammatory processes, one can only characterize post-hernioplasty inguinodynia as such after a minimum period of six months3. Its etiology is multifactorial and may be caused by damage to one or more inguinal region nerves, resulting in a pain of the neuropathic type and/or, due to the inflammatory process related to the use of the mesh or to other factors, rendering a somatic pain4. Its prevalence is quite variable and it today constitutes one of the modern surgeon’s great challenges, due to the negative impact on these patients’ quality of life5. In this sense, the present study aimed to

evaluate the incidence of chronic inguinal pain in patients submitted to inguinal hernioplasty with the Lichtenstein technique.

METHODS This was a descriptive, cross-sectional study conducted between June and August 2015 at the General Surgery Medical Residency Service of the Charity Foundation Surgery Hospital, in the city of Aracaju, State of Sergipe, Brazil. Initially, we selected patients registered in hospital files as admitted for inguinal hernia repair with the original Lichtenstein technique under spinal anesthesia, from February 2013 to February 2015, who had already completed at least six postoperative months. We applied a questionnaire on the presence of chronic inguinal pain. We invited those who confirmed it to a medical consultation, in which we analyzed the pain characteristics and its impact on quality of life using the WHOQOL-bref method. This work was approved by the Ethics Committee of the Charity Foundation Surgery Hospital, under registration number 12235809-01.

1 - Charity Foundation Surgery Hospital, Medical Residence in General Surgery, Aracaju, Sergipe State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 112-115


Dias Inguinodynia in patients submitted to conventional inguinal hernioplasty

113

Table 1 - Characteristics of patients with inguinodynia.

Patient

Type of pain

Feature

Duration (months)

Frequency (monthly)

NSP

IQL

1

Neuropathic

Paresthesia

12

8

5

No

2

Neuropathic

Paresthesia

07

8

3

No

3

Somatic and neuropathic

Paresthesia + Neuralgia

09

4

4

No

4

Somatic and neuropathic

Paresthesia + Hypoesthesia + Neuralgia

11

28

9

YES

5

Somatic and neuropathic

Paresthesia + Neuralgia

08

28

5

YES

6

Somatic and neuropathic

Paresthesia + Neuralgia

14

12 to 16

9

YES

7

Somatic and neuropathic

Paresthesia + Neuralgia

10

4

3

No

8

Somatic and neuropathic

Paresthesia + Neuralgia

24

1 to 2

2

No

9

Somatic

Neuralgia

12

4 to 8

4

No

10

Somatic and neuropathic

Paresthesia + Neuralgia

11

4

3

No

11

Somatic and neuropathic

Hypoesthesia + Neuralgia

24

8

3

NO

12

Neuropathic

Paresthesia + Hypoesthesia

20

4

2

No

NSP: numeric scale of pain; IQL: impact on quality of life.

We previously informed all patients about the research and advised those selected for medical consultation to sign an informed consent form. We performed statistical analyzes with the R Core Team 2015 software. The level of significance was set at 5%.

4.3. None of the patients with inguinodynia was under medical treatment for this condition. Table 1 shows the pain characteristics of patients with inguinodynia. Table 2 brings the values of ​​ the domains in patients with chronic inguinal pain that presented repercussion in quality of life, as calculated by the WHOQOL‑bref method.

RESULTS DISCUSSION We applied the telephone questionnaire to 158 operated patients. Regarding gender, 18 (11.4%) were women and 140 (88.6%) were men. As to laterality, 88 (55.7%) inguinal hernias were on the right side, 61 (38.6%), on the left side and nine (5.7%) were bilateral. The age ranged from 23 to 87 years, with a mean of 51.3 years. We identified 12 cases of inguinodynia (7.6%), all being male. Regarding the side of the inguinal hernia, six (50.0%) were on the right side, four (33.3%) on the left side and two (16.7%), bilateral. The age ranged from 25 to 87 years, with an average of 52 years. The pain intensity in the Numerical Pain Scale ranged from 2 to 9, with an average intensity around

The data present in the literature regarding the incidence of chronic pain are quite divergent. This is a consequence of different definitions, different moments of evaluation, different methods of measurement and the subjectivity of pain, a symptom faced in different ways by different peoples and cultures. For this reason, the most recent data on the subject are based on the international guideline for diagnosis and management of chronic pain after inguinal hernia surgery, published in 2011, which aims to standardize some basic concepts on the theme3. Still, some points display no consensus and comparisons between studies in the literature becomes difficult.

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Dias Inguinodynia in patients submitted to conventional inguinal hernioplasty

114

Table 2 - Areas affected in patients in whominguinodiniacaused impact on quality of life.

Patient

Physical domain

Psychological domain

Social domain

Environmental domain

Impact on quality of life

1

60.7%

75%

66.7%

65.6%

67%

2

67.9%

75%

91.7%

65.6%

75%

3

78.6%

66.7%

66.7%

65.6%

69.4%

The incidence of inguinodynia after hernioplasty can vary from 0.7 to 51%6. In our study, 7.6% of the patients had inguinodynia, which is compatible with that found in the world literature. Of these, only three (1.8%) reported pain that could be classified as significant, having an impact on quality of life. In the others (98.2%), despite the pain report, it had no repercussion in the usual activities. Most of the literature data on inguinodynia do not specify the degree of pain or its periodicity. Another factor that hinders the analysis of the topic is that the patient may develop chronic pain in variable periods, from the immediate postoperative one to years later, which implies a long-term follow-up to verify the occurrence or not of this complication. Thus, it is important that the studies provide information on the presence of pain related to the postoperative time of that sample studied. Works with longer follow-up (two to three years) reveal residual pain in 31% of patients and disabling pain in 3%7. Another limitation is the way of measuring pain. Some authors use only the information of pain presence or not and do not sub-classify its intensity. Others, however, classify pain according to the visual analogue scale (AVS) rating but varying from 0 to 5, 0 to 10 or 0 to 100. Such lack of standardization impairs a subdivision of pain intensity, making a patient who feels pain grade one (scale 0 to 10), once a month for six months after surgery, be classified as having inguinodynia as much as a patient who has pain grade eight, five times a week. In this way, a sub-classification would be important to facilitate the statistical analysis and consequently the standardization of more individualized treatment. We found a relative limitation in our evaluation since the initial contact for assessment of pain presence or absence was by telephone contact,

which may underestimate the presence of pain and hernia recurrence. In our study, we used AVS ranging from 0 to 10. We used the criterion of the Quality of Life Scale as a factor to define residual pain with or without repercussion on the quality of life and not only the score attributed to pain. In our series, we had patients with high grades, but without repercussion on quality of life, and patients with a low score as for intensity, but affecting their usual activities. The association of intensity with impairment in quality of life is important to understand how much this pain means to the patient. It is noteworthy that none of the patients in our series was entitled to receive social benefits that could justify reported complaints to obtain secondary gains, a situation unfortunately present in our society. The national literature is scarce in relation to these data and we rely on American and European data, whose population may present a greater or less tolerance to pain or even a lower acceptance or conformism regarding its presence. It is noticeable in the present study that even with 1.8% (3/158) of patients with pain that affect quality of life, none of these spontaneously sought the service where they underwent surgery or even another institution, even with all the support offered. None of the patients diagnosed as having inguinodynia was specifically monitored for such complication. When severe, inguinodynia can be the origin of affective disorders such as anxiety, depression, somatic comorbidities and cognitive impairment, drastically impairing patients’ quality of life. It is clear, then, that the consequences are not limited to the clinical domain, being associated with enormous socioeconomic impairment4. In our series, we did not have patients in this extreme. However, after

Rev. Col. Bras. Cir. 2017; 44(2): 112-115


Dias Inguinodynia in patients submitted to conventional inguinal hernioplasty

applications of the questionnaire on the impact caused by pain on quality of life, three patients, 25% of the patients who presented inguinodynia, reported interference in their usual activities and nine (75%) had occasional and sporadic pain, without interference in the daily routine. As for the prevalence of gender and the side affected by the inguinal hernia, the results of the present study corroborate the data observed in the literature that evidence that inguinal hernia is much more frequent in males, obeying a proportion of seven to nine men for each woman8. Of the patients evaluated, 11% were women and 89% were men.

115

In addition, in relation to the affected side, our study revealed a more frequent right hernia (55% of the total cases), which can be explained by a later descent of the right testicle, and consequent persistence of the processus vaginalis in the indirect inguinalhernia9. In summary, the prevalence of posthernioplasty chronic inguinal pain was 7.6%, with negative interference on quality of life in 25% of patients with inguinodynia and in 1.8% of all operated patients. In view of these findings, a rigorous postoperative follow-up of patients submitted to inguinal hernioplasty is necessary to diagnose and treat chronic postoperative pain.

R E S U M O Objetivo: avaliar a incidência de dor crônica e o seu impacto na qualidade de vida de pacientes submetidos à hernioplastia inguinal pela técnica de Lichtenstein. Métodos: trata-se de estudo transversal descritivo, de pacientes operados de hérnia inguinal pela técnica de Lichtenstein sob anestesia raquidiana, no período de fevereiro de 2013 a fevereiro de 2015, e que já haviam completado seis meses de pós-operatório. Os pacientes foram questionados sobre a presença de dor inguinal crônica e, caso confirmada, convidados a uma consulta na qual foi feita análise da qualidade da dor e seu impacto na qualidade de vida. Resultados: do total de 158 pacientes submetidos ao procedimento, 7,6% foram identificados como portadores de inguinodinia. Destes, houve impacto na qualidade de vida em 25%. Conclusão: observou-se incidência de inguinodinia pós-hernioplastia com repercussão na qualidade de vida semelhante à literatura mundial. Descritores: Hérnia Inguinal. Dor Crônica. Herniorrafia. Cirurgia Geral.

REFERENCES 1. Bittner R, Schwarz J. Inguinal hernia repair: current surgical techniques. Langenbeck’s Arch Surg. 2012;397(2):271-82. 2. Pulido-Cejudo A, Carrillo-Ruiz JD, Jalife-Montaño A, Zaldívar-Ramírez FR, Hurtado-López LM. Inguinodinia en postoperados de plastía inguinal con técnica de Lichtenstein con resección versus preservación del nervio ilioinguinal ipsilateral. Cir gen. 2012;34(1):18-24. 3. Alfieri S, Amid PK, Campanelli G, Izard G, Kehlet H, Wijsmuller AR, et al. International guidelines for prevention and management of post-operative chronic pain following inguinal hernia surgery. Hernia. 2011;15(3):239-49. 4. Bjurstrom MF, Nicol AL, Amid PK, Chen DC. Pain control following inguinal herniorrhaphy: current perspectives. J Pain Res. 2014;7:277-90. 5. Minossi JG, Minossi VV, Silva AL. Manejo da dor inguinal crônica pós-hernioplastia (inguinodinia). Rev Col Bras Cir. 2011;38(1):59-65.

6. Nikkolo C, Lepner U. Chronic pain after open inguinal hernia repair. Postgrad Med. 2016;128(1):69-75. 7. Fränneby U, Sandblom G, Nordin P, Nyrén O, Gunnarsson U. Risk factors for long-term pain after hernia surgery. Ann Surg. 2006;244(4):212-9. 8. Dabbas N, Adams K, Pearson K, Royle G. Frequency of abdominal wall hernias: is classical teaching out of date? JRSM Short Rep. 2011;2(1):5. 9. Burcharth J. The epidemiology and risk factors for recurrence after inguinal hernia surgery. Dan Med J. 2014;61(5):B4846. Received in: 01/10/2016 Accepted for publication: 26/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Paulo Vicente dos Santos Filho E-mail: paulovicentefilho@gmail.com bgdias@globo.com

Rev. Col. Bras. Cir. 2017; 44(2): 112-115


DOI: 10.1590/0100-69912017002002

Original Article

Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers Impacto do curativo de espuma não aderente com Ibuprofeno na vida dos pacientes com úlcera venosa Geraldo Magela Salomé1; Lydia Masako Ferreira, TCBC-SP1. A B S T R A C T Objective: to evaluate pain in patients with lower limb venous ulcer who used non-adherent Ibuprofen foam dressing (IFD). Methods: we conducted a prospective study of patients with lower limb venous ulcers treated from April 2013 to August 2014. We used the Numerical Scale and McGill Pain Questionnaire, performing the assessments at the moment of inclusion of the patient in the study and every eight days thereafter, totaling five consultations. We divided the patients into two groups: 40 in the Study Group (SG), who were treated with IFD, and 40 in the Control Group (CG), treated with primary dressing, according to tissue type and exudate. Results: at the first consultation, patients from both groups reported intense pain. On the fifth day, SG patients reported no pain and the majority of CG reported moderate pain. Regarding the McGill Pain Questionnaire, most patients of both groups reported sensations related to sensory, affective, evaluative and miscellaneous descriptors at the beginning of data collection; after the second assessment, there was slight improvement among the patients in the SG. After the third consultation, they no longer reported the mentioned descriptors. CG patients displayed all the sensations of these descriptors until the fifth visit. Conclusion: non-adherent Ibuprofen foam dressing is effective in reducing the pain of patients with venous ulcers. Keywords: Varicose Ulcer. Lower Extremity. Pain Measurement. Ibuprofen. Quality of life. Patient-Centered Care.

INTRODUCTION

V

enous ulcers are a consequence of chronic venous insufficiency, due to venous hypertension caused by valvular incompetence of the superficial and deep veins, venous obstruction or a combination of these factors1,2. They most commonly affect the lower limbs and commit about 5% of the adult population in Western countries, with a prevalence of 0.3%. Their occurrence increases with age, being higher than 4% in individuals over 65 years old1,3. They may present exudate and odor, with the need to change dressings several times a day, with an impact on the lifestyle. It is common for the patient to present frustration and hopelessness related to treatment, since some of these lesions can take months to heal4-7. They cause pain, edema, loss of mobility and withdrawal from work, often leading to disability retirement. As a consequence of the pain, which aggravates or causes difficulty in locomotion, and restriction of activities of daily living and leisure, venous ulcers can lead to changes in

quality of life and self-esteem, and determine anxiety and depression, which may contribute to delay the ulcer healing process8-15. The Ibuprofen foam dressing (IFD) is a non-adherent dressing, formed by foam attached to a semipermeable polyurethane film that allows Ibuprofen release into the wound by the presence of fluids or exudate. It is an innovative technology that promotes better control of the exudate, ensures a minimum risk of leakage or maceration of the skin, brings pain relief during the use time and during its exchange and promotes a humid environment16-18. This study aimed to evaluate the impact of non-adherent Ibuprofen foam dressing in pain control of patients with venous ulcers.

METHODS We carried out a controlled, randomized, analytical and prospective study at the São João Ambulatory of the Dr. José Antônio Garcia Coutinho

1 - Sapucaí Valley University, Professional Master’s Degree in Applied Health Sciences, Pouso Alegre, MG, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 116-124


Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

Faculty of Health Sciences, after approval by the Ethics in Research Committee under number 534,263. We studied 80 patients, divided into two groups with 40 patients each: Study Group (SG), treated with IFD, and Control Group (CG), treated with primary dressing, according to tissue type and exudate. Inclusion criteria were: age equal or above 18 years, ankle/arm ratio between 1.0 and 1.4, patients who were taking pain medication and who were not being treated with compressive therapy. Exclusion criteria were: patients whose wounds presented clinical signs of infection, allergy to Ibuprofen or presence of erysipelas adjacent to the lesion. We excluded patients who missed the outpatient visits, those who were taking pain medication during the study and patients who, during the study, showed clinical signs of infection or allergy. We performed the study from April 2013 to August 2014. We collected the first data at the time of inclusion of the patient in the study, and then every eight days, totaling five visits. In these consultations, we evaluated the wound and changed the primary dressing, but the patients were instructed to change the secondary dressing whenever saturation occurred. We randomized patients by sealed and opaque envelopes, which were stored at the randomization central. An independent individual generated a sequence of random numbers, placing them one by one in the sealed envelopes. Patients were drawn consecutively, through withdrawal of the envelope and allocation in one of the groups. Participants answered a questionnaire on sociodemographic and clinical data. To quantify the intensity of pain, we used the Numerical Pain Scale, graded from 0 to 10, where 0 means absence of pain and 10, the worst pain eve felt. Pain intensity was classified as painless (0), mild pain (1-3), moderate (46), and severe (7-10)19,20. We evaluated the pain quality with the application of the McGill Pain Questionnaire. This questionnaire consists of words known as descriptors, as they describe the sensation of pain that the patient may be feeling. The descriptors are organized into four major groups and into 20 subgroups. Each set of subgroups evaluates a group. The descriptors cover

117

the areas: sensory (subgroup of 1 to 10), affective (subgroup of 11 to 15), evaluative (subgroup 16) and miscellaneous (subgroup of 17 to 20)19,20. The sensorydiscriminative group (subgroups 1 to 10) refers to the pain’s mechanical, thermal, vivid and spatial properties; the affective-motivational group (subgroups 11 to 15) describes the affective dimension in the aspects of tension, fear and neurovegetative responses; The descriptors of the cognitive-evaluative component (subgroup 16) allow the patient to express the overall evaluation of the pain experience. Subgroups 17 through 20 comprise miscellaneous items. Each subgroup consists of two to six qualitatively similar descriptors, but with nuances that make them different in terms of magnitude. Thus, for each descriptor a number indicates its intensity. The McGill questionnaire can render the number of descriptors chosen and the pain index. The number of descriptors chosen corresponds to the words that the patient chose to explain the pain. The highest possible value is 20, since the patient can only choose at most one word per subgroup. The pain index is obtained with the sum of the intensity values ​​of the chosen descriptors. These indices can be obtained in total and for each of the four components of the questionnaire: sensitive, affective, evaluative and miscellaneous subgroup. We performed the statistical analysis with SPSS 11.5, using the Mann-Whitney and Chi-square tests. For all statistical tests, we considered significance levels of 5% (p≤0.05).

RESULTS The sociodemographic variables of the participants can be seen in table 1. We verified that the majority of the participants of both groups were white, female, aged over 60, retired and smokers. With regard to schooling, 18 participants (45%) of the SG were illiterate and 29 patients (72.50%) of the CG had only elementary education. Regarding the lesion, table 2 shows that the majority of patients in both groups had lived with the ulcer for six to ten years and the lesions presented exudate and odor.

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Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

118 Table 1. Sociodemographic variables of the study participants.

Variables

Group

 

Study Group

Control Group

p-value

n

%

n

%

White

33

82.50

28

70.00

Black

07

17.50

12

30.00

* 0.001

Total

40

100.00

40

100.00

< of 50 years

01

2.50

2

5.00

50 to 59 years

03

7.50

01

2.50

60 to 69 years

31

77.50

35

87.50

* 0.002

70 to 79 years

05

12.50

01

2.50

> of 80 years

00

00

01

2.50

Total

40

100.00

40

100.00

Female

28

70.00

26

65.00

Male

12

30.00

14

35.00

* 0.003

Total

40

100.00

40

100.00

No

11

27.50

11

27.50

Yes

29

72.50

29

72.50

* 0.003

Total

40

100.00

40

100.00

Literate

00

00

18

45.00

Complete elementary school

04

10

01

2.50

Incomplete elementary school

29

72.50

13

32.50

Incomplete high school

02

5.00

03

7.50

0.067

Complete high school

04

10.00

05

12.50

College level

01

2.50

00

00

Total

40

100.00

40

100.00

Unemployed

00

00

05

12.50

Retired

22

55.00

26

65.00

Housewife

10

25.00

09

22.50

Housekeeper

06

15.00

00

00

0.087

Caregiver

01

2.50

00

00

Craftsman

01

2.50

00

00

Total

40

100.00

40

100.00

Race

Age Group

Gender

Smoker

Schooling

Profession

Chi-square test of Pearson; * Level of statistical significance p<0.05. Rev. Col. Bras. Cir. 2017; 44(2): 116-124


Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

119

Table 2. Wound-related variables.

Variables

Group Study Group

Control Group

p-value

n

%

n

%

< of 12 months

04

10.00

02

5.00

1 to 5 years

06

15.00

03

7.50

6 to 10 years

25

62.50

31

77.50

* 0.001

> from 11 years

05

12.50

04

10.00

Total

40

100.00

40

100.00

Yes

22

55.00

32

80.00

No

18

45.00

08

20.00

* 0.001

Total

40

100.00

40

100.00

Yes

23

57.50

31

77.50

No

17

42.50

09

22.50

* 0.001

Total

40

100.00

40

100.00

Time of injury

Exudate

Odor

Chi-square test of Pearson; * Level of statistical significance p<0.05.

Table 3 shows that the majority of patients in both groups had diabetes mellitus, hypertension, but no heart disease. Table 4 shows that in the first data collection, patients in both groups reported intense pain; in the second, the majority of SG patients reported moderate pain. In CG, 20 (50%) reported moderate pain and 19 (47.50%) had severe pain. In the third data collection, the majority of SG patients reported mild pain and CG patients reported moderate pain. In the fourth assessment, most SG patients reported no pain. In CG, most reported moderate pain. At the fifth visit, most SG patients reported no pain. In CG, most reported moderate pain. Table 5 shows that the majority of patients in both groups reported sensory, affective, evaluative and miscellaneous descriptors. CG individuals continued to report these descriptors until the fifth visit, with a slight improvement, but SG patients showed significant improvement during the first and even in the fifth data collection.

DISCUSSION In Brazil, chronic venous disease is the 14th cause of temporary withdrawal from work. These data represent a serious public health problem, affecting several age groups, different ethnicities, both genders, reflecting public spending and interference in the quality of life of patients and their families. It was found that the majority of the patients were smokers and with a low level of education, data that are similar to those of other studies 5-7,17,21,22. Among the study participants, women predominated. It is inferred that the occurrence of venous ulcer in the female gender is associated with hormonal factors, pregnancy, puerperium and the higher incidence of varicose veins, which may favor the onset of chronic venous insufficiency. This predominance is also due in part to female longevity, since up to the age of 40 the number of cases is evenly distributed between both genders23-25.

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Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

120 Table 3. Disease-related variables.

Variables

Group

Study Group

Control Group

p-value

n

%

n

%

Diabetes Mellitus

Yes

08

20

03

7.50

No

32

80

37

92.50

* 0.001

Total

40

100.00

40

100.00

Yes

14

35

20

50

No

26

65

20

50

* 0.001

Total

40

100.00

40

100.00

Yes

10

25

05

12.50

No

30

75

35

87.50

* 0.001

Total

40

100.00

40

100.00

Arterial Hypertension

Cardiopathy

Chi-square test of Pearson; * Level of statistical significance p<0.05.

With regard to smoking, it impairs tissue oxygenation, decreases the body’s resistance, makes it more susceptible to infections and delays healing. In addition, smoking alters collagen synthesis, hampering wound healing. Nicotine produces vasoconstriction, which increases the risk of ischemia and the development of ulcers, and ulcers, when already present, have difficulty in healing. In these cases, the cellular process is interrupted and abnormal functions of the healing process derive from systemic or local factors, or both26. Wound pain results from tissue injury and the perception of pain depends on numerous factors related to the patient, type of wound, quantity and intensity of external stimuli19,20. The skin is richly innervated, which gives it the ability to capture various types of stimuli, and the presence of infection and necrosis aggravates the wounds’ painful process. Chronic pain can be considered as the perpetuation of acute pain, has no biological function of alertness and generates suffering. In general, neurovegetative responses such as those found in acute pain do not occur, resulting from the adaptation of neuronal systems27.

Pain is one of the main causes of suffering for any sick person. National and international studies report that approximately 80% of people’s demand for health services is pain-motivated. Chronic pain affects 30 to 40% of Brazilians and is the main cause of absenteeism, sick leave, health-related retirements, workers’ compensation and low labor productivity28,29. Pain is a very common symptom in patients with venous ulcers and its prevalence varies between 80 and 96% in this group. It may be persistent and/or exacerbated during dressing changes. Pain can also negatively influence healing, as the painful stimulus is associated with the release of inflammatory mediators, which potentially reduce tissue repair and regeneration16,30-32. In the present study, all patients in the two groups reported severe pain at the beginning of data collection, but the participants of the SG, who were treated with the non-adherent Ibuprofen foam dressing, showed significant pain improvement in the second week of treatment. Regarding the CG, after the fourth consultation, the patients reported moderate pain, while SG patients reported no pain.

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Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

121

Table 4. Total score of the numerical pain scale.

Numeric pain scale   1st Assessment 0 (absence of pain) 1 to 3 (mild) 4 to 6 (moderate) 7 to 10 (intense) Total Average Standard deviation nd 2 Assessment 0 (absence of pain) 1 to 3 (mild) 4 to 6 (moderate) 7 to 10 (intense) Total Average Standard deviation rd 3 Assessment 0 (absence of pain) 1 to 3 (mild) 4 to 6 (moderate) 7 to 10 (intense) Total Average Standard deviation th 4 Assessment 0 (absence of pain) 1 to 3 (mild) 4 to 6 (moderate) 7 to 10 (intense) Total Average Standard deviation th 5 Assessment 0 (absence of pain) 1 to 3 (mild) 4 to 6 (moderate) 7 to 10 (intense) Total Average Standard deviation

Group Study Group n %

Control Group n %

p-value  

00 00 06 34 40 7.88 1.871

00 00 15.00 85.00 100.00  

00 02 05 33 40 8.25 2.619

00 5.0 12.50 82.50 100.00  

    * 0.001      

00 07 30 03 40 4.53 1.320

00 17.50 75.00 7.50 100.00  

00 01 20 19 40 6.80 2.451

00 2.50 50.00 47.50 100.00  

    * 0.001      

00 38 02 00 40 1.90 0.900

00 95.00 5.00 00 100.00  

00 01 26 13 40 6.12 2.178

00 2.50 65.00 32.50 100.00  

    * 0.001      

34 06 00 00 40 0.15 0.362

85.00 15.00 00 00 100.00  

00 02 28 10 40 5.18 1.470

00 5.0 70.00 25.00 100.00  

    * 0.001      

39 01 00 00 40 0.03 0.158

97.50 2.50 00 00 100.00  

03 10 22 05 40 4.43 1.079

7.50 25.00 55.00 12.50 100.00  

      * 0.001    

Mann-Whitney test. * Level of statistical significance p<0.05. Rev. Col. Bras. Cir. 2017; 44(2): 116-124


Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

122 Table 5. Total score of the McGill Pain questionnaire descriptors.

McGill Pain questionnaire

Descriptors

Sensory

Affective

Evaluative

Miscellaneous

p-value

n (%)

n (%)

n (%)

n (%)

40 (100)

40 (100)

39 (97.50)

40 (100)

* 0.0001

22 (55.00)

27 (67.50)

27 (67.50)

28 (70)

Control

30 (75.00)

34 (85.00)

21 (52.50)

40 (100)

* 0.0001

Study

20 (50.00)

13 (32.50)

11 (27.50)

19 (47.50)

Control

29 (72.50)

11 (27.50)

16 (40)

35 (87.50)

* 0.0001

Study

7 (17.50)

4 (10.00)

5 (12.50)

4 (10.00)

Control

18 (45.00)

24 (60.00)

29 (72.50)

10 (25.00)

* 0.0001

Study

4 (10.00)

2 (5.00)

1 (2.50)

3 (7.50)

44 (88.00)

44 (88.00)

15 (30.00)

15 (30.00)

* 0.0001

1 (2.50)

00 (00.0)

00 (00.0)

1 (2.50)

Type of group First assessment Control Study Second assessment

Third assessment

Fourth assessment

Fifth assessment Control Study

Mann-Whitney test. * Level of statistical significance p <0.05.

In a study with non-adherent Ibuprofen foam dressing, the authors concluded that this it was effective in relieving pain16. In our study, patients treated with IFD also showed significant improvement after the first week of treatment. A study in which the authors described the characteristics of pain in patients with chronic foot ulcers, applied the numerical scale and McGill Pain Questionnaire to 90 patients. The mean pain intensity reported was 7.56 and the sensitive descriptors were more frequently used to describe the pain. The authors concluded that it is necessary for the professionals, when evaluating the patients with such wounds, to use an instrument to evaluate the pain and elaborate a care plan so that they can have an improvement in pain and quality of life33,34. The McGill Pain Questionnaire assesses the sensory, affective, and evaluative aspects of pain, describing the patients’ painful experience. The sensory-

discriminative dimension evaluates the temporalspatial, mechanical and thermal aspects of pain; the affective-motivational dimension involves aspects of tension, fear, self-punishment and neurovegetative responses; and the cognitive-evaluative dimension evaluates the overall situation of the individual and represents a judgment based on sensory and affective characteristics, previous experience and the meaning of the situation19,20,35. In another study with 24 pain patients, the authors investigated the effect of non-adherent Ibuprofen foam dressing. Persistent pain in the wound presented a decrease of a mean of 6.3±2.2 to 3.0±1.7 after 12 hours and remained low thereafter. Pain during dressing change also declined and remained low. As we did, the authors concluded that the nonadherent Ibuprofen foam dressing reduced the pain of patients with chronic venous ulcers36.

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Salomé Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers

123

R E S U M O Objetivo: avaliar a dor em pacientes portadores de úlcera venosa de membros inferiores que utilizaram curativo de espuma não aderente com Ibuprofeno (CEI). Métodos: estudo prospectivo de pacientes portadores de úlceras venosas de membros inferiores tratados no período de abril de 2013 a agosto de 2014. Foram utilizados os questionários Escala Numérica e Questionário de Dor de McGille, as avaliações eram feitas no momento da inclusão do paciente no estudo e a cada oito dias, totalizando cinco consultas. Os pacientes foram divididos em dois grupos: 40 no Grupo Estudo (GE), que foram tratados com CEI, e 40 no Grupo Controle (GC), tratados com curativo primário, conforme o tipo de tecido e exsudato. Resultados: na primeira consulta os pacientes de ambos os grupos relataram dor intensa. No quinto dia os pacientes do GE relataram ausência de dor e a maioria do GC relatou dor moderada. Com relação ao Questionário de Dor de McGill, a maioria dos pacientes de ambos os grupos, no início da coleta de dados, relataram sensações relacionadas aos descritores sensorial, afetivo, avaliativo e miscelânea, sendo que entre os pacientes do GE houve discreta melhora após a segunda consulta. Após a terceira consulta já não referiram os descritores citados. Os pacientes do GC manifestaram todas as sensações desses descritores até quinta a consulta. Conclusão: o curativo de espuma não aderente com Ibuprofeno é eficaz na redução da dor de pacientes portadores de úlceras venosas. Descritores: Úlcera Varicosa. Extremidade Inferior. Medição da Dor.Ibuprofeno. Qualidade de vida. Assistência Centrada no Paciente.

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Received on: 02/10/2016 Accepted for publication in: 15/12/2016 Conflict of interest: None. Source of financing: none. Mailing address: Geraldo Magela Salomé E-mail: salomereiki@univas.edu.br geraldoreiki@hotmail.com.br

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DOI: 10.1590/0100-69912017002003

Original Article

Transaxillary single-port subtotal parathyroidectomy: feasibility study in cadavers Paratireoidectomia subtotal transaxilar single-port: estudo de viabilidade em cadáver Alexandre Elmães de Marsillac, TCBC-RJ1; Rossano Kepler Alvim Fiorelli, TCBC-RJ1; Henrique Neubarth Phillips, ACBC-RJ1; Pietro Novellino, ECBC-RJ1; André Lacerda Oliveira3; Ricardo Paiva A. Scheiba Zorron, TCBC-RJ2. A B S T R A C T Objective: to test the minimally invasive technique of single-port transaxillary subtotal parathyroidectomy in non-formalized cadavers to evaluate its viability and reproduction. Method: we performed ten subtotal parathyroidectomies through a transaxillary TriPort access in cadavers. The technique consisted of access through the axillary fossa, creating a subcutaneous tunnel to the anterior cervical region, for handling of the thyroid gland and dissection and resection of the parathyroid glands. Results: all surgeries were successful. The mean time of surgery was 65 minutes (57-79 min), with uncomplicated identification of all anatomical structures. There was no need for complementary incisions in the cervical region. Conclusion: the transaxillary single-port subtotal parathyroidectomy technique was feasible and reproducible, suggesting an alternative for minimally invasive cervical surgery. Keywords: Parathyroidectomy. Endoscopy. Cadaver. Minimally Invasive Surgical Procedures.

INTRODUCTION

T

he emergence of new minimally invasive techniques for parathyroidectomy in the 1990s allowed surgeons to perform a traditional surgical procedure with a technique that allows less trauma, better surgical exposure and better dissection. In the hands of experienced surgeons, a minimally invasive procedure should achieve at least the same results, with the major advantage of reducing invasive trauma and improving aesthetic outcome. Laparoscopy contributed to these results, led to minimally invasive neck surgery to be developed and several new techniques arose. The logical sequence of the surgical procedures of the future should be, following decreasing invasiveness criteria, the execution of surgeries through single access, thus preventing issues inherent to incisions1-9. The technique of minimally invasive video assisted parathyroidectomy (MIVAT), developed by Miccoli, has become the most widespread9,10. With such new techniques, however, many doubts arose about the safety of minimally invasive surgery, and new

studies were published comparing open surgery with endoscopic one11-13. The axillary approach was then used as an alternative to hide the scar, but another trocar was needed to access the thyroid gland, usually through the Axillo-Bilateral-Breast Approach (ABBA), creating a wide dissection and increasing complications risks14-16. With the idea of natural ​​ orifice surgery 17 (NOTES), Witzel et al. performed a sublingual transoral access for thyroidectomy in a study with animals in 2007. Benhidjeb et al.18 followed the study and used the same technique in cadavers, making the first cases in humans19,20. With single portal surgery consecrated as the surgery of the moment, transaxillary singleport21 thyroidectomy seems to be more plausible. After a previous study, which aimed to establish a standard for transaxillary single-port thyroidectomy in cadavers, our team continued to develop this technique, now for transaxillary singleport unilateral parathyroidectomy. Thus, the objective of this study was to develop and improve the surgical technique of parathyroidectomy, using a single transaxillary access.

1 - Federal University of the State of Rio de Janeiro (UNIRIO), Department of General and Specialized Surgery, Professional Masters in Videoendoscopic Techniques, Rio de Janeiro, Rio de Janeiro State, Brazil. 2 - Charité Hospital, Center for Innovative Surgery, Berlin, Brandenburg, Germany. 3 - North Fluminense State University (UENF), Department of Post-Graduation, Campos, Rio de Janeiro State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 125-130


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Figure 1. Two-cm incision in the axillary sulcus. Figure 2. Making of the subcutaneous tunnel.

METHODS We carried out the study at the Anatomical Institute of the Federal University of the State of Rio de Janeiro (UNIRIO), in the years 2013 and 2014, using ten fresh frozen cadavers prior to their formalization. Inclusion criteria were cadavers of both genders, middleaged, without previous neck surgery, and BMI <30. In the operative technique, we placed the cadaver in dorsal decubitus with the upper limb extended to 270° and flexed at the elbow with the hand under the head. A monitor sit at the head of the cadaver, and the surgeon, as well as the assistant, remained below the ipsilateral arm. The procedure started with a 2cm incision in the axillary sulcus ipsilateral to the parathyroid to be resected, followed by dissection of the subcutaneous tissue with Kelly’s forceps, placement of the TriPort and insulation with CO2 (4 to 8 mmHg) (Figure 1).

We then proceeded to the subcutaneous tunnel, with blunt dissection with a 30° endoscope, 10mm in diameter, and cutting until reaching the neck, above the pectoral muscle, passing over the clavicle (Figure 2). Then we opened the platysma muscle and bluntly separated the pre-thyroid muscles, identifying the thyroid gland. An ascending dissection of the thyroid gland followed with scissors, rotating it medially on its longitudinal axis with an apprehension forceps for identification of the recurrent laryngeal nerve and parathyroids (Figures 3 and 4). We then apprehended the parathyroid followed by its dissection and section with scissors. We removed the whole gland through the incision, protected by the TriPort, and performed wound synthesis with intradermal suture (Figure 5).

Figure 3. Identification of the recurrent laryngeal nerve.

Figure 4. Parathyroid identification.

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The present study shows the feasibility of neck surgery, such as thyroidectomy and parathyroidectomy, through a single access. Since Gagner6 performed an

endoscopic subtotal parathyroidectomyin 1996, many surgeons began to look for a less invasive way of doing the surgical procedures in the neck and especially trying to avoid visible scarring as in open surgery. However, even with new techniques, although with good clinical results, the adoption of endoscopic procedures has been weak, due to issues such as steep learning curve and limited training, and lack of surgeons with the capacity to teach the new techniques. The MIVAT technique, performed through a 2cm incision in the anterior cervical region, is the most widespread and employed procedure for minimally invasive surgery, described in 1997 for parathyroidectomy for primary hyperparathyroidism. It has been observed that it could also be used in thyroid surgeries and in 2002, Miccoli et al.10 carried out a multicenter study with 336 patients. There were with seven transient recurrent laryngeal nerve lesions and one permanent lesion (0.3%), nine cases of transient hypoparathyroidism, and two cases of permanent hypoparathyroidism (0.67%). The disadvantages of this surgery are the scar, even if small, in the neck, the contraindication in large glands, and the impossibility to perform lymphadenectomy in the central compartment, which suggests that the main indication for MIVAT are benign diseases. In order to conceal the surgical scar, the transoral, sublingual approach to thyroidectomy, despite anatomical complexity, was relatively easy and added parathyroidectomy and thyroidectomy

Table 1. Time for the subcutaneous tunnel

Table 2. Operative time

Figure 5. Final aspect of the scar.

RESULTS The transaxillary parathyroidectomy was successful in all cases. It was possible to visualize the two glands on the studied side, as well as the recurrent laryngeal nerve. The mean time of preparation of the subcutaneous tunnel for parathyroid access was 35.1 minutes (29-42) (Table 1). The mean surgery time was 65 minutes (5779) (Table 2).

