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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

MARCH 2017

Dr K K Aggarwal

Dr R N Tandon

Dr Dilip Kumar Dutta

Dr Kakali Sen

National President IMA

Honorary Secretary General, IMA

Honorary Editor, JIMA

Honorary Secretary, JIMA

CONTENTS Editorial : u How to Screen for Cervical Cancer — Dilip Kumar Dutta, Indranil Dutta.......................................5 Key Note Address — Dr. Ketan Desai..........................................................................................................8 Original Articles : u Effect of magnesium sulphate infusion on intraoperative propofol requirements in neurosurgical patients receiving balanced anaesthesia — Sankari Santra, Ratul Basu, Santa Saha-Roy, Bibhu Kalyani Das ..............................................10 u Role of topicalcyclosporine 0.05% in vernal keratoconjunctivitis — Swati Agarwal, Sanjiv Gupta, Bhartendu Agarwal ........................................................................15 u A comparative study of hypofractionated external beam radiotherapy versus conventional external beam radiotherapy in locally advanced carcinoma of uterine cervix — Swapan Kumar Mallick, Madhumay Pal, Krishnangshu Bhanja Choudhury......................19 Observational Studies : u Onychomycosis : dermatophytes to yeasts; an experience in and around Mumbai, India — Rupali S Suryawanshi, Shashir W Wanjare, Avani H Koticha, Preeti R Mehta.......................23 u Accidental fetal injuries during cesarean section deliveries — J B Sharma, M Goyal, S Kumar, K K Roy........................................................................................27 Case Reports : u Perigraft seroma : an uncommon complication of aneurysm repair — Reetu John, Edwin Stephen, Shyamkumar Nidugala Keshava, Sunil Agarwal ...............................31 u Mesh migration into sigmoid colon following inguinal hernia repair — Beena B Vaidya, Samir H Vadher, Vipin K Sisodia, Saurabh Jambu, Nishant Bansal, Jatin Bhojani............................................................................................................32 u Giant mucinous cystadenoma of appendix presenting as lump right iliac fossa : a rare presentation — S S Rathore, Mohan Lal, Anil Kumar......................................................34 Book Review...............................................................................................................................................36 Obituary .....................................................................................................................................................36 2

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

MARCH 2017

Editorial

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

MARCH 2017

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION Founder Hony Editor Founder Hony Business Manager Ex-officio Members

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Hony Editor Hony Secretary Hony Associate Editors

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Assistant Secretary

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Sir Nilratan Sircar Dr Aghore Nath Ghosh Dr Santosh Kumar Mandal Hony. Joint Secretary, IMA (Hqs), Kolkata Dr Santanu Sen Hony Jt Finance Secretary, IMA (Hqs), Kolkata Dr Dilip Kumar Dutta Dr Kakali Sen Dr Amitabha Bhattacharya Dr Dipanjan Bandyopadhyay Dr Gopal Das

OFFICE BEARERS OF IMA (HQs) National President Dr K K Aggarwal Honorary Secretary General Dr R N Tandon

IMA CGP (Chennai) Dean of Studies Dr V C Shanmuganandan (Karnataka) Honorary Secretary Dr R Gunasekaran (Tamil Nadu)

IMA AMS (Hyderabad) Chairman Dr Joseph Mani (Kerala) Honorary Secretary National President-Elect (2017-2018) Dr Ravi S Wankhedkar (Maharashtra) Dr Sadanand Rao Vulese (Telangana)

Immediate Past National President Dr S S Agarwal (Rajasthan)

National Vice-Presidents Dr Roy Abhram Kallivayalil (Kerala) Dr K Prakasam (Tamil Nadu) Dr Mahendra Choudhary (Gujarat) Dr Parmanand Prasad Pal (Bihar)

IMA AKN Sinha Institute (Patna) Director Dr Sarbari Dutta (Bengal) Honorary Executive Secretary Dr Raman Kumar Verma (Bihar)

Honorary Finance Secretary Dr V K Monga (Delhi)

JIMA (Calcutta) Honorary Editor Dr Dilip Kumar Dutta (Bengal) Honorary Secretary Dr Kakali Sen (Bengal)

Honorary Joint Secretaries Dr Vinod Khetarpal (Delhi) Dr Anil Goyal (Delhi) Dr Ashwini Kumar Dalmiya (Delhi) Dr Santosh Kumar Mandal (Bengal) Dr B B Gupta (Delhi) Honorary Assistant Secretaries Dr Dinesh Sahai (Delhi) Dr Amrit Pal Singh (Delhi) Honorary Joint Finance Secretaries Dr Manjul Mehta (Delhi) Dr Santanu Sen (Bengal)

Your Health (Calcutta) Honorary Editor Dr Ashok Kumar Chatterjee (Bengal) Honorary Secretary Dr Meenakshi Gangopadhyay (Bengal) IMA N.S.S.S. (Ahmedabad) Chairman Dr Kirti M Patel (Gujarat) Honorary Secretary Dr Yogendra S Modi (Gujarat)

IMA N.P.P.Scheme (Thiruvananthapuram) Chairman Dr Krishna M Parate (Maharashtra) Honorary Secretary Dr Jayakrishnan A V (Kerala) Apka Swasthya (Varanasi) Honorary Editor Dr Vivek Kumar (Uttar Pradesh) Honorary Secretary Dr Sanjay Kumar Rai (Uttar Pradesh) IMA Hospital Board of India Chairman Dr R V Asokan (Kerala) Honorary Secretary Dr Jayesh M Lele (Maharashtra) IMA National Health Scheme Chairman Dr Ashok SAdhao (Maharashtra) Honorary Secretary Dr Alex Franklin (Kerala) IMA National Pension Scheme Chairman Dr Sudipto Roy (Bengal) Honorary Secretary Dr K V Devadas (Kerala)

Dr Dilip Kumar Dutta

Dr Indranil Dutta

MD, PhD, FRCOG (Hon), FICOG, FIAMS, FICMCH, MAMS, DACOG (USA), DPS (Germany) Senior Vice-President IMA Bengal Branch (1916-17) Dean, Indian Academyt of Obstetrics & Gynecology (IAOG) 2015 Vice Chairman, ISAR Bengal 2015-2017 Central Working Committee Member, IMA HQs National Editor of 'Jogi Journal' Director, GICE, Kalyani, Nadia, WB Author of 36 books (Obstetrics and Gynaecology) Honorary Editor, Journal of the Indian Medical Association (JIMA)

MBBS, M.S (Obst & Gynae), FIAOG, FAGE Dip. Advanced Laparoscopic Surgery (Kiel,Germany) Fel.USG, Fel. Endo.Surg, Fel. Infertility (Bnglr, Agra) Fel. Gynae Oncology. (CNCI, Kol) Assistant Professor, IQ City Medical College, Durgapur, WB Guest Editor, JIMA

Screening for Cervical Cancer

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ut of 12% of all cancers in women, It is second most common cancer in women worldwide, the commonest cancer in developing countries, about half a million new cases each year, more than Âź million deaths each year, Yet cervical cancer is both preventable and curable.

In third world countries more than 80% of cervical cancers are in developing countries, screening, when it is available , is limited to a few urban areas, screening is of sub optimal quality. The incidence will rise, especially in Africa, as a result of the AIDS pandemic most cancers (>80%) including those of the cervix, are seen at a late stage (stages 3 and 4 ). Facilities for treatment do not exist in most areas Reasons for late diagnosis: lack of knowledge by the population about the symptoms, a fatalistic attitude towards cancer and unawareness about the possibility of cure, lack of knowledge by the medical and paramedical staff, lack of or disorganized screening programs and lack of health care facilities Cervical cancer and HPV: HPV, which is sexually transmitted is responsible for over 90%of cases of cancer of the cervix are caused by an infection, the virus enters the cells of the cervix and slowly causes cellular changes that can result in cancer, women generally infected in their teens or early twenties, but invasive cancer may not develop for as long as 10 to 20 years, Immuno-depression may greatly shorten this interval, Many of the otherwise healthy women would shed or eliminate the virus before age 30 Cytology screening : It is the mainstay of early detection of cervical cancer, adequate screening services are not available in developing countries and will not be available for many decades, only about 25% of women above 35 years of age could be properly screened even if the number of cytologists were to increase 10 fold. Since cytology based screening programs for cervical cancer cannot be provided on a large scale in developing countries (lack of trained staff, program logistics and quality assurance) alternative approaches are needed. Good screening methods — Characteristics : The disease should be one that is frequent with an impact on public health ( high morbidity and mortality), The sensitivity of the screening procedure should be high (>60%), The specificity should also be high, The test procedure should be acceptable to the population and financially 5


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

affordable, Treatment facilities for the disease should be available and should have a positive impact on morbidity and mortality. To be effective, any screening program has to involve at least 70-80% of the population and be well organized to include a good recall system. Community based programmes including screening, diagnosis, treatment, Quality control systems for screening, reading, colposcopy, Data collection for feedback and improving of services and Epidemiological pattern well defined are essential. Community based education is best done by people who have experience in this area, Develop and test appropriate and effective methods. Train staff at all levels before starting the programme, Taking Pap smears: nurses midwifes, laboratory technicians, doctors, Reading Pap smears : cytotechnicians under supervision of cytopathologist, Treatment : doctors, nurses. Who to screen : Look at peak age incidence in the area and start screening 5 years before, In most countries this would be at 30 to 35 years then screen until age 60 to 65 years, Women who have had no smear until age 60 or 65, can have one and then exit the programme too. Frequency : VIA every 2-3 years, Pap smear every 5 to 10 years. Methods of Screening — Clinical down staging : Involves looking at the cervix in a symptomatic woman with a speculum to detect early stage cancer, abnormal findings need to be further investigated. Data from cross sectional studies in India indicate that the test results in 40 – 70 % referral of pathological cases, The method is not intended for the detection of disease at the pre-invasive stage. The method could only be recommended in very low resource settings. But it is in this same setting that there is not enough facilities for the management of invasive cancer. Therefore, the method cannot be recommended as a primary method of screening. Unaided Visual Inspection of the Acetic Acid treated cervix (VIA): Visual inspection of cervix treated with 3-5 % acetic acid aims to detect CIN. Good lighting is imperative, Has been used for over 15 years in many studies in developing countries. Many have compared VIA to screening cytology. Sensitivity of VIA is 60-90% with an average of 70% depending on

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training offered to service providers. Cytology is 4085%.VIA may be particularly useful in developing countries where cytology is unreliable, follow-up rates low and resources limited.VIA + another method eg, Cytology or HPV/DNA may be an attractive process even in well to do settings; that is a two stage screening process. Colposcopy is done to : Look at the cervix for problem areas when a Pap test was abnormal. If an area of abnormal tissue is found, a biopsy is often done, Check a sore or other problem (such as genital warts) found on or around the vagina and cervix, Follow up on abnormal areas seen on a previous colposcopy. It can also be done to see if treatment for a problem worked, Look at the cervix for problem areas if an HPV test shows a high-risk type of HPV. PAP Smears : Cytological screening using the papanicolaou smear is the established method of screening. A reduction in both the incidence of and mortality from cervical cancer has been demonstrated in many countries. These have been countries with well organised national programmes based on cytological screening. In most developing countries, limited financial, logistic and manpower resources have inhibited the establishment of national screening services. The problems associated with this method are : high costs , requirement of skilled technical staff labour intensive reading and reporting of smears, inadequate follow up of abnormal smears, high false negative rates. To improve on the results of Pap smears the following improvements have taken place-Use of cytobrushes, Liquid-based cytology, Automation, combination with other methods eg : HPV/DNA Several approaches to HPV/DNA testing are available and include : Hybrid capture – sensitivity very high for oncogenic types of HPV, PCR, In site hybridisation tests. If HPV testing is combined with cytological screening, the screening interval can be safely increased. But the HPV test should not be used before 30 years. Combining Pap smear + HPV screen allows us to space screening intervals to 8-10 years since HPV has a negative predictive value of 100%.

Disclaimer The information and opinions presented in the Journal reflect the views of the authors and not of the Journal or its Editorial Board or the Publisher. Publication does not constitute endorsement by the journal. JIMA assumes no responsibility for the authenticity or reliability of any product, equipment, gadget or any claim by medical establishments/institutions/manufacturers or any training programme in the form of advertisements appearing in JIMA and also does not endorse or give any guarantee to such products or training programme or promote any such thing or claims made so after. — Hony Editor


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

MARCH 2017

Keynote address

Dr Ketan Desai President World Medical Association Ladies and Gentleman, It is indeed a matter of great privilege to be in the midst of this illustrious gathering of my professional community. To deliver a keynote address on the aspect of ‘Men’s Health’ to the knowledgeable congregation is indeed a huge challenge and a tough task. But in all humility, I take the onus of venturing in with whatever little at my disposal. Health has been a matter of paramount importance for men and mankind ever since antiquity. The trends and transitions on the same have several ‘benchmarks’, which stand out as speaking monumental ‘milestones’. One of the important aspects under the said rubric definitely pertains to ‘Men’s health’. It is a matter of observed knowledge that Men use health services less frequently than women, visit a doctor later in the course of condition thus bearing poorer health outcomes. They die, on average, 4.9 years earlier than women and suicide, and Homicide four times as often as women. Men die in accidents about twice as often as women and mortality due to acquired immune deficiency syndrome (AIDS) is three times the rate of women. Men are likely to engage in more high-risk behaviors and work at more dangerous occupations which makes them more vulnerable. To top it all, Men are less informed about health issues, less likely to utilize preventive and healthcare services, suffer from the effects of substance abuse at a higher rate have a greater tendency to engage in antisocial behavior, and more likely to be uninsured, lack a social support network and be homeless.There are a few findings which are eye openers in as much as that on average men live about 3-5 less years than women.1 in 2 men, while 1 in 3 women, will be diagnosed with cancer in their lifetime. Men lead in 9 out of the top ten causes of death. It is for these very reasons the gender specific health is deriving increasing attention in last three decades amongst the researchers, academic scholars and health professionals alike. The approaches that govern this arena do recognize that in addition to having different reproductive health needs, women and men have different risks for specific diseases and disabilities and they also differ in their health related beliefs and behaviours. Gender specific health approaches go beyond physiology to explore how socio-cultural, psychological and behavioural factors influence the physical and mental health of men and boys, as well as how these factors interact with and mediate men’s biological and genetic risks. The last decade has witnessed a substantial rise in the level of interest in the ‘Men’s health’ amongst scholars and health scientists internationally. Despite this positive trend, frankly speaking very little is known about the subject. Till recently there has been no professional journal devoted to the gender specific physical and mental health concerns of men and boys. The ‘International Journal of Men’s Health’ turns out to be a reflection of growing maturity in the said arena. It has to be borne in mind that what we currently understand about Men’s health is fragmented in several ways. It is fragmented by the individual disciplinary lenses through which we view men’s health as epidemiologists, health educators, medical anthropologists, physicians, psychiatrists, ethnographers, psychologists, public health workers, social workers, and sociologists. The ‘divergence’ is huge and substantial and ‘convergence’ is virtually non-existing. It is interesting to note that sociologists have much to teach about the male body, the meanings ascribed to and engendered in male bodies, how the body is itself regulated by institutional forces, how various populations of men embody masculinity, and how the male body is used as a vehicle for negotiating the often perilous landscape of masculinity. Men in most parts of the world are more likely than women to use their bodies in high risk activities such as physically dangerous sports and physical fighting. Decades of research have shown a strong link between high risk behaviours and low levels of mono-amine oxidase an enzyme involved in the metabolic breakdown and regulation of neurotransmitters in brain, which has a strong genetic determination. In terms of brain functioning scientists have evolved a variety of differences between women and men. Blended with this is the material reality that the health related beliefs and behaviours that men and boys adopt are influenced and often determined by a wide variety of social and economic structures. They have a profound influence in shaping men’s health and behaviour as well.

