October 2016 Vol. 34, No. 4 Vol. 34, No. 4, October 2016 Official Journal of the Bangladesh College of Physicians and Surgeons BCPS Bhaban, 67 Shaheed Tajuddin Ahmed Sarani Mohakhali, Dhaka-1212, Bangladesh

EDITORIAL BOARD ADVISORY BOARD The Journal of Bangladesh College Professor Md. Sanawar Hossain of Physicians and Surgeons is a Chairman Professor Kanak Kanti Barua Dr. Quazi Tarikul Islam Professor Md. Ruhul Amin peer reviewed Journal. It is Professor A.B.M. Muksudul Alam published four times a year, Professor T.I.M. Abdullah-Al-Faruq Editor-In-Chief (January, April, July and October). Dr. Khan Abul Kalam Azad Professor Shahana Akhter Rahman Professor Md. Abdul Jalil Chowdhury It accepts original articles, review Editors Professor Md. Azizul Kahhar articles, and case reports. Professor Abdul Kader Khan Dr. Zafar Ahmed Latif Professor Sayeba Akhter Complimentary copies of the Dr. A. N. M. Zia-ur-Rahman Professor Md. Abul Kashem Khandaker journal are sent to libraries of all Dr. Emran Bin Yunus Professor Mohammod Shahidullah medical and other relevant Dr. Parveen Fatima Professor Quazi Deen Mohammad Dr. U. H. Shahera Khatun Professor Kohinoor Begum academic institutions in the Dr. Syed Atiqul Haq Professor Quazi Tarikul Islam country and selected institutions Professor Choudhury Ali Kawser Dr. Fakhruddin Mohammad Siddiqui abroad. Dr. Syeda Afroza Professor Iffat Ara Dr. Md. Ridwanur Rahman Professor Nazmun Nahar While every effort is always made Professor Major Gen. (Retd.) Md. Ali Akbar Dr. Nooruddin Ahmed Professor Shamsuddin Ahmed by the Editorial Board and the Dr. Khwaja Nazim Uddin members of the Journal Committee Dr. Md. Abdul Hamid Editorial Staff to avoid inaccurate or misleading Dr. A.H.M. Rowshon Afsana Huq Dr. Tapan Kumar Saha Mohammed Ibrahim information appearing in the Dr. A.B.M. Bayezid Hossain Journal of Bangladesh College Dr. Md. Titu Miah PUBLISHED BY of Physicians and Surgeons, Dr. Tripti Rani Das Dr. Khan Abul Kalam Azad Dr. Dipi Barua information within the individual on behalf of the Bangladesh College Dr. Rubina Yasmin article are the responsibility of its of Physicians and Surgeons Dr. Mohammad Robed Amin author(s). The Journal of Bangladesh Dr. S.M. Anwar Sadat PRINTED AT College of Physicians and Surgeons, Dr. (Col) Md. Abdur Rab Asian Colour Printing its Editorial Board and Journal Dr. Shariff Asfia Rahman 130 DIT Extension Road Committee accept no liability Dr. S.M. Quamrul Akther Fakirerpool, Dhaka-1000 Dr. Aparna Das whatsoever for the consequences Dr. Syed Ghulam Mogni Mowla ANNUAL SUBSCRIPTION of any such inaccurate and misleading Dr. Tanveer Ahmed Tk. 400/- for local and US$ 40 for information, opinion or statement. overseas subscribers

ADDRESS OF CORRESPONDENCE Editor-in-Chief, Journal of Bangladesh College of Physicians and Surgeons, BCPS Bhaban, 67, Shaheed Tajuddin Ahmed Sarani Mohakhali, Dhaka-1212, Tel : 8825005-6, 8856616, 9884189, 9884194, 9891865 Ext. 124, Fax : 880-2-8828928, E-mail : Editor’s e-mail: [email protected] Journal of Bangladesh College of Physicians and Surgeons (JBCPS)

INFORMATION FOR AUTHORS

MANUSCRIPT PREPARATION AND SUBMISSION A manuscript number will be mailed to the corresponding Guide to Authors author within two working days. The Journal of Bangladesh College of Physician and The cover letter should include the corresponding Surgeons, provides rapid publication (quarterly author’s full address and telephone/fax numbers and publication) of articles in all areas of the subject. The Journal should be in an e-mail message sent to the editor, with welcomes the submission of manuscripts that meet the the file, whose name should begin with the first author’s general criteria of significance and scientific excellence. surname, as an attachment. Papers must be submitted with the understanding that The Journal of Bangladesh College of Physicians and they have not been published elsewhere (except in the Surgeons will only accept manuscripts submitted as e- form of an abstract or as part of a published lecture, review, mail attachments or triplicate Hard copy with a soft copy or thesis) and are not currently under consideration by Article Types another journal published by INTERNATIONAL FIve types of manuscripts may be submitted: RESEARCH JOURNALS or any other publisher. Editorials: It will be preferably written invited only and The submitting (Corresponding) author is responsible usually covers a single topic of contemporary interest. for ensuring that the article’s publication has been signed approved by all the other coauthors. 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The following separate page : information provides guidance in preparing manuscripts o Title page o Summary/abstract for this journal. o Text Conditions for submission of manuscript: o Acknowledgement • All manuscripts are subject to peer-review. o References o Tables and legends. • Manuscripts are received with the explicit understanding that they are not under simultaneous Pages should be numbered consecutively at the upper consideration by any other publication. right hand corner of each page beginning with the title page • Submission of a manuscript for publication implies the transfer of the copyright from the author to the I. A. 1. a. General Principles publisher upon acceptance. 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References to “correlations,” and “sample.” Where scientifically papers accepted but not yet published should be appropriate, analyses of the data by such variables designated as “in press” or “forthcoming”; authors as age and sex should be included. should obtain written permission to cite such papers I. A. 8. 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For scientific articles, obtain with other relevant studies, state the limitations of written permission and confirmation of accuracy from the study, and explore the implications of the findings the source of a personal communication. Some but for future research and for clinical practice. not all journals check the accuracy of all reference citations; thus, citation errors sometimes appear in • Link the conclusions with the goals of the study the published version of articles. To minimize such but avoid unqualified statements and conclusions errors, references should be verified using either an not adequately supported by the data. In particular, electronic bibliographic source, such as PubMed or avoid making statements on economic benefits and print copies from original sources. costs unless the manuscript includes the appropriate economic data and analyses. Avoid claiming priority • Authors are responsible for checking that none of the references cite retracted articles except in the or alluding to work that has not been completed. context of referring to the retraction. For articles State new hypotheses when warranted, but label published in journals indexed in MEDLINE, the them clearly as such. ICMJE considers PubMed the authoritative source I. A. 9. References for information about retractions.

I. A. 9. a. General Considerations Related to I. A. 9. b. Reference Style and Format References • References should be numbered consecutively in • Although references to review articles can be an the order in which they are first mentioned in the efficient way to guide readers to a body of literature, text. review articles do not always reflect original work • Identify references in text, tables, and legends by accurately. Readers should therefore be provided Arabic numerals in superscript. with direct references to original research sources • References cited only in tables or figure legends whenever possible. should be numbered in accordance with the • On the other hand, extensive lists of references to sequence established by the first identification in original work of a topic can use excessive space on the text of the particular table or figure. the printed page. Small numbers of references to key original papers often serve as well as more exhaustive I. A. 10. 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Illustrations (Figures) • Measurements of length, height, weight, and volume • Figures should be either professionally drawn and should be reported in metric units (meter, kilogram, photographed, or submitted as photographic-quality or liter) or their decimal multiples. digital prints. In addition to requiring a version of • Authors should report laboratory information in the figures suitable for printing, both local and International System of Units (SI). . (for example, JPEG / GIF) • Drug concentrations may be reported in either SI or • Authors should review the images of such files on a mass units, but the alternative should be provided computer screen before submitting them to be sure in parentheses where appropriate. they meet their own quality standards. For x-ray films, scans, and other diagnostic images, as well as I. A. 14. 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Figures should be numbered send the required number of copies of the manuscript consecutively according to the order in which they and figures; they are all needed for peer review and have been cited in the text. editing, and the editorial office staff cannot be • If a figure has been published previously, expected to make the required copies. acknowledge the original source and submit written • Manuscripts must be accompanied by a cover letter, permission from the copyright holder to reproduce conflicts of interest form, authorship and declaration, the figure. Permission is required irrespective of proforma of which is available in JBCPS web site. Editing and peer review: All submitted manuscripts are D Title page contains all the desired information subject to scrutiny by the Editor in-chief or any member (vide supra) of the Editorial Board. 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Proof of Vancouver system. accepted manuscript may be sent to the authors, and • Language and grammar should be corrected and returned to the editorial office D Uniformity in the language within one week. No addition to the manuscript at this D Abbreviations spelt out in full for the first time stage will be accepted. All accepted manuscripts are D Numerals from 1 to 10 spelt out edited according to the Journal’s style. D Numerals at the beginning of the sentence spelt Submission Preparation Checklist out As part of the submission process, authors are required • Tables and figures to check off their submission’s compliance with all of D No repetition of data in tables/graphs and in the following items, and submissions may be returned text to authors that do not adhere to these guidelines. D Actual numbers from which graphs drawn, Check Lists provided Final checklists before you submit your revised article D Figures necessary and of good quality (colour) for the possible publication in the Journal of Bangladesh D Table and figure numbers in Arabic letters (not College of Physicians and Surgeons: Roman) 1. Forwarding/Cover letter and declaration form D Labels pasted on back of the photographs (no 2. Authorship and conflicts of interest form names written) D Figure legends provided (not more than 40 3. 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D Mention conflict of interest if any • Abstract • Discussion D Do not use subheadings in the abstract D Avoid unnecessary explanation of someone D Give full title of the manuscript in the Abstract else work unless it is very relevant to the study page D Provide and discuss with the literatures to D Not more than 200 words for case reports and support the study 250 words for original articles D Mention about limitation of your study D Structured abstract (Including introduction, methods, results and discussion, conclusion) • Conclusion provided for an original article and D Give your conclusion (Introduction, results and discussion , D Any recommendation conclusion) for case reports. D Key words provided – arrange them in • Acknowledgement alphabetical order (three – five ) D Acknowledge any person or institute who have helped for the study • Introduction D Word limit 150 -200 words • Reference D Pertinent information only D Abide by the Vancouver style • Material and Methods D Use reference at the end of the sentence after D Study Design the full stop with superscript D Duration and place of study • Legends D Ethical approval D Table D Patient consent D Figures D Statistical analysis and software used. Journal of Bangladesh College of Physicians and • Result Surgeons ISSN: 1015-0870 D Clearly present the data Indexed on HINARI, EMSCO, DOAJ, Index Copernicus, D Avoid data redundancy Ulrichs Web, Google Scholar, CrossRef, ProQuest, D Use table information at the end of the Scientific Common. sentence before full stop between the small bracket BanglaJOL is supported by IN JOURNAL OF BANGLADESH COLLEGE OF PHYSICIANS AND SURGEONS Vol. 34, No. 4, Page 182-242 October 2016 CONTENTS

EDITORIAL Hurdles in Management of Extra pulmonary Tuberculosis 182 HAMN Ahasan, CS Bala,

ORIGINAL ARTICLES Obstetrical Outcome of Grand Multipara 184 J Khatun Association of Bacterial Vaginosis with Preterm Delivery 188 TR Das, K Fatema, S Chowdhury, F Noor, R Ara, B Chakma, M Parveen, MJB Ali Incidence of Gallbladder Carcinoma in Thick Walled Gallbladder in Comparison with that 193 of Normal Thickness – A Study of 300 Cases MM Hasan, SZ Laila, MH Mamun Hepatitis B Virus, Hepatitis C Virus Markers and Serum Alanine Amino-Transferase (ALT) 199 Levels in a Young Adult Population of Sylhet District I Perveen, M Saha, KK Dhar, MS Islam

REVIEW ARTICLE Management of Sepsis: Recent Advancement 206 MI Patwary, MZJ Bari, IT Isha

CASE REPORTS Transient Acute Myeloid Leukemia in a Newborn with Down’s Syndrome 213 ZSM Haque, N Jahan, BK Raha, M Hasan, M Begum, AWS Rob, S Yasmin, SKA Hasnat, T Farhana Laparoscopic Management of Tubal Ectopic of Heterotopic Pregnancy 218 E Saha, J Das, M Moniruzzaman, CR Bacher Marshall Syndrome or PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenopathy) Syndrome 222 MUH Begum Postoperative Transient Intractable Hyperacusis in Posterior Cingulate Gyrus Lesion 225 Causing Partial Complex Seizure FH Chowdhury, MR Haque

IMAGES IN MEDICAL PRACTICE A Patient with Recurrent Hypokalaemia 228 CS Bala, I Reza, MABI Momen, HAMN Ahasan

LETTER TO THE EDITOR 231

COLLEGE NEWS 233

FROM THE DESK OF THE EDITOR IN CHIEF 243 EDITORIAL Hurdles in Management of Extra pulmonary Tuberculosis

Tuberculosis is an ancient disease. It was thought that involvement are also common and may cause the mystery of tuberculosis had been solved to a great catastrophic complication. Tuberculosis of chronic extent with the discovery of the Mycobacterium and ulcers and sinuses anywhere in the body specially of anti-TB drugs. But the fact is that still it is a threatening perianal regions, anal tags are not uncommon. Other public health concern for the 21st century. In 2014, 9.6 less common sites includes splenic tuberculosis, million people were diagnosed as new cases of genitourinary tuberculosis, breast, scars including that tuberculosis and 380,000 patients died of tuberculosis.1 of laparoscopic ports, etc. Many mysteries of tuberculosis are being unfolded day Atypical presentations of extra pulmonary tuberculosis by day. Pulmonary tuberculosis has been in the focus are elusive and is the main cause of diagnostic difficulty. of attention for last three centuries because of its Atypical organ and tissue involvement is another cause overwhelming symptoms, complications, transmissibility of delay in diagnosis. Constitutional symptoms and and mortality. Tuberculosis can involve almost every pyrexia of unknown origin (PUO) and this may be the organ of the body. Extra pulmonary Tuberculosis (EPTB) only diagnostic clue in many cases. Furthermore EPTB occurs alone or along with a pulmonary tuberculosis or has diverse manifestations which may mimic other patients with disseminated tuberculosis. EPTB diseases making it more diagnostically challenging, more constitutes about 20 per cent of all cases of tuberculosis frequently associated with diagnostic delay, The in immunocompetent patients. Disease patterns have diagnosis of extra pulmonary tuberculosis needs a high changed, with a higher incidence of disseminated and index of suspicion from varied clinical presentations. extra pulmonary disease. Physicians should obtain a thorough history regarding The risk of extra pulmonary tuberculosis increases with common immunosuppressive conditions focusing on advancing immunosuppression.2 Extra pulmonary risk behaviors for human immunodeficiency virus (HIV) involvement can be seen in more than 50 percent of infection. 7 3,4 patients with concurrent AIDS and tuberculosis. There is Difficulty in Diagnosis in many aspects Extra-pulmonary TB (EPTB) makes up over 40% cases in .Definitive diagnosis of tuberculosis involves Australia and more than half when EPTB definitions demonstration of M. tuberculosis by microbiological, include concurrent PTB co-infection. This proportion has cytopathological or histopathological methods. Tissue/ been reportedly increasing in Australia and many low relevant body fluids must be obtained for diagnostic prevalence countries.5 In Turkey the most commonly seen testing for histopathological, cytopathological and two types of EPTB were genitourinary TB (27.2%) and micrbiological diagnosis. It’s a challenge to find meningeal TB (19.4%).6 So it is evident that there is a representative tissue/body fluid. Samples obtained from wide variation of prevalence of extra pulmonary TB from relatively inaccessible sites are paucibacillary, region to region and society to society. decreasing the sensitivity of diagnostic tests. Since the The reason for the increase in EPTB remains unclear. conventional smear microscopy has a low sensitivity Increased prevalence of conditions that results in with a range of 0%–40%, negative results cannot exclude immunosuppression like HIV infection, diabetes, increased the presence of TB. The reported yields of mycobacterial aging population, substance abuse and use of culture vary from 30% up to 80%. It usually takes 2–8 immunosuppresive agents like chemotheraputic and weeks to receive the results, which is too slow to help biological DMARDS and prolong use of corticosteroids treatment decisions. Sometimes histopathology reports may contribute to this. If we consider delay and difficulty are inconclusive leaving the physicians in a dilemma. It of diagnostic difficulty of EPTB and missed cases, it is remains a daunting task to differentiate tuberculosis likely that actual proportion of EPTB will be much higher with other granulomatous diseases with these sorts of than estimated. reports. In that case clinicians have to rely on the supporting clinical, radiological and endoscopic Lymph nodes are the most common site of involvement. evidences. A negative smear for acid-fast bacillus, a Neurological, pleural, pericardial, abdominal and Skeletal lack of granulomas on histopathology, and failure to Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 culture Mycobacterium tuberculosis do not exclude the Referrence: diagnosis. It is the time for using PCR, as it can detect 1. World TB report 2015, 20th edition, World Health as few as 10 mycobacteria and Rapid NAAT based Organization tests like Gene Xpert MTB/RIF. Gene Xpert was highly 2. Jones BE, Young SM, Antoniskis D, Davidson PT, Kramer sensitive for TB detection in lymph node samples and F, Barnes PF. Relationship of the manifestations of moderately sensitive for the detection of TB meningitis tuberculosis to CD4 cell counts in patients with human (80.5% and 83.1%, respectively), lower sensitivity was immunodeficiency virus infection. Am Rev Respir Dis shown (46.4%) for testing pleural fluid. Serological tests 1993;148:1292-7 are available but mostly confined for research.8 3. Rieder HL, Snider DE Jr, Cauthen GM. Extrapulmonary The Management of EPTB remains a very difficult for tuberculosis in the United States. Am Rev Respir Dis the physicians even at this day of nanotechnology. 1990;141:347-51 There is no consensus regarding the management. 4. Chaisson RE, Schecter GF, Theuer CP, Rutherford GW, Large-scale studies are not available on the treatment Echenberg DF, Hopewell PC. Tuberculosis in patients with of extra pulmonary TB especially in relation to the the acquired immunodeficiency syndrome. Clinical duration of treatment and use of corticosteroids. features, response to therapy, and survival. Am Rev Respir Modification and extended duration are necessary for Dis 1987;136:570-4 extra pulmonary tuberculosis. A nine month regimen is 5. Diagnosis and Management of Extra-Pulmonary recommended, apart from meningitis, other central Tuberculosis in a Low-Prevalence Country: A Four Year nervous system (CNS) involvement, miliary disease, and Retrospective Study in an Australian Tertiary Infectious bone and joint TB, for which a one-year regimen is Diseases Unit. PLoS ONE 11(3): e0149372. doi:10.1371/ recommended instead. Some authorities may further journal.pone.0149372) prolong treatment for CNS tuberculoma and stage III meningitis. On pharmacokinetic consideration in relation 6. (demographic and microbial characteristics of extrapulmonary tuberculosis cases diagnosed in Malatya, to cerebrospinal fluid penetration, there may also be a Turkey, 2001-2007 Selami Gunal1, Zhenhua Yang2, Mansi role of giving pyrazinamide for more than 3 months. Agarwal2, Mehmet Koroglu3, Zeynep Kazgan Arýcý4, Duration of Anti Tb regimen are 6(2+4) months in most Riza Durmaz1* Gunal et al. BMC Public Health 2011, guideline, 12(2+10) months recommended by American 11:154) Thoracic Society, Infectious disease society of America, CDC etc.9, We practice extending the regimen for 2 years 7. Golden MP, Vikram HR. Extrapulmonary tuberculosis: an in case of Tubercular meningitis and Skeletal TB. overview. Am Fam Physician 2005;72:1761-8. Pyrazinamide must be present in the regimens. 8. Arzu N. Zeka, Sezai Tasbakan, Cengiz Cavusoglu. Evaluation of the GeneXpert MTB/RIF Assay for Rapid (J Bangladesh Coll Phys Surg 2016; 34: 182-183) Diagnosis of Tuberculosis and Detection of Rifampin Resistance in Pulmonary and Extrapulmonary Specimens Professor HAM Nazmul Ahasan J. Clin. Microbiol. December 2011 vol. 49 no. 12 4138- Professor of Medicine, Popular Medical College 4141 and 9. Wang JY, Lee MC, Shu CC, Lee CH, Lee LN, Chao Dr. Chandra Shekhar Bala KM, Chang FY. Optimal duration of anti-TB treatment Junior Consultant (Medicine) in patients with diabetes: nine or six months? Chest. 2015 National Institute of Neurosciences & Hospital Feb;147(2):520-8. doi: 10.1378/chest.14-0918.

183 ORIGINAL ARTICLES Obstetrical Outcome of Grand Multipara J KHATUN

Summary: Result: It was found that incidence of grand multipara was Intruduction: Pregnancy in grand multipara has been 6.60%. Majority of the patient were between 31–35 years old considered as high risk because there are higher chance of (43%). 66% patients never had anternal checkup, Caesarean complication during pregnancy, labour and puerperium. section was high about 47%. Complications during labour Objective: To evaluate various maternal and fetal were also high. It was about 51.67%. Maternal morbidity complication associated with a grand multipara during was about 16%. Perinatal mortality was about 11%. pregnancy, delivery and puerperium. Conclusion: This study showed that grand multipara is a Methods: This prospective study was carried out from 1st major risk for obstetrical outcome and needs strick supervision January 2008 to 31st December 2008 in Obstetrics & and good antenatal, intranatal and postnatal care. Gynecology Department of Sylhet MAG Osmani Medical Key words : Grand multipara, Fetal outcome, Maternal College & Hospital, Sylhet. 300 grand multipara pregnant outcome, Risk fector. patients were selected those who got admitted in Department of Obstetrics & Gynecology, SOMCH during that period. (J Bangladesh Coll Phys Surg 2016; 34: 184-187)

Introduction: as a high risk labour because of complications, like Parity refers to the number of previous pregnancies of uterine atony,postpartum hemorrhage, obstructed more than 28 weeks and , grand multipara is the condition labour,ruptured uterus and higher incidence of operative of giving birth following 5 or more previous delivery. Increase rate of operative delivery due to pregnancies.1 Grand multiparity is still high in abnormal position and big baby and maternal exhaustion Bangladesh among women of low socio – economic The main purpose of this study was to evaluate the class and in those getting married at a young age. Other maternal and fetal outcome of grand multipara patient . factors contributing to its prevalence are illiteracy and Materials and methods: religious beliefs. The definition of grand multipara varies This study was a hospital based Observational cross 1-5 5 from study to study . Toohey, et al have used the sectional study, carried out in IPD (inpatient department) definition of parity greater or equal to 5. The International of Obstetrics and Gynecology of Sylhet M.A.G Osmani Federation of Gynaecology and Obstetrics in 1993 Medical College and Hospital (SOMCH), Sylhet in th defined grand multipara as delivery of 5 or more infants. between 1st January 2008 to 31st December 2008. Total The incidence of grand multipara is very low in 300 grand multipara pregnant patients were selected economically developed countries. It occurs in some those who got admitted in department of Obstetrics & population or community mainly in those where Gynecology, SOMCH Data was collected by using a contraception is not accepted because of specific preformed questionnaire and check list. Cases were religious or cultural beliefs.6 Grandmultipara is selected according to inclusion and exclusion criteria. associated with a long list of complication, which include, Relevant infromations (according to questionnaire) were preterm labour, anemia, pendulous abdomen, taken from patients. Data was processed manually and malpresentation, pre-eclampsia, placentaprevia and analyzed with the help of SPSS (Statistical package for abuptio placenta. Labour among grand multiparous social sciences) Version 16.0. patients is not without complications and is regarded Results: Address of Correspondence: Dr. Jamila Khatun, Associate In SOMCH total 300 grand multipara patients out of Professor, Department of Obstetrics and Gynecology, Sylhet 4539 obstretic patient were admitted from January 2008 M.A.G Osmani Medical College, Sylhet. to December 2008 giving the incidence of 6.6% and Received: 24 March 2014 Accepted: 26 May 2016 following results were found. Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Table-l Table-lV

Age distribution Mode of delivery

SL No Age in No. of patient percentage SL No Mode of No of patient Percentage years n-300 delivery n-300 1 16-20 0 0 % 1 Vaginal delivery 147 49% 2 21-25 0 0 % 2 LSCS 141 47% 3 26-30 96 32% 3 Forceps delivery 12 4% 4 31-35 129 43% Total 300 100% 5 36-40 60 20% 6 41-> 15 5% Table lV: Operative intervention in the form of caesarean Total 300 100% section was high (47%).