DISCUSSION

Cadaver

Tunnel time

Cadaver

Operative Time

1

42min

1

79min

2

39min

2

74min

3

38min

3

68min

4

40min

4

70min

5

35min

5

63min

6

33min

6

62min

7

34min

7

62min

8

30min

8

57min

9

29min

9

57min

10

31min

10

58min

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to NOTES techniques17-20. It seems to be a promising surgery, since the glands have their embryonic origins at the base of the tongue and migrate to the anterior cervical region, being a natural path to go through during surgery. However, it requires studies with larger samples to demonstrate its real importance. Lee et al.21 devised the single-port axillary endoscopic thyroidectomy. However, in their study, they used an adapted system, with an AlexisÂŽ and a glove, in whichhe inserted three 5mm trocars, in the first, third and fifth fingers. To create the subcutaneous space, they used an acrylic bar and CO2 gas inflating at a pressure of 4 to 6 mmHg. They used a flexible 5mm endoscope, as well as a Sonosurg scissors. Thyroid resection began at the upper pole toward the lower pole with identification and preservation of the recurrent laryngeal nerve and parathyroids. The gland was withdrawn and a suction drain was inserted. The results were good and there were no complications. In the article, they noted that the 5mm range helped to avoid the clash of instruments by creating two imaginary planes, upper plane for the camera and lower plane for the instruments. Another important point detected was the use of instruments of different lengths, preventing the surgeon from colliding with his forceps. More recently, Kang et al.22 showed the feasibility and safety of robotic surgery in transaxillary thyroidectomy. There are, however, limitations to robotic surgery due to the high cost and specific training, thus not being accessible to all endoscopic surgeons. There is also a need for larger incisions for the robotic arms. With the new generation of robots and patentsexpiration, there may be cost reduction and accommodation for single-port surgery. Lee et al.23 studied 259 patients, 96 in the endoscopic group and 163 in the robotic group, comparing the two techniques. Both groups had similar operative times, as well as length of hospital stay and blood loss, but the number of lymph nodes removed was higher in the robotic group (P.004). In a meta-analysis comparing robotic with endoscopic surgery, Lin et al.24 did not observe statistical difference regarding operative time and conversions for open surgery. However, the robotic arm obtained a greater number of complications, the authors suggesting

that there is no clinical benefit for robotic surgery, when compared with the endoscopic one, in the accomplishment of thyroidectomies. In a study by Phillips et al.25, using the same access for thyroidectomy in animals and cadavers, they observed that it was possible to perform the procedure, with identification of all anatomical structures and preservation of the parathyroid glands. Based on this work, we performed this study aimed at the excision of the parathyroid glands, preferentially for adenomas. In our study, the use of the TriPort gave us greater freedom of movement with the tweezers, even in a 2cm incision. This access is possible both for thyroidectomy and for parathyroidectomy, avoiding a scar in the cervical region and transferring it to the axillary region. One can extend the scar if the size of the surgical specimen is large, without hampering aesthetics. It is a procedure requiring a team of professionals with experience in Single-Port surgery, since the tweezers work in parallel with the camera and there is collision between them. Laparoscopic tweezers of different sizes can minimize the problem of collisions by keeping the surgeon and the assistant a little further from each other. The space is restricted, but sufficient to work with safety, enabling, with clarity, the identification of noble structures. In addition to not leaving a visible scar, another advantage is that there is no need for neck hyperextension, a position that causes postoperative pain and is limited in patients with cervical pseudoarthrosis. Among the disadvantages of the technique is its use in patients with lesions larger than 4cm, since it is difficult to dissect and remove the specimen through the subcutaneous tunnel, and in those with disease in multiple glands, due to the need for bilateral dissection. However, since most of the primary hyperparathyroidisms is from single glands, the techniqueis perfectly feasible. This technique was later used in a patient at the Klinikum Bremerhaven Hospital, Bremerhaven, Germany, but with small differences. The subcutaneous tissue was dissected with a rigid acrylic bar through the access in the left axillary fossa until reaching the anterior neckregion. After installation of the TriPortÂŽ, CO2 was injected with a pressure of 6mmHg and the pre-thyroid muscles were dissected with identification

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Marsillac Transaxillary single-port subtotal parathyroidectomy: feasibility study in cadavers

of the thyroid gland and its medial rotation, which allowed the visualization of the parathyroid adenoma in the thyroidupper pole. The gland was resected using Harmonic Ace® Curved Shears25. With the described technique, it was possible to perform parathyroidectomy with easy identification

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of the noble structures, demonstrating that the surgery is feasible and can be carried out by surgeons with experience in advanced endoscopic surgery. A study with more cases is still necessary so that the transaxillary surgery technique becomes a routine in parathyroid surgery.

R E S U M O Objetivo: testar a técnica minimamente invasiva de paratireoidectomia subtotal transaxilar single-port em cadáveres não formalizados para avaliar sua viabilidade e reprodução. Método: foram realizadas dez paratireoidectomias subtotais por via transaxilar através de acesso por TriPort em cadáveres. A técnica realizada consistiu em acesso pela fossa axilar, criando-se um túnel subcutâneo até a região cervical anterior, para manuseio da glândula tireoide e dissecção e ressecção das paratireoides. Resultados: todas as cirurgias foram realizadas com sucesso. O tempo médio de cirurgia foi 65 minutos (57-79 min), com identificação, sem dificuldades, de todas as estruturas anatômicas. Não houve necessidade de incisões complementares na região cervical. Conclusão: a técnica de paratireoidectomia subtotal transaxilar single-port foi viável e reprodutível, sugerindo uma alternativa para a cirurgia cervical minimamente invasiva. Descritores: Paratireoidectomia. Endoscopia.Cadáver. Procedimentos Cirúrgicos Minimamente Invasivos.

REFERENCES 1. Kalloo AN, Singh VK, Jagannath BS, Niiyama H, Hill SL, Vaughn CA, et al. Flexible transgastric peritoneoscopy: a novel approach to diagnostic and therapeutic interventions in the peritoneal cavity. Gastrointest Endosc. 2004;60(1):114-7. 2. Zorron R, Palanivelu C, Galvão Neto MP, Ramos A, Salinas G, Burghardt J, et al. International multicenter trial on clinical natural orifice surgery-NOTES IMTN study: preliminary results of 362 patients. Surg Innov. 2010;17(2):142-58. 3. Lehmann KS, Ritz JP, Wibmer A, Gellert K, Zornig C, Burghardt J, et al. The German registry for natural orifice translumenal endoscopic surgery: report of the first 551 patients. Ann Surg. 2010; 252(2):263-70. 4. Meining A, Feussner H, Swain P, Yang GZ, Lehmann K, Zorron R, et al. Natural orifice transluminal endoscopic surgery (NOTES) in Europe: summary of the working group reports of the Euro-NOTES meeting 2010. Endoscopy. 2011;43(2):140-3. 5. Muenscher A, Dalchow C, Kutta H, Knecht R. The endoscopic approach to the neck: a review of the literature, and overview of the various techniques. Surg Endosc. 2011;25(5):1358-63. 6. Gagner M. Endoscopic subtotal parathyroidectomy in patients with primary hyperparathyroidism. Br J Surg. 1996;83(6):875.

7. Hüscher CS, Chiodini S, Napolitano G, Recher A. Endoscopic right thyroid lobectomy. Surg Endosc. 1997;11(8):877. 8. Gagner M, Inabnet WB 3rd. Endoscopic thyroidectomy for solitary thyroid nodules. Thyroid. 2001;11(2):161-3. 9. Miccoli P, Pinchera A, Cecchini G, Conte M, Bendinelli C, Vignali E, et al. Minimally invasive, video-assisted parathyroid surgery for primary hyperparathyroidism. J Endocrin Invest. 1997;20(7):429-30. 10. Miccoli P, Bellantone R, Mourad M, Walz M, Raffaelli M, Berti P. Minimally invasive video-assisted thyroidectomy: multiinstitutional experience. World J Surg. 2002;26(8):972-5. 11. Ikeda Y, Takami H, Sasaki Y, Takayama J, Kurihara H. Are there significant benefits of minimally invasive endoscopic thyroidectomy? World J Surg. 2004;28(11):1075-8. 12. Inabnet WB 3rd, Jacob BP, Gagner M. Minimally invasive endoscopic thyroidectomy by a cervical approach. Surg Endosc. 2003;17(11):1808-11. 13. Oertli D, Harder F. Surgical approach to thyroid nodules and cancer. Baillieres Best Pract Res Clin Endocrinol Metab. 2000;14(4):651-66. 14. Bärlehner E, Benhidjeb T. Cervical scarless endoscopic thyroidectomy: axillo-bilateral-breast approach (ABBA). Surg Endosc. 2008;22(1):154-7. 15. Shimazu K, Shiba E, Tamaki Y, Takiguchi S, Taniguchi E, Ohashi S, et al. Endoscopic thyroid

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surgery through the axillo-bilateral breast approach. Surg Laparosc Endosc. 2003;13(3):196-201. Koh YW, Park JH, Kim JW, Lee SW, Choi EC. Endoscopic hemithyroidectomy with prophylactic ipsilateral central neck dissection via an unilateral axillo-breast approach without gas insufflation for unilateral micropapillary thyroid carcinoma: preliminary report. Surg Endosc. 2010;24(1):188-97. Witzel K, von Rahden BH, Kaminski C, Stein HJ. Transoral access for endoscopic thyroid resection. Surg Endosc. 2008;22(8):1871-5. Benhidjeb T, Wilhelm T, Harlaar J, Kleinrensink GJ, Schneider TA, Stark M. Natural orifice surgery on thyroid gland: totally transoral video-assisted thyroidectomy (TOVAT): report of first experimental results of a new surgical method. Surg Endosc. 2009;23(5):1119-20. Karakas E, Steinfeldt T, Gockel A, Westermann R, Kiefer A, Bartsch DK. Transoral thyroid and parathyroid surgery. Surg Endosc. 2010;24(6):1261-7. Richmon JD, Pattani KM, Benhidjeb T, Tufano RP. Transoral robotic-assisted thyroidectomy: a preclinical feasibility study in 2 cadavers. Head Neck. 2011;33(3):330-3. Lee D, Nam Y, Sung K. Single-incision endoscopic thyroidectomy by the axillary approach. J Laparoendosc Adv Surg Tech A. 2010; 20(10):839-42.

22. Kang SW, Lee SC, Lee SH, Lee KY, Jeong JJ, Lee YS, et al. Robotic thyroid surgery using a gasless, transaxillary approach and the da Vinci S system: the operative outcomes of 338 consecutive patients. Surgery. 2009;146(6):1048-55. 23. Lee J, Lee JH, Nah KY, Soh EY, Chung WY. Comparison of endoscopic and robotic thyroidectomy. Ann Surg Oncol. 2011;18(5):1439-46. 24. Lin S, Chen ZH, Jiang HG, Yu JR. Robotic thyroidectomy versus endoscopic thyroidectomy: a meta-analysis. World J Surg Oncol. 2012;10:239. 25. Phillips HN, Fiorelli RK, Queiroz MR, Oliveira AL, Zorron R. Single-port unilateral transaxillary totally endoscopic thyroidectomy: a survival animal and cadaver feasibility study. J Minim Access Surg. 2016;12(1):63-7.

Received in: 22/09/2016 Accepted for publication: 15/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Rossano Kepler Alvim Fiorelli E-mail: fiorellirossano@hotmail.com hnphillips@gmail.com

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DOI: 10.1590/0100-69912017002005

Original Article

Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions Avaliação da expressão de Telomerase (hTert), Ki67 e p16ink4a em lesões intraepiteliais cervicais de baixo e alto graus Ana Paula Szezepaniak Goulart1; Manoel Afonso Guimarães Gonçalves1; Vinicius Duval da-Silva1. A B S T R A C T Objective: to study the association between the histological grading of cervical intraepithelial neoplasia (CIN I, CIN II and CIN III) and the immunohistochemical expression for p16ink4a, hTert and Ki67, as well as to evaluate the relationship of these markers with the risk of recurrence after surgical treatment. Methods: we studied a historical cohort of 94 women with intraepithelial lesions CIN I (low grade), CIN II and CIN III (high grades) submitted to conization or electrosurgical excision of the transformation zone. We evaluated all surgical specimens for immunohistochemical expression of p16ink4a, hTert and Ki67. Results: the mean age was 38.2 years; p16ink4a was absent in most CIN I cases. In patients with CIN II or I/II (association of low and high-grade lesions), we observed p16ink4a ≤10%. In patients with CIN III, we found a higher expression frequency of p16ink4a >50%. In CIN I, the majority had Ki67≤10% and low frequency of Ki67>50%. In the CIN III category, there were fewer patients with Ki67≤10%, and Ki67 was absent in most patients of CIN II and III groups. There was no association between hTert expression and histologic grade. There were no statistically significant differences between the expression of the markers in patients with and without recurrence. Conclusion: there was a statistically significant association of p16ink4a and Ki67 with histological grade. The markers’ expression, as for disease recurrence, was not statistically significant in the period evaluated. Keywords: Cervical Intraepithelial Neoplasia. Telomerase. Immunohistochemistry. Recurrence.

INTRODUCTION

C

ervical cancer is the third most common malignant neoplasm among women (90% of cases in developing countries), and in Brazil it accounts for 9.3% of gynecological malignancies. Worldwide, 500,000 new cases per year are diagnosed, accounting for 250,000 annual deaths1. The National Cancer Institute (INCA) recommends that cervical cytopathological screening be done every three years after two consecutive negative tests in patients aged 25 and 64 years, provided that the samples are satisfactory and representative of the squamous-column junction2. The malignant neoplasm of the cervix is ​​preceded by a long phase of precursor, usually asymptomatic, lesion, characterized by cervical intraepithelial neoplasia (CIN), which may persist for 10 to 20 years. In 1976, Zur Hausen3 demonstrated the relationship between the HPV virus infection and the

onset of genital tract neoplasias. Infection is more common in young patients; however, sexual behavior, age, smoking, parity and use of contraceptives are also risk factors for this neoplasia1. On the other hand, not all patients infected with the virus have the same disease progression, since this behavior is linked to environmental factors, immunity, host genetics and cellular factors4. The use of molecular markers has helped the pathologists in the definition of doubtful cases and in the identification of women at high risk for disease recurrence after treatment of cervical intraepithelial neoplasias5. p16ink4a, a tumor suppressor protein, is overexpressed in cases of dysplasia, presenting a high sensitivity as it correlates with the dysplasia severity. Current studies indicate that p16ink4a is a useful biomarker for high-risk lesions and for progression prediction in low-risk ones. These studies show a significant association between the degree of cervical lesion and the distribution and intensity of p16ink4a expression5,6.

1 - São Lucas Hospital, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Gynecology and Pathology Service, Porto Alegre, Rio Grande do Sul State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 131-139


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Goulart Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

Ki67 is another cell proliferation marker expressed at all stages of the cell cycle, except in the G0 phase, and which, although not specifically involved in the cervical carcinogenic process, has an independent predictive value as to grading and evaluating disease progression7. Telomerase is a ribonucleic enzyme complex that allows telomere maintenance in 90% of cancer cases. In normal somatic cells, telomerase activity is low or undetectable, and telomeres shorten at each cell division. The hTert is the telomerase reverse transcriptase, being the most important factor in the formation of functional telomerase. The activation of telomerase establishes telomere length maintenance, acting in the transformation of dysplasia into malignant neoplastic alterations and in the maintenance of phenotypically more aggressive cell populations8. The hTert is present in 28.5% of CIN I, in 87.5% of CIN II and in 95% of CIN III9. Among the existing treatments for the management of cervical intraepithelial neoplasias, in our hospital we perform the conization and the electrosurgical excision of the transformation zone (LEEP) techniques. The former has the advantage of allowing lesion resection and margins evaluating without the presence of fulguration artifacts by the passage of electric current, but removes a larger volume of cervical stroma, which can lead to adverse reproductive outcomes. The LEEP technique is a technically simpler procedure, which can be done in an outpatient setting under local anesthesia. On the other hand, margins may be inadequate for evaluation due to histological artifacts caused by thermal damage, have a higher risk of bleeding and may cause cervical stenosis in up to 6% of patients10. The literature recommends that patients’followup should be for at least one year with a cervical cytopathological exam (CP) and with semestral colposcopy after surgery, since this is the period of greatest risk of recurrence of cervical lesions11. The recurrence rate of high-grade intraepithelial lesions after surgical excision varies from 5% to 10%4,12,13. The complication associated with the surgical treatment of such lesions are bleeding, external cervical orifice stenosis, infertility, shortening

of the cervix and risk of preterm labor, isthmo-cervical incompetence, low birth weight fetuses, cesarean section and premature membranes rupture14. Therefore, to analyze the association between recurrence after surgical treatment and the expression of immunohistochemical markers according to the graduation of high and low grade intraepithelial lesions would allow the suspension of a rigorous clinical follow-up and the reduction of overdiagnosis and overtreatment in patients affected by this disease. To date, there is no description of the concomitant evaluation of the three immunohistochemical markers – p16ink4a, Ki67 and hTert – in high and low grade intraepithelial lesions. As already described, the only marker that has well established utility in the evaluation of progression, not recurrence, of these lesions is p16ink4a 15. Other markers are still poorly studied and, therefore, there are few published papers regarding Ki67 and hTert, with no established accuracy for use in clinical practice, although they appear to display a difference according to their expression between high and low grade lesions16. Furthermore, the behavior of CIN II is still uncertain, and so far, this lesion receives the same treatment as CIN III, a standardized conduct based on the 1991 Bethesda consensus17. However, in recent years, its aggressiveness has been questioned, since it behaves dubiously, with a significant number of cases showing good evolution, spontaneous regression or indolent behavior6,7. The establishment of recurrence risk markers for this type of lesion is thus innovative, and could define which patients would require surgical treatment and which would be likely to remain in clinical follow-up. This answer does not yet exist in the literature.

METHODS We studieda historical cohort in which we analyzed 94 patients divided into three groups with cervical intraepithelial lesions, CIN I, CIN II and CIN III, submitted to conization or LEEP. We followed the patients for two years to determine disease recurrence. The sample consisted of patients from the Gynecology outpatient clinic of the São Lucas Hospital

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Goulart Evaluation of Telomerase (hTert), Ki67 and p16ink4a expressions in low and high-grade cervical intraepithelial lesions

of the Pontifical Catholic University of Rio Grande do Sul (PUCRS), who underwent cervical cytopathological examination followed by colposcopy with biopsy of suspicious areas and subsequent diagnosis of CIN. We recruited patients by (consecutive) convenience sampling. All cases of the study had the histological examinations reviewed by a second pathologist with clinical experience superior to twenty years. Inclusion criteria were patients aged 18 years or older, submitted to LEEP or conization, and with a six-month postoperative follow-up (cervical CP, colposcopy and cervix biopsy if necessary) for at least two years, whose surgical specimens had margins free of cervical intraepithelial neoplasia. Exclusion criteria were patients with human immunodeficiency virus (HIV) or other immunosuppressive disorders, and pregnancy. We performed the immunohistochemistry technique on tissues fixed in formalin and included in paraffin. The detection method used for screening tissue antigens was avidin-biotin peroxidase. We produced 3-μm thick histological sections on a Leica RT2150 rotary microtome. The slides were deparaffinized in a histological oven at 69° C, two incubations in xylol, five incubations with 99° ethyl alcohol, washing in running water until complete removal and then maintained in a PBS buffer. Antigen retrieval utilized a 6.0-pH citrate buffer for 20 minutes. Endogenous peroxidase activity was blocked with 5% hydrogen peroxide solution in methyl alcohol. Incubation with the primary antibody was performed in a BOD incubator at 5°C. To detect the antigenantibody reaction, we used biotinylated secondary antibody and avidin-HRP complex. We performed staining with Diamine Benzidine (DAB, DAKO) as the chromogen. Finally,we counterstained the slides with Harris haematoxylin, dehydrated in a series of 99° ethyl alcohol, clarified in xylene and mounted with Canadian balsam. The clones used for the markers were E6H4 to p16ink4a, MM1 to Ki67 and 2C4 to hTert. For the detection of p16ink4a, Ki67 and hTert, we used slides without cervical intraepithelial neoplasia as negative controls and, as positive controls, slides with high cervical intraepithelial neoplasia (CIN III). Regarding the interpretation of the markers, we

133

considered the nuclear staining as positive for the cells expressing p16ink4a. We graded the expression intensity for p16ink4a in CIN as negative if none of the cells displayed staining, and as positive, if they expressed staining as a percentage (less than 10%, 11% to 50% or more than 50%). We considered Ki67 positive only if the nuclei of the cells showed staining and we determined the percentage of cells expressing it in less than 10%, 11% to 50% or more than 50%. We considered hTert positive also if the cell nucleus was stained. The expression was considered positive if the cells expressed staining and negative when there was no expression. We inputted the data in the Excel 2010 software and later exported to the SPSS v.20.0 program for statistical analysis. We described categorical variables by frequencies and percentages and analyzed them with the Chi-square test. We described the quantitative variables with symmetrical distribution by the mean and standard deviation, comparing two categories with the Student t test for independent samples, and three categories or more, with the Analysis of Variance (ANOVA) test. We described quantitative variables with asymmetric distribution by median and the interquartile range (25th and 75th percentiles), comparing two categories with the Mann-Whitney test, and three or more categories, with the Kruskal-Wallis test. We set the significance level at 5%. The project was approved by the Scientific Committee of the Postgraduate Program in Medicine and Health Sciences and by the Ethics Committee / PUCRS (protocol no. 109403/2014).

RESULTS Patients’ mean age was 38 years, with a standard deviation of 11.7; 37% used combined oral contraceptives and 26% did not use any contraceptive method. Only 31% were smokers, the mean number of children was two and the average of the first intercourse was at 16 years. The surgical approach was conization in 79.8% of patients. The most frequent anatomic and pathological findings were CIN III (52%), followed by CIN I (14.9%) and

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Table 1. Histological grade and the expression of Immunohistochemistry markers

CIN I

CIN I/II* and II

CIN III

CIN II and III

p16

≤10

P 0.026

ink4a

3 (23.1)

5 (38.5)

8 (16.7)

-

-

1 (7.7)

3 (6.2)

2 (16.7)

>50

3 (23.1)

3 (23.1)

28 (58.3)

4 (33.3)

Absent

7 (53.8)

4 (30.8)

9 (18.8)

6 (50.0)

11-50

Ki67

0.032

≤10

9 (64.3)

5 (38.5)

11 (22.4)

5 (41.7)

11-50

3 (21.4)

1 (7.7)

9 (18.4)

-

>50

2 (14.3)

7 (53.8)

27 (55.1)

5 (41.7)

-

-

2 (4.1)

2 (16.7)

Absent hTert

0.677

Positive

7 (50.0)

7 (53.8)

30 (62.5)

5 (45.5)

Negative

7 (50.0)

6 (46.2)

18 (37.5)

6 (54.5)

Data presented by n (%) and compared with the Chi-square test. Data in bold are data whose adjusted residue had absolute value greater than 1.96. * High grade cervical intraepithelial lesion associated with the one of low grade.

CIN II (12.8%). Among those who relapsed, most were carriers of CIN I, followed by carriers of CIN III. The total number of recurrences among the 94 patients operated, regardless of the type of procedure, was 23 (24.5%). Recurrence was more common in patients who underwent LEEP, 31%, being 22% in those submitted to conization. There was a statistically significant association between p16ink4a and Ki67 and histological grade, as shown in Table 1. Figures 1, 2 and 3 show the expression of immunohistochemical markers. There was no statistically significant difference between age, smoking, parity, age of first sexual intercourse and number of sexual partners and the different histological grades ordisease recurrence. When comparing the markers between subjects with and without recurrence, there were also no statistically significant differences.

and mortality in developing countries, andgood control in developed countries whose screening programs are effective18. Works have found that the immunohistochemical markers p16ink4a and Ki67 are more accurate in identifying precursor lesions in patients under 30 years with cervical cytopathological examination compatible with low grade intraepithelial lesion. The expression of these markers is associated with the severity of histological lesions. In the Possati-Resende et al. study18, patients underwent cervical biopsy,

DISCUSSION Cervical carcinoma has a high potential for prevention. In our country, however, it is a public health problem.Studies have shown high incidence

Figure 1. p16ink4a; 200x magnification. Nuclear cells with marker expression in more than 50%.

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Figure 2. Ki67; 200x magnification. Nuclear cells with marker expression in more than 50%.

Figure 3. hTert; 200x magnification. Positivity in nuclear cells.

and the expression of p16ink4a and Ki67 was present in 46.5% of CIN I, 82.8% of CIN II and 92.8% of CIN III. In our study, p16ink4a was overexpressed by the immunohistochemical method in more than 50% of the cells of each sample in 43.3% of the cases, presenting a strong intensity in 48.9% of the exams. The Ki67 marker was expressed in 43.6% of the cases (positive in more than 50% of the sample). The hTert was positive in 56.5% of the cases studied. Although the incidence of cervical neoplasms has decreased, there are still many diagnoses of cancer in cervical lesions with a high potential for regression and, consequently, of inadequate and excessive treatments. In this context, the use of immunohistochemical markers helps the pathologist in the histological evaluation of such lesions19. According to American guidelines, patients with suspected high-grade cervical intraepithelial neoplasia and overexpressed p16ink4a benefit from surgical treatment. The positivity for this marker is linked to the onset of oncogenic transformation for the development of cancer and its use would allow the detection of pre-neoplastic lesions and the reduction of unnecessary aggressive treatments19. The importance of studying these markers is due to the wide variability of interpretation among observers and the poor reproducibility of cytomorphological criteria, mainly regarding the use of hematoxylin and eosin for the histological diagnosis of cervical intraepithelial neoplasias, as well

as its classification in the categoriesCIN I, II and III. We minimized this limitation in this study through the evaluation and concordance of diagnosis by two pathologists, one original interpreter of the case and one reviewer. The use of these markers complements the doubtful diagnoses, avoiding unnecessary treatments20,21. The presence of Ki67 in CIN I and CIN II in uterine cervix specimens is a strong independent predictive factor for graduation and disease progression, in addition to displaying an interobserver reproducibility of 100%22. The literature shows that the evaluated immunohistochemical markers, p16ink4a, Ki67 and hTert, are clearly associated with histological grade. Some studies have found an association with the risk of progression to high-grade neoplasias and cancer, but none showed that their overexpression is associated with recurrence after treatment. The CIN recurrence rate usually ranges from 5% to 10%4,12,13. However, in the study by Serati et al.23, who followed patients for ten years, recurrence occurred in 19.4% of the free-margin excisions and was twice as common with the LEEP technique. Although we included in our study only surgical pieces with free margins, the incidence of recurrence of 24.5% was high when compared with the rates described in the literature. On the other hand, Malapati et al.24 followed 717 eligible patients after LEEP and observed postoperative persistence/recurrence of 24.7%. The most common type of recurrence was CIN I (47.8%), followed by CIN III (34.8%), and most occurred within

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the first six months after treatment (56%). There was no difference between the expression of the analyzed immunohistochemical markers and disease recurrence, even when evaluated individually at each histological grade. This fact may be due to the small number of cases and the subdivision of the markers expression positivity in below 10%, 1150% and greater than 50%, unlike other studies in which the quantitative analysis was made in absolute numbers, a method that still presents limitations for implementation in the surgical pathology diagnostic routine. The study by Cardoso et al.4 was one of the few that showed statistical significance between p16ink4a overexpression and disease recurrence, as did Nam et al.25. Fonseca et al.26 demonstrated that p16ink4a was overexpressed in 43% of the recurrences, with high intensity in 58% of them, though this finding was not statistically significant. In a group of 90 patients with cervical intraepithelial neoplasia with overexpressed p16ink4a and Ki67, there was progression in 15 cases (17%), two cases in the group of 25 patients with CIN I (8%) and 13 cases in the group of 65 patients with CIN II (20%)22. In our study, Ki67 expression was positive in 10% or less in CIN I and overexpressed in more than 50% of each sample in 53% of CIN II and 55% of CIN III (p=0.032). Age, smoking, number of children, age of first intercourse, and number of sexual partners showed no significant difference in disease recurrence. Contrary to our findings, the literature shows that age greater than or equal to 35 years and smoking are risk factors for recurrence, as well as larger cytological alterations, high-risk preoperative HPV infection, positive endocervical margins, and HIV infection24,27,28. The expression of p16ink4a related significantly to the histological grade in this study. It was negative in 53% of CIN I, overexpressed in more than 50% of CIN III in 58% of cases and expressed in a lower percentage (equal or less than 10%) in 38.5% of the cases of CIN II (p=0.026). We observed a lower percentage of positivity for p16ink4a in CIN II than in CIN III, although both overexpressed this marker with high intensity (53.8% of CIN II and 62.5% of CIN III). In the study of GenovĂŠs6, evaluating 92 patients,

p16ink4a was overexpressed in seven of the 54 patients with CIN I and in 17 of the 23 patients with CIN II. The study emphasizes that the diagnosis of CIN II should not rely solely on the positivity of this marker, and its absence does not imply lesionregression. Regarding the risk of progression, a study evaluating 52 patients with CIN II showed disease regression in 28 cases, progression to CIN III in 13 and persistence of the lesion in 11 cases. In those who progressed, 91% of the lesions had overexpressed p16ink4a, with strong intensity29. As for hTert, the literature also describes its overexpression in highgrade intraepithelial lesions (p<0.001) in 88% to 90% of the samples, while low-grade intraepithelial lesions have low expression in 94% of cases30. It can be inferred that the expression of this marker represents an early manifestation of the dysplastic process, therefore being overexpressed in 45% of CIN I, 70% of CIN II and 80% (p=0.024)31. In our study, hTert did not show statistical significance in relation to the histological grade (p=0.677), although it was positive in 62.5% of the NCI III, 53.8% of CIN II and 50% of CIN I. Although the expression of immunohistochemical markers was positive in CIN II and CIN III, we observedvariable expression, showing a more intense and higher percentage of cells in high grade dysplasia. Such behavior of CIN II shows that this lesion probably has a behavior of lower aggressiveness when compared to CIN III. According to Wilkinson et al.32, the regression rate of CIN II is similar to that of CIN I in a follow-up of two years (17%x12%). This poses a risk of overtreatment of such lesions, mainly in women under 25 years of age, since the risk of developing cervical cancer in untreated women with high-grade dysplasia is less than 1.5%. Despite the importance of the use of immunohistochemical markers in the progression of cervical intraepithelial neoplasias, also evidenced in our study, there was no association between the markers and the recurrence of dysplastic lesions. New studies are needed, as well as the prospection of new markers, to establish with better precision the characteristics of these lesions and to allow conservative management in those that present a more indolent behavior.

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R E S U M O Objetivo: estudar a associação entre a graduação histológica das neoplasias intraepiteliais cervicais (NIC I, NIC II e NIC III) e a expressão imuno-histoquímica para p16ink4a, hTert e Ki67, assim como, avaliar a relação destes marcadores com o risco de recorrência após tratamento cirúrgico. Métodos: estudo de coorte histórica de 94 mulheres portadoras de lesões intraepiteliais NIC I (baixo grau), NIC II e NIC III (altos graus), submetidas à conização ou à excisão eletrocirúrgica da zona de transformação. Todas as peças cirúrgicas foram avaliadas quanto à expressão imuno-histoquímica para p16ink4a, hTert e Ki67. Resultados: a média de idade das pacientes foi 38,2 anos. Nas pacientes NIC I, a p16ink4a estava ausente na maioria dos casos; nas pacientes NIC II ou I/II (associação de lesões de baixo e alto graus), observou-se frequência de p16ink4a≤10%. Nas pacientes NIC III, observou-se maior frequência de expressão de p16ink4a>50%. Na categoria NIC I, a maioria apresentava Ki67≤10% e baixa frequência de Ki67>50%. Na categoria NIC III houve menor número de pacientes com Ki67≤10%, sendo que a maior parte das pacientes tinha Ki67 ausente nos grupos NIC II e III. Não houve associação entre a expressão do marcador imuno-histoquímico hTert e a graduação histológica. Não houve diferenças estatisticamente significativas entre as expressões dos marcadores em pacientes com e sem recorrência. Conclusão: houve associação estatisticamente significativa apenas de p16ink4a e Ki67 com a graduação histológica. A expressão dos marcadores em relação à recorrência da doença não foi estatisticamente significativa no período avaliado. Descritores: Neoplasia Intraepitelial Cervical. Telomerase. Imuno-Histoquímica. Recidiva.

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15. Darragh TM, Colgan TJ, Thomas Cox J, Heller DS, Henry MR, Luff RD, et al. The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol. 2013;32(1):76-115. Erratum in: Int J Gynecol Pathol. 2013;32(4):432. Int J Gynecol Pathol. 2013;32(2):241. 16. Fujii T, Saito M, Hasegawa T, Iwata T, Kuramoto H, Kubushiro K, et al. Performance of p16INK4a/Ki-67 immunocytochemistry for identifying CIN2+ in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion specimens: a Japanese Gynecologic Oncology Group study. Int J ClinOncol. 2015;20(1):134-42. 17. Solomon D, Nayar R. Sistema Bethesda para citopatologia cervicovaginal. 2a ed. Rio de Janeiro: Revinter; 2005. 18. Possati-Resende JC, Fregnani JH, Kerr LM, Mauad EC, Longatto-Filho A, Scapulatempo-Neto C. The Accuracy of p16/Ki-67 and HPV Test in the Detection of CIN2/3 in Women Diagnosed with ASC-US or LSIL. PLoS One. 2015;10(7):e0134445. 19. Pacchiarotti A, Galeotti S, Bellardini P, Chini F, Collina G, Dalla Palma P, et al. Impact of p16(INK4a) immunohistochemistry staining on interobserver agreement on the diagnosis of cervical intraepithelial neoplasia. Am J Clin Pathol. 2014;141(3):367-73. 20. Calil LN, Edelweiss MI, Meurer L, Igansi CN, Bozzetti MC. p16 INK4a and Ki67 expression in normal, dysplastic and neoplastic uterine cervical epithelium and human papillomavirus (HPV) infection. Pathol Res Pract. 2014;210(8):482-7. 21. Walts AE, Bose S. p16, Ki-67, and BD ProExC immunostaining: a practical approach for diagnosis of cervical intraepithelial neoplasia. Hum Pathol. 2009;40(7):957-64. 22. Kruse AJ, Baak JP, Janssen EA, Kjellevold KH, Fiane B, Lovslett K, et al. Ki67 predicts progression in early CIN: validation of a multivariate progression-risk model. Cell Oncol. 2004;26(1-2):13-20.

23. Serati M, Siesto G, Carollo S, Formenti G, Riva C, Cromi A, et al. Risk factors for cervical intraepithelial neoplasia recurrence after conization: a 10-year study. Eur J Obstet Gynecol Reprod Biol. 2012;165(1):86-90. 24. Malapati R, Chaparala S, Cejtin HE. Factors influencing persistence or recurrence of cervical intraepithelial neoplasia after loop electrosurgical excision procedure. J Low Genit Tract Dis. 2011;15(3):177-9. 25. Nam EJ, Kim JW, Hong JW, Jang HS, Lee SY, Jang SY, et al. Expression of the p16 and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection. J Gynecol Oncol. 2008;19(3):162-8. 26. Fonseca FV, Tomasich FD, Jung JE, Maestri CA, Carvalho NS. The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment. Rev Col Bras Cir. 2016;43(1):35-41. 27. Fu Y, Chen C, Feng S, Cheng X, Wang X, Xie X, et al. Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization. Ther Clin Risk Manag. 2015;11:851-6. 28. de Mello Silva MV, Coutinho IC, de Andrade Herรกclio S, Fittipaldi HM Jr, Katz L. Factors associated with the persistence/recurrence of CIN2/3 in women submitted to loop electrosurgical excision procedure in a teaching hospital in northeastern Brazil: a case-control study. J Low Genit Tract Dis. 2014;18(4):286-90. 29. Omori M, Hashi A, Nakazawa K, Yuminamochi T, Yamane T, Hirata S, et al. Estimation of prognoses for cervical intraepithelial neoplasia 2 by p16INK4a immunoexpression and high-risk HPV in situ hybridization signal types. Am J Clin Pathol. 2007;128(2):208-17. 30. Wang PH, Chen GD, Chang H, Yang SF, Han CP, Lin LY, et al. High expression of human telomerase reverse transcriptase in high-grade intraepithelial neoplasia and carcinoma of uterine cervix and its correlation with human papillomavirus infection. Reprod Sci. 2007;14(4):338-48.

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31. Bravaccini S, Sanchini MA, Amadori A, Medri L, Saragoni L, Calistri D, et al. Potential of telomerase expression and activity in cervical specimens as a diagnostic tool. J Clin Pathol. 2005;58(9):911-4. 32. Wilkinson TM, Sykes PH, Simcock B, Petrich S. Recurrence of high-grade cervical abnormalities following conservative management of cervical intraepithelial neoplasia grade 2. Am J Obstet Gynecol. 2015;212(6):769.e1-7.

Received in: 11/08/2016 Accepted for publication: 26/09/2016 Conflict of interest: none. Source of funding: none. Mailing address: Ana Paula Szezepaniak Goulart E-mail: anapgoulart@hotmail.com calpetry@ig.com.br

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DOI: 10.1590/0100-69912017002006

Original Article

Does the Attention Deficit Hyperactivity Disorder interfere with bariatric surgery results? O Transtorno de Déficit de Atenção e Hiperatividade interfere nos resultados da cirurgia bariátrica? Doglas Gobbi Marchesi, TCBC-ES1; Jovana Gobbi Marchesi Ciriaco2; Gustavo Peixoto Soares Miguel, TCBC-ES1; Gustavo Adolfo Pavan Batista, ACBC-ES1; Camila Pereira Cabral, ACBC-ES1; Larissa Carvalho Fraga1. A B S T R A C T Objective: to analyze possible negative effects of Attention Deficit Hyperactivity Disorder (ADHD) on the success of bariatric surgery. Methods: we evaluated forty patients undergoing bariatric surgery and with regular post-operative follow-up of at least one year. To all, we applied the questionnaire advocated in the fourth edition of the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association for ADHD, as well as analyzed their postoperative data. Results: fifteen (38%) patients presented a positive questionnaire for ADHD. Patients with ADHD presented higher BMI than patients without the disorder (45.8 vs. 40.9 kg/m2, p=0.017), and the difference remained in all postoperative stages. There was no statistically significant difference in surgery success (33.3% x 66.7%, p=0.505) or in BMI reduction (30.71% x 31.88%, p=0.671) one year after the procedure. Conclusion: ADHD patients have a higher BMI. However, the presence of ADHD does not influence the success of bariatric surgery and the reduction of BMI. Keywords: Bariatric surgery. Obesity. Attention Deficit Disorder with Hyperactivity.

INTRODUCTION

O

besity is a chronic disease that affects an increasing number of individuals worldwide1,2. There are estimates of overweight prevalence of 50.6%3. It is associated with a significant increase in morbidity and mortality and raises the incidence of several diseases, among them hypertension, diabetes mellitus, metabolic syndrome4-7. Bariatric surgery is a definitive treatment for morbid obesity and presents good long-term results, with loss of up to 70% excess weight8. The most commonly performed technique in Brazil and the world is the Roux-en-Y Gastric Bypass (RYGB). Despite the great efficiency of bariatric surgery, about 10 to 20% of patients submitted to it regain weight after the procedure9,10. Both the weight regain and the procedure failure are due to multiple factors. Psychiatric disorders such as anxiety, depression and attention-deficit / hyperactivity disorder (ADHD) are listed among them9,10.

ADHD is a neurological disorder of genetic causes11,12, present in about 5% of the adult population13,14. Symptoms revolve around the triad of inattention, restlessness, and impulsivity of varying degrees15. The etiology of ADHD is still unknown, but recent studies suggest alterations in the reward mechanism, also related to eating disorders and obesity16. There is evidence of increased ADHD incidence among obese and of greater difficulty in adherence to treatments and weight control17. However, few studies have evaluated the prevalence of ADHD in candidates for bariatric surgery and no study has evaluated its possible effects on the success of this procedure. The purpose of this study was to evaluate the effect of the presence of ADHD on the results of bariatric surgery.

METHODS We conducted a retrospective, observational study under the approval of the Ethics in Research

1 - Federal University of Espírito Santo, Department of Surgical Clinics, Vitória, Espírito Santo State, Brazil. 2 - Federal University of Espírito Santo, Department of Internal Medicine, Vitória Espírito Santo State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 140-146


Marchesi Does the Attention Deficit Hyperactivity Disorder interfere with bariatric surgery results?

141

Committee (CEP) of the Federal University of Espírito Santo (UFES) (CAAE: 05524512.3.0000.5060). We analyzed the specific charts of the bariatric surgery program of patients undergoing bariatric surgery from November 2011 to May 2013, according to the inclusion and exclusion criteria mentioned below. After the selection of the volunteers, we obtained a list of 122 patients, who were invited to attend the Bariatric Surgery Outpatient Clinic of the Cassiano Antônio de Moraes University Hospital (HUCAM), where they signed the Informed Consent Form. The inclusion criteria were patients submitted to the RYGB, respecting the indications of bariatric surgery according to the guideline of the National Institute of Health (NIH)6, postoperative time

greater than one year,and regular follow-up with the multidisciplinary team. Exclusion criteria were diagnosis of neurological and/or psychiatric diseases and use of psychoactive medications, to avoid confusion bias due to symptoms’ masking. After this initial screening, we included 40 patients for data evaluation, according to the algorithm shown in figure 1. After data collection, we performed a descriptive analysis with mean, standard deviation, median, absolute frequency and percentage, as well as maximum and minimum values, and drew up a profile of the cohort, recording data such as schooling, marital status, profession, age, ethnicity and comorbidities, seenin table 1.