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MARCH 2017

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In defining men’s health there is an ever present risk of normalizing men’s experiences and universalising risk taking and poor physical or mental wellbeing as characteristics of all men. However, the health and behaviour of men who are economically, socially and politically disadvantaged can differ greatly from the health and behaviour of other men. While economically disadvantaged men are exposed to many of the underlying factors that contribute to poor health, their risks are compounded by additional social and other linked factors. Men’s poor health beliefs and behaviours were historically believed to reflect an underlying masculine personality. Recent theories, however suggest that cognitions and behaviours are not an effect of people’s personality, on the contrary they are what personalities are made of. Women and men think and act in the gendered ways not because of their role identities, but they are demonstrating cultural concepts of femininity and masculinity. Health beliefs and behaviours, such as dismissing the need for health or engaging in high risk behaviour are used by men as means to prove they are ‘real men’. Men’s relative access to social power and resources and their positioning in relation to women and to other men, also contributes to shaping their health related beliefs and behaviours. Diseases and illness can alter relationships of social power between women and men and reduce men’s status in hierarchy of masculinity. Men at times are reluctant to address their health needs for fear that other men will perceive about him as ‘unmanly’ or in any other manner. As such, the imperative need is to understand and decipher various ‘concerns’ and ‘considerations’ with strategic initiatives to address to evolution of models of Men’s health in the context of micro and macro health determinants, personal and societal interactions amongst complex intersections with other personal, social, economic, cultural and political health determinants. Globalization creates new challenges and opportunities for an international field of men’s health. The various healthcare delivery systems, the perceived ‘limitations’ there under and the ‘inequities’ that are wide and vivid in the context of available resources add to the problem. The net result is that a vital area, which needs to be tackled as a priority has not been extended the desired importance and remains unattended in a huge and substantial manner. Inspite of the concerns and challenges that confront the scenario as of now, the factual reality is that we have women clinics across the world but do not have any men’s clinic which speaks volumes about the desired gap on this very count. It is true that most women patients will invariably choose a lady doctor to have their private discussions pertaining to their health. As against this men often do not go in for any private discussion pertaining to their health problems and factually the concept of affording of private listening is far from desired. This has resulted in the field being freely extended to Ayurveda doctor without any genuine remedial measure at their disposal. As such, it is imperative that men’s clinics need to be started with core focus on prostate and erectile dysfunction. It is for this very reason a conference of this magnitude upholding the vital theme turns out to be a significant ‘game changer’, which would definitely invoke a desired ‘paradigm shift’, which is much needed and is keenly awaited. I am sure that the expert deliberations on the vital aspects of this theme at this conference would definitely bring into an acute focus the ‘concerns and challenges’ that confront the ‘core issues’ and would indeed bring out the ‘blue print’ of the ‘desired initiatives’ on the said count including a ‘translatory time bounded action plan’ of consequence and relevance alike. This blue print should ensure that every general practitioner should have a weekly men’s health clinic. Likewise, men’s health executive package should be different that of women and it should be subjected to a substantial public gaze in the form of desired advertisements. The Medical Council of India, should take necessary initiatives in incorporation of the core issues of men and women’s health as separate inclusions in appropriate subjects at different levels so that it becomes a part of teaching and learning at under graduate as well as post graduate levels. In the fitness of things it would be appropriate if every branch of Indian Medical Association takes recourse to having men’s health as a theme covered under the Continuing Medical Updates so that practicing professionals get well versed on the said count. I record my compliments for the organizers of this notable conference and bringing to fore a wide ranging discussion and debate on the vital theme of ‘Men’s Health’ in all its manifestations. Thank you.


JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

MARCH 2017

Original Article Effect of magnesium sulphate infusion on intraoperative propofol requirements in neurosurgical patients receiving balanced anaesthesia Sankari Santra , Ratul Basu , Santa Saha-Roy , Bibhu Kalyani Das 1

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Magnesium, one of the N-methyl-D-aspartate (NMDA) antagonists, may be a useful adjunct to anaesthesia and analgesia. The present randomized placebo controlled, double blind study was designed to investigate whether an intravenous administration of magnesium sulphate reduces propofol consumption during balanced anaesthesia in neurosurgical patients. Sixty adult patients undergoing elective craniotomy under general anaesthesia were randomly divided into two groups (n=30 per group). The patients in ‘magnesium group’ received magnesium sulphate (30mg/kg as a bolus, then 10mg/kg/hour) whereas the patients in the ‘control group’ received same volume of 0.9% sodium chloride. Controlled ventilation through oral endotracheal tube with nitrous oxide in oxygen was done. Anaesthesia was maintained with propofol (administered according to the bi-spectral index), fentanyl (adjusted according to heart rate and mean arterial pressure) and rocuronium (adjusted to provide complete depression of the first twitch after train-offour stimulation). To maintain a predetermined anaesthetic depth, mean hourly dose requirements of propofol in the magnesium group was 4.1 ± 0.48mg/kg/hour versus 7.73 ± 0.49mg/kg/hour in the control group (p<0.001). No adverse effect was observed magnesium with administration. The magnesium group required significantly less fentanyl and rocuronium (p<0.001). Intravenous administration of magnesium sulphate reduces propofol infusion requirements. These results suggest that magnesium administration may have an effect on anaesthesia or analgesia and may be a useful adjunct in balanced anaesthesia during elective craniotomy. [J Indian Med Assoc 2017; 115: 10-14]

Key words : Magnesium sulphate, propofol, balanced anaesthesia, elective craniotomy.

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and cardiac depression. On the other hand, 60% reduction in minimum alveolar concentration of halothane was demonstrated in magnesium treated rats. This result was due to central effect of the ion, but this has not been substantiated . Recently, the importance of magnesium in anaesthetic practice has been highlighted . It has been suggested that magnesium has the potential to treat and prevent pain by acting as an antagonist of N-methyl-D aspartate (NMDA) receptors . In some clinical studies, peri-operative administration of magnesium sulphate reduced intraoperative and post-operative analgesic requirements in patients undergoing arthroscopic knee surgery or elective abdominal hysterectomy . In one of the studies, when propofol infusion rate was held constant and the fentanyl dose was adjusted to haemodynamic end points, opioid requirements were reduced . In other studies, magnesium has been used as an adjuvant during general anaesthesia . However there are limited studies regarding effects of magnesium sulphate infusion in reducing anaesthetic requirements in elective craniotomy.

agnesium is the fourth most abundant cation in the body and the second most abundant intracellular cation . It has numerous physiological activities including activating many enzymes involved in energy metabolism and protein synthesis .Magnesium acts as a natural calcium antagonist by regulating calcium access into the cell . At the beginning of last century, magnesium sulphate was proposed as a general anaesthetic . Although magnesium was regarded as a central nervous system (CNS) depressant, its anaesthetic effect was shown to result from cerebral hypoxia after progressive respiratory 1,2

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Department of Anaesthesia, Bangur Institute of Neurosciences, Kolkata 700025 1 MD, Post Doctoral Certificate Course (Neuroanaesthesia), Associate Professor 2 MD, Post Doctoral Certificate Course (Neuroanaesthesia), RMO, Department of Anaesthesia, NRS Medical College, Kolkata 700014 3 MD, Assistant Professor, Department of Biochemistry, Bangur Institute of Neurosciences, Kolkata 700025 4 MD, Retired Professor and Ex Head of the Department of Anaesthesia, Bangur Institute of Neurosciences, Kolkata 700025, at present Director of Academic Development, Institute of Neurosciences, Kolkata 700017

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Accordingly, the present study was designed to assess the effect of intra-operatively administered magnesium sulphate infusion on propofol requirement during elective craniotomy. MATERIALS AND METHODS The study was carried out at Bangur Institute of Neurosciences, IPGME&R, Kolkata, after approval of the Institutional Ethics Committee. Sixty adult patients of 2060 years of age, ASA grade I and II, undergoing supratentorial craniotomy were selected for the study. Patients, allergic to study drug, or suffering from cardiac, pulmonary, renal, hepatic or haematological disorders were excluded. Patients having pregnancy, obesity and prior treatment with calcium channel blocker or anticoagulants were also excluded from the study. Informed consents were taken from the potential subjects prior to including them in the study during pre-anaesthetic check up. They were randomly allocated into two groupsMagnesium group (n=30) and Control group (n=30). Thorough pre-anaesthetic check- up and counseling had been done prior to anaesthesia. Before induction of anaesthesia, routine monitoring [heart rate (HR), arterial oxygen saturation (SpO2), electrocardiography (ECG)] was started. An arterial line was inserted in radial artery to measure systemic blood pressure and blood sampling. The level of anaesthesia was monitored with bi-spectral index (BIS). The BIS electrodes were placed on the forehead and were connected to BIS (A-2000 BISTM monitor, Aspect TM Medical System Inc., Norwood, MA, USA). Magnesium group was received magnesium sulphate 30mg/kg, administered as a slow intravenous (IV) bolus before the induction of anaesthesia and then 10mg/kg/hour by continuous infusion till the closure of dura mater. The same volume of isotonic saline (0.9%) was administered to the control group. After pre-oxygenation for 3minutes, anaesthesia was induced with fentanyl 2µg/kg and propofol in increments of 20mg every 5seconds until BIS reached a predetermined value of 60. Lignocaine 1% (1mg/kg) was given to all patients to reduce pain caused by injection of propofol. After induction of anaesthesia supramaximal train-of-four (TOF WatchR, Organon Ltd, Dublin, Ireland) had been measured at 20 seconds interval. When a stable twitch response was established (at least three successive equal responses to TOF stimulation) rocuronium 1mg/kg was administered via a fast flowing IV infusion over 5seconds. Orotracheal intubation was performed after complete (T1 = 0%) single twitch depression. The time from the start of anaesthesia induction to reaching a BIS level of 60 had been recorded. Anaesthesia was maintained by N2O in O2 and Propofol infusion and intermittent fentanyl injection. Propofol infusion was started at the rate of 10mg/kg/hour and titrated to maintain BIS in the range of 45-60. The hourly

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consumption of propofol was recorded as mg/kg/hour. Dose adjustment of fentanyl was based on standard clinical signs and haemodynamic measurements. Inadequate analgesia defined as an increase in heart rate and mean arterial pressure (MAP) of more than 20% of baseline and was managed with fentanyl (0.5-1mg/kg), if BIS is within standard anaesthetic range. Muscle relaxation was achieved by rocuronium adjusted to provide complete depression of the first twitch after TOF stimulation. Throughout the operation PaCO2 level between 30-35mm Hg and normothermia were maintained. Approximately 30 minutes before the end of surgery or when dura was closed, magnesium infusion and rocuronium were discontinued. Patients were allowed to recover spontaneously until the return of T1 = 25%. Propofol was discontinued on skin closure. Patients were reversed with glycopyrolate 0.004mg/ kg and neostigmine 0.05mg/kg when BIS reached 80. After return of TOF ratio (T4/T1) to 70% and BIS 80 patients were extubated. Patients were transferred to recovery unit and were assessed neurologically for any signs of hypermagnesemia or any adverse effects. Pre- and post-operative serum magnesium level was estimated by Calmagite Dye method13. Data were expressed as mean ± SD. The requirement of propofol was compared between the two groups by Student’s unpaired t-test. Within each group, changes in haemodynamic parameters were assessed by repeated measures of analysis of variance (ANOVA) followed by Student’s paired t-test for comparison between two individual time points. Categorically variables were compared by Chi-square test or Fisher’s exact test, whichever is appropriate. The analysis was conducted on an intention to treat basis. A two tailed ‘p’ value <0.05 was considered statistically significant. RESULTS This is a prospective parallel group, double blind and controlled study involving 60 patients divided into two groups. In magnesium group (N = 30), patients received magnesium sulphate and those in control group (N = 30) received normal saline, along with propofol as continuous infusion. The patient characteristics in both groups were comparable with respect to age, weight, and duration of surgery (Table 1). All patients underwent the same type of surgery. Time interval between start of induction and achieving of BIS60 and recovery time are shown in Table 1. Induction of anaesthesia (BIS = 60) was achieved in 54.5 ± 2.39 sec in magnesium group and in 81.8 ± 3.25sec in control group (p<0.0001). The recovery time was shorter in control group, 7.34min versus 9.56min (p<0.001). The mean intraoperative propofol consumption in the control group was significantly higher than that in magne-


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3, Table 1 — Patient Characteristics, Time interval between start of induction and BIS60 and Recovery time Magnesium Group (mean ± SD)

Control Group (mean ± SD)

40.87 ± 10.7 17 : 13 58.93 ± 3.19 5.6 ± 1.05

38.97 ± 11 14 : 16 58.03 ± 3.67 6.32±1.04

Mean Age Sex (M : F) Mean Body weight (Kg) Duration of Surgery (hour) Time interval between start of induction & BIS60 (in seconds) Recovery time (in minutes)

81.8 ± 3.25 7.34 ± 1.07

Table 5 — Comparison of BIS between Magnesium Group & Control Group at various time points

Table 2 — Requirement of propofol Propofol requirement (mg/kg/hr)

1 2 3 4 5 6

st

nd

rd

th

54.5 ± 2.39** 9.56 ± 1.04**

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

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th

th

Magnesium Group (mean ± SD)

Control Group (mean ± SD)

8.24 ± 0.45 4.53 ± 0.45* 3.38 ± 0.42* 3.39 ± 0.4* 3.27 ± 0.27* 2.95 ± 0.08*

9.45 ± 0.3 7.26 ± 0.29 6.87 ± 0.34 6.95 ± 0.32 6.74 ± 0.3 6.72 ± 0.45

hour hour hour hour hour hour

* Correlation is significant at < 0.001 level

** Correlation is significant at < 0.001 level

Table 3 — Pre- and post operative Magnesium concentration (meq/L)

sium group (Table 2). Dose requirements of propofol were Magnesium Group Control Group 4.53mg/kg/hour and 3.38mg/kg/hour in second and third (mean ± SD) (mean ± SD) hour of operation in magnesium group in comparison to 7.26mg/kg/hour and 6.87mg/kg/hour in control group. Pre-operative 1.9 ± 0.23 1.97± 0.27 Post operative 3.65 ± 0.45 1.6 ± 0.24** Mean hourly dose requirement of propofol in magnesium group was 4.1 ± 0.48mg/kg/hour versus 7.73 ± ** Correlation is significant at < 0.001 level 0.49mg/kg/hour in control group. Thus there was statistically significant (p < 0.001) reduction of dose requirement of propofol in magnesium group. Dose changes associated with fluctuating depth of anaesthesia. reduction of propofol was found in second and third hour Meticulous use of depth of anaesthesia monitors (BIS, in comparison to first hour in both groups. haemodynamic parameters) with continuous infusion of Preoperative serum magnesium concentrations were anaesthetic drugs during intraoperative period is compared with the postoperative serum magnesium mandatory. The lack of accumulation and rapid recovery concentrations (Table 3). Patients in control group had index makes propofol suitable agent for continuous significantly lower serum magnesium concentration infusion. postoperatively compared with preoperatively. In this The principal findings of this study was continuous group, serum magnesium level decreased from 1.97 ± administration of magnesium sulphate reduces propofol 0.27meq/L to 1.6 ± 0.24meq/L. In magnesium group, requirement during intraoperative period. Induction of serum magnesium concentration significantly increased anaesthesia with propofol was more rapid in the presence from 1.9 ± 0.23meq/L to 3.65 ± 0.45meq/L. The of magnesium, but recovery was slower. We used an magnesium group required significantly less fentanyl (300 objective, quantitative measure of the anaesthetic state ± 45mg versus 500 ± 75mg) and rocuronium (100 ± 25mg (BIS) to guide anaesthetic requirements and to determine versus 120 ± 35mg). end points . The effects of magnesium on propofol Haemodynamic variables such as mean arterial blood consumption could be related to a sedative effect of pressure and heart rate were also monitored in order to magnesium, but evidence for such an effect is conflicting. identify any effects related to study drug. There was no Magnesium has been reported to produce general statistical difference between two groups (Table 4). Bispectral index between two groups at various time points has been compared (Table 5). In both groups, changes in BIS with time were Table 4 — Comparison of Mean Arterial Pressure (MAP) and Heart Rate between not statistically significant. 14-17

magnesium group & control group at various time points

DISCUSSION

The primary objective of neuroanaesthesia is to provide adequate conditions for good neurosurgical condition like good muscle relaxation, haemodynamic stability, adequate brain relaxation and timed neurological evaluation. The main advantage of using continuous infusion is provision of a state that would facilitate a s u rg e o n ’s f u n c t i o n a n d prevention of major haemodynamic

Mean Arterial Pressure (mm of Hg) Magnesium Group Control Group (mean ± SD) (mean ± SD) Baseline After induction After intubation Intra operative Post operative

80.57 ± 8.58 76.31 ± 8.85 83.4 ± 13.37 80.29 ± 10.21 82.17 ± 9.44

81.74 ± 9.49 78.09 ± 8.77 82.14 ± 15.14 78.09 ± 8.77 84.97 ± 10.4

Heart Rate (beats/min) Magnesium Group Control Group (mean ± SD) (mean ± SD) 73.43 ± 6.61 71.3 ± 1.34 71.3 ± 1.11 70.3 ± 1.03 70.6 ± 1.00

Correlation of all variables with controls is insignificant (p > 0.05)

70.47 ± 5.58 73.7 ± 1.24 72.7 ± 0.84 72.23 ± 1.06 69.23 ± 1.26

Baseline 89.5 ± 3.67 After induction After intubation Intra operative

Magnesium Group (mean ± SD)

Control Group (mean ± SD)