Table l: Highest number of (43%) grand multipara Table-V belonged to 31-35 years. Complications during delivery Table-ll SL No Complication no of patient percentage Antenatal Check up 1 Prolonged Labour 68 22.67% SL No ANC No, of patient percentage 2 Obstructed Labour 34 11.33% n-300 3 Retain placenta 30 10.00% 1 Regular 45 15% 4 PPH 23 7.63% 2 Irregular 57 19% 3 No 198 66% Total 155 51.63% Total 300 100% Table V: Major number of the patient suffered from Table ll: Majority of the patient (66%) had no ANC. Prolonged Labour (22.67%) and Obstructed Labour (11.33%), PPH (7.63%). Table- lll Table-VI Presence of risk factors during admission of patient Maternal morbidity following delivery SL No Risk factor No. of patient Percentage SL No Types of no of patient percentage 1 Anaemia 280 90% morbidity 2 Pre Eclampsia 55 17.33% 1 Hypertension 17 5.66% 3 Eclampsia 4 1.33% 2 Wound Infection 15 5.0% 4 Malpresentation 34 11.33% 3 Psychosis 12 4.0% 5 Oligohydramnios 2 0.66% 4 Retention of urine 4 1.33% 6 Polyhydramnios 7 2.33% 7 APH 10 3.33% Total 48 15.99% 8 DM 5 1.66% Table Vl: Grandmultipara suffered from different types Table lll: Major number of grandmultipara patient of morbidity such as Hypertension (5.66%), Wound suffered from anaemia (90%), PE (17.33%) Infection (5.0%), psychosis (4.0%) Retention of urine Malpresentation(11.33) APH(3.33%). (1.33%)

185 Obstetrical Outcome of Grand Multipara J Khatun

Table-Vll This findings agree with the findings done by Sibai et al11 while Vehskari et al9. Foetal Status In this study, more number of cases(47%) required SL No Condition of no of patient Percentage caesarean section. In contrast to the study done by Foetus n-300 Munium et al2, who found no significant difference in 1 Live birth 267 89% the prevalence rate of caesarean section or normal 2 Still birth 35 11% delivery. However, in other studies conducted by Evaldson13, Ozumba14 and Irvine15 increased caesarean Total 300 100% section rate was found among grand multipara which correlates with this study. In this present study it was Table Vll: showed that live birth was 89% and still birth observed that prolonged labour was 22.67%, this finding was11% co-relates with that of other studies.13-15 This study Discussion: had shown thad increased incidence of obstructed Grandmaultipara is well known risk factor for the labour (11.33%) in grandmultipara. Which was pregnant women with increased risk of maternal and consistence with other studies.13-15,17 In this study PPH fetal morbidity and mortality. There is increased was 7.63%. This agree with the study done in Nigeria.16 incidence of obstetrical and medical complications1. For In this study, live fetal outcome was 89%, and still birth cultural and religious reasons grandmaultipara is not 11%. This still birth in our study is higher compared to uncommon in our country. Lack of family planning study by Saadia, et al6. It could be related to the fact results in the ultimate increase in the number of that most of patients arrived late having an already grandmaultipara women. The present study findings intrauterine death or with hypoxic babies. were discussed and compared with previously published relevant studies. Conclusion: The frequency(6.60%) of grand multipara found in this Grandmultipara still had high risk pregnancy. In this study was comparable with other studies2-5. This study study grand maultipara was also associated with adverse found a higher number of these women in age group maternal and fetal outcomes. Most grand maultipara between 31-35 years (43%). This finding was consistent were of older age and poor socio-economic status. So with the study of Saadia et al6. However, a higher improvement in social class, health education, use of frequency of grand multiparity in the age group >35 contraception and good antenatal and intrapartum years has been reported by Munium et al2 and Karim et monitoring are needed. al7. While Samueloff et al8 reported the highest number of women in the age group between 30-35 years. In this Reference: study most of the patient (66%) did not receive any 1. Bai J, Wong FW, Bauman A, Mohsin M. Parity and pregnancy outcomes. Am J Obset Gynecol. 2002; 186: antenatal check up. Similar result was also found by 274-8 Karim et al7. This study showed anaemia was 90%. This 2. Munium S, Rahbar MH, Rizvi M, Mushtaq N. The effect was because there was not enough interval between of grand multiparity on pregnancy related complications: pregnancies for the women to replenish the iron stores. The Aga Khan University experience. J Pak Med Assoc. This finding was higher than reported by Munium et 2000; 50: 54-8. 2 6 7 al , Saadia et al and Karim et al . 3. Seidman DS, Armmon Y, Roll D, Stevensaon DK Gale R. Hypertensive disorder of pregnancy was 5.66%. This Grand multiparity: an obstetric or neonatal risk factor? Am J Obset Gynecol. 19988 ; 158: 1034-9 was explained by increased age of this group. The same finding were Vehaskari et al9, Maymon et al10 and Al- 4. Samueloff A, Mor-Yousef S, Seideman DS , Rabinowiz R, 11 Simn A, Schenker JG Grand Multipara- a nation wide Sibia et al . Antepartum haemorrhage was found in survey, Isr J Med Sci 1989;25 : 625-9 3.33% Azziz FA12 had reported ante partum haemorrhage 5. Toohey JS, Keegan KA Jr, Morgan MA, Francics J Task S, significantly increased in grandmultipara. In this current deVeciana M. The “dangerous multipara’’ fact or fiction? study it was observed that malpresentation was 11.33%. Am J Obstet Gynecol. 1995; 172:683-6

186 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

6. Fayed HM, Abid SF and Stervens B. Risk factors in extreme 11. AL-Sibai MH. Rahman MS Rahhman J. Obstetric problems grand multiparity, Int J Gynecol obstet 1993 41 17-22 in the grand multipara : a clinical study of 1330 cases. J Obstet Gynaaecol(Lahore) 1987 :8(2):135-8 6. Saadia Z, Farrukh R, Naheed F, Maternal outcome in grand multoparas. Ann King Edard Med Coll. 2002; 8:207-10 12. Azziz FA. Pregnancy and labour of grand mult iparous Sudances women. Int J Gnaecol obset. 1980 Sep- 7. Azziz Karim s, Memon AM, Qadir N. Grandmultiparity- Oct;18(2):144-6 A continuing problem in developing countries. Asia oceania 13. Evaldson GR. The grand multiparity in modern obstetrics. J Obset Gynaecol 1988;158:155-60 Gynecol Obstet Invest. 1990: 30:217-30 8. Samueloff A. Schimmel MS, Eidelman Al. Grand 14. Ozumba BC, lgwegbe AO. The challenge of multiparity. Is it a perinatal risk? Clin Perinatol. 1998;25: grandmaultiparity in Nigerian obstetrics practice. Int J 529-38 Gynaecol obstet. 1992;27:259-64 9. Vehaskari A, Lahtinen J,Terho J Hazards of grand 15. IrvineLM Otigbah C, Crawford and Satchell, Grand multiparity,: Ann Chir Gynaecol Fenn. 1968; 57(4): multiparity; an obstetric problemnin Great Britain in the 476-84 90s? J Obset Gynecol 1996; 16: 217 10. Maymon E, Ghezzi F, Shoham-Vardi I, Hersgkowitz R, 16. Ogedengbe OK,Ogunmokun AA Grandmultiparity in Franchi M, KatzM Mazor M. Peripartum complications Lagos, Nigeria. Niger Postgrad Med J.2003 Dec: 10 (4):216-9 in grand multiparous women: para 6-9 versus para > or =10. : Eur J Obstet Gynaecol Reprod Biol. 1988 17. Vedat- A, Hasan- B, Islam- A. Rupturre of uterus inlabour. Oct;81(1):21-5 1st J.M.Sci 1993-oct; 29[4]: 179-87.

187 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 Association of Bacterial Vaginosis with Preterm Delivery TR DASa, K FATEMAb, S CHOWDHURYc, F NOORd, R ARAe, B CHAKMAf, M PARVEENg, MJB ALIh

Summary: Results: Mean (±SD) age of BV negative and positive subjects Objective: To find out the effect of bacterial vaginosis on were 24.59+5.18 and 23.89+4.77 years respectively (statistically preterm delivery. Bacterial vaginosis (BV) is one of most the not significant). Although socioeconomic status, educational common presentation of women in their reproductive age status and gravida did not statistically show any significant group. Its prevalence is relatively high in the obstetric difference between two groups. Significantly high number of BV population which is mostly responsible for preterm delivery. positive women delivered prematurely (73%) compared to BV negative (25.4%) (P<0.001). Mean (±SD) gestational age also Methods: This study tried to find out effect of BV on preterm differed significantly 37.49+2.53 vs 35.24+2.33 weeks (P<0.001). delivery. The study included 100 pregnant women aged 15 to 35 years, between 28-36 weeks of gestation, with abnormal Conclusion: This study conclude that abnormal bacterial colonization is indicative of bacterial vaginosis that is vaginal discharge and clinically suspected BV. Obstetrics strongly associated with preterm delivery. outpatient department of BSMMU was selected for the study. The study population was divided into two groups (63 culture Key words: Bacterial vaginosis, Preterm delivery negative and 37 culture positive for BV). (J Bangladesh Coll Phys Surg 2016; 34: 188-192)

Introduction: Bacterial vaginosis remains as the most common cause Bacterial vaginosis (BV) is characterized by a shift in the of vaginal discharge in women of reproductive age and is vaginal flora from the normally predominant lactobacillus associated with increased susceptibility to human to dominate sialidase enzyme-producing mixed flora immunodeficiency virus (HIV) and sexually-transmitted including Gardnerella vaginalis Mobiluncus, infections (STI) and preterm delivery2. 1 Prevotella, Bacteroides and Mycoplasma species . Bacterial vaginosis was previously regarded as a harmless condition. But new evidence has demonstrated a. Prof. Dr. Tripti Rani Das, Professor, Department of association of bacterial vaginosis with several obstetric Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka and gynaecological conditions and disorders, including b. Dr. Kaniz Fatema, Assistant Prof. Department of Obstetrics spontaneous abortion, preterm labour, premature rupture and Gynaecology, Bangabandhu Sheikh Mujib Medical of membrane, placental infection, wound infection and University (BSMMU), Shahbagh, Dhaka. pelvic inflammatory disease (PID)3. c. Dr. Shiuly Chowdhury, Associate Professor, Department of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib At present, the diagnosis of bacterial vaginosis is Medical University (BSMMU), Shahbagh, Dhaka. generally made by applying the Amsel method, where d. Dr. Farah Noor, Consultant, Department of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib Medical University four criteria are taken into consideration: (a) presence (BSMMU), Shahbagh, Dhaka. of abnormal vaginal discharge, (b) elevated vaginal pH e. Dr. Rowson Ara, Medical Officer, Department of Obstetrics (>4.7), (c) positive amine odour, and,(d) presence of clue and Gynaecology Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka. cells on vaginal gram-smear. All are accepted as hallmark 4 f. Dr. Bidisha Chakma, Medical Officer, Department of of bacterial vaginosis . Though clinical diagnosis of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib bacterial vaginosis is widely used, only a single sign or Medical University (BSMMU), Shahbagh, Dhaka. clinical test has a poor sensitivity and specificity. g. Dr. Mehera Parveen, Medical Officer , Department of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib There is increased evidence that ascending infection Medical University (BSMMU), Shahbagh, Dhaka. from the lower genital tract is an important cause of h. Dr. Murshid Jahan Binte Ali, Medical Officer , Department preterm labour5,6,7,8. STI, such as syphilis, gonorrhoea, of Obstetrics and Gynaecology Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka. trichomoniasis and chlamydial infection have been Address of Correspondence: Prof. Dr. Tripti Rani Das, implicated in some but not all studies. More attention is Professor, Department of Obstetrics and Gynaecology, being given to bacterial vaginosis, a condition in which Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka. E-mail: … there is an overgrowth of anaerobic and other bacteria Received: 9 Nov. 2014 Accepted: 1 Sept. 2016 in the vagina with corresponding decrease Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 in the number of lactobacilli. In both, case-control and Swab sample from all cases were subjected to wet-film, prospective studies, bacterial vaginosis has been gram-stain, and amine test for diagnosis of bacterial associated with preterm deliveries9. vaginosis by applying Amsel clinical criteria4.

The present study was carried out to detect abnormal Laboratory procedure: bacterial colonization of the genital tract, indicative of Measurement of vaginal fluid: The pH level was bacterial vaginosis in pregnancy and assess its determined by placing litmus paper against the lateral association with adverse outcome of pregnancy such vaginal wall. The colour was then compared with the as preterm low-birth-weight babies. colours and corresponding pH value on a standard chart. Methods: Amine test or Whiff test: Amine odour was smelled by This prospective cross-sectional study was carried out placing the vaginal secretion on the glass slide by in the Department of Obstetrics and Gynaecology in adding 10% KOH to the sample. collaboration with Department of Microbiology and Wet-mount preparation: The swab sample was mixed Immunology, Bangabandhu Sheikh Mujib Medical with a drop of normal saline on a slide and a cover-slip University (BSMMU), Dhaka, during January 2005 to was placed over it. The slide was then examined under December 2006. light-microscope at X400 for observation of clue cells. The presence of Trichomonas vaginalis, Candida One hundred (100) pregnant women who fulfilled species, pus cells and epithelial cells were also noted. inclusion and exclusion criteria attending outpatient Department of Obstetrics and Gynaecology of BSMMU Gram-stain preparation: Methanol fixed dried smear Hospital were selected. Inclusion criteria were; age 15 were stained with Koploff’s modification of gram-stain to 35 years, between 28 to 36 weeks of gestation, with for detection of clue cells and evaluation of bacterial abnormal vaginal discharge, and clinically suspected of morphotype under light-microscope at X1000. bacterial vaginosis. Exclusion criteria were ruptured All relevant data for each individual study subjects were membrane, prior tocolysis, placenta praevia, cervical recorded on a predesigned data collection sheet and cerclage, presence of purulent cervical mucous plug on appropriate statistical analyses were done using speculum examination, history of vaginal douche on computer based software, Statistical Package for Social the day of examination and history of sexual intercourse Science (SPSS). within last 72 hours. Results: Women enrolled in the study were explained about the Table-I shows characteristics of the study population. nature and purpose of the study, and only those who Mean (±SD) age of BV negative and BV positive cases gave written/verbal consent were included in the study. were 24.59±5.18 (range 15-35) and 23.89±4.77 (range 15- The selected women were divided into two groups 33) years (statistically no significant difference). based on clinical Amsel criteria4: (a) culture negative Sociodemographic status of BV negative and positive (n=63) and (b) culture positive (n=37) for BV. cases showed no significant difference, and most of the Specimen collection: women of both the groups were from low and middle class families. Educational status of BV negative and A clean unlubricated speculum was placed in the vagina positive cases also showed no significant difference. and the vaginal pH was measured with pH strip. Sterile Gravidity was not significantly associated between BV cotton swabs were used to obtain materials from the negative and positive cases. In BV positive and negative posterior fornix for a vaginal smear. Vaginal swab samples groups, respectively, 29 (46%) and 20 (54.1%) were were collected from each patient. primiparous, and 34 (54%) and 17 (45.9%) were Vaginal swab sample: Swab collected from the posterior multiparous. Mean (±SD) gestational age at delivery fornix of vagina was rolled on two glass slides; the were 37.49±2.53 (range 32-41) and 35.24±2.33 (range 32- smears were air-dried and then fixed with methanol for 39) weeks in BV negative /and positive group, respectively (highly significant difference, P<0.001). gram-stain. This swab was also used to prepare wet- mount and then examined microscopically for clue cells, Table-II shows effect of BV on preterm delivery. Out of trichomonads, yeast, pseudohyphae and pus cells. 63 BV negative women, there were 16 (25.4%) preterm

189 Association of Bacterial Vaginosis on Preterm Delivery TR Das et al

Table-I

Characteristics of the study subjects

Parameters BV negative BV positive P value (n=63) (n=37) Age (years) 24.59±5.18 23.89±4.77 >0.50ns Mean±SD 15-35 15-33 Range No. (%) No. (%) Socioeconomic statusLow 24 (38.1) 15 (40.5) >0.10ns Middle 18 (28.6) 15 (40.5) High 21 (33.3) 7 (18.9) Educational status Illiterate 5 (7.9) 3 (8.1) >0.50ns Class I-V 13 (20.6) 10 (27.0) Class VI-X 23 (36.5) 10 (27.0) SSC + 22 (34.9) 14 (37.8) Gravidity Primi 29 (46.0) 20 (54.1) >0.10ns Multi 34 (54.0) 17 (45.9) Duration of gestation (weeks) 37.49+2.53 35.24+2.33

Chi-square test/Unpaired Student’s ‘t’ test, ns = Not significant, *** = Significangt

Table-II

Pregnancy outcome

Delivery BV negative BV positive P value (n=63) (n=37) No. (%) No. (%) Preterm 16 (25.4) 27 (73.0) < 0.001*** Term 47 (74.6) 10 (27.0)

Chi-square test, *** = Significant deliveries compared to 47 (74.6%) term deliveries. higher prevalence of BV in the obstetric population has However, out of 37 BV positive women, there were 27 been held responsible for the higher incidence (10%) of (73%) preterm deliveries and 10 (27%) term deliveries preterm delivery which could be reduced by screening (highly significant, P< 0.001). and treating the condition10. Treating BV before the women conceive is now accepted as a better way of Discussion: preventing complication during pregnancy10. Existing Bacterial vaginosis (BV) is one of the most common data indicate a very strong association between genital presentation in women of reproductive age attending tract infections and spontaneous preterm labour and gynaecology outpatient department. The relatively preterm birth, and offers the possibility of promising

190 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 new interventions to prevent this complication of Kingdom and Indonesia, where incidence of preterm pregnancy. delivery with BV positive cases ranged from 2 to 2.8 and 16,17,18 The vaginal flora during pregnancy is notable for an 3.5 and 6.9 . increase in lactobacilli which along with other bacteria Higher incidence in our cases was possibly due to the helps to maintain the acidity of vagina through the inclusion of cases in last trimester of pregnancy. The production of lactic acid2. Thus, this low pH encourages selection of cases in last trimester of pregnancy prevent further growth of lactobacilli and other acidophilic us to analyze very early loss of pregnancy among women organism and helps to prevent overgrowth with more with BV, which may account for the lower estimated risk pathogenic bacteria. This physiologic alteration of flora that we found. during pregnancy may serve to protect the fetus which In this study, high incidence was found in 27 (73%) of becomes progressively more benign during preterm labour in BV cases compared to 16 (25.4%) in 11 pregnancy . Alterations of this normal vaginal non-BV cases, which is significantly higher compared environment can lead to adverse outcome of pregnancy. to studies by MacDonald et al., who reported 15 percent The first case-control study reported by Eschenbach et in BV cases19. Similar studies by McGregor reported al. in 1984 showed the presence of bacterial vaginosis 18.8 percent PTL in BV cases compared to 9.7 percent in in high percentage of women with preterm labour (PTL), non –BV cases. 43%) This lower incidence of PTL in BV cases could be compared to control (14%). Besides, bacterial vaginosis attributed to the high quality antenatal care available to has also been associated with an increased risk of pregnant women. It seems that early detection and preterm birth (PTB), premature ruptured membrane treatment of BV cases in our society can also prevent (PROM) and intraamniotic infection”. this complication.

In recent years, an increasing suspicion has led us to Conclusion: studies between altered vaginal bacterial flora and low- Our findings demonstrated a significant effect of birth-weight (LEW), preterm birth (PTB) and premature bacterial vaginosis on preterm delivery. Our finding also rupture of membrane (PROM). Recent many reports added to the existing evidence that bacterial vaginosis indicate a strong association between BV with PTL and is an independent risk factor for preterm birth and 12 PROM . suggests that the timing of this infection in gestation A total of 100 pregnant women aged 15-35 years, significantly affect this risk. Timely detection and between 28 and 36 weeks of gestation, with abnormal intervention could easily prevent bacterial vaginosis- vaginal discharge and clinically suspected of bacterial related adverse pregnancy outcome. vaginosis were enrolled in this study. Based on Amsel References: clinical criteria and culture, 37 percent women were 1. Blackwell AL, Thomas PD, Wareham K, Emery SK. Health identified to have bacterial vaginosis, which is slightly gains from screening for infection of the lower genital higher than that of Fule et al. and James et a/., who tract in women attending for termination of pregnancy. reported 31 and 30 percent cases of BV, respectively13'14. Lancet 1993, 342:206-10. This higher incidence in the present study may be due 2. Eschenbach DA, Hillier SL, Critchlow C, Stevens C, to mandatory inclusion of clue cells on saline wet-mount DeRousen T, Holmes KK. Diagnosis and clinical as a marker of BV for every case. Depending on manifestation of bacterial Ivaginosis. Am J Obstet Gynecol population studied, prevalence of bacterial vaginosis 1988; 158:819-28. was reported to be between 10 to 40 percent among 3. McGregor JA, French JI, Richter R, Milligan K, McKinney pregnant women in the United States15. J, Petterson E. Bacterial vaginosis in pregnancy. Obstet Gynecol 2000; 55:1-19. In the present study, preterm delivery was 27 (73%) in 4. Amsel R, Totten PA, Spiegel CA, Chen KCS, Eschenbah BV positive cases, which is significantly higher than 16 DA, Homles KK. Nonspecified vagitis: diagnostic criteria (25.4%) BV negative cases. Similar studies were carried and microbial and epidemiological association. Am J Med out in the United States, Scandinavia, the United 1983; 74:14-22.

191 Association of Bacterial Vaginosis on Preterm Delivery TR Das et al

5. Blackwell AL, Phillips I, Fox AR, Barlow D. Anaerobic 13. Fule RP, Kalpana K, Jahagirdar VL, Saoji AM. Incidence vaginosis (nonspecific vaginitis): clinical, microbiological of Gardenerella vaginalis infection in pregnant women and therapeutic findings. Lancet 1983; ii: 1379-82. and nonpregnant women with nonspecific vaginitis. 6. Spiegel CA, Davick; P,Totten PA. Gardnerella vaginalis Indian J Med Res 1990; 91:360-3. and anaerobic bacteria in the etiology of bacterail 14. James JA, Thomason JL, Gelbart SM. Is trichomoniasis is (nonspecific) vaginosis. Scand J Infect Dis Suppl 1983; often associated with bacterial vaginosis in pregnant 40:41-6. adolescents. Am 1 Obstet Gynecol 1992; 166:859-63. 7. Masfari AN, Duerden BI, Kinghorn GR. Quantitative studies of vaginal bacteria. Genitourin Med 1986; 62: 15. Pheifer TA, Forsyth PS, Durfee MA, Pollock HM, Homles 256-63. KK. Nonspecific vaginitis: role of Haemophilus vaginalis and treatment with metronidazole. N Engl J Med 1978; 8. Hoist E. Reservoir of four organisms associated with bacterail vaginosis suggests lack of sexual transmission. J 298:1429-34. Clin Microbiol 1990; 28:2035-9. 16. Piot P, van Dyke E, Godts P, Vanderheyden J. The vaginal 9. Hillier SL, Krohn MA, Nugent RP, Gibbs RS. Characteristics microbial flora in nonspecific vaginitis. Eur J Clin of three vaginal flora patterns assessed by gram-stain Microbiol 1982; 1:301-6. among pregnant women (for the Vaginal Infection and 17. Hill GB, Eschenbach DA, Holmes KK. Bacteriology of Prematuriry Study Group). Am J Obstet Gynecol 1992; the vagina. Scand J Urol Nephrol Suppl 1985; 86:23-39. 166:938-44. 18. van der Meijden WI, Duivenvoorden HJ, Both-Patoir 10. Hay PE. Recurrent bacterial vaginosis. Curr Infect Dis HC, Hazen-Engelsman ME, Drogendijk AC. Clinical and Rep 2000; 2:506-12. laboratory findings in women with bacterial vaginosis and 11. Lament RF, Fisk NM. The role of infection in the aetiology trichomoniasis versus controls. Eur J Obstet Gynecol of preterm labour. In: Studd JWW, editor, Progress in Reprod Biol 1988; 28:39-52. obstetrics and gynaecology, vol. 10. Edinburth: Churchill Livingstone, 1993: 135-58. 19. MacDonald HM, O’Loughlin JA, Jolley P, Vigneswaren R, 12. McGregor JA. Preterrn birth and infection: pathogenic McDonald PJ. Vaginal infection and preterm labour. Clin possibilities. Am J Reprod Immunol 1988; 16:123-32. Obstet Gynecol 1991; 98:427-35.

192 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 Incidence of Gallbladder Carcinoma in Thick Walled Gallbladder in Comparison with that of Normal Thickness – A Study of 300 Cases MM HASANa, SZ LAILAb, MH MAMUNc

Summary: number of the patients fall into fourth and fifth decades. 42 Background: Gall bladder carcinoma (GBC) is the most (14%) patients were found to have thick walled GB by pre- common biliary tract cancer. Delayed presentation and early operative sonography and during surgery. spread of tumor made it one of the lethal tumors with poor Histopathologically 13 (4.33%) patients were diagnosed as prognosis. GBC. Maximum patient (52.33%) had chronic cholecystitis. Objective: The objective of this study is to find out the Incidence of malignancy were higher (84.62%) in patients incidence of GBC in thick walled gall bladder (GB) in having thicke walled GB. comparison with that of normal wall thickness. Conclusion: GBC may present as focal or diffuse asymmetric Methods: This prospective study was carried out in Combined wall thickening or even in GB having normal wall Military Hospital (CMH) Dhaka, CMH Momenshahi and thickness. As early diagnosis and effective treatment can CMH Ghatail during the period of June 2007 to June 2014. significantly reduce the morality and morbidity all specimen A total 300 patients underwent cholecystectomy were studied should be examined histopathologically. retrospectively. Diagnosis was confirmed by histopathological examination. Key words: Cholecystectomy, Gall bladder carcinoma, Thick walled gall bladder. Results: Out of 300 patients 254 (84.88%) were female (male : female = 1:5.52), age range 28 to 79 years. Maximum (J Bangladesh Coll Phys Surg 2016; 34: 193-198)

Inteoduction: Globally, there is a prominent geographical Gallbladder carcinoma (GBC) is the most common biliary inconsistency in GBC incidence that draws a parallel tract cancer, accounting for 3% of all tumors.1 GBC is with the prevalence of cholelithiasis.4 Numerous hard to detect and diagnose in its early stages because reports propose an association between chronic S. it usually has very slight symptoms or is asymptomatic. typhi carriage and elevated risk of GBC.5 But once the diagnosis is confirmed, most of these Incidental gallbladder carcinoma (IGBC) is defined as patients often have metastasis and invasion. GBC suspected for the first time during cholecystectomy Furthermore, GBC is not sensitive to radiotherapy and or accidentally found on histological examination of the chemotherapy. All of these characteristics made GBC a gallbladder (GB).6 With the increase of highly lethal tumor with a 5 years survival rate of less cholecystectomies since the wide acceptance of 2 3 than 5% and a median survival of only 3 months. laparoscopic cholecystectomy (LC), the incidental diagnosis of GBC is more frequent.7 Unsuspected GBC a. Dr. Md Mahboob Hasan, Lt Colonel, Classified Specialist in surgery, CMH Ghatail, Shaheed Salahuddin Cantonment, can be discovered incidentally following 1% of routine 8 Ghatail, Tangail cholecystectomies diagnosed either intra-operatively b. Dr. Syeda Zeenat Laila, Major, Classified Specialist in or subsequent to histological analysis following Paediatrics, Armed Forces Hospital, OKP-5, Kuwait. cholecystectomy.9 c. Dr. Md Monjur Hasan Mamun, Medical Officer (Clinical Diffuse GB wall thickening may be caused by a wide Neurosurgery), National Institute of Neuroscience & range of GB diseases and extracholecystic pathologic Hospital, Dhaka. conditions. It can result from a broad spectrum of Address of Correspondence: Md Mahboob Hasan, Lt Colonel, Classified Specialist in Surgery, CMH Ghatail, Shaheed Salahuddin pathologic conditions, including surgical and Cantonment, Ghatail, Tangail, Cell: 01723660642, 01715011637, nonsurgical diseases. In most cases it’s cause can be E-mail: [email protected]. determined by correlation of the clinical presentation Received: 22 Nov. 2017 Accepted: 29 Oct. 2016 and associated imaging findings. GBC has various Incidence of Gallbladder Carcinoma in Thick Walled Gallbladder in Comparison MM Hasan et al. imaging appearances, ranging from a polypoid 254 (84.88%); Male: Female is 1: 5.52. A total 42 (14%) intraluminal lesion to an infiltrating mass replacing the patients had thick walled GB and 258 (86%) patients GB GB, and it may also present as diffuse mural thickening.10 had normal wall thickness (Table – 1). In this study we tried to find out the incidence of GBC in All patients were evaluated by sonography to determine relation with wall thickness. the wall thickness. Thirty six (12%) patients were found to have thick walled GB. And in 10 (3.33%) patients Materials and Methods: contracted GB was found (Table – 2). This observational study has been carried out in Combined Military Hospital (CMH) Dhaka, CMH All resected specimen were examined Momenshahi and CMH Ghatail during the period of histopathologically. Incidence of GBC were 4.33%. June 2007 to June 2014. A total 300 patients underwent Maximum 157 (52.33%) patients had features of chronic cholecystectomy were studied retrospectively. inflammation. 54 (18%) specimens revealed nonspecific Diagnosis confirmed by histopathological examination. findings (Table – 3). Patients with clinically suspected or diagnosed Incidence of malignancy was higher (84.62%) in patients malignancy and intraoperatively obvious growth with with thick walled GB. Out of 13 cases 10 (76.92%) were or without signs of metastasis were excluded from the female. Incidence were more in patients of >60 years of study. age group (46.15%) irrespective of wall thickness (Table -4). A detailed history was taken from the patients. Physical findings were recorded properly. In all 13 malignant cases the initial diagnosis was GB stone in 11 (84.62%) and GB polyp in 2 (15.36%) patients Patients diagnosed as GBC received further treatment (Table – 5). under hepatobiliary surgeon and oncologist. All the patients were followed up regularly during their stay in Out of the all 13 GBC, maximum 7 (53.85%) were well the hospital and as out patient. differentiated adenocarcinoma, 4 (30.77%) were moderately differentiated. Only 1 (7.96%) patient each Results: had poorly differentiated and non-specific