Figure 1. Algorithm of patient selection.

Table 1. Characterization of the sample.

Variables Gender Marital Status Profession

Results Male = 8% Female = 93% Married = 68% Not married = 32% With profession = 70% No occupation = 30%

Age

Average ± SD = 48.3 ± 10.2 Median = 50

Weight

Average ± SD = 110.9 ± 19.2 Median = 109.5

BMI

Average ± SD = 43.9 ± 6.1 Median = 42.6

Ethnicity

White = 25% Brown = 43% Black = 33%

Schooling

Incomplete Junior high= 26% Complete Junior high= 11% Complete High school = 34% Incomplete High school= 11% Incomplete College = 5% Complete College= 13%

ADHD

Type of ADHD n= absolute number of patients.

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Positive = 38% Negative = 62% Pure attention deficit = 27% Pure hyperactivity = 27% Mixed = 56%


Marchesi Does the Attention Deficit Hyperactivity Disorder interfere with bariatric surgery results?

142 Table 2. Relationship between number of Comorbidities and ADHD.

ADHD Yes No

n 15 25

Median 4.00 2.00

Number of Comorbidities Average Standard deviation 3.13 1.25 2.32 2.32

p-value* 0.075

* Mann-Whitney Test.

We followed the patients at the institutionâ&#x20AC;&#x2122;s bariatric surgery outpatient clinic with programmed returns for three months, six months and one year. We evaluated variables such as weight, body mass index (BMI), percentage of BMI loss, and success of bariatric surgery (defined as loss of 50% or more of excess weight, considering a BMI of 258,18). In addition, researchers previously trained by a neurologist applied the Adult-Self Report Scale (ASRS) structured questionnaire11, for the diagnosis of ADHD. The questionnaire has 18 questions, the answers of which are divided into five groups (never, rarely, sometimes, often, very often), and grouped in part A (nineattention deficit questions) and part B (nine hyperactivity questions). For ADHD diagnosis, we used the criteria of the fourth American Diagnostic and Statistical Manual of Mental Disorders (DSMIV)19 of the American Psychiatry Society, and deemed present when six or more responses were positive in part A or part B, or both, not considering the sum of the positive answers in the two parts. We divided the patients into two groups: with ADHD and without ADHD. In the comparative analysis, for categorical variables, the statistical technique used was the chi-square test. For metric variables between two groups, we used the t-test for mean (parametric) and the Mann-Whitney test (non-parametric) for the comparisons. Statistical significance was set at p <0.05.

We observed a statistically significant difference in BMI at all times of follow-up. (Table 3). When comparing the percentage of BMI loss, ADHD individuals had a statistically significant difference in six months; however, this difference did not persist after 12 months (Figure 2). Both in the absolute weight loss assessment and in the comparative analysis of surgery success, there was no statistically significant difference between the groups with and without ADHD (Table 4).

DISCUSSION The relationship between ADHD and obesity became clear in recent years, both because of similar etiopathogeneses16 and because of the difficulty in adhering to treatments and weight control17. Concomitantly, despite the efficiency of bariatric surgery, a not insignificant portion of the patients, up to 20%, presented weight regain and the associated relapse of some comorbidities9,10. Faced with this situation, review studies performed to evaluate psychosocial predictors of failure in bariatric surgery have shown that the vast majority of studies are conflicting and inconclusive20, 21. This result is Figure 2. Percentage reduction of BMI.

RESULTS Of the 40 patients evaluated in the one-year period, 24 (60%) were successful. The ADHD group showed a higher average of comorbidities, but there was no statistically significant difference (Table 2).

Yes= with ADHD; No= no ADHD.

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Table 3. BMIaccording to ADHD.

Variables BMI (pre-op)

BMI (3 months)

BMI (6 months)

BMI (12 months)

ADHD

n

Median

Average

Standard deviation

Yes

15

45.80

47.09

6.75

No

25

40.90

42.03

4.98

Yes

13

37.80

40.15

6.01

No

24

32.60

34.82

4.61

Yes

11

34.50

36.42

5.51

No

23

29.50

30.98

4.07

Yes

15

31.00

32.49

6.16

No

25

27.10

28.52

3.85

p-value* 0.017

0.007

0.003

0.022

* Mann-Whitney Test.

due in part to the fact that manybariatric surgery teamsautomaticallyconsider patients diagnosed with psychiatric disorders as ineligible for the procedure20. The prevalence of 38% of ADHD found in our sample was in line with the studies that evaluated obese patients in general17,22,23 and with a value far above that found in patients in bariatric surgery programming24,25. Studies evaluating the obese population in general found a prevalence of ADHD between 27.4 and 32.2%,17,22,23 but one of the studies identified a higher incidence in individuals with BMI=40kg/m2 22. Two of these studies used as a diagnostic method a semi-structured interview and psychological follow-up17,22. Pagoto et al.23 used the same ASRS scale that we used in our study, but considered as positive the patients that met four criteria only. Thus, these studies opted for greater sensitivity in diagnosis. On the other hand, studies in groups of patients in preoperative bariatric surgery showed prevalence between 10.2 and 12.1%24,25. However, Gruss et al.24 considered positive only those patients who fulfilled criteria in two scales. When evaluating only the ASRS use, they found a prevalence of 29.3%, which is the closest to our result. We also note that these two studies used the ASRS scale with the patient reading and completing it alone, while in our study the researchers/interviewers conducted the questionnaire, as previously trained. We consider this

adaptation necessary since we work with a portion of the population of low socioeconomic level, which would compromise the understanding of the questionnaire and its due fulfillment. In addition, we increased the accuracy of the diagnosis and avoided false-negative results. Regarding comorbidities, we observing no difference between the patients with ADHD and the group without the disorder. We found no articles in the literature comparing these variables. We believe that the obesity degree directly influences the number of comorbidities6, without direct influence of ADHD. We observed that the BMI of patients with ADHD were higher than of those without the diagnosis. An American epidemiological study of 2013 with 34,653 people directly interviewed by psychiatrists confirmed that there was a significant difference in both weight and BMI in ADHD individuals26, which corroborates our results. Our success rate with surgery was 60% after one year. However, some factors may have negatively influenced this result. The maximum weight loss can occur up to the second postoperative year27. Our serieshad a large proportion of blacks, who display less weight loss in bariatric surgery28. Finally, weight loss after bariatric surgery is usually lower in superobese patients and in diabetics29,30. Thus, one expects that in a sample with a high percentage of diabetics and

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Marchesi Does the Attention Deficit Hyperactivity Disorder interfere with bariatric surgery results?

144 Table 4. Weight loss according to presence of ADHD.

BMI percentage loss (%) Postoperative period 3 months

6 months

12 months

ADHD

n

Median

Average

Standard deviation

Yes

13

16.56

15.92

3.40

No

24

16.71

17.03

3.88

Yes

11

23.21

22.93

4.73

No

23

26.57

26.56

4.61

Yes

15

31.40

30.71

10.04

No

25

31.88

31.88

7.17

p-value 0.390

0.041

0.671

Weight loss in 12 months (Kg) ADHD

n

Median

Average

Standard deviation

Yes

15

33.40

37.93

15.78

No

25

33.50

33.23

9.38

p-value 0.586

Success in 12 months Yes

No

ADHD

n

%

n

%

Yes

8

33.3

7

43.8

No

16

66.7

9

56.2

p-value 0.505

Success= loss greater than 50% of excess weight. T test for means to BMI, Mann-Whitney test for weight and Chi-square test for success.

superobese like ours, with 37.5% diabetics and 15% superobese, the percentage of excess weight loss is lower than the general average. Several studies analyzed this fact, such as the one from Schauer et al.31, who had a sample of 275 patients, 6.5% of them diabetic, who presented a mean weight loss of 68.8%31. Wittgrove et al.30 found 17% of diabetics and observed 80% weight loss in 18 months, but considering only the diabetic population the value was approximately 70%. When assessing ADHD with the evolution of patients after Gastric Bypass, we found no significant differences between the groups, leading to the belief that ADHD did not influence the procedure success. Although we found a single difference in the percentage of BMI loss at six months, this trend did not persist in the 12-month period. Even with limited sample size, lacking sufficient external validity to prove that ADHD would

affect surgery success, the data are relevant because there is a huge shortage of such studies. It is known that individuals with ADHD have a higher mean BMI and even less weight loss with clinical obesity treatment17. Concurrently, the higher the BMI, the greater the surgical morbidity and mortality32. Thus, it is expected that the treatment of such patients since the preoperative period allows better weight loss before the procedure and provides reduction of surgical complications. We conclude from our study that patients with ADHD have a higher BMI on average. However, bariatric surgery success of was not affected by the disease. This study has limitations on the sample size of and may not have statistical strength for definitive conclusions. However, these are preliminary results and further prospective studies are needed, with larger samples, longer follow-up times and multivariate analysis of the different confounding factors.

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Marchesi Does the Attention Deficit Hyperactivity Disorder interfere with bariatric surgery results?

145

R E S U M O Objetivos: analisar possíveis efeitos negativos do Transtorno do Déficit de Atenção e Hiperatividade (TDAH) no sucesso da cirurgia bariátrica. Métodos: foram avaliados 40 pacientes submetidos à cirurgia bariátrica e com acompanhamento pós-operatório regular mínimo de um ano. Todos foram submetidos ao questionário preconizado na quarta edição do Diagnostic and Statistical Manual (DSM-IV) da Associação Americana de Psiquiatria para TDAH e analisados os dados pós operatórios. Resultados: quinze (38%) pacientes apresentaram questionário positivo para TDAH. Os pacientes com TDAH apresentaram IMC maior do que os pacientes sem o transtorno (45,8x40,9 Kg/m2; p=0,017), mantendo-se a diferença em todas as etapas do pós-operatório. Não foi encontrada diferença estatisticamente significativa no sucesso da cirurgia (33,3% x 66,7%; p=0,505), e na redução do IMC (30,71% x 31,88%; p=0,671) após um ano do procedimento. Conclusão: pacientes com TDAH apresentam maior IMC, entretanto, a presença do TDAH não apresenta influência no sucesso da cirurgia bariátrica e na redução do IMC. Descritores: Cirurgia Bariátrica. Obesidade. Transtorno do Déficit de Atenção com Hiperatividade.

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tric surgery: a systematic review. Obes Surg. 2013;23(11):1922-33. 10. Sjöström CD, Lissner L, Wedel H, Sjöström L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study. Obes Res. 1999;7(5):477-84. 11. Matthews M, Nigg JT, Fair DA. Attention deficit hyperactivity disorder. Curr Top Behav Neurosci. 2014;16:235-66. 12. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57(11):1313-23. 13. Polanczyk GV, Casella EB, Miguel EC, Reed UC. Attention deficit disorder/hyperactivity: a scientific overview. Clinics (Sao Paulo). 2012;67(10):1125-6. 14. Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics. 2012;9(3):490-9. 15. Mattos P, Palmini A, Salgado CA, Segenreich D, Grevet E, de Oliveira IR, et al. Brazilian consensus of specialists on the diagnosis of attention-deficit/ hyperactivity disorder in adults. Rev Psiquiatr Rio GdSul. 2006;28(1):50-60. 16. Johnson RJ, Gold MS, Johnson DR, Ishimoto T, Lanaspa MA, Zahniser NR, et al. Attention-deficit/hyperactivity disorder: is it time to reappraise the role of sugar consumption? Postgrad Med. 2011;123(5):39-49. 17. Levy LD, Fleming JP, Klar D. Treatment of refractory obesity in severely obese adults following

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management of newly diagnosed attention deficit hyperactivity disorder. Int J Obes (Lond). 2009;33(3):326-34. Geloneze B, Pareja JC. Cirurgia bariátrica cura a síndrome metabólica? Arq Bras Endocrinol Metab. 2006;50(2):400-7. American Psychiatric Association. Diagnostic and statistical manual of mental disorders DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; 1994. van Hout GC, Verschure SK, van Heck GL. Psychosocial predictors of success following bariatric surgery. Obes Surg.2005;15(4):552-60. Herpertz S, Kielmann R, Wolf AM, Hebebrand J, Senf W. Do psychosocial variables predict weight loss or mental health after obesity surgery? A systematic review. Obes Res. 2004;12(10):1554-69. Altfas JR. Prevalence of attention deficit/hyperactivity disorder among adults in obesity treatment. BMC Psychiatry. 2002;2:9. Pagoto SL, Curtin C, Bandini LG, Anderson SE, Schneider KL, Bodenlos JS, et al. Weight loss following a clinic-based weight loss program among adults with attention deficit/hyperactivity disorder symptoms. Eat Weight Disord. 2010;15(3):e166-72. Gruss B, Mueller A, Horbach T, Martin A, de Zwaan M. Attention-deficit/hyperactivity disorder in a prebariatric surgery sample. Eur Eat Disord Rev. 2012;20(1):103-7. Alfonsson S, Parling T, Ghaderi A. Screening of adult ADHD among patients presenting for bariatric surgery. Obes Surg. 2012;22(6):918-26. Cortese S, Faraone SV, Bernardi S, Wang S, Blanco C. Adult attention-deficit hyperactivity disorder

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Received in: 17/10/2016 Accepted for publication: 01/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Doglas Gobbi Marchesi E-mail: doglas.marchesi@gmail.com doglas.marchesi@ebserh.gov.br

Rev. Col. Bras. Cir. 2017; 44(2): 140-146


DOI: 10.1590/0100-69912017002007

Original Article

Bacterial genus is a risk factor for major amputation in patients with diabetic foot Gênero bacteriano é fator de risco para amputação maior em pacientes com pé diabético Natália Anício Cardoso1; Lígia Túlio Pinho Navarro2-4.

de

Loiola Cisneiros2; Carla Jorge Machado2; Juliana Merlin Cenedezi2; Ricardo Jayme Procópio3,4;

A B S T R A C T Objective: to evaluate whether bacterial genus is a risk factor for major amputation in patients with diabetic foot and infected ulcer. Methods: we conducted a case-control, observational study of 189 patients with infected ulcers in diabetic feet admitted to the Vascular Surgery Service of the Risoleta Tolentino Neves Hospital, from January 2007 to December 2012. The bacteriological evaluation was performed in deep tissue cultures from the lesions and amputation was considered major when performed above the foot’smiddle tarsus. Results: the patients’mean age was 61.9±12.7 years; 122 (64.6%) were men. The cultures were positive in 86.8%, being monomicrobial in 72% of the cases. In patients with major amputation, Acinetobacter spp. (24.4%), Morganella spp. (24.4%), Proteus spp. (23.1%) and Enterococcus spp. (19.2%) were the most frequent types of bacteria. The most commonly isolated species were Acinetobacter baumannii, Morganella morganii, Pseudomonas aeruginosa and Proteus mirabilis. As predictors of major amputation, we identified the isolation of the generaAcinetobacter spp. and Klebsiella spp., serum creatinine ≥1.3mg/dl and hemoglobin <11g/dl. Conclusion: the bacterial genera Acinetobacter spp. and Klebsiella spp. identified in infected ulcers of patients with diabetic foot were associated with a higher incidence of major amputation. Keywords: Diabetic Foot. Foot Ulcer. Infection. Amputation.

INTRODUCTION

T

he diabetic foot disease is the major cause of hospitalization and costs for diabetic patients. It is a major public health problem, since diabetes mellitus affects about 415 million people worldwide1-3. Patients with diabetic foot present high rates of amputation, with a 25-fold higher risk when compared to patients without diabetes3. About 40% to 60% of non-traumatic lower limb amputations performed worldwide are due to diabetes complications, and 80% of such amputations are preceded by foot ulcers4,5. Foot ulcers will occur in approximately 25% of diabetic6. Among the clinical conditions associated with diabetic foot, such as neuropathy, deformities and ischemia, and comorbidities such as advanced age, heart disease, coronary disease, cerebrovascular disease, renal insufficiency and respiratory failure, ulcer infection is associated with higher mortality and high

rates of lower limb amputation7,8. About 40% to 80% of ulcers in diabetic patients progresses with infection and this is considered a clinical marker of systemic impairment and high mortality4,9,10. Superficial and acute infections are usually monomicrobial and caused by Gram-positive aerobic cocci, mainly staphylococci and/ or streptococci1,6,9,11. In deep, chronic or complicated infections, there is predominance of Gram-negative bacteria8.They are polymicrobial in 60 to 80% of cases, with Gram-positive (Staphylococcus spp., Streptococcus spp. and Enterococcus spp.), Gram-negative (Glucosefermenting bacilli of the Enterobacteriacea family and non-glucose fermenters, such as Pseudomonas spp. and Acinetobacter spp.) and anaerobic (mainly Bacteroides)6,9. It is important to verify if the bacterial genus isolated in infected diabetic foot ulcers is a predictive factor of lower limb amputation. This study aims to evaluate whether the bacterial genus is a risk factor for amputation in patients

1 - Federal University of Minas Gerais, Post-Graduate Program in Applied Sciences for Surgery and Ophthalmology, Faculty of Medicine, Belo Horizonte, Minas Gerais State, Brazil. 2 - Federal University of Minas Gerais, Faculty of Medicine, Belo Horizonte, Minas Gerais State, Brazil. 3 - Risoleta Tolentino Neves Hospital, Vascular Surgery Service, Belo Horizonte, Minas Gerais State, Brazil. 4 - Clinics Hospital, Federal University of Minas Gerais, Vascular Surgery Service, Belo Horizonte, Minas Gerais State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 147-153


Cardoso Bacteria generais a risk factor for major amputation in patients with diabetic foot

148

with diabetic foot and infected ulcers. Secondarily, it aims to verify if polymicrobial infection and reinfection also correlate with major amputation.

METHODS We conducted a case-control, observational study of 189 patients with infected diabetic foot ulcers admitted to the Vascular Surgery Service of Risoleta Tolentino Neves Hospital, a tertiary university hospital in Belo Horizonte, Minas Gerais State, Brazil, from January 2007 to December 2012. All patients had a deep tissue bacteriological culture. We excluded patients who had the collection of biological material with swab and who underwent minor amputation. We considered a minor amputation when performed below the middle tarsus of the foot, and major, when above the middle tarsus. The ulcers analyzed were all deep and were graded according to the Wagner Classification as ≥3, which corresponds to ulcers that compromise deep tissues. We considered as negative cultures where there was no bacterial growth. Those with growth of two or more bacteria, we considered polymicrobial. We considered as reinfection cultures where there

was growth of bacteria of different species in cultures carried out at different periods. We collected the following variables after access to patients’ electronic records: age, gender, surgeries, death, serum hemoglobin and creatinine levels, and bacteriological (genus and species) results. The case group consisted of patients who underwent major amputation and the control group, of patients who did not. For statistical analysis, was used the Stata/ SE 12.0 software for Mac. We expressed continuous variables as mean and standard deviation, and analyzed them using the Student’s t-test. We assessed categorical variables with the Pearson’s chi-square or Fisher’s test (if the expected number of cases in a category were less than five). We determined the predictive factors for major amputation by means of logistic regression analyzes. Values that ​​ were statistically significant in the Wald test (univariate analysis) were included in a multivariate model and the final model was obtained by sequential deletion of variables, based on the Wald and Hosmer and Leme show tests. We measured the statistical significance of the final model by the Hosmer and Leme show test (p<0.05).

Table1. Comparison of the different studied variables between groups of patients.

Major Amputation Total (n=189)

Yes (n=78)

No (n=111)

p-value

61.9 (± 12.7)

63.8 (± 10.5)

60.6 (± 13.9)

0.0895

Males, n (%)

122 (64.6)

54 (69.2)

68 (61.3)

0.259

Average of highest serum creatinine level (SD)

1.95 (± 1.8)

2.49 (± 2.4)

1.57 (± 1.1)

< 0.001 ***

Average of lowest serum hemoglobin level (SD)

8.93 (± 2.6)

7.35 (± 1.7)

10.0 (± 2.5)

< 0.001 ***

120 (63.5) 43 (22.8) 26 (13.8)

42 (53.9) 21 (26.9) 15 (19.2)

78 (70.3) 22 (19.8) 11 (9.9)

0.054

Patients with positive cultures, n (%)

164 (86.8)

68 (87.2)

96 (86.5)

0.890

Patients with polymicrobial cultures, n (%)

53 (28.0)

25 (32.1)

28 (25.2)

0.304

Patients with reinfection, n (%)

40 (21.2)

24 (30.8)

16 (14.4)

0.007 * *

Hospital readmission, n (%)

81 (42.9)

37 (47.4)

44 (39.6)

0.286

Mortality n (%)

30 (15.9)

18 (23.1)

12 (10.8)

0.023 *

Average age in years (SD)

Cultures undergone by patients, n (%) 1 culture 2 cultures > 2 cultures

Notes: * p < 0.05; ** p < 0.01; p < 0.001; SD: Standard Deviation. Rev. Col. Bras. Cir. 2017; 44(2): 147-153


Cardoso Bacteria generais a risk factor for major amputation in patients with diabetic foot

149

Table 2. Comparison between the groups of patients according to the bacterial genera isolated in deep tissue cultures.

Major Amputation Total (n=189)

Yes (n=78)

No (n=111)

p

Enterococcusspp. n (%)

28 (14.8)

15 (19.2)

13 (11.7)

0.152

Staphylococcusspp. n (%)

30 (15.9)

8 (10.3)

22 (19.8)

0.077

Streptococcusspp. n (%)

12 (6.4)

4 (5.1)

8 (7.2)

0.764

27 (14.3)

19 (24.4)

8 (7.2)

0.001 * *

Citrobacterspp. n (%)

9 (4.8)

4 (5.1)

5 (4.5)

0.999

Escherichia spp. n (%)

27 (14.3)

9 (11.5)

18 (16.2)

0.366

Enterobacterspp. n (%)

20 (10.6)

9 (11.5)

11 (9.9)

0.720

8 (4.2)

6 (7.7)

2 (1.8)

0.067

Morganellaspp. n (%)

35 (18.5)

19 (24.4)

16 (14.4)

0.083

Proteusspp. n (%)

35 (18.5)

18 (23.1)

17 (15.3)

0.176

Pseudomonasspp. n (%)

37 (19.6)

13 (16.7)

24 (21.6)

0.398

5 (2.7)

4 (5.1)

1 (0.9)

0.094

2 (1.1)

1 (1.3)

1 (0.9)

0.999

Gram-positive genera

Gram-negative genera Acinetobacterspp. n (%)

Klebsiellaspp. n (%)

Serratiaspp. n (%) Stenotrophomonasspp. n (%)

Notes: ** p < 0.01. The frequencies were calculated based on the total sample of 189 patients.

This study was approved by the Ethics in Research Committee of the Federal University of Minas Gerais (CAEE: 33623414.6.0000.5149) and authorized by the Nucleus of Education, Research and Extension of the hospital where the study was conducted.

RESULTS Table 1 brings the data regarding the total and per group samples, as well as their comparison. The mean patients’age was 61.9 years (±12.7), and 122 (64.6%) were males. Patients who underwent major amputation had a higher mean serum creatinine level, 2.49mg/dl (±2.4), and a lower mean serum hemoglobin level, 7.35g/dl (±1.7), compared with patients who did not undergo amputation. Regarding hospitalization, 57.1% of the patients were hospitalized only once, while 81 (42.9%) had to be admitted more than once. The hospital mortality in the study period was 15.9%, and it was higher among patients submitted to major

amputation (23.1%) than those who did not undergo amputation (10.8%). Of the 189 patients, 164 (86.8%) had positive cultures; 120 (63.5%) had only one deep tissue bacteriological culture, while 43 (22.8%) had two and 26 (13.8%), more than two cultures during the hospitalization period. Among the 164 patients with positive cultures, 72% presented monomicrobial cultures and 28%, polymicrobial ones. There was reinfection in 21.2% of patients. The most commonly isolated bacteria in the samples of the patients who underwent major amputation were Acinetobacter spp. (24.4%), Morganella spp. (24.4%), Proteus spp. (23.1%) and Enterococcus spp. (19.2%). Acinetobacter spp.was the most frequent isolate from patients undergoing amputation when compared with patients not submitted to it. The most frequent species in the samples of the patients who underwent major amputation were, in descending order, Acinetobacter baumannii, Morganella morganii, Pseudomonas aeruginosa and Proteus mirabilis.

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150

Of the 23 variables analyzed in Tables 1 and 2, five were predictive factors associated with increased amputation risk, as observed in Table 3. These were: serum creatinine levels ≥1.3mg/dl, serum hemoglobin levels <11g/dl, rate of reinfection, mortality and isolation of Acinetobacter spp.in the infected ulcers. On the other hand, the multivariate logistic model revealed that major amputation was independently and positively associated with serum hemoglobin levels <11g/dl, serum creatinine levels >1.3mg/dl and growth, in deep tissue cultures,of Acinetobacter spp. and Klebsiella spp.(Table 4). We should note that polymicrobial culture and reinfection were not predictive of major amputation.

DISCUSSION Although diabetic patients have many serious comorbidities, infected ulcer is considered a risk factor for

major amputation7,8. In the studied sample, the isolation of the bacterial genera Klebsiella spp. and Acinetobacter spp. was a predictive factor for major amputation. These bacteria are associated with nosocomial infections and are considered opportunistic pathogens. They cause infection, especially in patients with low immunity or who have undergone invasive procedures, characteristic of the patients studied. In addition, these microorganisms can develop antimicrobial resistance, which makes it difficult to treat the infection and, therefore, may increase the amputation risk12,13. The microbiological profile of the sample studied had a predominance of Gram-negative bacteria. Isolation of Gram-negative bacteria, observed in 66% of deep lesions’ cultures (Wagner Classification ≥3), was also more frequent in a study carried out at the Central Hospital of the São Paulo Holy Home14. In our sample, 86.8% of the patients had bacterial isolation in deep tissue cultures. We thus

Table 3. Univariate analysis of 23 the clinical and bacteriological variables.

Age, by year Gender, male Creatinine ≥ 1.3 mg/dL Hemoglobin < 11 g/dL Positive cultures Polymicrobial cultures Reinfection Rehospitalization Mortality Acinetobacterspp. Citrobacterspp. Escherichia spp. Enterococcusspp. Enterobacterspp. Klebsiellaspp. Morganellaspp. Proteusspp. Pseudomonasspp. Staphylococcusspp. Serratiaspp. Stenotrophomonasspp. Streptococcusspp.

Odds Ratio 1.02 0.70 2.26 0.55 1.06 1.40 2.64 1, 37 2.48 4.15 1.15 0.67 1.79 1.19 4.54 1.91 1.66 0.73 0.46 5.95 1.43 0.70

95% Confidence Interval 0.99-1.05 0.38-1.30 1.25 – 4.09 0.46 – 0.67 0.45-2.51 0.74-2.65 1.29-5.40 0.77-2.47 1.11-5.50 1.71-10.05 0.30-4.41 0.29-1.59 0.80-4.02 0.47-3.01 0.89-23.13 0.91-4.01 0.79-3.47 0.34-1.53 0.19-1.10 0.65-54.26 0.09-23, 19 0.20-2.40

Notes: * p < 0.05; ** p < 0.01; p < 0.001. Rev. Col. Bras. Cir. 2017; 44(2): 147-153

P 0.091 0.260 0.007 * * < 0.001 *** 0.890 0.305 0.008 ** 0.287 0.026 0.002 ** 0.843 0.368 0.156 0.720 0.068 0.086 0.179 0.399 0.081 0.114 0.802 0.566


Cardoso Bacteria generais a risk factor for major amputation in patients with diabetic foot

151

Table 4. Multivariate analysis of the variables associated with major amputation.

Odds Ratio

95% confidence interval

p-value

Creatinine ≥ 1.3 mg/dL

1.23

0.99-1.52

0.053

Hemoglobin < 11 g/dL

20.5

4.30-97.4

< 0.001

Acinetobacterspp.

3.32

1.25-8.77

0.016

Klebsiellaspp.

9.82

0.96-100.7

0.054

observed negative cultures in 13.2% of the patients, probably due to the use of antibacterials prior to the collection of biological material, which occurred with many of our patients previously treated in other health units8. Studies indicate that diabetic foot infections are polymicrobial in nature6,9. In this study, polymicrobial culture was not a risk factor for major amputation, since monomicrobial cultures prevailed (72%). Other authors also observed the predominance of the isolation of only one bacterial species in diabetic foot ulcers deep tissue cultures1,15-17. Some factors may have contributed to obtaining these monomicrobial cultures: 1) In ulcers with a short evolution time, monomicrobial isolation prevails16. In this study, we cannot safely determine the ulcers’evolution time. 2) Patients who use antibacterial agents before collecting the biological sample for culture may have altered results, as treatment-sensitive bacteria are eliminated, persisting antibacterial-resistant bacteria that are then isolated. As previously reported, many patients may have been admitted to the institution after previous antibiotic treatment. Finally, in severe ulcer infections, anaerobic bacteria can be isolated9. The institution’s microbiology laboratory carries out cultures only for facultative anaerobes, and these cultures are mainly required in cases of osteomyelitis. In this sample, we found no records of facultative anaerobes in cultures. In this study, 40 (21.2%) patients presented with ulcer reinfection, which was not a risk factor for major amputation. However, among the patients undergoing amputation, 30.8% had reinfection, where as among the non-amputation patients, the reinfection rate was 14.4% (p=0.007). Reinfected ulcers may display delayed healing, which may increase the risk of limb amputation18.

In addition to the microbiological profile, we identified other factors associated with major amputation. A serum hemoglobin level of less than 11g/dl was one such risk factor. One-fourth of diabetic patients have anemia19. It is believed that the association of anemia with increased amputation is due to decreased tissue oxygenation, which can lead to difficulties in healing and infection control15,20. A serum creatinine level equal to or greater than 1.3mg/dl was also a risk factor for major amputation. Diabetes mellitus is one of the leading causes of chronic kidney disease, which manifests in about 20 to 40% of diabetic patients21. Ulcer healing is prolonged with increased serum creatinine, which increases the risk of amputation22- 24. In this study, patients who underwent major amputation (23.1%) had a higher hospital mortality compared with patients not submitted to amputation (10.8%, p=0.023). The overall hospital mortality was 15.9% and is related to the various comorbidities and complications that these patients present, such as heart disease, coronary disease, cerebrovascular disease, renal failure, respiratory failure and peripheral arterial disease. In this sample, patients with a mean age greater than 60 years and males (64.6%) predominated, but there were no differences regarding the risk of infection in relation to genderor age. Eighty-one (42.9%) patients returned to the institution, most of them due to infectious complications related to the amputation. However, this high rehospitalization rate was not associated with major amputation, though increasing morbidity and costs. Among the limitations of this study are the fact that it is retrospective, the limitation of the laboratory in performing cultures for strict anaerobes

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Cardoso Bacteria generais a risk factor for major amputation in patients with diabetic foot

and the collection of material for culture in patients possibly using antibacterials prior to hospitalization. In conclusion, the bacterial genera Acinetobacter spp. and Klebsiella spp. identified in infected ulcers of patients with diabetic foot were

associated with major amputation. In addition, serum creatinine levels ≥1.3mg/dl and hemoglobin <11g/dl were also risk factors for major amputation. Nevertheless, polymicrobial cultures and ulcerreinfection did not influence the level of amputation.

R E S U M O Objetivo: avaliar se gênero bacteriano é fator de risco para amputação maior em pacientes com pé diabético e úlcera infectada. Método: estudo observacional do tipo caso-controle de 189 pacientes com úlcera infectada em pé diabético admitidos pelo Serviço de Cirurgia Vascular do Hospital Risoleta Tolentino Neves, no período de janeiro de 2007 a dezembro de 2012. A avaliação bacteriológica foi realizada em cultura de tecido profundo das lesões e a amputação foi considerada como maior quando realizada acima do médio tarso do pé. Resultados: a média de idade dos pacientes foi 61,9±12,7 anos e 122 (64,6%) eram homens. As culturas foram positivas em 86,8%, sendo monomicrobianas em 72% dos casos. Nos pacientes com amputação maior, os gêneros de bactérias mais frequentes foram Acinetobacter spp. (24,4%), Morganella spp. (24,4%), Proteus spp. (23,1%) e Enterococcus spp. (19,2%) e as espécies mais isoladas foram Acinetobacter baumannii, Morganella morganii, Pseudomonas aeruginosa e Proteus mirabilis. Identificou-se como fatores preditivos para amputação maior o isolamento dos gêneros Acinetobacter spp. e Klebsiella spp.,e níveis séricos de creatinina ≥1,3mg/dl e de hemoglobina <11g/dl. Conclusão: os gêneros bacterianos Acinetobacter spp. e Klebsiella spp. identificados nas úlceras infectadas dos pacientes com pé diabético associaram-se a maior incidência de amputação maior. Descritores: Pé Diabético. Úlcera do Pé. Infecção. Amputação.

REFERENCES

1. Hadadi A, Omdeh Ghiasi H, Hajiabdolbaghi M, Zandekarimi M, Hamidian R. Diabetic foot: infections and outcomes in Iranian admitted patients. Jundishapur J Microbiol. 2014;7(7):e11680. 2. Martins-Mendes D, Monteiro-Soares M, Boyko EJ, Ribeiro M, Barata P, Lima J, et al. The independent contribution of diabetic foot ulcer on lower extremity amputation and mortality risk. J Diabetes Complications. 2014;28(5):632-8. 3. International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Brussels, Belgium: International Diabetes Federation; 2015. 4. Amaral Júnior AH, Amaral LAH, Bastos MG, Nascimento LC, Alves MJM, Andrade MAP. Prevention of lower-limb lesions and reduction of morbidity in diabetic patients. Rev bras ortop. 2014;49(5):482-7. 5. Hingorani A, LaMuraglia GM, Henke P, Meissner MH, Loretz L, Zinszer KM, et al. The management of diabetic foot: A clinical practice guideline by the Society for Vascular Surgery in collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg. 2016;63(2 Suppl):3s-21s. 6. Spichler A, Hurwitz BL, Armstrong DG, Lipsky BA. Microbiology of diabetic foot infections: from Louis

Pasteur to ‘crime scene investigation’. BMC Med. 2015;13:2. 7. Mills JL, Sr., Conte MS, Armstrong DG, Pomposelli FB, Schanzer A, Sidawy AN, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg. 2014;59(1):220-34.e1-2. 8. Turhan V, Mutluoglu M, Acar A, Hatipoglu M, Onem Y, Uzun G, et al. Increasing incidence of Gram-negative organisms in bacterial agents isolated from diabetic foot ulcers. J Infect Dev Ctries. 2013;7(10):707-12. 9. Akhi MT, Ghotaslou R, Asgharzadeh M, Varshochi M, Pirzadeh T, Memar MY, et al. Bacterial etiology and antibiotic susceptibility pattern of diabetic foot infections in Tabriz, Iran. GMS Hyg Infect Control. 2015;10:Doc02. 10. Perim MC, Borges Jda C, Celeste SR, Orsolin Ede F, Mendes RR, Mendes GO, et al. Aerobic bacterial profile and antibiotic resistance in patients with diabetic foot infections. Rev Soc Bras Med Trop. 2015;48(5):546-54. 11. Lipsky BA, Aragon-Sanchez J, Diggle M, Embil J, Kono S, Lavery L, et al. IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev. 2016;32 Suppl 1:45-74.

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12. Martins AF, Barth AL. Acinetobacter multirresistente – um desafio para a saúde pública. Sci Med. 2013;23(1):56-62. 13. Scarpate ECB, Cossatis JJ. A presença da Klebsiella pneumoniae produtora de ß-lactamase de espectro estendido no ambiente hospitalar. Saúde & Ambiente em Revista. 2009;4(1):1-11. 14. Ohki AV, Galvão RC, Marques CG, Santos VP, Casteli Júnior V, Caffaro RA. Perfil microbiológico nas infecções profundas do pé diabético. Arq Med Hosp Fac Ciênc Med Santa Casa São Paulo. 2010;55(1):15-7. 15. Aziz Z, Lin WK, Nather A, Huak CY. Predictive factors for lower extremity amputations in diabetic foot infections. Diabet Foot Ankle. 2011;2. 16. Banu A, Noorul Hassan MM, Rajkumar J, Srinivasa S. Spectrum of bacteria associated with diabetic foot ulcer and biofilm formation: A prospective study. Australas Med J. 2015;8(9):280-5. 17. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132-73. 18. Garcia-Morales E, Lazaro-Martinez JL, Aragon-Sanchez J, Cecilia-Matilla A, Garcia-Alvarez Y, Beneit-Montesinos JV. Surgical complications associated with primary closure in patients with diabetic foot osteomyelitis. Diabet Foot Ankle. 2012;3. 19. He BB, Xu M, Wei L, Gu YJ, Han JF, Liu YX, et al. Relationship between Anemia and Chronic Com-

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plications in Chinese Patients with Type 2 Diabetes Mellitus. Arch Iran Med. 2015;18(5):277-83. Desormais I, Aboyans V, Bura A, Constans J, Cambou JP, Messas E, et al. Anemia, an independent predictive factor for amputation and mortality in patients hospitalized for peripheral artery disease. Eur J Vasc Endovasc Surg. 2014;48(2):202-7. Abreu KC, Motta EAP, Lima GO. Prevalência dos fatores de risco em pacientes com nefropatia diabética atendidos em um centro de referência em nefrologia do estado do Maranhão. Rev Ciênc Saúde. 2014;16(2). Akha O, Kashi Z, Makhlough A. Correlation between amputation of diabetic foot and nephropathy. Iran J Kidney Dis. 2010;4(1):27-31. Shojaiefard A, Khorgami Z, Larijani B. Independent risk factors for amputation in diabetic foot. Int J Diabetes Dev Ctries. 2008;28(2):32-7. Brasileiro JL, Oliveira WTP, Monteiro LB, Chen J, Pinho Jr EL, Molkenthin S, et al. Pé diabético: aspectos clínicos. J Vasc Br. 2005;4(1):11-21.