90.8 ± 3.42 50.2 ± 3.69 50.3 ± 3.14 48.67 ± 1.11

49.4 ± 3.37 49.9 ± 1.94 48.2 ± 1.62

Correlation of all variables with controls is insignificant (p > 0.05)

anaesthesia and enhance the activity of local anaesthetic agents18,19. In these studies, depressant effects on the CNS of animals injected with magnesium salts were reported. In one study, a narcotic state in human beings undergoing surgical operations was achieved by magnesium sulphate infusion5. However, Aldrete and colleagues suggested that this anaesthetic state was actually a sleep-like state caused by cerebral hypoxia from progressive respiratory and cardiac depression20. When ventilation was maintained, even very high levels of serum magnesium produced no CNS depression7. In healthy volunteers, intravenous administration of magnesium failed to induce sleep even at magnesium concentration 10 times higher than normal. The subjects felt and heard everything happening up to when the magnesium level exceeded 7mmol litre-1. There were no signs of anaesthesia, but the hand-grip force was markedly reduced6. On the contrary, increasing the magnesium dose was found to be associated with reductions in halothane MAC in rats7. With this data, Thompson and colleagues suggested that anaesthetics to be titrated carefully in patients receiving magnesium. Magnesium is an antagonist of NMDA receptor. In experimental study, intravenous administration of Mg2+ in rats reduces halothane MAC in a dose dependent manner. Many NMDA antagonists also reduce the MAC of other anaesthetic agents in vivo7,21. The exact mechanism of propofol action has not yet been fully elucidated. But it has been suggested that the action of propofol is to promote the function of the b1 subunit of g- amino butyric acid (GABA) through activation of Chloride channel and thereby enhances the inhibitory synaptic transmission. Propofol also inhibits the NMDA subtype of the glutamate receptor. This action may also contribute to the inhibition of the excitatory synaptic transmission. Inhibition of NMDA mediated excitatory neurotransmission may contribute to the anaesthetic, amnesic, and anticonvulsant properties of propofol22. Therefore, aforementioned action mechanisms suggest that magnesium sulphate when coadministered with propofol potentiates anaesthetic effects and NMDA antagonism of propofol. Another mechanism could involve the reduction of catecholamine release through sympathetic stimulation, by which magnesium

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might decrease peripheral nociceptor sensitisation or the stress response to surgery17. The haemodynamic profiles of the patients were also monitored in order to identify any effects related to magnesium administration. There was no statistically significant difference between the groups as well as within each group. In our study, the amount of fentanyl and rocuronium administered for the magnesium group were significantly less than the control group. This is not surprising, as the analgesic effect of magnesium and its effect at neuromuscular junction are well known. The fentanyl requirement was adjusted according to haemodynamic changes as a measure of intraoperative pain. This is considered a limitation of our study, as heart rate and MAP could change for many other reasons. Also, magnesium inhibits the release of catecholamines and might blunt the haemodynamic responses to inadequate analgesia. These anti-adrenergic actions have led to the use of magnesium during surgery for phaeochromocytoma23 and to evaluation of its efficacy in attenuating the response to endotrachial intubation24. However, the doses used in these studies, either as a bolus or as a infusion, were twice as high as the dose we used in our study. Therefore we included only ASA grade I and II patients in whom heart rate and MAP increases are likely caused by pain perception. The changes of serum magnesium concentrations were investigated during several clinical studies. It was noticed that serum magnesium concentrations decrease during anaesthesia and became normo-magnesemic 1-3 days after major surgery25,26,27. Magnesium decline has been identified as playing a crucial role in traumatic brain injury and its supplementation has been found to improve neurologic outcome28. Its neuroprotective effects have been demonstrated in both animal and human studies29,30. In our present study, serum magnesium concentrations also decreased in control group. The present finding corroborates with the study where they found patients in the magnesium group showed higher serum Mg2+concentration than patients in the saline group31. In another study, an inverse relation was found between serum magnesium concentration and cumulative postoperative analgesic consumption9. Disadvantages of magnesium sulphate like hypotension, bradycardia can occur intraoperatively but none of our patients has shown these side effects. There have been cases of magnesium toxicity lead to cardiac arrest and death. However magnesium toxicity begins at serum concentration of 2.5mMol/L which is much higher than magnesium group in this study32. CSF magnesium level remains unchanged during anaesthesia and plasma concentration is not parallel with CSF magnesium concentration33. However, we did not measure CSF Mg2+concentration in present study. As magnesium is a central nervous system depressant, delayed recovery from anaesthesia no doubt, is


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a disadvantage of magnesium sulphate infusion. Though control group in this study had shorter recovery time (7.34 min versus 9.56 min) than magnesium group, clinically it was not significant. This study has shown the possible effects of magnesium sulphate in reducing the anaesthetic requirements for balanced anaesthesia. When used judiciously, magnesium is safe and cost effective supplement to general anaesthetic regimen with propofol, fentanyl and rocuronium as it reduces the anesthetic and analgesic requirements. Though, we did not evaluate the cost/ effective analysis of this cheap medication compared to anaesthetic medications, Schultz-Stubner et al showed that a 2 hour anaesthetic without magnesium could cost 21-35% more than in magnesium group . In conclusion, because of its low price, well established safety profile and critical physiological role, magnesium sulphate may emerge as a valuable adjunct in neuroanaesthesia. 34

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REFERENCES Fawcett WJ, Haxby EJ, Male DA — Magnesium: physiology and pharmacology. Br J Anaesth 1999; 83: 302-20. James MFM — Clinical use of magnesium infusions in anaesthesia. Anesth Analg 1992; 74: 129-36. Iseri LT, French JH — Magnesium: nature’s physiologic calcium blocker. Am Heart J 1984; 108: 188-93 Meltzer SJ, Auer J — Physiological and pharmacological studies on magnesium salts. II. The toxicity of intravenous injection; in particular the effects upon the centers of the medulla. Am J Physiol 1906; 15: 387-405 Peck CH, Meltzer SJ — Anesthesia in human beings by intravenous injection of magnesium sulphate. JAMA 1916; 67: 1131-3. Somjen G, Hilmy M, Stephen CR — Failure to anesthetize human subjects by intravenous administration of magnesium sulphate. Pharmacol Ther 1966; 154: 652-9. Thompson SW, Moscicki JC, Difazio CA — The anesthetic contribution of magnesium sulphate and ritodrine hydrochloride in rats. Anesth Analg 1988; 20: 1273-5. Woolf CJ, Thompson SWN — The induction and maintenance of central sensitization is dependent on Nmethyl-D aspartate receptor activation: implication for the treatment of post injury pain and hypersensitivity states. Pain 1991; 44: 293-9. Koing H, Wallner T, Marhofer P, Andel H, Horauf K, Mayer N — Magnesium sulfate reduces intra and postoperative analgesic requirements. Anesth Analg 1998; 87: 206-10. Tramer MR, Schneider J, Marti RA, Rifat K: Role of magnesium sulfate in postoperative analgesia. Anesthesiology 1996; 84: 340-47. Gupta K, Vohra V, Sood J — Magnesium as an adjuvant during general anaesthesia. Anaesthesia 2006; 61: 105863. Lee DH, Known IC — Magnesium sulphate has beneficial effects as an aadjuvent during general anaesthesia for caesarean section. Br J Anaesth 2009; 103: 861-6. Gindler E — Clin Chem 1971; 17: 662. Lui J, Singh H, White PF — Electroencephalographic bispectral index correlates with intraoperative recall and depth of propofol induced sedation. Anesth Analg 1997; 84: 185-9. Vernon J, Lang E, Sebel P, Manberg P — Prediction of movement using BIS electroencephalographic analysis during propofol / alfentanil or isoflurane / alfentanil anesthesia. Anesth Analg 1997; 80: 780-5.

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16 Glass PSA, Bloom M, Kearse L, Rosow C, Sebel P, Manberg P — Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836-47. 17 Gan TJ, Glass PS, Windsor A, BIS Utility Study Group — Bispectra index monitoring allows faster emergence and improved recovery from propofol, alfentanil and nitrous oxide anesthesia. Anesthesiology 1997; 87: 808-15. 18 Meltzer SJ, Auer J — Physiological and pharmacological studies on magnesium salts. II Narcotizing effects of magnesium salts upon nerve fibres. Am J Physiol 1906; 16: 233-8. 19 Countinho EM — Calcium, magnesium and local anesthesia. J Gen Physiol 1966; 49: 845-6. 20 Aldrete AJ, Barnes DR, Aikawa K — Does magnesium produce anesthesia? Evaluation of its effects on the cardiovascular and neurologic systems. Anesth Analg 1968; 47: 423-33. 21 Hudspith MJ — Glutamate: a role in normal brain function, anaesthesia, analgesia and CNS injury. Br J Anaesth 1997; 78: 731-47. 22 Reves JG, Glass PSA, Lubarsky DA — Nonbarbiturate intravenous anesthetics, Anesthesia, 5th edition. Edited by Miller RD, Cucchiara RF, Miller RD Jr, Reves JG, Roizen MF, Savarese JJ. Philadephia, Churchill Livingstion, 2000, 228-72. 23 James MFM — Use of magnesium sulphate in anaesthetic management of pheochromocytoma: a review of 17 anesthetics. Br J Anaesth 1989; 62: 616-23. 24 James MFM, Beer RE, Esser JD — Intravenous magnesium sulphate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989; 68: 772-6. 25 Schulz- Stubner S, Wettmann G, Reyle-Hahn HM, Rossaint R — Magnesium as part of balanced general anaesthesia with propofol, remifentanil and mivacurium: a double blind randomized prospective study in 50 patients. Eur J Anaesthesiol 2001; 18: 723-9. 26 Okuda T, Kura M, Hatsnoka K, Izumi T, Kogu Y — Changes in ionized magnesium concentration during general anaesthesia. Masui 1999; 48: 136-40. 27 Togashi H, Kasuda H, Inoue S, Hotta Y, Fukuda H. Serum and urinary magnesium during and after cardiac surgery. Masui 1998; 47: 704-8. 28 Van den Heuvel C, Vink R — The role of magnesium in traumatic brain injury. Clin Calcium 2004; 14: 9-14. 29 Health DL, Vink R — Neuroprotective effect of MgSO and MgCl in closed head injury: A comparative phosphorus NMR study. J Neurotrauma 1998; 15: 183-9. 30 Smith DH, Okiyma K,Gennarelli TA, McIntosh TK — Magnesium treatment attenuates cognitive dysfunction following experimental brain injury. Neurosci Lett 1993; 157: 211-4. 31 Ryu JH, Kang MH, Park KS and Do SH — Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Anaesthesia 2008; 100: 397-403. 32 Durlach J, Durlach V, Bac M, Bara M, Guiet Bara A — Magnesium and therapeutics. Magnesium Research 1994; 73: 313-28. 33 Fuchs-Buder T, Tramer MR, Tassonyi E — Cerebrospinal fluid passage of intravenous magnesium sulfate in neurosurgical patients. J Neurosurg Anesthesiol 1997; 9: 324-8. 34 The Magpie trial collaborative group — Do women with preeclampsia and their babies benefit from magnesium sulphate? The Magpie Trial: a randomized placebocontrolled trial. Lancet 2002; 359: 1877-90. 4

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Original Article Role of topicalcyclosporine 0.05% in vernal keratoconjunctivitis 1

1

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Swati Agarwal , Sanjiv Gupta , Bhartendu Agarwal

To evaluate the efficacy and safety of topical cyclosporine A 0.05% in managing vernal keratoconjunctivitis. Patients between 5 - 20 years with vernal keratoconjunctivitis were included in this study who fulfilled the inclusion and exclusion criteria. All patients were treated with topical cyclosporine A 0.05% for 90 days. Symptoms and signs were given score and recorded at baseline (0 day), 7th day, 14th day, 30th day and 90th day. Intraocular pressure and detailed ocular examination were done on all visits. The mean score for severity of signs and symptoms decreased maximal at 30 days. No side effect of the treatment with topical cyclosporine A 0.05% eye drops were observed. Topical cyclosporine A 0.05% eye drops were found to be safe and effective in treatment of patients with Vernal Keratoconjunctivitis. [J Indian Med Assoc 2017; 115: 13-6]

Key words : Topical cyclosporine A 0.05% , vernal keratoconjunctivitis.

V

ernal keratoconjunctivitis (VKC) is a chronic recurrent non infectious allergic disease that generally affects children and young adult. Three forms of vernal keratoconjunctivitis are palpebral, limbal, mixed. Cornea can be involved in up to 50% of cases. Recent evidence suggests that more than one immune mechanism may be involved in the origin of disease . Topical corticosteroid has been used for treatment in these cases as they provide relief quickly but there is rapid recurrence of symptoms following their discontinuation. There is also a potential of adverse effects of corticosteroid. Such as secondary glaucoma, dry eye syndrome, infective condition of ocular surface as well as steroid induced cataract. Cyclosporine A is a cyclic polypeptide consisting of 11 amino acids produced as a metabolite of the fungus species Beauveria nivea. it is a potent immunomodulator that inhibits the clonal expansion of T helper/inducer subset of lymphocyte and the release of interleukins. Ophthalmologists all over the world have therefore ,been looking better modalities of treatment which could be more effective and safe. Topical cyclosporine has been tried in some clinical trials and has been demonstrated to be effective in both palpebral and limbal forms of VKC. However as only limited literature is available on this, therefore this study was undertaken with the aim to

evaluate the efficacy and safety of cyclosporine (0.05%) ophthalmic solution in treatment of VKC.

1

MATERIAL AND METHODS

(I) Selection of patient: Reference population: the study was aimed at being able to project its results to all the patients of vernal keratoconjunctivitis in North India. Source population: patients of vernal keratoconjunctivitis in the city of Lucknow (U.P.) and adjoining areas. Sampling frame: comprisesd of vernal keratoconjunctivitis patients attending the ophthalmic outpatient department of C.S.M.M.U Lucknow. Study sample: the patients of vernal keratoconjunctivitis who had not received any vernal keratoconjunctivitis targeted therapy for a period of one week before study enrolment(wash out period) were included in this study after informed consent.. Inclusion criteria • Diagnostic criteria: all patients of age group of 5-20 years attending the ophthalmic outpatient department of ophthalmology fulfilling following subjective and objective criteria were included in this study. • Any one of subjective criteria + any one objective criteria - limbal or palpebral sign &/or corneal sign (A) Subjective criteria 1 - Itching 2 - Redness 3 - Watering

2,3

Department of Ophthalmology, Chhatrapati Shahuji Maharaj Medical University, Lucknow 226003 1 MS (Ophthalmol), Associate Professor 2 MS (Ophthalmol), Consultant Surgeon, Lucknow 226019 15


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4 - Discharge (B)Objective criteria (I) Limbal sign(a) Gelatinous opacification (b) Limbal nodule (c) Horner Trantas spot (II) Palpebral signs (a) Cobblestone appearance or presence of papillae (III) Corneal signs (a) Punctuate epithelial keratitis (b) Superficial pannus (c) Shield‘s ulcer Exclusion criteria 1 - Pregnant or lactating mothers 2 - Contact lens wearers during the period of study 3 - Patients with ocular disorders such as glaucoma ,blepharitis or uveitis 4 - Patients aged less than 5 years and more than 20 years are excluded. 5 - Previous reported allergy to corticosteroid or to any component of the study. 6 - Ocular trauma or recent surgery in either eyes 7 - Patient taking oral steroid. Study design: This is a tertiary care center based randomized, single blind, comparative prospective, interventional study. (II) Method of Evaluation: For all patients a detailed history and examination were done for the following symptoms and signs subsequently graded as described below: (1) Itching in eyes 0 : No desire to scratch or rub eyelids 1 : Occasional desire to scratch eye lids but not completely absent 2 : Frequent desire to scratch or rub eyelids 3 : Constant desire to scratch or rub eyelids (2) Tearing 0 : Normal tear production 1 : Sensation of tears but not spilling over lids 2 : Infrequent spilling of tears 4 : Nearly constant spilling of tears (3) Discharge 0 : No discharge 1 : Roapy discharge in cul-de-sac 2 : Presence of crust on awakening 3 : Lids tightly matted with discharge (4) Photophobia 0 : No difficulty 1 : Mild difficulty causing squinting 2 : Dark glass necessary 4 : Difficulty causing to stay indoor Grading of signs: (1) Conjunctival hyperemia 0 : A normal quiet eye : some subjects will exhibit

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rare vessels that are naturally prominent either by location or a large normal vessel diameter 1 : Mild- Slightly dilated blood vessels is typically pink; can be quadrantic 2 : Moderate- .more apparent dilation of blood vessels;vessel color is more intense (redder); involves the vast majority of the vessel bed. 3 : Severe- Numerous and obvious dilated blood vessels; in absence of chemosis the colour is deep red; in the presence of chemosis the leaking interstitial fluid may make the colour appear less red or even pinkish;is not quadrantic. (2) Limbal nodule 0 : Absent 1 : In one quadrant 2 : In two quadrant 3: In three quadrant or more (3) Papillary hypertrophy 0 : No evidence 1 : Mild papillary hyperemia 2 : Hyperemia with hazy view of tarsal vessel 3 : Papillary hypertrophy ;non visualization of tarsal vessel (4) Punctate keratitis 0 : No evidence 1 : In one quadrant 2 : In two quadrant 3 : In three or more quadrant Best corrected visual acuity and Intra-ocular pressure was recorded and ophthalmic examination was done in all patients which included best corrected visual acuity, slit lamp biomicroscopy and measurement of intra ocular pressure by goldmann applanation tonometer. Sample size: A total of 56 patients were enrolled in this study with confidence level 95%, sampling error ±10, and population 600 (number of patients of vernal keratoconjunctivitis attending outpatient department) Out come measure Statistical analysis was done on SPSS statistical analysis software. To test the significance of the change in the severity of symptoms and signs at different time interval unpaired t test was used. p=0.05 was labelled as significant. OBSERVATION AND DISCUSSION

A total of 56 patients were enrolled and 44 patients completed the study. Study was completed between August 2010 and July 20111. Gender : out of 44 patients in this study, 31 were male and 13 were female 22 eyes (50%) patients were in age group 5-10 years.

JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3,

Type of vernal keratoconjunctivitis Out of the 44 patients, the predominant form noted was palpebral type having 22 patients (50%), followed by mixed type 20 patients (45.45%) and limbal form 2 patients (4.54%). Six patients (13.63%) had histories of other allergic conditions Efficacy analysis : Analysis of efficacy was computed from data of patients who had completed the 90 day trial period and who met inclusion criteria without any violation during the study. The total symptom and sign score, as well as individual symptoms and signs were compared between groups at baseline and at each follow up visit (Fig 1). The mean of total symptoms plus signs score at baseline and day 90 is shown in Table 1. In patients using topical cyclosporine no significant change in intra ocular pressure was seen. As seen in Table 2 and Fig 2 A total of four symptoms (itching, tearing, photophobia, discharge) and four signs (conjunctival hyperemia, papillae, limbal nodule, punctate keratitis). This was done in accordance with previous standard studies of topical treatment on patients with VKC . A total of 56 patients registered, with 44 completing the study. In our study it was observed that the disease had more prevalence in male(70.45%) as compared to female 4

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Table 2 — Comparison of mean score of intra ocular pressure from baseline in at different time interval N=44

Mean±SD

Baseline Day 7 Day 14 Day 30 Day 90

13.95±2.19 14.09±1.89 14.20±2.22 14.40±1.70 14.29±1.78

Change in t-value p-value Significance severity from baseline mean ± SD 0.13±1.97 0.25±2.04 0.45±1.95 0.34±2.05

0.45 0.81 1.55 1.10

P=0.64 P=0.42 P=0.13 P=0.18

Not significant Not significant Not significant Not significant

Fig 2 — Intra ocular pressure pressure at different time period using topical cyclosporine

(29.54%). This is in concordance with studies by Sayegh F(1978) . However Stefano bonini(1999) reported the M/F ratio as 3:2 in patients with less than 20 years. The predominant form of VKC was palpebral (n=22, 50%) and followed by mixed type (n=20, 45.45%) and least common type was limbal type (n=2, 4.54%).. A within group analysis revealed that the all symptoms and sign scores statistically decreased from base line. With respect to each symptoms, paired t test shows that change in reduction of severity of itching was significant at different time interval from base line(0 day) to 90th day in and the reduction was maximum at 30th day and 90th day there was recurrence of itching but there was a significant difference from base line (p=0.001) thus we observed that cyclosporine causes significant reduction in itching. Fig 1 — Showing a comparison of all signs and symptoms at There was significant reduction of watering and baseline and at day 90 discharge from base line (0 day) to 90th day (p<0.001) and maximum reduction at 30th Table 1 — Average value of signs and symptoms at different time lines day. At 90th day there was recurrence in Signs & Symptoms Baseline Day 7 Day 14 Day 30 Day 90 watering and discharge but not severe as base line. Itching 1.76±0.81 0.82±-0.7 0.61±0.60 0.56±0.60 1.0±0.80 In limbal nodule there was significant watering 1.70±0.92 0.70±-0.7 0.59±0.60 0.31±0.40 0.71±0.80 Discharge 1.50±1.13 0.68±0.74 0.64±0.48 0.39±0.65 0.64±0.84 reduction from base line (0 day) to 90th day Limbal nodule 1.09±1.01 0.52±0.74 0.45±0.70 0.43±0.60 0.84±0.90 (p<0.001). Recurrence found at day 90. Photophobia 0.63±0.78 0.31±0.5 0.13±0.40 0.11±0.30 0.15±0.40 Papillary hypertrophy 1.81±0.89 1.79±0.9 1.70±0.90 1.63±0.90 1.61±0.90 In photophobia and papillary Keratitis 0.44±0.84 0.29±0.7 0.13±0.34 0.06±0.90 0.11±0.38 hypertrophy, there was significant reduction Redness 1.09±0.86 0.77±0.8 0.52±0.70 0.65±0.70 1.06±0.90 from base line (0 day) to 90th day (p<0.001). 5

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Reduction in punctate keratitis (p=0.014) at 90th day was seen. In redness, maximum reduction of redness was present at 30th day and reduction was significant (p=0.001). On 90th day redness was equal to base line. There was no significance difference in intra ocular pressure at 90th day from base line (0 day) (p=0.18). Cyclosporine has maximum effect in most of the symptoms and signs at 30th day. Recurrences were present in all symptoms and signs except photophobia and papillary hypertrophy at 90th day. But all the recurrences of symptoms and signs are not equal to baseline except redness. Cyclosporine has no effect on intra ocular pressure. Thus cyclosporine is effective in treatment of vernal keratoconjunctivitis but after 30 days effect is reduced . Joginder Pal et al also found recurrence during study period after 3 months and supports our study. The study was designed to assess the use of topical cyclosporine (0.05%) in vernal keratoconjunctivitis and that it is safe Cyclosporine has no sight threatening side effect like rise in IOP, cataract but there was recurrence of symptoms after one month use. Thus according to our study cyclosporine should be a first line drug of treatment of vernal keratoconjunctivitis to avoid the sight threatening side effect of steroid. The education of the patient and his or her parents as to the prolonged and recurrent nature of VKC is one of the first aims of treatment. Understanding the cyclical nature of this disease may minimize the patient’s frequent changes of topical ocular therapy and the use of alternative therapies of dubious efficacy. 7,8,9

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CONCLUSION

The following conclusions can be drawn from this clinical trial of 90 days to see the efficacy and safety of cyclosporine 0.05% in treatment of vernal keratoconjunctivitis (VKC). (1) Vernal keratoconjunctivitis is more common in male. (2) The most common form of VKC is palpebral followed by mixed and limbal types.

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(3) Topical cyclosporine 0.05% is effective in controlling the symptoms and signs of VKC. (4) Cyclosporine 0.05% causes a statistically significant reduction of symptoms and signs on 30th day, but at 90th day recurrence of symptoms and signs occur but not as severe as baseline. (5) Overall cyclosporine is safe for topical use. (6) Further study are needed to evaluate the combination for patient of vernal keratoconjunctivitis. Duration and dose titration of these two individual drugs can be studied and decided to reach to a optimum safe and effective therapeutic regime. REFERENCES 1 Mendicute J, Aranzasti C, Eder F, Ostolaza JI, Salaberria M — Topical cyclosporin A 2% in the treatment of vernal keratoconjunctivitis. Eye 1997; 11: 75-8. 2 Leonardi A, Borghesan F, Avarello A, Plebani M, Secchi AG — Effect of lodoxamide and disodium cromoglycate on tear eosinophil cationic protein in vernal keratoconjunctivitis. Br J Ophthalmol 1997; 81: 23-6. 3 McGill JI, Holgate ST, Church MK, Anderson DF, Bacon A — Allergic eye disease mechanisms. Br J Ophthalmol 1998; 82: 1203-14. 4 Ozcan AA, Ersoz TR, Dulger E — Management of severe allergic conjunctivitis with topical cyclosporin a 0.05% eyedrops. Cornea 2007; 26: 1035-8.

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Original Article A comparative study of hypofractionated external beam radiotherapy versus conventional external beam radiotherapy in locally advanced carcinoma of uterine cervix Swapan Kumar Mallick1, Madhumay Pal2, Krishnangshu Bhanja Choudhury3 The objective of this study was to determine whether hypofractionated radiation was an effective alternative to conventional radiation for patients of locally advanced cervical cancer in terms of pelvic control and survivals. Advanced histopathologically proven squamous cell carcinoma of cervix of International Federation of Gynecology and Obstetrics (FIGO) Stages (2009) IIB to stage IVA were analyzed for this study. The patients in investigational arm (arm A) received external beam radiotherapy (EBRT) of 3900cGy(centiGray) in 13 fractions in two and half weeks, 5 days in a week, followed by high dose rate brachytherapy (HDR BT) and patients in conventional radiation arm (arm B) received conventional EBRT of 4600cGy in 23 fractions in four and half weeks,5 days in a week, followed by HDR BT. All patients in both groups had complete response irrespective of stage when evaluated at 1 month post treatment. Acute toxicities in both groups were comparable. When comparing the late small/large intestinal toxicities, 5 (25%) patients developed mild to moderate diarrhea with abdominal colic in arm A. But in arm B only three (15%) patients developedmild to moderate diarrhea (p value 0.615).The 34 months disease free survival was 65% in arm A in comparison to 50% in Arm B, a non-significant statistical difference (log rank test p value 0.386) justifying hypofractionated EBRT in treating advanced carcinoma cervix is both convenient and tolerable in our setting. [J Indian Med Assoc 2017; 115: 19-22 & 30]

5 Tabbara KF, al-Kharashi SA — Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomised, double masked trial comparing the effects on severe vernal keratoconjunctivitis. Br J Ophthalmol 1999; 83: 180-4. 6 Bonini Stefano, Bonini Sergio, Lambiase A, Marchi S, Pasqualetti P, Zuccaro O et al — Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup. Ophthalmology 2000; 107: 1157-63. 7 Joginder pal, Manisha Nada —Topical cyclosporine versus fluoromethalone in vernal keratoconjunctivitis. AIOC 2008 proceedings p 224. Ebook – http://www.edudoc.com/ebook/fluoromethalone.html. 8 Gupta V, Sahu PK — Topical cyclosporin A in the management of vernal keratoconjunctivitis. Eye 2001; 15: 39-41. 9 Kaan G, Ozden O — Therapeutic use of topical cyclosporine. Ann Ophthalmol 1993; 25: 182-6.

Key words : Hypofractionated radiation, cervical cancer.

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radiotherapy of 3900 cGy in 13 equal fractions over 2½ weeks(17 days) will be compared with conventional fractionated external beam radiotherapy of 4600 cGy in 23 equal fractions over 4½ weeks (31days) along with 3 (three) fractions of HDR BT of 7Gy per fraction at weekly intervals given to both arms. MATERIALS AND METHODS This was a single institutional, prospective, openlabel, comparative, interventional, non-crossover, twoarm, parallel group, randomized controlled study. During the period from January 2009 to April, 2012, patients of locally advanced histopathologically proven squamous cell carcinoma of cervix of FIGO stage (2009) IIB to stage IVA were selected for study. The inclusion criteria were age 30 to 60 years, KPS status more than 70, histology proven squamous cell carcinoma of cervix, FIGO (2009) stages IIB to IVA, no prior anticancer chemotherapy and/or radiotherapy, serum creatinine level < 1.5 mg/dl, no co-morbid diseases like diabetes mellitus, hypertension, veno-occlusive disease, renal disorder, hypothyroidism, residing in rural area (as defined by

ancer cervix is the commonest malignancy in Indian female population accounting for 25-30% of all female cancers-its incidence being 70 per 100000 women. Locally advanced stage (FIGO stages IIB-IVA) carcinoma of uterine cervix is the most common stage of presentation of carcinoma cervix in our hospital and common modality of treatment is conventional radiation. But for many patients with low socioeconomic condition and long distance to travel from place of residence associated with shortage of inpatient treatment facility, conventional radiation of 4 / weeks could not be administered and if it is administered inherent delays in treatment occur due to delay in getting admitted. The net outcome is poor therapeutic control. Here altered radiation fractionation may provide an advantage over conventional radiation fractionation schedule. In our study hypofractionated external beam 1

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We are requesting you to send Evidence based Article To : Hony. Editor, Journal of the Indian Medical Association (JIMA), 53, Sir Nilratan Sarkar Sarani (Creek Row), Kolkata 700014 Dr. Dilip Kumar Dutta Hony. Editor, JIMA

Dr. Kakali Sen Hony. Secretary, JIMA

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Department of Radiotherapy, Medical College, Kolkata 700073 1 MBBS, MD (Radiotherapy), Assistant Professor 2 MBBS, MD (Radiotherapy), Associate Professor, Department of Radiotherapy, Midnapore Medical College and Hospital, Midnapore 721101 3 MBBS, MD (Radiotherapy), Assistant Professor, Department of Radiotherapy, RG Kar Medical College, Kolkata 700004 19


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Office of the Registrar General and Census Commissioner, India) with distance from tertiary hospital at least 30 kms) and willing to give informed consent for participation in the study according to Helsinki declaration. Patients with simultaneous or prior malignancy within 5 years, previously treated cervical cancer, biopsy proven or radiographic evidence of metastatic disease and life expectancy of less than 6 months were excluded from the study. The external beam radiation was designed to include primary as well as regional extension of the disease. The field size was planned according to the size of pelvis and stage of the disease. Anterioposterior - posterioanterior (AP-PA) portals were commonly employed and"4 field box" radiation portals were used instead of anterioposterior posterioanterior (AP-PA) fields if the inter field distance (IFD) was more than 20 cms. Gamma ray telecobalt 60, average energy 1.25 MeV with SSD of 80 cms was the source of EBRT. The patients in arm A (investigational arm) received 3900cGy in 13 fractions in two and half weeks followed by high dose rate brachytherapy and patients in arm B (conventional radiation arm) received conventional EBRT 4600 cGy in 23 fractions in four and half weeks followed by brachytherapy. Brachytherapy was started two weeks after completion of EBRT.The specification of a target dose was in terms of dose to a point at or near the centre of the target volume. The intracavitary brachytherapy using remote after loading device (Microselectron HRD) with Iridium 192 sources were used with the standard intracavitary applicators. The dose delivered was 7 Gy to point A in once a week application, for 3 weeks. Primary end point of the study was response rates assessed as per Response Evaluation Criteria in Solid Tumors, (RECIST) older Version 1.0 four weeks after completion of treatment to determine immediate response to treatment. Thereafter response was assessed every month on follow up upto 6 months and every 2 months subsequently. Response assessment was done clinically and radiological investigations were used whenever appropriate. The definition used to define response are as follows: Complete Response (CR) is the disappearance of all target lesions, Partial Response (PR) is at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started and Progressive Disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started

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or the appearance of one or more new lesions (all measurable lesions up to a maximum of five lesions per organ and ten lesions in total, representative of all involved organs, should be identified as target lesions and recorded and measured at baseline). The secondary endpoints of study were toxicity comparison and disease free survival assessment. Acute and chronic Morbidity were assessed as per Toxicity criteria of the Radiation Therapy Oncology Group (RTOG). Disease-free survival (DFS) is defined as time span from date of completion of treatment until date of first recurrence, locoregional or systemic. Disease Free Survival (DFS) comparison was done by Kaplan-Meier analysis with Mantel-Cox test. STATISTICAL ANALYSIS Patient accrual was completed within first 4 months of study and follow up period planned for 36 months for last recruited patient in this study. It was a simple randomization procedure by lottery in 1:1 allocation. The method of allocation concealment was sequentially numbered and sealed in opaque envelopes. Continuous data was summarized as Mean ± SD and categorical variables as frequencies. Fisher Exact probability test with Freeman Halton Extension test and Chi square test for comparison of categorical data of demographic, stage profiles, treatment response and toxicity profiles and for continuous variables independent t test was used for comparison. All tests were 2 tailed with p value less than 0.05 taken to be significant. We estimated the actuarial values of the Disease Free Survival (DFS) by KaplanMeier analysis with Mantel-Cox test, with SPSS (version 17.0) statistical software. Data are presented as 3 years and 4months actuarial values. RESULTS