The youngest patient of this series was 28 years and adenocarcinoma. Invasion was pT1 in 11 (84.62%) and oldest was of 79 years. Male 46 (15.12%) and Female: pT2 in 2 (15.38%) patients (Table – 6). Table-I Age and Sex distribution in relation with GB wall thickness (n=300) Condition of Sex Age (years) Total Percentage GB Wall Male Female <40 41–50 51 – 60 >60 Thick 07 35 13 18 09 02 42 14% (16.67%) (83.33%) (30.95%) (42.56%) (21.43%) (4.76%) Normal 39 219 79 105 59 15 258 86% (15.12%) (84.88%) (30.62%) (40.70%) (22.87%) (5.81%) Total 46 254 92 123 68 17 300 100 (15.12%) (84.88%) (30.62%) (40.70%) (22.87%) (5.81%)

M:F = 1:5.52 Table -II Sonographic findings of GB wall (n=300) Sonographic findings No. of patients Percentage % Normal wall thickness 254 84.67 Thick wall (>3mm) 36 12 Contracted GB 10 3.33 * 6 patients had thick walled GB found duting surgery

194 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Table-III

Histopathological Diagnosis: (n=300)

Histopathological Diagnosis Total Percentage (%) Chronic Cholecystitis 157 52.33 Cholesterosis 05 1.67 Acute Cholecystitis 11 3.67 Epithelial Hyperplasia 59 19.67 Tuberculosis 01 0.33 Carcinoma GB 13 4.33 Non specific findings 54 18 Total 300 100

Table-IV

Incidence of Ca in comparison to wall thickness (n=13)

Condition of Sex Age (years) Total Percentage GB Wall Male Female 30–40 41–50 51 – 60 >60 % Thick 03 08 - 02 05 04 11 84.62 Normal - 02 -- 01 01 02 15.38 Total 03 10 - 02 05 06 13 100 (23.08%) (76.92%) (15.38%) (38.46%) (46.15%)

Table-V

Clinical diagnosis in the 13 cases of gallbladder carcinoma (n=13)

Clinical Diagnosis No. of patients Percentage (%) GB stone 11 84.62 GB polyp > 1 Cm 02 15.38

Table-VI

Histopathological Characteristics of Ca (n=13)

Histopathological Characteristics No. of patients Percentage (%) Type Well differentiated adenocarcinoma 07 53.85 Moderately differentiated adenocarcinoma 04 30.77 Poorly differentiated adenocarcinoma 01 7.69 Non-specific adenocarcinoma 01 7.69 Invasion

pT1 11 84.62 pT2 02 15.38

195 Incidence of Gallbladder Carcinoma in Thick Walled Gallbladder in Comparison MM Hasan et al.

Discussion: gallbladder symptoms22,23 has a relatively high Cancer of the GB is uncommon, although it is the fifth sensitivity for the detection of GBC at advanced stages, most common gastrointestinal malignancy11 and is found but it is limited in the diagnosis of early lesions. Although incidentally in 1% to 3% of cholecystectomy CT scan is a valuable investigation for suspected cases specimens.12 2.5 new cases detected per 100,000 of GBC with a reported sensitivity of 80% and 100%, it inhabitants per year. It has a high mortality rate as its is not routinely used to investigate patients with GB diagnosis is most of times achieved at advanced stages disease symptoms. Pre-operative diagnosis depends of the disease, because of the scarcity of symptoms.13 mainly on a high index of clinical suspicion especially in elderly patients with gallstones. Some authors24 Countries with a high incidence of GBC include Chile, suggested criteria for early diagnosis of GBC in presence Poland, India, and Japan. There is also a very high of the combination of female sex, old age, silent incidence of this cancer among women in Northern India gallstones presenting at late age, abnormal liver function (21.5/100,000) and female Native American Indians (14.5/ test and thickened wall of the GB on ultrasonic 100,000).14 Our patient was of Bangladeshi (ie, the Indian examination (plus criteria), but these criteria are not yet subcontinent) origin. critically evaluated.25 The majority of reports suggest that GBC is two to six GBC may present as focal or diffuse asymmetric wall times more prevalent in women and the incidence peaks thickening in 20–30% of cases.2 Diffuse GB wall in the seventh decade of life15,16 In this study out of 13 thickening is a frequently detected finding on cross- malignant cases 10 (76.92%) were female. Incidence were sectional imaging in clinical practice; this finding can more in patients of >60 years of age group (46.15%) result from a broad spectrum of pathologic conditions. irrespective of wall thickness. Among these conditions, acute cholecystitis, chronic There is a strong association between cholelithiasis and cholecystitis, GBC, and adenomyomatosis are common GBC, with gallstones found in nearly 80% of all cases. diseases that cause diffuse or focal GB wall thickening.26 Other risk factors for GBC include a calcified GB (known When GBC manifests as wall thickening, it is challenging as porcelain gall•bladder), a long common channel, and to diagnose because it mimics the appearance of more a chronic typhoid carrier state. Adenomas figure less common acute and chronic inflammatory conditions of prominently or not at all in the list of precursors.17 the GB.27 Majority of GBC patients have associated gallstones. According to several authors, the upper limit for With the advent of ultrasonography more patients are normality of the GB wall thickness is 3 mm. However, in being diagnosed with gallstones and are being subjected patients under inappropriate fasting, the parietal to cholecytectomy. IGBC is found in 0.2–2.9 % of all thickness may exceed such a limit because of the organ’s 18 cholecytectomies done for gallstone disease. A smooth muscle con-traction.13 GB wall thickening is common characteristic is the presence of gallstones and classified as mild (between 4 and 7 mm), marked (> 7 19 chronic GB inflammation. Cholelithiasis is found in mm), and in focal or diffuse. As a rule, systemic diseases approximately 85% of people with GBC. The association such as heart, renal or hepatic failure cause diffuse and between cholelithiasis and GBC ranges from 2.3 to 34.4 less marked thickening, contrary to tumor lesions that in case control studies.20 In our study 84.62% patients cause focal and more exuberant thickening, frequently of GBC had cholelithiasis which is almost similar to this. greater than 10 mm.26 Clinical presentation of the disease is often vague or Ultrasonography is the method of choice for the study delayed relative to pathologic progression, contributing of the GB, with a high sensitivity in the detection of wall to advanced staging and dismal prognosis at the time thickening.13 Real-time elastography using acoustic of diagnosis.21 Unfortunately, the preoperative radiation force impulse (ARFI) is a new emerging diagnosis of early-stages of gallbladder carcinoma is technique, which uses high intensity focused difficult due to its non-specific symptoms. The ultrasound to evaluate the tissue stiffness in the liver, symptoms of GBC overlap with the symptoms of breast, and other organs.28 It has also been shown to gallstones and biliary colic. Sonography is a routinely differentiate between benign and malignant nodules in requested technique for investigating patients with various organs.29

196 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Magnetic resonance imaging has been shown to be References: valuable in the evaluation of GB wall thickening, but it 1. A. Jemal, R. Siegel, E. Ward et al. “Cancer statistics, still plays a small diagnostic role.30 Because of its high 2006,” Ca-A Cancer Journal for Clinicians, 2006, vol. 56, no. 2, p. 106–130. cost and low specificity, MRI is not used to diagnose chronic cholecystitis.31, 32 In our study 42 (14%) patients 2. Abhishek Vijayakumar, Avinash Vijayakumar, Vijayraj Patil, M. N. Mallikarjuna, and B. S. Shivaswamy. Early had thick walled GB out of them 36 were diagnosed Diagnosis of Gallbladder Carcinoma: An Algorithm sonographically and 6 cases were found dering surgery. Approach, ISRN Radiology, Volume 2013, Article ID On histopathological examination 11 (84.62%) GBC cases 239424, 6 pages. had thick walled GB which is very high. 3. M. I. M. De Zoysa, S. K. L. A. De Silva and A. Illipe-ruma. Is Routine Histological Examination of the Gall-bladder GBC is associated with macroscopic abnormalities in all Specimens Justifiable? Ceylon Medical Journal, 2010, Vol. cases. Therefore histopathology should be restricted 55, No. 1, p. 3-16. to only those specimens which reveal a macroscopic 4. V. Nagaraja and G. D. Eslick. Systematic review with meta- 33 abnormality. The question of a selective approach to analysis: the relationship between chronic Salmonella sending all GBs for histology following typhi carrier status and gall-bladder cancer. Alimentary cholecystectomy has been postulated in many journals Pharmacology & Therapeutics, April 2014, Volume 39, Issue 8, pages 745–750. but as yet no guidelines have been published in light of such concern.3, 33 5. Nath G, Singh YK, Kumar K, et al. Association of carcinoma of the gallbladder with typhoid carriage in a The only effective treatment for GBC is operative typhoid endemic area using nested PCR. J Infect Dev resection, and an open technique is preferred. Ctries 2008; 2: 302–7. Unfortunately, as is often the case, the lack of presurgical 6. Jin K, Lan H, Zhu T, He K, Teng L. Gallbladder carcinoma differential diagnosis hampers the planning of surgery.34 incidentally encountered during laparoscopic cholecystectomy: how to deal with it. Clin Transl Oncol. Evidence has emerged that suggests early GBC (pT1) 2011 Jan;13(1):25-33. need not be treated further than the cholecystectomy 7. Wei-Jie Zhang, Gui-Fang Xu, Xiao-Ping Zou, Wei-Bing that was previously performed in order to obtain the Wang, Jun-Chi Yu, Guo-Zhong Wu and Chun-Lei Lu. tissue sample. In other words, although early Incidental Gallbladder Carcinoma Diagnosed During or macroscopic findings indicative of GBC could After Laparoscopic Cholecystectomy, World Journal of theoretically be missed in a selective method, no further Surgery, 2009, Volume 33, Number 12 2651-2656] treatment is necessary in such early pathogenic 8. Akyurek N, Irkorucu O, Salman B, Erdem O, Sare M, stages.35 In this study 84.62% cases were in pT stage. Tatlicioglu E. Unexpected gallbladder cancer during 1 laparoscopic cholecystectomy. J Hepatobiliary Pancreat According to this study incidence of GBC is very high Surg. 2004;11:357–361. on thick walled GB. But we found two patients of GBC 9. Malik IA. Clinicopathological features and management having normal wall thickness. So we recommend all of gallbladder cancer in Pakistan: a prospective study of resected specimen should be examined 233 cases. J Gastroenterol Hepatol; 2003; 18(8): 950-3. histopathologically. 10. Adriaan C. van Breda Vriesman, Marc R. Engelbrecht, Robin H. M. Smithuis, Julien B. C. M. Puylaert. Diffuse Conclusion: Gallbladder Wall Thickening: Differential Diagnosis. Diffuse GB wall thickening can result from a broad American Journal of Roentgenology. 2007;188: 495-501. spectrum of pathological conditions, including surgical 11. D’Hondt M, Lapointe R, Benamira Z, Pottel H, Plasse and non-surgical diseases. GBC may present as focal or M, Letourneau R, et al. Carcinoma of the gallbladder: diffuse asymmetric wall thickening or even in GB having Patterns of presentation, prognostic factors and survival rate. An 11-year single centre experience. Eur J Surg normal wall thickness. Combined with well known risk Oncol. Jun 2013;39(6):548-53. factors such as increasing age, female sex, ethnicity 12. Gore RM, Yaghmai V, Newmark GM, Berlin JW, Miller and working on a when-in-doubt policy whereby if there FH. Imaging of benign and malignant disease of the are any suspicions whether small or large, all GB should gallbladder. Radiol Clin N Am 2002; 40:1307-1323. be sent for histology, thus clinicians will be able to put 13. Barbosa ABR, Souza LRMF, Pereira RS, D’Ippolito G. into action a more evidence-based approach to send Gallbladder wall thickening at ultrasonography: how to specimens to pathology. interpret it? Radiol Bras. 2011 Nov/Dez;44(6):381–387.

197 Incidence of Gallbladder Carcinoma in Thick Walled Gallbladder in Comparison MM Hasan et al.

14. Miller G, Jarnagin WR. Gallbladder carcinoma. Eur J Surg Cholecystectomy, Report Of Three Cases. The Internet Oncol. 2008;34:306-312. Journal of Surgery. 2010 Volume 25 Number 2. 15. Duffy A, Capanu M, Abou-Alfa GK, et al. Gallbladder 26. Van Breda Vriesman AC, Engelbrecht MR, Smithuis RH, cancer (GBC): 10-year experience at Memorial Sloan- Puylaert JB. Diffuse gallbladder wall thickening: Kettering Cancer Centre (MSKCC). J Surg Oncol; 2008; differential diagnosis. AJR 2007; 188:495 –501. 98: 485. 27. Soo Jin Kim, Jeong Min Lee, Jae Young Lee, Se Hyung Kim, Joon Koo Han, Byung Ihn Choi and Jin Young Choi, 16. Konstantinidis IT, Deshpande V, Genevay M, et al. Trends Analysis of Enhancement Pattern of Flat Gallbladder Wall in presentation and survival for gallbladder cancer during Thickening on MDCT to Differentiate Gallbladder Cancer a period of more than 4 decades: a single-institution from Cholecystitis, American Journal of Roentgenology. experience. Arch Surg; 2009; 144: 441. 2008;191: 765-771. 17. Vivek Trivedi, Vivek V. Gumaste, Shaojun Liu, Joel Baum. 28. B. J. Fahey, R. C. Nelson, D. P. Bradway, S. J. Hsu, D. M. Gallbladder Cancer: Adenoma-Carcinoma or Dysplasia- Dumont, and G. E. Trahey, “In vivo visualization of Carcinoma Sequence? Gastroenterology & Hepatology abdominal malignancies with acoustic radiation force Volume 4, Issue 10 October 2008, p- 735-37. elastography,” Physics in Medicine and Biology, 2008, 18. Sivaprakash Rathanaswamy, Sanjeev Misra, Vijay Kumar, vol. 53, no. 1, p. 279–293. Chintamani, Jaipalreddy Pogal, Akash Agarwal, Sameer 29. S. H. Cho, J. Y. Lee, J. K. Han, and B. I. Choi, “Acoustic Gupta. Incidentally Detected Gallbladder Cancer - The radiation force impulse elastography for the evaluation Controversies and Algorithmic Approach to Management. of focal solid hepatic lesions: preliminary findings,” Indian Journal of Surgery, June 2012, Volume 74, Issue 3, Ultrasound in Medicine and Biology, 2010, vol. 36, no. 2, pp 248-254. pp. 202–208. 19. Eldon A. Shaffer, Gallbladder Cancer: The Basics. 30. Atul Kapoor, Aprajita Kapoor, and Goldaa Mahajan, Gastroenterology & Hepatology Volume 4, Issue 10 Differentiating Malignant From Benign Thickening of October 2008, p- 737-41 the Gallbladder Wall by the Use of Acoustic Radiation Force Impulse Elastography, JUM November 1, 2011 20. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer vol. 30 no. 11 1499-1507. worldwide: geo•graphical distribution and risk factors. Int 31. Altun E, Semelka RC, Elias J. Acute cholecystitis: MR J Cancer. 2006;118:1591-1602. findings and differentiation from chronic cholecystitis. 21. Reid KM, Ramos-De la Medina A, Donohue JH: Diagnosis Radiology 2007; 244:174–183. and surgical management of gallbladder cancer: a review. 32. Smith EA, Dillman JR, Elsayes KM, Menias CO, Bude J Gastrointest Surg 2007; 11: 671-681. RO. Cross-sectional imaging of acute and chronic 22. Furlan A, Ferris JV, Hosseinzadeh K, Borhani AA: gallbladder inflammatory disease. AJR Am J Roentgenol Gallbladder carcinoma update: multimodality imaging 2009; 192:188–196. evaluation, staging, and treatment options. AJR Am J 33. Mittal R, Jesudason MR, Nayak S. Selective Roentgenol; 2008; 191(5): 1440-7. histopathology in cholecystectomy for gallstone disease. 23. Rodríguez-Fernádez A, Gómez-Río M, Medina-Benitez A, Indian J Gastroenterol. 2010 Jan;29(1):26-30. et al.: Application of modern imaging methods in diagnosis 34. Jian-Bin Hu, Xiao-Nan Sun, Jing Xu, Chao He. Port site of gallbladder cancer. J Surg Oncol; 2006; 93: 650-664. and distant metastases of gallbladder cancer after laparoscopic cholecystectomy diagnosed by positron 24. Mohamed A, Emran F, Ghanem N, Mohamed A: Gallbladder emission tomography, World J Gastroenterol. Nov 7, Carcinoma, Improving Diagnosis and Outcome. The 2008; 14(41): 6428–6431. Internet Journal of Surgery; 2010; Volume 23, Number 2. 35. John-Patrick Devine Byars, Kishore Pursnani. An 25. F. Emran, S.Y. AL_shami, M. Abukhater, K. Alternative Approach to Sending All Gallbladders for ALMohaimeed, A.A. Mohamed: Port-Site Metastasis Histology Following Cholecystectomy? Surgical Science, From Gallbladder Carcinoma After Laparoscopic 2012, 3, 15-20.

198 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 Hepatitis B Virus, Hepatitis C Virus Markers and Serum Alanine Amino-Transferase (ALT) Levels, in a Young Adult Population of Sylhet District I PERVEENa, M SAHAb, KK DHARc, MS ISLAMd

Summary: HCV. Women were all negative for HBsAg or anti HCV. Objective: To find out the seroprevalence of the hepatitis B None had co-infection with HBV and HCV. Mean ALT and and C viruses in a young adult population along with AST levels of study population were 31.85 I.U./L and 26.18 I.U./L respectively and were not found to vary with age and estimation of aminotransferase levels. And so as to increase sex. Mean ALT levels were more in in HBsAg positive cases the awareness and augment preventive measures against these (42.03 I.U/L vs. 31.5 I.U./L, P .000) and HCV infected cases viral hepatitis related morbidity. (49 I.U./L vs. 31.51 I.U./L, P.000) than non-infected persons. Methods: A total of 2611 apparently healthy young adults Conclusion: Hepatitis B infection is of intermediate were screened from January 2010 to December 2010 at a endemicity among young adults while hepatitis C virus Medical Checkup center of Sylhet for hepatitis B surface infection is low among this group. Mean amino transferase antigen (HBsAg), hepatitis C virus antibody (anti HCV), levels were higher in asymptomatic infected persons in alanine aminotransferase (ALT) and aspertate comparison to non-infected person. We suggest the need for aminotransferase (AST) levels. revision of upper limit of normal for ALT in our population for early detection and treatment of liver diseases. Results: Out of 2611 subjects 2536(97.1%) were male and Key Words: Hepatitis B virus, hepatitis C virus, alanine 75(2.9%) were female with comparable mean ages (29.08 vs. amino-transferase, young adults. 30.6 years, P .056). A total of 77(3.0%) men were HBsAg positive and only four (0.16%) men were positive for anti (J Bangladesh Coll Phys Surg 2016; 34: 199-205)

Introduction: B surface antigen (HBsAg) positivity was 5.5% among Chronic hepatitis B virus (HBV) and hepatitis C virus the general population of a semi-urban area near Dhaka (HCV) infections are global challanges. Globally 350 city2. The reported prevalence of HBsAg in selected million people are suffering from chronic (lifelong) population of Bangladesh ranges between 2-3.5%3-5. infections and more than one million people die each The prevalence is much higher in high risk group 6-9. year from liver cirrhosis and liver cancer1. In the Middle East and Indian sub-continent, HBV infection is of According to World Health Organization (WHO), 130- intermediate endemicity with chronic HBV carriage rate 170 million persons are chronically infected worldwide with 10 of 2-5% among general population1. In Bangladesh, hepatitis C virus (HCV). Approximately 10% to 20% of there is paucity of information on the prevalence of chronic HCV infection cases, will progress to cirrhosis and HBV infections. According to a recent report hepatitis hepatocellular carcinoma.10. The highest prevalence rates are reported from developing poor countries from Africa a. Irin Perveen, Associate Professor of Gastroenterology, and Asia. Estimates of HCV prevalence in Southeast Asian 11, 12 Enam Medical College, Dhaka, Bangladesh. countries are 2.0% to 3.8% for the general 13 b. Madhusudan Saha, Associate Professor of Gastroenterology, population,12.5% for patients with chronic liver disease , North East Medical College, Sylhet, Bangladesh. and more than 90% for injecting drug users14. Currently, c. Kishore Kumar Dhar, Internee Doctor, North East Medical there is limited information on the HCV prevalence and risk College, Sylhet, Bangladesh. factors in the general population of Bangladesh. The d. Md Shamsul Islam, Registrar of Medicine, North East Medical reported seroprevalence of HCV among people of an College, Sylhet, Bangladesh. impoverished area of Bangladesh15, rural area,16 healthy Address of Correspondence: Irin Perveen, B-11, Tropical blood donors3 and drug addicts17 were 0.2 %, 0.6%, 0.25% kader Garden, 335 Tongi Diversion Road, Bara Magh Bazar, and 15.0% respectively. Dhaka-1217, Bangladesh. Phone numbers: +8801552365100, E-mail address: [email protected], Serum alanine aminotransferase (ALT) concentration is Received: 25 July 2015 Accepted: 28 September 2016 the most widely used sensitive and reliable marker of Hepatitis B Virus, Hepatitis C Virus Markers and Serum Alanine I Perveen et al. liver diseases. Several population-based studies have book of the medical centre. Physical examination and found slightly increased ALT levels within the current laboratory investigations including markers for several normal range to be closely related to comorbidities and infectious diseases and drugs of abuse were carried out mortality.18-20 Current upper limit of normal (ULN) for as required by the countries recruiting the workers. ALT level were set, on average, ranging from 30 U/L to Consents were taken for blood tests Immediately following the interview, a 10-mL aliquot of blood was 50 U/L over the past 10 years. Such thresholds, however, drawn from each participant to test for hepatitis B surface vary tremendously among hospitals, research centers antigen (HBsAg), anti- HCV and serum alanine amno- and geographic locations. The normal range of serum transerase (ALT) and aspertate amno-transerase (AST) ALT for any laboratory test is the mean value plus two levels. standard deviations in a supposedly healthy reference population, and the upper limit of normal (ULN) is Data analysis established statistically as the value at the 97.5th Data were analyzed using the SPSS version 20.0 statistical program. Prevalence estimates of cases percentile.21 Currently, several studies have been positive for HBsAg and anti-HCV were stratified by reevaluated the ULN ALT in different countries by demographic characteristics. A ÷2 test was used for involving different age groups. And the recommended comparisons between proportions, while Students t test ULN ALT was 30 U/L for men and 19 U/L for women was used for comparisons of means, with á set at the respectively.18, 22-24 Based on the previous results it is 5% level. found that, recent ULN ALT greatly increase the number of asymptomatic patients with abnormal ALT values, Ethics Participation was voluntary and informed consent for and would identify more patients with nonalcoholic fatty interviewing and blood tests was obtained. Participants liver disease (NAFLD) and clinically mild HBV/HCV who tested positive for HBsAg or anti-HCV were offered infection. posttest counseling by specialists. The study protocol We have no data regarding the upper limit of normal for was approved by the Ethics Committee of Northeast ALT in our population. Most of the laboratories follow Medical College of Sylhet, Bangladesh. the manufacturer’s recommendation (40 - 65 I.U./L) for a particular analyzer to establish ULN ALT without healthy Result: volunteer testing. It is evident that HBV and HCV Out of 2614 participants, 3 cases were excluded for very infections are rapidly spreading in developing countries high level (> 1000 I.U./L) of SGPT and SGOT level. One due to the lack of health education, poverty, illiteracy of them had bilirubin level 7.30 mg/dl. Viral markers were and lack or cost of proper vaccination. As many negative in all three subjects. chronically infected individuals remain asymptomatic, Among the remaining 2611 subjects, 2536(97.1%) were and thus undetected for many years, we planned this male and 75(2.9%) were female with comparable mean serological study to determine the seroprevalence of HBsAg and anti-HCV and to estimate corresponding ages (29.08±6.767 vs. 30.6±7.600, P .056). Out of this serum ALT levels among a group of apparently healthy study population, 77(3.0%) male were HBsAg positive people coming for medical checkup for the purpose of while none of the women were HBsAg positive. Study jobs in the Middle East. We hoped that the findings population mostly belonged to 21-40 years group might guide eventually the development, adaptation, (n=2351, 90.0%) and HBsAg positivity among this group and evaluation of management strategies. were 2.85% (n=67) (table 2). Only four men (0.16%) were positive for anti HCV and women were all negative for Methodology anti HCV. None had co-infection with HBV and HCV. Hepatitis C virus (HCV) and hepatitis B virus (HBV) seroprevalence study was undertaken among 2611 Mean ALT and AST levels of study population were subjects coming for medical checkup in one of three 31.85 I.U./L(range, 17-226 I.U./L) and 26.18 I.U./L(range referrence centers of Sylhet district. All were young ,14- 211 I.U./L) respectively and mean values were 8.15 adults applying for job visas to different Middle East unit and 13.82 unit lower than upper level of normal countries. Data were collected by the trained staff from values(40 I.U./L). No significant difference was noted the medical center over a period of 10 months, September in these enzyme levels in males and females (table 1). 2011 to June 2002 and were recorded in the registry No significant difference was noted in ALT and AST

200 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 levels in more than 40 years and less than 40 years all 4 had ALT more than 30 I.U./L. In female ALT level >19 group (table 2). Mean bilirubin level of study population was found in 98.7%(n=74) and in 96.0%(n=72) ALT was was 0.667±.258 mg/dl (range .10-7.30mg/dl). No less than 40 I.U./L. Similarly AST levels more than 40 significant difference was noted in the mean bilirubin I.U./L was found in 2.3 % (n =58) non-infected subjects level in HBV and HCV infected persons than non- and in 22.0%(n=17) of HBsAg positive cases(P 0.000 ). infected persons (table 3 and 4) Mean ALT and AST levels were significantly more in in ALT levels more than 40units/L was found in 107 cases; HBsAg positive cases than HBsAg negative cases among them 78 cases (3.1%) were both HBSAg and anti (table3). These two levels were also significantly more HCV negative while 26 cases (33.8%) were HBsAg in anti HCV positive cases than anti HCV negative cases positive (P 0.000) and 3(75.0%) were anti HCV positive. (table 4). The ALT and AST values in HBsAg and anti ALT level more than 30 I.U. was found in 77.4% (n=55) of HCV negative subjects (n=2530) at 97.5th percentile were HBsAg positive males while In anti HCV positive males 49 I.U./L and 40I.U./L respectively.