Received in: 01/10/2016 Accepted for publication: 01/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Natália Anício Cardoso E-mail: natyanicio@hotmail.com

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DOI: 10.1590/0100-69912017002008

Original Article

Customized acrylic implants for reconstruction of extensive skull defects: an exception approach for selected patients Implantes de acrílico customizados para a reconstrução de defeitos extensos da calota craniana: uma abordagem de exceção para pacientes selecionados Rafael Denadai Pigozzi da Silva, AsCBC-SP1; Cesar Augusto Raposo-Amaral1; Marcelo Campos Guidi1; Cassio Eduardo Raposo-Amaral1; Celso Luiz Buzzo1. A B S T R A C T Objective: to present our experience in the surgical treatment of extensive skullcap defects with customized acrylic implants. Methods: we conducted a retrospective analysis of patients with extensive skull defects undergoing acrylic cranioplasties between 2004 and 2013. We carefully selected all patients and classified surgical results based on three scales (craniofacial esthetics, improvement of facial symmetry and need for additional surgery). Results: fifteen patients underwent cranioplasty with intraoperative acrylic implants, whether manually customized (46.67%) or made with prototyped three-dimensional biomodels (53.33%). There were two (13.33%) complications (one infection with implant withdrawal and one seroma). We considered the craniofacial aesthetics excellent (50%), the degree of improvement of craniofacial symmetry satisfactory (57.14%), and the overall mean of surgical results according to the need for new surgeries was 1.5±0.52. Conclusion: cranioplasties of patients with extensive skullcap defects should obey careful and predetermined criteria, both for selection and for the acrylic implant customization method. Keywords: Craniofacial Abnormalities. Acrylic Resins. Surgery, Plastic

INTRODUCTION

I

n the mid-1960s, Dr. Paul Tessier, the father of modern craniofacial surgery, revolutionized the surgical approach to craniofacial deformities by introducing new surgical concepts and techniques1. Since then, breakthroughs have been consistently established in the Craniofacial surgery field, and the principles founded by Dr. Tessier continue to be the standard in craniofacial care1. Among the innumerable principles described by him, there is the graft of the cranial bone for craniofacial reconstruction2. The mechanical, immunological and Techniques of autologous cranial grafts detailed in a series of seminal articles by Tessier et al.2,3 clearly state that this should be the standard material for craniofacial reconstructions, including in cranioplasties for congenital or acquired (oncological exertion, trauma or infection) skullcap defects. Thus, the vast majority of patients have been reconstructed with autogenous tissues (particu-

larly, bone grafts) in our and other centers3-8. However, the reconstructive approach of a portion of patients with extensive skullcap defects has been a major challenge for plastic surgeons working in the field of reconstructive surgery, as it often requires a large amount of tissue/material and complex surgical procedures soas to achieve the functional and aesthetic goals9,10. In this particular group of patients, alloplastic implants may be a therapeutic option, although none of the described materials have the same success rate or predictability of the cranial autogenous bone3-11. Moreover, it is important to emphasize that even with proper planning and follow-up, the inclusion of any alloplastic material is associated with numerous complications9,12-17. Therefore, considering the risks inherent to the use of alloplastic materials, such conduct should be considered as the exception approach in the scope of craniofacial reconstructions, and should be applied only in a restricted and well selected portion of patients9,12-17.

1 - SOBRAPAR Hospital, Institute of Craniofacial Plastic Surgery, Campinas, Sao Paulo State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 154-162


Silva Customized acrylic implants for reconstruction of extensive skull defects: an exception approach for selected patients

Therefore, the objective of the present study was to present the experience of a Brazilian craniofacial plastic surgery institution in the surgical reconstruction of extensive skullcap defects with customized acrylic implants, emphasizing that this should be an exception conduct, and highlighting the importance of patients’ selection, as well as the risks associated with the use of alloplastic materials.

METHODS This was a retrospective observational study of all patients with extensive skullcap defects treated surgically at the SOBRAPAR Hospital between January 2004 and March 2015. We included only patients submitted to cranioplasty with acrylic implants by the same group of plastic surgeons who were not lost topostoperative follow-up (minimum of 12 months). We collected demographic, clinical, and surgical data through medical records, photographs, cranial computed tomography (CT) with three-dimensional reconstruction (3D), 3D prototypes of the craniofacial skeleton (when available) and clinical consultations with all patients included. The study was approved by the Ethics in Research Committee of the SOBRAPAR Hospital (002/15), and is in accordance with the Helsinki Declaration of 1975, perfected in 1983. Surgical approach In our center, only a particular and restricted group of carefully selected patients has been reconstructed with non-autogenous material. Thus, acrylic cranioplasty has been an exception course and is indicated only in patients with extensive skullcap defects (defined as defects greater than 25cm2)8,1820 , primarily to adequately protect the brain and secondarily to restore the curvature/craniofacial aesthetics. For this, we carefully assessed all patients with cranial bone defects through history (defect etiology, history of trauma, radiation and/or previous interventions) and physical examination (location and size of defects and quality of surrounding tissues). The soft parts (scalp) should provide adequate coverage for the implants; Portions of scar tissue

155

(“thin and contracted tissues”) were excised with or without tissue expansion. Incomplete craniofacial growth21 and the presence of infection (active or recent), hydrocephalus, cerebral edema and/or allergy to acrylic components were contraindication criteria for such an approach. Customization of implants We customized the acrylic implants manually or with the help of a 3D biomodel prototype. The choice between the customization methods has been based on: a) the size of the defects8,18-20 (defects >25cm2 and >200cm2 have been preferably reconstructed with implants obtained manually and with the aid of 3D technology, respectively); and b) the preferences of the surgical team and of the patients/families, who received all the explanations about the differences and similarities of each method (detailed in the sequence). In-situ customization Initially, the powder (copolymer) and liquid (monomer) components were mixed at a ratio of approximately 2:1 with sterile vaseline. The mixture with a soft moldable consistency was poured over the defect of the skullcap and the implant was then cast in situ with a metal spatula, looking for an implant with smooth surface, adequate curvature and implantdefect fitting without movements. The process of implant hardening was accompanied by heat release (exothermic polymerization). In order to attenuate thermal effects to the surrounding tissues during polymerization, we take a few precautionary steps: 1) we carefully arranged a wet gelfoam interface and sterile glove (or sterile plastic bag) between the alloplastic and the bone collar and the underlying dura mater; 2) we continuously irrigated the alloplastic with cooled saline throughout the process. Once solid, the implant surfaces were carefully abraded it to mimic the contours of a normal skullcap. Prototyping-based customization The 3D biomodels used for implants customization were prototyped by the Renato Archer Center for Information Technology (CTI – http://www. cti.gov.br)22. In summary, craniofacial tomographic

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Silva Customized acrylic implants for reconstruction of extensive skull defects: an exception approach for selected patients

Figure 2. 3D Biomodel and implant fixed in the skullcap.

Figure 1. Craniofacial computed tomography with three-dimensional reconstruction: (Above) extensive skullcap defect and (Below) customized implant.

images in the DICOM format were processed with specific software (InVesalius and Rhinoceros) and transformed into Standard Triangulation Language (STL) format, creating the 3D virtual model of the craniofacial skeleton with the bone defect and the personalized implant (Figures 1 and 2). Subsequently, a physical replicate (3D biomodel of the craniofacial skeleton with the defect of the skullcap and the respective implant) was created with polyamide, by rapid prototyping. The 3D biomodel was then sent free of charge to our center. We use the 3D biomodel as a positive mold to make a negative silicone rubber or alginate mold. The soft and moldable consistency blend (detailed above) was then poured into the negative mold. The positive mold was pressed onto the alloplastic to obtain the proper thickness. Finally, if necessary, we abraded the surfaces/edges to allow proper fitting of the implant in the 3D biomodel. Thus, we obtained an acrylic implant with exactly the same morphology as the positive template (prototyped implant). The implant was then sterilized in ethylene oxide. Recently, CTI has also shipped the custom acrylic implant. Thus, the donor implant is sterilized in ethylene oxide and used in the patient, without the need to be customized in our center.

Surgical interventions By means of coronal access (always distant from the cranial defect), subgaleal detachment and elevation of the periosteal flap, we carefully exposed the defect of the skullcap so as not to damage the dura mater. In the event of exposure / involvement of the frontal sinus, were performed cranialization, obliteration of the frontonasal duct and coverage with a pericranial flap. This was followed by the in-situ customization or fitting of the prototypebased implant. We then attached the implant to the bone margins with steel wires or metal screws. We proceeded with periosteal flap coverage, closure and tubular drainage. All patients received antibiotics for at least seven days and regular postoperative evaluation. Evaluation of surgical results A single plastic surgeon, who had no prior contact with the patients, evaluated the surgical results of the individuals who did not have the acrylic implants removed during the postoperative followup. For this, we used craniofacial photographs took by a professional photographer in a professional studio with three flashes. We classified preoperative and postoperative (12 months) photographs of all patients according to three previously published scales23-25: 1) Craniofacial aesthetics: excellent, good, regular or poor23. 2) Degree of improvement of craniofacial symmetry24: satisfactory result, craniofacial symmetry; partially satisfactoryresult, global improvement of craniofacial symmetry, however craniofacial asymmetry can still be detected; or unsatisfactory result, absence of noticeable improvement of the craniofacial symmetry after the surgical interventions. 3) Need for additional cranial surgery25: category I, does not require surgical revision; Category II, requires minor surgical revisions of the cranial contour; Category III, requires extensive surgeries (surgical

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157

Table 1. Distribution of patients (n=15) undergoing cranioplasties for reconstruction of skullcap defects.

Acrylic custom implants

* Age (years) M±SD

Male/Female n (%)

Cranioplasty Indication n (%) Congenital Tumor

Seizure ** (Yes/No) n (%)

Trauma

Manual (n=7) (85.71) 6/1 (14.29) 26±12.29 1 (14.29) 1(14.29) 5 (71.43) 1(14.29)/6(85.71) 3D Biomodel 7 (87.5)/1 (12.5) (n=8) Total (n=15)

13 (88.67)/2 (13.33)

29±9.23

2 (25)

27.6±10.47 3 (20)

-

6 (75)

Prior Cranioplasty Attempt (Yes/No) n (%)

VPS (Yes/No) n (%)

Local infection*** (Yes/No) n (%)

Size of the defects

-/7 (100)

1(14.29)/6(85.71) 1(14.29)¥/6(85.71) >25cm2

3(37.5) / 5(62.5)

2 (25) / 6 (62.5)

- / 8 (100)

1(12.5)¥¥/7(87.5) >200cm2

4 (33.33)/11

2(13.33)/13(88.67)

1 (6.67) / 14

2(13.33)/13(88.67) >25cm2

1 (6.67) 11(73.33)

3D, three-dimensional; n, number of patients; Ventricle-peritoneal shunt VPS; *, at the time of the cranioplasties; **, all receiving anticonvulsant therapy; ***, previously treated (>6 months of first clinic visit in our Center); ¥, cranioplasty with acrylic with unsatisfactory result 15 years before the cranioplasty held in our Centre (old acrylic removed intraoperatively); ¥¥, cranioplasty held with particulate bone that was reabsorbed (11 months before the cranioplasty held in our Center); -, missing.

intervention less than the main surgery); or Category IV, requires a complete new surgical intervention, similar to the main surgery. All data was compiled in Excel for Windows (Microsoft Corporation, USA). For the descriptive analysis, we used the mean for metric variables and the percentages for categorical ones.

an average follow-up of 7.89±2.47 years (2.4 to 11), there were no cerebrospinal fistulas, subcutaneous or extradural hematomas, implant migration, and/or new neurological deficits. In one (6.67%) patient, there was a need to remove the implant after infection and in another (6.67%) a postoperative seroma occurred (Table 2). Excluding the patient (6.67%) submitted to acrylic removal, we obtained an excellent craniofacial aesthetic appearance in seven (50%) of the 14 remaining patients. The degree of craniofacial symmetry improvement was considered satisfactory (eight patients – 57.14%) or partially satisfactory (six cases – 42.86%) and the overall mean of the surgical results classified according to the need for new surgeries was 1.5±0.52, between categories I and II (Figures 3 and 4 and Table 3). In this series, there

RESULTS We included fifteen patients submitted to cranioplasties with acrylic implants (Table 1). All had cranial contour asymmetry. We performed 15 cranioplasties for the reconstruction of extensive skullcap defects (greater than 25 cm2), seven (46.67%) with manually modified acrylic implants and eight (53.33%) with prototyped 3D biomodels (Table 2). At

Table 2. Distribution of aspects related to the cranioplasties carried out for reconstruction of extensive skullcap defects (n=15).

Acrylic custom implants

Anatomic location of cranioplasty n (%) Left Frontal Right Left Right Fronto- Left Frontal* + Fronto- FrontoFrontal** temporo- Temporal Occipital parietal** parietal** parietal

Manual (n=7) 3 (42.86) 3D Biomodel (n=8)

-

1 (14.29) 1 (14.29) 1 (14.29)

5 (62.5) 1 (12.5) 1 (12.5)

-

-

1 (12.5)

Surgical Time (H) M ± SD

Transfusion (Yes/No) n (%)

Postoperative complications n (%)

Hospitalization Postop Time Follow-up Infection (D) (Y) + M±SD M±SD Seroma Implant removed

1 (14.29) 2.07±0.53 1(14.29) / 6(85.71) 1.57±0.53 -

2.63±0.92 1(12.5) / 7 (87.5)

Total (n=15) 8 (53.33%) 1 (6.67) 2 (13.33) 1 (6.67) 1 (6.67) 1 (6.67) 1 (6.67) 2.37±0.79 2 (13.33) / 13

-

1 (14.29) 8±1.15

2±0.76

1 (6.67)

-

5.93±2.95

1.8±0.68

1 (6.67) 1 (6.67) 6.89±2.47

3D, three-dimensional; H, hour; D, days; Y, years; *, extensive commitment, with medial involvement; **, No medial commitment; -, absent. Rev. Col. Bras. Cir. 2017; 44(2): 154-162


Silva Customized acrylic implants for reconstruction of extensive skull defects: an exception approach for selected patients

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Table 3. Distribution of surgical results according to surgical interventions (n=14).

Acrylic custom implants Surgical results

Total (n=14) n (%)

Manual (n=7) n (%)

3D Biomodel (n=7) n (%)

Excellent

4 (57.14)

3 (42.86)

7 (50)

Good

2 (28.57)

3 (42.86)

5 (35.71)

Regular

1 (14.29)

1 (14.29)

2 (14.29)

-

-

-

Satisfactory result

4 (57.14)

4 (57.14)

8 (57.14)

Partially satisfactory result

3 (42.86)

3 (42.86)

6 (42.86)

-

-

-

Category I

4 (57.14)

3 (42.86)

7 (50)

Category II

3 (42.86)

4 (57.14)

7 (50)

Category III

-

-

-

Category IV

-

-

-

Total (M±Sd)

1.43 ± 0.53

1.57 ± 0.53

1.5 ± 0.52

Craniofacial esthetic26

Poor Improvement of craniofacial symmetry28

Unsatisfactory result Need for additional surgery

29

n, number of patients; M, mean; SD, standard deviation; 3D, three-dimensional; *, one patient had the implant removed postoperatively (infection); -, absent.

was no poor, unsatisfactory result, category III and/ or category IV according to the previously published scales23-25.

DISCUSSION Cranioplasty has been routinely applied in craniofacial plastic surgery centers to reverse the physiological status after craniectomies (trepanate syndrome), to protect brain structures and to improve the craniofacial contour of patients with defects in the skullcap. In the literature, numerous factors (medical history, location and size of defects and reconstruction material) have been relevant in the scope of cranioplasties9,10,17,19. It is immense the variety of organic (autografts, allografts and xenografts), synthetic organic (hydroxyapatite) and inorganic (acrylic, silicone, porous polyethylene, titanium mesh, among others)11 materials that has been applied in the reconstruction of such defects9,10,17, with different success rates4,7,9,10,12-17,19,20,23,26.

By direct influence of Dr. Tessier, Prof. Dr. Cassio Menezes Raposo do Amaral (founder of the SOBRAPAR Hospital) established that the tissue substitutions based on autogenous tissues should guide the surgical treatments performed at our center. In addition, as members of a plastic surgery training center, the “replace like with like” principle of Dr. D. Ralph Millard Jr has been systematically passed on to all training residents. Thus, over the last 37 years, as defenders of these concepts, we have routinely reconstructed the skullcap bony defects with bone grafts obtained from the skullcap according to Dr. Tessier2,3. Other centers also support the reconstructive approaches of cranial defects with autogenous tissues, specifically obtained from the skullcap4,5,7,8. Although the autogenous bone graft remains the gold standard for surgical reconstruction of most craniofacial bone defects2,3-5,7-11, a specific portion of patients, such as those included in the present study, have been reconstructed with alloplastics12-17,19,20,23,27. To date, there is no ideal alternative material9,10,17 and there are characteristics that have been considered

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Figure 3. Before and after implant cranioplasty.

relevant in the choice of non-autogenous materials: 1) availability, 2) biocompatibility with surrounding tissue, 3) cranial contour, 4) easy molding, 5) sufficient strength to protect the intracranial content, 6) low likelihood of resorption, and 7) radiolucency (compatible with imaging tests)9,10,17. As acrylic implants are inert, easily available, inexpensive, radiolucent and resistant to absorption9,10,13,20, like other groups13,14,20, we prefer this material among the non-autogenous ones for reconstructions of extensive cranial defects, always respecting well-defined criteria for patient selection and follow-up. Due to the lack of osseointegration, we and 9,10 others believe that acrylic should not be used in patients without established skeletal growth, although there are experiments20 on the temporary use of acrylic based on the difficulty of bipartising the skullcap. However, this concept has recently been â&#x20AC;&#x153;demystifiedâ&#x20AC;?28 and cranial bony grafts can be obtained in children under three years of age. In this context, different investigations9,12-17 have revealed numerous complications with this material. Infection has been the most commonly reported complication in acrylic cranioplasties, ranging from 3% to 20%9,12-17. Numerous analyzes12,14-16 defined the factors associated with infections, including cranioplasty failure (implant removal), frontal and orbital defects with

Figure 4. Before and after implant cranioplasty.

frontal sinus involvement, extensive brain resections and the presence of ventriculoperitoneal shunt. Therefore, all these factors should be carefully investigated in the preoperative period, allowing adequate selection and preparation of patients12,14-16. However, although it is possible to achieve low infection rates in cranioplasties with acrylic implants as long as patients are carefully selected12,14-16, it is important to mention that since this material will never be integrated into the skullcap, there is a potential risk of infection and exposure at any time during the postoperative follow-up7. In addition, implants have been removed during infection, as described in our and other experiments7,14,20. Thus, patients with satisfactory results may present infection with extrusion, requiring implant removal, with complete loss of the obtained initiallyresult. Such risk, inherent in the use of alloplastics, should be carefully pondered in the preoperative period and the patient/family members should be adequately oriented regarding the risk of complications, even after a long postoperative period.

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Still within the scope of acrylic cranioplasties, the implants can be customized with or without the aid of prototyped 3D biomodels, as reported here. Cranioplasties with acrylic implants customized in situ have disadvantages, such as the need for intraoperative time to prepare the mixture, mold the implant and wait for hardening, as well as the risks of local thermal injury13. Cranioplasties with prototyped acrylic implants have also been reported by different groups14. It is undeniable that computer-aided design and computer-aided manufacturing (CADCAM) technology developed in recent decades has increased the armamentarium of the plastic surgeon who deals with complex defects and deformities of the craniofacial skeleton27. We have used the 3D biomodels prototyped by the CTI for the preoperative simulation and training of residents in the monobloc frontofacial advancement craniofacial surgeries and facial bipartition surgeries. We have also defined the accuracy of the reproducibility of craniofacial skeletal measurements in the 3D biomodels prototyped by the CTI29. Such a method undoubtedly has multiple advantages, such as a shorter operative time related to the manipulation of the implant and the absence of local thermal effects13. However, cost increases as the technology is incorporated into the therapeutic process13,27. Although the overall costs have been reduced with the 3D biomodel donation by CTI29, there is a potential increase in time between the indication of cranioplasty and its realization, as delays can occur in the many stages of the 3D biomodel manufacturing process. For example, because the quality of prototy-

ping is dependent on tomographic images with 1mm slices and with good quality13,27, in the Brazilian Unified Health System (SUS) that has waiting queues for these tests and that lacks quality tomography scanners available in all services, it is not uncommon to find poor quality exams without adequate standardization and delays in performing and delivering CT scans. In this series of carefully selected patients, we obtained an overall improvement of aesthetics and craniofacial symmetry with both methods of implant customization, following the trends reported by other groups13,14,19,23. In addition, our patients were classified, on average, between categories I and II and, therefore, required minor surgical revisions of the craniofacial contour, as previously reported14. We must be careful about the influence that the industry has had on publications related to the technology used in bone substitutes, as pointed out by Rogers and Greene11. It is important to emphasize that the results obtained in the present study were limited to one restricted portion of carefully selected patients and therefore should not be extrapolated to other bone defects, in which reconstructions with the skullcap grafts remain the gold standard1-3,30. In this retrospective study, we presented the surgical approach of patients with extensive cranial defects, based on our 11-year experience. According to the surgical results presented and discussed, the cranioplasties for these patients should be carefully indicated, obeying predetermined criteria for patient selection and customization of the acrylic implant.

R E S U M O Objetivo: apresentar nossa experiência no tratamento cirúrgico dos defeitos extensos da calota craniana com implantes de acrílico customizados. Métodos: análise retrospectiva de pacientes com defeitos extensos da calota craniana submetidos à cranioplastias com acrílico entre 2004 e 2013. Todos os pacientes foram criteriosamente selecionados e os resultados cirúrgicos foram classificados com base em três escalas (estética craniofacial, melhora da simetria facial e necessidade de cirurgia adicional). Resultados: Quinze pacientes foram submetidos à cranioplastia com implantes de acrílico customizados manualmente no intraoperatório (46,67%) e confeccionados com base em biomodelos tridimensionais prototipados (53,33%). Mesmo respeitando critérios de seleção, houve duas (13,33%) complicações (infecção com retirada do implante e seroma). A estética craniofacial foi considerada excelente (50%), o grau de melhora da simetria craniofacial foi considerado satisfatório (57,14%) e a média global dos resultados cirúrgicos de acordo com a necessidade de novas cirurgias foi 1,5±0,52. Conclusão: as cranioplastias dos pacientes com defeitos da calota craniana extensos devem ser criteriosamente indicadas, obedecendo a critérios pré-determinados de seleção dos pacientes, bem como, do método de customização do implante de acrílico. Descritores: Anormalidades Craniofaciais. Polimetil Metacrilato. Cirurgia Plástica

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Silva Customized acrylic implants for reconstruction of extensive skull defects: an exception approach for selected patients

REFERENCES

1. Wolfe SA. Paul Tessier, creator of a new surgical specialty, is recipient of Jacobson Innovation Award. J Craniofac Surg. 2001;12(1):98-9. 2. Tessier P. Autogenous bone grafts taken from the calvarium for facial and cranial applications. Clin Plast Surg. 1982;9(4):531-8. 3. Tessier P, Kawamoto H, Posnick J, Raulo Y, Tulasne JF, Wolfe SA. Taking calvarial grafts, either split in situ or splitting of the parietal bone flap ex vivo-tools and techniques: V. A 9650-case experience in craniofacial and maxillofacial surgery. Plast Reconstr Surg. 2005;116(5 Suppl):54S-71S; discussion 92S-4S. 4. Lee HJ, Choi JW, Chung IW. Secondary skull reconstruction with autogenous split calvarial bone grafts versus nonautogenous materials. J Craniofac Surg. 2014;25(4):1337-40. 5. Chang TJ, Choi JW, Ra YS, Hong SH, Cho YH, Koh KS. Changes in graft thickness after skull defect reconstruction with autogenous split calvarial bone graft. J Craniofac Surg. 2014;25(4):1241-4. 6. Kumar AR, Tantawi D, Armonda R, Valerio I. Advanced cranial reconstruction using intracranial free flaps and cranial bone grafts: an algorithmic approach developed from the modern battlefield. Plast Reconstr Surg. 2012;130(5):1101-9. 7. Sahoo N, Roy ID, Desai AP, Gupta V. Comparative evaluation of autogenous calvarial bone graft and alloplastic materials for secondary reconstruction of cranial defects. J Craniofac Surg. 2010;21(1):79-82. 8. Zins JE, Langevin CJ, Nasir S. Controversies in skull reconstruction. J Craniofac Surg. 2010;21(6):1755-60. 9. Shah AM, Jung H, Skirboll S. Materials used in cranioplasty: a history and analysis. Neurosurg Focus. 2014;36(4):E19. 10. Goldstein JA, Paliga JT, Bartlett SP. Cranioplasty: indications and advances. Curr Opin Otolaryngol Head Neck Surg. 2013;21(4):400-9. 11. Rogers GF, Greene AK. Autogenous bone graft: basic science and clinical implications. J Craniofac Surg. 2012;23(1):323-7. 12. Reddy S, Khalifian S, Flores JM, Bellamy J, Manson PN, Rodriguez ED, Dorafshar AH. Clinical

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outcomes in cranioplasty: risk factors and choice of reconstructive material. Plast Reconstr Surg. 2014;133(4):864-73. Jaberi J, Gambrell K, Tiwana P, Madden C, Finn R. Long-term clinical outcome analysis of poly-methyl-methacrylate cranioplasty for large skull defects. J Oral Maxillofac Surg. 2013;71(2):e81-8. Kumar AR, Bradley JP, Harshbarger R, Stevens F, Bell R, Moores L, Armonda R. Warfare-related craniectomy defect reconstruction: early success using custom alloplast implants. Plast Reconstr Surg. 2011;127(3):1279-87. De Bonis P, Frassanito P, Mangiola A, Nucci CG, Anile C, Pompucci A. Cranial repair: how complicate disfilling a â&#x20AC;&#x153;holeâ&#x20AC;?? J Neurotrauma. 2012;29(6):1071-6. Gooch MR, Gin GE, Kenning TJ, German JW. Complications of cranioplasty following decompressive craniectomy: analysis of 62 cases. Neurosurg Focus. 2009;26(6):E9. Neovius E, Engstrand T. Craniofacial reconstruction with bone and biomaterials: review over the last 11 years. J Plast Reconstr Aesthet Surg. 2010;63(10):1615-23. Uygur S, Eryilmaz T, Cukurluoglu O, Ozmen S, Yavuzer R. Management of cranial bone defects: a reconstructive algorithm according to defect size. J Craniofac Surg. 2013;24(5):1606-9. Marchac D, Greensmith A. Long-term experience with methylmethacrylate cranioplasty in craniofacial surgery. J Plast Reconstr Aesthet Surg. 2008;61(7):744-52; discussion 753. Raposo-Amaral CE, Raposo-Amaral CA. Changing face of cleft care: specialized centers in developing countries. J Craniofac Surg. 2012;23(1):206-9. Raposo-Amaral CE, Denadai R, Camargo DN, Artioli TO, Gelmini Y, Buzzo CL, et al. Parry-Romberg syndrome: severity of the deformity does not correlate with quality of life. Aesthetic Plast Surg. 2013;37(4):792-801. da Silva JV, Martins TA, Noritomi PY. Scaffold informatics and biomimetic design: three-dimensional medical reconstruction. Methods Mol Biol. 2012;868:91-109. Marbacher S, Andereggen L, Erhardt S, Fathi

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AR, Fandino J, Raabe A, Beck J. Intraoperative template-molded bone flap reconstruction for patient-specific cranioplasty. Neurosurg Rev. 2012;35(4):527-35; discussion 535. Xie Y, Li Q, Zheng D, Lei H, Pu LL. Correction of hemifacial atrophy with autologous fat transplantation. Ann Plast Surg. 2007;59(6):645-53. Denadai R, Raposo-Amaral CA, Marques FF, Ghizoni E, Buzzo CL, Raposo-Amaral CE. Strategies for the optimal individualized surgical management of craniofacial fibrous dysplasia. Ann Plast Surg. 2016;77(2):195-200. Moreira-Gonzalez A, Jackson IT, Miyawaki T, Barakat K, DiNick V. Clinical outcome in cranioplasty: critical review in long-term follow-up. J Craniofac Surg. 2003;14(2):144-53. Gerstle TL, Ibrahim AM, Kim PS, Lee BT, Lin SJ. A plastic surgery application in evolution: three-dimensional printing. Plast Reconstr Surg. 2014;133(2):446-51. Vercler CJ, Sugg KB, Buchman SR. Split cranial bone grafting in children younger than 3 years

old: debunking a surgical myth. Plast Reconstr Surg. 2014;133(6):822e-827e. 29. Almeida AB, Raposo-do-Amaral CE, Ferreira DM, Hotta L, Raposo-do-Amaral CA, Silva JVL, et al. Modelo tridimensional do esqueleto craniofacial: precisĂŁo de uma ferramenta para o planejamento cirĂşrgico. Rev Bras Cir Craniomaxilofac. 2009;12(1):5-9. 30. Wolfe SA. Frontal cranioplasty: risk factors and choice of cranial vault reconstructive material. Plast Reconstr Surg. 1986;77(6):901-4.

Received in: 16/10/2016 Accepted for publication: 18/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Rafael Denadai Pigozzi da Silva E-mail: denadai.rafael@hotmail.com rdenadaip@hotmail.com

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DOI: 10.1590/0100-69912017002010

Original Article

Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases Carcinoma ductal invasor: relação de características anatomopatológicas com a presença de metástases axilares em 220 casos Ranniere Gurgel Furtado de Aquino1,3; Paulo Henrique Diógenes Vasques, TCBC-CE1; Diane Isabelle Magno Cavalcante2; Ayane Layne de Sousa Oliveira3; Bruno Masato Kitagawa de Oliveira4; Luiz Gonzaga Porto Pinheiro, ECBC-CE5. A B S T R A C T Objective: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma. Methods: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-BloomRichadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases. Results: the mean patients’age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001). Conclusion: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases. Keywords: Breast Neoplasms. Lymphatic Metastasis. Pathology, Surgical. Neoplasm Grading.

INTRODUCTION

B

reast cancer is the most common malignant neoplasm in the world and still accounts for a number of unfavorable outcomes that make it the second leading cause of cancer death in women1. The variety of outcomes observed in clinical practice demonstrates that the biological behavior of this disease can still be uncertain and often does not depend on the type of treatment offered to the patient, which indicates that the mechanisms involved in this process are not fully known. Morphological, genetic and enzymatic methods allow us to evaluate its degree of aggressiveness and are routinely used satisfactorily2,3. Anatomopathological analysis, due to its simplicity, speed and low-cost, is still widely used for its reliability

even in the face of current molecular and genetic approaches4. The tumor histological grade (HG) is one of the most important anatomopathological features. The Nottingham classification system, which is a modification of the Scarff-Bloom-Richardson (SBR)5,6 one, is the most commonly used classification system to determine HG in breast cancer7. In 1991, its prognostic value was demonstrated for the first time5, and since then several studies have validated it, which has made it a recommended classification system worldwide8,9. In breast cancer, HG indicates the degree of tumor tissue differentiation, established through a semiquantitative evaluation of the tumor’s morphological characteristics: tubular grade (TG), pleomorphism or nuclear grade (NG), and Number of mitoses per large increase field – mitotic index (MI)5.

1 - Federal University of Ceará (UFC), Post-graduation Program in Surgery, Fortaleza, Ceara State, Brazil. 2 - Federal University of Ceará (UFC), Department of Pathology and Legal Medicine, Fortaleza, Ceara State, Brazil. 3 - University of Fortaleza (UNIFOR), Faculty of Medicine, Fortaleza, Ceara State, Brazil. 4 - Federal University of Ceara (UFC), Faculty of Medicine, Fortaleza, Ceara State, Brazil. 5 - Federal University of Ceará (UFC), Department of Surgery, Fortaleza, Ceara State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 163-170


Aquino Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases

164

Another aspect analyzed is the tumor size. Currently, it has a high prognostic value, since it is highly related to disease aggressiveness. Tumors with larger diameters are associated with axillary lymph node involvement, lower disease free interval, and mortality. Small tumors are invariably related to a better prognosis both for overall survival and diseasefree time10,11. Regarding the presence of angiolymphatic invasion, it is known that the involvement of peritumoral blood and lymphatic vessels is necessary for metastasis to occur in most cases. In cases of breast cancer, these findings are directly associated with axillary lymph node involvement and worse prognoses12-14. The axillary status reflects the involvement or not of the axillary lymph nodes by neoplastic cells. It is one of the most important prognostic factors of invasive carcinoma, since patients with diseasefree armpits display better prognosis, both for overall and for disease-free survival. Survival at ten years is associated with the number of lymph nodes involved15. Due to its indisputable clinical applicability and the different outcomes still observed in our clinical practice, this study aimed to verify the relationship between the tumor anatomopathological characteristics and the axillary metastatic involvement, since this is an excellent predictor of aggression and prognosis.

METHODS

This is a cross-sectional study based on the histopathological analysis of surgical specimens of patients with breast cancer of the invasive ductal histological subtype who underwent surgical treatment by mastectomy or quadrantectomy and investigation of the presence of axillary metastases by sentinel lymph node biopsy or axillary emptying. The patients were treated at the Mastology Service of the Assis Chateaubriand School Maternity from January 2005 to December 2014, and we carried out the research at the Department of Pathology and Legal Medicine – DPML –, Faculty of Medicine of the Federal University of Ceará (UFC), between February and May 2015. We selected female patients with confirmed histological diagnosis of invasive ductal carcinoma, regardless of age, who did not undergo neoadjuvant chemotherapy. We excluded cases that did not have sufficient material in good condition for histological processing and evaluation or did not meet the selection criteria. The following variables were analyzed: Nuclear Grade (NG), Tubular Grade (TG), Mitotic Index (MI) and Histological Grade (HG) by the ScarfBloom-Richardson (SBR) method modified by Elston and Ellis5, which considers the sum of the tubular, nuclear and mitotic index scores (Table 1). We also studied the presence of angiolymphatic invasion,

Table 1. Scores for assessment of tubular and nuclear grades, and mitotic index.

Criteria Tubular Grade

Nuclear Grade

Mitotic Index *

Description Tubular formation present in:

Score

More than 75% of the tumor.

1

10 to 75% of the tumor.

2

Less than 10% of the tumor.

3

Mild nuclear atypia. Regular and uniform small cores.

1

Moderate nuclear atypia. Moderate size and variability.

2

Intense nuclear atypia. Striking variability and the presence of nucleoli.

3

0 to 5 mitoses per large magnification field.

1

6 to 10 mitoses per large magnification field.

2

More than 11 mitosis per large magnification field.

3

* For Nikon microscope (0.44 mm field diameter and 40x magnification). Rev. Col. Bras. Cir. 2017; 44(2): 163-170


Aquino Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases

165

Figure 1. A) Distribution of casuistry by age group (n=220); B) Distribution of tumor size by its largest diameter in centimeters, according to the number of cases (n=220).

metastasis to axillary lymph nodes and tumor diameter. We made the histological sections 5μmthick, processed them from the paraffin-embedded tumor tissue stained with Hematoxylin and Eosin (HE) and observed them under light microscopy (Nikon CX40 model microscope). We considered: HG 1- Well differentiated (sum of 3 to 5 scores); HG 2- Moderately differentiated (sum of 6 to 7 scores); HG 3- Poorly differentiated (sum of 8 to 9 scores). We confirmed angiolymphatic invasion (AI) by histopathological examination and considered it present when tumor cells invaded the lumen of blood vessels and/or peritumoral lymphatic vessels. We assessed axillary metastases (Mx) by the histopathological study of lymph nodes harvested during surgery. We considered the cases positive for axillary metastasis when we found the presence of breast tissue neoplastic cells infiltrating the lymph nodes. We measured tumor diameter (TD) in centimeters from the specimen sent to anatomopathological study. For this study, we considered the largest diameter measured in the primary tumor. We performed statistical analysis using the SPSS® software version 20.0, using the chisquare test, in order to show the correlation of each anatomopathological variable with the presence or absence of axillary metastases, considering p<0.05 as statistically significant.

This study was approved by the Ethics in Research Committee of the Pro-Rectory of Research of the Federal University of Ceará, via Plataforma Brasil, under the number 651,657.

RESULTS We studied 220 cases of invasive ductal carcinoma. The mean patients’age was 56.81 years ± 13.28. The minimum age was 35 years and the maximum, 93, and the patients less than 50 years old predominated (Figure 1A). Tumor size ranged from 0.13 to 22 cm, with a mean of 2.23cm ± 2.79; we also recorded isolated cases of extensive tumors (Figure 1B). When analyzing the degree of differentiation of the tumors regarding the histological grade and its variables, we observed a predominance of poorly differentiated tumors. HG3, TG3 and NG3 prevailed in this series, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution in this study, respectively 82 (37.2%), 68 (31%) and 70 (31.8%) (Table 2). We classified tumors according to their largest diameter and distributed them in two groups: less than or equal to 2cm and greater than 2cm. Tumor ≤2.0 cm were more prevalent (142 – 65.5%). The involvement of peritumoral blood and/or lymphatic vessels was present in most of the cases studied, being represented by 65% of ​​ the sample (n=144) (Table 2).

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Table 2. Distribution of frequencies of anatomopathological variables according to the occurrence of axillary metastases.

Axillary Metastasis (Mx) Variable

Histological Grade (HG)

Tubular Grade (TG)

Nuclear Grade (NG)

Mitotic Index (Mi)

Tumor diameter (TD) Angiolymphatic Invasion (AI)

Absent (n-%)

Present (n-%)

Total n=220 (n/%)

p-value

1

22-10%

22-10%

44-20%

0.0743

2

23-10.5%

46-21%

69-31.4%

3

33-15%

74-33.6%

107-48.6%

1

8-3.6%

11-5%

19-8.6%

0.2207

2

10-4.5%

31-14%

41-18.6%

3

61-27.7%

99-45%

160-72.7%

1

18-8.2%

21-9.5%

39-17.7%

0.2131

2

28-12.7%

46-21%

74-33.65%

3

33-15%

74-33.6%

107-48.6%

1

38-17.3%

44-40%

82-37.2%

0.039

2

19-8.6%

49-22.3%

68-31%

3

21-9.6%

49-22.3%

70-31.8%

≤2cm

38-17.3%

40-18.1%

78-35.5%

0.0003

>2cm

34-15.5%

108-49%

142-65.5%

Absent

58-26.4%

18-8.2%

76-34.5%

< 0.0001

Present

19-8.6%

125-56.8%

144-65.5%

When relating the histological grades and their variables with the presence of axillary metastases, we observed that the variables that prevailed in the cases with metastatic disease were those that indicated less tissue differentiation: HG3, TG3 and NG3. However, when analyzing the relation with the occurrence of axillary metastases, we found no statistical significance, with p=0.07,

p=0.22 and p=0.21, respectively (Figures 2A, 2B and 3A). When analyzing the number of mitoses per microscopic field, we observed that the highest mitotic indexes was significantly related (p=0.03) with the occurrence of axillary metastases (Figure 3B). Tumor diameter and angiolymphatic invasion were also statistically correlated with

Figure 2. Grouped distribution according to the metastatic involvement of axillary lymph nodes (n=220). A) Histological grade; B) Tubular grade. Rev. Col. Bras. Cir. 2017; 44(2): 163-170


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Figure 3. Grouped distribution according to the metastatic involvement of axillary lymph nodes (n = 220). A) Nuclear Grade; B) Mitotic index.

axillary involvement in the present study. The group of cases that presented tumors >2.0cm in their largest diameter and cases in which angiolymphatic invasion was present presented more axillary metastases, with p=0.0003 and p<0.0001, respectively (Figure 4).

DISCUSSION Breast cancer has several outcomes in spite of the treatments used, and the presence of axillary metastases is a strong indicator of poor prognosis15. Therefore, it is important in the clinical practice to better know the tumor characteristics that can predict aggressiveness and axillary involvement. The morphological aspects are directly related to tumors evolution and, in this context, the main determinant is the degree of cellular differentiation5,16,17.

Hammond et al.18 and Fitzgibbons et al.19 considered HG as the first-choice morphological feature to predict prognosis in cases of breast cancer. Leong et al.20 evidenced HG as a good predictor of prognosis. However, they stated that low-grade tumors might also present unfavorable outcomes, with axillary metastases in cases with a long survival time. Nevertheless, Younes et al.21 studied cases of breast cancer without axillary involvement and could not establish a relationship between HG and the patientsâ&#x20AC;&#x2122;prognosis. Lopes et al.22, analyzing the relationship between HG and distant recurrence in five years, also did not find statistical significance. Ladekarl23 considers that there are flaws in the reproducibility of HG that compromise its clinical applicability as a prognostic factor. In this study, we could not establish a significant correlation between HG and axillary involvement either.