Between January 2009 to April, 2012, fifty(50) patients with locally advanced squamous cell carcinoma of cervix were initially enrolled for inclusion in the study. Ten(10) patients were left out of study after failing to comply with the eligibility criteria. The remaining 40 (forty) patients were randomized for study. The accruals of all patients were completed within the stipulated 4 months after initiation of study. Twenty (20) patients in arm A and 20 patients in arm B were analyzed. The baseline parameters of the patients in both the groups were comparable (Table 1). All patients in both groups had complete response irrespective of stage when evaluated at 1 month post treatment(Table 2). Acute toxicities in both groups were comparable. All patients were treated symptomatically and completed the planned radiation therapy (Table 3). When comparing the late small/large intestinal toxicities, 5 (25%) patients developed mild to moderate diarrhea with abdominal colic in arm A. But in arm B only three (15%) patients developed mild to moderate diarrhea (p value 0.615). In both the arms one patient developed grade I late bladder

radiation complication (p value 1).The 34 months disease free survival was 65% in arm A in comparison to 50% in Arm B, non-significant statistical difference (log rank test p value 0.386) (Table 4). Out of 13 patients in arm A, 9 had recurrence within the pelvis, of which 6 had associated obstructive uropathy, 2 had abdominal paraaortic lymphadenopathy and 2 had distant thoracic and left supraclavicular lymph nodal metastases. In patients receiving conventional radiation 8 had pelvic recurrences with another 1 having thoracic metastases. Seven (7) patients had obstructive uropathy. Those with obstructive uropathies underwent percutaneous nephrostomy. All patients with loco-regional recurrences and distant metastases went on to receive paclitaxel, carboplatin or gemcitabine chemotherapeutic drugs, either as single or combination therapy. DISCUSSION

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effect was more in early stage patients . The study of R. Pearcey et al did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m to radical RT as given in their trial forInternational Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease >5 cm or histologically confirmed pelvic lymph node involvement . They concluded that careful attention to RT details is important for achieving optimum outcome for patients with this disease. Furthermore due to elevated serum creatinine levels, cisplatin may sometimes have to be omitted from treatment protocols, thereby leaving option for conventional fractionation alone. Altered fractionation provides an alternative to conventional radiation for these patients. The aim with altered fractionation schedules is to increase the therapeutic ratio and increase tumor control or decrease normal tissue side effects or a combination of both. However the most important consequence of altering a fractionation schedule is that late effects are more sensitive to the changes in size of dose per fraction, and acute reactions are more sensitive to the rate of dose accumulation. The basic rationale for hypofractionation is that the use of large dose fractions allows higher total doses to be administered within the tolerance of late responding normal tissues, and this translates into a higher biologically effective dose to the tumor. For this rationale 3

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Cancer cervix is the commonest malignancy in Indian female accounting for 25-30% of all female cancers its incidence being 70 per 100000 women. Though with an effective screening system, that allows diagnosis of premalignant conditions and early malignancy, it could be prevented, at least partly still in a third world country like India, majority of cases are presenting in advanced stages. The National Cancer Institute (NCI) issued a clinical alert in February 1999 with regard to positive survival advantages found with cisplatin based concurrent chemoradiation in each of five randomized prospective Phase-III trials for cervix cancer . Patient population included those with FIGO IB2-IVA in which primary radiotherapy was planned, or patients with poor prognosis Stage I-IIA lesions following surgical Table 1 — Patient, disease and treatment parameters resection. All the trials demonstrated significant survival benefit when compared Baseline parameters Groups P value with irradiation alone. The risk of death from Arm A (n=20) Arm B (n=20) cervical cancer was decreased by 30-50% Age (in years)* 49.4 ± 5.87 48.35 ± 7.42 0.623# with concurrent chemoradiation. Based on Age at marriage (in years)* 16.95 ± 1.85 18.70 ± 1.49 0.929# these results, the NCI clinical announcement Age of first child birth (in years)* 18.60 ± 1.81 18.15 ± 1.87 0.445# suggested that strong consideration should be 50.0% 9 45.0% 0.907 given to the incorporation of concurrent Karnofsky performance 70% 10 status 80% 7 35.0% 7 35.0% cisplatin based chemoradiation in women 90% 3 15.0% 4 20.0% who require irradiation as a component of treatment for cervix cancer. A systematic Socioeconomic Middle 7 35% 5 25% 0.490 65% 15 75% review of all known randomized controlled conditions rural modified Low 13 t r i a l s d o n e b y G r e e n s u g g e s t s udaipareekh scale chemoradiation improves overall survival FIGO Stage FIGO stage IIB 6 30.0% 5 25.0% 0.831 and progression free survival, with absolute FIGO stage IIIA 3 15.0% 4 20.0% FIGO stage IIIB 10 50.0% 9 45.0% benefits of 12% and 16% respectively. While FIGO stage IVA 1 5.0% 2 10.0% accepting that chemoradiotherapy is perhaps the new standard of care according to the Hemoglobin (gm/dl)* 10.90 ± 1.95 11.11 ± 1.61 0.706# western literature we need to remember that Leucocyte (x 109 cells/L) 6.25 ± 1.55 6.60 ± 1.43 0.463# these results were obtained in a trial setting, in Total duration of treatment (in days) 53.35 ± 3.27 67.00 ± 7.89 <0.001** women from affluent countries with good nutritional and performance status. The *Mean ± SD #Independent sample t test **significant p value (<0.05) review also shows that the beneficial Parameters for demographic profile included residence in rural areas and socioeconomic 1

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status using Modified UdaiPareek Scale for rural population.


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ment ratio is lower. Hypofractionated radiotherapy can be considered in a select group of patients where local disease FIGO staging Groups is extensive and hence unsuitable for conventional Arm A (n=20) Arm B (n=20) fractionation. In clinical trial at the Radiotherapy Department, IIB 6 30.0% 5 25.0% IIIA 3 15.0% 4 20.0% University College Hospital, Ibadan, four hundred and IIIB 10 50.0% 9 45.0% eighty patients with histologically confirmed carcinoma IVA 1 5.0% 2 10.0% of the uterine cervix were randomized into 2 groups to either receive hypofractionated radiotherapy (HF-230 In both the treatment arms all patients achieved complete response. patients-study group) or conventional fractionated radiotherapy (CFR-250 patients-control Table 3 — Acute RTOG radiation induced toxicities group) between December 1988 and Organ tissue RTOG toxicties Arm A (n=20) Arm B (n=20) P value November 1992 . The 5-year survival rate for HF patients in Stages I, II, III and IV were, Skin Grade 0 14 70.0% 16 80.0% respectively, 91.3%, 67.2%, 40.2% and 18.0% Grade 1 5 25.0% 4 20.0% 0.716 while for CFR patients in Stages I, II, III and IV Grade 2 1 5.0% 0 0.0% were respectively, 92.8%, 69.2%, 42.5% and Gastrointestinal Grade 0 13 65.0% 11 55.0% 19.6%. Though early radiation adverse effects (lower) Grade 1 5 25.0% 6 30.0% 0.819 were similar in CFR and HF patients, marked Grade 2 2 10.0% 3 15.0% late adverse radiation effects were observed in HF patients than in CFR patients. Complete Hemoglobin Grade 0 (>11) 2 10.0% 4 20.0% (gm%) Grade 1 (11-9.5) 8 40.0% 7 35.0% 0.880 response rate and local tumour controls were Grade 2 (<9.5-7.5) 7 35.0% 7 35.0% found to be similar in the HF and CFR patients. Grade 3 (<7.5-5.0) 3 15.0% 2 10.0% This study revealed that with similar 5-year White Blood Cells Grade 0 (> 4.0) 9 45.0% 8 40.0% survival, complete response rate and local (x1000) Grade 1 (3-<4) 9 45.0% 10 50.0% 0.999 tumour control in HF and CFR patients, while Grade 2 (2-<3) 2 10.0% 2 10.0% a significantly higher late radiation adverse effects recorded in HF patients, conventional ratio for the tumor cells must be greater fractionated radiotherapy is the preferred form of radiation to hold, the a /b therapy in the management of carcinoma of the uterine than that for the dose limiting normal tissue. cervix.The researchers concluded that administration of Acute responding tissues as a class have a higher a/b hypofractionated radiotherapy for cervical cancer patients ratio than late responding normal tissues. Because of the with the aim of maximizing the use of few available kinetic similarity between the tumors and acutely radiotherapy facilities, as currently obtained in some responding normal tissue it may be predicted that tumors radiotherapy centres in Nigeria will result in high post also tend to have a higher a/b ratio (with prostate as an treatment morbidity . exception). Other rationales for hypofractionation are In another study at Tata Memorial hospital, Mumbai, radio-sensitization through redistribution and lesser medical records of 62 women with advanced carcinoma dependence on oxygen effect. cervix IIIB treated during 1994-1996 were reviewed. With large fractional doses, the influence of tumor cell Patients were treated with standard pelvic portals to a total hypoxia is reduced on two counts. First the proportion of dose of 39Gy in 13 fractions over 17 days followed by hypoxic cells needs to be higher to increase significantly intracavitary brachytherapy. Forty-eight patients the surviving fraction, and second, the oxygen enhance completed the planned treatment and were considered suitable for analysis of late reactions and survival. The 5year disease free survival was 59% and the overall survival was 50% at the mean follow up Table 4 — Disease free survival comparison, log rank test p value 0.386 of 40 months. Twenty-one (44%) patients (nonsignificant) developed acute gastrointestinal toxicity of Summary Means for survival times (in months) which 5 patients had grade III and one patient Groups Total N of Censored Estimate Std. 95% Confidence had grade IV reaction. Ten patients (21%) N Events Error Interval N Percent Lower Upper developed acute genitourinary complications, Bound Bound 13 patients (27%) had late rectal reactions and 10 patients (20%) had late bladder Arm A 20 7 13 65.0% 25.227 2.670 19.993 30.460 complications. Three patients had grade I, five Arm B 20 10 10 50.0% 22.029 2.743 16.653 27.405 Table 2 — Stage wise response rate (p value 0.831)

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1.926

19.907

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Observational Study Onychomycosis : dermatophytes to yeasts; an experience in and around Mumbai, India Rupali S Suryawanshi1, Shashir W Wanjare2, Avani H Koticha2, Preeti R Mehta3 Onychomycosis is a fungal nail infection having wide range of prevalence in different geographical regions. It becomes imperative to know prevalent causative agent in local area to improve quality of life of patients. To study epidemiological, clinical and laboratory aspects of onychomycosis. Study was carried out prospectively at a tertiary care teaching hospital. Nail scrapings of 630 clinically suspected cases of onychomycosis over a period of 5 years were subjected to KOH examination and culture. Young adults in age group of 21-40 years (67.61%) were predominantly affected with male to female ratio of 1.8:1. Overall prevalence of onychomycosis of the present study is 58.41%. Yeasts were isolated in 47.86%, dermatophytes in 30.71% and non dermatophytic filamentous fungi in 21.43%. Present study demonstrates a shift in causative agents from dermatophytes to yeasts. [J Indian Med Assoc 2017; 115: 23-6]

Key words : Onychomycosis, yeasts, dermatophytes, non dermatophytic filamentous fungi.

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nychomycosis is a fungal infection of nails which can be caused by dermatophytes, yeasts or nondermatophytic moulds1. It is responsible for up to 50% of all nail diseases and 30% of all fungal infections2. Onychomycosis has varied worldwide distribution ranging from 2% to 50%3. Various risk factors associated with this condition are reduced peripheral circulation, diabetes, nail trauma, difficulty to maintain proper nail hygiene, chronic smoking, communal bathing etc. Clinically, onychomycosis is classified as distal lateral subungual onychomycosis, proximal subungual onychomycosis, white superficial onychomycosis and total dystrophic onychomycosis4. Onychomycosis is not a life threatening condition. It causes cosmetic problem to the patient. The infected nail may serve as a chronic reservoir, giving rise to repeated mycotic infection thus posing an important public health problem5. It can have significant negative effects on patient’s emotional, social, occupational functioning. There are many skin conditions like psoriasis, lichen planus, onychogryphosis which may be clinically confused with onychomycosis. Therefore, it is necessary to have a clinical suspicion and correct laboratory diagnosis of this condition before starting treatment for better results. Species identification is of paramount importance as the clinical outcome of antifungal

agents varies as to whether the etiological agent is yeast, dermatophyte, or other mould. There is paucity of such data available in tropical country like India. Prevalence of regional onychomycosis is not available. Hence this study was conducted to know epidemiological, clinical and laboratory aspects of onychomycosis. MATERIAL AND METHODS

After obtaining institutional ethics committee permission, study was carried out prospectively over a period of 5 years ie, January 2008 to December 2012. Suspected cases of onychomycosis referred to mycology division of a tertiary care hospital were included in the study. Detailed clinical history and examination findings were noted. Patients on antifungal agents were excluded from the present study. Specimen collection was done from most severely affected nail. Nail scrapings were collected on filter paper after cleaning the affected nail with 70% alcohol to remove contaminants. All specimens were subjected to microscopy and culture. Specimen was kept in 10% KOH for a period of 24 hours to dissolve the keratin and examined microscopically for presence of fungal elements . Specimens were inoculated onto Sabouraud’s dextrose agar with antibiotic, Sabouraud’s dextrose agar with antibiotic and 5% cycloheximide and Dermatophyte test medium (DTM) and were incubated in a BOD incubator at 30°C for 4 weeks. The pathogenic filamentous organisms 4

Department of Microbiology, Seth G S Medical College and KEM hospital, Mumbai 400012 1 MBBS, MD, Assistant Professor 2 MBBS, MD, Additional Professor 3 MBBS, MD, Professor and Head 23


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were identified by gross morphology, microscopic examination with lactophenol cotton blue preparation and slide culture. If a dermatophyte was isolated, it was considered as a pathogen. Nondermatophytic mould or yeast was considered significant if they were isolated repeatedly in pure culture in atleast three culture tubes. Yeast like growth was further speciated by use of germ tube, urease, corn meal agar and chrome agar inoculation. RESULTS

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Table 1 — Distribution of patients of onychomycosis according to age and gender Age group (Years) 0-10 11-20 21-30 31-40 41-50 51-60 61-70 > 70 Total

Male 0 27 155 121 70 20 10 2 405

Female 0 10 78 72 40 15 8 2 225

Total (Percentage) 0 37 (5.87%) 233 (36.98%) 193 (30.63%) 110 (17.46%) 35 (5.56%) 18 (2.86%) 4 (0.63%) 630