Table-I Liver function test profile according to sex Male Female P-value N=2536 N=75 HBsAg positive 77(3.0%) 0 .171 Anti HCV positive 4(0.16%) 0 N S Mean ALT 31.9 ±12.4 I.U./L 29.4±7.2 I.U./L 0.073 Mean AST 26.2±10.4 I.U./L 24.1±5.9 I.U./L .077 Mean bilirubin .67±.23 mg/dl .58±.15 mg/dl 0.001

Table-II Liver function tests according to age category Age category P-value HBsAg positive <20 years(n=48) 1 (2.08%) 0.482 21-40 years(n=2351) 67 (2.85%) >40 years(n=212) 9 (4.3%) Anti HCV positive <20 years(n=48) 0 0.453 21-40 years(n=2351) 3 (.13%) >40 years(n=212) 1 (.47%) Mean ALT level <20 years(n=48) 29.3±7.7 I.U/L 0.331 21-40 years(n=2351) 31.9±12.5 I.U/L >40 years(n=212) 31.7±10.3 I.U/L Mean AST level <20 years(n=48) 23.96±6.8 I.U/L 0.248 21-40 years(n=2351) 26.3±10.5 I.U/L >40 years(n=212) 25.7±8.1 I.U/L Mean bilirubin level <20 years(n=48) .78±.44mg/dl 0.007 21-40 years(n=2351) .67±.26mg/dl >40 years(n=212) .65±.19mg/dl

201 Hepatitis B Virus, Hepatitis C Virus Markers and Serum Alanine I Perveen et al.

Table-III

Mean bilirubin, mean ALT and mean AST levels in HBsAg positive subjects

HBsAg positive HBsAg & Anti HCV negative P-value N=77 N=2530 Mean Bilirubin (mg/dl) .72±.25 .67±.26 .084 Mean ALT(I.U./L) 42.0±17.3 31.5±11.9 .000 Mean AST( I.U./L) 34.3± 13.96 25.9±10.0 .000

Table-IV

Mean bilirubin, mean ALT and mean AST levels in Anti HCV positive subjects

Anti HCV HBsAg & Anti HCV P-value positive negative N=4 N=2530 Mean Bilirubin (mg/dl) .53±.05 .67 ±.26 .271 Mean ALT(I.U./L) 49.0 ±14.9 31.5±11.9 .000 Mean AST( I.U./L) 40.0±11.78 25.9±10.05 .000

Discussion: among surgically operated patients,6 9.7% among HBsAg is the most reliable biological biomarker of commercial sex workers(CSWs),7 19% among hepatitis chronic HBV infection, and the antibody against patients29; and 47% among hepatocellular carcinoma.30 hepatitis B core antigen (anti-HBc) is an important marker The estimates of HBV exposures were far higher when for surveying the burden of HBV infection for identifying anti HBc was used as marker for HBV infection among 25 both past and current HBV infection. Thirty years urban slum (22.6%),15 drug addicts (27.8%)17 and healthy ago Islam et al. in 1984, reported a seroprevalence 7.8% adults and children(21.1%) 4 . Anti HBc positivity was of HBsAG among apparently healthy workers applied much higher in the high-risk groups of Dhaka: 24.1% in 26 for jobs in foreign countries. Thirty years later we non-IDUs and 31.8% in IDUs 17; 35.2% among women found a seroprevalence of 2.95%, which corresponds at a STD clinic 9; 48.1% among truck drivers and 27 to the findings of Rumi et al, who reported a prevalence helpers,28 49.3% among women living near a truck of 4.4% among healthy workers. stand,31 and 73% among CSWs .7 The apparently low The HBsAg prevalence of 2.95% among our study prevalence of HBV infection in the present study may population corresponds to the range of 2-7% reported be due to use of single marker or may reflect the true low by previous studies from the selected population: 2% prevalence among non-vulnerable population. 3 among healthy blood doners , 3% among healthy adults The 0.15% prevalence of anti-HCV observed in our 4 5 and children and 3.5% among pregnant women. The study population is lower than that reported from high- prevalence also corresponds to reports among high- risk groups of Dhaka: 0.8% among truck drivers and 8 risk group: 8.0% among drug addicts, 5.9% among truck helpers,28 0.9% among women at a STD clinic,9 1.6% 28 drivers and helpers. Lack of proper health care, lower among women living near a truck stand,31; 5.8% in non- socioeconomic status, less public awareness about the IDUs and 24.8% in IDUs,17 and 13% among hepatitis HBV transmission and lack of vaccination are proposed patients.29 The report corresponds to the findings of reason for high prevalence of HBV. High prevalence Ashraf et al. where seroprevalence among population also reported in other high risk groups of Dhaka: 7.6% of an impoverished area were .2%.15 Our results of Ant among women at a sexually transmitted disease (STD) HCV prevalence was much lower than other South Asian 9 8 clinic , 8% among intravenous drug users (IDUs) , 8.6% countries.11, 12 As HCV infection is rare, and as a

202 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 consequence co-infection with HBV and HCV is much patients remained outside the scope of antiviral rarer in our subjects. In the context of the absence of an treatment and these patients may inadvertently exposed HCV vaccine and the prohibitive cost of HCV treatment to many hepatotoxic medications. for the vast majority of the world’s HCV-infected We cannot comment on healthy ULN ALT as other population, identification and elimination of risk factors diseases like NAFLD and metabolic disorders were not for HCV remains the only option for reduction of HCV- excluded by ultrasonography/MRI, liver biopsy and related disease burden for most developing economies. other relevant tests. But when HBV, HCV infection cases ALT is a good indicator of health and meets most of the were excluded, at 97.5th percentile ALT level was 49 I.U/ accepted criteria for a screening test.32. Current upper L. this level is higher than recently recommended ULN limit of normal (ULN) for ALT levels (30-50I.U./L)were ALT.22-24 set based on the studies conducted prior to the There are some limitations of our study. First, we did not introduction of hepatitis C virus(HCV) testing and prior perform some diagnostic tests for HBV, e.g. anti-HBc IgM, to the development of concept of nonalcoholic fatty the presence of which indicates acute infection; and anti- liver disease(NAFLD). For a number of reason HBs that differentiates susceptible persons from those researchers support the lowering the ULN to achieve immune persons, which can be due either to natural appropriate screening and medical attention for patients infection or hepatitis B vaccination. Second, we did not with borderline ALT levels. First, screening using the perform some diagnostic tests for HCV, e. g. recombinant past range of normal serum ALT values might immunoblot assay (RIBA) to confirm HCV exposure, or underestimate the prevalence of CLD. Second, polymerase chain reaction (PCR) to detect HCV infected considering the natural courses of NAFLD or chronic individuals. All the above limitations are mainly due to HBV/HCV infections, disease progression with study cost constraints, mostly related to laboratory tests. significant degrees of necroinflammatory activity and The third limitation is that the familial clustering effects fibrosis of liver might occur in patients with persistently of hepatitis viruses, and risk factors for acquisition of normal ALT levels.27-31According to current guidelines, viral hepatitis were not assessed. The fourth limitation is antiviral therapy should be initiated with evidence of that the study was conducted in a selected population of viral replication in all patients with serum ALT levels Sylhet district, and may not reflect all of Bangladesh. A more than twice the ULN and in selected patients with serum ALT levels one to two times the ULN.27, 35 final limitation is the relatively short observation window, Adjustment of the ULN by defining borderline ALT levels which may have missed important secular trends in the as abnormal would allow more vigorous surveillance background prevalence of both the hepatitis B and C and earlier initiation of treatment. Third, Consistent viruses. with this finding, borderline rise of ALT values are early Conclusions: indicators of co-morbidities associated with lifestyle and The results of our study indicate an intermediate level 37 with liver injury due to hepatic steatosis. of endemicity of HBV infection as 2.95% our valuable In the present series mean ALT level was 31.93 I.U./L young adult population were HBsAg positive. However, (range17-226 I.U./L). It was not found to vary we observed a much lower prevalence of HCV infections significantly with age (P 0.331) and sex (P .073). Mean in the same community. We hope that this endemic ALT level in HBsAg positive subjects was significantly presence of HBV virus, would make awareness among more than in HBsAg negative subjects (P .000)(table 3). our health care providers and policy makers in designing When ULN ALT was considered as 40I.U./L only 33% and implementing effective preventive programmes. The HBsAg positive subjects were found to have raised findings also highlighted the need for prevention and ALT, but when upper level was lowered to 30 I.U./L, control of HBV and HCV infections in Bangladesh by 71.4% HBsAg positive subjects were found to have implementing universal hepatitis B vaccination and abnormal ALT values. In case of hepatitis C infection creating public awareness to prevent viral transmission. this percentages raised to 100% from 75.0%. From our We suggest the need for revision of Upper Limit of study results it is apparent that with currently adopted Normal for ALT in our population for early detection ALT values a good number of HBV and HCV infected and initiation of treatment of liver diseases.

203 Hepatitis B Virus, Hepatitis C Virus Markers and Serum Alanine I Perveen et al.

Long-term population-based surveillance studies, with 9. Bogaerts J, Ahmed J, Akter N, Begum N, Rahman M, extended HBV serology, are needed for more accurate Nahar S, et al. Sexually transmitted infections among married women in Dhaka, Bangladesh: unexpected high assessment of the hepatitis B and hepatitis C disease prevalence of hetpes simplex type 2 infection. Sex Transm burden in our country, the impact of vaccination, and to Infect 2001;77: 114-9. guide prioritization of limited health care resources. 10. Hepatitis C. [http://www.who.int/mediacentre/factsheets/ Further studies are also required to confirm the familial fs164/en/] 2000. Accessed November 25, 2006 clustering effect, for exploring transmission dynamics 11. .Ratanasuwan W, Sonji A, Tiengrim S, Techasathit W, and to identify risk factors for viral hepatitis. Suwanagool S. Serological survey of viral hepatitis A, B, and C at Thai Central Region and Bangkok: a population Acknowledgements base study. Southeast Asian J Trop Med Public Health We acknowledge with gratitude the commitment of the 2004;35:416–420] Popular Medical Checkup Centre, Sylhet which provide 12. Ishida T, Takao S, Settheetham-Ishida W, Tiwawech D. unrestricted support to the present research efforts. The Prevalence of hepatitis B and C virus infection in rural authors are grateful to Dr. Mahbubur Rahman and ethnic populations of Northern Thailand. J Clin Virol 2002; 24:31–35.] Khalequzzaman for their excellent review of the 13. Pramoolsinsap C, Sumalnop K, Busagorn N, Kurathong S. manuscript. Prevalence and outcomes of HBV and anti-HCV References: seropositive patients with chronic liver disease and hepatocellular carcinoma. Southeast Asian J Trop Med 1. Hepatitis B [http:// www. who. int/ mediacentre/ factsheets/ Public Health 1992; 23: 6–11. fs204/ en] 2008. 14. Luksamijarulkul P, Plucktaweesak S. High hepatitis C 2. Mahtab MA, Rahman S, Karim MF, Khan M, Foster G, seroprevalence in Thai intravenous drug abusers and Solaiman S, et al. Epidemiology of hepatitis B virus in qualitative risk analysis. Southeast Asian J Trop Med Bangladeshi general population. Hepatobiliary Pancreat Public Health 1996; 27:654–658. Dis Int 2008, 7: 595–600. 15. Ashraf H, Alam NH, Rothermundt C, Brooks A, Bardhan 3. Saha SK, Banik RK, Saha MR, Habibullah MM, Mamun- P, Hossain L, et al. Prevalence and risk factors for hepatitis Al-Mahtab. Prevalence of Transfusion Transmitted B and C virus infections in an impoverished urban Infection in Healthy Blood Donors in Sir Salimullah community in Dhaka, Bangladesh. BMC Infectious Medical College Dhaka, Bangladesh. Euroasian Journal of Diseases 2010; 208, DOI: 10.1186/1471-2334-10-208 Hepato- Gastroenterology 2011;1: 68-70. DOI 10.5005/ jp-journals-10018-1015 16. Safiullah ABM, Bhuiyan MMR, Miah MAR and Raihan ASMA. Prevalence of hepatitis C virus infection in rural 4. Zaki H, Darmstadt GL, Baten A, Ahsan CR, Saha SK. adult population of Bangladesh. Bangladesh Med Res Seroepidemiology of hepatitis B and delta virus infections Counc Bull 2009, 35: 30–32. in Bangladesh. J Trop Pediatr 2003, 49: 371–4. 17. Shirin T, Ahmed T, Iqbal A, Islam I, Islam N. Prevalence 5. Rumi MA, Begum K, Hassan MS, Hasan SM, Azam MG, and risk factors of hepatitis B virus, hepatitis C virus and Hasan KN, et al. Detection of hepatitis B surface antigen human immunodeficiency virus infections among drug in pregnant women attending a public hospital for addicts of Bangladesh. J Health Popul Nutr 2000; 18(3): delivery: implication for vaccination strategy in 145-150. Bangladesh. Am J Trop Med Hyg 1998, 59: 318–22. 18. Kim HC, Nam CM, Jee SH, Han KH, Oh DK, Suh II. 6. Ahmad Q, Chowdhury SG, Islam MN, Khan FD, Alam Normal serum aminotransferase concentration and risk MR, Miah AH. HBsAg amongst unscreened operated of mortality from liver diseases: prospective cohort study. patients. Bangladesh Med Res Counc Bull 1991, 17: BMJ 2004:328: 983. doi: 10.1136/bmj.38050.593634.63 11–6. 19. Kang HS, Um SH, Seo YS, An H, Lee KG, Hyun JJ, et al. 7. Sattar H, Islam MN. Hepatitis B virus markers among Healthy range for serum ALT and the clinical significance the prostitutes of Dhaka. Bangladesh Med Res Counc Bull of “unhealthy” normal ALT levels in the Korean 1996, 22: 8–11. population. J. Gastroenterol. Hepatol. 2011; 26: 292–9. 8. Mustafa M, Islam MN, Rahman M, Salauddin AK. 20. Chang Y, Ryu S, Sung E, Jang Y. Higher concentrations of Prevalence of hepatitis B surface antigen (HBsAg) among alanine aminotransferase within the reference interval parenteral drug abusers at Dhaka. Bangladesh Med Res predict nonalcoholic fatty liver disease. Clin. Chem. 2007; Counc Bull 1989, 15: 1–7. 53: 686–92.

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21. Pratt DS, Kaplan MM. Evaluation of abnormal liver- 30. Khan M, Haq S, Ahmed N, Matin MA. Etiology and clinical enzyme results in asymptomatic patients. N Engl J Med profile of hepatocellular carcinoma in Bangladesh. 2000; 342: 1266–71. Bangladesh Med Res Counc Bull 1997; 23: 16-24. 22. Schwimmer JB, Dunn W, Norman GJ, Pardee PE, 31. Gibney L, Macaluso M, Kirk K, Hassan MS, Schwebke J, Middleton MS, et al. SAFETY study: alanine Vermund SH, et al. Prevalence of infectious diseases in aminotransferase cutoff values are set too high for reliable Bangladeshi women living adjacent to a truck stand: HIV/ STD/hepatitis/genital tract infections. Sex Transm Infect detection of pediatric chronic liver disease. 2001, 77: 344–50. Gastroenterology 2010;138: 1357-1364, 1364 e 1351- 1352. doi: 10.1053/j.gastro.2009.12.052 32. Kim WR, Flamm SL, Di Bisceglie AM, Bondenheimer HC. Public Policy Committee of the American Association 23. Van der Poorten D, Kenny DT, Butler T, George J. Liver for the Study of Liver Disease. Serum activity of alanine disease in adolescents: a cohort study of high-risk aminotransferase (ALT) as an indicator of health and individuals. Hepatology 2007; 46: 1750-1758. doi: disease. Hepatology 2008; 47: 1363-1373. 10.1002/hep.21918 33. Puoti C, Magrini A, Stati T, Rigato P, Montagnese F, 24. Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Rossi P, et al. Clinical, histological, and virological features Vecchio E et al. Updated definitions of healthy ranges for of hepatitis C virus carriers with persistently normal or serum alanine aminotransferase levels. Ann Intern Med abnormal alanine transaminase levels. Hepatology 1997; 2002;137: 1–10. 26: 1393–8. 25. Deinhartd F. Serum markers of hepatitis viruses in natural 34. Wong VW, Wong GL, Tsang SW, Hui AY, Chan AW, Choi disease and after vaccination. Prog Liver Dis 1982, 7: PC, et al. Metabolic and histological features of non- 451–67. alcoholic fatty liver disease patients with different serum alanine aminotransferase levels. Aliment Pharmacol Ther 26. Islam MN, Islam KM, Islam N. Hepatitis-B virus infection 2009; 29: 387–96. in Dhaka, Bangladesh. Bangladesh Med Res Counc Bull 1984, 10: 1–6. 35. Park JY, Park YN, Kim DY, Paik YH, Lee KS, Moon BS, et al. High prevalence of significant histology in 27. Rumi MA, Siddiqui MA, Salam MA, Iqbal MR, Azam MG, asymptomatic chronic hepatitis B patients with genotype Chowdhury AK, et al. Prevalence of infectious diseases C and high serum HBV DNA levels. J Viral Hepat 2008; and drug abuse among Bangladeshi workers. Southeast 15: 615–21. Asian J Trop Med Public Health 2000, 31: 571–4. 36. Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma 28. Gibney L, Saquib N, Metzger J, Choudhury P, Siddiqui M, BC, et al. Virologic and histologic features of chronic Hassan M. Human immunodeficiency virus, hepatitis B, hepatitis B virus-infected asymptomatic patients with C and D in Bangladesh’s trucking industry: prevalence persistently normal ALT. Gastroenterology 2008; 134: and risk factors. Int J Epidemiol 2001, 30: 878–84. 1376–84. 29. Khan WI, Sultana R, Rahman M, Akhter H, Haq JA, Ali L, 37. Chang Y, Ryu S, Sung E, Jang Y. Higher concentrations of et al. Viral hepatitis: recent experiences from serological alanine aminotransferase within the reference interval studies in Bangladesh. Asian Pac J Allergy Immunol 2000, predict nonalcoholic fatty liver disease. Clin Chem 2007; 18: 99–103. 53: 686–92.

205 REVIEW ARTICLES Management of Sepsis: Recent Advancement MI PATWARYa, MZJ BARIb, IT ISHAc

Summary: multi organ failure (MOF). Making an early, accurate Sepsis is a systemic, deleterious host response to infection diagnosis of septic shock is the key to increasing survival leading to acute organ dysfunction secondary to documented rates. With no specific, effective anti-sepsis therapies or suspected infection and septic shock i.e. sepsis plus available, management focuses on haemodynamic hypotension not reversed with fluid resuscitation. Severe sepsis stabilization and rapid resuscitation, early source control, is a major healthcare problem with an extremely high adequate and appropriate antibiotics, organ support and mortality rate of 30-60% and it is one of the most common modulation of the septic responses are the cornerstones of reasons for critically ill patients to be admitted to an intensive treatment. care unit (ICU). Excessive inflammation and coagulation Key Words: Sepsis, severe sepsis, Septic shock. and suppression of fibrinolysis are the hallmarks of Sepsis. Our medical concern is to manage sepsis and to prevent (J Bangladesh Coll Phys Surg 2016; 34: 206-212)

Introduction: an effort to reduce the risk of death from sepsis, the Sepsis is defined as a severe infection with some degree Surviving Sepsis Campaign (SSC) was initiated in 2002 of associated organ dysfunction (i.e. presence of SIRS from the collaboration of the European Society of 1 in the setting of infection) and affects a large proportion Intensive Care Medicine (ESICM), the International of the critically ill population. In recent years, it has Sepsis Forum (ISF), and the Society of Critical Care become clear that perhaps the most important as•pect Medicine (SSCM). In 2004, the SSC produced the of the management of patients with sepsis is early ‘‘Surviving Sepsis Campaign guidelines for management recogni•tion so that administration of antibiotics, source of severe sepsis and septic shock,’’ one of the most control measures and effective resuscitation strategies can be started as soon as possible after onset. Early recognized consensus statements regarding the 1 management with adequate antimicro•bials and rapid treatment of sepsis (most recently updated in 2012). resuscitation to restore and stabilize hemodynam•ic This review will discuss the epidemiology, status has been shown to be associated with improved pathophysiology, and diagnostic and therapeutic out•comes.1-5However, diagnosis of sepsis is not always approach to patients with sepsis, severe sepsis, and easy, especially in critically ill patients with other septic shock in acute care settings. conditions and signs and symptoms that can mimic .4-6 severe infection Epidemiology: The morbidity and mortality of sepsis in low- and middle- Despite the documented impact of sepsis in developed income countries (LMICs) are believed to be countries, literature on its incidence, prevalence, and disproportionately high, due to environmental mortality in developing countries is sparse.8-11The degradation, widespread malnutrition, and higher rates global burden of sepsis lies in LMICs. As a surrogate 7-10 of bacterial, parasitic, fungal and HIV infection. In marker for sepsis, over 90% of worldwide deaths due to pneumonia, meningitis, and other infections occur in a. Prof. Dr. Md. Ismail Patwary, Professor, Department of less developed nations (specific etiology usually gram Medicine, Sylhet Women’s Medical College. b. Dr. Mohammad Zabed Jillul Bari, Assistant Professor, positive or gram negative septicemia and rarely fungi, Department of Medicine, Sylhet MAG Osmani Medical viruses). Globally, an estimated 70% of the 9 million College. annual neonatal and infant deaths are attributable to c. Dr. Ishrat Tahsin Isha, Assistant Registrar, Department of Medicine, Sylhet Women’s Medical College. sepsis, and more than half of these occur in Asia and Received: 9 Sept. 2015 Accepted: 4 Oct. 2016 Sub- Saharan Africa.9, 12-13 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Pathophysiology: directly involved the pathophysiology and occasionally In sepsis multiple organ dysfunction syndrome(MODS)- impaired the cellular or the organ function.1-3 [Ischemic encephalopathy, diminished myocardial Table-I contractility, ARDS, ATN, DIC, Hemorrhagic enteropathy, Cortical cell lipid depletion in adrenal gland SIRS criteria.1 etc.] appears to result from a cascade of organism-related factors, circulating immune or inflammatory mediators, Presence of two or more of the following; 0 0 diffuse endothelial cell injury, disturbed hemostasis or 1. Temperature ≥38 C (100.4 F) or ≤360 C (96.80 F) tissue/organ hypoperfusion, and microcirculatory 2. Heart rate >90/min abnormalities (microaggregation of microthrombi). In 3. Respiratory rate >20/min or patients with severe sepsis, derangements of PaCO2 <32 mm Hg inflammation and coagulation are tightly linked. Free 4. White blood cell count >12,000/ L–1 or radicals, superoxide’s, proteolytic enzymes are also <4000/ L–1

Table-II

Diagnostic Criteria for Sepsis:1

General variables Fever (> 38.3°C) Hypothermia (core temperature < 36°C) Heart rate > 90/min Tachypnea Altered mental status Significant edema or positive fluid balance (> 20 mL/kg over 24 hr) Hyperglycemia (plasma glucose > 140 mg/dL or 7.7 mmol/L) in the absence of diabetes Inflammatory variables Leukocytosis (WBC count > 12,000 ìL–1) Leukopenia (WBC count < 4000 ìL–1) Normal WBC count with greater than 10% immature forms Increased plasma C-reactive protein Increased plasma procalcitonin Hemodynamic variables Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40 mm Hg in adults ) Organ dysfunction variables Arterial hypoxemia (Pao2/Fio2 < 300) Acute oliguria (urine output < 0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase > 0.5 mg/dL or 44.2 ìmol/L Coagulation abnormalities (INR > 1.5 or aPTT> 60 s) Paralytic Ileus Thrombocytopenia (platelet count < 100,000 ìL–1) Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or 70 ìmol/L) Tissue perfusion variables Hyperlactatemia (> 1 mmol/L) Decreased capillary refill

207 Management of Sepsis: Recent Advancement MI Patwary et al.

Table-III

Severe Sepsis1

Sepsis-induced hypotension Lactate above normal limit (more than 1 mmol/L) Urine output < 0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation Acute lung injury with Pao2/Fio2 < 250 in the absence of pneumonia as infection source Acute lung injury with Pao2/Fio2 < 200 in the presence of pneumonia as infection source Creatinine> 2.0 mg/dL (176.8 ìmol/L) Bilirubin > 2 mg/dL (34.2 ìmol/L) Platelet count < 100,000 ìL Coagulopathy (INR> 1.5)

Clinical assessment: of organ dysfunction. During history taking, the focus should be on detecting 1-3, 14-17 risk factors for infection (such as age, chronic disease, Common laboratory studies include: immunosuppressive drugs, AIDS, preexisting • Complete blood count (white blood cell count comorbidities i.e. DM, Renal failure, bleeding disorder including a differential of subtypes and measure of bands, haemoglobin and haematocrit, platelets), etc.).Caution should be advised in geriatric patients, as they may not be able to communicate traditional • Chemistries(electrolytes, bicarbonate, creatinine, symptoms (e.g. dysuria in occult urinary tract infections). glucose), The physical examination should be used to identify • Prothrombin time (PT) possible foci of source control. A critical action at this • Liver transaminases, bilirubin, point is the measurement, documentation, and evaluation of vital signs, including temperature, blood • Arterial or venous blood gas analysis with the pressure (BP), heart rate (HR), respiratory rate (RR) and inclusion of a serum lactate level, oxygen saturation (if below 90% then supplemental • Urinalyses are of high-yield, particularly in patients Oxygen should be immediately applied). Repeated older than 65 recording of these parameters will be used to evaluate • Chest radiography is to identify sources of clinical improvement or deterioration and trigger specific pulmonary infection and causes of respiratory interventions.1, 14-15 distress, Consistently analyzing the vital signs for the presence • Cultures as clinically appropriate before antimicrobial of SIRS criteria in any possible patient with sepsis will therapy with no significant delay (> 45 minutes) in aid in the early recognition of critical illness. Importantly, the start of antimicrobials. At least 2 sets of blood vital sign derangements may be absent early in elderly cultures (both aerobic and anaerobic bottles) be patients. Specific physical exam findings that are obtained before antimicrobial therapy predictive of sources of infection include indwelling devices (e.g., intravascular or urinary catheters), rales, • Urine, pus, ascetic fluid, pleural fluid, may be sent abdominal tenderness, and evidence of CNS infection. for culture where appropriate A cardiovascular and volume status assessment, Treatment and management including auscultation, mucous membranes, skin colour General management: The key principles of management and turgor, peripheral pulses, capillary refill and edema of sepsis include early recognition, titrated fluid should be undertaken at this stage as well.1, 14-15 resuscitation, adequate source control, obtain blood Investigations: cultures prior to administration of antibiotics, administer Initial laboratory and radiographic testing is aimed at broad spectrum antibiotics, and organ support. Prompt locating a source of infection and identifying evidence recognition of the septic patient is critical, and early