Figure 4. Grouped distribution according to the metastatic involvement of axillary lymph nodes (n = 220). A) Tumor diameter; B) Angiolymphatic invasion. Rev. Col. Bras. Cir. 2017; 44(2): 163-170


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We did not find a significant relationship between NG and the occurrence of axillary metastases when considered in isolation. This finding is in agreement with those of Lopes et al.22, who, studying the relation of the NG with the metastatic relapse in five years, did not observe statistical correlation. Martinez-Arribas et al.24 found a direct relation of NG3 with worse prognosis when associated with immunohistochemical parameters, such as absence of hormonal receptors and high Cerb-B2 and Ki67. MI is a variable of the histological grade established by counting the number of mitoses per high magnification field. Lopes et al.22 showed that a mitotic count greater than ten per field was associated with axillary metastases and with systemic relapse in five years. In the study by Medri et al.25, the high number of mitoses was associated with a greater probability of distant metastases in cases of previously negative axilla breast cancer. Caly et al.26, Baak et al.27 and van Diest et al.28 analyzed MI as a prognostic factor and considered

it as effective as HG, tumor size and NG in cases of breast cancer. In our series, the results agree with the literature presented here, since tumors with high MI statistically related with the metastatic involvement of axillary lymph nodes. Barbosa et al.29 observed that tumor size has a significant correlation with axillary lymph node involvement. A meta-analysis involving 11 studies30 concluded that tumor size >2cm and angiolymphatic invasion indisputably increase the probability of axillary lymph node involvement. The literature data presented here corroborate the results of our study, which demonstrated that the present AI was significantly associated with axillary metastases and tumor diameter >2cm. High mitotic indexes, tumors with a diameter >2.0cm and the presence of angiolymphatic invasion were individually associated with the occurrence of axillary metastases in the cases studied and should therefore continue to be part of the initial evaluation of breast cancer and direct the conducts despite current molecular and genetic classifications.

R E S U M O Objetivo: analisar a relação das características anatomopatológicas com o comprometimento axilar em casos de carcinoma ductal invasor. Métodos: estudo transversal de 220 pacientes com câncer de mama, submetidas à mastectomia radical ou quadrantectomia com esvaziamento axilar, oriundos do Serviço de Mastologia da Maternidade Escola Assis Chateaubriand, Ceará, Brasil. Os tumores foram submetidos a processamento histológico e, em seguida, foram determinados os graus histológico (GH), tubular (GT), nuclear (GN), índice mitótico (IM) pela classificação de Scarff-Bloom-Richadson, verificada a presença de invasão angiolinfática (IA) e mensurado o maior diâmetro do tumor (DT). Tais variáveis foram correlacionadas com a presença de metástases axilares. Resultados: a média de idade das pacientes foi 56,81 anos ± 13,28. O tamanho do tumor variou de 0,13 a 22 cm, com média de 2,23cm ± 2,79. Os GH3, GT3 e GN3 prevaleceram: n=107 (48,6%), n=160 (72,7%) e n=107 (48,6%), respectivamente. Os índices mitóticos 1, 2 e 3 apresentaram distribuição homogênea: n=82 (37,2%), n=68 (31%) e n=70 (31,8%), respectivamente. Não foi evidenciada relação do GH, GT e GN com a ocorrência de metástases axilares (p=0,07; p=0,22 e p=0,21). Índices mitóticos 2 e 3 apresentaram relação com a o ocorrência de metástases axilares (p=0,03). Tumores maiores do que 2cm e casos com invasão angiolinfática apresentaram maior índice de metástases axilares (p=0,0003 e p<0,0001). Conclusão: índices mitóticos elevados, tumores com diâmetro maior do que 2cm e presença de invasão angiolinfática apresentaram isoladamente relação com a ocorrência de metástases axilares. Descritores: Neoplasias da Mama. Metástase Linfática. Patologia Cirúrgica. Gradação de Tumores.

REFERENCES 1. Ban KA, Godellas CV. Epidemiology of breast cancer. Surg Oncol Clin North Am. 2014;23(3):409-22. 2. Vich P, Brusint B, Alvarez-Hernández C, Cuadrado-Rouco C, Diaz-García N, Redondo-Margüello E. Update of breast cancer in primary care (I/V). Semergen. 2014;40(6):326-33. 3. Shah R, Rosso K, Nathanson SD. Pathogenesis, prevention, diagnosis and treatment of breast cancer.

World J Clin Oncol. 2014;5(3):283-98. 4. Aquino RGF, Pinheiro LGP, Ferreira MVP, Cavalcante DIM, Oliveira ALS, Gomes NN, et al. Ductal carcinoma of the breast: morphological aspects according to the age. J Bras Patol Med Lab. 2015;51(4):252-7. 5. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403-10. 6. Zhang R, Chen HJ, Wei B, Zhang HY, Pang ZG, Zhu

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Aquino Invasive ductal carcinoma: relationship between pathological characteristics and the presence of axillary metastasis in 220 cases

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26. Caly M, Genin P, Ghuzlan AA, Elie C, Fréneaux P, Klijanienko J, et al. Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases. Anticancer Res. 2004;24(5B):3283-8. 27. Baak JP. The relative prognostic significance of nucleolar morphometry in invasive ductal breast cancer. Histopathology. 1985;9(4):437-44. 28. van Diest PJ, Baak JP, Matze-Cok P, Wisse-Brekelmans EC, van Galen CM, Kurver PH, et al. Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. Hum Pathol. 1992;23(6):603-7. 29. Barbosa EM, Francisco AARF, Araujo Neto JT, Alves EMF, Tavares MGM, Góes JCS. Fatores clínico-patológicos de predição do acometimento axilar

em pacientes com metástases de câncer de mama no linfonodo sentinela. Rev Bras Ginecol Obstet. 2010;32(3):144-9. 30. Degnim AC, Griffith KA, Sabel MS, Hayes DF, Cimmino VM, Diehl KM, et al. Clinicopathologic features of metastasis in nonsentinel lymph nodes of breast carcinoma patients. Cancer. 2003;98(11):2307-15. Received in: 13/09/2016 Accepted for publication: 11/10/2016 Conflict of interest: none. Source of funding: Coordination of Improvement of Higher Level Personnel – CAPES. Mailing address: Ranniere Gurgel Furtado de Aquino E-mail: rannieregurgel@hotmail.com rannieregurgel@gmail.com

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DOI: 10.1590/0100-69912017002011

Original Article

Analysis of obese patients’ medical conditions in the pre and postoperative periods of bariatric surgery Análise das condições clínicas de pessoas obesas em período pré e pós-operatório de cirurgia bariátrica Anderson da Silva Rêgo1; Aline Zulin2; Sandro Scolari2; Sônia Silva Marcon1; Cremilde Aparecida Trindade Radovanovic1. A B S T R A C T Objective: to compare the clinical conditions of obese patients in the pre and postoperative period of bariatric surgery. Methods: we carried out a descriptive, retrospective, quantitative study by consulting the charts of 134 patients who underwent bariatric surgery in the period from 2009 to 2014. We collected the data between September and November 2015. We performed a descriptive statistical analysis and comparative analysis of anthropometric, metabolic, biochemical and clinical variables, considering six months before and after surgery. Results: the majority of the patients were female (91.8%), with a higher prevalence (35%) in the age group 18-29 years old, complete high-school education (65.6%) and grade III obesity (60.4%). Six months after surgery, weight and lipid profile reduction were significant in both genders, but the impact on biochemical, anthropometric, metabolic and clinical parameters was significant only in female subjects, with a reduction in morbidities associated with obesity, such as arterial hypertension, diabetes mellitus, dyslipidemia and metabolic syndrome and in the use of drugs to control them. Conclusion: bariatric surgery was effective in weight loss, with improvements in anthropometric, metabolic and biochemical parameters and in the reduction of morbidities associated with obesity. Keywords: Obesity. Bariatric surgery. Nutrition Assessment.

INTRODUCTION

T

he demographic, epidemiological and socioeconomic transition, and its consequent changes in life and alimentary habits, are determinant factors for the obesity increase in the population, mainly in developed and highly industrialized countries. Obesity, in turn, triggers social and psychological damages such as depression, low self-esteem and social isolation, with negative effects on quality of life1,2. The Brazilian Ministry of Health estimated that in 2014, 52.5% of the country’s population was overweight, a considerable increase of 9.5% in the index compared with the year 20063. It emphasized that, of the people with excess weight in the age group between 35 and 64 years, 17.9% are females, are already obese, and with low schooling. Obesity favors the increase of chronic diseases, such as systemic arterial hypertension, diabetes mellitus and cancer, responsible for 72% of deaths in the country3. Bariatric surgery is a viable option for the significant and rapid weight loss and also as a strategy to

maintain metabolic rates, and even for the reduction and remission of obesity-related chronic diseases4. Surgical indication must occur after a rigorous multiprofessional evaluation, with assessment of nutritional status, anthropometric measures, and psychological conditions to follow medical and nutritional recommendations after the procedure. This is because the success of surgical treatment essentially depends on the emotional balance and changes in the individual’s lifestyle4,5. Bariatric surgery has been innovating over the years and its technique has become less and less invasive, providing fast and better recovery6. It allows weight loss of about 40% of the initial weight in a period of six to 12 months, generating large changes in daily habits and attributions, whether in a social or family environment and also in body image7,8. In this aspect, knowing the benefits of the surgical procedure, such as weight loss and the improvement of the metabolic parameters, is relevant for proposing actions that can avoid complications, promoting self-care and improving the quality of life6. Thus, the objective of this study was to compare the

1 - State University of Maringá, Post-Graduate Program in Nursing, Maringá, Parana State, Brazil. 2 - Dr. Sandro Scolari Surgery Institute, Maringá, Parana State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 171-178


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Rêgo Analysis of obese patients’ medical conditions in the pre and postoperative periods of bariatric surgery

clinical conditions of obese people in the pre and postoperative period of bariatric surgery.

steatosis and cardiopathies); c) biochemical parameters: fasting glycemia, erythrocytes, total cholesterol, LDL and HDL cholesterol, triglycerides, transaminases (AST, ALT), alkaline phosphatase and gamma‑gt – GGT); and d) use of medications. All collected variables related to the pre and postoperative periods. We defined as eligible for the study every patient whose charts contained data records of the period of six months before to six months after surgery. Thus, we included 134 patients. We used the recommendation of the Brazilian Society of Cardiology, which considers the parameters of NCEP-ATP III, to identify the presence of metabolic syndrome (MS) in the combination of the following components: high blood pressure or use of antihypertensives, high values of triglycerides and cholesterol, abdominal circumference >102cm for men and >88cm for women and high fasting glucose or use of hypoglycemic agents9.

METHODS This is a descriptive, retrospective, quantitative study conducted at a Bariatric Surgery Institute that performs on average eight bariatric surgeries per month, by the same medical professional, located in the city of Maringá - PR. We collected data from September to December 2015, based on the medical records of individuals who underwent bariatric surgery in the period from 2009 to 2014. For this purpose, was used a script consisting of the following variables: a) nutritional status (weight, height, body mass index – BMI); b) presence of associated morbidities (systemic arterial hypertension – SAH, diabetes mellitus – DM, metabolic syndrome – MS, dyslipidemia, hepatic Table 1. Socio-demographic data of patients undergoing bariatric surgery.

Male

Female

Total

N

%

N

%

N

%

18 to 29 years

2

18.2

45

36.5

47

35.0

30 to 39 years

3

27.3

40

32.6

43

32.1

40 to 49 years

3

27.3

25

20.3

28

20.9

50 to 59 years

2

18.2

12

9.8

14

10.5

≥ 60 years

1

9.1

1

0.8

2

1.5

Illiterate

-

-

2

1.6

2

1.5

Junior-high School

2

18.2

6

4.8

8

6.0

High School

2

18.2

86

70.0

88

65.6

College Education

7

63.6

29

23.6

36

26.9

Grade II

3

27.3

50

40.7

53

39.6

Grade III

8

72.7

73

59.3

81

60.4

Gastric Sleeve

11

100

115

93.5

126

94.1

Gastric Bypass

-

-

8

6.5

8

5.9

Age

Study years

Degree of Obesity

Type of surgery

Source: Maringá Bariatric Surgery Institute, 2015. Rev. Col. Bras. Cir. 2017; 44(2): 171-178


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173

Table 2. Comparison of obesity-associated morbidities in the pre and postoperative periods of Bariatric Surgery.

Male

Associated Morbidities

Preoperative

Postoperative

N

%

N

%

Yes

6

54.5

3

27.3

No

5

45.5

8

72.7

Yes

2

18.2

2

18.2

No

9

81.8

9

81.8

Yes

6

54.5

1

9.1

No

5

45.5

10

90.9

Yes

6

54.5

0

0

No

5

45.5

11

100

Yes

11

100

5

45.5

No

-

-

6

54.5

Yes

8

72.7

4

36.4

No

3

63.3

7

63.3

Female Preoperative

p*

Postoperative

N

%

N

%

26

21.2

16

13

97

78.8

107

87

21

17.1

4

3.3

102

82.9

119

96.7

47

35.8

5

4.1

79

64.2

118

95.9

52

42.3

-

-

71

57.7

123

100

47

38.2

17

13.8

76

61.8

106

86.2

79

64.2

14

11.3

44

35.8

109

88.7

p*

Arterial Hypertension 0.121

0.000

Diabetes Mellitus 0.345

0.001

Dyslipidemia 0.545

0.005

Hepatic Steatosis -

-

Metabolic Syndrome -

0.000

Use of Medications 0.212

0.031

Source: Maringá Bariatric Surgery Institute, 2015. * Pearson’s Chi-square test.

To classify obesity according to BMI, we adopted the criteria proposed by the World Health Organization10,11, recommended by the Brazilian Society of Endocrinology and Metabolism12. According to this criterion, nutritional status is classified as low weight (BMI <18.5), eutrophic (BMI between 18.5 and 24.9 kg/m2), overweight (BMI 25‑29.9 kg/m2), obesity grade I (BMI 30‑34.9 kg/m2), obesity grade II (BMI 35‑39.9 kg/m2) and obesity grade III (BMI >40kg/m2). We entered the data into the Microsoft Excel 2010® software and, after conference, we transferred them to the IBM SPSS® software, version 20.0. For all statistical tests, we set significance at 5% (p≤0.05). We presented the descriptive analysis in absolute frequency and percentage. We used the Shapiro-Wilk test to verify the variables’ normality. When the normality assumption was verified, we used the paired “t” test to compare the mean of the anthropometric and biochemical variables in the pre

and postoperative period. To measure the association between the explanatory and outcome variables, we used the Pearson chi-square test. We developed the study in accordance with the ethical precepts disciplined by Resolution 466/12 of the National Health Council and the research project was approved by the Standing Committee on Ethics in Research with Humans (COPEP) of the State University of Maringá (opinion no. 1246542).

RESULTS Of the 134 patients evaluated, the majority were female (91.8%). Among them, there was a higher prevalence in the age group of 18 to 29 years (36.5%), complete high-school education (70%) and more than half had grade III obesity (59.3%). Men were more prevalent in the 30-49 age group (54.6%), the majority (63.6%) had college education and grade III obesity

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Table 3. Comparison of nutritional status in the pre and postoperative periods of Bariatric Surgery.

Male

Female

Preoperative

Postoperative

Preoperative

Postoperative

N

N

%

N

N

%

Eutrophic

1

9.1

21

17.0

Overweight

7

63.6

61

49.6

Obese Grade I

3

27.3

29

23.5

12

9.9

%

%

Obese Grade II

3

27.3

50

40.6

Obese Grade III

8

72.7

73

59.4

Source: Maringá Bariatric Surgery Institute, 2015.

(72.7%) (Table 1). The most used surgical technique was the Gastric Sleeve, in 94.1% of the patients. Table 2 shows that the reduction of arterial hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome and use of medications in the postoperative period were only significant for the female patients. Table 3 presents information related to nutritional status. We observed that grade III obesity was more prevalent among men (72.7%). After surgery, a large part (63.6%) passed into the overweight class. Among women, 59.4% had grade III obesity and in the postoperative period, 49.6% became overweight. The results of the comparison between the means of the anthropometric variables in the pre and postoperative periods show reduction in both weight and BMI, with significant value in both genders. As for the metabolic parameters, there was a significant increase in the HDL levels in female patients. The values of ​​ the biochemical parameters of total proteins, ferritin, AST, ALT and GGT showed a significant reduction in both genders. The values ​​of LDL, total cholesterol and triglycerides also showed a significant reduction in both genders. Erythrocytes, albumin, and alkaline phosphatase presented value changes in the female patients’ results (Table 4).

DISCUSSION The majority of patients undergoing bariatric surgery in our study were female, which corroborates with results of other studies performed in different regions of the country2,13-15.

It is noteworthy that six months before surgery, most of the individuals had grade III obesity. The weight loss and the change in obesity classification described in table 3 were also verified in a study that adopted the same parameters and identified that many patients classified as high-grade obese before the surgical procedure presented lower grades and even normal weight six months after surgery16. The comorbidities associated with obesity improved between the bariatric surgery pre and postoperative periods. Dyslipidemia, present in most patients of both genders in this study, had a significant reduction in females, which also showed a significant decrease in Total and LDL cholesterol and triglycerides, and an increase in HDL cholesterol. Bariatric surgery allowed changes in eating habits, characterized by the ingestion of foods in small amounts, with lower caloric value and allowed weight reduction and adoption of healthy habits. Studies have shown that reducing dyslipidemia reduces the risk of cardiovascular diseases17,18. We also observed reduction in the percentages of SAH and DM. These results are similar to those of other studies whose results point to a gradual reduction of weight and improvement in metabolism, with a decrease in hypertension and DM19. As observed by other authors, there was also a reduction in the use of medications for treatment and control of comorbidities associated with obesity20,21. Ghiassi et al.21 found that bariatric surgery was beneficial not only for the patient’s general health, but also for the reduction of costs resulting from the purchase of medications and activities related to the

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Table 4: Comparison of the metabolic, biochemical and anthropometric parameters of obese patients in the pre and postoperative periods of Bariatric Surgery.

Male

Female

Preoperative

Postoperative

Preoperative

Postoperative

Mean ± SD **

Mean ± SD

Mean ± SD

Mean ± SD

Weight (kg)

116.1 ± 18.0

81.4 ± 14.3

0.000

107.1 ± 15.6

76.2 ± 14.2

0.000

BMI (kg/m ²)

39.4 ± 2.5

27.5 ± 2.4

0.000

40.6 ± 3.7

28.4 ± 4.0

0.000

HDL (mg/dl)

52.8 ± 32.1

56.8 ± 10.3

0.667

53.1 ± 19

57.8 ± 14.9

0.001

LDL (mg/dl)

114.5 ± 31.8

96.1 ± 29.0

0.036

114.5 ± 31.7

107.4 ± 32.6

0.008

TC (mg/dl)

196.6 ± 35.0

168.9 ± 29.2

0.018

195.8 ± 36.5

186.3 ± 33.2

0.006

TG (mg/dl)

168.1 ± 82.7

97.2 ± 57.8

0.009

150 ± 70

110.4 51.7 ±

0.000

Fasting glucose (mg/dl)

120.9 ± 31.9

91.5 ± 17.4

0.001 118.6 ± 131.9

85.5 ± 10.8

0.006

4.79 ± 0.46

4.54 ± 0.14

0.052

4.62 ± 0.38

4.34 ± 0.49

0.000

Total protein (g/dl)

7.4 ± 0.5

6.9 ± 0.6

0.013

7.7 ± 5.6

6.8 ± 0.6

0.09

Albumin (g/dl)

4.2 ± 0.2

4.2 ± 0.4

0.933

4.1 ± 0.4

4.0 ± 0.3

0.033

91.3 ± 34.7

89.5 ± 31.2

0.379

Parameters

p*

p*

Anthropometric

Metabolic

Biochemical Red blood cells (Mi/mm3)

Serum iron (ug/dl)

84.2 ± 30.3

85.41 ± 33.10 0.868

Ferritin (ng/ml)

293.6 ± 168.0 210.7 ± 139.7 0.017 142.8 ± 114.3

118.3 ± 82.5

0.002

Vit. B12 (pg/ml)

404.9 121.9 ± 369.0 ± 212.7 0.487 358.3 ± 247.8

322.9 ± 91.5

0.117

AST (U/l)

23.7 ± 6.9

18.3 ± 4.1

0.026

26.2 ± 18.6

21.4 ± 15.7

0.000

ALT (U/l)

33.2 ± 16.3

19.2 ± 6.2

0.031

29.6 ± 24

21.3 ± 9.7

0.000

Alkaline Phosphat. (U/l)

70.1 ± 27.3

59.6 ± 23.8

0.069

76.6 ± 19.4

65.5 ± 18.6

0.000

Gamma-GT (U/l)

36.4 ± 18.6

21.5 ± 11.1

0.027

41.5 ± 55.8

25.6 ± 20.3

0.001

Source: Maringá Bariatric Surgery Institute, 2015. * Paired t test (p<0.05); ** Standard Deviation; TC: Total cholesterol; TG: Triglycerides.

control of comorbidities. Others, however, found that although there is a reduction in the use of drugs for treatment and control of the main diseases associated with obesity, there is an increase in the use of other medications, mainly nutritional supplements20. In Brazil, we found no studies addressing the reduction of costs related to the purchase of medicines after bariatric surgery. One study, however, has addressed the reduction in drug use to control weight regain22. We believe that it is important to quantify the economic impact of non-use of disease control drugs, especially for high blood pressure and diabetes mellitus, most prevalent chronic diseases, and responsible for most causes of death, in the country23. Hepatic steatosis, identified by elevated levels of AST, ALT, GGT and biopsy specimens, also showed reduction after bariatric surgery. Other authors also

observed a 46.6% reduction in steatosis among the individuals studied24-27. A meta-analysis carried out in the United Kingdom indicated a reduction of liver enzymes, considered markers of liver function and liver damage, statistically associated with the reduction of hepatic steatosis shortly after surgery25. The reduction of hepatic steatosis is due to changes in food habits. On the other hand, the reduction of dietary intake due to gastric reduction, in addition to causing weight loss, generates nutritional deficiencies, especially in the first year after surgery28. In our study, the results pointed to a significant reduction in the number of red blood cells in women due to the reduction of gastric volume and the production of gastric juice, responsible for the initial iron metabolism. With the stomach reduction, the digestion of food becomes more time consuming,

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especially those rich in protein and fiber, which are also rich in iron, which causes satiety, decreasing the number and quantity of food intake29. The values of ​​ ferritin also showed a significant reduction. We should note that the not significant reduction in vitamin B12 and serum iron levels in both genders may be due to the short postoperative follow-

up, a period in which there is still a large reserve of micronutrients30 . Our study demonstrated that bariatric surgery was effective in weight loss, with improvement of anthropometric, metabolic and biochemical parameters, and in the reduction of morbidities associated with obesity.

R E S U M O Objetivo: comparar as condições clínicas de pacientes obesos em período pré e pós-operatório de cirurgia bariátrica. Método: estudo descritivo, retrospectivo, de abordagem quantitativa, por meio de consulta ao prontuário de 134 pacientes submetidos à cirurgia bariátrica no período de 2009 a 2014. Os dados foram coletados entre os meses de setembro e novembro de 2015.  Foi realizada análise estatística descritiva e comparativa das variáveis antropométricas, metabólicas, bioquímicas e clínicas, considerando seis meses antes e após a cirurgia. Resultados: a maioria dos pacientes era do sexo feminino (91,8%), com maior prevalência (35%) na faixa etária de 18 aos 29 anos, com ensino médio completo (65,6%) e obesidade grau III (60,4%). Seis meses após a cirurgia, a redução do peso e o perfil lipídico foram significativos em ambos os sexos, mas o impacto nos parâmetros bioquímicos, antropométricos, metabólicos e clínicos foi significativo apenas nos indivíduos do sexo feminino, com redução das morbidades associadas à obesidade como hipertensão arterial, diabetes mellitus, dislipidemia e síndrome metabólica e na utilização de medicamentos. Conclusão: a cirurgia bariátrica foi eficaz na perda ponderal de peso, com melhoras nos parâmetros antropométricos, metabólicos e bioquímicos e na redução de morbidades associadas à obesidade. Descritores: Obesidade. Cirurgia bariátrica. Avaliação Nutricional.

REFERENCES 1. Camargo APPM, Barros Filho AA, Antonio MARGM, Giglio JS. A não percepção da obesidade pode ser um obstáculo no papel das mães de cuidar de seus filhos. Ciênc saúde coletiva, 2013;18(2):323-33. 2. Oliveira DM, Meregui MAB, Jesus MCP. A decisão da mulher obesa pela cirurgia bariátrica à luz da fenomenologia social. Rev esc enferm USP. 2014;48(6):970-6. 3. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Vigilância de Doenças e Agravos não Transmissíveis e Promoção da Saúde. Vigitel Brasil 2014: vigilância de fatores de risco e proteção para doenças crônicas por inquérito telefônico / Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância de Doenças e Agravos não Transmissíveis e Promoção da Saúde. Brasília: Ministério da Saúde, 2015. 4. Marcelino LF, Patrício ZM. A complexidade da obesidade e o processo de viver após a cirurgia bariátrica: uma questão de saúde coletiva. Ciênc saúde coletiva. 2011;16(12):4767-76. 5. Prevedello CF, Colpo E, Mayer ET, Copetti H. Análise do impacto da cirurgia bariátrica em uma po-

pulação do centro do estado do Rio Grande do Sul utilizando o método BAROS. Arq Gastroenterol. 2009;46(3):199-203. 6. Barros LM, Frota NM, Moreira RAN, Araújo TM, Caetano JA. Avaliação dos resultados da cirurgia bariátrica. Rev Gaúcha Enferm. 2015;36(1):21-7. 7. Miranda NPN, Conti MA, Bastos RR, Laus MF, Almeida SS, Ferreira MEC. Imagem corporal de adolescentes de cidades rurais. Ciênc saúde coletiva. 2014;19(6):1791-801. 8. Nassif PAN, Lopes AD, Lopes GL, Martins PR, Pedri LE, Varaschim M, et al. Alterações nos parâmetros pré e pós-operatórios de pacientes com síndrome metabólica, submetidos a Bypass gastrointestinal em Y de Roux. ABCD, arq bras cir dig. 2009;22(3):165-70. 9. Sociedade Brasileira de Cardiologia. Diretrizes da Sociedade Brasileira de Cardiologia: pocket book 2013-2015. Coordenação Luiz Carlos Bodanese. 7a ed rev. São Paulo:OMNIFARMA; 2015. 10. Obesity: preventing and managing the global epidemic. Report of a who Consultation. World Health Organ Tech Rep Ser 2000; 894:i-xii, 1-253. 11. World Health Organization. Obesity: Preventing and Managing the Global Epidemic; Report of a

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Surg Obes Relat Dis. 2012;8(3):269-74. Pajecki D, Halpern A, Cercato C, Mancini M, Cleva R, Santo MA. Tratamento de curto prazo com liraglutide no reganho de peso após cirurgia bariátrica. Rev Col Bras Cir. 2012;40(3):191-5. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Análise de Situação de Saúde. Plano de ações estratégicas para o enfrentamento das doenças crônicas não transmissíveis (DCNT) no Brasil 2011-2022 / Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Análise de Situação de Saúde. Brasília: Ministério da Saúde, 2011. Silva LGO, Manso JEF, Silva RARN, Pereira SE, Saboya Sobrinho CJ, Rangel CW. Relação entre o estado nutricional de vitamina A e a regressão da esteatose hepática após gastroplastia em Y-de-Roux para tratamento da obesidade classe III. ABCD, arq bras cir dig. 2012;25(4):250-6. Bower G, Toma T, Harling L, Jiao LR, Efthimiou E, Darzi A, et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg. 2015;25(12):2280-9. Tai CM, Huang CK, Hwang JC, Chiang H, Chang CY, Lee CT, et al. Improvement of nonalcoholic fatty liver after bariatric surgery in morbidly obese Chinese patients. Obes Surg. 2012;22(7):1016-21. Caiazzo R, Lassailly G, Leteurtre E, Baud G, Verkindt H, Raverdy V, et al. Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic fatty liver disease: a 5-year controlled longitudinal study. Ann Surg. 2014;260(5):893-8; discussion 898-9. Ramos NMCPJ, Magno FCCM, Cohen L, Rosado EL, Carneiro JRI. Perda ponderal e presença de anemias carenciais em pacientes submetidos à bypass gástrico em Y-de-Roux em uso de suplementação de vitaminas e minerais. ABCD, arq bras cir dig. 2015;28(1):44-7. Leiro LS, Melendez-Araújo MS. Adequação de micronutrientes da dieta de mulheres após um ano de bypass gástrico. ABCD, arq bras cir dig. 2014;27(Suppl 1):S21-5.

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30. Carvalho IR, Loscalzo IT, Freitas MFB, Jordão RE, Friano TC. Incidência da deficiência de vitamina B12 em pacientes submetidos à cirurgia bariátrica pela técnica Fobi-Capela (Y-de-Roux). ABCD, arq bras cir dig. 2012;25(1):36-40.

Received in: 22/09/2016 Accepted for publication: 09/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Anderson da Silva Rêgo E-mail: anderson0788@hotmail.com andersondsre@gmail.com

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DOI: 10.1590/0100-69912017002012

Original Article

Immediate reconstruction with autologous fat grafting: influence in breast cancerregional recurrence Reconstrução imediata com enxerto autólogo de gordura: influência na recorrência local de câncer de mama Camile Cesa Stumpf1; Jorge Villanova Biazus1; Fernando Schuh Ângela Erguy Zucatto1; Rodrigo Cericatto1; José Antônio Crespo Cavalheiro1; Andrea Pires Souto Damin1; Márcia Portela Melo1. A B S T R A C T Objective: to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. Methods: this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman’s technique (lipofilling group). All patients had invasive carcinoma and were operated by a single surgeon from 2004 to 2011. The postoperative follow-up time was 36 months. Results: the overall incidence of local recurrence was 2.4%. No patient in the lipofilling group had local recurrence during the study period. For systemic recurrence, the rates obtained were 3.7% (one patient) for the fat grafting group and 1.8% (three patients) for the conservative surgery group without reconstruction. Conclusion: there was no significant difference for local or systemic recurrence in the groups studied. Immediate autologous fat grafting appears to be a safe procedure. Keywords: Breast Neoplasms. Neoplasm Recurrence, Local. Breast. Transplantation, Autologous. Reconstruction.

INTRODUCTION

A

utologous fat grafting is widely used in plastic surgery to restore contour, increase volume and improve irradiated skin in breast reconstructive surgery1-4. The risk of tumor recurrence is unknown when this type of reconstruction is performed simultaneously to conservative surgery, because there are no studies in the literature that use this method in the immediate breast reconstruction. Rigotti et al.5 described local and regional recurrence after radical mastectomy with fat graft reconstruction in 6.5% of 137 patients in 7.6 years of follow-up. The author considered this incidence comparable to that observed in large randomized trials after mastectomy. Rietjens et al.6 evaluated 158 patients who underwent 194 fat grafting procedures. He observed only one case of local recurrence, but probably already existed before fat grafting, since the diagnosis was made only two weeks after the procedure. The data were not considered relevant. Petit et al.7, on their turn, conducted a case-control study,

in which 321 patients who underwent fat grafting for late breast reconstruction were compared with 642 women with similar cancer treatment, but without reconstruction. Invasive tumors accounted for 89% of the cases, 61% of the patients underwent mastectomy and the mean follow-up was 56 months after primary surgery and 26 months after the fat grafting procedure. They diagnosed eight cases of local recurrence in the fat grafting group and 19 in the control group. There was no significant difference in patients with invasive carcinoma. In the group of patients with intraepithelial carcinoma who underwent fat grafting, local recurrence increased (p<0.001). Of the local recurrences in the group of intraepithelial carcinomas, three occurred after mastectomy and one after conservative surgery. A systematic review by Claro et al.8 demonstrated that these three studies evaluated a total of 616 patients (mean follow-up of 45.17 months) with 14 cases of local recurrence (2.27%). In most recurrencecases, the initial treatment of breast cancer was mastectomy. They identified no significant

1 - Clinics Hospital of Porto Alegre, Breast Unit, Porto Alegre, Rio Grande do Sul State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 179-186


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Stumpf Immediate reconstruction with autologous fat grafting: influence inbreast cancerregional recurrence

differences in the cumulative incidence of cancer risk for patients undergoing fat graft reconstruction. Using the same database, in 2013 Petit et 9 al. exclusively evaluated patients with intraepithelial carcinoma, as they showed a higher risk of recurrence after fat grafting. There were 59 women with intraepithelial carcinoma undergoing fat grafting, and 118 women with no fat grafts as controls. They observed nine local recurrences, six in the fat grafting group and three in the control group (18% vs. 3%, p=0.02), confirming an increased risk. In the control group, however, there was a lower rate of recurrence compared with the rate generally found in patients with intraepithelial carcinomas, of 1% per year, suggesting that the different incidence found may not be statistically significant. The objective of the present study was to compare rates of locoregional and systemic recurrence of breast cancer in patients submitted to autologous fat grafting simultaneously to conservative treatment with patients who underwent conservative treatment without reconstruction.

METHODS This is a historical cohort study of patients with invasive breast cancer submitted to conservative surgical treatment between January 2004 and December 2011 in the Mastology Sector of the Clinics Hospital of Porto Alegre. We studied 194 patients, divided into two groups: group 1 or lipofilling group, with 27 patients undergoing breast conservative surgery with immediate autologous fat grafting in the years 2010 and 2011 (year of beginning of the intervention) and group 2 or breast conservative surgery (BCS) group, with 167 patients undergoing conservative surgery without breast reconstruction, from 2004 to 2009. We perfumed the fat grafting by the Coleman technique and applied the fat grafting in different directions in the breast, including the tumor bed. In this technique, fat is liposuctioned from any part of the body, most commonly the abdomen, through a liposuction system under low pressure. This lipospired tissue is centrifuged and separated into three

phases: blood, oil and purified adipose tissue. The oil and blood are discarded and the purified adipose tissue is injected into the retroglandular and subcutaneous region in small amounts and in different directions, including the tumor bed. In this way, the contact surface between the injected adipocytes and the receptor tissue is increased, increasing the probability of nutrition and incorporation of the new tissue. Bolus injection should not be performed because the excess fat in one place may not be absorbed, inducing the formation of areas of fatty necrosis. It is mandatory to graft a greater amount of adipose tissue than the defect itself because part of the transferred fat is reabsorbed. In experimental studies, up to 90% of transplanted adipose tissue may be lost, but clinical observation shows that the mean resorption is between 40% and 60%. The patients studied had invasive breast carcinoma, clinical stages I and II, submitted to conservative surgery, with negative margins, and were followed up for 36 months. The follow-up consisted of clinical evaluations every three months, with ultrasound and mammography every six months for evaluation of local recurrence, as well as chest X-ray, abdominal ultrasonography and bone scintigraphy for evaluation of systemic recurrence. We excluded patients who had already been treated for breast cancer. A single observer collected and reviewed the patientsâ&#x20AC;&#x2122; records. The following variables were studied: age, tumor size, histological grade, staging, tumor type, hormone receptor expression, resection margins status, type of adjuvant treatment and presence or absence of local or systemic recurrence. We also evaluated serious postoperative complications that could delay adjuvant treatment and time to relapse diagnosis. We entered the data into a SPSS (Statistical Package for Social Sciences, version 18.0) worksheet. For the statistical analysis, we compared the data using the chi-square test for categorical variables and the Studentâ&#x20AC;&#x2122;s t or Mann-Whitney tests for continuous variables. We estimated recurrence curves using the Kaplan Meier method, and usedthe log rank test to compare the recurrence curves between groups. This difference has alpha =0.05 for a difference of 30%,

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Table 1. Clinical and histological characteristics of the patients with invasive ductal carcinoma who underwent either conservative surgery with lipofilling or only conservative surgery.

BCS* + Lipofilling (n=27)

BCS (n=167)

Age (mean in years)

53.6 ± 10.9

56,4 ± 12.0

Tumor size (mm)

24.3 ± 10.5

20.6 ± 12.0

I

7 (25.9)

38 (22.8)

II

9 (33.3)

85 (50.9)

III

11 (40,7)

44 (26.3)

I

7 (25.9)

78 (46.7)

II

20 (74.1)

89 (53.3)

IDC

24 (88.9)

149 (89.20

ILC

3 (11.1)

18 (10.8)

Present

22 (81.5)

128 (76.6)

Absent

5 (18.5)

39 (23.4)

Present

22 (81.5)

116 (69.5)

Absent

5 (18.5)

51 (30.5)

Overexpressed

3 (11.1)

19 (11.4)

Not overexpressed

20 (74.1)

137 (82.0)

Undertermined

4 (14.8)

11 (6.6)

1 (3.7)

26 (15.6)

Adjuvant chemotherapy

17 (63.0)

62 (37.1)

Adjuvant radiotherapy

27 (100)

163 (97.3)

1 (1-2)

2 (1-4)

Histological grading

Clinical staging (TNM)

Histology

Estrogen receptor

Progesterone receptor

HER2

Neoadjuvant chemotherapy

Time to start of adjuvant therapy (months)

Categorical variables described as n (%); Symmetric quantitative variables described as means ± standard deviation; Asymmetric quantitative variables described as means (P25-P75); BCS- Breast Conservative Surgery; IDC- invasive ductal carcinoma; ILC- invasive lobular carcinoma.

power of 80%. The results were considered significant at p<0.05. The present study was approved by the Ethics in Research Committee of the Clinics Hospital of Porto Alegre, under number 13-0401, and financed by the Mastology Sector of Clinics Hospital.

RESULTS The evaluation of the clinical and histological characteristics of each group did not reveal any statistically

significant difference. The mean age was 53.6±10.9 years in the lipofilling group and 56.4±12.0 years in the BCS group. All tumors were invasive carcinomas: 173 invasive ductal carcinomas and 21 invasive lobular carcinomas. The mean tumor size was 24.3±10.5mm in the lipofilling group and 20.6±12.0 in the BCS group. The mean time between surgery and the beginning of adjuvant treatment was one month in the lipofilling group and two months in the BCS group (Table 1). In the BCS group, 26 patients (15.6%) underwent neoadjuvant chemotherapy, compared with only one (3.7%) in the lipofilling group.

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Table 2. Recurrence in the lipofilling and breast conservative surgery groups.

BCS* + Lipofilling (n=27)

BCS (n=167)

1 (3.7)

7 (4.2)

Yes

7 (25.9)

38 (22.8)

No

9 (33.3)

85 (50.9)

Yes

7 (25.9)

78 (46.7)

No

20 (74.1)

89 (53.3)

Overall recurrence Local recurrence

Systemic recurrence

Categorical variables described as n (%); *BCS- Breast Conservative Surgery.

We identified systemic recurrence in one patient (3.7%) in the lipofilling group and in seven (4.2%) in the BCS group. Comparison of the different types of recurrence did not reveal any statistically significant differences between the groups (Table 2). We diagnosed local recurrence in four patients (2.4%) in the BCS group and none in the lipofilling group. Of the recurrences identified, one presented as a nodule, one with microcalcifications and two with cutaneous presentation. We made the diagnoses of local recurrence by physical examination in three patients and by mammography, inone. The evaluation of each group, according to the type of recurrence, did not show any differences in the incidence of local and systemic recurrence, and we did not find differences in disease-free survival (Figures 1, 2 and 3).

times, which may suggest that recurrence was not associated with the fat graft procedure. BiazĂşs et al.11 carried out a study at the Clinics Hospital of Porto Alegre, Brazil, in which the autologous fat graft procedure was performed simultaneously with conservative surgery. Twenty patients older than 21 years, clinical stages I and II, underwent conservative surgery with immediate reconstruction with autologous fat according to the Coleman technique. Immediate injection of autologous adipose tissue facilitates repair of hard-to-resolve defects, which are often amplified by radiotherapy, especially in the inner and upper breast quadrants. These patients underwent adjuvant treatment following protocols of patients submitted to Figure 1. Disease-free survival curve in lipofilling and conservative surgery groups up to time of recurrence.