Six hundred and thirty clinically suspected cases of onychomycosis were included in the study. 405 (64.28%) were males and 225 (35.72%) were females with male to Table 2 — Comparison of microscopy and culture in clinically female ratio of 1.8:1. suspected cases of onychomycosis Young adults were most commonly affected in the age group 21 to 30 years (36.98%) followed by 31 to 40 years KOH Culture Positive Negative Total (30.63%) (Table 1). When occupational history was analyzed, it was Positive 186 (29.52%) 88 (13.96%) 274 (43.49%) observed that there were 55.87% farmers, 19.04% Negative 94 (14.92%) 262 (41.58%) 356 (56.51%) housewives, 12.69% laborers, 3.65% students and Total 280 (44.46%) 350 (55.54%) 630 remaining 8.75% were doctors, office workers, retired persons. Fingernails were affected in 440 (69.84%) patients while in 125 (19.84%) patients toenails were affected. In T mentagrophyte, T tonsurans, T verrucosum, T 65 (10.32%) patients, both the finger and toenails were violaceum. There were few cases of M ferrugineum affected. (0.71%) and E floccosum (0.71%). Distal lateral subungual onychomycosis was the most Among the non-dermatophyte filamentous fungi common manifestation in 320 (50.79%) cases followed by Fusarium spp (10%) was the most common isolate fol proximal subungual onychomycosis (26.34%), white superficial onychomycosis (17.14%) and total dystrophic onychomycosis (5.72%). Table 3 — Isolation of fungi over period of 5 years (2008-2012) Of 630 clinically suspected cases, 368 (58.41%) were confirmed either by Species No of isolates direct microscopy and/or culture (Table 2008 2009 2010 2011 2012 Total Percentage 2). Direct microscopy could identify All yeast & Yeast 274 cases (43.49%) whereas 280 like fungi : (44.46%) cases were confirmed by C albicans 12 6 18 14 6 56 20.00% C tropicalis 4 6 10 6 6 32 11.43% culture, 186 (29.52%) cases were C parapsillosis 0 4 12 4 18 38 13.57% positive by both microscopy and C kefyr 0 0 2 0 0 2 0.71% culture. Tricosporoon spp 0 0 2 2 2 6 2.14% Total 16 16 44 26 32 134 47.86% Among the 280 isolates, yeasts (47.86%) were predominant followed Dermatophytes : T rubrum 4 6 5 12 16 43 15.36% by dermatophytes (30.71%) and nonT mentagrophyte 6 6 4 4 2 22 7.86% T tonsurans 3 1 1 1 2 8 2.86% dermatophyte filamentous fungi T verrucosum 1 0 2 0 0 3 1.07% (21.43%) (Table 3). T violaceum 1 0 2 2 1 6 2.14% Of the yeast isolates, isolation of M ferrugineum 0 0 2 0 0 2 0.71% non-albicans candida (25.71%) was E floccosum 0 0 2 0 0 2 0.71% Total 15 13 18 19 21 86 30.71% more than C albicans (20%). Non albicans candida isolated were C Non dermatophytic filamentous fungi : parapsillosis (13.57%), C tropicalis Fusarium spp 12 6 4 0 6 28 10.00% Aspergillus spp 4 2 4 2 2 14 5.00% (11.43%) and C kefyr (0.71%). Paecilomyces spp 0 0 0 0 2 2 0.71% T rubrum (15.36% ) accounted for Cladosporium 0 0 4 0 4 8 2.86% majority cases of dermatophytic Curvularia 0 0 4 2 0 6 2.14% Alternaria 0 0 2 0 0 2 0.71% onychomycosis followed by Total 16 8 18 4 14 60 21.43% other trichophyton species namely

lowed by Aspergillus spp (5%). Phaeoid fungi namely Cladosporium (2.86%), Curvularia (2.14%), Alternaria (0.71%) were also isolated. DISCUSSION Onychomycosis is a chronic infection of nails affecting quality of life. Though this condition has got poor attention in earlier days due to less awareness in community, its prevalence is now increasing with wide spectrum of causative agents. The disease occurs worldwide with varying prevalence in different geographical areas. In this study, prevalence of onychomycosis is 58.41%. In India, different studies reported prevalence ranging from 37.78% to 54.5%6-9. It has been reported to involve both the sexes of all age groups. In our study, maximum numbers of patients having onychomycosis were in the age group of 21 to 40 years (67.61%) (Table 1). Patients of this age group are more prone to trauma because of their outdoor activities making their nails more exposed to fungi. Alternately, young population may be more sensitive towards cosmetic damage of nails and approach clinicians on time. In the present study, there were no patients below age group of 10 years. This could be attributed to size of nail bed and rate of growth of nail plate. The small size of nail bed provides lesser area for fungal invasion, whereas increased growth rate of nail plate in children helps to the elimination of fungi. This finding correlates well with other studies8,10,11. Few authors have reported higher prevalence of onychomycosis in elderly age group12,13. But in our study only 9.05% of patients above age of 60 years were affected. This may be due to ignorance about the disease in this age group and partly due to asymptomatic nature of this condition. It is said that onychomycosis is a disease of women because of their more involvement in wet work5,6. However, in our study, males were found to be more affected than females (Table 1). This male preponderance could be due to their increased outdoor activities, type of occupation and increased use of ill fitting foot wares. This makes them more vulnerable to trauma and subsequent entry of fungi. This finding is similar with other studies14. Some authors have postulated that this gender difference may be due to differences in hormone levels that result in a different capacity to inhibit the growth of dermatophytes1417 . We observed that fingernails (69.84%) were most commonly affected site followed by toenails (19.84%). In 65 (10.32%) patients both the finger and toenails were affected. This finding is similar to that reported by other authors9,10. Distal lateral subungual onychomycosis (50.79%) was the most common pattern followed by other clinical patterns namely proximal subungual onychomycosis (26.34%), white superficial onychomycosis (17.14%) and

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total dystrophic onychomycosis (5.72%). K Narotham Reddy et al, Kaur R, et al have also reported similar findings10,18. Microscopic examination with KOH and culture are the two laboratory tools used to confirm onychomycosis. In this study, direct microscopy using KOH could identify 43.49% cases whereas 44.46% cases were confirmed by culture. 29.52% cases were positive by both microscopy and culture (Table 2). In 14.92% culture positive cases, KOH was negative. This might be due to difference in sensitivity of these methods. Sensitivity of both these methods depends upon various factors right from method of sampling, preparation of sample up to final interpretation of result9. Hence both the tools are complimentary to each other. Use of both these methods is advocated in routine diagnostic mycology laboratories. Dermatophytes are said to be the most common fungi associated with onychomycosis19,20. They have been responsible for 90% of toe nail and 50% of finger nail infections18. Few workers have reported equal incidence between dermatophytes and yeasts21. Scenario is changing from dermatophytes to yeasts which is the case even in our study. In our study yeasts (47.86%) are the predominant pathogen followed by dermatophytes (30.71%) and non-dermatophyte filamentous fungi (21.43%). Similar findings were shown by other researchers6,13. Overall prevalence of C albicans in our study was 20% whereas that of non-albicans was 25.71%. The prevalence of C albicans showed steady decline over a period of 5 years (2008 to 2012). Among non albicans candida, the prevalence of C parapsillosis was 13.57% and C tropicalis was 11.43%. There was uniform increase in number of isolates of C parapsillosis over 5 years showing shift from C albicans to non-albicans candida mainly C parapsillosis. Our finding is in contrast with the findings of Gelotar et al, M Gerami shoar et al who have not reported any shift from C albicans to non-albicans candida6,13. Onychomycosis due to candida is a sign of immune suppression22. Systemic treatment wi th itraconazole or fluconazole is usually effective against all candida species and not much resistance has been reported from candida isolates of onychomycosis22. Hence with changing trends and a shift to non-albicans candida, antifungal susceptibility testing should be recommended. More studies will be required to analyze resistance pattern. Among dermatophytes isolated, T rubrum (15.36%) was the most common isolate followed by T mentagrophyte (7.86%). Some workers have shown T rubrum as most common agent while some found T mentagrophyte as the most common pathogen7,9,10. Thus there may be a change in the species of dermatophytes


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with respect to geographical area. There were two cases of E floccosum in our study. Interestingly both these isolates were seen from health care workers. Therefore more studies are needed to enlighten association of E floccosum to health care workers. Isolation rate of non-dermatophytic filamentous fungi was 21.43% of which Fusarium (10%) was the predominant isolate. M Leelavathi et al, Shrijana Gurung et al have also reported similar findings in their study . It is interesting to note that dematiecious fungi namely Cladosporium (2.86%), Curvularia (2.14%), Alternaria (0.71%) have been isolated in our study. Thus, role of these nondermatophytic fungi as a cause of onychomycosis should not be ignored. Due to presence of periungual inflammation, nondermatophytic onychomycosis can be clinically suspected. Treatment with only systemic antifungals is effective in cases of Aspergillus infection whereas Fusarium infections are difficult to eradicate. Their treatment should always be associated with topical treatment and avulsion of affected nail along with systemic antifungals . Hence laboratory confirmation of these fungi is a must for betterment of patients. To conclude, it is observed that young adults were most commonly affected owing to their outdoor activities. Commonly affected site was fingernail with distal lateral subungual onychomycosis being usual clinical pattern. There is change in causative agent over a period of time from dermatophytes to yeasts. C parapsillosis and C albicans have emerged as leading cause of onychomycosis. Therefore, though onychomycosis does not impose serious public health problem, the etiological diagnosis this condition is imperative to improve quality of life. 12,23

24,25

REFERENCES 1 Weitzman I, Summerbell RC — The dermatophytes. Clin Microb Rev 1995; 8: 240-59. 2 Scher P — Onycomycosis: A significant medical disorder. J Am Acad Dermatol 1996; 35: S2-5. 3 Sharma S, Capoor MR, Deb M, Ramesh V, Agrawal P — Epidemiologic and clinicomycologic profile of onychomycosis from north India. Int J Dermatol 2008; 47: 584-87. 4 Chander J — Dermatophytosis. In: Textbook of Medical Mycology. 2nd ed. New Delhi: Mehta Publishers, 2002: 10004. 5 Neupane S, Pokhrel DB, Pokhrel BM — Onychomycosis: A clinico-epidemiological study. Nepal Med Coll J 2009; 11: 92-95. 6 Gelotar P, Vachhani S, Patel B, Makwana N — Prevalence of fungi in fingernail onychomycosis. Journal of Clinical and Diagnostic Research 2013; 7: 250-2. 7 Ahuja S, Malhotra S, Hans C — Etiological Agents of Onychomycosis from a Tertiary Care Hospital in Central Delhi, India. Indian Journal of Fundamental and Applied Life Sciences 2011; 1: 11-14. 8 Satpathi P, Achar A, Banerjee D, Maiti A, Sengupta M, Mohata A — Onychomycosis in Eastern India - study in a peripheral tertiary care centre. Journal of Pakistan

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Association of Dermatologists 2013; 23: 14-19. 9 Kaur R, Kashyap B, Bhalla P — A five year survey of onychomycosis in New Delhi, India: Epidemiological and Laboratory aspects. Indian J Dermatol 2007; 52: 39-42. 10 Reddy KN, Srikanth BA, Sharan TR, Biradar PM — Epidemiological, Clinical and Cultural Study of Onychomycosis. American Journal of Dermatology and Venereology 2012; 1: 35-40. 11 Kaur T, Puri N — Onychomycosis - a clinical and mycological study of 75 cases. Our Dermatol Online 2012; 3: 172-77. 12 Leelavathi M, Tzar M N, Adawiah J — Common Microorganisms Causing Onychomycosis in Tropical Climate. Sains Malaysiana 2012; 41: 697-700. 13 Gerami shoar M, Zomorodian K, Emami M, Tarazoei B, Saadat F — Study and Identification of the Etiological Agents of Onychomycosis in Tehran, Capital of Iran. Iranian J Publ Health 2002; 31: 100-04. 14 Gupta A K, Jain HC, Lynde CW, Watteel GN, Summerbell RC — Prevalence and epidemiology of unsuspected onychomycosis in patients visiting dermatologists’ offices in Ontario, Canada - a multicenter survey of 2001 patients. International Journal of Dermatology 1997; 36: 783-87. 15 Thomas J, Jacobson GA, Narkowicz CK, Peterson GM, Burnet H, Sharpe C — Toenail onychomycosis: an important global disease burden, Review article. J Clin Pharm Ther 2010; 35: 497-519. 16 Eliane Alves DFS, de Almeida LMM, Guilhermetti E — Frequency of onychomycoses caused by yeasts in Maringa, Parana, Brazil. Anais Brasileiros de Dermatologia 2007; 82: 151-6. 17 Clemons KV, Schar G, Stover EP, D Felman, DA Stevens —Dermatophyte-hormone relationships: characterization of progesterone-binding specificity and growth inhibition in the genera Trichophyton and Microsporum. Journal of Clinical Microbiology 1988; 26: 2110-5. 18 Kaur R, Kashyap B, Bhalla P — Onychomycosisepidemiology diagnosis and management. Indian J Med Microbiol 2008; 26: 108-16. 19 Elewski BE — Onychomycosis - Pathogenesis, Diagnosis and Management. Clinical Microbiology Reviews 1998; 415-29. 20 Szepietowski JC — Selected clinical aspects of onychomycosis. Mikol Lek 2004; 11: 119-28. 21 Gupta M, Sharma NL, Kanga AK, Mahajan VK, Tegta GR — Onychomycosis: Clinico-mycologic study of 130 patients from Himachal Pradesh, India. Indian J Dermatol Venereol Leprol 2007; 73: 389-92. 22 Rogers K, Wood N, Morris AJ — Antifungal susceptibility of non-albicans Candida species causing fingernail onychomycosis. Journal of the New Zealand Medical Association 2004; 117: 1201. 23 Gurung S, Yegneshwaran PP, Bhutia PY, Gupta A, Bairy I, Jagtap P, et al — Onychomycosis in two geographically distinct regions in India. Archives of Clinical Microbiology 2012; 3: 1-6. 24 Tosti A, Piraccini BM, Lorenzi S, Iorizzo M — Treatment of nondermatophyte mold and Candida onychomycosis. Dermatol Clin 2003; 21: 491-7. 25 Tosti A, Piraccini BM, Lorenzi S — Onychomycosis caused by nondermatophytic molds: clinical features and response to treatment of 59 cases. J Am Acad Dermatol; 42: 217-24.

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Observational Study Accidental fetal injuries during cesarean section deliveries J B Sharma1, M Goyal2, S Kumar3, K K Roy3 To investigate the incidence, type, location and risk factors for fetal injuries during cesarean section deliveries. The incidence of various fetal injuries in total 1850 cesarean sections performed by the authors over last 10 years was noted. The fetal injuries were correlated with the indication of cesarean section and whether the cesarean section was emergency or elective. Fetal injuries were divided into lacerations (mild, moderate and severe), fractures and hematoma. The incidence of cesarean section delivery was 18.2 percent. Out of total 1850 cesarean section deliveries, there were 14 fetal injuries with an incidence of 0.76 percent. The various fetal injuries observed were lacerations in 11 cases (0.59%) being mild in 5 cases and moderate in 6 cases, fractures in 2 cases (0.10%), subdural hematoma in one case (0.05%). The incidence was higher in cesarean section performed for cord prolapsed (12.5%) followed by malpresentation (4.62%). Fetal accidental injuries, though uncommon, can occur during cesarean section deliveries, especially for emergency cesarean section necessitating counseling of women about them prior to cesarean. [J Indian Med Assoc 2017; 115: 27-30]

Key words : Fetal injuries, cesarean section, laceration, fracture, accidental.

A

most of them heal well, some can cause handicap or even death . The present study was conducted to evaluate the incidence of various fetal injuries in various types of cesarean section deliveries and to correlate them with various indications of cesarean section.

ccidental and unintentional fetal injuries during ce-sarean section deliveries are usually considered preventable complications1. Cesarean sections are performed for various maternal and fetal indications to decrease maternal and perinatal mortality and morbidity2. The various complications of cesarean delivery are increased risk of infection, transfusion, prolonged hospitalization in immediate period and increased risk of morbidly adherent placenta and scar rupture in future pregnancy2,3. The rising rate of cesarean deliveries especially for non judicious indications, like cesarean on demand throughout the world is alarming4. The incidence of accidental fetal injuries during cesarean section delivery varies from 0.7 to 1.9%5-7. The various risk factors for fetal injuries include emergency cesarean section for fetal distress and cord prolapse, second stage cesarean section, ruptured membranes, surgeon’s experience1,7-9. In these conditions, speed of surgery required to deliver the baby quickly and safely can be associated with fetal laceration10. Fetal injuries are also more common when an inverted ‘T’ incision or ‘J’ incision is made into the uterus as compared to transverse or vertical incision10. The incidence of fetal laceration has been found to be higher in non vertex presentations5,10. Most (70%) lacerations occur on face, head and ear; while

10,11

MATERIAL AND METHODS

The incidence of various fetal injuries in cesarean sections performed by the authors over last 10 years (January 2000 to February 2010) in one unit of Department of Obstetrics and Gynecology at All India Institute of Medical Sciences, New Delhi, India was noted. The data also included cesarean section performed by the first author in previous hospital Maulana Azad Medical College, New Delhi from January 2000 to June 2003. Being a retrospective analysis, ethical clearance was not necessary. Cesarean sections were divided into emergency and elective depending upon the indication. The various fetal injuries like lacerations, fracture and hematoma were noted and correlated with the type of cesarean section and also with the various indications of cesarean section. Fetal lacerations were divided into three groups (as per recommendation of Dessole et al ) : mild when it is limited to the skin; moderate where it involves skin and muscles; and severe where it is deep involving skin, muscle, bone and other structures like nerves. Mild lacerations were treated by adhesive plaster conservatively while moderate and severe lacerations were sutured. Fractures were treated by paediatrician and orthopedician as per hospital policy. 2

Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi 110029 1 MD, FRCOG, Additional Professor 2 MD, DNB, Senior Resident 3 MD, Professor 27


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Statistical analysis was performed using SPSS package (2007). Crude odd ratios (OR) and confidential interval (CI) were calculated for the types of cesarean section and fetal injuries. For difference in the rates amongst the two groups and in relation to various indications of cesarean section, Chi square test was used and a probability (p) value of <0.05 was considered statistically significant. Multiple logistic regression analysis was used for confounders of indication of cesarean section. RESULTS