208 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 localization along the sepsis spectrum of illness helps measurable endpoints at the 3- and 6-h marks.1Values to define the early goals of management. A key significantly below this may be suggestive of distinction should be made between sepsis and severe hypovolaemia and the potential need for additional fluid sepsis/septic shock (SS/SS), the latter of which are the resuscitation. This intervention alone has been shown focus of the Surviving Sepsis Campaign guidelines. It to reduce mortality.21-22In ProCESS trial; aggressive fluid is recommended that patients with SS/SS should resuscitation (an average of 4.4 L in the first 6 h in this undergo a protocol-driven approach which is suggested study) causes reduce mortality.20 by Rivers study in 2001 and supported by meta analysis Fluid selection: Crystalloids as the initial fluid of choice 18-19 in 2008. It is a goal-directed approach to therapy of in the resuscitation of severe sepsis and septic shock. SS/SS patients (early goal-directed therapy, EGDT) and Albumin is needed in the fluid resuscitation of severe demonstrates a 16% absolute reduction in sepsis and septic shock when patients require .18-19 hospitalmortality However, the ProCESS trial, a substantial amounts of crystalloids. Initial fluid challenge recent multicenter randomized trial of over 1300 patients or goal in patients with sepsis-induced tissue 20 demonstrated no such benefit. hypoperfusion is to achieve a minimum of 30 mL/kg of Initial resuscitation: The goals during the first 6 hrs of crystalloids.1, 21-22 1 resuscitation: Vasopressors: Vasopressor therapy initially to target a a) Central venous pressure 8–12 mm Hg mean arterial pressure (MAP) of 65 mm Hg b) Mean arterial pressure (MAP) e” 65 mm Hg .Norepinephrine as the first choice vasopressor. Epinephrine is added when an additional agent is needed c) Urine output e” 0.5 mL/kg/hr to maintain adequate blood pressure. Vasopressin 0.03 d) Central venous (superior vena cava) or mixed units/minute can be added to norepinephrine (NE) with venous oxygen saturation 70% or 65%, respectively intent of either raising MAP in refractory hypotension In patients with elevated lactate levels targeting and have beneficial hemodynamic and renal function 6 resuscitation to normalize lactate.1 effects .Dopamine is an alternative vasopressor to norepinephrine only in highly selected patients. Low- In such instances, a goal-directed approach to therapy dose dopamine should not be used for renal protection1 is recommended by consensus guidelines with

Table-IV

Surviving Sepsis Campaign Bundles1

To be completed within 3 hours: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate e” 4mmol/Lto be completed within 6 hours: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) > 65 mm Hg 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate > 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP) - Measure central venous oxygen saturation (ScvO2) 7) Remeasure lactate if initial lactate was elevated *Targets for quantitative resuscitation included in the guidelines are CVP of >8 mm Hg, ScvO2 of >70%, and normalization of lactate

209 Management of Sepsis: Recent Advancement MI Patwary et al.

Inotropic Therapy should be removed promptly. When infected A trial of dobutamine infusion 20 micrograms/kg/min be peripancreatic necrosis is identified, definitive administered or added to vasopressor in the presence intervention is best delayed until adequate demarcation of myocardial dysfunction or signs of hypoperfusion.1 of viable and nonviable tissues has occurred. Selective In a recent, multicenter trial comparing norepinephrine oral decontamination and selective digestive and dopamine, both were equally efficacious at reversing decontamination should be introduced to reduce the 1, 23 hypotension and there was no significant difference in incidence of ventilator-associated pneumonia. mortality, though there were more arrhythmias in the Corticosteroids 1 dopamine group. Intravenous hydrocortisone is not encouraged to treat Antimicrobial Therapy adult septic shock patients if adequate fluid resuscitation Administration of effective intravenous antimicrobials and vasopressor therapy are able to restore within the first hour of recognition of septic shock and hemodynamic stability. Corticosteroids were not shown severe sepsis is the norm. Initial empiric anti-infective to be beneficial in SS/SS and in fact, potentially worsened therapy should be one or more drugs that have activity outcomes. However, a later study by Annane et al against all likely pathogens (bacterial and/or fungal or demonstrated that patients with vasopressor- viral) and that penetrate inadequate concentrations into unresponsive septic shock when treated with low-dose tissues. Antimicrobial regimen should be reassessed hydrocortisone and fludrocortisones causes shock daily. Before starting antimicrobials blood /urine culture reversal and reduces mortality. However a follow-up large should be sent. Combination empirical therapy for multicenter trial (CORTICUS), showed that septic shock neutropenic patients with severe sepsis may be needed. patients who responded to vasopressors, did not show a 1, 24-28 Empiric combination therapy should not be administered survival benefit with low-dose steroids. for more than 3–5 days (till culture report comes) Blood Product Administration .Duration of therapy typically 7–10 days; longer courses Once tissue hypoperfusion has resolved, target may be appropriate in patients who have a slow clinical hemoglobin is 7.0 –9.0 g/dL in adults. In patients with response. Antiviral therapy may be initiated as early as severe sepsis, administer platelets when counts are possible in patients with severe sepsis or septic shock <10,000/mm3 in the absence of apparent bleeding. of viral origin.1 Prophylactic platelet transfusion is advised when The choice of empirical antibacterial therapy varies counts are < 20,000/mm3 if there is a significant risk of significantly based on patient characteristics. Important bleeding. Platelet counts (e”50,000/mm3) are advised considerations include the most likely source(s) of for active bleeding, surgery, or invasive procedures .1 infection, recent antibiotics (last 3 months), recent health care exposure (e.g., hospitalization), underlying chronic Glucose Control disease, local pathogens and drug resistance. Patients Insulin should be started when 2 consecutive blood with recent antibiotic exposure have an elevated glucose levels are>10mmol/L (>180mg/dl) in ICU patient incidence of high-risk infections such as methicillin- with severe sepsis. Blood glucose values should be resistant Staphylococcus aureus (MRSA) and monitored every 1–2 hrs until glucose values and insulin 1 Pseudomonas aeruginosa, whereas those with recent infusion rates are stable and then every 4 hrs thereafter. healthcare exposure have increased likelihood of being In resource-limited settings, check blood glucose levels colonized with extended spectrum beta-lactamase in all patients. In the presence of mild hyperglycaemia, (ESBL)-producing bacteria.1 one should be careful about precipitating hypoglycaemia by insulin which may be more harmful.2 Source Control A specific anatomical diagnosis of infection requiring Renal Replacement Therapy consideration for emergent of source control. If Renal replacement therapies and intermittent intravascular access devices or indwelling catheter are hemodialysis may be required in patients with a possible source of severe sepsis or septic shock, they Bicarbonate Therapy. Sodium bicarbonate is not

210 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 recommended in patients with hypoperfusion-induced Supporting evidence lactic acidemia when pH is ≥7.1. Administration of human recombinant activated protein C is no longer recommended. The drug failed to show a Deep Vein Thrombosis Prophylaxis survival benefit for patients with severe sepsis and Patients with severe sepsis should receive prophylaxis septic shock .1 against venous thromboembolism (VTE) with daily subcutaneous LMWH. Combination of pharmacologic Conclusion: therapy and intermittent pneumatic compression devices Severe sepsis is a major healthcare problem with an may be needed.1 extremely high mortality rate of 30-60%. Consensus guidelines exist with specific recommendations for a Stress Ulcer Prophylaxis bundled approach to the treatment of septic patients, H2 blocker or proton pump inhibitor should be given to and in particular, those with SS/SS. Our medical concern patients with severe sepsis/septic shock with bleeding is to manage sepsis and to prevent MOF. Early sepsis risk.1 recognition (e.g. serum lactate measurement), Mechanical Ventilation of Sepsis-Induced Acute optimization of oxygen delivery (e.g. fluid resuscitation Respiratory Distress Syndrome (ARDS) and vasopressors) and infection treatment (e.g. Target tidal volume of 6 mL/kg body weight is appropriate antibiotics and infection control, preceded recommended in patients with sepsis-induced ARDS. by blood cultures) may result in a significant reduction Positive end-expiratory pressure (PEEP) should be in mortality and morbidity. applied to avoid alveolar collapse at end expiration. References: Mechanically ventilated sepsis patients should be 1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, maintained with the head of the bed elevated to 30-45 Opal SM, et al. Surviving sepsis campaign: international degrees to limit aspiration and to prevent ventilator- guidelines for management of severe sepsis and septic associated pneumonia.1, 29 shock. Crit Care Med 2013; 41:580–637. 2. Angus DC, van der Poll T. Severe Sepsis and Septic Shock. The inflammatory response to sepsis can cause lung N Engl J Med 2013; 369:840-51 injury and the development of ARDS. In a landmark 3. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, multicenter randomized trial of lung-injured patients, Cook D,et al. 2001 SCCM/ESICM/ACCP/ATS/SIS those who underwent mechanical ventilation had a 9% international sepsis definitions conference. Crit Care absolute reduction in mortality.29-30 Med 2003; 31: 1250–56. Immunoglobulins and Selenium 4. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for Intravenous immunoglobulin and selenium is not sepsis and organ failure and guidelines for the use of recommended in adult patients with severe sepsis or innovative therapies in sepsis. Crit Care Med 1992; septic shock..1 20:864–74. Sedation, Analgesia, and Neuromuscular blockade in 5. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR et al. Epidemiology of severe sepsis Sepsis in the United States: analysis of incidence, outcome, and Continuous or intermittent sedation should be minimized associated costs of care. Crit Care Med 2001; 29:1303– in mechanically ventilated sepsis patients. 1310. Neuromuscular blocking agents (NMBAs) should be 6. Nguyen HB, Smith D. Sepsis in the 21st century: recent avoided in the septic patient without ARDS.1 definitions and therapeutic advances. Am J Emerg Med 2007; 25:564–571. Nutrition 7. Cheng AC, West TE, Peacock SJ. Surviving sepsis in Initiate oral or enteral feedings rather than either developing countries. Crit Care Med 2008; 36(8): complete fasting or only intravenous glucose within 2487-8. the first 48 hours. Avoid full caloric feeding in the first 8. Cheng AC, West TE, Limmathurotsakul D, Peacock SJ. Strategies to reduce mortality from bacterial sepsis in week rather low dose feeding (up to 500 calories per adults in developing countries. PLoS Med 2008; 5: 1 day), gradually increasing as tolerated is recommended. 175-80

211 Management of Sepsis: Recent Advancement MI Patwary et al.

09. Baelani I,Jochberger S, Laimer T,OtienoD,Kabutu J, Wilson 20. ProCESS Investigators. Yealy DM, Kellum JA, Huang I, et.al. Availability of critical care resources to treat DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized patients with severe sepsis or septic shock in Africa: a trial of protocol-based care for early septic shock. N Engl self-reported, continent-wide survey of anaesthesia J Med 2014; 370: 1683–93. providers. Crit Care 2011; 15:R10. 21. Vincent JL, Gerlach H. Fluid resuscitation in severe sepsis 10. Black RE, Cousens S,Johnson HL, LawnJE, Rudan I, and septic shock: an evidence-based review. Crit Care Bassani DG, et al. Global, regional, and national causes of Med 2004; 32:S451–54. child mortality in 2008: a systematic analysis. Lancet 22. Marik PE, Monnet X, Teboul JL. Hemodynamic 2010; 375 (9730): 1969–87. parameters to guide fluid therapy. Ann Intensive Care 11. Zambon M, Ceola M, Almeida-de-Castro R, Gullo A, 2011; 1:1. Vincent JL. Implementation of the surviving sepsis campaign guidelines for severe sepsis and septic shock: 23. Marshall JC, Maier RV, Jimenez M, Dellinger EP, et al. we could go faster. J Crit Care 2008; 23:455–60. Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med 12. Jawad I, Lukšiæ I, Rafnsson SB. Assessing available 2004; 32(11 Suppl.): S513–26. information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Global Health 2012; 24. Guidet B, Martinet O, Boulain T, Philippart F, Poussel JF, 2: 010404. Maizel J, et al. Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs. 0.9% NaCl 13. Dünser MW, Festic E, Dondorp A, Kissoon N, Ganbat T, fluid replacement in patients with severe sepsis: the KwizeraA, et al. Recommendations for sepsis CRYSTMAS study. Crit Care 2012; 16: R94. management in resource-limited settings. Intensive Care Med 2012; 38:557–74. 25. Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, Åneman A, et al. Hydroxyethyl starch 14. Cohen J, Brun-Buisson C, Torres A, Jorgensen J. Diagnosis 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl of infection in sepsis: an evidence-based review. Crit Care Med 2004; 32(11 Suppl.):S466–94. J Med 2012; 367: 124–34. 15. Maki DG, Kluger DM, Crnich CJ. The risk of blood stream 26. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, infection in adults with different intravascular devices: a Lansang MA, et al. Corticosteroid treatment for sepsis: a systematic review of 200 published prospective studies. critical appraisal and meta-analysis of the literature. Crit Mayo Clin Proc 2006; 81:1159–71. Care Med 1995; 23:1430–9. 16. Lamy B, Roy P, Carret G, Flandrois JP, Delignette-Muller 27. Annane D, Sébille V, Charpentier C, Bollaert PE, François ML. What is the relevance of obtaining multiple blood B, Korach JM, et al. Effect of treatment with low doses samples for culture? A comprehensive model to optimize of hydrocortisone and fludrocortisone on mortality in the strategy for diagnosing bacteremia. Clin Infect Dis patients with septic shock. JAMA 2002; 288:862–71. 2002; 35:842–50. 28. Sprung CL, Annane D, Keh D, Moreno R, Singer M, 17. Nguyen HB, Kuan WS, Batech M, Shrikhande P, FreivogelK, et al. Hydrocortisone therapy for patients Mahadevan M, Li CH, et al. Outcome effectiveness of with septic shock. N Engl J Med. 2008 Jan 10; 358: 111- the severe sepsis resuscitation bundle with addition of 24 lactate clearance as a bundle item: a multi-national 29. Ventilation with lower tidal volumes as compared with evaluation. Crit Care 2011; 15:R229. traditional tidal volumes for acute lung injury and the 18. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, acute respiratory distress syndrome. The Acute KnoblichB, et al. Early goal-directed therapy in the Respiratory Distress Syndrome Network. N Engl J Med. treatment of severe sepsis and septic shock. N Engl J Med 2000 May 4; 342: 1301-1308. 2001; 345: 1368–77. 30. Drakulovic MB, Torres A, Bauer TT, Nicolas JM, Nogué 19. Jones AE, Brown MD, Trzeciak S, Shapiro NI, Garrett JS, S, Ferrer M, et al. Supine body position as a risk factor for Heffner AC, et al. The effect of a quantitative nosocomial pneumonia in mechanically ventilated resuscitation strategy on mortality in patients with sepsis: patients: a randomized trial. Lancet 1999 Nov 27; a meta-analysis. Crit Care Med 2008; 36: 2734–9. 354(9193):1851-58.

212 CASE REPORTS Transient Acute Myeloid Leukemia in a Newborn with Down’s Syndrome ZSM HAQUEa, N JAHANb, BK RAHAc, M HASANd, M BEGUMe, AWS ROBf, S YASMINg, SKA HASNATh, T FARHANAi

Summary: persisted for 4 weeks, after which the hemogram and the We report the case of a newborn with Down's syndrome differential WBC count returned to normal and a final associated with transient acute myeloid leukemia (AML). The diagnosis of transient acute myeloid leukemia was made. Only leukemic presentation resolved spontaneously without treatment few cases of congenital leukemia with Down's syndrome have just 4 weeks after birth. A 2 days old newborn presented with been reported in the literature. In Down's syndrome, AML respiratory distress, lethargy, poor suck and mild whether transient or not, generally shows cytogenetic and hepatosplenomegaly with features of Down's syndrome. Total molecular aspects that differ from those of adult acute leukemias. white cell count was 144,000/cmm with blasts 92%. Other Septic Key words: Down's syndrome, Transient myeloproliferative work up was negative. Peripheral blood smear revealed hyper disease, Transient leukemia. leukocytosis and presence of blast cells. Flow cytometric analysis (J Bangladesh Coll Phys Surg 2016; 34: 213-217) revealed acute myeloid leukemia. The peripheral blast cells

Introduction: of newborn infants. Because the leukemic picture Down's syndrome (DS) or constitutional trisomy 21 was resolves spontaneously, the disorder has been called linked to leukemia for the first time in a case report transient myeloproliferative disorder (TMD), transient published in 19301.The incidence of acute leukemia in blastemia, or transient abnormal myelopoesis. Now the patients with DS is 14 times higher than in unaffected disease is commonly referred to as “transient leukemia” children, and the disease is mainly myelogenous2. (TL). Typically, TL is diagnosed in clinically normal Transient abnormal myelopoesis is almost unique to children with DS via the casual detection of leukocytosis with circulating blast cells. The characteristic feature of Down's syndrome, and probably occurs in about 10% transient leukemia in DS patients is that the TL a. Prof. Zabrul SM Haque, Professor of Neonatology, Ad-din disappears on its own without treatment in just a few Medical College Hospital, Dhaka, Bangladesh. months. The typical and persistent spontaneous b. Dr. Nasim Jahan, Assistant Professor of Neonatology, Ad- remission of the leukemic presentation in 4 to 6 weeks din Medical College Hospital, Dhaka, Bangladesh. suggests a transient disruption of the granulocytopoietic c. Dr. Biplob Kumar Raha, Assistant Professor of Neonatology, 3 Ad-din Medical College Hospital, Dhaka, Bangladesh. system . The TMD is a clonal disease characterized by d. Dr. Mahmuda Hassan, Associate Professor of Neonatology, accumulation of immature megakaryoblast in fetal liver Ad-din Medical College Hospital, Dhaka, Bangladesh. and peripheral blood, a picture indistinguishable from e. Dr. Mariam Begum, Assistant Professor of Neonatology, AL4, 5, 6. We report the case of Down's syndrome with Ad-din Medical College Hospital, Dhaka, Bangladesh. f. Dr. AWS Rob, Assistant Professor of Neonatology, Ad-din transient acute leukemia presented in NICU at Ad-din Medical College Hospital, Dhaka, Bangladesh. Medical College Hospital. g. Dr. Sabina Yasmin, Indoor Medical Officer of Neonatology, Ad-din Medical College Hospital, Dhaka, Bangladesh. Case Report: h. Dr. SKA hasnat, Indoor Medical Officer of Neonatology, A term female baby born to 25 years old mother of non Ad-din Medical College Hospital, Dhaka, Bangladesh. consanguineous marriage by Lower Segment Ceasarian i. Dr. Tasnim Farhana, Indoor Medical Officer of Neonatology, Ad-din Medical College Hospital, Dhaka, Section (LUCS) due to maternal Gestational Diabetes Bangladesh. Mellitus (GDM). There was no history of cytotoxic Address of Correspondence: Dr. Nasim Jahan, Assistant drug intake or exposure to radiation during antenatal professor, Department of Neonatology, Ad-din Medical College Hospital, Dhaka. Mob. 01757078207, Email: [email protected] period. Special emphasis was given to elicit the history Received: 25 September 2013 Accepted: 6 April 2016 of maternal fever, rash or lymphadenopathy in the Transient Acute Myeloid Leukemia in a Newborn with Down's Syndrome ZSM Haque et al. mother in the first trimester to rule out intrauterine decreased. Flow cytometric analysis reveals acute infection. Her birth weight was 3.3 kg, and APGAR myloid leukemia; overall findings are suggestive of score was 8/10 and 9/10 at one and five minutes acute myeloid leukemia without maturation. Exchange respectively. On 2nd day the baby developed difficulty transfusion was done on day 8. Total WBC count in breathing. Her respiratory rate was 70/min, Heart was reduced to 37,620/cmm. The infant was followed rate was 180/min, no cyanosis was observed and SpO2 and monitored without any specific treatment for >95% with 2L O2 by nasal cannula, and temperature leukemia. The peripheral blast cells persisted for 4 was with in normal limit. No lymph nodes were palpable. weeks, after which the hemogram and the differential Physical examination revealed features of Down's WBC count returned to normal (WBC- 19,770/ cu mm, syndrome (dysmorphic facies, epicanthic folds, Hb 8.2, PC- 68,000/cu mm), and peripheral blast cells hypotonia, and simian crease in hands). She was disappeared. Respiratory distress improved in course tachypnic, berath sound vesicular with no added of time with restriction of the fluid and lowering of sound. Her blood pressure of all four limbs were within leucocytes number possibly had affect on normal limits, there was a systolic murmur over left improvement of vitals. The case was labeled as lower sternal area. Abdomen was distended with Transient Acute Myeloid leukaemia (AML). hepato-splenomegaly, Liver was palpable 4 cm from Karyotyping showed Triosomy 21. Bone marrow right costal margin at mid clavicular line and spleen morphology and Cytogenetic studies and serial blood was 3 cm below left costal margin. A clinical diagnosis counts were suggested. The baby also had congenital of Down's syndrome with congenital heart disease was heart disease and intestinal obstruction. Surgical made. Total white cell count was 145000/cmm with consultation was taken for double bubble appearance blasts 92%. Peripheral smear revealed Anisocytic with of the abdominal X-ray and surgical intervention anisochromic RBC morphology. WBC was increased could not be taken due to poor general condition of in number with shift to the lef, majority cells were the baby. We also planned to do the Echo cardiogram immature mononuclear cells, morphologically wich finally could not be performed in our center for resembling blast, Platelet was normal initially then the mechanical dysfunction of the machine.

Table-I

Serial lab report

Investigations Day 1 Day 4 Day 7 Day 9 Day 12 Day 15 Day 19 Day 22 Day 32 (‘post exchange) WBC (/cmm) 121,91 134,600 145,000 37,620 60,500 40,970 24,530 19,770 13,140

Atypical cell 70% 82% 92% 50% 50% 30% 25% 0%

Hb% 14.4 14.3 12.5 11.9 14.5 13.8 11.6 8.2 10.1

Platelets (/cmm) 283,000 220,000 196,000 141,000 144,000 187,000 35,000 68,000 26,000

X-ray abdomen Double bubble shadow

USG of abdomen Hepatic calcification , Bilateral echogenic kidney

Flow cytometry Blasts are positive for CD34, CD33, CD41, CD61, glycophorin A, and often CD7 and CD36.

214 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Fig. -1: Chromosome analysis (Karyotype): Trisomy 21

215 Transient Acute Myeloid Leukemia in a Newborn with Down's Syndrome ZSM Haque et al.

Fig.-2: Flow cytometry:

Fig.-3: Peripheral Blood film showing Blast cells

216 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Discussion: Conclusion: The diagnosis of TMD usually occurs during the first The course of congenital leukemia is one of rapid weeks after birth and is observed as hydrops fetalis. deterioration and death from hemorrhage and infection. The elevated blood count associated with hepatomegaly While diagnosing congenital leukemia, the condition of is the common symptom in an asymptomatic neonate. transient leukemia in Down's syndrome should always Infants with TMD can also display occasionally be kept in mind as the later entity is associated with jaundice and bleeding diastheses, respiratory distress complete remission. coupled with ascites, pleural effusion, signs of heart References: failure, and skin infiltrates. There is megakaryocytic 1. Cannon HE. Acute lymphatic leukemia: report of a case infiltration and liver fibrosis, likely caused by excess in an eleventh month Mongolian idiot. New Orleans Med cytokines secreted from the megakaryoblasts. The full Surg J 1930; 94(3):289–93. clinical TMD may develop only at the second or third 2. Kojima S, Matsayama T, Sato T. Down’s syndrome and week of life. Laboratory tests are significant for either acute leukemia in children: an analysis of phenotype by thrombocytosis or thrombocytopenia accompanied by use of monoclonal antibodies and electron microscopic elevated leukocytes with excess of blasts.This findings platelet peroxidase reaction. Blood 1990;76:2348-2353. consistant with our case.The cause of thombocytopenia 3. Coulombel L, Derycke M, Villeval JL. Characterization after two weeks of life could be due to direct effect of of the blast cell population in two neonates with Down’s leukemia on the bone morrow of the baby or could be syndrome and transient myeloproliferative disorder. Br J Haematol 1987;66: 69-76. sepsis which was clinicaly evident with negative blood culture result. Also hypersplenia could have contribution 4. Hitzler J.K, Cheung J, Li Y, Scherer S.W, Zipursky A. GATA1 mutations in transient leukemia and acute to thrombocytopenia in our case. The differential megakaryoblastic leukemia of Down's syndrome Blood diagnosis includes leukoerythroblastic reaction 2003;101(11):4301-4304. associated with prematurity, sepsis, or asphyxia. 5. Malinge S, Izraeli S, Crispino J.D. Insights into the However, the blasts of TMD usually persist for several manifestations, outcomes, and mechanisms of weeks, and GATA1mutations are invariably found5. Flow leukemogenesis in Down's syndrome. Blood 2009; cytometry reveals that blasts are positive for CD34, 113(12):2619–2628. CD33, CD41, CD61, glycophorin A, and often CD7 and 6. Pine S.R, Guo Q, Yin C, Jayabose S, Druschel C.M, CD365,7. Savasan & Ravindranath (2003) observed that Sandoval C. Incidence and clinical implications of GATA1 blasts of DS children with AMKL express CD36, in mutations in newborns with Down's syndrome. Blood 2007; 110(6): 2128-2131. contrast to the low or no expression of CD36 in AML without DS8. If 25% of blast cells are not detected, the 7. Langebrake C, Creutzig U, Reinhardt D. Immuno- phenotype of Down's syndrome acute myeloid leukemia diagnosis of AMKL can be given by the megakaryocytic and transient myeloproliferative disease differs markers CD41, CD61 and CD42a. The immunophenotype significantly from other diseases with morphologically of the blasts in AMKL is generally similar to TMD, except identical or similar blasts. Klinische Pädiatrie 2005 that the percentage of CD34 cells may be lower in AMKL ;217(3): 126-134. 5,6,. In our case flow cytometric analysis reveals CD13, 8. Savasan S.B.S, Ravindranath Y. Cd36 Expression Is CD33, CD36, CD117, MPO myeloid markers &CD34 & Associated With Superior In Vitro Ara-C Sensitivity In CD45 are positive. Several treatment approaches have Acute Megakaryocytic Leukemia With And Without Down's Syndrome.Medical and Pediatric Oncology been used, including exchange transfusion, 2003;41(10):274-275. leukapheresis, and low dose cytarabin 9. Exchange 9. Al-Kasim F, Doyle JJ, Massey GV. Incidence and treatment transfusion was done in our case. Although baby of potentially lethal diseases in transient leukemia of recovered from leukemia but was expired from sepsis in Down's syndrome: Pediatric Oncology Group Study. J another hospital at 56 days of age. Pediatr Hematol Oncol 2002;24(1) : 9-13.