DISCUSSION In 2014, Brenelli et al.10 published a prospective study of 59 patients who underwent 75 breast fat grafting procedures. All patients had undergone prior conservative treatment for oncological reasons and had a breast defect. They observed immediate complications in three cases, two cases of fat necrosis and one of cellulitis. Three cases of local recurrence were observed (4%) at 34 months of follow-up, 1.4% per year, an acceptable rate for conservative surgery. They diagnosed recurrences at different follow-up

Log rank test (p=0.902); BCS- breast conservative surgery.

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Stumpf Immediate reconstruction with autologous fat grafting: influence inbreast cancerregional recurrence

Figure 2. Disease-free survival curve in lipofilling and conservative surgery groups up to time of systemic recurrence.

Log rank test (p=0.521); BCS- breast conservative surgery.

conservative surgery and are now under clinical and radiological follow-up. Autologous fat grafting is a less invasive technique and results in a high level of patient satisfaction12-14. In 2016, MoltĂł Garcia et al.15 published preliminary results of 37 immediate reconstructions of quadrantectomies with autologous fat grafting. They included both benign and malignant tumors. They avoided fat grafting in the same region of the quadrantectomy. All cases studied, with one year of follow up, showed excellent aesthetic results, even after radiotherapy. The complication rate was low and oncological safety was not compromised. Autologous fat graftinghas been used for correction of body contouring or to correct soft tissue defects in different specialties for many years. In recent years, fat grafting has also been applied to restore breast contour and to stimulate neovascularization of irradiated mammary tissue that is chronically ischemic. Fat grafts supplement volume in unsatisfactory breast reconstruction results with breast implants, reduces capsular contracture, and improves the quality of breast reconstruction16-19. The technique was developed and applied by the Mastology Sector of the Clinics Hospital of Porto Alegre and has shown efficacy in patients with small breasts presenting with tumors in the inner and upper breast quadrants20.

183

Figure 3. Disease-free survival curve in lipofilling and conservative surgery groups up to time of local recurrence.

Test log rank (p=0.419) BCS- breast conservative surgery.

In our group of patients submitted to immediate fat grafting and with 36 months of followup, we observed no local recurrence and there was only one case of systemic recurrence, comparable to the systemic recurrence rates described in the literature9,21. Some studies have shown a greater number of local recurrence in patients with intraductal carcinoma undergoing fat grafting in late reconstruction, but the numbers were not significant, since the control population showed a lower recurrence rate than expected (1% per year)5,7. We cannot compared that study to ours because the great majority of patients had undergone mastectomy, whereas the object of our study was only conservative procedures9. We do not have studies about the risk or delay in the diagnosis of relapse in patients who were submitted to immediate fat grafting in the tumor bed of conservative surgery, because the first procedures with this technique were included in the study by BiazĂşs et al.11, and these patients are still in follow-up. As all patients were treated following the institutional adjuvant protocols, we believe that there will be no difference between the two groups. From a cosmetic point of view, Schultz 12 et al. evaluated 44 patients who underwent fat grafting after conservative surgery or after breast reconstruction to correct deformities. Patients reported

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improvement in irregularities as well as in breast shape, in addition to increased volume and improved breast tissue consistency. Other authors have obtained the same aesthetic results11,13,14. This technique, as demonstrated by de Baclam et al.22, has been effective in the correction of deformities in the supero-medial quadrant of the reconstructed breast. Largo et al.23, in a systematic review, reported that seven out of 12 studies aimed at gaining volume after fat grafting had good or excellent results. However, only Zocchi and Zuliani24 used a standard protocol for satisfaction assessment (excellent, good, fair and insufficient). The other studies did not specify how they assessed patient satisfaction. Regarding imaging tests, we verified that fat grafting does not cause additional difficulties in the radiological evaluation of suspicious alterations25-28. Radiologists can distinguish, with a high level of confidence, calcifications due to fat necrosis from those related to breast cancer29. Claro et al.8 reported that, in 17 studies with 2,560 patients, the rate of abnormal radiographic changes after fat grafting was 13% after a 12-month follow-up, data similar to changes that are visualized after any breast surgical procedure. The most common abnormal radiological findings were cysts (74.6%) and microcalcifications (13.4%). In addition, there was no statistically significant difference in

breast tissue density and in Breast Imaging Reporting and Data System (BIRADS) classification before and after breast fat grafting in 20 patients with no history of breast disease23,25. In any case, failure to diagnose a new cancer is a problem that can occur after any breast surgery. Therefore, the same surveillance used to monitor patients after conservative breast treatment should be used after fat graft reconstruction29. Despite the limitation of the study by the small number of patients in the lipofilling group, the use of fat grafting in conservative surgery seems safe. Induction of a new tumor or accelerated growth of a pre-existing one by fat grafting has also not been confirmed in other studies, as well as there is no scientific evidence of breast cancer or local recurrence after fat grafting in conservative surgery. The technique is promising in patients with invasive cancer. It is simple and provides restoration of shape and volume, with natural texture. This approach may replace more complex procedures, such as intervention in the other breast to obtain symmetry, and is a good alternative in small and medium volume breasts. With the success of the technique, women with larger tumors and with an unfavorable tumor/breast volume ratio for conservative surgery tend to benefit from this type of reconstruction.

R E S U M O Objetivo: avaliar recorrência local e sistêmica do câncer de mama em pacientes submetidas ao enxerto autólogo de gordura na reconstrução imediata após cirurgia conservadora para o câncer de mama. Métodos: estudo de coorte histórica em que foram comparadas 167 pacientes submetidas à cirurgia conservadora sem reconstrução com 27 pacientes submetidas ao tratamento conservador com reconstrução imediata do enxerto, seguindo técnica de Coleman. Todas as pacientes eram portadoras de carcinoma invasor e foram operadas por um único cirurgião, no período de 2004 a 2011. O tempo de acompanhamento pós-operatório foi 36 meses. Resultados: a incidência global de recidiva local foi 2,4%. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (uma paciente) para o grupo lipoenxertia e 1,8% (três pacientes) para grupo da cirurgia conservadora sem reconstrução. Conclusão: não houve diferença significativa para recorrência local ou sistêmica nos grupos estudados. O enxerto autólogo imediato de gordura parece ser um procedimento seguro. Descritores: Reconstrução. Mama. Neoplasias da Mama. Recidiva Local de Neoplasia. Transplante Autólogo.

REFERENCES 1. Pearl RA, Leedham SJ, Pacifico MD. The safety of autologous fat transfer in breast cancer: lessons from stem cell biology. J Plast Reconstr Aesthet Surg. 2012;65(3):283-8.

2. Lohsiriwat V, Curigliano G, Rietjens M, Goldhirsch A, Petit JY. Autologous fat transplantation in patients with breast cancer: “silencing” or “fueling” cancer recurrence? Breast. 2011;20(4):351-7. 3. Illouz YG. The fat cell “graft”: a new technique to fill depressions. Plast Reconstr Surg. 1986;78(1):122-3.

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4. Ogawa M, Hyakusoku H, Ishii N, Ono S. Fat grafting to the breast. Plast Reconstr Surg. 2008;121(2):702-3. 5. Rigotti G, Marchi A, Stringhini P, Baroni G, Galiè M, Molino AM, et al. Determining the oncological risk of autologous lipoaspirate grafting for post-mastectomy breast reconstruction. Aesthetic Plast Surg. 2010;34(4):475-80. 6. Rietjens M, De Lorenzi F, Rossetto F, Brenelli F, Manconi A, Martella S, et al. Safety of fat grafting in secondary breast reconstruction after cancer. J Plast Reconstr Aesthet Surg. 2011;64(4):477-83. 7. Petit JY, Botteri E, Lohsiriwat V, Rietjens M, De lorenzi F, Garusi C, et al. Locoregional recurrence risk after lipofilling in breast cancer patients. Ann Oncol. 2012;23(3):582-8. 8. Claro F Jr, Figueiredo JC, Zampar AG, Pinto-Neto  AM. Applicability and safety of autologous fat for reconstruction of the breast. Br J Surg. 2012;99(6):768-80. 9. Petit JY, Rietjens M, Botteri E, Rotmensz N, Bertolini F, Curigliano G, et al. Evaluation of fat grafting safety in patients with intraepithelial neoplasia: a matched-cohort study. Ann Oncol. 2013;24(6):1479-84. 10. Brenelli F, Rietjens M, De Lorenzi F, Pinto-Neto A, Rossetto F, Martella S, et al. Oncological safety of autologous fat grafting after breast conservative treatment: a prospective evaluation. Breast J. 2014;20(2):159-65. 11. Biazús JV, Falcão CC, Parizotto AC, Stumpf CC, Cavalheiro JA, Schuh F, et al. Immediate reconstruction with autologous fat transfer following breast-conservative surgery. Breast J. 2015;21(3):268-75. 12. Schultz I, Lindegren A, Wickman M. Improved shape and consistency after lipofilling of the breast: patients’ evaluation of the outcome. J Plast Surg Hand Surg. 2012;46(2):85-90. 13. Beck M, Amar O, Bodin F, Lutz JC, Lehmann S, Bruant-Rodier C. Evaluation of breast lipofilling after sequelae of conservative treatment for cancer. A prospective study of ten cases. Eur J Plast Surg. 2012;35(3):221-8.

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14. Cigna E, Ribuffo D, Sorvillo V, Atzeni M, Piperno A, Calò PG, et al. Secondary lipofilling after breast reconstruction with implants. Eur Rev Med Pharmacol Sci. 2012;16(12):1729-34. 15. Moltó García R, González Alonso V, Villaverde Doménech ME. Fat grafting in immediate breast reconstruction. Avoiding breast sequelae. Breast Cancer. 2016;23(1):134-40. 16. Hamza A, Lohsiriwat V, Rietjens M. Lipofilling in breast cancer surgery. Gland Surg. 2013;2(1):7-14. 17. Chan CW, McCulley SJ, Macmillan RD. Autologous fat transfer--a review of the literature with a focus on breast cancer surgery. J Plast Reconstr Aesthet Surg. 2008;61(12):1438-48. 18. Rigotti G, Marchi A, Galiè M, Baroni G, Benati D, Krampera M, et al. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg. 2007;119(5):1409-22; discussion 1423-4. 19. Missana MC, Laurent I, Barreau L, Balleyguier C. Autologous fat transfer in reconstructive breast surgery: indications, technique and results. Eur J Surg Oncol. 2007;33(6):685-90. 20. Coleman SR. Structural Fat Grafting [Chapter 47]. St Louis: Lippincott; 2007. p.480-5. 21. Elder EE, Kennedy CW, Gluch L, Carmalt HL, Janu NC, Joseph MG, et al. Patterns of breast cancer relapse. Eur J Surg Oncol. 2006;32(9):922-7. 22. de Blacam C, Momoh AO, Colakoglu S, Tobias AM, Lee BT. Evaluation of clinical outcomes and aesthetic results after autologous fat grafting for contour deformities of the reconstructed breast. Plast Reconstr Surg. 2011;128(5):411e-8e. 23. Largo RD, Tchang LA, Mele V, Scherberich A, Harder Y, Wettstein R, et al. Efficacy, safety and complications of autologous fat grafting to healthy breast tissue: a systematic review. J Plastic Reconstr Aesthet Surg. 2014;67(4):437-48. 24. Zocchi ML, Zuliani F. Bicompartmental breast lipostructuring. Aesthetic Plast Surg. 2008;32(2):313-28. 25. Veber M, Tourasse C, Toussoun G, Moutran M, Mojallal A, Delay E. Radiographic findings after

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breast augmentation by autologous fat transfer. Plast Reconstr Surg. 2011;127(3):1289-99. 26. Gosset J, Guerin N, Toussoun G, Delaporte T, Delay E. [Radiological evaluation after lipomodelling for correction of breast conservative treatment sequelae]. Ann Chir Plast Esthet. 2008;53(2):178-89. (French) 27. Carvajal J, PatiĂąo JH. Mammographic findings after breast augmentation with autologous fat injection. Aesthet Surg J. 2008;28(2):153-62. 28. Rubin JP, Coon D, Zuley M, Toy J, Asano Y, Kurita M, et al. Mammographic changes after fat transfer to the breast compared with changes after breast reduction: a blinded study. Plast Reconstr

Surg. 2012;129(5):1029-38. 29. Coleman SR, Saboeiro AP. Fat grafting to the breast revisted: safety and efficacy. Plast Reconstr Surg. 2007;119(3):775-85. Received in: 02/10/2016 Accepted for publication: 09/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Camile Cesa Stumpf E-mail: camystumpf@gmail.com

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DOI: 10.1590/0100-69912017002013

Original Article

Profile of skin cancer in Pomeranian communities of the State of Espírito Santo Panorama do câncer da pele em comunidades de imigrantes Pomeranos do Estado do Espírito Santo Patrícia Henriques Lyra Frasson1; Danilo Schwab Duque1; Estanrley Barcelos Pinto1; Giulia Cerutti Dalvi1; Sammy Zogheib Madalon1; Tarcizo Afonso Nunes3; Paulo Roberto Merçon de-Vargas2. A B S T R A C T Objectives: to evaluate the profile of skin cancer in Pomeranian communities of the State of Espírito Santo, composed of descendants of European immigrants, regarding gender and age at diagnosis, lesion size and histological type. Method: we studied histopathological reports of 3,781 patients operated between 2000 and 2010, with resection of 4,881 lesions. We assessed histological type, lesion size, age and gender of the patients at diagnosis and their correlations in the 11-year period. Results: the histopathological examination revealed basal cell carcinoma in 3,159 patients (83.5%), squamous cell carcinoma in 415 (11%), melanoma in 64 (1.7%), and 143 patients (3.8%) had combined lesions of basal cell carcinoma and squamous cell carcinoma. As to size, 47.1% measured between 5.1 and 10mm. The age group of 61 to 70 years was the one that sustained the largest number of surgical interventions (24.3%). There was a predominance of the female gender (2,027, 53.6%) in relation to the male (1,754, 46.4%). Conclusion: basal cell carcinoma was the most frequent histological type. The prevalences of squamous cell carcinoma and melanoma were below the national estimate of the National Cancer Institute. The diagnosis of tumors occurred at more advanced ages (above 60 years) and there was an increase in the incidence and size of skin tumors in the male population. Keywords: Skin Neoplasms. Carcinoma, Basal Cell. Carcinoma, Squamous Cell. Occupational Exposure. Emigrants and Immigrants.

INTRODUCTION

S

kin cancer is the most common malignant neoplasm among Brazilians1, making it a serious public health problem. Its incidence has been increasing in recent years and this is mainly due to sun exposure. In 1859, the state of Espírito Santo received a significant number of Pomeranians, immigrants from the region between Germany and Poland, who fled the persecution of the tsarist regime. It is one of the largest concentrations of Pomeranians in Brazil, with the majority residing in the interior of the state, farmingbeing their main activity. Prolonged exposure to the sun associated with skin type (white, light eyes and hair) has contributed to the appearance of several skin lesions over the years. Pomeranians live far from the capital and still have communication difficulties because not all of them speak Portuguese. Some members of

this community only speak their own dialect. These characteristics contributed to the delay in the diagnosis and treatment of skin cancer, culminating with large tumors and deformities caused by neoplasia. Realizing this fact, in 1986, the Dermatology and Plastic Surgery Services of the Federal University of Espírito Santo created the University Extension Project entitled “Dermatological Assistance Program to Pomeranian Farmers in Espírito Santo” (PAD). This project is developed in partnership with the state health secretariat, cityhalls and the Lutheran church, to guarantee treatment in loco to this population, in a campaign regime. Annual visits are carried out in the 11 municipalities with the highest number of Pomeranians, focusing on guidance, diagnosis and treatment of skin cancer. Each campaign comprises 300-500 clinical visits and 60 to 100 surgical procedures. The surgical specimens are sent to the Pathology Department of the Cassiano Antonio Moraes University Hospital (HUCAM-UFES).

1 - Federal University of Espírito Santo, Department of Specialized Medicine, Plastic Surgery Service, Vitória, Espírito Santo State, Brazil. 2 - Federal University of Espírito Santo, Department of Pathology, Vitória, Espírito Santo State, Brazil. 3 - Federal University of Minas Gerais, Department of Surgery, Surgery Service, Belo Horizonte, Minas Gerais State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 187-193


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The objective of this research was to evaluate the profile of skin cancer in the 11 communities served by the PAD, regarding patients’histological type, tumor size, age and gender.

METHODS This is a retrospective study on records to the patients attended by the PAD between 2000 and 2010 carried out in the archives of the HUCAM-UFES Pathology Service. The research was approvedby the Ethics in Research Committee of the Federal University of Espírito Santo, under number 093/2010. The patients were evaluated once a year in each municipality. In the dermatological evaluation, when diagnosed with actinic keratosis, they received treatment with 5% fluorouracil or imiquimode for topical use, cryotherapy, or surgery in hypertrophic cases. Lesions suggestive of carcinoma, melanoma or atypical melanocytic lesions were referred for surgical treatment, in loco, with the plastic surgery team. Large-volume lesions or patients without adequate clinical conditions were referred for treatment in the state capital. A surgical treatment was performed on 5,543 patients and 7,225 skin lesions were excised. Medical students supervised by two plastic surgeons performed the procedures. The surgical specimens were sent to the HUCAM Pathology Service, which generated 7,225 histopathological reports, as described in Table 1. Table 1. Histopathological diagnosis of surgical specimens obtained by the Program of Dermatological Assistance Pomeranian Farmers (PAD) between 2000 and 2010.

Diagnosis

N

%

BCC*

4,195

58.1

SCC**

606

8.4

Melanoma

80

1.1

Premalignant lesions***

1,367

18.9

Other malignant neoplasms

14

0.2

Other benign tumors

963

13.3

Total

7,225

100

* BCC: Basal Cell Carcinoma; ** SCC: Squamous Cell Carcinoma; Premalignant lesions: actinic keratosis and atypical melanocytic nevi.

We studied 4,881 reports of 3,781 patients, of which 1,754 were male (46.4%) and 2,027 female (53.6%). The majority, 3,296 patients (87.2%), were farmers. The age ranged from ten to 99 years, 52.7% being over 60, with a median of 62. The number of surgical procedures varied from one (78.8%) to seven (0.03%) per individual, totalizing the resection of 4,881 lesions. We categorized the size of the lesion in its largest diameter with intervals of 5mm and evaluated it considering only one lesion per individual, according to the mean, median, standard deviation and linear regression. We categorized age at 10-year intervals and assessed it according to mean, median, standard deviation and linear regression, and gender, by means of simple frequency analysis. We carried out the data analysis data by individual, considering only one lesion, with random exclusion of the other lesions. From the data obtained, were made correlations between the variables (age, histological diagnosis, tumor size and gender), as described below. We entered and analyzed the data in an Excel spreadsheet (Microsoft®) and SPSS 19.0 program (IBM®). We summarized the nominal variables by simple frequency and the dimensional ones by the mean, median and standard deviation. We used concordance analyzes and linear regression, and the level of significance was a=0.05. We considered a significant trend the one whose estimated regression model obtained p<0.05.

RESULTS Histopathological examination revealed basal cell carcinoma (BCC) with variations in 3,159 patients (83.5%), squamous cell carcinoma (SCC) in 415 (11%), melanoma in 64 (1.7%) and combined BCC and SCC in 143 patients (3.8%). In the analysis by number of lesions, the histopathological examination presented 4,195 BCC (85.9%), 606 SCC (12.4%) and 80 melanomas (1.7%). When evaluating the BCC/SCC ratio by the linear regression model, there was no tendency towards increase in this proportion (p=0.233), but we noticed a

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Table 2. Size of tumors categorized according to the number of individuals.

Size of the lesion

N

%

0 to 5 mm

793

21

5.1 to 10 mm

1,782

47.1

10.1 the 15 mm

765

20.2

15.1 to 20 mm

254

6.7

Above 20mm

171

4.5

Without information

16

0.4

Total

3,781

100

Figure 1. Number of surgical procedures performed on men and women over the course of 11 years.

disproportion of the number of BCC in relation to the number of SCCs, whose mean was 7.32. Skin tumors showed the following measurements: BCC ranged from 1mm to 78mm, median of eight; SCC, from 2.2 to 45mm, and melanoma, from 2mm to 46mm, both with a median of 10mm. During the evaluated period, there was a tendency to increase in the mean tumors size evidenced by the linear regression (p=0.047). After categorization, we observed that 47.1% of the tumors measured between 5.1 and 10 mm, the other measures showing lower percentages (Table 2). Considering all patients, the mean age at diagnosis was 60.7 years. The age group of 61 to 70 years was the one that sustained the largest number of surgical interventions, 23.7%. Considering the histological diagnosis, the mean patients’ age was 50.27 years for melanoma, 60.53 years for BCC and 62.4 years for SCC (Table 3).

Through the correlation between age and diagnosis by the Kruskal-Wallis test, there was a significant difference in the histopathological diagnosis. Using the Dunn Test, we found that all diagnoses differed from each other and the highest ages were in patients with combined lesions (concomitant BCC and SCC), followed by SCC, BCC, and melanoma. There was no significant difference between genders. There was a predominance of the female gender (2,027, 53.6%) over the male (1,754, 46.4%), but without significance. The linear regression analysis, however, revealed a growing tendency of skin cancer diagnosedin men and decreasing in women, with a consequent increase in the male/female ratio over the years (Figure 1). When comparing the tumor largest diameter with the patients’ age groups and using the Spearman’s correlation coefficient, we observed that there was a significant, though weak, correlation between age and lesion size, whose coefficient was 0.096. That is, as age increases, the size of the lesion also increases (Figure 2).

Table 3. Age according to patients’ histologic diagnosis and gender.

Age Variables

Test results */** and Dunn test Standard p deviation value

N

Min

Max

Median

Average

3,158

16

99

61

60.53

14.73

* Histopathological SCC Diagnosis Melanoma

415

14

95

62

62.4

14.53

64

10

88

47

50.27

20.76

Combined

143

33

88

68

65.56

11.99

Male

1,754

12

98

62

60.85

14.15

Female

2,027

10

99

62

60.66

15.41

BCC

** Gender

0.000

0.986

* Kruskal-Wallis test; n= number of patients; BCC= basal cell carcinoma; Combined= BCC+SCC. **Mann-Whitney Test; age expressed in years; SCC= squamous cell carcinoma. Rev. Col. Bras. Cir. 2017; 44(2): 187-193

average posts

Statistically significant difference (p < 0.05)

1,870.26

SCC, Melanoma and combined

2,008.48

BCC, Melanoma and combined

1,324.14

BCC, SCC and combined

2,248.56

BCC, SCC and melanoma

1,890.16

1,890.80


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Figure 2. Correlation between age and tumor size.

As for histological diagnosis, only the BCC differed from all others, being the one that had the smallest lesions. Patients diagnosed with SCC, melanoma, and combined lesions had lesions of similar size. Males (median 9mm) had higher lesion size values​​ than females (median 8mm). There was a significant difference between lesion size, histopathological diagnosis and gender.

DISCUSSION The histopathological diagnosis in the analyzed population differs from the world and the country statistics, with 85.94% BCC and 12.41% SCC, a BCC/SCC ratio ranging from 4.33 to 11.71, with a mean of 7.32:1. This is well above the numbers in the literature, from 3:1 and 1.64% melanoma, similar to the study by Ferreira and Nascimento2, but much lower than described in the literature2,3. Actinic keratosis is recognized as a potential SCC precursor. However, true transformation rates are difficult to measure and estimates range from <0.1% to 0.6% per year until malignant transformation of 20% to 25% of the lesions4,5. Although it is not possible to predict which keratoses could progress to SCC, it is accepted that the presence of keratosis is a risk marker for the patient and therefore should be treated to avoid possible morbidity and mortality4,6. Thus, early intervention recommended in this program for this condition, could explain the decrease in the

diagnosis rate of squamous cell carcinoma and the increase in the BCC/SCC ratio. At the Global Skin Cancer Conference, in 2011, was reported that most of the economic burden of melanoma is a result of the treatment of nevi, especially in young patients. In agreement with this research4, this study credits the low rate of diagnosis of melanoma to the early resections of suspicious melanocytic lesions. In the literature, the diameter of skin cancer lesions ranged from 1.7mm to 3.9mm3,6,7. In this work, even with the educational actions for the population, the diameter varied between 1mm and 78mm. This result is much higher than expected and with a significant increasingtendency, as verified by the linear regression analysis (p=0.047), with a mean annual increase percentage of 0.002%. The BCC were the smallest, with a median of 8mm, SCC and melanomas with median of 10mm, and the combined lesions with 9.3mm. By analyzing the lesionslarger diameter and comparing it with the age groups, we verified a significant association, that is, the lesion diameter at diagnosis tends to be higher in groups of more advanced ages. Lesions in males were larger in diameter than those in females were. Although the size found was greater than expected, the median of all lesions was below 2cm in their largest diameter, that is, the TNM categories of skin tumors remained below T1 (≤2cm). The analysis of the mean ages of patients with different clinical types of cutaneous cancer revealed data similar to those in the literature3,8-12, whose mean remained over 60 years. The age group of 61 to 70 years was the one that sustained the largest number of surgical interventions (24.3%). Regarding the three types of tumors, the patients mean age was 50.27 years for melanoma (similar to the data from the Brazilian Melanoma Group), 60.53 years for BCC (a result similar to that found in the studies developed by Bariani et al.10 and Silveira et al.13) and 62.4 for SCC. When comparing the patients mean age during the study 11‑year period, there is a trend towards the diagnosis of skin tumors at more advanced ages and the main histological types found were combined lesions (BCC associated with SCC), followed by SCC.

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Frasson Profile of skin cancer in Pomeranian communities of the State of EspĂ­rito Santo

The incidence of carcinoma was higher in women (53.7%), but without significance in comparison to men, which is similar to studies by Ferreira and Nascimento2 and Machado Filho et al.9, but in disagreement with other publications14-16. However, linear regression analysis showed a tendency to increase in the number of diagnoses in men and decreasing in women. When analyzing the care curve (Figure 1), we concluded that, after 11 years, the trend is that diagnoses of skin cancer in men exceed the number of women, as observed in the literature. We believed that, over the years, continuous action on the same communities would lead to a reduction in the size of the lesions and in the age at diagnosis would tend to fall. This forced us to review the data and carry out a joint analysis of the obtained results. Culturally and for aesthetic reasons, women tend to seek medical services more often than men, which enables diagnosis and treatment in early stages of disease. The progressive increase in surgeries in men, however, suggests that working with this community provided access to all family members, including the male population. This fact may explain the change in the expected results curve, since the diagnosis in men occurred at a higher age than in the women, and the delay in the search for care would explain the larger diameter of such lesions. Thus, the larger size of the lesions may be translated into a repressed demand of men, presenting with lesions greater than the womendo at diagnosis. The increase in the number of skin cancer diagnoses is expected, since the aggression imposed on the environment has caused the reduction of the ozone layer and protection against ultraviolet radiation. Another contributing factor is exposure to the sun during work or the worship of body tanning. Patients with current age of 55 years received the first guidelines when they were about 30 years old, and had the opportunity to prevent or start treatment. The diagnosis in older patients reflects the use of adequate protection during youth, be it chemical or of barrier, as well as the early resection of pre-malignant lesions. Although visits are given only once a year in each municipality, the program is important because the patient has access to the dermatologist and the plastic surgeon at the same time, without the need to

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go to the capital or to regional centers. The presence of community members who participate as volunteers or as health agents contributes to the credibility of the program in the community. The results of this research show the profile of skin cancer in the population of these 11 municipalities and consolidate the importance of specific treatment to these populations and to others with similar characteristics. Investing in early prevention and treatment programs may reduce the prevalence of SCC and melanoma, keeping the age of diagnosis concentrated at 60 years. The most relevant result of this program, however, is the patientsâ&#x20AC;&#x2122; prevention and cure. Skin cancer is the most prevalent tumor in the population. Therefore, health policies aimed at prevention and early treatment are necessary. The dermatological care program greatly contributes to the management of skin cancer in these communities, but it cannot be adopted as an isolated treatment policy. It should also be seen as a means of providing training to local professionals. In addition, visits by health professionals help to continually remind the importance of basic measures and ensure access to health care for a community with unique characteristics. There must be continuous investment in education, training of health agents, encouragement to self-examination, guidelines on the emergence of suspicious lesions and establishment of a pathway for patientsâ&#x20AC;&#x2122; referral for evaluation with a multidisciplinary team, in loco or through teleconference. The delivery of digital photodermatoscopy for evaluation in specialized regional centers with subsequent access to the surgeon is an alternative for patients residing in distant areas. The adoption of a unique identification number of the individual, through the SUS card, will enable the creation of a more reliable database, allowing to know the actual number of patients with lesions removed, regardless of where the patient was treated, the evolution, and to plan treatment adequately. BCC is the most frequent skin cancer in Pomeranian communities. The prevalence of SCC and melanoma is in decline. The diagnosis of tumors occurred in older patients and there was an increased incidence and size of tumors in the male population. Tumors, although showing growth, remained on average, smaller than 2cm.

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R E S U M O Objetivos: avaliar o panorama do câncer de pele em comunidades pomeranas do Estado do Espírito Santo, compostas por descendentes de imigrantes europeus, quanto ao sexo e idade ao diagnóstico, tamanho da lesão e tipo histológico. Método: foram avaliados laudos histopatológicos de 3781 pacientes operados entre os anos de 2000 e 2010, com ressecção de 4881 lesões. Foram avaliados tipo histológico, tamanho das lesões, idade e sexo dos pacientes ao diagnóstico e suas correlações no período de 11 anos. Resultados: o exame histopatológico evidenciou carcinoma basocelular em 3159 pacientes (83,5%), carcinoma espinocelular em 415 (11%), melanoma em 64 (1,7%) e 143 pacientes (3,8%) apresentaram lesões combinadas de carcinoma basocelular e carcinoma espinocelular. Quanto ao tamanho, 47,1% media entre 5,1 e 10 mm. O grupo etário de 61 aos 70 anos foi o que sofreu o maior número de intervenções cirúrgicas (24,3%). Houve predomínio do sexo feminino (53,6%, n=2027) em relação ao masculino (46,4%, n=1754). Conclusão: o carcinoma basocelular foi o tipo histológico mais frequente. As prevalências do carcinoma espinocelular e do melanoma se situaram abaixo da estimativa nacional do Instituto Nacional de Câncer. O diagnóstico dos tumores ocorreu em idades mais avançadas (acima de 60 anos) e houve aumento da incidência e dimensões dos tumores de pele na população masculina. Descritores: Neoplasias Cutâneas. Carcinoma Basocelular. Carcinoma de Células Escamosas. Exposição Ocupacional. Emigrantes e Imigrantes.

REFERENCES 1. Brasil. Ministério da Saúde. Instituto Nacional de Câncer José de Alencar Gomes da Silva. Estimativa 2012: incidência de câncer no Brasil. Rio de Janeiro: Inca; 2011. 2. Ferreira FR, Nascimento LFC. Câncer cutâneo em Taubaté (SP) – Brasil, de 2001 a 2005: um estudo de prevalência. An Bras Dermatol. 2008;83(4):317-22. 3. Castro LGM, Freire MA, Toyama CL, Britto TL, Gomes AP. Câncer de pele em clínica particular em São Paulo-SP. An Bras Dermatol. 1996;71(6):471-6. 4. Bechelli LM, Curban GV. Compêndio de dermatologia. São Paulo:Atheneu; 1978. 5. Zalaudek I, Whiteman D, Rosendahl C, Menzies SW, Green AC, Hersey P, et al. Update on melanoma and non-melanoma skin cancer. Annual Skin Cancer Conference 2011, Hamilton Island, Australia, 5-6 August 2011. Expert Rev Anticancer Ther. 2011;11(2):1829-32. 6. Zalaudek I, Giacomel J, Schmid K, Bondino S, Rosendahl C, Cavicchini S, et al. Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model. J Am Acad Dermatol. 2011;66(4):589-97. 7. Naldi L, DiLandro A, D’Avanzo B, Parazzini F. Host-related and environmental risk factors for cutaneous basal cell carcinoma: evidence from an Italian case-control study. J Am Acad Dermatol. 2000;42(3):446-52.

8. Maafs E, De la Barreda F, Delgado R, Mohar A, Alfeirán A. Basal cell carcinoma of trunk and extremities. Int J Dermatol. 1997;36(8):622-8. 9. Machado Filho CAS, Fagundes DS, Sender F, Saraiva GL, Paschoal LHC, Costa MCC, et al. Neoplasias malignas cutâneas: estudo epidemiologico. An Bras Dermatol. 1996;71(6):479-84. 10. Bariani RL, Nahas FX, Barbosa MV, Farah AB, Ferreira LM. Carcinoma basocelular: perfil epidemiológico e terapêutico de uma população urbana. Acta Cir Bras. 2006;21(2):66-73. 11. Nasser N. Epidemiologia dos cânceres espinocelulares. Blumenau (SC) – Brasil, de 1980-1999. An Bras Dermatol. 2004;79(6):669-77. 12. Nasser N. Epidemiologia dos carcinomas basocelulares em Blumenau, SC, Brasil, de 1980-1999. An Bras Dermatol. 2005;80(4):363-8. 13. Silveira ML, Casalechi HL, Casalechi VL, Novo NF, Barbo MLP, Ruiz LRB. Estudo epidemiológico dos carcinomas basocelulares, na população atendida no Conjunto Hospitalar de Sorocaba, no período de 2001 a 2005. In: XI Encontro Latino-Americano de Iniciação Científica e VII Encontro Latino-Americano de Pós-Graduação; 2007; São José dos Campos(SP): Universidade do Vale do Paraíba, 2007. 14. Kumar P, Orton CI, McWilliam LJ, Watson S. Incidence of incomplete excision in surgically treated basal cell carcinoma: a retrospective clinical audit. Br J Plast Surg. 2000;53(7):563-6. 15. Mureau MA, Moolenburgh SE, Levendag PC, Hofer SO. Aesthetic and functional outcome fol-

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Frasson Profile of skin cancer in Pomeranian communities of the State of EspĂ­rito Santo

lowing nasal reconstruction. Plast Reconstr Surg. 2007;120(5):1217-27. 16. Telfer NR, Colver GB, Morton CA; British Association of Dermatologists. Guidelines for the management of basal cell carcinoma. Br J Dermatol. 2008;159(1):35-48.

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Received in: 12/09/2016 Accepted for publication: 01/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Patricia Henriques Lyra Frasson E-mail: patricialyra@uol.com.br patricialyra@gmail.com

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DOI: 10.1590/0100-69912017002014

Original Article

Tracheobronchial injuries in chest trauma: a 17-year experience Lesões traqueobrônquicas no trauma torácico: experiência de 17 anos Roberto Saad Jr, TCBC-SP1; Roberto Gonçalves, TCBC-SP1; Vicente Dorgan Neto, TCBC-SP1; Jacqueline Arantes G. Perlingeiro, TCBC-SP1; Jorge Henrique Rivaben, ACBC-SP1; Márcio Botter, TCBC-SP1; José César Assef, TCBC-SP1. A B S T R A C T Objective: to discuss the clinical and therapeutic aspects of tracheobronchial lesions in victims of thoracic trauma. Methods: we analy‑ zed the medical records of patients with tracheobronchial lesions treated at the São Paulo Holy Home from April 1991 to June 2008. We established patients’ severity through physiological (RTS) and anatomical trauma indices (ISS, PTTI). We used TRISS (Trauma Revised Injury Severity Score) to evaluate the probability of survival. Results: nine patients had tracheobronchial lesions, all males, aged between 17 and 38 years. The mean values ​​of the trauma indices were: RTS ‑ 6.8; ISS ‑ 38; PTTI ‑ 20.0; and TRISS ‑ 0.78. Regarding the clinical picture, six patients displayed only emphysema of the thoracic wall or the mediastinum and three presented with hemodynamic or respiratory instability. The time interval from patient admission to diagnosis ranged from one hour to three days. Cervicotomy was performed in two patients and thoracotomy, in seven (77.7%), being bilateral in one case. Length of hospitalization ranged from nine to 60 days, mean of 21. Complications appeared in four patients (44%) and mortality was nil. Conclusion: tracheobronchial tree trauma is rare, it can evolve with few symptoms, which makes immediate diagnosis difficult, and presents a high rate of complications, although with low mortality. Keywords: Bronchi. Thoracic Injuries. Thoracic Surgery. Trachea.

INTRODUCTION

T

racheobronchial lesions resulting from both closed and penetrating thoracic trauma are rare and often fatal. The bronchial treehas great elasticity and mobility. It is naturally protected by the shoulder girdle, in all its extension in the cervico-thoracic transition, anteriorly by the mandible and sternum, posteriorly by the spinal column and laterally by the bones and muscles of the costal grid. Hence, it is rarely affected by thoracic trauma. In general, the incidence of tracheobronchial lesions ranges from 0.3 to 1%. In large urban trauma centers, with 2,500 to 3,000 admissions per year, two to four tracheobronchial lesions occurannually. In 1,178 necropsies after trauma, 33 (2.8%) patients with tracheobronchial lesions were found, of which 27 (81.8%) died almost immediately after trauma1. The larynx and cervical trachea are most often subject to open lesions, whereas the thoracic trachea and bronchi are sites of lesions caused by closed trauma. In the last decades, with the improvement of prehospital care and transportation, the number of patients with this type of trauma who arrive alive in

the emergency room has increased2-5. Success in the diagnosis and treatment of such lesions requires a high level of suspicion, particularly in closed trauma, in which they may go unnoticed due to the occurrence of associated lesions. Some authors report rates of 25 to 68% of immediately undiagnosed tracheobronchial lesions3,6. The clinical picture may be poor, which hampers diagnosis and, consequently, postpones treatment, compromising the restoration of pulmonary function and determining the appearance of complications and death. In this study, after 17 years of experience, we aimed to analyze the difficulty of diagnosis, the most appropriate treatment, complications and mortality.

METHODS We conducted a review of the trauma protocols and medical records of all patients who were victims of closed or penetrating chest trauma treated at the Emergency Department of the Department of Surgery of the Faculty of Medical Sciences of the São Paulo Holy Home, between 1991 and 2008. This study

1 - Faculty of Medical Sciences of the São Paulo Holy Home, Department of Surgery, São Paulo, São Paulo State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 194-201


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was approved by the Ethics and Research Committee of the Faculty of Medical Sciences the São Paulo Holy Home (protocol # 052/11). We included all patients with tracheobronchial lesions above the age of 14. Younger individuals were treated at the Pediatric Service. We excluded cases with iatrogenic lesions (intubation, surgical manipulation), those exposed to the ingestion of chemical agents or those who sustained injuries caused by hot vapors. We characterized patient severity by the physiological (RTS – Revised Trauma Score) and anatomical (ISS – Injury Severity Score, and PTTI – Penetrating Thoracic Trauma Index). We used the TRISS – Trauma Revised Injury Severity Score – to evaluate the probability of survival. It consists of the combination of physiological (RTS) and anatomical (ISS) parameters with the patient’s age and the mechanism of trauma. The RTS, created by Champion et al.7, in 1989, ranges from 0 to 7.84, and the highest values​​ are associated with a better prognosis. This index is based on the Glasgow coma scale, systolic blood pressure and respiratory rate at admission. The ISS and the PTTI aim at evaluating the organs affected and quantifying the associated complications. The ISS, proposed by Baker et al.8, varies from 1 to 75: the higher this index, the greater the trauma severity. It relies on the degree of injury of each organ for each body segment. The analyzed variables included age, gender, etiologic agent, trauma mechanism, hemodynamic status at admission, diagnosis, treatment, complications and mortality. Although the number of cases was small, we mainly sought to quantify the time that was necessary to make the diagnosis between the arrival of the victim and the finding of the tracheobronchial lesion.