From January 2000 to February 2010, a total of 1850 cesarean section were performed by the various cesarean sections with no classical cesarean section. Skin incision was transverse in most cesarean sections (80.7%) while it was vertical in the rest (19.3%). In one case with malpresentation, inverted ‘T’ incision had to be given to deliver a fetus with transverse lie while the incision extended laterally on sides in three cesareans; one case for malpresentation, and two cases for cephalopelvic disproportion. Table 1 gives details of various fetal injuries in relation to different indications of cesarean section. There were a total of 14 fetal injuries out of 1850 cesarean sections making an incidence of fetal injuries to be 0.76 percent. The highest injury rate was observed in cesarean section performed for cord prolapse (12.5%) followed by cesarean section performed for malpresentation (4.62%). The incidence was 0.87%, 0.8%, 0.44% and 0.2% for cesarean sections done for fetal distress, previous two cesarean sections, chronic fetal hypoxia and cephalopelvic disproportion, respectively. Out of 1850 cesarean sections, 1265 (68.4%) were elective while 585 (31.6%) were emergency. Fetal injuries were more commonly observed in emergency cesarean section (6 cases; 1.02%) as compared to elective cesarean section (8 cases; 0.63%). They were also significantly more common in cesarean section performed for cord prolapse (12.5%) than for cephalopelvic disproportion (0.2%){p=0.03, RR=36.14}. Table 2 gives distribution of fetal laceration as mild, moderate and severe in relation to fetal presentation and also other types of fetal injuries. Cesarean section was performed for cephalic presentation in 1785 cases, breech presentation in 55 cases while it was done for transverse lie in 10 cases. There were 11 cases (0.59%) of fetal lacerations while there were 2 cases of fractures (0.10%) and one case (0.05%) of subdural hematoma in cephalic presentation. There were 7 cases (0.47%) of scalp lacerations with 3 cases of mild lacerations and 4 cases of moderate lacerations. There was one case of moderate laceration over face. There was no case of severe laceration in any cesarean section. In cesarean section performed for breech presentation, there were total 3 lacerations over buttocks with 2 cases being mild and one case being moderate lacera

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Table 1 — Incidence of fetal injuries during cesarean section per indication Indication

No of Fetal Injury CI (95%) cesarean injuries per section (n) indication(%)

Fetal distress during labour Malpresentation Fetal hypoxia (chronic- IUGR, PIH) Cephalopelvic disproportion Previous two cesarean Cord prolapse Total 1850

577 65

5 3

0.87 4.62

0.3-2.01 0.9-12.9

450 500 250 8 14

2 1 2 1 0.76

0.44 0.2 0.8 12.5 0.4-1.27

0.06-1.6 0.001-1.1 0.1-2.86 0.3-52.65

significantly higher in emergency cesarean section (1.02%)as compared to that in elective cesarean section (0.63%) which is expected as fetus is required to be delivered quickly in emergency cesarean section for fetal distress especially cord prolapse. Dessole etal also observed a higher rate of fetal injury in emergency than elective cesarean section deliveries. This may be related to critical time period available to avoid the risk of fetal morbidity and death . The uterine incision in these emergency cesarean sections is usually rapid and surgeon may inadvertently cause fetal injury with scalpel . The lower uterine segment during labor may only be 2 to 3 mm thick making fetus more to injuries with scalp incision . Absence of amniotic fluid due to prolonged rupture of membranes is a further predisposing factor to cause fetal injuries as fetus lies directly under the uterus without protective amniotic fluid . However, Weiner and Westwood did not find a correlation between fetal laceration and indication of cesarean section. In the present study we observed two cases of scalp injury in cesarean section performed for previous two cesarean sections. In both cases, the uterine scar was very fibrosed and difficult to cut requiring 3-4 stab incisions. The last stab incision inadvertently became deeper causing fetal scalp injury. In the present study, cesarean section performed for malpresentation was a high risk factor for fetal injury causing 4.62% injuries. Other authors have also observed higher incidence of fetal injuries in non vertex presentations as compared to vertex presentation . Fetal injuries tend to occur more commonly with inverted ‘T’ and ‘J’ shaped incision as compared to transverse or vertical lower segment incision as observed in our study as well as observed by other author . Out of total 14 fetal injuries in the present study, there were 11 fetal lacerations with 8 (72.7%) on scalp or face and 3(27.3%) on buttocks (in breech presentation). Other authors have also reported 70% lacerations occurring on face, head or ear; 20% occurring on buttocks, legs and ankle and 10% on the back . Lacerations have been classified as mild (skin involvement only), moderate (skin and muscle involvement) and severe (involving skin, muscle, bone and nerves) . Fortunately in the present study, out of 11 lacerations, 5 (45.5%) were mild while 6 (54.5%) were moderate lacerations. There were no severe laceration as it may be associated with long term fetal sequelae including permanent scarring, handicap or even death while mild to moderate lacerations may be of cosmetic significance only . Prevention of fetal injuries during cesarean section deliveries is by using general surgical principles which include meticulous suctioning at the site of uterine entry . 1

2

2

2

Table 2 — Frequency of fetal injuries according to fetal presentation, location and type Injury

Location

Mild

Moderate Severe

2,10

Laceration : (a) Cephalic presentation

6

Scalp Face Buttock

3 2

4 1 1

0

(b) Breech presentation Fracture Other injuries

Clavicle 1 Femur 1 Subdural hematoma 1

tion. Hence the incidence of fetal lacerations was much higher in cesarean section performed for breech presentation than for cephalic presentation. Mild lacerations were managed conservatively using adhesive plaster while moderate lacerations were sutured. There were 2 cases of fractures with fracture femur in one case and fracture clavicle in another case. Fracture femur was unexpected in a case of elective cesarean section performed for breech presentation. When blood tests of the baby were done, he was found to be suffering from congenital rickets explaining the cause of fracture. The fracture healed well by the use of plaster of Paris for 6 weeks. There was one case of fracture clavicle in a case of emergency cesarean section for deep transverse arrest. The fracture healed well by splinting. Two cases of scalp laceration were seen in cases of previous two cesarean sections performed before. There was fibrosis in previous cesarean scar site and it was difficult to cut the area necessating repeated use of blade causing scalp laceration. Hence fetal injuries were more common in emergency cesarean and cesarean for cord prolapse. DISCUSSION

In the present retrospective study, out of total 1850 cesarean section deliveries (585 elective and 1265 emergency), 14 cases of fetal injuries were observed making an incidence of 0.76 percent which is in accordance with the 0.7 to 1.9 percent in the literature. In the present study ,the incidence of fetal injuries was

2-10

2,10

10

2

2,10,11,12

13

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Removal of retractor before fetal head delivery also minimizes fetal injury . Methods of uterine entry used to reduce fetal injuries include scoring the uterus along the whole length of planned incision site with a scalpel and then bluntly entering uterine cavity by inserting a finger into central of the uterine incision . The uterine incision is then extended in both directions by retraction with index fingers only and not with the scalpel . We routinely use this method of opening the uterus which probably explains the lower incidence of fetal injuries in the present study. Another method of uterine entry is by grasping the lateral edges of the uterine incision with ring forceps or Allis clamps, elevating the uterine incision away from the presenting part of the fetus and completing the entry with the help of scissors . Keeping the membranes intact to help them to buffer the scalpel from the fetal parts also decreases the incidence of fetal injuries during cesarean deliveries . Fetal injuries are usually underreported and are often not published making it difficult to estimate the exact incidence and making risk reporting and patient counseling more difficult and problematic. Management of fetal injuries depends upon the type and severity of injuries. Most of the mild lacerations are superficial and heal spontaneously and are usually managed by the adhesive plaster or topical tissue adhesives like 2-octylcyanoacrylate . Moderate to severe lacerations need immediate cosmetic surgery for consideration of primary repair of deep structures and skin approximation. Hence accurate assessment of the wound especially with regard to wound tension and careful application of the adhesive to ensure adequate wound eversion is essential for optimum outcome. In the present study, 5 cases of mild lacerations healed well with conservative treatment with the help of adhesive plasters while 6 cases of moderate lacerations required suturing and healed well without leaving any permanent scar mark or long term sequelae. Similarly fracture clavicle healed well with splint while fracture femur which occurred unexpectedly in an elective cesarean section for breech presentation, required plaster of Paris for healing and is on follow up with orthopaedician. In this case the new born had congenital rickets which explained the unexpected fracture and was treated later with medical treatment. Sometimes scars can increase in size with the growth of the baby causing cosmetic problems as reported by Gajjar and Spencer . In conclusion, fetal injuries though uncommon can occur during cesarean section and may rarely cause long term sequelae. Hence, women should be counseled about the risks especially during difficult and emergency cesarean section to avoid litigation. Moreover, care should be performed during cesarean section by following surgical principles to minimize fetal injuries. 10

1,10

10

1,10

10

10,14

10


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JOURNAL OF THE INDIAN MEDICAL ASSOCIATION, VOL 115, NO 3, REFRENCES 1 Gerber AH — Accidental incision of the fetus during cesarean section delivery. Int J Gynecol Obstet 1974; 12: 46-8. 2 Dessole S, Cosmi E, Balata A — accidental fetal laceration during cesarean delivery: experience in an Italian level III university hospital. Am J Obstet Gynecol 2004; 191: 1673-7. 3 Clark SL, Koonings RP, Phelan JP — Placenta praevia accrete and prior cesarean section. Obstet Gynecol 1985; 66: 89-92. 4 Menacker F, Declercq E, Macdorman MF — Cesarean delivery: background, trends and epidemiology. Semin Perinatol 2006; 30: 235-41. 5 Smith JF, Hernandez C, Wax JR — Fetal laceration injury at cesarean delivery. Obstet Gynecol 1997; 90: 344-6. 6 Wiener JJ, Westwood J — Fetal lacerations at cesarean section. J Obstet Gynecol 2002; 22: 23-4. 7 Alexander JM, Leveno KJ, Hauth J — Fetal injury associated with cesarean delivery. Obstet Gynecol 2006; 108: 885-90. 8 Haas DM, Ayres AW — Laceration injury at cesarean

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section. J Matern Fetal Neonatal Med 2002; 11: 196-8. 9 Puza S, Roth N, Macones GA, Mennuti MT, Morgan MA — Does cesarean section decrease the incidence of major birth trauma? J Perinatol 1998; 18: 9-12. 10 Gajjar K, Spencer C — Fetal laceration injury during cesarean section and its long term sequelae: A case report. Am J Ostet Gynecol 2000; 4e. 11 Durham JH,Sekula-Perlman A, Callery RT — Iatrogenic brain injuryduring emergency cesarean section. Acta Obstet Gynecol Scand 1998; 77: 238-9. 12 Bowes WA — Clinical aspects of normal and abnormal labour. In: Creasy RK, Resnik R, editors. Maternal-fetal medicine. 4 ed. Philadelphia : WB Saunders; 1999; 541-68. 13 Abuhamad A, O’Sullivan MJ — Operative technique for cesarean section. In : Plauche WC, Morrison JC, O’Sullivan MJ, eds. Surgical obstetrics. Philadelphia: WB Saunders; 1992: 417-29. 14 Saraf S — Facial laceration at cesarean section: experience with tissue adhesive. Eplasty 2009; 9: e3.

Case Report Perigraft seroma : an uncommon complication of aneurysm repair Reetu John1, Edwin Stephen2, Shyamkumar Nidugala Keshava3, Sunil Agarwal2

th

Perigraft seroma is an uncommon condition that occurs following aortic aneurysmal repair. The diagnosis of this condition requires both clinical features and CT scan. The main complication includes infection, graft thrombosis and mass effect. The treatment options are repeated aspirations and re-operation with changing the graft. However most usually resolve spontaneously. [J Indian Med Assoc 2017; 115: 31]

Key words : Perigraft seroma, Aortic aneurysmal repair.

(Continued from page 22)

had grade II and five had grade III late rectal toxicity. The authors concluded that the survival in patients treated with hypofractionated radiotherapy appeared comparable to that of standard fractionation and that hypofractionated radiotherapy could certainly be considered in a select group of patients where the local disease is extensive and is unsuitable for conventional treatment .

6

10

REFERENCES 1 NCI Clinical Announcement: Concurrent Chemoradiation for Cervical Cancer. Washington, DC, United States Department of Public Health, February 1999. 2 Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan Edward V, Fowler Jr WC, Clarke-Pearson DL, Liao S-Y Randomized — Comparison of Fluorouracil Plus Cisplatin Versus Hydroxyurea as an Adjunct to Radiation Therapy in Stage IIB-IVA Carcinoma of the Cervix With Negative ParaAortic Lymph Nodes: A Gynecologic Oncology Group and Southwest Oncology Group Study. J Clin Oncol 1999; 17: 1339-48. 3 Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, MutchDG — Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999; 15: 1137-43. 4 Rose PG, Bundy BN, Watkins EB, M, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S — Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer. N Engl J Med 1999; 340: 1144-53. 5 Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe W

7

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E, Suggs CL, Walker JL, Gersell D — Cisplatin, Radiation, and Adjuvant Hysterectomy Compared with Radiation and Adjuvant Hysterectomy for Bulky Stage IB Cervical Carcinoma. N Engl J Med 1999; 340: 1154-61. Peters W A, Liu PY, Barrett R, Gordon W Jr, Stock R, Berek, JS, DiSaia, PJ, Souhami L, Grigsby P, Alberts DS — Cisplatin and 5-Fluorouracil plus radiation therapy are superior to radiation therapy as adjunctive in high-risk early stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: report of a phase III inter GROUP STUDY. (Abstract) Gynecol Oncol 1999. Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ — Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 2001; 358: 781-6. R Pearcey, M Brundage, P Drouin, J Jeffrey, D Johnston, H Lukka, G MacLean, L Souhami, G Stuart, D Tu — Phase III Trial Comparing Radical Radiotherapy With and Without Cisplatin Chemotherapy in Patients With Advanced Squamous Cell Cancer of the Cervix. J ClinOncol 2002; 20: 966-972. Campbell OB, Akinlade IB, Arowojolu A, Babarinsa IA, Agwimah RI, Adewole IF — Comparative evaluation of hypofractionated radiotherapy and conventional fractionated radiotherapy in the management of carcinoma of the cervix in Ibadan, Nigeria. Afr J Med Med Sci 2000; 29: 253-8. Muckaden MA, BudrukkarAN,Tongaonkar HB, Dinshaw KA — Hypofractionated Radiotherapy in Carcinoma Cervix IIIB Tata Memorial Hospital Experience. Indian Journal of Cancer 2002; 39: 127-34.

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W

e report a case of perigraft seroma which is an uncommon condition that occurs following aortic aneurysmal repair.

mechanism is leakage of ultrafiltrate through the graft which may be related to mechanical causes or a low grade infection2. The main complications include infection, graft thrombosis and mass effect, however those requiring intervention are seen in only 20%3. The treatment options include repeated aspirations and re-operation with changing the graft. However most usually resolve spontaneously (65%).

CASE REPORT A 33 year old hypertensive male, presented with intermittent back pain for a duration of one year. Imaging revealed a saccular suprarenal abdominal aortic aneurysm measuring 8.5 cm in diameter, involving the origin of renal arteries. There were air pockets noted within the thrombus which suggested an aortoenteric fistula. He underwent aneurysm repair, bypass of the right renal artery from thoracic aorta using polytetrafluoroethylene (PTFE) bypass graft, left auto-renal transplant and duodenal repair to close the fistula. His post operative period was uneventful. A follow up CTA done 36 months later showed low density area with Hounsfield Fig 1 — A representative CTA axial image at the infra-renal level, performed 36 months following unit of 36 around the graft with no surgical treatment, which demonstrates a low density area in the perigraft region (arrow) enhancement. Based on the clinical features and CT scan findings, REFERENCES perigraft seroma was considered. As the patient was asymptomatic it was decided not to intervene and instead to 1 Evelyn Kat, D Neil Jones, Jim Burnett, Robert Foreman, follow him up. A repeat CTA after a year did not show any change Robin Chok, Michael R Sage — Perigraft Seroma of Open in the imaging findings. Aortic Reconstruction, AJR 2002; 178: 1462-4. A perigraft seroma is usually diagnosed after 3 months of 2 Yuka Kondo, Akihito Muto, Alan Dardik — Masayasu Nishibe surgery as it takes that amount of time for any postoperative and Toshiya Nishibe, Perigraft seroma after surgical haematoma and fluid to resolve1. It occurs more frequently than aortoiliac aneurysm repair with knitted polyester graft: previously reported. The exact etiology is unknown. Several Report of two cases. Annals of Vascular diseases 2009; 1: theories have been postulated. Some studies state that it may be 44-6. immunological with increased levels of humoral fibroblast inhibition, induced by the graft acting as a foreign body. Another 3 Kadakol AK, Nypaver TJ, Lin JC, Weaver MR, Karam JL, Reddy DJ, Haddad GK, Shepard AD — Frequency, risk factors, and management of perigraft seroma after open abdominal aortic aneurysm repair. J Vasc Surg 2011; 54: 637-43.