217 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 Laparoscopic Management of Tubal Ectopic of Heterotopic Pregnancy E SAHAa, J DASb, M MONIRUZZAMANc, CR BACHERd

Summary: some precautions during laparoscopic procedure & post A heterotopic pregnancy is a rare complication of pregnancy operative period which can help for continuation of in which both extra-uterine (ectopic pregnancy) and intrauterine pregnancy. In our clinical experience, this is intrauterine pregnancy occur simultaneously. The prevalence an extreme rare disorder and we feel interest to report this of heterotopic pregnancy is estimated at 0.6- 2.5: 10,000 case. A heterotopic pregnancy can result from a natural pregnancy. It is a challenge for obstetrician to manage the conception; it requires a high index of suspicious for early tubal pregnancy without interruption of intrauterine and timely diagnosis; a timely intervention can result in a pregnancy. Here we describe a case who had left tubal alive successful outcome of the intrauterine fetus. ectopic pregnancy & also intrauterine alive pregnancy Key words: Laparoscopic surgery, Tubal pregnancy, simultaneously after a natural conception. This patient was heterotopic pregnancy. managed successfully with laparoscopic left salpingectomy, and intrauterine pregnancy has been continuing. There are (J Bangladesh Coll Phys Surg 2016; 34: 218-221)

Introduction: pregnancy & also intrauterine pregnancy Heterotopic pregnancy is defined as the presence of simultaneously after spontaneous conception that was simultaneous pregnancies in two different implantation diagnosed by using two dimensional ultrasound sites. The most frequent observed manifestation is the (2DUS). In our clinical experience, this is an extremely presence of an intrauterine pregnancy and an ectopic rare disorder and we feel interest to report this case. pregnancy that is usually located in the uterine tube, Purposes of this case report is to review the diagnosis most commonly in its ampullary portion (80%)1. of a heterotopic pregnancy, management the tubal Abdominal pregnancy is a rare ,can present as extra pregnancy without interruption of intrauterine uterine portion of heterotopic pregnancy2. Cornual pregnancy, precautions to be taken during the surgical pregnancy was also reported. The prevalence of procedure & to mention post operative care to handle heterotopic pregnancy is estimated at 0.6 - 2.5 : 10,000 this type of case. pregnancy3. The incidence of heterotopic pregnancy is Case Report: around 1/30,000 in spontaneous pregnancy. This is an A 19 years old lady, housewife, married for 3 years, with increasingly common complication of assisted irregular menstrual cycle, seeking baby for 8 months reproductive technology. The incidence of those cases reported to a private outpatient clinic . Her clinical are greater ranging from 1/100 to 1/3,6004,5. diagnosis was Polycystic Ovarian Syndrome (PCOS) & Here we describe a case of heterotopic pregnancy she was advised to take folic acid & Metformin. After during first trimester who had left tubal alive ectopic few days, she presented with amenorrhea for 5 weeks, followed by scanty menstruation for 7 days. She gave a. Dr Eti Saha, Assistant professor( gynae ), Khulna Medical no history of nausea, vomiting or abdominal pain or College, Khulna. mastalgia. On examination, she was found b. Dr Jharna Das, Assistant professor, Institute of Nuclear, haemodynamically stable. After 10 days she felt nausea, Medicine and allied science, Khulna Medical College. her urine for pregnancy test was positive. On c. Dr Mollik Moniruzzaman, Consultant (anaesthesia); Transvaginal Ultrasonogram (TVS) she was diagnosed Shaheed SK Abu Naser, Specialised Hospital, Khulna. as a case of heterotopic pregnancy, both are viable about d. Dr Citta Ranjan Bachher, Director, Shibsha clinic, Khulna. 7 weeks 2 days duration, one is intrauterine and another Address for Correspondence: Dr. Eti Saha, 15/2,Ahsan Ahamed road, Khulna, Bangladesh. Mobile: 01715- 292641, is in left tubal area. Opinion from another sonologist email: [email protected] also gave the same report. After proper counseling Received: 30 April 2014 Accepted: 17 August 2016 laparoscopy was done. On laparoscopy uterus was Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

TVS report

found uniformly enlarged about 8 weeks size, right tube, Discussions: both ovaries were healthy and left tube swollen and Spontaneous heterotopic pregnancy is a rare clinical congested but not ruptured. Then left sided and potentially dangerous condition. It can be a life Salpingectomy was done without any manipulation of threatening condition and can be easily missed with the uterus. Post operatively her intrauterine pregnancy was diagnosis being over looked. The importance of early supported with inj. Human Chorionic Gonadotrophin diagnosis and treatment for the ectopic pregnancy and Dydrogesterone up to 14 week. Pregnancy was becomes clear because of the high risk of tubal rupture. continue upto term with satisfactory growth of fetus It is a challenge for obstetrician to manage the tubal and the patient was free of any complications. Patient pregnancy without interruption of intrauterine delivered a healthy female baby, there was no pregnancy. This case was diagnosed at 7 weeks which abnormality in baby. was intact and alive.

219 Laparoscopic Management of Tubal Ectopic of Heterotopic Pregnancy E Saha et al.

The early diagnosis of heterotopic pregnancy is often laparoscopy may reduce the risk of uterine irritability difficult because the clinical symptoms are lacking. by decreasing the need for uterine manipulation . Around 50% of heterotopic pregnancies are Decreased uterine irritability results in lower rates of asymptomatic. Common presenting symptoms and signs spontaneous abortion and preterm delivery14. are abdominal pain, adenexal mass, peritoneal irritation, Regardless of the surgical approach, the use of sutures enlarged uterus, hypovolaemic shock with or without or staples rather than electrocautery or intra myometrial vaginal bleeding6. injection of vasopressin – minimizes the risk of diminishing blood flow to the surviving intrauterine Diagnosing this clinical occurrence is a challenge, given 15 the complexity of the possible clinical and laboratory pregnancy, particularly during cornual resection . The manifestation. The recent advances of trans vaginal ectopic component in case of rupture is always treated sonography (TVS) helped in the early diagnosis of surgically and the intrauterine pregnancy is expected to heterotopic pregnancy. TVS has proven to be an continue normally. Exploratory laparotomy is appropriate invaluable tool in the diagnosis of this condition. The when a ruptured ectopic pregnancy is associated with typical image of heterotopic pregnancy on TVS are the severe intra abdominal haemorrhage. There are some presence of an intra uterine gestation with an ectopic precautions to be taken during surgery - the patient is 0 tubal pregnancy contained an embryo7 or a tubal ring placed supine in a 10 Trendelenburg position, Veress was present in which the tube had not ruptured, an needle inserted carefully into the abdomen to avoid adenexal mass with a concentric echogenic rim of tissue, perforating the gravid uterus, laparoscopy should be a gestational sac, surrounding a hypo echoic empty performed without the use of an intra cervical uterine centre,8 or there are no conclusive adenexal findings manipulator, choice of laparoscopic salpingostomy, and the diagnosis of ectopic pregnancy may be based salpingectomy or cornual resection depends on the on ultrasound features, such as “hematoperitoneum, location of the ectopic within the fallopian tube or its hematosalpinx and free fluid in the peritoneum or the remnant. 9 pelvis e.g. in the pouch of Douglas” . The sensitivity Conclusion: of TVS in diagnosing heterotopic pregnancy is only A heterotopic pregnancy can result from a natural 10 56% at 5-6 weeks . Even with TVS, the adenexal sac conception; it requires a high index of suspicious for can be mistaken for a hemorrhagic corpus luteum or early and timely diagnosis; a timely intervention can 1 ovarian cyst. If the â- hCG levels are higher for the result in a successful outcome of the intrauterine fetus. period of gestation with an intrauterine pregnancy, one Ultrasonographers must methodically examine the entire must look for a co existent tubal pregnancy11. So role of pelvic region, particularly in women who have had pelvic early transvaginal sonography & serum â- hCG level surgery, PID or who are conceiving after a workup to after missed periods help in early diagnosis. fertility. Early diagnosis is the key of successful The choice of surgical or medical treatment of treatment and delivery. heterotopic pregnancy depends upon the hemodynamic status of the patient and the expertise of the physician. References: The laparoscopic approach is technically feasible for 1. P. W. Callen, “Ultrasonography in obstetrics and gynecology,” in Ectopic Pregnancy, D. Levine, Ed., both cases without disrupting the course of an Saunders Elsevier, Philadelphia, Pa, USA, 5th edition pp. intrauterine pregnancy. In case the ectopic pregnancy 1020–1047. was detected early and was unruptured treatment 2. Michael D. Scheiber, Marcelle I. Cedars , Case Report: options include expectant management with aspiration Successful non-surgical management of a heterotopic and installation of potassium chloride or prostaglandin abdominal pregnancy following embryo transfer with into the gestational sac12. Systemic methotrexate or local cryopreserved–thawed embryos , Hum. Reprod. (1999) injection of MTX cannot be used in a heterotopic 14 (5): 1375-1377. doi: 10.1093/humrep/14.5.1375 pregnancy owing to its toxicity, although some authors 3. Bello GV, Schonolz D, Moshirpur J, et al.: Combined have used instillation of a small dose13. pregnancy: The Mount Sinai experience. Obstet Gynecol Surv 41:603 (1986). There are many advantages of laparoscopy in the 4. H. Fernandez and A. Gervaise, “Ectopic pregnancies after pregnant patient. The improved visualization in infertility treatment: modern diagnosis and therapeutic

220 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

strategy,” Human Reproduction Update, vol. 10, no. 6, monochorionic monoamniotic twin pregnancy: A case pp. 503–513, 2004. report. Perinat J 2006;14:96-100. 5. H. M. Xiao, F. Gong, Z. H. Mao, H. Zhang, and G. X. Lu, 11. Hassani KI, El Bouazzaoui A, Khatouf M, Mazaz K. “Analysis of 92 ectopic pregnancy patients after in vitro Heterotopic pregnancy: A diagnosis we should suspect fertilization and embryo transfer,” Journal of Central South more often. J Emerg Trauma Shock 2010;3:304. University, 2004;31(4): 584–587. 12. Lialios GA, Kallitsaris A, Kabisios T, Messinis IE. Ruptured 6. Reece EA, Petrie RH, Sirmans MF, Finster M, Todd WD. heterotopic interstitial pregnancy: rare case of acute Combined intrauterine and extrauterine gestations: a abdomen in a Jehovah2 s witness patient. Fertil Steril review. Am J Obstet Gynecol 1983;146:323-30. 2008;90:1200.e15-7. 7. Poujade O, Ducarme G, Luton D. Luton Cornual 13. Oyawoyea S, Chander B, Pavlovic B, Hunter J, Gandir heterotopic pregnancy: a case report. J Med Case Reports AA. Heterotopic pregnancy: successful management with 2009;3:7233 aspiration of cornual/interstitial gestational sac and 8. Fleischer AC, Pennell RG, McKee MS, Worrell JA, Keefe installation of small dose of methotrexate. Fetal Diagn B, Herbert CM, et al. Ectopic pregnancy: features at Ther 2003;18:1-4. transvaginal sonography. Radiology 1990;174:375-8. 14. SAGES GUIDELINES 23 - Laparoscopy and Trimester 9. Bourgon DR. Ectopic prgenancy. eMedicine. Available of Pregnancy. from: http://www.emedicine.com/radio/topic231.htm [last 15. Sherer DM, Scibetta JJ, Sanko SR. Heterotopic quadruplet accessed on 2008 Jan 15]. [last cited on 2005 Dec 5]. gestation with laparoscopic resection of ruptured 10. Dundar O, tutuncu L, Mungen E, Muhcu M, Yergok YZ. interstitial pregnancy and subsequent successful outcome Heterotopic pregnancy: Tubal ectopic pregnancy and of triplets. Am J Obstet Gynecol. 1995;172(1):216-217.

221 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 Marshall Syndrome or PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenopathy) Syndrome MUH BEGUM

Summary: ulcers in the tongue with inflamed tonsils, covered with Marshall Syndrome PFAPA (Periodic Fever, Aphthous thick exudates and pharyngeal wall was inflamed and Stomatitis, Pharyngitis, Adenitis) Syndrome is a chronic folliculated. There was just palpable liver. Laboratory condition, typically starting 2-5 years old, in which fever investigations performed but it was without serological occurs periodically (lasts for 3-7 days), accompanied by confirmation. Throat swab culture was negative. The child aphthous-like ulcers, pharyngitis and/or cervical adenitis. received steroid (Prednisolone) with favorable outcome. The patients have no clinical symptoms between episodes Subsequently, the patient presented with similar episodes and it is required to exclude all other diseases before of fever which disappeared within 24 hours of single dose confirming the diagnosis. The dramatic response to of prednisolone. After Ranitidine (H2 blocker) treatment with steroid helps diagnosing PFAPA. We are prophylaxis the patient remains asymptomatic for about presenting the case of an 8 years male patient, with the one and half years. With our best knowledge this is the first case report of Marshall Syndrome or PFAPA Syndrome history of recurrent episodes of fever (onset at the age of in Bangladesh. two), oral ulcer and difficulty in deglutition who constantly received antibiotic therapy and or antifungal Key Words: Marshall syndrome, PFAPA syndrome. prescribed by different doctors. Clinically the patient was (J Bangladesh Coll Phys Surg 2016; 34: 222-224) febrile, mildly pale, cervical lymphadenopathy, aphthous

Introduction: Case report: The Marshall Syndrome or PFAPA (Periodic Fever, An 8 years old boy reported to out patient department Aphthous stomatitis, Pharyngitis, and Adenitis) syndrome of Northern Private Medical College Hospital, Rangpur is a clinical entity that was first recognized by Gary Marshall, with the history of recurrent fever, oral ulcer and Alexander Lawton, and colleagues in 19871. It is difficulty in deglutition since 2 years of age. He characterized by an onset before the age of 5 years; quite experienced the similar attack every 2 to 3 months regularly recurring episodes of fever, with at least one of interval. Each episode was associated with high fever the three associated constitutional signs of aphthous (duration 2 to 3 days) and symptoms persist 7 to 8 days stomatitis, pharyngitis, or cervical adenitis without any with or without treatment. For last six years his parents signs of upper respiratory tract infection; completely took him repeatedly to ENT specialist and other different asymptomatic inter-febrile periods with normal growth and doctors including village doctors, general practitioners development and the exclusion of cyclic neutropenia, and specialized doctors. In each visit he was prescribed immunodeficiency and auto-inflammatory syndromes2. It with antibiotics, anti- pyretic, analgesics, and anti-fungal oral gel or antiseptic mouth wash. He was also treated usually begins between the ages of two and five years and with homeopathic medicine. This scenario created much attacks ceases before 10 years of age in most patients3. worry and apprehension to parents about their child. Many treatment have been used with variable results The boy has two other siblings, one brother and a sister, including antibiotics, non-steroid anti-inflammatory drugs, all are healthy. The boy was also worried and depressed acetylsalicylic acid, colchicine, antiviral medicines, steroids, about disease. His parents did not suffer from such cimetidine, and tonsillectomy1 physical illness. Clinically, the patient was weighed 16 kg, ill-looking, Address of Correspondence: Dr Most. Umme Habiba Begum, 0 Associate Professor, Department of Pediatrics, Rangpur depressed in mood, febrile (temperature 101 F), mildly Community Medical College, Rangpur. Mobile: 01712546647, pale, non tender discrete cervical (anterior chain) and 01521248085, e-mail: [email protected], [email protected] sub-mandibular lymphadenopathy. Examination of oral Received: 10 August 2014 Accepted: 17 February 2016 cavity and throat showed aphthous ulcers in base and Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

mg/dl (Normal- upto 6.0mg/dl). Throat swab culture was negative. Ultrasound of abdomen showed normal finding. He was prescribed with Prednisolone 1.5 mg/kg per day for five days and Ranitidine 5 mg/kg per day along with Paracetamol. Patient was followed up on second day and became afebrile on the same day after single dose of steroid therapy. He had almost remission of all other symptoms. After 2 months, patient again presented with similar symptoms and treated only with Prednisolone. The patient also reported after 5 months

with similar attack and he was given Ranitidine (H2- blocker) prophylaxis. He is symptom free now for about one and half years.

Discussion: The PFAPA syndrome is a chronic disease of unknown Fig.-1: Enlarged tonsils, aphthous ulcer and etiology. The diagnosis of this disease is difficult erythematous pharynx with exudates. because none of its clinical symptoms are pathognomic, and there is no specific biologic abnormality. The Table-I symptoms may mimic other recurrent fever4. It is typically started in young children, in which high fever occurs Diagnostic criteria for Marshall/PFAPA syndrome4 periodically at intervals of about 3–5 weeks, frequently (Source: Thomas et al. 1999 from; accompanied by aphthous ulcers, pharyngitis and/or www.orpha.net/PFAPA.pdf /January 2004) cervical adenitis5. The Marshall/PFAPA syndrome is defined clinically and diagnosis is made by exclusion. It Regularly recurring fever with an early age of onset (<5 has diagnostic criteria also (Table 1) 6. The origin of this years of age) syndrome is unknown. There is a slight male Symptoms in the absence of upper respiratory tract predominance but no predilection for a particular ethnic infection with at least one of the following clinical signs: or racial group. Familial cases are rare3. a) aphthous stomatitis In 1987, Marshall et al. reported a previously b) cervical lymphadenitis undescribed periodic fever syndrome of unknown cause c) pharyngitis in 12 children. These patients presented with febrile Exclusion of cyclic neutropenia episodes that recurred every 2 to 12 weeks. In all cases, Completely asymptomatic interval between episodes the onset of symptoms started before 5 years of age and the fever reached high temperature (40 to 41°C) Normal growth and development lasting approximately 5 days. Fever was associated with pharyngitis and stomatitis in 75% cases, cervical margins of tongue; both tonsils were inflamed, enlarged reactive adenopathies in 66.6% cases, and other minor and covered with thick exudates; pharyngeal wall was symptoms such as headache, abdominal pain, nausea, inflamed and folliculated. There was just palpable liver; vomiting, chills and malaise. None of these children were no other organomegaly or physical sign. The patient immunodeficient1. In a study, Tasher et al. identified was suspected as Marshall syndrome and investigation four different patterns in disease evolution. The most was done. Investigations showed, Hemoglobin -9.4 gm/ common pattern (42%) was characterized by episodes dl, ESR- 36 mm in 1st hour,TLC-10x109/L, N-51%, L-46%, becoming gradually shorter and less frequent over time. M-01%, E-02%; PBF- RBC series of cells were markedly A unique and common course was remissions and hypochromic, no evidence of hemolysis, white cells and relapses, reported in (26%) children. Remissions lasted platelet series were adequate and normal; CRP- <6.0 up to 3 years. No change in frequency was reported in

223 Marshall Syndrome or PFAPA (Periodic Fever, Aphthous Stomatitis MUH Begum et al.

28% children. The least common pattern (4%) was prednisolone (steroid) and Ranitidine (H2 blocker) are characterized by episodes becoming gradually more the therapeutic options currently used. But further frequent over time7. studies are needed to identify laboratory markers that There are no diagnostic tests for PFAPA syndrome. The would help to identify Marshall / PFAPA Syndrome patients and allow the best therapeutic approach to be diagnosis is based on clinical criteria and exclusion of defined. other possible causes of recurrent fever in children. During febrile attacks, patients present elevation of white References: blood cell (neutrophils) and of acute phase reactants8. 1. Marshall GS, Edwards KM, Butler J, Lawton AR; Syndrome Normal acute phase reactants are usually found during of periodic fever, pharyngitis, and aphthous stomatitis. J the inter-febrile periods. Procalcitonin levels, a Pediatr. 1987; 110:43-46. significant marker of bacterial infections do not usually 2. Susanna Esposito, Sonia Bianchini, Miriam Fattizzo, Elena Baggi, Paola Marchisio, Donato Rigante.The enigma of increase during febrile attacks, and serum levels of periodic fever, aphthous stomatitis, pharyngitis and immunoglobulins A, G and M are also normal. The results adenitis syndrome.J Pediatr Infect Dis;. 2014; 33 (6); of urine and blood cultures, chest radiography and liver 650-652 function test are normal. Only serum IgD level may be 3. Shai Padeh, Brezniak N, Zemer D, Pras E, Livneb A, slightly high9. The episodes are frequently associated Langevitz P, et al. Periodic fever with aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome; J Pediatr. with leukocytosis and an elevation in the ESR. The fevers 1999;135;98-101. are unresponsive to antibiotics and non-steroid anti- 4. Cazeneuve C, Genevieve D, Amselem S, Hentgen V, Hau inflammatory drugs. The use of oral prednisone controls I, Reinert P. MEFV gene analysis in PFAPA. J Pediatr. symptoms but does not prevent the next episode.4,10 2003;143:140-141. In our case, symptoms were started in 2 years of age 5. Thomas, Kenneth Tyson; Feder, Lawton, Edwards; Periodic fever syndrome in children; J Pediatr (Retrieved). with repeated relapses and short remissions. Patient 2008;135: 1–5. had typical clinical features of Marshall/PFAPA 6. Thomas KT, Feder HM, Lawton AR, Edwards KM; syndrome. There was no family history, genital ulcer, Periodic fever syndrome in children. J Pediatr 1999; arthritis, rash, peritonitis or pleurisy. Investigation 135; 15-21. showed normal finding except high ESR and low 7. D Tasher, E Somekh, and I Dalal; PFAPA syndrome: new hemoglobin. There was dramatic treatment response with clinical aspects disclosed. Arch Dis Child. 2006; 91: 981–984. prednisolone and remission for about one and half years after Ranitidine (H blocker) prophylaxis. 8. Cecilia Lazea, Rodica Manasia, Calin Lazar. Marshall 2 Syndrome –a challenge in medical practice. Pediatr Conclusion: Croat.2015; 59: 39-43 Marshall Syndrome should be suspected in children 9. Takao Yoshihara, Imamura T, Yokori K, Mayumi Shibata, Gen Kano, Shinya Osone. Potential use of procalcitonin with periodic fever associated with pharyngitis, cervical concentration as a diagnostic marker of the PFAPA adenitis and aphthous stomatitis. It has a considerable syndrome. Eur J Pediatr. 2007; 166;621-622 socioeconomic impact on families because of the 10. Feder HM Jr. Periodic fever, aphthous stomatitis, number of lost school, or working days, and the physical pharyngitis,adenitis: a clinical review of a new syndrome. and psychological costs of the disease. Use of oral J Pediatr. 2000;12: 253-256.

224 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 Postoperative Transient Intractable Hyperacusis in Posterior Cingulate Gyrus Lesion Causing Partial Complex Seizure FH CHOWDHURYa, MR HAQUEb

Summary: probably this is the first report of hyperacusis related to posterior A young man of 19 who underwent surgical excision of a cingulate gyrus surgery. small right posterior cingulate gyrus cystic lesion for complex Key Words: Posterior cingulate gyrus lesion, Complex partial partial seizure. Postoperatively he developed intractable hyperacusis and persisted for several days. Here we report the seizure, Hyperacusis. case of post operative intractable hyperacusis that developed after surgery in posterior cingulate gyrus and in the literature (J Bangladesh Coll Phys Surg 2016; 34: 225-227)

Introduction: antiepileptic (pre operatively he was on tab. Isolated lesion in cingulated gyrus causing partial carbamazepine 200mg two tab. 8hourly and tab seizure is not uncommon. Cingulate gyrus is an important phenytoin 100mg one tab. 8hourly).His hearing tests part of limbic system that deals with memory processing including Pure Tone Audiometry (PTA) were normal. and emotional aspects of sensory input to brain. There Interictal Scalp EEG reported abnormal electrical are some connections and association of cingulate discharge from right medial parietal cortex. MRI showed gyrus with hearing mechanism. Here we report transient a small (1x1.5x1.5 cm) cystic lesion on posterior cingulate intractable hyperacusis after surgical excision of a small gyrus on right side (Fig. 1A,B&C). On MRI middle ear lesion in right sided posterior cingulated gyrus through and internal ear anatomy was noirmal on both sides. inter hemispheric approach. The lesion was initially static for four years. Last follow- up MRI showed slight increase in size of the lesion. Case report: Then after counseling (regarding seizure and nature of A right handed young university student of 19 years lesion) we went for surgical excision. The operation was presented with complex partial seizure for 5 years. There performed under general anesthesia (Anaesthesia was was dizziness followed by paresthesias in left foot induced with thiopentone 300 mg and fentanyl 125 ìg. followed by unconsciousness (and fall) for 80-100 sec. Tracheal intubation was facilitated with suxamethonium There was no history of olfactory or auditory 90 mg. Anaesthesia was maintained with halothane in a hallucination, tonic-clonic events or bowel-bladder mixture of O2 and N2O in addition to intermittent doses incontinence. He had no history hearing disturbances, of vicuronium(0.1mg/kg) and fentanyl. Monitoring tinnitus or vertigo. Initially there was 1-3 attack of such parameters included were ECG, pulse oximetry , end- event per year that began to increase in frequency. The tidal capnography , arterial BP, central venous pressure frequency was 2-3 attack per month in the last year (CVP), and urine output. ) We removed the lesion before surgery. From the beginning he was on through interhemispheric approach after posterior parietal craniotomy extending on the both side of sagital 1. Dr. Forhad Hossain Chowdhury, Assistant professor, suture with right sided preponderance.Post operatively Neurosurgery, National Institute of Neurosciences and he was on inj.Phenytoin, inj ceftiraxone, inj.omeprazole Hospital, Dhaka, and diclofenac suppository. From 2nd post operative 2. Dr. Md. Raziul Haque, Associate professor, Dept. of Neurosurgery, Dhaka Medical college Hospital, Dhaka. day (POD) patient developed severe intractable hyperacusis. For which he had to isolate in a silent room Address Correspondence to: Chowdhury Forhad Hossain, Assistant professor, Neurosurgery, National Institute of where we communicated with very few words in very Neurosciences and Hospital, Dhaka, Bangladesh. Phone slow volume. Even then at that time he used to put a +8801711949570, e-mail- [email protected] cotton ball in both external acoustic canals. This Received: 28 July 2015 Accepted: 6 October 2016 hyperacusis persisted in same intensity for next five Postoperative Transient Intractable Hyperacusis in Posterior Cingulate FH Chowdhury & MR Haque

Fig.-1: MRI of brain T2W saggital (A), coronal (B) and axial (C) images showing posterior cingulate gyrus cystic Lesion. days. From 8th POD the intensity of hyperacusis began lobes, in all patients, sound elicited activation in the to decrease and it became tolerable on 12th POD and frontal lobes and occipital lobes. The parahippocampus hearing became normal on 21st POD. After operation he was activated in 2 of 3 patients. Furthermore, the was seizure free till last follow up (12 month after precentral and postcentral gyri, superior and inferior operation).In 1st six month after operation he was on parietal lobules, thalamus, midbrain, claustrum, insula, Tab. phenytoin 100 mg daily then it was stopped. His posterior cingulate gyrus, and orbital and rectal gyrus hearing was also normal at last follow up. were also activated in one patient. The neural network Histopathology reported grade 1 astrocytoma. associated with idiopathic hyperacusis might be associated with the frontal lobes and parahippocampus.3 Discussion: fMRI of brain showed threat-related words compared The five layered cingulate gyrus sits atop the corpus to neutral words activated left posterior cingulate gyrus callosum and can be broadly divided into two segments: in eighty percent person with activation most prominent the anterior cingulate (areas 24, 25, and 33) which is in the retrosplenial region.4 Epilepsy surgery for lesions concerned with vocalizing and emotional and motoric involving the cingulate gyrus represents a small fraction functioning involving the hands, and regulating of all epilepsy surgery cases, with good seizure outcome autonomic and endocrine activities; and the posterior and low rates of post-operative permanent deficits. Post (area 23) cingulate which is involved in visual-spatial operative complications includes temporary and tactile analysis as well as motor output and memory. postoperative supplementary motor area (SMA) The posterior cingulate gyrus is richly interconnected syndrome, mild hand or leg paresis, respectively. Post- with the superior parietal lobe (area 7) the operatively, 62% of patients were seizure-free and 76% parahippocampal (inferior) temporal and superior had a satisfactory seizure outcome .5Assessment of temporal lobe (area 22), frontal lobe, caudate, putamen, morbidity following resection of cingulate gyrus gliomas substantia nigra, pulvinar of the thalamus, and dorsal bt Tate MC et al6 demonstrated that 29% of patients hypothalamus.1 In addition, the posterior cingulate experienced a new or worsened neurological deficit projects to the red nucleus in the midbrain (which also immediately after surgery. The most common deficits receives frontal motor fibers) and to the spinal cord. were supplementary motor area (SMA) syndrome (20%), Cingulate gyrus contains fasciculum cingulum that form weakness (6%), and sensory changes (2%). SMA the Papez circuit and involved in memory mechanism.2 syndrome than patients with anerior cingulate gyrus The neural network associated with idiopathic lesion. Only 4% of patients had a persistent neurological hyperacusis is still not well known. Hwang JH et al3 deficit at 6 months postoperatively. A similar morbidity studied the brain activation of 3 middle-aged patients profile was observed in the subset analysis of patients with mild to moderate hyperacusis by functional with tumors confined to the cingulate gyrus, with no magnetic resonance imaging while they were listening additional morbidity related to known cingulate-specific to white noise binaurally. In addition to the temporal functions. Surgical morbidity is primarily a function of