RESULTS

Figure 1. Bronchial lesion diagnosed by computed tomography. Noti‑ ce continuity solution in the right stem bronchus and accu‑ mulation of air, just below the lesion.

Regarding the clinical picture, six patients presented only emphysema of the thoracic wall or the mediastinum and they arrived hemodynamically stable in the Emergency Room. At admission, three presented with hemodynamic or respiratory instability, one with hypertensive pneumothorax, one with open pneumothorax and one with massive hemothorax. The trauma indices averages observed in the nine individuals with tracheobronchial lesions are shown in Table 1. The time interval required from patient admission to diagnosis ranged from one hour to three days, the majority within 24 hours (Table 2). Bronchoscopy was performed in six cases and detected the lesions in four of them: one patient with a left tracheal lesion 4cm from the vocal folds, one with a tracheal lesion 2cm from the carina, one with a left bronchial lesion, and one with a bilateral stem bronchial lesion, but diagnosed only of the left lesion, Table 1. Average values of trauma indexes.

Nine patients had tracheobronchial lesions, which meant an average of 0.5 patients per year. All were male, aged between 17 and 38 years, mean of 26. The lesions were produced by penetrating wounds in six cases (66.6%), four of them by firearm projectiles and two by stabbing. The remaining three patients were victims of closed traumas, all run over.

Index

Average values

RTS

6.8

ISS

38

PTTI

20

TRISS

0.78

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Figure 2. Chest radiograph. â&#x20AC;&#x153;Fallen lungâ&#x20AC;? sign and complex scapular fracture to the left, denoting a high-energy trauma.

1.5cm from the carina, the lesion on the right going unnoticed. In the others, the diagnosis was imminently clinical-radiological. As for evolution and treatment, the patients were submitted to pleural drainage on admission. The bubbling in the drainage system suggestive of a large bronchopleural fistula was observed in six (66.6%) patients. All patients underwent surgery, and the time elapsed between admission and the operative procedure ranged from one hour to thirty days, most in 30 hours, due to the difficulty in diagnosis. In both cases of cervical tracheal lesions, the diagnosis was immediate, and primary suture of the lesions was performed, without tracheostomy. One of them, a victim of gunshot injury, had an associated esophageal lesion that was debrided and sutured, with a muscular flap interposition between the esophagus and the trachea. Posterolateral thoracotomy was performed in seven (77.7%) patients, three on the left, three on the right and one bilateral. Regarding the type of lesion found in the intraoperative period, we observed a partial airway section in seven (70%) cases and a complete section in three (30%). It is worth remembering that there were nine patients, but with a total of ten main respiratory tree injuries. One of the patients, a victim of infraclavicular gunshot wound with an intrathoracic tracheal lesion

2cm from the carina in its membranous portion, also had an esophageal lesion 25cm from the upper dental arch and a thoracic duct lesion. Access was through a right thoracotomy, withdebridement and suture of the trachea and esophagus wounds, and ligation of the thoracic duct. The esophageal lesion was tangential. This patient evolved with pleural empyema, but with good resolution and hospital discharge in nine days. One patient had three gunshot wounds, one in the face, one left paravertebral and one abdominal. At admission, he had abdominal pain, oral bleeding, subcutaneous emphysema and pneumothorax. He was initially submitted to thoracic drainage, exploratory laparotomy and suture of the lip wound. Intraoperative pan-endoscopy was normal. He evolved well, but with persistent image of pulmonary collapse at chest radiograph and small air leak through the chest drain. The bronchoscopy was repeated and there was no evidence of airway lesion. Computed tomography of the chest was performed, showing an image suggestive of injury to the bronchus in the upper right lobe (Figure 1). He was submitted to right thoracotomy, which revealed an almost complete lesion, with ischemia of the remaining tissue in the emergence of the upper lobebronchus, and it was decided to complete the section of the bronchus, resecting all ischemic areas, with its subsequent reimplantation. There was no associated vascular lesion. There was immediate pulmonary re-expansion, but as a result of spinal cord injury and paraplegia, he evolved with pneumonia and the total hospitalization time reached 60 days. The patient with stabbing wound on the back admitted in shock was drained and operated soon after admission. The exploratory laparotomy showed no lesion and he was then submitted to right thoracotomy due to hemodynamic instability and air leakage through the chest drain. The findings were a lesion in the bronchus to the inferior lobe and a concomitant arterial lesion, with active bleeding. Right inferior lobectomy was performed. He evolved with air fistula for seven days and partial atelectasis of the middle lobe that remained for ten postoperative days, but with satisfactory resolution with respiratory physiotherapy.

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Table 2. Characterization of patients with tracheobronchial injury.

Associated injuries

Diagnostic procedure

Surgery

Length of stay

1 hour

Left Thoracotomy

9 days

Empyema Discharge

Clinical and x-ray

On admission

Cervicotomy

11 days

Discharge

No

Bronchoscopy

3 days

Left Thoracotomy

60 days

Discharge

Left and right Stem bronchus

No

Bronchoscopy

1 day

Bilateral Thoracotomy

10 days

Discharge

Esophageal injury, chest Gunshotwound (hemothorax)

Bronchoscopy

3 hours

Cervicotomy

14 days

Discharge

Age

Trauma

Findings

1

26

Gunshot

Low trachea

Esophageal injury

Bronchoscopy

2

38

Stabbing

Cervical trachea

No

3

28

Closed trauma

Left stem bronchus

4

32

Gunshot

Diagnosis (time)

Evolution

5

17

Gunshot

Cervical trachea

6

19

Closed trauma

Left stem bronchus

No

Clinical and x-ray

8 hours

Left Thoracotomy

40 days

Empyema Discharge

7

24

Gunshot

Right stem bronchus

Gunshotwounds in face and abdomen

Clinical and x-ray

48 hours

Right Thoracotomy

16 days

Discharge

No

Clinical and x-ray

1 hour

Right Thoracotomy

12 days

Atelectasis of middle lobe associated with air leakage. Discharge

No

Clinical and x-ray

72 hours

Right Thoracotomy

18 days

Discharge

8

20

Stabbing

Lower lobar bronchus

9

34

Closed trauma

Left stem bronchus

In the case of closed trauma with left bronchus lesion diagnosed three days after trauma, the radiograph at admission and during evolution showed persistent pneumothorax even after drainage and without air fistula. Chest tomography confirmed this image (sign of the “fallen lung”), also showing animportant pulmonary contusion, including extensive contralateral lung involvement (Figure 2). This patient was operated after clinical improvement of the pulmonary contusion, with 30 days of injury. The intraoperative finding was a partial lesion of the stem bronchus next to the carina, with exposure of the mucosa, requiring resection of the injured segment with end-to-end anastomosis. In another patient with closed trauma, there was pneumothorax on the admission, which was drained. During arteriography to assess a possible subclavian lesion, he evolved with significant air

leakage through the drain and, due to the unavailability of bronchoscopy, underwent bronchography showing a contrast “stop” image in the left stem bronchus. Left thoracotomy was performed, revealing a complete stem bronchus lesion, being treated with pneumonectomy. There was no associated vascular lesion. The time of mechanical ventilation was prolonged and tracheostomy was performed. He presented with pleural empyema and was discharged after 40 days of hospitalization. The length of hospital stay in our series ranged from nine to 60 days, with a mean of 21. Of the nine patients, three (33.3%) evolved with complications, two pleural empyemas and one middle lobe atelectasis associated with air leakage. There were no deaths in this series. Of the nine patients, five (55.5%) had associated lesions. Table 2 brings the patients’characteristics.

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DISCUSSION Tracheobronchial lesions are rare, occurring in 1% to 3% of patients with closed trauma and 2% to 9% of those who suffered penetrating cervical and/ or thoracic injuries3,4. In our series of nine patients with tracheobronchial lesions, two were due to closed trauma. There are other causes of injury: foreign body aspiration, inhalation wounds and even iatrogenic injuries, such as intubation lesions, but they are uncommon. Cervical tracheal lesions are generally produced by penetrating wounds, being rare in the closed trauma, which preferentially causes lesions in the intrathoracic trachea and stem bronchus, 80% of which up to 2.5cm from the carina. Although most studies show a higher incidence of lesions in the right stem bronchus, considered less protected by the mediastinal structures, in our series the two patients with closed trauma had lesions in the left bronchus. There was a cervical tracheal injury with a stabbing wound and another with a gunshot wound3,5,9-13. The clinical picture varies according to lesion location and severity, and may not be immediately expressed, such as in closed trauma where it is believed to occur in up to two thirds of the tracheobronchial lesions, especially when on the left. In one of our cases, the diagnosis was made after three days and the lesion was on the left. Subcutaneous and mediastinal emphysema were the most common signs. We did not observe hemoptysis, and pneumothorax occurred in all patients with intrathoracic airway lesions. These are non-specific signs, such as dyspnea, but should be particularly valued when they persist even after initial treatment such as chest drainage. The radiological findings suggestive of tracheobronchial lesions are pneumothorax, pneumomediastinum, subcutaneous emphysema with air in the deep cervical fascias and a specific but not very sensitive signal is the â&#x20AC;&#x153;fallen lungâ&#x20AC;?, generally seen in cases of complete bronchial transection. The literature highlights the presence of pneumothorax in 70% and pneumomediastinum in up to 60% of the cases. The presence of fractures of the first three ribs and sternumclavicular disjunction should also prompt suspicion3,4,9,11,12.

It is important to highlight that up to 10% of patients with tracheobronchial lesions may present normal radiological examination in the immediate post-trauma period6,14. Radiological changes are non-diagnostic, but the presence of pneumomediastinum, persistent refractory pneumothorax, atelectasis and subcutaneous emphysema should raise the clinical suspicion of airway injury, and in this case, bronchoscopy should be the examination of choice, which should locate and characterize the lesion4. The presence of blood in the airways or difficulty in visualizing the distal bronchial tree may compromise the exam power of resolution. Therefore, some authors recommend repeating the bronchoscopy in the face of clinical suspicion. In intubated patients, where possible, the tube should be removed for proper evaluation4,6,11,15. Regarding bronchography, it is believed to have value for chronic lesions, but it is not a recommended test for the diagnosis of injuries soon after trauma, being even contraindicated in this phase by some authors9. We had a single case where it was performed, suggesting a bronchial injury that was confirmed intraoperatively, but it is not our exam of choice. It is worth noting that the diagnosis is not recognized in 79% of patients, since the peribronchial tissues maintain the airway flow temporarily satisfactory10. The ability of computed tomography to make this diagnosis has been improving lately, having been decisive in one of our patients, in whom bronchoscopy did not show the bronchial lesion16-19. Recently, with the advent of multi-channel tomography, the methodâ&#x20AC;&#x2122;s resolution power in the diagnosis of tracheobronchial lesions has been highlighted20-24. As for associated lesions, the esophagus is the most exposed organ in cervical tracheal trauma, reason why it should always be investigated2,4. In our series, of the two cervical tracheal wounds, one had an esophageal lesion that was debrided and sutured. In closed trauma, the incidence of esophageal injury is very low (less than 1%), but this diagnosis should not be forgotten. Due to the same mechanism of trauma, other lesions should be investigated, such as pulmonary contusion associated with multiple rib fractures, scapular fracture and vascular lesions4,5,12. We had one patient with scapular-humeral disjunction and brachial plexus lesion, with concomitant subclavian injury, and another with severe pulmonary

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contusion associated with multiple rib and scapula fractures,with important left shoulder deformity. Of the thoracic penetrating injuries, only one had arterial lesion associated with the bronchial injury and this patient underwent inferior lobectomy due to intraoperative hemodynamic instability. Regarding the approach to tracheobronchial lesions, it is believed that the majority can be treated by debridement and primary repair, both in penetrating and closed trauma4,6,11,14. In some situations, end-toend anastomosis may be necessary in both cervical and intrathoracic lesions, and tracheostomy is not mandatory. Small airways lacerations can be treated non-operatively, in selected, hemodynamically stable patients without associated lesions4,9,14. The lesions repair was done with nonabsorbable monofilament suture or with Polyglactin (Vicryl) in separate stitches. A muscle flap was used between the trachea and the esophagus in the combined lesion in one of our cases, as some authors suggest, to avoid late tracheoesophageal fistulas13,19. The access of choice for the intrathoracic lesions is the right thoracotomy, which allows to approach the majority of the intrathoracic lesions, avoiding the aortic arch and better exposing the airway, leaving the left thoracotomy, and even the sternotomy, for more distal left lesions or more complex ones7,11. Pulmonary resections are an alternative, especially in cases of vascular lesions associated with hemorrhage, which makes the bronchial repair difficult. We had two cases in which this was the option: one right inferior lobectomy with vascular lesion and one left pneumonectomy due to complete

lesion in the emergence of the stem bronchus, though without vascular injury. The excellence of anesthesia is fundamental for the success of the procedure, both in terms of adequate positioning of the endotracheal tube and in the control of airways pressure5,9. In our series, we achieved selective intubation in only three cases and this certainly facilitated the approach to the lesion. In the postoperative period, the correct positioning of the tube is also essential, preserving the suture line and reducing pressure on it. In special situations, particularly in complex and extensive lesions, the use of stents to avoid stenosis has been discussed and can be maintained for six to 18 months5,6. We have no experience with the use of airway prostheses in trauma in our Service, and it is our conduct to operate the patient as soon as possible. The overall estimated mortality for tracheobronchial lesions is 30%. We did not have deaths in our series, but our casuistry is very small. The authors consulted suggest that early diagnosis and treatment of tracheobronchial lesions are associated with better results, with a greater possibility of primary repair, preserving as much as possible the functioning pulmonary parenchyma, and minimizing the risks of stenosis, empyema and other complications, more common in late repairs. We had two patients who evolved with pleural empyema, one with associated lesion of the intrathoracic esophagus and the other operated after thirty days of injury. The other patients had a good evolution. We believe that the mechanism of trauma and clinical findings should be valued in the suspicion of airway injury and justify the insistence on early diagnosis.

R E S U M O Objetivo: discutir os aspectos clínicos e terapêuticos de lesões traqueobrônquicas em vítimas de trauma torácico. Métodos: análise de dados dos prontuários de pacientes com lesões traqueobrônquicas atendidas na Santa Casa de São Paulo no período de abril de 1991 a junho de 2008. A caracterização da gravidade dos doentes foi feita por meio de índices de trauma fisiológico (RTS) e anatômicos (ISS, PTTI). O TRISS (Trauma Revised Injury Severity Score) foi utilizado para avaliar a probabilidade de sobrevida. Resultados: nove doentes tinham lesões traqueobrônquicas, todos do sexo masculino, com idades entre 17 e 38 anos. Os valores médios dos índices de trauma foram: RTS- 6,8; ISS- 38; PTTI-20,0; TRISS-0,78. Com relação ao quadro clínico, seis apresentaram apenas enfisema de parede torácica ou do mediastino e três doentes se apresentaram com instabilidade hemodinâmica ou respiratória. O intervalo de tempo necessário para se firmar o diagnóstico, desde a admissão do doente, variou de uma hora a três dias. Cervicotomia foi realizada em dois pacientes e toracotomia foi realizada em sete (77,7%), sendo bilateral em um caso. O tempo de internação variou de nove a 60 dias, média de 21 dias. Complicações apareceram em quatro pacientes (44%) e a mortalidade foi nula. Conclusão: o trauma da árvore traqueobrônquica é raro, pode evoluir com poucos sintomas, o que dificulta o diagnóstico imediato, e apresenta alto índice de complicações embora com baixa mortalidade. Descritores: Brônquios. Traumatismos Torácicos. Cirurgia Torácica. Traqueia.

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REFERENCES 1. Marsico GA. Lesões da traqueia e grandes brônquios. In: Marsico GA. Trauma torácico. 1a ed. Rio de Janeiro: Revinter; 2006. p.147-58. 2. Bertelsen S, Howitz P. Injuries of the trachea and bronchi. Thorax. 1972;27(2):188-94. 3. Deslauriers J, Beaulieu M, Archambault G, LaForge J, Bernier R. Diagnosis and long-term follow-up of major bronchial disruptions due to nonpenetrating trauma. Ann Thorac Surg.1982;33(1):32-9. 4. Amauchi W, Birolini D, Branco PD, Oliveira MR. Injuries to the tracheobronchial tree in closed trauma. Thorax. 1983;38(12):923-8. 5. Taskinen SO, Salo JA, Halttunen PE, Sovijärvi AR. Tracheobronchial rupture due to blunt chest trauma: a follow-up study. Ann Thorac Surg. 1989;48(6):846-9. 6. Kiser AC, O`Brien SM, Detterbeck FC. Blunt tracheobronchial injuries: treatment and outcomes. Ann Thorac Surg. 2001;71(6):2059-65. 7. Champion HR, Saco WJ, Copes WS, Gann DS, Gennarelli TA, Flanagan ME. A revision of the Trauma Score. J Trauma. 1989;29(5):623-9. 8. Baker SP, O’Neill B, Haddon W Jr, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974;14(3):187-96. 9. Soothill EF. Closed traumatic rupture of the cervical trachea. Thorax.1960;15(1):89-92. 10. Angood PB, Attia EL, Brown RA, Mulder DS. Extrinsic civilian trauma to the larynx and cervical trachea--important predictors of long-term morbidity. J Trauma. 1986;26(10):869-73. 11. Roxburgh JC. Rupture of the tracheobronchial tree. Thorax.1987;42(9):681-8. 12. Mussi A, Ambrogi MC, Ribechini A, Lucchi M, Menoni F, Angeletti CA. Acute major airway injuries: clinical features and management. Eur J Cardiothorac Surg. 2001;20(1):46-51; discussion 51-2. 13. Cassada DC, Munyikwa MP, Moniz MP, Dieter RA Jr, Schuchmann GF, Enderson BL. Acute injuries of the trachea and major bronchi:

importance of early diagnosis. Ann Thorac Surg. 2000;69(5):1563-7. 14. Edwards WH Jr, Morris JA Jr, DeLozier JB 3rd, Adkins RB Jr. Airway injuries. The first priority in trauma. Am Surg. 1987;53(4):192-7. 15. Kirsh MM, Orringer MB, Behrendt DM, Sloan H. Management of tracheobronchial disruption secondary to nonpenetrating trauma. Ann Thorac Surg. 1976;22(1):93-101. 16. Chen JD, Shanmuganathan K, Mirvis SE, Kileen KL, Dutton RP. Using CT to diagnose tracheal rupture. AJR Am J Roentgenol. 2001;176(5):1273-80. 17. Noboru N, Fumio M, Shunsuke Y, Kichizo K, Masayuki Y, Sadaki, et al. Chest radiography assessment of tracheobronchial disruption associated with blunt chest trauma. J Trauma. 2002;53(2):372-7. 18. Balci AE, Eren N, Eren S, Ulkü R. Surgical treatment of post-traumatic tracheobronchial injuries: 14-year experience. Eur J Cardiothorac Surg. 2002;22(6):984-9. 19. Helmy N, Platz A, Stocker R, Trentz O. Bronchus rupture in multiply injured patients with blunt chest trauma. Eur J Trauma. 2002;28(1):31-4. 20. Le Guen M, Beigelman C, Bouhemad B, Wenjïe Y, Marmion F, Rouby JJ. Chest computed tomography with multiplanar reformatted images for diagnosing traumatic bronchial rupture: a case report. Crit Care. 2007;11(5):R94. 21. Faure A, Floccard B, Pilleul F, Faure F, Badinand B, Mennesson N, et al. Multiplanar reconstruction: a new method for diagnosis of tracheobronchial rupture? Intensive Care Med. 2007;33(12):21738. Epub 2007 Aug 8. 22. Kaewlai R, Avery LL, Asrani AV, Novelline RA. Multidetector CT of blunt thoracic trauma. Radiographics. 2008;28(6):1555-70. 23. Savas R, Alper H. Fallen lung sign: radiographic findings. Diagn Interv Radiol. 2008;14(3):120-1. 24. Tamura M, Oda M, Matsumoto I, Fujimori H, Shimizu Y, Watanabe G. Double-barrel reconstruction for complex bronchial disruption due to blunt thoracic trauma. Ann Thorac Surg. 2009;88(6):2008-10.

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Received in: 19/07/2016 Accepted for publication: 01/10/2016 Conflict of interest: none. Source of funding: none. Mailing address: Roberto Gonรงalves E-mail: rgtorax@yahoo.com.br

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DOI: 10.1590/0100-69912017002016

Original Article

Surgery in Brazilian Health Care: funding and physician distribution Cirurgia no Sistema Brasileiro de Saúde: financiamento e distribuição de médicos Nivaldo Alonso1; Benjamin B. Massenburg2; Rafael Galli1; Lucas Sobrado1; Dario Birolini, ECBC-SP1. A B S T R A C T Objective: to analyze demographic Brazilian medical data from the national public healthcare system (SUS), which provides free universal health coverage for the entire population, and discuss the problems revealed, with particular focus on surgical care. Methods: data was obtained from public healthcare databases including the Medical Demography, the Brazilian Federal Council of Medicine, the Brazilian Institute of Geography and Statistics, and the National Database of Healthcare Establishments. Density and distribution of the medical workforce and healthcare facilities were calculated, and the geographic regions were analyzed using the public private inequality index. Results: Brazil has an average of two physicians for every 1,000 inhabitants, who are unequally distributed throughout the country. There are 22,276 board certified general surgeons in Brazil (11.49 for every 100,000 people). The country currently has 257 medical schools, with 25,159 vacancies for medical students each year, with only around 13,500 vacancies for residency. The public private inequality index is 3.90 for the country, and ranges from 1.63 in the Rio de Janeiro up to 12.06 in Bahia. Conclusions: A significant part of the local population still faces many difficulties in accessing surgical care, particularly in the north and northeast of the country, where there are fewer hospitals and surgeons. Physicians and surgeons are particularly scarce in the public health system nationwide, and better incentives are needed to ensure an equal public and private workforce. Keywords: General Surgery. Public Health Administration. Public Policy. Surgery Department, Hospital. Medically Underserved Area.

INTRODUCTION

I

n 1988, Brazil developed a national public healthcare system (SUS), which provides free universal health coverage for the population and is managed by all levels of the government. It is a complex and dynamic system that still faces many difficulties. There are several aspects that should be taken in consideration to explain the difficulties in healthcare, including the geographic area, the size of the population, and the differences in distribution of this population. Brazil is a developing country of continental dimensions, it is the most populous country in South America with a population of over 200 million inhabitants. It is one of world’s largest economies and a regional leader in Latin America. However, it continues to have economic and social inequalities that plague many other developing countries. It has three levels of autonomous government – federal, 26 states and a federal district, along with 5.570 municipalities. Since 1991, Brazil has been considered an urban country with low demographic

density, as around 75% of the total population lives in an urban area1. Brazil could be mistaken for a developed country if only the gross domestic product (GDP) were considered, as it is the sixth largest in the world, valued at US$ 2,254 trillion2. However, a closer look reveals that the human developing index (HDI) ranks at 79th in the world3. This can best be explained by the socioeconomical discrepancies among different regions. The country has five geographical regions with variable demographic, economic, social, cultural and health conditions, leading to widespread social inequalities: North, Northeast, Southeast, South and Midwest. Attaining a high quality of surgical and anesthesia care is the one of the key concepts in achieving healthcare equality for all people today. Drs. Farmer and Kim noted that there are five billion people without access to surgery around the world, largely in low and middle income countries (LMIC)4. Similarly, there are over 500,000 post-delivery maternal mortalities each year who did not have access to a cesarean section. Thus, they concluded that surgery is “an indivisible and an indispensable part of healthcare”.

1 - Faculty of Medicine at the University of São Paulo, Department of Surgery, São Paulo, São Paulo State, Brazil. 2 - Harvard Medical School, Program in Global Surgery and Social Change, Boston, Massachusetts, United States of America. Rev. Col. Bras. Cir. 2017; 44(2): 202-207


Alonso Surgery in Brazilian Health Care: funding and physician distribution

Evidence and metrics to evaluate the quality of a health system, particularly for surgical procedures, are often imprecise. Recent systematic reviews of surgical care in LMIC have concluded that surgeries correcting congenital deformities and cesarean sections are quite cost effective, especially compared to other public health interventions5,6. More specifically, previous studies compared the benefits of cleft lip repair as it related to an individual’s lifetime income, which can increase by almost ten times for those who had surgery when compared to those without surgical repair7. Though the numbers of physician and medical school are considered important aspects in the evaluation of a health system, the geographic distribution can also play a role in the quality of access to healthcare. According to the Brazilian Federal Council of Medicine, the country currently has 257 medical schools, more than the United States and China with 149 and 150, respectively8, but they are not homogeneously distributed in the country. Additionally, most of the medical schools in Brazil are private. Medical data in Brazil is still scarce, especially in the more remote areas of the country and even more so in terms of surgical care. In this aspect, the book Medical Demography in Brazil9,10 by the Brazilian Federal Council of Medicine (CFM) and the Regional Council of Medicine of the State of São Paulo (CREMESP) is pioneer. It is a national study that provides primary data about different aspects of healthcare, most notably physician distribution. With this in mind, the authors sought to further analyze existing Brazilian medical data and discuss the problems revealed, with particular focus on surgical care.

METHODS Raw data was obtained from the both volumes of the book Medical Demography in Brazil, from 2011 and 20139,10. Further information was collected from the CREMESP and CFM (Brazilian Federal Council of Medicine), which conglomerates all Medical Specialty Societies. The CFM uses four different databases: AMS (Sanitary Medical Assistance), IBGE (Brazilian

203

Institute of Geography and Statistics), CNES (National Database of Healthcare Establishments) and RAIS (Annual Recordings of Healthcare Information). Data for comparison from other countries was collected from the WHO World Health Statistics 2014. The authors also reviewed previous literature on the costeffectiveness and impact of surgery in a patient’s life. This study also uses the Public/Private Inequality Index (PPII) as characteristic measure of the workforce10. The PPII is a ratio of the density of physicians working in the private sector, divided by the density of physicians working in the public sector, for a determined region. Both of these densities are divided by the patient population of either the public or private health sector. Therefore, the higher the ratio, the larger the shift towards the private system and away from the public healthcare system, in terms of workforce distribution. This is used to give some epidemiological data regarding the medical workforce throughout Brazil and serves to measure sector inequality.

RESULTS Brazil has an average of two physicians for every 1,000 inhabitants, who are unequally distributed throughout the country (Figure 1). There are 22,276 board certified general surgeons, with a ratio of 11.49 for every 100,000 people. Most of them are located in the southeast of the country (Figure 2). The population density follows a similar pattern, though there are still higher ratios of general surgeons in the South, Southeast and Midwest when compared to the North and Northeast (Figure 2). The country has 94.070 health facilities, with 52.021 public and 42.049 private facilities (Figure 3)11. Brazil currently has 257 medical schools, with 25,159 vacancies for medical students each year. Following medical school, there are around 13,500 vacancies for residency. Overall, of 388,015 practicing physicians in Brazil, though 180,136 physicians (46.43%) have no residency training9,10. The PPII is shown in figure 4, and ranges from 1.63 in the Rio de Janeiro up to 12.06 in Bahia. The PPII is 3.90 for the entire nation of Brazil9,10.

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Figure 1. The density of physicians in Brazil by region.

According to the WHO, Brazil annually spends a total of US$1,035 per capita (8.9% of GDP) on healthcare, compared to US$8467 (17.7% of GDP) in the United States and US$4474 (11.3% of GDP) in Germany12. In Brazil, 45.7% of this expenditure is public, compared to 47.8% in the Unites States and 76.5% in Germany13.

DISCUSSION The national public healthcare system (SUS) was developed to ensure that every citizen has access to effective and free healthcare. Nevertheless, a high but uncertain percentage of the population has little access to health professionals and thus lives under very low-quality healthcare. The growth of physicians in Brazil has been nearly exponential for at least 40 years. From 1970 to 2012, the number of physicians grew 557.72%. Comparatively, the population only grew by 101.84%. Even though the growth of the medical workforce vastly outweighs the population expansion, the federal government recently established a higher national

Figure 2. The proportion of general surgeons and the population who live and work in each region.

target of 2.5 doctors per 1,000 inhabitants – Brazil has already reached 400.000 doctors and a density of two doctors per 1,000 inhabitants. However, there is no plan to reduce inequalities in the concentration and distribution of physicians among regions and municipalities, or between the public and private sectors of health, which is, in fact, one of the major problems encountered in Brazilian healthcare. Brazil has adopted the strategy of the “overflow” of professionals and is determined that the additional professionals will settle in the locations that are currently underserved. This disorganized settlement is even less effective, considering that the number of specialists and the questionable quality of their training, leading to further worsening of the quality of surgical treatment. The quantity of physicians has been increasing successfully, but the quality of their medical training has remained stagnant. The shortage of physicians and surgeons is a problem worldwide. However, in the particular case of Brazil, what draws attention is the unequal distribution throughout the country, with physicians more concentrated in the south, southeast and along the coast (Figures 1 and 2). General hospitals distribution follows a similar pattern (figure 4). As previously reported, Brazil has around 22,276 board certified general surgeons and 18,236 anesthesiologists9, which compares to more populous countries such as the USA, for instance, which has around 23,000 general surgeons14. Furthermore, analyzing the public/private inequality index (PPII), reveals that physicians are much more concentrated in the private healthcare system. The national PPII is 3.90, which means that patients in the private system have access to nearly four times as many physicians as patients in the public sector. The range displayed throughout regions and states is dramatic. In Bahia, in the northeast region, the ratio is 12.06, suggesting that the patients in the public sector have access to less than 10% of the number physicians that may be accessed in the private sector. In the southeast region, the ratio comes down to 2.05 in São Paulo and 1.63 in Rio de Janeiro (Figure 4). Only 25% of the population of Brazil is covered by a private health insurance15, with the remaining 75% completely relying on public care.

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Alonso Surgery in Brazilian Health Care: funding and physician distribution

Figure 3. The distribution and characteristics of public and private health facilities in Brazil by region.

Perhaps one of the most aggravating factors to this situation is the questionable quality of recent medical graduates â&#x20AC;&#x201C; 55% medical of recent graduates from SĂŁo Paulo failed the exam applied by the CREMESP16. Additionally, there is a large lack of vacancies in medical residency to all graduates. Most graduates of medical schools in Brazil have not completed residency training: of 388,015 practicing physicians in Brazil, 46.43%, or 180,136, have no residency training9,10. Since there are no medical residency positions for all of these doctors, many of them will remain untrained. There are only enough vacancies in residency for 52% of the 15,751 medical students who graduate in Brazil in 2011. Though the number of residency vacancies has been raised to around 13,500 in 2014, the number of medical school graduates has also increased to 25,159. Thus, only 54% of medical students have a position in residency available to them. The geographic distribution of these positions also follows the distribution of specialized physicians, further compounding the problem. The southeastern states, particularly SĂŁo Paulo, act as a specialist center, as they are typically the places with the best general healthcare infrastructure. These states receive residents from other Brazilian states, and retain many of them for the rest of their career. The inadequate distribution of specialized human resources throughout Brazil may be due to a lack of attractiveness to work in the more remote regions. Lack of basic infrastructure in these more rural areas is a barrier to surgical workforce recruitment. Ultimately, this poor distribution of the medical and surgical workforce certainly contributes to the low quality of surgical care in certain regions of the country.

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There is no evidence that suggests that there are places that are overcrowded with surgeons and hospitals, though it is clear that certain regions have large deficiencies in workforce and thus insufficient surgical treatment. This lack of healthcare infrastructure also may be a direct consequence of the scarce investment. In terms of healthcare expenditure, Brazil is far below other well-developed countries. According to the WHO, Brazil annually spends a total of US$ 1,035 per capita (8.9% of GDP) on healthcare, compared to US$ 8,467 (17.7% of GDP) in the United States and US$ 4,474 (11.3% of GDP) in Germany12. In Brazil, 45.7% of this expenditure is public, compared to 47.8% in the Unites States and 76.5% in Germany13. The access to healthcare data and statistics is still scarce in Brazil, creating some limitations to this study. The regions with limited data are typically the regions with poor health coverage as well. One concern with the data used in this study is the overlap between several different medical associations, recording similar indicators. For instance, a general surgeon may be registered in two different states, or may have another title, so he may not be recognized as a general surgeon, in certain datasets. With this in mind, the authors still believe the study has important implications in

Figure 4. The Public Private Inequality Index of the medical workforce in Brazil by state.

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identifying the problems with the health system in Brazil, particularly regarding surgical care. A significant part of the local population still faces many difficulties in accessing surgical care. It is especially concerning in the north and northeast of the country, where there are fewer hospitals and surgeons, and the population relies almost completely on the public health system. Physicians and particularly surgeons are scarce in the public health system nationwide, and better incentives should be created to ensure an equal public and private workforce. The lack of public investment in healthcare is evident when compared to other countries of similar sized and

developed countries. Improving the healthcare system should involve investing in infrastructure and creating long-lasting projects to attract healthcare providers to the low-income areas of the country. In the current setting with restricted resources, it is important to prioritize highly cost-effective interventions.

ACKNOWLEDGEMENTS

The authors thank Prof. Dr. Mario Scheffer and Alex Cassenote Jr for their help in this manuscript with suggestion for writings and interpretation of their data in their publication Demografia Médica.

R E S U M O Objetivo: analisar dados demográficos do Sistema Único de Saúde (SUS) brasileiro, que promove cobertura de saúde universal a toda população, e discutir os problemas revelados, com particular ênfase nos cuidados cirúrgicos. Métodos: os dados foram obtidos a partir dos bancos de dados de saúde pública da Demografia Médica, do Conselho Federal de Medicina, do Instituto Brasileiro de Geografia e Estatística e do Cadastro Nacional dos Estabelecimentos de Saúde. A densidade e a distribuição do trabalho médico e dos estabelecimentos de saúde foram avaliadas, e as regiões geográficas foram analisadas usando o índice de desigualdade público-privado (IDPP). Resultados: o Brasil tem, em média, dois médicos por 1000 habitantes, que são desigualmente distribuídos no país. Tem 22.276 cirurgiões gerais certificados (11,49 por 100.000 habitantes). Existem no país 257 escolas de medicina, com 25.159 vagas por ano, e apenas cerca de 13.500 vagas de residência médica. O índice de desigualdade público-privado é de 3,90 para o país e varia de 1,63 no Rio de Janeiro até 12,06 na Bahia. Conclusão: uma parte significativa da população brasileira ainda encontra muitas dificuldades no acesso ao tratamento cirúrgico, particularmente na região norte e nordeste do país. Médicos e, particularmente, cirurgiões são escassos no sistema público de saúde e incentivos devem ser criados para assegurar uma força médica igual no setor público e no setor privado em todas as regiões do país. Descritores: Cirurgia Geral. Sistema Único de Saúde. Assistência à Saúde.

REFERENCES 1. Birolini D, Ferreira EA, Rasslan S, Saad R Jr. Surgery in Brazil. Arch Surg. 2002;137(3):352-8. 2. World Bank Group. GDP (current US$) [Internet]. Washington, DC; 2013 [cited 2015 nov 04]. Available from: http://data.worldbank.org/indicator/NY.GDP. MKTP.CD 3. United Nations Development Programme Human. Development Report 2014 [Internet]. New York; c1990-2014 [cited 2015 Apr 04]. Available from: http://hdr.undp.org/en/data. 4. Farmer PE, Kim JY. Surgery and global health: a view from beyond the OR. World J Surg. 2008;32(4):533-6. 5. Grimes CE, Henry JA, Maraka J, Mkandawire NC, Cotton M. Cost-effectiveness of surgery in lowand middle-income countries: a systematic review. World J Surg. 2014;38(1):252-63.

6. Chao TE, Sharma K, Mandigo M, Hagander L, Resch SC, Weiser TG, et al. Cost-effectiveness of surgery and its policy implications for global health: a systematic review and analysis. Lancet Glob Health. 2014;2(6):e334-45. 7. Corlew DS. Estimation of impact of surgical disease through economic modeling of cleft lip and palate care. World J Surg. 2010;34(3):391-6. 8. Conselho Federal de Medicina. Rede dos Conselhos de Medicina [Internet]. Brasília; c2010-2015 [cited 2015 Apr 04]. Available from: http://portal.cfm.org. br/ 9. Scheffer M. Demografia médica no Brasil. São Paulo: Conselho Federal de Medicina; 2013. 10. Scheffer M. Demografia médica no Brasil. São Paulo: Conselho Federal de Medicina; 2011. 11. Instituto Brasileiro de Geografia e Estatística [Internet]. Rio de Janeiro; 2015 [cited 2015 jan 9]. Available from: http://ibge.gov.br/home/

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12. World Bank Group. Health expenditure per capita (current US$) [Internet]. Washington, DC; 2013 [cited 2015 nov 04]. Available from: http://data. worldbank.org/indicator/SH.XPD.PCAP. 13. World Bank Group. Health expenditure, public (% of total health expenditure) [Internet]. Washington, DC; 2013 [cited 2015 nov 04]. Available from: http://data.worldbank.org/ indicator/SH.XPD.PUBL. 14. Poley S, Belsky D, Gaul K, Ricketts T, Fraher E, Sheldon G. Longitudinal trends in the U.S. surgical workforce, 1981-2006. Bull Am Coll Surg. 2009;94(8):27-31. 15. Brasil. Ministério da Saúde. DATASUS. Informações de Saúde. Brasília: Ministério da Saúde; 2015

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[cited 2015 jan 9]. Available from: http://www2. datasus.gov.br/DATASUS/index.php?area=02. 16. CREMESP. Imprensa [Internet]. São Paulo; 2014 [acesso em 2015 jan 3]. Available from: http://www. cremesp.org.br/?siteAcao=Imprensa&acao=sala_ imprensa&id=271 Received in: 23/10/2016 Accepted for publication: 19/01/2017 Conflict of interest: none. Source of funding: none. Mailing address: Nivaldo Alonso E-mail: nivalonso@gmail.com

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DOI: 10.1590/0100-69912017002004

Review Article

Incidence of colorectal cancer in young patients Incidência de câncer colorretal em pacientes jovens Fábio Guilherme C. M. de Campos, TCBC-SP1; Marleny Novaes Figueiredo1; Mariane Monteiro1; Sérgio Carlos Nahas, TCBC-SP1; Ivan Cecconello, ECBC-SP1. A B S T R A C T Sporadic colorectal cancer (CRC) is traditionally diagnosed after de sixth decade of life, although a small percentage of cases are diagnosed in patients under 40 years of age, and incidence is increasing. There exists a great volume of controversy regarding clinical outcome of young patients diagnosed with colorectal cancer (CRC) when compared to elder counterparts. Our aims were to evaluate the rate of CRC in young patients, to review the pertaining literature and to discuss outcomes and clinical prognosis. A retrospective review involving patients with CRC was undertaken, focusing on age at diagnosis. The information extracted from this literature review showed a trend towards a decreased incidence in older people with an opposite effect among adolescents and young adults. Moreover, biological aggressiveness in young adults diagnosed with CRC has not been fully recognized, although it is usually diagnosed later and in association with adverse histological features. Besides that, these features don’t affect outcome. These apparent increase in CRC incidence among young patients during the last decades raises the need for a greater suspicious when evaluating common symptoms in this group. Thus, educational programs should widespread information for both population and physicians to improve prevention and early diagnosis results. Keywords: Colorectal Neoplasms. Age. Incidence. Young Adult. Prognosis.