Department of Radiodiagnosis, Christian Medical College, Vellore 632004 1 MBBS, DMRD, MD, Assistant Professor 2 MBBS, MS, Professor, Department of Vascular Surgery 3 MBBS, DMRD, MD, FRCR, FRANZCR, Professor 31


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Case Report Mesh migration into sigmoid colon following inguinal hernia repair Beena B Vaidya1, Samir H Vadher2, Vipin K Sisodia2, Saurabh Jambu3, Nishant Bansal4, 4 Jatin Bhojani Lichenstein tension free hernia repair is most commonly performed surgical procedure in a patient of groin hernia. Complications in hernia surgery are common. We report an unusual complication in a case of hernioplasty where the prolene mesh migrated into abdominal cavity. This patient presented with difficulty in passage of stool with mass palpable in left iliac fossa, fifteen months post-operatively. On colonoscopy scope could not be passed beyond rectum suggestive of stricture. Despite Lichenstein tension free hernia repair being a safe technique patient may often present with late and rare complication of mesh migration. [J Indian Med Assoc 2017; 115: 32-3]

Key words : Hernioplasty, mesh migration, sigmoid mass.

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ernioplasty is a common procedure carried out in our institute, at about thirty surgeries per month. Common surgical complications of hernia surgery are – seroma formation, superficial wound infection, recurrence and neuralgia. Rare but serious complication includes mesh infection and mesh migration. We present a case of mesh migration after Lichenstein tension free hernioplasty with incorporation into the wall of sigmoid colon, which has not been reported previously.

tomography scan of abdomen revealed circumferential wall thickening with luminal narrowing involving the sigmoid colon with anterior and posterior wall thickness measuring 13mm each and descending colon loaded with feces. Perilesional mesenteric thickening and fat stranding was noted (Fig 1). The Liver appeared normal in size, shape and showed few foci of calcification of right lobe of liver. Colonoscopy was done, but scope could not be passed beyond 10-15 cm from anal verge suggestive of stricture. Patient was posted for surgery. Intra-operatively, the sigmoid colon appeared dilated and a mass lesion was present which was adherent to adjacent parietal peritoneum and inferiorly to bladder (Fig 2). The Transverse and Descending colon were massively dilated. The Sigmoid mass was dissected and limited resection done. The Descending colon and the sigmoid colon distal to mass brought out as double barrel colostomy. On macroscopic

CASE REPORT

A case of 45 years old male presented in October 2008 with chief complaint of left inguino-scrotal swelling. Physical examination revealed left sided recurrent inguinal hernia . The patient was operated 8 years ago for bilateral heniorraphy with recurrence of swelling on left side within month of surgery. Patient was a chronic smoker also. Patient was operated for left sided hernioplasty. Intraoperatively sigmoid colon was the content which was reduced and meshplasty done using 15cm x 10cm size prolene mesh. Patient was discharged on fourth post op day. This patient again came to us in March 2010 (15 months after previous surgery) with complains of chronic constipation and left lower abdominal lump. Clinical examination revealed an abdominal mass in left iliac fossa. Routine blood investigations were normal. Ultrasonography of abdomen was suggestive of thickening of the walls of the descending colon and the sigmoid. The lumen appeared narrowed and showed increased mucosal echogenicity. The surrounding fat appeared in flamed. Computerized 1,2

Fig 2 — Mass in distal part of Sigmoid colon

examination of cut section no evidence of foreign material could be seen. Cut section of specimen (Fig 3) was sent for biopsy which suggested inorganic material with foreign body giant cells and haemosiderin loaded macrophages, which was highly suggestive of mesh migration and incorporation into sigmoid colon. Patient was discharged after 12 days with colostomy. He was posted for colostomy closure in June 2010 and was discharged on 7th post-operative day following the colostomy closer without any complication. DISCUSSION

Open hernia surgery has been main line of management for hernia since centuries .When done correctly it is associated with minimal complication . Rare but serious complication like mesh rejection and mesh migration do occur . Mesh may migrate due to many reasons. Primary migration may occur due to technical fault, where mesh is not secured properly it passes through the path of least resistance or secondary it may migrate due to external elements which will result into migration through anatomical planes . However this is a slow process and presentation usually occurs over a period of time . When reviewing the literature, we found some cases involving migrating mesh. Two had migrated to cause small bowel obstructions, two presented as scrotal masses needing resection, two cases of erosion into the colon after intraperitoneal migration, one case had mesh migration in bladder after laparoscopic hernia repair, one patient had small bowel volvulus due to mesh migration . No case of mesh migration and incorporation into sigmoid colon after open inguinal hernia repair has been so far reported. Such cases may present with simple complains like pain to complications like obstruction, mass, fistulas, perforations. There are several factors responsible for such an unusual complication, such as patient factor (family history, chronic smoking obesity, recurrent hernia) and to some extent the technical skill of the surgeon . In conclusion it should also be recognized that mesh complications, particularly migration, tend to occur years later 3,4

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Department of General Surgery, New Civil Hospital, Surat 395001 1 MS (Gen Surg), Additional Professor 2 MS (Gen Surg), Senior Resident 3 MBBS, 3rd year Resident 4MBBS, 2nd year Resident

Fig 1 — CT Plate Showing Sigmoid mass adherent to urinary Bladder 32

Fig 3 — Cut Section of sigmoid colon mass showing fibrous reaction due to mesh incorporation

after hernia surgery and should be considered in atypical patient presentations. REFRENCES

1 R McKay — Preperitoneal herniation and bowel obstruction post laparoscopic inguinal hernia repair: case report and review of the literature. Hernia 2008; 12: 535-7. Epub 2008. 2 Bringman S, Blomqvist P — Intestinal obstruction after inguinal and femoral hernia repair: a study of 33,275 operations during 1992-2000 in Sweden. Hernia 2005; 9: 178-83. Epub 2009. 3 Leber GE, Garb JL, Alexander AI, Reed WP — Long-term complications associated with prosthetic repair of incisional hernias. Arch Surg 1998; 133: 378-82. 4 Lange B, Lange C, Markus PM, Becker H — Mesh penetration of sigmoid colon following a Transabdominal preperitoneal hernia repair. Surg Endosc 2003; 17: 157. Epub 2002. 5 Jeans S, Williams GL, Stephenson BM — Migration after Open Mesh Plug Inguinal Hernioplasty: a Review of the Literature. Am Surg 2007; 73: 207-9. 6 P Nordin, P Bartelmess, C Jansson, C Svensson, G Edlund — Randomized trial of Lichtenstein versus Shouldice hernia repair in general surgical practice. British Journal of Surgery 2002; 89: 45-9. 7 Goswami R, Babor M, Ojo A — Mesh erosion into caecum following laproscopic repair of inguinal hernia (TAPP): a case report and literature review. J Laproendosc Surg TechA 2007; 17: 669-72. 8 Ferrone R, Scarone PC, Natalini G — Late complication of open inguinal hernia repair: small bowel obstruction caused by intraperitoneal mesh migration. Hernia 2003; 7: 161-2. Epub 2003. 9 Ojo P, Abenthroth A, Fielder P, Yavorek G — Migrating mesh mimicking malignancy. Am Surg 2006; 73: 1210-1. 10 Liang X, Cai XJ, Yu H, Wang YF — Strangulated bowel obstruction resulting from mesh plug migration after open inguinal hernioplasty: case report. Chin Med J (Engl) 2008; 121: 183-4. 11 Stout CL, Foret A, Christie DB, Mullis E — Small Bowel Volvulus Caused by Migrating Mesh Plug. Am Surg 2007; 73: 796-7. 12 EC Nelson, TJ Vidovszky — Composite mesh migration into the sigmoid colon following ventral hernia repair. Hernia 2011; 15: 101-3.


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Case Report

the diagnostic therapy should be surgical, a laparoscopic approach is not always advised . Sonography usually shows a cystic encapsulated lesion with liquid content adjacent to cecum. CT/NMR scan shows a low density, encapsulated, thin-walled mass that does not contain contrast medium and communicates directly with the cecum. Other solid or cystic abdominal and peritoneal tumors could also be visualised by these methods. Barium enema could point out a failure of the appendix to fill with contrast medium and signs of the extra luminal compression in the ileocecal region . The "sign of volcano" is a pathognomonic colonoscopy finding . Classical surgical approach is the best therapy option with intraoperative abdominal cavity exploration. Appendectomy is advised for focal or diffuse mucosal hyperplasia and cystadenoma when the appendiceal base is intact. Cecal resection is performed for cystadenoma with a large base and right colectomy is recommended for cystadenocarcinoma. Other surgical procedures depend upon the existence of associated tumors. In cases of disseminated pseudomyxoma peritonei, ultrasonic surgical aspirator can be used . Laparoscopic approach to cystadenoma of the appendix is safe if surgery can be performed without grasping the lesion and if the specimen is removed through the abdominal wall using a bag . To conclude, accurate preoperative diagnosis and intraoperative exploration of the whole abdomen can improve the prognosis of patients with appendiceal mucocele. 5

Giant mucinous cystadenoma of appendix presenting as lump right iliac fossa : a rare presentation S S Rathore1, Mohan Lal2, Anil Kumar3

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Mucinous cystadenoma of appendix is rare condition and represents one of the three entities with common name mucocele of appendix. Mucocele is found in 0.3% of all appendicectomy specimens. We are presenting a case of Giant mucinous cystadenoma of appendix as a tense, cystic, mobile lump in right iliac fossa. The patient underwent laprotomy with appendicectomy. [J Indian Med Assoc 2017; 115: 34-5]

Key words : Appendix, mucocele, mucinous Cystadenoma.

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appendix: imaging fi ndings. AJR Am J Roentgenol 1992; 159: 69-72 Isaacs KL, Warshauer DM — Mucocele of the appendix: computed tomographic, endoscopic, and pathologic correlation. Am J Gastroenterol 1992; 87: 787-9. Keating JP, Frizelle FA — Use of ultrasonic surgical aspirator in operative cytoreduction of pseudomyxoma peritonei. Dis Colon Rectum 2000; 43: 559-60. Zagrodnik DF 2nd, Rose DM — Mucinous cystadenoma of the appendix: diagnosis, surgical management, and followup. Curr Surg 2003; 60: 341-3. Navarra G, Asopa V, Basaglia E, Jones M, Jiao LR, Habib NA — Mucous cystadenoma of the appendix: is it safe to remove it by a laparoscopic approach? Surg Endosc 2003; 17: 833-4.

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45 years old housewife presented to us with dull aching pain in right iliac fossa for 6 month, vomiting for 15 days, and constipation for 10 days. Examination — She was an average built lady. Her pulse, respiration and temperature were normal. Liver and spleen could not be palpated. There was a mobile lump in the right iliac fossa, 10x5 cm in size, mobile from side to side, firm in consistency. Investigations — Routine investigations including Hb, TLC, RFT, LFT, were within normal limits. Xray FPA was normal. Ultrasonography was suggestive of mass in right iliac fossa? intussusception. Management — On laprotomy there was a tense mucocele of appendix filled with gelatinous material, in right paracolic gutter, approx 10x5x5 cm size (Fig 1 &2). One soft lymph node in mesoappendix was present. Rest of abdomen was grossly normal. Appedicectomy and lymph node excision was done. Histopathology — Histopathology showed mucocele of the appendix caused by mucinous Cystadenoma and lymph node showing chronic non specific lymphadenitis.

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REFERENCES

Fig.1 — Intraoperative giant mucocele of appendix with intact base

DISSCUSSION Mucinous cystadenoma of the appendix is a rare condition and represents one of the three entities with the common name mucocele of the appendix. Mucocele of the appendix is a descriptive term for an appendix distended by mucus, secondary to mucinous cystadenoma (63%), mucosal hyperplasia (25%), mucinous cystadenocarcinoma (11%) and retention cyst1. Overall, appendiceal mucoceles make up about 0.3% of appendix specimens2. Clinical symptomatology of these patients is not specific. Abdominal pain is present in 64% of the patients and palpable ileo-cecal mass in 50% of them. Disease course is asymptomatic in 25% of the patients even when they have large tumors. Urinary infection and haematuria are often associated (20%)3.

1 Higa E, Rosai J, Pizzimbono CA, Wise L — Mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma of the appendix. A re-evaluation of appendiceal "mucocele". Cancer 1973; 32: 1525-41. 2 Woodruff R, McDonald JR — Benign and malignant cystic tumors of the appendix. Surg Gynecol Obstet 1940; 71: 7505. 3 Minni F, Petrella M, Morganti A, Santini D, Marrano D — Giant mucocele of the appendix: report of a case. Dis Colon Rectum 2001; 44: 1034-6. 4 Jones CD, Eller DJ, Coates TL — Mucinous cystadenoma of the appendix causing intussusception in an adult. Am J Gastroenterol 1997; 92: 898-9. 5 Gonzales Moreno S, Shmookler BM, Sugarbaker PH — Appendiceal mucocele. Contraindication to laparoscopic appendectomy. Surg Endosc 1998; 12: 1177-9. 6 Madwed D, Mindelzun R, Jeffrey RB Jr. Mucocele of the

Guest House of IMA at Kolkata One Deluxe Single Bedded Room (AC) Rs. 800.00 per day One Deluxe Double Bedded Room (AC) Rs. 700.00 per bed per day Three Triple Bedded Room (AC) Rs. 600.00 per bed per day Two Four Bedded Room (AC) Rs. 600.00 per bed per day One Double Bedded Room (Non-AC) Rs. 400.00 per bed per day Fig.2 — Mucocele of appendix- Specimen

Contact : Intestinal obstruction caused by intussusception and intestinal bleeding are rare complications . Although a proper preoperative diagnosis is recommended, fine needle biopsy should not be performed because of the risk of pseudomyxoma dissemination. For the same reason, though

Department of Surgery, Dr S N Medical College, Jodhpur 342001 1 MS (Gen Surgery), Associate Professor 2 MS (Gen Surgery), Senior Resident 3 MS (Gen Surgery), Assistant Professor

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Book Review "Practical Use of Biostatistics" by Prof Abhiram Behera, 1st Edition 2016, Published by Paras Medical Publishers, 5-1475, 1st floor, Putlibowli, Hyderabad 500095, India, 21.5 cm x 14 cm, pp 1-350. I have great pleasure in writing a review on “Practical Use of Biostatistics”. This is in-fact a long felt need for the medical graduates and post-graduates pursuing a carrier on research in medicine and allied subjects. Considering such a lucid elaboration on the subject every medical student will be able to grasp the subject. It will help to carry out epidemiological survey which is very much essential for health-planners. Students and researchers will be able to carry-out data analysis on different research projects in relation to thesis and dissertation that are an essential part of any post-graduate degree. The book has a total thirteen chapters which includes (1) Introduction to statistics, (2) Descriptive statistics, (3) Sampling technique, (4) Probability, (5) Correlation and regression, (6) Test of significance, (7) Non-parametric test, (8) Analysis of variance, (9) Introduction to Multivariable, (10) Demography and vital statistics, (11) Computer in Medicine. The last two chapters are of immense value and consist of Statistical table and Multiple Choice Questions.

While going through the chapter of Demography and vital statistics I was so excited that all post-graduate students under our department of General Medicine were advised to read about demographic cycle, population pyramid in India, census and its importance, basic indices of vital events and measures of morbidity. Similarly application of computers in medicine is a must for every student. Medical planning and decision making implications requires computer assisted diagnosis and research. In fact author has rightly pointed out that Integrated Hospital Management System is only possible through proper usage of computers. Since the author is very sincere in presenting such an apparently complex subject, he deserves heartiest congratulations and I wish every success to Mr Abhiram Behera BA(Stat), MA(Stat), LLB, MPS (IIPS) as an author. The binding and presentation by Paras Medical Publisher, Hyderabad-New Delhi is also praiseworthy. Needless to say the book is a must for every college library and persons maintaining a personal library. Past Hony Editor, JIMA Prof Anup Kumar Bhattacharya Kolkata

OBITUARY

Dr Ashit Baran Choudhury Dr Ashit Baran Choudhury was born on 16th October, 1952 in Dhubri (Assam). Completed his schooling in Tuensang, where his father was deputed as a representative of Assam Government in NEFA (North East Frontier Agency). Due to love for Nagas, Dr Choudhury’s father close to stay back in Nagaland when he was given the option to rejoin this mother institution. Dr Choudhury proved his father’s decision right when he became the first student to passed 1st Division from Government High School, Tuensang under Assam Board in the year 1968. After passing out from GME in 1977, Dr Choudhury joined Civil Hospital, Dimapur and worked there for 3 years (1977 to 1980) followed by a brief stint at Ramakrishna Mission Hospital, Dimapur. He started his private practice in 1980 in a small clinic attached to a pharmacy near Railway Gate, Dimapur. The hordes of patients, who turned up from far and wide, were a proof of his clinical acumen and humane nature. He married in 1985 and couple was blessed with a daughter in the following year. As a husband and father, he ensured that both his wife and daughter were empowered and financially independent. Throughout his 40 years of clinical practice, he gave selfless service to the people of Nagaland. Other than treating patients in charity and giving free medications, he was also actively involved in relief works in remote villages, providing financial help to the needy and pioneering the set-up of medical organizations in Nagaland. He passed away on 23rd February, 2017, May his soul rest in eternal peace.

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