226 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016 surgical trajectory rather than the particular cingulate the posterior cingulate gyrus connected to hearing region resected.6 von Lehe M, et al7 studied a series of cortex or hearing pathway that was stimulated by the glioma in cingulated gyrus where 18% of the tumor was surgery. If such an area was present, is it present in all located in the posterior (parietal) part of the cingulate human? Whether is it dormant or active? If dormant gyrus, and in 82% the tumor was in the anterior (frontal) when does it become active? What are the connecting part. In 26% cases the glioma was solely located in the tracts? Can it be applied for the treatment of deafness? cingulate gyrus, and in 74% the tumor extended to the Till today we do not know the answers. In future we supracingular frontal/parietal cortex. 61% cases had may get the answer. seizures as the presenting symptom, 24% suffered from Reference: a hemiparesis/hemihypesthesia, and 12% had aphasic 1. Deveinsky O.,Morrell MJ.,Vogt BA. Contributions of symptoms. Postoperatively, 34% cases suffered from a anterior cingulate cortex to behaviour. Brain 1995; transient supplementary motor area syndrome, all of 118:279-306 whom had tumors in the anterior cingulate gyrus. In the 2. Chowdhury FH & Khan AH. Papez Circuit: An Anatomical early postoperative period (30 days) a new deficit Study by Cadaveric Dissection. Pan Arab Journal of occurred in 13% cases (mild motor deficits or aphasic Neurosurgery 2010;14(2):75-80 symptoms). One patient had a major bleeding episode 2 3. Hwang JH., Chou PH., Wu CW., Chen JH., Liu TC. days after surgery and was in a persistent vegetative Brain activation in patients with idiopathic hyperacusis. state.7 American Journal of Otolaryngology - Head and Neck Medicine and Surgery2009;30, 432-434 Common causes of hyperacusis are head injury, ear 4. Maddock RJ, Buonocore MH. Activation of left posterior damage (i.e from barotrauma, sounds, toxins or cingulate gyrus by the auditory presentation of threat- medication), Middle ear pathology (i.e.infection, tumor related words: an fMRI study. Psychiatry Res. 1997 Aug & trauma and surgery), Lyme disease, air bag 8;75(1):1-14 deployment,viral infections involving the inner ear or 5. von Lehe M, Wagner J, Wellmer J, Clusmann H, Kral T. facial nerve (Bell’s palsy), temporomandibular joint Epilepsy surgery of the cingulate gyrus and the fronto- (TMJ) syndrome, William syndrome, multiple sclerosis, mesial cortex. Neurosurgery. 2011 Sep 23. [Epub ahead irritating lesion in hearing pathway. facial nerve palsy of print] above the geniculate ganglion of various etiologies. 6. Tate MC, Kim CY, Chang EF, Polley MY, Berger MS. Very rarely it can be occurred toxins and myopathy Assessment of morbidity following resection of cingulate 8 gyrus gliomas. Clinical article. J Neurosurg. 2011 involving stapedius muscle. Per operative or post Mar;114(3):640-7. Epub 2010 Oct 8. operative drugs that the patient received had no report 7. von Lehe M, Schramm J.Gliomas of the cingulate gyrus: to cause hyperacusis. In this case the cause of surgical management and functional outcome. Neurosurg hyperacusis was not understood by our acquired Focus. 2009 Aug;27(2):E9 knowledge. We think, in the cingulate gyrus of the 8. Baguley DM. Hyperacusis. J R Soc Med.2003; 96(12): patient there might be a hearing augmentation area in 582-585

227 IMAGES IN MEDICAL PRACTICE A Patient with Recurrent Hypokalaemia CS BALAa, I REZAb, MABI MOMENc, HAMN AHASANd

(J Bangladesh Coll Phys Surg 2016; 34: 228-230)

Fig.-1:

This is the CT Scan of abdomen of a patient who is 37 pain, dryness of mouth or grittiness of eye. She was not year-old lady presented with repeated episodes of high on any medication. Her urine analysis revealed plenty grade fever with chills and rigor, increase frequency of pus cell with few RBC but Urine Culture and sensitivity and burning sensation during micturation for one year. could not reveal growth of any organism. Neutrophilic She noticed frequent passage of small stone like particles leukocytosis was noted in full blood count. Renal for the last 3 months. She had profound generalized function test within normal limit. Her Potassium was weakness. She had history of similar episodes of disease 1.9mmol/Liter with raised Chloride (124 mmol/L) level and hospital admission one year back. and decreased bicarbonate level(21 mmol/L. Her Venous H On physical examination She was febrile and was so blood P was within 7.3. Her Urinary Potassium excretion weak to move her limbs. She had no history of joint was high (74.78 mmol/24 hours). Her serum calcium,

Phosphate and serum PTH were normal within limit. a. Dr. Chandra Shekhar Bala, Junior Consultant (Medicine), Plain X-ray KUB region showed bilateral renal NINS and Hospital. calcification. USG of whole abdomen showed multiple b. Dr Ishrat Reza, Registrar, Medicine, Popular Medical calculi mostly periphery of both kidneys. College, Dhaka. Ultrasonography could not opine conclusively whether c. Dr. Md A Basit Ibne Momen, Asstt Registrar(Medicine). it was multiple large calculi or medullary calcifications d. Prof. H.A.M. Nazmul Ahasan, Professor of Medicine, of both kidneys. Popular Medical College, Dhaka. Address of Correspondence: Dr. Chandra Shekhar Bala, Junior CT scan of abdomen showed symmetrical medullary Consultant (Medicine), NINS and Hospital. calcification of both kidney. Renal parenchyma shows Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Fig.-2: CT abdomen sagital view(on the left) and X-ray KUB (on the right) of the same patient.

normal width with normal size, shape and position of and ureteric colic. The condition can progress to chronic kidneys. Pelvicaliceal sytem is not dilated and have no kidney failure, and the prognosis depends on the calculus or mass lesion. underlying cause. Laboratory examinations may reveal microscopic pyuria even in the absence of urinary Acid load test revealed persistently raised urinary pH infection. This condition differs from kidney stones by (above 6.8) in the following eight hours after intake of the formation of calculi in the excretory tract. The ammonium chloride (0.1 mg/Kg body weight). In normal increase in calcium content in the kidneys occurs in individual it would have fall below 5.2 between 2nd and three phases (chemical, microscopic and macroscopic) 5th hour after ingestion of ammonium chloride . This is with different degrees of kidney damage. Macroscopic consistent with renal tubular acidosis. The final nephrocalcinosis is classified as cortical (3% of cases), diagnosis was Distal Renal Tubular Acidosis with medullary (97% to 98% of cases) or mixed (involving Nephrocalcinosis with recurrent Urinary tract Infection. the renal cortex and medulla).2 Discussion: Nephrocalcinosis can be detected using imaging Nephrocalcinosis is associated with generalized increase examinations such as radiography, ultrasound or in the concentration of calcium and the deposition of computed tomography. Axial computed tomography calcium salts in the renal parenchyma1. The most without contrast is considered adequate for common causes of this condition are primary differentiating cortical and medullary nephrocalcinosis hyperparathyroidism, renal tubular acidosis, medullary and demonstrating the relationship between sponge kidney, idiopathic hypercalciuria, hyperoxaluria calcifications in the parenchyma and the calyceal (primary, enteric or toxic), secondary hypercalcemia (sarcoidosis, neoplasm and osteoporosis) and drugs system, allowing the precise localization of the (including furosemide, acetazolamide and amphotericin calcifications. B) . This condition has no clinical symptoms in the early Nephrocalcinosis with low serum potassium is shrinks phase, except in cases of nephrolithiasis (kidney stone) the differentials to few conditions like Bartter’s

229 A Patient with Recurrent Hypokalaemia CS Bala et al. syndrome, Liddle syndrome, Primary hyperadrenalism and aldosterone stimulation.6 Hypercalciuria, and Distal Renal Tubular Acidosis(dRTA).3 This patient hyperphosphaturia, hypocitraturia and a high urinary has acidosis and increased urinary potassium excretion. pH are the main events that predispose RTA patients to Acid load test revealed inability to acidify urine following develop renal stones. Urinary citrate is an inhibitor of ammonium chloride intake. Thus we reached the final the crystal aggregation and precipitation. When citrate diagnosis of Distal Renal Tubular Acidosis(dRTA). We excretion is reduced, more calcium is chelated, thus 7,8 excluded other possible cause of nephrocalcinosis. aggravating urolithiasis and nephrocalcinosis. Distal RTA (RTA type I) is a rare disorder characterized References: by non-anion gap hyperchloremic acidosis and 1. Monk RD, Bushinsky DA. Nephrolithiasis and hypokalemia. In this condition, the alpha intercalated nephrocalcinosis. Johnson RJ, Feehally J, cells of the cortical collecting duct of the distal nephron eds. Comprehensive Clinical Nephrology. 2nd ed. Mosby; 2003. 731-4. fail to secrete acid into the urine. This failure of acid secretion leads to an inability to acidify the urine to a 2. Tasic V, Gucev Z. Nephrolithiasis and Nephrocalcinosis in Children - Metabolic and Genetic Factors. Pediatr pH <5.5. Because renal excretion is the primary means Endocrinol Rev. 2015 Sep. 13 (1):468-76. of eliminating acid from the body, there is consequently 3. Evan AP, Lingeman J, Coe F, et al. Renal histopathology a tendency towards systemic acidemia. This leads to of stone-forming patients with distal renal tubular the clinical features of RTA type I, which include: Normal acidosis. Kidney Int. 2007 Apr. 71(8):795-801 anion gap hyperchloremic metabolic acidosis; 4. Batlle D, Moorthi KM, Schlueter W, Kurtzman N. Distal Hypokalemia (from multiple mechanisms, but often renal tubular acidosis and the potassium enigma. Semin severe during periods of stress); Nephrocalcinosis; Nephrol 2006 Nov;26(6):471- 478. Nephrolithiasis (related to an inability to acidify urine); 5. Brenner RJ, Spring DB, Sebastian A, McSherry EM, Genant Hypercalciuria, and low urinary citrate); Loss of calcium HK, Palubinskas AJ, et al. Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis from bones (which can cause rickets in children and in various types of renal tubular acidosis. N Engl J Med 4 osteomalacia in adults). The clinical manifestations of 1982 Jul;307(4):217-221 RTA type I depend upon the disease type and severity 6. Blake-Palmer KG, Karet FE. Cellular physiology of the of the disease. Brenner et al. indicated that type I RTA renal H+ATPase. Curr Opin Nephrol Hypertens 2009 Sep;18(5):433-438 occurred more frequently in patients older than 18 years of age and had a female predominance.5 Hypokalemia 7. Rothstein M, Obialo C, Hruska KA. Renal tubular acidosis. Endocrinol Metab Clin North Am 1990 Dec;19(4):869- probably results from increased kaliuresis due to renal 887. tubular leakage, decreased proximal tubular 8. Simpson DP. Citrate excretion: a window on renal reabsorption in the face of acidosis and hypocapnia, metabolism. Am J Physiol 1983 Mar;244(3):F223-F234.

230 LETTER TO THE EDITOR

(J Bangladesh Coll Phys Surg 2016; 34: 231-132)

To We do agree with the limitations of the study as well as Editor-in-chief the recommendations made by the authors. Journal of Bangladesh College of Physicians and Never the less such studies are encouraging for the surgeons. future physicians to develop an antibiogram for CAP. Subject: Letter to editor on the original article “Clinical Thanking You Presentation of Bacterial Etiology of Adult Community Prof. (Dr.) S.M Hafiz Acquired Pneumonia. Professor of Medicine Dear Sir, Dhaka Medical College & We would like to thank Dr. Md. Abdus Salam, Dr. Md. Dr. Syed Zakir Hossain Robed Amin and Prof. Quazi Tarikul Islam through you Assistant Professor of Medicine for choosing an excellent topic for primary research work Dhaka Medical College on Clinical Presentation of Bacterial Etiology of Adult Community Acquired Pneumonia. Community acquired Dear Sir pneumonia (CAP), the sixth most common cause of death worldwide, represents a significant disease Thank you very much for your attention and critical burden for the community, particularly in the elderly. analysis of our original article “Clinical Presentation of From this study we came to know the bacterial etiology, Bacterial Etiology of Adult Community Acquired pattern of antibiotic sensitivity in CAP in our context. It Pneumonia which was published in june 2016 in JBCPS. is known that the role of empiric therapy in the In this observational study, we did not found any management of CAP is tremendous, as overall clinical correlation between the symptoms and signs of outcomes are the same for both pathogen directed pneumonia with specific bacterial organism. This treatment and empiric antibiotic treatment. It is observation was also seen in different studies in and praiseworthy that the researchers defined representative around Bangladesh in Asia1,2,3. This indicates that the sputum sample which should contain > 25 granulocytes prototype presentation of Pnuemonia cannot be and < 10 epithelial cells per low power field microscopic differentiated as per bacterial etiology through clinical view. We would be obliged if some of my quarries are presentation. addressed. From this study we could not correlate Your observation is correct that the cases admitted in between the clinical presentation and bacterial etiology. hospital with low CURB 65 may be indeed treated in For admission of a patient with CAP CURB-65 should community setting. But in our study we selected cases have a score of 2 or more. In this study more than 90% of pneumonia (Clinical and radiological consolidation of study subjects were in CURB-65 score 1, which proven) to identify the sensitivity pattern and not just essentially can be treated at the community level without selected cases who actually needed hospitalization for admission. The study also failed to show the resistant treatment. This selection is also to see the pattern of pattern of antibiotics in CAP. For empirical treatment of sensitivity and resistant of antibiotics in community the CAP in the community the knowledge of both cases as well as few hospital needed pneumonia cases. sensitivity and resistant pattern of antibiotics are essential. Last but not the least this study was conducted The study found around 53% cases of confirmed between January 2010 to December 2010 therefore may bacterial aetiology of CAP cases where Strep be well out of context from recent pattern of antibiotic Pneumonia is the commonest organism. If you follow sensitivity. We would like to draw the attention of the the discussion, you will find the resistant pattern has editor-in-chief in this regard. been mentioned. It was observed from this study that Letter to the Editor isolated Klebsiella strain was mostly resistant to We again appreciate your critical analysis on this commonly used antibiotics for CAP. Other isolated important paper and suggestions. We hope this organisms like Pseudomonas, Escherichia coli, were observational study would stimulate other researchers also resistant to B -lactamase inhibitor, Macrolides and to do study on CAP including clinical trial for evidence third generation cephalosporin. The good news is that based practice to develop in Bangladesh. the commonest organism of strep pneumonia is still Thanking you having sensitivity to commonly used antibiotics use in community (3rd generation cephalosporin and clarithromycin).But for gram negative cases, the study Dr. Md. Robed Amin showed sensitivity mostly to meropenam which is not Associate Professor included in the empirical treatment modality. So the gram Dhaka Medical College negative cases of pneumonia may need separate groups of drugs (including meropenam) if empirical treatment is References: 1. Ngeow YF, Suwanjuthab S, Chantarojanasririb T, Wangc chosen in community. F, Sanield M, Alejandriad M. An Asian study on the We are also concerned like you that the study showed prevalence of atypical respiratory pathogens in data of 2010 and in meanwhile the sensitivity and Community Acquired Pneumonia. International Journal of Infectious Diseases 2005;(9):144—153. resistant pattern may changes already. This 2. Ashraf H, Jahan SA, Alam NH, Mahmud R, Kamal SM.Day- observation actually seeks regular monitoring of care management of severe and very severe pneumonia, aetiology and sensitivity of antibiotics in Institution without associated co-morbidities such as severe malnutrition, based antibiogram which need to be established as in an urban health clinic in Dhaka, Bangladesh. Archives quickly as possible. Otherwise the empirical based Diseases of Children2008;93:490–494 selection would stimulate drug resistant pneumonia 3. Sohn JW, Park SC, Choi YH, Woo HJ, Chjo YK, Lee JS to develop in our country especially for Gram negative etal. Atypical pathogens as etiologic agents in Hospitalized patients with Community Acquired Pneumonia in korea:A organism and may also involve the commonest prospective multi-center study. Journal of Korean Medical organism of Strep Pneumonia. Science 2006

232 COLLEGE NEWS

(J Bangladesh Coll Phys Surg 2016; 34: 233-242)

College news Examinations news: Results of FCPS Part-I, Part-II and MCPS examination held in July are given bellow: 3248 candidates appeared in FCPS Part-I, examinatin held in July, 2016 of which 272 candidates came out successful. Subject wise results are as follows: Result of FCPS Part-I Examination (July, 2016)

SL. No. Subject July-2015 Total Candidate Total Passed Percentage % 1. Anaesthesiology 109 8 7.34 2. Biochemistry 5 0 0.00 3. Dentistry 193 3 1.55 4. Dermatology & Venereology 47 3 6.38 5. Family Medicine 2 0 0.00 6. Haematology 13 2 15.38 7. Histopathology 13 0 0.00 8. Medicine 920 59 6.41 9. Microbiology 16 1 6.25 10. Obst. & Gynae 704 105 14.91 11. Ophthalmology 84 21 25.00 12. Otolaryngology 89 4 4.49 13. Paediatrics 359 41 11.42 14. Physical Medicine & Rehabilitation 30 1 3.33 15. Psychiatry 6 2 33.33 16. Radiology & Imaging 34 4 11.76 17. Radiotherapy 35 7 20.00 18. Surgery 589 11 1.87 19 Transfusion Medicine Total 3248 272 8.37

The following candidates satisfied the Board of Examiners and are declared to have passed the FCPS - II Examinations held in July, 2016 subject to confirmation by the council of Bangladesh College of Physicians and Surgeons

Roll No. Name From where graduated Subject Roll No Name From Where Graduate Subject 130001 Umme Habiba Ferdaushi Sher-E-Bangla Medical College, Barisal Cardiology 140001 Md. Abdul Hannan MAG Osmani Medical College, Sylhet Cardiovascular Surgery 140002 Md Faizus Sazzad Dinajpur Medical College, Dinajpur Cardiovascular Surgery 170001 Hurjahan Banu Khulna Medical College, Khulna Endocrinology and Metabolism 550001 Dr. Mst. Tajmira Sultana Sir Salimullah Medical College, Dhaka Feoto-Maternal Medicine College News

Roll No. Name From where graduated Subject

290001 Md. Shariful Islam Shaheed Ziaur Rahman Medical College, Bogra Neuro-Surgery 290002 Patoary Mohammed Faruque Sir Salimullah Medical College, Dhaka Neuro-Surgery 340001 Abul Kalam Azad Mymensingh Medical College, Mymensingh Orthopaedic Surgery 340002 Mirza Osman Beg Comilla Medical College, Comilla Orthopaedic Surgery 540001 Bithi Debnath Dhaka Medical College, Dhaka Paediatric Neurology & Development 410001 Iqbal Ahmed Rajshahi Medical College, Rajshahi Plastic and Reconstructive Surgery 410003 Md. Shahin Shah Rangpur Medical College, Rangpur Plastic and Reconstructive Surgery 410004 Mst. Masuma Sarker Dhaka Medical College, Dhaka Plastic and Reconstructive Surgery 410005 Afrina Sharmin Z.H. Sikder Women¿s Medical College, Dhaka Plastic and Reconstructive Surgery 500002 Dr. Ujjal Barua Comilla Medical College, Comilla Urology 500008 Shafiqur Rahman Sir Salimullah Medical College, Dhaka Urology 110004 Debashish Das Jahurul Islam Medical College, Bajitpur Anaesthesiology 110010 Khalid Nur Md. Mahbub Sir Salimullah Medical College, Dhaka Anaesthesiology 110013 Raju Ahmed Sher-E-Bangla Medical College, Barisal Anaesthesiology 110015 Md. Ahsanul Kabir Sir Salimullah Medical College, Dhaka Anaesthesiology 110018 Md. Abdul Jabbar Mymensingh Medical College, Mymensingh Anaesthesiology 150001 Dr.Sultana Parveen Dhaka Dental College, Dhaka Conservative Dentistry and Endodontics 150002 Shiren Sultana Pioneer Dental College, Dhaka Conservative Dentistry and Endodontics 160001 Bilqis Akter Sher-E-Bangla Medical College, Barisal Dermatology and Venereology 240013 Israt Zerin Eva Dhaka Medical College, Dhaka Medicine 240016 Shuvojit Sen Armed Forces Medical College, Dhaka Medicine 240031 Tania Tajreen Chittagong Medical College, Chittagong Medicine 240044 Rozina Sultana Rangpur Medical College, Rangpur Medicine 240056 Dr.Atiquzzaman Dhaka National Medical College, Dhaka Medicine 240070 Md. Ajmirul Hoque Sarkar Rajshahi Medical College, Rajshahi Medicine 240071 Nasir Uddin Ahmed Chittagong Medical College, Chittagong Medicine 240086 Ishrat Binte Reza Bangladesh Medical College, Dhaka Medicine 240095 Mohammad Kafil Uddin Chittagong Medical College, Chittagong Medicine Chowdhery 240104 Abhizit Pandit Sir Salimullah Medical College, Dhaka Medicine 240107 Dr. Mostofa Kamal Chowdhury Dhaka Medical College, Dhaka Medicine 240112 Dr. Suman Kanti Chowdhury Dhaka Medical College, Dhaka Medicine 240121 Mazharul Islam Sher-E-Bangla Medical College, Barisal Medicine 240123 Shabnam Jahan Hoque Dhaka Medical College, Dhaka Medicine 240125 Md. Mahbubul Alam Mymensingh Medical College, Mymensingh Medicine 240126 Hasan Hafizur Rahman Dhaka Medical College, Dhaka Medicine 240131 Dr. Mrinmay Kumar Podder Mymensingh Medical College, Mymensingh Medicine 240139 Humayra Jesmin Rajshahi Medical College, Rajshahi Medicine 240140 Muhammad Abdullah Chittagong Medical College, Chittagong Medicine Jahed Khan 240150 Md. Moniruzzaman Asraf Rajshahi Medical College, Rajshahi Medicine 240167 Md. Saiful Malek Rajshahi Medical College, Rajshahi Medicine

234 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Roll No. Name From where graduated Subject 240177 Soumitra Roy MAG Osmani Medical College, Sylhet Medicine 240182 Md. Shyfullah Rajshahi Medical College, Rajshahi Medicine 240210 Md. Amzad Hossain Mymensingh Medical College, Mymensingh Medicine 240212 Tridip Kanti Barman Sir Salimullah Medical College, Dhaka Medicine 240213 Ashim Kumar Saha Khulna Medical College, Khulna Medicine 240215 Md. Naheed Hasan Dhaka Medical College, Dhaka Medicine 240218 Fouzia Anar Dhaka Medical College, Dhaka Medicine 240221 Shantonu Kumer Saha Dhaka Medical College, Dhaka Medicine 240222 Dr. Goutam Talukder MAG Osmani Medical College, Sylhet Medicine 240234 Sanjoy Kumer Paul Chittagong Medical College, Chittagong Medicine 240235 Nira Ferdous Z.H. Sikder Women¿s Medical College, Dhaka Medicine 240251 Azimun Nessa Mymensingh Medical College, Mymensingh Medicine 240252 Rubyat Hasan Chowdhury Mymensingh Medical College, Mymensingh Medicine 240262 Mohammad Kamrul Islam MAG Osmani Medical College, Sylhet Medicine 240265 Mohammad Saydur Rahman Mymensingh Medical College, Mymensingh Medicine 240280 Dr. Md. Mahidul Alam Rajshahi Medical College, Rajshahi Medicine 240294 Md. Ruhul Amin Sarkar Sir Salimullah Medical College, Dhaka Medicine 240307 Meherunnesa Mukta Rangpur Medical College, Rangpur Medicine 240314 Md. Mamun-Or-Rashid Mymensingh Medical College, Mymensingh Medicine Ibne Harun 240315 Abu Hayat Mohammod Sir Salimullah Medical College, Dhaka Medicine Waliur Rahman 240318 Faria Quadir Sher-E-Bangla Medical College, Barisal Medicine 240321 Afsana Rahman Dhaka Medical College, Dhaka Medicine 240323 Dr. Milton Barua Chittagong Medical College, Chittagong Medicine 240330 Mohammad Jane Alam Sher-E-Bangla Medical College, Barisal Medicine 240340 Md. Jahangir Kabir Khulna Medical College, Khulna Medicine 240341 Dr. J.M. Ariful Islam Mymensingh Medical College, Mymensingh Medicine 240355 Md. Ashiq Iqbal Rajshahi Medical College, Rajshahi Medicine 240357 Mohammad Shohel Khan Shaheed Ziaur Rahman Medical College, Bogra Medicine 240358 Muhammed Saiful Islam Sir Salimullah Medical College, Dhaka Medicine 240365 Muhammad Ataul Gani Osmani Sir Salimullah Medical College, Dhaka Medicine 240366 Issa Muhammad Baker Shaheed Ziaur Rahman Medical College, Bogra Medicine 240367 Md. Habibul Ghani Mymensingh Medical College, Mymensingh Medicine 240368 Dr. Anupam Das Rangpur Medical College, Rangpur Medicine 240369 Rahatun Nayeem Sir Salimullah Medical College, Dhaka Medicine 240375 Z.H.M.Nazmul Alam MAG Osmani Medical College, Sylhet Medicine 240377 Abdullah Al-Muti Rangpur Medical College, Rangpur Medicine 240400 Dr. B.U.M Wahid Ahmed MAG Osmani Medical College, Sylhet Medicine 240429 Md Elias Bhuiyan Sir Salimullah Medical College, Dhaka Medicine 240439 Mohammad Lokman Hakim Chittagong Medical College, Chittagong Medicine 240455 Rozana Rouf MAG Osmani Medical College, Sylhet Medicine 240462 Amrita Kumar Deb Nath Dhaka Medical College, Dhaka Medicine