INTRODUCTION

C

olorectal cancer (CRC) is the commonest malignancy in the gastrointestinal tract and the third leading cause of cancer associated death in the world. Usually, CRC is thought as a common disease affecting old people, with most cases diagnosed during the 5th and 6th decades and a higher prevalence among men1. Therefore, it is often thought of as a disease of the elderly, what makes screening not usually recommended for those individuals younger than 50 years, considered to have an average risk of carcinogenesis. The definition of what age would be considered young for a patient developing CRC is controversial. In an interesting retrospective study, O’Connell et al.2 collected data on 6425 patients from 55 manuscripts in the literature. While the majority of articles (n=37) defined “young” those patients under 40 years of age, four articles (7%) focused attention on patients younger than 35 years, 14 articles (25%) looked at patients before 30 years and only one article looked at patients before 25 years.

According to the literature, a non-worthless fraction of CRC patients are diagnosed before 40 years in approximately 0.8 to 14.6%3. Furthermore, recent publications have documented a disproportional increase in CRC incidence among young people4. Especially within this young group, one recognizes the need to investigate if the malignancy represents an apparent sporadic CRC or if it is associated with some form of hereditary CRC (mainly Familial Adenomatous Polyposis or Lynch Syndrome) or inflammatory bowel disease. Attempts to describe clinical, pathological and molecular features in young patients have reached controversial conclusions regarding tumour grade and disease stage at diagnosis. So far, there is no consensus if age should be considered an adverse independent prognostic factor if other features such as topography and staging are considered together. However, it is commonly accepted that diagnosis in young patients is always difficult, because both patient and the doctor usually don’t give credit to the presenting symptoms, leading to a frequent unfavorable outcome of the disease5.

1 - Colorectal Surgery Division (Gastroenterology Department). Hospital das Clinicas (HC-FMUSP), Faculty of Medicine, São Paulo University of Medical, Sao Paulo State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 208-215


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The present study is based on literature review and aims to discuss some relevant issues within this context, such as clinicopathological features, prognosis and the need for earlier detection. EPIDEMIOLOGY OF CRC It is widely known that lifetime risk is around 5% and risk increases with age, where more than 90% occurring in people aged 50 and over. For this reason, current guidelines recommend screening after this age for people with no risk factors associated with the disease6. During the past decades, there is a trend in decreasing the incidence of CRC in older people with an opposite effect among adolescents and young adults7,8, a change that has been attributed to an inadequate screening and lifestyle risk factors related to obesity and diet profile9. Recent data from the National Cancer Institute (NCI) revealed that here has been a steady decline in the incidence of CRC in patients aged 50 years or older, but the opposite trend has been observed for young adults. For patients 20 to 34 years, the incidence rates of localized, regional, and distant colon and rectal cancers have increased. An increasing incidence rate was also observed for patients with rectal cancer aged 35 to 49 years10. Similar results came from the Surveillance Epidemiology and End Result (SEER) database (from 2000 to 2008), that detected a 10% overall increase in CRC, mainly in those <50 years of age, versus a 20% decrease in those >50 years of age11. Since Bacon and Sealy12 published, in 1939, one of the earliest retrospective article focusing CRC in the young, different aspects regarding its incidence and clinicopathological features have been reported. In a review of in the literature, CRC in the â&#x20AC;&#x153;youngâ&#x20AC;? population represented approximately 7% of the total number of CRC patients in the 55 selected articles2. These authors found smaller figures in West countries, emphasizing that the higher rates reported in developing countries were due, in part, to the higher population of younger people in these countries. Regarding gender distribution, most studies found no significant difference, with a cumulative total of 2,554 men (51.4%) and 2,497 women (48.6%).

The NCI database from 2004-2008 revealed that the median age at CRC diagnosis was 70 years; in young people, CRC rates varied from 0.1% before 20 years to 1.1% between 20 and 34 and 3.8% between 35 and 44. The annual incidence increases from ten cases per million at age 20 years to 100 cases per one million at the age of 45 years. However, after reaching the age fifty, it is estimated that about one in 2,000 people will develop colorectal cancer per year. The chances of becoming a CRC sufferer rise accordingly every year after. After age 65, this rate increases to almost three in 1,00011. In the literature, most publications only report the incidence of CRC in patients with less than 40 years of age2,3,5. As may be noted in table 1, the published series present great variation due to biases associated with single-institution experiences and referral centers. A publication from the American Cancer 13 Society showed that the overall incidence per 100,000 individuals has increased during 19922005 among adults from 20 to 49 years by 1.5% per year in men and 1.6% per year in women. The highest increases occurred in patients among 20-29 years of age with 5.2% and 5.6% increase for man and women, respectively. In this study, the authors also found that rates increased in each 10-year age grouping (20-29, 30-39, and 40-49 years) among nonTable 1. Incidence of CRC in patients with less than 40 years of age.

Author

Local

% CRC in young

Chen et al., 1999

Taiwan

10.1%

Alici et al., 2003

Istanbul

18%

De Silva et al., 2000

Sri Lankan

Isbister et al., 1992

Saudi Arabia

23%

Smith et al., 1989

United States

2.8%

Adloff et al., 1986

France

3.0%

Keating et al., 2006

New Zealand

5.5%

Soliman et al., 1997

Egypt

35.6%

Singh et al., 2002

Nepal

28.6%

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19.7%


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Hispanic Whites. Furthermore, this incidence increase was predominantly driven by rectal cancer, which increased 3.5% per year in men and 2.9% per year in women over the 13-year study interval. In a retrospective study using data from the Surveillance Epidemiology and End Results (SEER) Cancer Registry, Meyer et al.14 identified 7,661 colon and rectal cancer patients under age 40 years between 1973 and 2005. After calculating the change in incidence over time for colon and rectal cancers, the researches described that while colon cancer rates remained flat, rectal cancer rates have been increasing. Between 1984 and 2005, rectal cancer rate rose 3.8% per year. This finding led the authors state that â&#x20AC;&#x153;in young people presenting with rectal bleeding or other common signs of rectal cancer, endoscopic evaluation should be considered in order to rule out a malignancyâ&#x20AC;?. They also suggested that more frequent endoscopic evaluation could decrease the documented delay in diagnosis among young people. But, as the overall incidence of rectal cancer is relatively low, the authors did not advocate for a change in screening guidelines. Davis et al.8 evaluated the rates of change in CRC incidence within the SEER database (19872006), reporting that people older than 50 had decreasing incidences, and colon and rectal cancer increased 56% and 94%, respectively. They also noted a higher incidence across age groups 20-49 years in 2006 than in 1987. Most significantly, the highest increase (67%) occurred from age 40-44 (from a low of 10.7 per 100,000 in 1988 to 17.9 per 100,000 in 2006). These findings have raised the question to consider age-based colonoscopic screening beginning at age 40. This is especially true for men, as they have a higher risk of developing advanced neoplasia at any age when compared to women, and an earlier screening might detect more asymptomatic pre-neoplastic and neoplastic colonic lesions15. In this context, the perspective of establishing aggressive diagnostic efforts in young patients presenting rectal bleeding is supported by the idea that age may influence clinicopathological

features and outcome of CRC16,17. For decades, a more aggressive biological behaviour has been attributed to CRC in young patients, who are diagnosed in more advanced stages. Young age has also been considered a predictor of poor survival7. However, investigation of these features in sporadic tumors occurring in young patients have led to controversial results, as there are studies reporting that they have similar histopathological features and rates of advanced stage when compared to older patients18,19. CLINICAL AND PATHOLOGICAL CHARACTERISTICS IN YOUNG PATIENTS The literature discloses many publications focusing on CRC age-related disparities regarding delayed diagnosis, tumor biology, recurrence rates, treatment and outcomes. A worse prognosis is usually attributed to the finding of a more advanced disease among younger patients. In this regard, most comparative studies focusing clinicopathological features and survival have shown that the young patients also present more commonly with stages III or IV disease20,21 although it is not clear whether the prognosis differs stage for stage from older individuals2,17,22. In some series, advanced stage is the only independent prognostic variable 23, 24. Furthermore, there has been documented a greater prevalence of mucinous20,25 or less differentiated tumors26,27 in this group. Although mucinous tumors represent 10-16% of all colorectal adenocarcinomas, they occur in 20 to 64%of young individuals3,21,26. In a study comparing 59 patients younger than versus 416 older than 40 years during a 20-years period, Ganapathi et al.17 found a higher frequency of tumors with poor differentiation (43% vs. 16%, p<0.001), T4 stage (47% vs. 30%, p=0.005) and vascular invasion (VI; 38% vs. 29%, p=0.13) in the younger group. Multivariate analysis showed T4 status (p=0.001) and vascular invasion (p=0.002) as independent prognostic factors for overall survival and T4 status (p=0.004) as independent factor influencing disease-free survival. When comparing clinical and histopathological parameters of 244 patients aged 50 years or less with

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1,718 patients aged more than 50 years, Schellerer et al.28 found that although young patients present with more aggressive histopathological subtypes and less early stages, cancer-related survival was not less favorable. Similar findings were found in series comparing only patients with rectal cancer, reporting poorer histological differentiation, more advanced pathologic stage and no difference in long-term survival22. However, a study using a prospective database from Taipei Veterans General Hospital29 identified 69 patients with mean age of 33.5 years, and the elderly group consisted of 253 patients with mean age of 83.4 years from 2001 to 2006. Younger patients had a higher incidence of mucinous cell type (14.5% vs. 6.3%, p=0.05), poorly differentiated adenocarcinoma (26.1% vs. 6.3%, p<0.001) and more advanced disease (82.6% vs. 41.9%, P<0.001). The comparison of prognosis in these groups with different onset ages revealed that the young had poorer disease-free survival (67.2% vs. 79.3%, p=0.048), and cancer-specific survival (44.1% vs. 73.1%, p<0.001). Similarly, a study from the British Columbia Cancer Agency showed that 78 (0.47%) patients among 16,732 treated during a 20-year period were younger than 30 years of age. Data from 62 of these patients displayed 49% and 27% in stages III and IV, respectively. In this young cohort, the 5-year survival appeared inferior to that expected, although 5-year survival among patients with stage IV disease was observed to be higher than expected16. Thus, the majority of young patients usually present with later stages tumors at diagnosis, data confirmed by two reviews2,30. Moreover, it has been considered a rare disease in very young patients (below 20 years of age)31,32. Due to that, it has been questioned that the diagnosis in advanced stages is a result of less diagnostic efforts directed towards an apparent healthy group. However, in a series published by our group, there was no difference regarding symptoms duration (13.8 vs. 14.5 months; p=0.5) between the young and control groups3. Another fact that may decrease clinical suspicion of

malignancy is that symptoms are commonly credited to benign anorectal diseases and a positive family history of CRC is referred by less than 27% of young patients16. Regarding the anatomical distribution, it has been documented that CRC in young people is confined to a topography distal to the splenic angle of the colon in more than 80% of the cases, which is why they usually determine rectal bleeding, abdominal pain, fecal changes and mucorrhea. IMPORTANT GENETIC ASPECTS In a recent review article regarding young colorectal patients, Ciarrocchi and Amicucci33 concluded that colon carcinoma in young adults appears to be a distinct disease characterized by biological aggressiveness, but prognosis is not worse due to a better performance status at time of surgical intervention. CRC carcinogenesis occurs over a number of years and is related to combination of gene alterations and two separate destabilizing pathways (chromosomal instability and intragenic mutation)34. However, the spectrum of somatic mutations contributing to the pathogenesis of CRC is likely to be far more extensive than previously appreciated, with individual lesions harboring an average of nine mutant genes each. In addition, each tumor studied had a distinct mutational gene signature35. Microsatellite instability (MSI) is considered a hallmark of the mutator pathway in colorectal carcinogenesis, being found in 15% of sporadic CRC and in a higher percentage of young patients (<45 years). Most of the remaining CRC may follow the classic suppressor pathway. MSI occurs from the mutational inactivation of the DNA mismatch repair genes (hMSH2 and hMLH1 in Lynch Syndrome), as well as from epigenetic inactivation of hMLH1 in sporadic CRC. Although mutator pathway (including microsatellite instability, hMLH1 promoter methylation, and hMSH2 and hMLH1 mutation patterns) has been implicated in younger-age-onset colorectal carcinogenesis, many tumors may evolve from different genetic events other than hMSH2 and hMLH1 mutations frequently identified in Lynch Syndrome36.

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Thus, it is not surprising that cancers that emerge from different mutational pathways should differ clinically. Previous case-control studies reported that 58%37and 47%38 of CRC in patients 35 years of age or younger and 40 years of age or younger, respectively, had high-frequency MSI. In an interesting study within 124 young (<50 years old) people in Hong Kong population (recognized to have an unusually high incidence of CRC in the young), Ho et al.39 found that the MSI incidence increased significantly with decreasing age at diagnosis. For those aged 30 to 49, MSI tumors were located mainly at the proximal colon, while they tended to be at the distal large bowel. However, for exceptionally young patients (<30 years), this observation suggested a differential activity of the MMR pathway in colorectal carcinogenesis in different age groups. FINAL CONSIDERATIONS After summarizing the available data regarding CRC in young patients, it is possible to abstract important information from the present review. Within this group, CRC is usually diagnosed later, when an advanced disease leads to a poorer prognosis. As an apparent increase in the CRC incidence in young is still ongoing, a higher suspicious diagnostic criteria is necessary when evaluating young patients with common symptoms. Moreover, educational and preventive programs should provide consciousness information about alert symptoms. The finding of a CRC in young patients raises not only diagnostic challenges, but also management issues. When dealing with a young patient, it is worthy to separate sporadic CRC from those originating from hereditary syndromes such as Lynch Syndrome or Familial Adenomatous Polyposis. However, even for CRC patients under 40 years of age, the prevalence of positive family history of cancer is under 27%40. It is well recognized that young CRC patients associated with hereditary syndromes have an increased metachronous cancer rate after colonic partial resection. Thus, an adequate preoperative approach should identify this select group in order to deliver appropriate surgical decision regarding the colectomy extent and familial surveillance.

In the case of sporadic cancers, there exist suggestions to consider a more extended colectomy in the management of patients under 50 years of age. However, performance of an extended colectomy in this group is not always associated with improvement in disease-free survival or mortality, besides the 3% occurrence of metachronous cancer41. This fact explains why most surgeons would not alter surgical decision without a proof of genetic disease. In this situation, factors such as health conditions, quality of sphincter muscles, opportunity and willing to adopt long-term follow-up, and mainly the existence of affected relatives may help the surgeon to choose the best option case by case, after offering the patient complete information. This is what happened with our second patient, who was treated by total colectomy. Consequently, the issue of age at diagnosis naturally raises the discussion of performing genetic testing (IHC, MSI) before treatment, although there is no agreement to offer preoperative investigation based only in this criteria, without a suggestive family history or the presence of other histological risk factors for Lynch Syndrome42. Even knowing that most surgeons would not change their surgical decision in the absence of a genetic evaluation, it is right to suppose the opposite when facing a young patient that developed a CRC on the basis of a genetic mutation. Even today, most RCC appear sporadically dependent on several factors such as diet, obesity, intestinal microbiota, alcohol intake, smoking, and germ or somatic mutations. In young people, the participation of genetic mechanisms is greater and, in order to increase the effectiveness of CRC detection at an earlier age, young adults should know the effects and criteria of screening through advertising campaigns. Clarification in primary medical care sectors, emphasis on the subject in undergraduate medical courses and enhancement of public laws should also be remembered. Then, the data and all this controversy presented here bring support to suggest a modification in current recommendations, as there is an opportunity to improve medical and population education regarding CRC risks.

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R E S U M O O câncer colorretal (CCR) esporádico é tradicionalmente diagnosticado após a sexta década de vida, embora uma pequena porcentagem de casos seja diagnosticada em doentes abaixo dos 40 anos de idade, e a incidência está aumentando. Existe uma grande controvérsia a respeito da evolução clínica de doentes jovens portadores de CCR em comparação aos mais idosos. Os objetivos deste estudo foram avaliar a prevalência de CCR em doentes jovens, rever a literatura pertinente e discutir suas características mais importantes nesta faixa etária. Para tanto realizou-se revisão da literatura envolvendo doentes com CCR com foco na idade ao diagnóstico. A informação extraída da revisão de literatura demonstrou uma tendência de redução da incidência em pessoas mais idosas com efeito oposto em adolescentes e adultos jovens. Sua agressividade biológica ainda não foi claramente reconhecida, embora seja usualmente diagnosticado mais tardiamente e em associação com características histológicas adversas. Apesar disso, estas características não afetam a evolução. Este aparente aumento na incidência de CCR entre pacientes jovens durante as últimas décadas levanta a necessidade de uma maior suspeita diagnóstica na avaliação de sintomas comuns neste grupo. Assim, programas educacionais devem disseminar informação tanto para população como para médicos a fim de melhorar a prevenção e o diagnóstico precoce. Descritores: Neoplasias Colorretais. Idade. Incidência. Adulto Jovem. Prognóstico.

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16. Al-Barrak J, Gill S. Presentation and outcomes of patients aged 30 years and younger with colorectal cancer: a 20-year retrospective review. Med Oncol. 2011;28(4):1058-61. 17. Ganapathi S, Kumar D, Katsoulas N, Melville D, Hodgson S, Finlayson C, et al. Colorectal cancer in the young: trends, characteristics and outcome. Int J Colorectal Dis. 2011;26(7):927-34. 18. da Fonseca LM, da Luz MM, Lacerda-Filho A, Cabral MM, da Silva RG. Colorectal carcinoma in different age groups: a histopathological analysis. Int J Colorectal Dis. 2012;27(2):249-55. 19. Heys SD, Sherif A, Bagley JS, Brittenden J, Smart C, Eremin O. Prognostic factors and survival of patients aged less than 45 years with colorectal cancer. Br J Surg. 1994;81(5):685-8. 20. Safford KL, Spebar MJ, Rosenthal D. Review of colorectal cancer in patients under 40 years. Am J Surg. 1981;142(6):767-9. 21. Rodrigues MAM, Brein LC, Mendes EF, de Macedo AR, Franco M. Adenocarcinoma colorretal em pacientes com idade inferior a 40 anos: relato de 11 casos. AMB Rev Assoc Med Bras. 1985;31(1112):223-6. 22. Du CZ, Zhang JS, Li M, Zhao J, Peng YF, Yao YF, et al. [Comparison of pathologic and clinical characteristics of young and old patients with advanced rectal cancer after neoadjuvant radiotherapy]. Zhonghua Wai Ke Za Zhi. 2010;48(21):1616-20. Chinese. 23. Bülow S. Colorectal cancer in patients less than 40 years of age in Denmark, 1943-1967. Dis Colon Rectum. 1980;23(5):327-36. 24. Gardner B, Dotan J, Shaikh L, Feldman J, Herbsman H, Alfonso A, et al. The influence of age upon the survival of adult patients with carcinoma of the colon. Surg Gynecol Obstet. 1981;153(3):366-8. 25. Okuno M, Ikehara T, Nagayana M, Sakamoto K, Kato Y, Umeyana K. Colorectal carcinoma in young adults. Am J Surg. 1987;154(3):264-8. 26. Adloff M, Arnaud JP, Schloegel M, Thibaud D, Bergamaschi R. Colorectal cancer in patients under 40 years of age. Dis Colon Rectum.1986;29(5): 322-5.

27. Domergue J, Ismail M, Astre C, Saint-Aubert B, Joyeux H, Solassol C, et al. Colorectal carcinoma in patients younger than 40 years of age. Montpellier Cancer Institute experience with 78 patients. Cancer. 1988; 61(4):835-40. 28. Schellerer VS, Merkel S, Schumann SC, Schlabrakowski A, Förtsch T, Schildberg C, et al. Despite aggressive histopathology survival is not impaired in young patients with colorectal cancer: CRC in patients under 50 years of age. Int J Colorectal Dis. 2012;27(1):71-9. 29. Chou CL, Chang SC, Lin TC, Chen WS, Jiang JK, Wang HS, et al. Differences in clinicopathological characteristics of colorectal cancer between younger and elderly patients: an analysis of 322 patients from a single institution. Am J Surg. 2011;202(5):574-82. 30. Griffin PM, Liff JM, Greenberg RS, Clark WS. Adenocarcinomas of the colon and rectum in persons under 40 years old. A population-based study. Gastroenterology. 1991;100(4):1033-40. 31. Datta RV, LaQuaglia MP, Paty PB. Genetic and phenotypic correlates of colorectal cancer in young patients. N Engl J Med. 2000;342(2):137-8. 32. Kam MH, Eu KW, Barben CP, Seow-Choen F. Colorectal cancer in the young: a 12-year review of patients 30 years or less. Colorectal Dis. 2004;6(3):191-4. 33. Ciarrocchi A, Amicucci G. Sporadic carcinoma of the colon-rectum in young patients: a distinct disease? A critical review. J Gastrointest Cancer. 2013;44(3):264-9. 34. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342(2):69-77. 35. Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, et al. The consensus coding sequences of human breast and colorectal cancers. Science. 2006;314(5797):268-74. 36. Roh SA, Kim HC, Kim JS, Kim JC. Characterization of mutator pathway in younger-age-onset colorectal adenocarcinomas. J Korean Med Sci. 2003;18(3):387-91.

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37. Liu B, Farrington SM, Peterson GM, Hamilton SR, Parsons R, Papadopoulos N, et al. Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med. 1995;1(4):348-52. 38. Lukish JR, Muro K, DeNobile J, Katz R, Williams J, Cruess DF, et al. Prognostic significance of DNA replication errors in young patients with colorectal cancer. Ann Surg. 1998;227(1):51-6. 39. Ho JW, Yuen ST, Chung LP, Kwan KY, Chan TL, Leung SY, et al. Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients. Int J Cancer. 2000;89(4):356-60. 40. Mäkelä JT, Kiviniemi H. Clinicopathological features of colorectal cancer in patients under 40 years of age. Int J Colorectal Dis. 2010;25(7):823-8. 41. Klos CL, Montenegro G, Jamal N, Wise PE,

Fleshman JW, Safar B, Dharmarajan S. Segmental versus extended resection for sporadic colorectal cancer in young patients. J Surg Oncol. 2014;110(3):328-32. 42. Lynch PM. How helpful is age at colorectal cancer onset in finding hereditary nonpolyposis colorectal cancer? Clin Gastroenterol Hepatol. 2011;9(6):458-60. Received in: 25/11/2016 Accepted for publication: 06/01/2016 Conflict of interest: none. Source of funding: none. Mailing address: Fábio Guilherme C. M. de Campos E-mail: fgmcampos@terra.com.br

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DOI: 10.1590/0100-69912017002008

Technical Note

Robotic Transversus Abdominis Release (TAR): is it possible to offer minimally invasive surgery for abdominal wall complex defects? Transversus Abdominis Release (TAR) Robótico: é possível oferecer cirurgia minimamente invasiva para os defeitos complexos da parede abdominal? Maria Vitória França do Amaral1; José Ricardo Guimarães1; Paula Volpe, TCBC-SP2; Flávio Malcher Martins de Oliveira, TCBC-RJ3; Carlos Eduardo Domene, TCBC-SP2; Sérgio Roll, TCBC-SP4; Leandro Totti Cavazzola, TCBC-RS1. A B S T R A C T We describe the preliminary national experience and the early results of the use of robotic surgery to perform the posterior separation of abdominal wall components by the Transversus Abdominis Release (TAR) technique for the correction of complex defects of the abdominal wall. We performed the procedures between 04/2/2015 and 06/15/2015 and the follow-up time was up to six months, with a minimum of two months. The mean surgical time was five hours and 40 minutes. Two patients required laparoscopic re-intervention, since one developed hernia by peritoneal migration of the mesh and one had mesh extrusion. The procedure proved to be technically feasible, with a still long surgical time. Considering the potential advantages of robotic surgery and those related to TAR and the results obtained when these two techniques are associated, we conclude that they seem to be a good option for the correction of complex abdominal wall defects. Keywords: Robotics. Hernia, Abdominal. Minimally Invasive Surgical Procedures

INTRODUCTION

A

bdominal hernias represent a major public health problem, as it is believed that about 10% to 15% of the world population has or will have ventral abdominal hernias throughout life and it is estimated that more than 20 million herniorraphies are performed annually worldwide1,2. In addition, they are responsible for great morbidity, causing abdominal pain and discomfort resulting in dismissal from work and consequent economic loss, besides decrease in quality of life3. The repair of abdominal hernias has been the object of study of many researchers due to its diversity in the form of presentation and its rate of relapse. Its recurrence rate is about 24% after the first repair, 35% after the second and 39% after the third4. However, this rate varies according to the technique used for correction. Open surgery with suture closure was the first technique used and its recurrence rate reaches

more than 50%. This rate decreased considerably after the advent of meshes in the treatment of hernias, dropping to about 32% and, in selected cases, further reduced with the implementation of laparoscopy, with rates of 14 to 17%. Despite the notable reduction in recurrence rates of abdominal hernias with these advances, the search for new techniques and devices that could decrease them further continued, especially in the complex effects of the abdominal wall. The use of the component separation technique in the treatment of abdominal hernias attempts to minimize these indices, with reports of recurrence rates of 10 to 22%5. There is no gold standard for treating all ventral hernias, since the hernia and patients’characteristics are very heterogeneous. For the correction of bulky defects in which there is loss of domicile, it is important to take the peculiarities presented by these herniasinto consideration. In addition to reducing stress at the surgical site, it is also desired to restore the functionality of the abdominal wall, which is compromised in such

1 - Clinics Hospital of Porto Alegre, Service of General Surgery, Porto Alegre, Rio Grande do Sul State, Brazil. 2 - Nine of July Hospital, Service of Surgery of the Digestive System, São Paulo, São Paulo State, Brazil. 3 - Oswaldo Cruz German Hospital, Service of General Surgery, São Paulo, São Paulo State, Brazil. Rev. Col. Bras. Cir. 2017; 44(2): 216-219


Amaral Robotic Transversus Abdominis Release (TAR): is it possible to offer minimally invasive surgery for abdominal wall complex defects?

cases, and to expand the abdominal cavity so that it can receive the herniated contents back and prevent complications such as compartment syndrome. Among the options for reducing tension in the repair of these hernias are the use of meshes, muscle-aponeurotic flaps, autologous and heterologous grafts, progressive pneumoperitoneum and separation of components of the abdominal wall. Restoration of abdominal wall functionality can be achieved with the component separation technique. The expansion of the abdominal cavity can be done with progressive peneumoperitoneum, with the pharmacological blocking of the abdomen lateral musculature with the use of botulinum toxin or with the separation of components6-8. In view of all these peculiarities presented by bulky hernias, their treatment is still a challenge for surgeons6. Among the techniques mentioned, the concomitant use of a mesh and the separation of abdominal wall components presents potential advantages, as the components separation allows that all goals in the hernia treatment are achieved, that is, restoration of abdominal wall function, expansion of the abdominal cavity and tension reduction. However, since in these cases the strength of the abdominal muscle fasciasis often reduced, the mesh reinforcement would be adequate7.The components separation, however, is associated with complications such as skin ischemia, dehiscence, surgical site infection and formation of seroma due to extensive dissection of the subcutaneous tissue. With this, this technique underwent modifications and alternatives of muscle separation were developed5,7. One of them was the posterior separation of components, which has the advantage of avoiding subcutaneous dissection. Moreover, when performed by a minimally invasive technique (such as robotics), it is associated with lower rates of postoperative morbidity and shorter hospital stay5. The methods of posterior component separation are based on creating a space between the rectusabdominis muscle and its posterior sheath of six to eight centimeters for placement of the mesh in the position called sublay or retromuscular. However, this technique is inadequate for the treatment of major wall defects, as it does not allow dissection beyond the lateral border of the rectus sheath, rendering this

217

space insufficient9. The methods developed to increase this potential space, including TAR, reduced recurrence rates to 3-6%5,9. The objective of this study was to describe the Brazilian preliminary experience in the performance of the posterior separation of components of the abdominal wall by the transversus abdominis release technique with the use of a robotic system in the correction of complex defects of the abdominal wall and its early results. The procedures were performed at the Clinics Hospital of Porto Alegre (Porto Alegre, RS), Osvaldo Cruz German Hospital (SĂŁo Paulo, SP) Nine of July Hospital (SĂŁo Paulo, SP) between 04/02/2015 and 06/15/2015.

TECHNICAL NOTE

All patients signed an informed consent agreement, including the use of data with confidentiality. We started the procedure by puncturing the space of Palmer with a Veres needle for instillation of the pneumoperitoneum; we placed two trocars in the medial axillary line, with a distance of 10cm between them and docked the robot. We them performed a review of the abdominal cavity with release of adhesions. We made an incision in the rectus posterior sheath 0.5cm from its medial border. Next, we developed the retro-muscular space, extending it in the longitudinal axis from the xiphoid to the pubis, and laterally until the semilunar line. We identified the neurovascular bundle to preserve it (Figure 1). At 0.5cm medial to the semilunar line, we made an incision in the rectus posterior sheath to expose the transversus abdominis muscle. We opened the posterior lamina of the rectus sheath, identifying the preperitoneal space. We then dissected this space from the xiphoid to the suprapubic portion (Figure 2). We measured the defect to place the mesh. We placed the contralateral portals in mirror and inserted the mesh, fixing it in three cardinal points. We them docked the robot on the contralateral side behind the trocars to perform the same steps on the other side. After opening the posterior lamina of the rectus sheath for the development of the retromuscular space and identification and development of the preperitoneal space, we closed the posterior lamina of the rectus sheath and the peritoneal defects. We

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Amaral Robotic Transversus Abdominis Release (TAR): is it possible to offer minimally invasive surgery for abdominal wall complex defects?

Figure 1. Dissection of the rectusposterior sheath.

Figure 2. Transversus muscle section â&#x20AC;&#x201C; TAR.

then unrolled the mesh and complemented its fixation at the other cardinal points. We closed the anterior aponeurosis, removed the portals under direct vision and closed the wounds. The defect size ranged from seven to 15cm, with an average size of 11cm. The surgical time ranged from four to seven hours, with an average of five hours and 40 minutes. The hospitalization time ranged from two to five days, with an average of three days. We evaluated the procedureâ&#x20AC;&#x2122;s late outcome through the outpatient visits within a period of up to six months after surgery. Of the six patients submitted to the procedure, two presented postoperative complication: one developed hernia through the peritoneum and the other presented mesh extrusion, both complications corrected with a new surgical procedure. We observed no other complications and, to date, all patients have a good clinical course.

rates, as mentioned above, and can be performed by robotic surgery, which presents potential advantages over other techniques used to correct abdominal wall defects by adding the pros of minimally invasive surgery. When comparing open surgery with the use of the mesh and the laparoscopic surgery, it was found that the laparoscopic surgery has the advantages of allowing smaller incisions and consequently less surgical aggression. It presents a lower infection rate in the surgical site, allowing shorter hospitalization time, besides allowing the identification of hernial processes that could not be perceived by open surgery10-12. However, its recurrence rate, despite being lower than that of open surgery, did not reduce significantly. In addition, the long-term pain index presented by some patients is still a therapeutic challenge13. When comparing laparoscopic surgery with robotics, it was observed that the robot allows the accomplishment of angular movements due to the articulation of the clamp cuff, making complex procedures such as TAR feasible by minimally invasive technique. In addition, with the robot, lysis of adhesions on the abdomen anterior wall is facilitated and the sutures can be made with adequate force and tension and with short movements. The 3D view generated by the robot facilitates the unwinding of the mesh and allows its better positioning, besides helping in the accomplishment of the suture14,15. In the study by Novitsky et al.9, 24% of the patients had surgical site infection and 2% had hernia recurrence. Our mean surgical time was higher than

DISCUSSION TAR has been shown to be a good option for the correction of complex abdominal wall defects. With this technique, the placement of the mesh is more appropriate, since the mesh should extend eight to ten centimeters beyond the edge of the defect in the repair of large hernias. In addition, one can avoid the nerve section with TAR. The same does not happen with other techniques of posterior separation of the components, which end up causing atrophy of the rectus abdominis muscle and consequent abdominal flaccidity5,9. It is also associated with low recurrence

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Amaral Robotic Transversus Abdominis Release (TAR): is it possible to offer minimally invasive surgery for abdominal wall complex defects?

that reported by them (340 minutes and 235 minutes, respectively) and our mean hospitalization time was shorter (3 days and 5.1 days, respectively). We conclude that the national experience in the use of robotic surgery to perform TAR in the correction of abdominal wall complex defects showed

219

that the procedure is feasible, with an index of complications similar to the open one. However, new studies need to be performed to complement these findings, since our study presents a small sample and a short period of postoperative segment, our results being preliminary.

R E S U M O Descrevemos a experiência preliminar nacional na utilização da cirurgia robótica para realizar a separação posterior de componentes da parede abdominal pela técnica transversus abdominis release (TAR) na correção de defeitos complexos da parede abdominal e seus resultados precoces. As cirurgias foram realizadas entre 02/04/2015 e 15/06/2015 e o tempo de acompanhamento dos resultados foi de até seis meses, com tempo mínimo de dois meses. O tempo cirúrgico médio foi de cinco horas e 40 minutos. Dois pacientes necessitaram reintervenção por laparoscopia, pois um desenvolveu hérnia por migração peritoneal da tela e um teve escape da tela. A cirurgia provou ser factível do ponto de vista técnico, com um tempo cirúrgico ainda elevado. Tendo em vista as vantagens potenciais da cirurgia robótica e aquelas relacionadas ao TAR e os resultados obtidos ao se associar essas duas técnicas, conclui-se que elas parecem ser uma boa opção para a correção de defeitos complexos da parede abdominal. Descritores: Robótica. Hérnia Abdominal. Procedimentos Cirúrgicos Minimamente Invasivos.

REFERENCES 1. Mayagoitia Gonzalez JC. Hernias de la pared abdominal; el nacimiento de una sociedad médica. Rev Col Bras Cir. 2010;37(1):4-5. 2. Dabbas N, Adams K, Pearson K, Royle G. Frequency of abdominal wall hernias: is classical teaching out of date? JRSM Short Rep. 2011;2(1):5. 3. Park AE, Roth JS, Kavic SM. Abdominal wall hernia. Curr Probl Surg. 2006;43(5):326-75. 4. Slater NJ, Montgomery A, Berrevoet F, Carbonell AM, Chang A, Franklin M, et al. Criteria for definition of a complex abdominal wall hernia. Hernia. 2014;18(1):7-17. 5. Pauli EM, Rosen MJ. Open ventral hernia repair with component separation. Surg Clin North Am. 2013;93(5):1111-33. 6. Melo RM. “Hérnia complexas” da parede abdominal. Rev Col Bras Cir. 2012;40(2):90-1. 7. Heller L, Chike-Obi C, Xue AS. Abdominal wall reconstruction with mesh and components separation. Semin Plast Surg. 2012;26(1):29-35. 8. Barbosa MV, Ayaviri NA, Nahas FX, Juliano Y, Ferreira LM. Improving tension decrease in components separation technique. Hernia. 2014;18(1):123-9. 9. Novitsky YW, Elliott HL, Orenstein SB, Rosen MJ. Transversus abdominis muscle release: a novel approach to posterior component separation during complex abdominal wall reconstruction. Am J Surg. 2012;204(5):709-16. 10. Misiakos EP, Machairas A, Patapis P, Liakakos T. Lapa-

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roscopic ventral hernia repair: pros and cons compared with open hernia repair. JSLS. 2008;12(2):117-25. Misiakos EP, Patapis P, Zavras N, Tzanetis P, Machairas A. Current trends in laparoscopic ventral hernia repair. JSLS. 2015;19(3):e2015.00048. Liang MK, Berger RL, Li LT, Davila JA, Hicks SC, Kao LS. Outcomes of laparoscopic vs open repair of primary ventral hernias. JAMA Surg. 2013;148(11):1043-8. Beldi G. Technical feasibility of a robotic-assisted ventral hernia repair. World J Surg. 2012;36(2):453-4. Ballantyne GH, Hourmont K, Wasielewski A. Telerobotic laparoscopic repair of incisional ventral hernias using intraperitoneal prosthetic mesh. JSLS. 2003;7(1):7-14. Abdalla RZ, Garcia RB, Costa RID, Luca CRP, Abdalla BMZ. Procedimento de Rives/Stoppa modificado robô-assistido para correção de hérnias ventrais da linha média. ABCD, arq bras cir dig. 2012;25(2):129-32.

Received in: 18/10/2016 Accepted for publication: 15/12/2016 Conflict of interest: none. Source of funding: none. Mailing address: Maria Vitória França do Amaral E-mail: mariavitoria.301@gmail.com cavazzola@gmail.com

Rev. Col. Bras. Cir. 2017; 44(2): 216-219


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 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. The Advisory Board (in charge of the peer-review) receives the text anonymously and decides for its 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. I must contain at most 15 pages and 45 references. • 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, which can be accessed through the Brazilian College of Surgeons’ website (www.cbc.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).

FORM AND STYLE

• Text: The textual form of the manuscripts submitted for publication must be original and submitted in digital form (Word – .doc), double spacing and arial font, size 12. The images should be sent separately, in JPG, GIF or TIF formats, with the insertion site referred in the text. Articles should be concise and written in Portuguese, English or Spanish. Abbreviations must be in the lowest number possible and limited to the terms mentioned repeatedly, as long as they do not hamper the text understanding, and must be defined in their first appearance. • References: Must be predominantly of works published in the last five years, not forgetting to include national authors and journals, 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 ICMJEwww.icmje.org – CIERM RevColBras 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 AND FIGURES (maximum of six)

Tables and figures 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. 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. Authors who wish to publish colored figures in their articles can do so at a cost of R$ 650.00 for a figure per page. Additional figures on the same page will cost R$ 150.00 each. The payment will be effected a through bank payment slip, sent to the lead author when the article is aproved for publication. 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 interest, compliant with the 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 grant the copyright and 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 they 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) 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. 6) 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. 7) works already published or simultaneously submitted for evaluation in other periodicals will not be accepted. 8) Due to the journal’s high publication costs, starting with issue 1/2017, each approved article will have a cost of R$ 1,000.00 (one thousand reais) for the authors. If the lead author is a solvent 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 CBC Journal of Case Reports 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: http://www.revistadocbc.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”, which, however, went on to be published without due regularity. From 1974 on, the journal began to be published bi-monthly, on a regular basis, to the present day. In these more than 40 years of uninterrupted publication, the Journal of the CBC gained importance and scope. With standards and criteria for selection and publication of scientific articles in the area of General and specialist Surgery, including “peer review”, the Journal of the CBC falls along the lines of the main international journals and has an Editorial Board that evaluates the merits for publication of submitted manuscripts. With indexing in SciELO and Medline/Pubmed, the Journal of the Brazilian College of Surgeons gained greater visibility, greater importance and greater coverage in its primary purpose of science dissemination. The abbreviation for your title is Rev. Col. Bras. CIR., which should be used in bibliographies, footnotes and in references and bibliographic legends.

DOAJ NOTE

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 APCs

In view of the high cost for publication of the journal, from the issue 1/2017 on, every approved article will cost R$ 1000.00 (1000 reais) for the authors.

Indexing sources

• Latindex • LILACS • Scopus • DOAJ • Free Medical Journals • MEDLINE/PUBMED

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 (from the Magazine 1/2017 on)


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