235 College News

Roll No. Name From where graduated Subject

240498 Pritish Tarafder Khulna Medical College, Khulna Medicine 240502 Md. Abdul Hamid Chittagong Medical College, Chittagong Medicine 250001 Dr. Rezina Jasmine Rajshahi Medical College, Rajshahi Microbiology 300033 Bilkish Jahan Ferdushy Armed Forces Medical College, Dhaka Obst and Gynae 300069 Salma Akter Sir Salimullah Medical College, Dhaka Obst and Gynae 300072 Noor-E-Naharin Rajshahi Medical College, Rajshahi Obst and Gynae 300077 Nazmun Nahar Sir Salimullah Medical College, Dhaka Obst and Gynae 300087 Umme Rehnuma Tarannum Chittagong Medical College, Chittagong Obst and Gynae 300089 Fahmida Hoque Chittagong Medical College, Chittagong Obst and Gynae 300098 Sabiha Shimul Dinajpur Medical College, Dinajpur Obst and Gynae 300115 Mridula Kar Sher-E-Bangla Medical College, Barisal Obst and Gynae 300116 Farhana Parveen Sher-E-Bangla Medical College, Barisal Obst and Gynae 300132 Dr. Umme Abedin Saima Sher-E-Bangla Medical College, Barisal Obst and Gynae 300138 Kaoser Jahan Mymensingh Medical College, Mymensingh Obst and Gynae 300140 Ummay Salma Sher-E-Bangla Medical College, Barisal Obst and Gynae 300145 Ainun Nahar Sir Salimullah Medical College, Dhaka Obst and Gynae 300158 Ruma Afrose Rangpur Medical College, Rangpur Obst and Gynae 300176 Dr. Mousumi Saha MAG Osmani Medical College, Sylhet Obst and Gynae 300187 Laila Kamruzzahan Panna Rangpur Medical College, Rangpur Obst and Gynae 300191 Saida Bilkis Khanam Sir Salimullah Medical College, Dhaka Obst and Gynae 300203 Ivy Nasrin Dhaka Medical College, Dhaka Obst and Gynae 300207 Golshan Ara Kohinoor MAG Osmani Medical College, Sylhet Obst and Gynae 300210 Abanti Ghosh Rajshahi Medical College, Rajshahi Obst and Gynae 300213 Mitheel-Ibna Islam Rangpur Medical College, Rangpur Obst and Gynae 300221 Shamima Amir Mymensingh Medical College, Mymensingh Obst and Gynae 300223 Mst. Shabrin Akhter Sir Salimullah Medical College, Dhaka Obst and Gynae 300239 Sabah Sultana Rajshahi Medical College, Rajshahi Obst and Gynae 300247 Iffana Azam Jalalabad Ragib-Rabeya Medical College, Sylhet Obst and Gynae 300253 Manjan Ara Rajshahi Medical College, Rajshahi Obst and Gynae 300258 Lutfunnahar Shampa Dhaka Medical College, Dhaka Obst and Gynae 300265 Dina Layla Hossain Dhaka Medical College, Dhaka Obst and Gynae 300268 Ashfi Laila Elora Mymensingh Medical College, Mymensingh Obst and Gynae 300277 Farhana Haque Choudhury Rangpur Medical College, Rangpur Obst and Gynae 300283 Ummey Nazmin Islam Dhaka Medical College, Dhaka Obst and Gynae 300286 Syeda Farhana Ali Bangladesh Medical College, Dhaka Obst and Gynae 300288 Farhana Ahmed Nancy Bangladesh Medical College, Dhaka Obst and Gynae 300300 Farzana Nasrin Sir Salimullah Medical College, Dhaka Obst and Gynae 300301 Farzana Islam Khan MAG Osmani Medical College, Sylhet Obst and Gynae 300312 Nafisa Jesmin MAG Osmani Medical College, Sylhet Obst and Gynae 300314 Panchami Goshwami Dinajpur Medical College, Dinajpur Obst and Gynae 300322 Lucky Rahman Sir Salimullah Medical College, Dhaka Obst and Gynae 300327 Fatema Islam Sir Salimullah Medical College, Dhaka Obst and Gynae

236 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Roll No. Name From where graduated Subject 300336 Fatema Begum Faridpur Medical College, Faridpur Obst and Gynae 300341 Tania Akbar International Medical College, Tongi, Dhaka Obst and Gynae 300343 Sanjida Khan Jahurul Islam Medical College, Bajitpur Obst and Gynae 300350 Dr. Sharmin Akhter Shumi Sher-E-Bangla Medical College, Barisal Obst and Gynae 300351 Mst. Taslima Akther Chittagong Medical College, Chittagong Obst and Gynae 300363 Anika Tabassum Dhaka Medical College, Dhaka Obst and Gynae 300371 Shahida Akter Sir Salimullah Medical College, Dhaka Obst and Gynae 300374 Salma Akter Dhaka Medical College, Dhaka Obst and Gynae 300378 Rumana Akhter Shaheed Ziaur Rahman Medical College, Bogra Obst and Gynae 300385 Naz Yasmin Dhaka Medical College, Dhaka Obst and Gynae 300391 Mst. Israt Jahan Rangpur Medical College, Rangpur Obst and Gynae 300394 Farhana Khanam Faridpur Medical College, Faridpur Obst and Gynae 300409 Nusrat Jahan Dinajpur Medical College, Dinajpur Obst and Gynae 300416 Rehena Nasreen Kumudini Womens¿ Medical College, Tangail Obst and Gynae 300418 Umma Salma Chittagong Medical College, Chittagong Obst and Gynae 300422 Dr. Rukhsana Parvin Rajshahi Medical College, Rajshahi Obst and Gynae 300425 Khodeza Khanam Rajshahi Medical College, Rajshahi Obst and Gynae 300429 Shahnaz Mizan Chittagong Medical College, Chittagong Obst and Gynae 300430 Mumtahena Amir Dhaka Medical College, Dhaka Obst and Gynae 300438 Taslima Akther Dinajpur Medical College, Dinajpur Obst and Gynae 300441 Mohsina Haider Dhaka Medical College, Dhaka Obst and Gynae 300444 Jebunnaher Mymensingh Medical College, Mymensingh Obst and Gynae 300449 Mohammad Khayrul Bashar Khan Sher-E-Bangla Medical College, Barisal Obst and Gynae 300467 Rownok Jahan Rajshahi Medical College, Rajshahi Obst and Gynae 300475 Rifat Sultana Mymensingh Medical College, Mymensingh Obst and Gynae 300478 Subrata Kumar Bagchi Dhaka Medical College, Dhaka Obst and Gynae 300479 Jayanti Rani Dhar Rajshahi Medical College, Rajshahi Obst and Gynae 300484 Kazi Foyeza Akther Dinajpur Medical College, Dinajpur Obst and Gynae 300509 Dr. Ananya Bhattacharjee Sir Salimullah Medical College, Dhaka Obst and Gynae 300521 Sabreena Barkat Armed Forces Medical College, Dhaka Obst and Gynae 310002 Md. Emdad Hussain Rajshahi Medical College, Rajshahi Ophthalmology 310004 Dr. Rajiv Mothey University of Science & Technology Ophthalmology Chittagong (USTC) 310005 S M Rejwan Raju Dhaka Medical College, Dhaka Ophthalmology 310007 Most. Sanjida Akter Rajshahi Medical College, Rajshahi Ophthalmology 310008 Tanjila Hossain Z.H. Sikder Women¿s Medical College, Dhaka Ophthalmology 310014 Mahar Ali Sher-E-Bangla Medical College, Barisal Ophthalmology 310017 Md. Fakhrul Islam Mymensingh Medical College, Mymensingh Ophthalmology 310020 Nazmus Sakeb Bangladesh Medical College, Dhaka Ophthalmology 320001 Md. Talal Mamun Sappro Dental College, Dhaka Oral and Maxillofacial Surgery 320002 Dr. Sumanta Kumar Gain Dhaka Dental College, Dhaka Oral and Maxillofacial Surgery 320003 Mausumi Iqbal Sappro Dental College, Dhaka Oral and Maxillofacial Surgery 320004 Md. Abdul Hakim Rajshahi Medical College, Rajshahi Oral and Maxillofacial Surgery

237 College News

Roll No. Name From where graduated Subject

320005 Dr. Ashim Kumar Saha Dhaka Dental College, Dhaka Oral and Maxillofacial Surgery 320007 Sabiha Alam Bangladesh Dental College, Dhaka Oral and Maxillofacial Surgery 320008 Dr. Shamsul Alam Mohammad Sappro Dental College, Dhaka Oral and Maxillofacial Surgery Imran Hossain 320009 Sidratul Muntaha Dhaka Dental College, Dhaka Oral and Maxillofacial Surgery 330001 Marina Akhtar Rangpur Dental College, Rangpur Orthodontics and Dentofacial Orthopaedics 330017 Mohammad Lanzur Rahman Dhaka Dental College, Dhaka Orthodontics and Dentofacial Orthopaedics 350005 Md.Ariful Islam MAG Osmani Medical College, Sylhet Otolaryngology 350012 Dr. Horidas Kumar Paul Rangpur Medical College, Rangpur Otolaryngology 350021 Md.Nesar Uddin Dhaka Medical College, Dhaka Otolaryngology 350023 Md. Aminul Haque Sher-E-Bangla Medical College, Barisal Otolaryngology 350027 Sanjoy Das Sir Salimullah Medical College, Dhaka Otolaryngology 390002 Syeda Humaida Hasan Chittagong Medical College, Chittagong Paediatrics 390007 Farhana Afroze MAG Osmani Medical College, Sylhet Paediatrics 390013 Jahangir Alam Armed Forces Medical College, Dhaka Paediatrics 390014 Saira Khan Armed Forces Medical College, Dhaka Paediatrics 390015 Samia Chharra Armed Forces Medical College, Dhaka Paediatrics 390018 Dr. Rana Kumar Biswas Rajshahi Medical College, Rajshahi Paediatrics 390023 Dr. Tapon Kumar Roy Rajshahi Medical College, Rajshahi Paediatrics 390024 Dilruba Sultana Khulna Medical College, Khulna Paediatrics 390035 Anjana Basak Shaheed Ziaur Rahman Medical College, Bogra Paediatrics 390037 Mahboba Akther Sir Salimullah Medical College, Dhaka Paediatrics 390038 Dr. Shima Bhadra Chittagong Medical College, Chittagong Paediatrics 390040 Dr. Khaleda Begum Sir Salimullah Medical College, Dhaka Paediatrics 390042 Mohammad Nazmul Chittagong Medical College, Chittagong Paediatrics Islam Bhuiyan 390044 Sanchita Sarker Rajshahi Medical College, Rajshahi Paediatrics 390047 Md Nazmul Hassan Jahurul Islam Medical College, Bajitpur Paediatrics 390048 Salahuddin Ahmed Dhaka Medical College, Dhaka Paediatrics 390050 Dr. Khyrun Nahar Rangpur Medical College, Rangpur Paediatrics 390051 Meftahul Jannat Dhaka Medical College, Dhaka Paediatrics 390052 Dr. Laila Bilqis Sir Salimullah Medical College, Dhaka Paediatrics 390055 Muhammad Ismail Hasan MAG Osmani Medical College, Sylhet Paediatrics 390056 Dr. Md. Mozammel Haque Rajshahi Medical College, Rajshahi Paediatrics 390057 Abu Asma Comilla Medical College, Comilla Paediatrics 390058 Md. Arif Rabbany Mymensingh Medical College, Mymensingh Paediatrics 390059 Mohammad Morshad Alam MAG Osmani Medical College, Sylhet Paediatrics 390063 Shahreen Kabir Bangladesh Medical College, Dhaka Paediatrics 390064 Tasnim Ahmed Sir Salimullah Medical College, Dhaka Paediatrics 390069 Md. Iqbal Hossain Rajshahi Medical College, Rajshahi Paediatrics 390070 Tithi Islam Mymensingh Medical College, Mymensingh Paediatrics 390071 Nahid Farzana Chittagong Medical College, Chittagong Paediatrics

238 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Roll No. Name From where graduated Subject

390072 Most. Sabina Yasmin Dhaka Medical College, Dhaka Paediatrics 390075 Rubina Farzana Mymensingh Medical College, Mymensingh Paediatrics 390076 Farhana Afroz Dhaka National Medical College, Dhaka Paediatrics 390090 Sabita Rani Das Chittagong Medical College, Chittagong Paediatrics 390091 Rumi Myedull Hossain Dhaka Medical College, Dhaka Paediatrics 390099 Fauzia Nahid Sher-E-Bangla Medical College, Barisal Paediatrics 390102 Mahbuba Tajmila Rangpur Medical College, Rangpur Paediatrics 390103 Rafia Rashid Sir Salimullah Medical College, Dhaka Paediatrics 390104 Sk. Serjina Anwar Comilla Medical College, Comilla Paediatrics 390105 Sadia Khan Chittagong Medical College, Chittagong Paediatrics 390108 Dr. Sabiha Akther Rajshahi Medical College, Rajshahi Paediatrics 390114 Md. Abdul Wadud Sarker Chittagong Medical College, Chittagong Paediatrics 390115 Rubina Afroz Rana Rangpur Medical College, Rangpur Paediatrics 390118 Muhammad Obaidul Haque Chittagong Medical College, Chittagong Paediatrics 390119 Israt Jahan Anny Rajshahi Medical College, Rajshahi Paediatrics 390126 Kuntal Roy Dinajpur Medical College, Dinajpur Paediatrics 390127 Mst. Shanjida Sharmim Rangpur Medical College, Rangpur Paediatrics 390128 Ruhina Tasmeen Dhaka Medical College, Dhaka Paediatrics 390129 Dr. Jobaida Parvin Sher-E-Bangla Medical College, Barisal Paediatrics 390132 Dr. Nasren Akter Khulna Medical College, Khulna Paediatrics 390133 Subir De University of Science & Technology Paediatrics Chittagong (USTC) 390147 Farhana Rahman Jahurul Islam Medical College, Bajitpur Paediatrics 390159 Md.Farid Hossain Chittagong Medical College, Chittagong Paediatrics 390160 Dr. Ishrat Jahan Medical College for Women and Hospital, Dhaka Paediatrics 390161 Dr. Tahmina Islam Dhaka Medical College, Dhaka Paediatrics 390168 S.M. Nurun Nabi Mymensingh Medical College, Mymensingh Paediatrics 390171 Md.Mostafa Zaman Shaheed Ziaur Rahman Medical College, Bogra Paediatrics 390176 Taslima Sultana Dhaka Medical College, Dhaka Paediatrics 390177 Dr. Md. Rustam Ali Khulna Medical College, Khulna Paediatrics 390179 Md . Anwarul Azim MAG Osmani Medical College, Sylhet Paediatrics 390192 Biplob Kumer Saha Mymensingh Medical College, Mymensingh Paediatrics 390197 Salma Sultana Dhaka Medical College, Dhaka Paediatrics 390198 Syeda Makluka Morshed Sher-E-Bangla Medical College, Barisal Paediatrics 390200 Md. Homayun Shikdar Sher-E-Bangla Medical College, Barisal Paediatrics 390205 Dr Abu Sayeed Chowdhury MAG Osmani Medical College, Sylhet Paediatrics 390206 Dr Shamima Yeasmin Rajshahi Medical College, Rajshahi Paediatrics 390209 Masuma Akter Sher-E-Bangla Medical College, Barisal Paediatrics 390220 Dazy Barua Comilla Medical College, Comilla Paediatrics 400006 Fahad Islam BGC Trust Medical College, Chittagong. Physical Medicine & Rehabilitation 400007 Selina Nazir Chittagong Medical College, Chittagong Physical Medicine & Rehabilitation 400008 Musa Muhammad Hojaifa Sher-E-Bangla Medical College, Barisal Physical Medicine & Rehabilitation 400009 Lt. Col. (Dr.) S.M. Shahidul Sher-E-Bangla Medical College, Barisal Physical Medicine & Rehabilitation Haque

239 College News

Roll No. Name From where graduated Subject

400010 Aparajeya Bivab Bikash Baral Chittagong Medical College, Chittagong Physical Medicine & Rehabilitation 420001 Kamrun Nahar Naly Bangladesh Dental College, Dhaka Prosthodontics 430002 Dr. Md. Harunur Rashid Bangladesh Medical College, Dhaka Psychiatry 430004 Bushra Sultana Dhaka Medical College, Dhaka Psychiatry 450005 Rizwana Rahim Chowdhury Sindh Medical College, Karachi, Pakistan Radiology & Imaging 450009 Sumi Datta Chittagong Medical College, Chittagong Radiology & Imaging 450010 Mohammad Anwar Hossain Rajshahi Medical College, Rajshahi Radiology & Imaging 450011 Farah Nazlee MAG Osmani Medical College, Sylhet Radiology & Imaging 450012 Sohely Sultana Mymensingh Medical College, Mymensingh Radiology & Imaging 460001 Md. Ishtiaque Alam Jalalabad Ragib-Rabeya Medical College, Sylhet Radiotherapy 460003 Shamima Afroz Trina Comilla Medical College, Comilla Radiotherapy 460004 Ishrat Sultana Rajshahi Medical College, Rajshahi Radiotherapy 460005 Shaila Sharmin Rangpur Medical College, Rangpur Radiotherapy 460007 Mohammed Mehbub Ahsan Rony MAG Osmani Medical College, Sylhet Radiotherapy 480002 Md. Abu Imran Chittagong Medical College, Chittagong Surgery 480010 Saiful Islam Khan Khulna Medical College, Khulna Surgery 480021 Sardar Shahnabi Jafran Bangladesh Medical College, Dhaka Surgery 480029 Dr. Mohammod Ali Sher-E-Bangla Medical College, Barisal Surgery 480034 Md. Mahfuzul Momen MAG Osmani Medical College, Sylhet Surgery 480035 Md Ariful Islam Sir Salimullah Medical College, Dhaka Surgery 480038 Rubaiya Reza Tumpa Bangladesh Medical College, Dhaka Surgery 480043 Md. Masudar Rahman Rangpur Medical College, Rangpur Surgery 480046 Subrata Sarker Mymensingh Medical College, Mymensingh Surgery 480048 Abu Kawsar Mohammed Chittagong Medical College, Chittagong Surgery Naser Mazumder 480051 Md. Harun-Or-Rashid Mymensingh Medical College, Mymensingh Surgery 480052 Dr. Mohd. Sultanul Abedin Rajshahi Medical College, Rajshahi Surgery 480057 Mohammad Shahriar Faisal Mymensingh Medical College, Mymensingh Surgery 480063 Mohammad Al-Mamun Comilla Medical College, Comilla Surgery 480064 Md. Meshkat Uddin Khan Dinajpur Medical College, Dinajpur Surgery 480068 Habibun Nobi Md Shafiquzzaman Khulna Medical College, Khulna Surgery 480069 Apurba Kishore Paul MAG Osmani Medical College, Sylhet Surgery 480074 Rafiul Karim Khan Mymensingh Medical College, Mymensingh Surgery 480082 U Than Kyow Dinajpur Medical College, Dinajpur Surgery 480086 Shamol Kumar Paul Khulna Medical College, Khulna Surgery 480087 Liton Kumer Shaha Sir Salimullah Medical College, Dhaka Surgery 480089 Dr. Md. Ekramul Haque MAG Osmani Medical College, Sylhet Surgery 480090 Surjit Ghosh MAG Osmani Medical College, Sylhet Surgery 480092 Mohammad Saif Uddin MAG Osmani Medical College, Sylhet Surgery 480094 Abdullah Al Mamun Chowdhury Rangpur Medical College, Rangpur Surgery 480095 Dr Mohammad Monir Hossain Rajshahi Medical College, Rajshahi Surgery 480106 Nur Mohammod Sayed Bin Aziz Mymensingh Medical College, Mymensingh Surgery

240 Journal of Bangladesh College of Physicians and Surgeons Vol. 34, No. 4, October 2016

Roll No. Name From where graduated Subject 480121 Mir Rasekh Alam Ovi Dhaka Medical College, Dhaka Surgery 480122 Mohammad Kamruzzaman Dhaka Medical College, Dhaka Surgery 480137 Eliza Sultana Rajshahi Medical College, Rajshahi Surgery 480138 Md Nasir Uddin MAG Osmani Medical College, Sylhet Surgery 480140 Sayem Al Monsur Faizi Mymensingh Medical College, Mymensingh Surgery 480146 Proshanta Roy Dinajpur Medical College, Dinajpur Surgery 480147 Gouranga Kumar Bose Rajshahi Medical College, Rajshahi Surgery 480151 Fakir Amirul Islam Rangpur Medical College, Rangpur Surgery 480175 Md. Abu Sayem Sir Salimullah Medical College, Dhaka Surgery 480177 S. M. Minhajul Hasan Chowdhury Chittagong Medical College, Chittagong Surgery 480189 Morshed Ali Chittagong Medical College, Chittagong Surgery 480190 Dr. Saurav Sutar Sher-E-Bangla Medical College, Barisal Surgery 480197 Sonia Akter Enam Medical College, Savar, Dhaka Surgery 480200 Farid Uddin Ahamad Dhaka Medical College, Dhaka Surgery 480209 Dr. Faisal Ahme Chittagong Medical College, Chittagong Surgery 480228 Dr.Md. Abul Hosen Rajshahi Medical College, Rajshahi Surgery 480244 S.M.Syeed-Ul-Alam Sher-E-Bangla Medical College, Barisal Surgery 480248 Md. Rabiul Karim Rangpur Medical College, Rangpur Surgery 480251 Mohammad Fazlul Haque MAG Osmani Medical College, Sylhet Surgery 480264 Fayem Chowdhury Mymensingh Medical College, Mymensingh Surgery

The following candidates satisfied the Board of Examiners and are declared to have passed the MCPS Examinations held in July, 2016 subject to confirmation by the council of Bangladesh College of Physicians and Surgeons

Roll No Name From Where Graduate Subject 130011 Shovan Rahman Mymensingh Medical College, Mymensingh Preli - Medicine 290001 Md Amir Ali Mymensingh Medical College, Mymensingh Preli - Surgery 290002 Md. Kamal Hossen Mymensingh Medical College, Mymensingh Preli - Surgery 340004 Dr. Md. Mizanur Rahman Shaheed Ziaur Rahman Medical College, Bogra Preli - Surgery 410001 Mohammad Mominur Dinajpur Medical College, Dinajpur Preli - Surgery Rahman Khan 410002 Sudip Kumar Karmoker Rajshahi Medical College, Rajshahi Preli - Surgery 410005 Chowdhury Rashedul Mughni Armed Forces Medical College, Dhaka Preli - Surgery 500004 Md. Abu Sayed Mymensingh Medical College, Mymensingh Preli - Surgery

The following candidates satisfied the Board of Examiners and are declared to have passed the MCPS Examinations held in July 2016 subject to confirmation by the council of Bangladesh College of Physicians and Surgeons.

Roll No Name From Where Graduate Subject 110005 Md. Mahbubul Alam Sarker Chittagong Medical College, Chittagong Anaesthesiology 110010 Nelufa Tahera Rahman Dhaka Medical College, Dhaka Anaesthesiology 910001 Masuma Ahmed Salsabil Dhaka Medical College, Dhaka Clinical Pathology 910003 Md. Mahbur Rashid Sarker Shaheed Ziaur Rahman Medical College, Bogra Clinical Pathology 910005 Samia Mahmood Armed Forces Medical College, Dhaka Clinical Pathology 910006 Dr. S. M. Rashidul Kabir Dhaka Medical College, Dhaka Clinical Pathology

241 College News

Roll No. Name From where graduated Subject

910007 Fatema Akter Armed Forces Medical College, Dhaka Clinical Pathology 910009 Dr. Fahad Mohammad Sadat MAG Osmani Medical College, Sylhet Clinical Pathology 930001 Md. Jewel Rana Dhaka Dental College, Dhaka Dental Surgery 930005 Mohammad Rezaul Karim Ripon Dhaka Dental College, Dhaka Dental Surgery 930008 Md. Ataul Gani Sarker Dhaka Dental College, Dhaka Dental Surgery 160004 Md. Abdullah-Al Mamun Sir Salimullah Medical College, Dhaka Dermatology and Venereology 160010 Ayesha Siddika Sher-E-Bangla Medical College, Barisal Dermatology and Venereology 240038 Adnan Bashar Mymensingh Medical College, Mymensingh Medicine 240044 S.M.Showkat Ali University of Science & Technology Chittagong (USTC) Medicine 240074 Md. Mainuddin Sohel Chittagong Medical College, Chittagong Medicine 240083 Mohmmed Tauseef Sharip Chittagong Medical College, Chittagong Medicine 240116 Dr. A.B.M. Shafiuzzaman Mymensingh Medical College, Mymensingh Medicine 240118 Ahsan Ullah Chittagong Medical College, Chittagong Medicine 240122 Md Anamul Haque Sir Salimullah Medical College, Dhaka Medicine 240130 Taslima Akter Chittagong Medical College, Chittagong Medicine 240136 Prodip Kumar Sarkar Dhaka Medical College, Dhaka Medicine 240137 Dr Md Saiful Islam Patwary Sher-E-Bangla Medical College, Barisal Medicine 300004 Nishat Anam Borna Rajshahi Medical College, Rajshahi Obst and Gynae 300016 Dr. Maya Rani Das Sir Salimullah Medical College, Dhaka Obst and Gynae 300019 Dr. Sharmin Sultana Rajshahi Medical College, Rajshahi Obst and Gynae 300020 Md. Janibul Haque Dhaka Medical College, Dhaka Obst and Gynae 300028 Dr. Munthasir Yeashmin MAG Osmani Medical College, Sylhet Obst and Gynae 300038 Basabi Roy Khulna Medical College, Khulna Obst and Gynae 300056 Khadiza Siddique Mymensingh Medical College, Mymensingh Obst and Gynae 300060 Meem Shahrin Dhaka Medical College, Dhaka Obst and Gynae 300067 Hafiza Farzana Sher-E-Bangla Medical College, Barisal Obst and Gynae 300090 Dr. Mst. Anjuman Ara Kumudini Womens¿ Medical College, Tangail Obst and Gynae 300092 Dr. Fahmida Yesmin Sir Salimullah Medical College, Dhaka Obst and Gynae 310009 Subrina Afrin Ibrahim Medical College, Dhaka Ophthalmology 310017 Dr. S.M. Mosaddeka Islam Armed Forces Medical College, Dhaka Ophthalmology 310018 Sumaiya Sultana Binte Mosharraf Armed Forces Medical College, Dhaka Ophthalmology 310019 Tahmina Sultana Armed Forces Medical College, Dhaka Ophthalmology 310021 Hasan Jawad Khulna Medical College, Khulna Ophthalmology 310022 Mst. Mahbubay Habibah Rajshahi Medical College, Rajshahi Ophthalmology 310023 Tazbir Ahmed Ibrahim Medical College, Dhaka Ophthalmology 310025 Md. Abdur Rashid Khulna Medical College, Khulna Ophthalmology 350005 Ummey Ayeman Sharmin Armed Forces Medical College, Dhaka Otolaryngology 430002 Fahmida Ferdous Dhaka National Medical College, Dhaka Psychiatry 450002 Mosammat Arina Sultana Rajshahi Medical College, Rajshahi Radiology & Imaging 450004 Md. Faijus Saleheen Shaheed Mansur Ali Medical College, Dhaka Radiology & Imaging 450006 Md. Tarif Al Mostakim Armed Forces Medical College, Dhaka Radiology & Imaging 460002 Samina Islam Comilla Medical College, Comilla Radiotherapy 480023 Md. Saiful Islam Khan Rangpur Medical College, Rangpur Surgery 480043 Mohammad Aminul Islam Chittagong Medical College, Chittagong Surgery 480044 Quazi Sabran Uddin Ahmed Rajshahi Medical College, Rajshahi Surgery

242 FROM THE DESK OF EDITOR in CHIEF

(J Bangladesh Coll Phys Surg 2016; 34: 243)

Dear Fellow, Adult Population of Sylhet District” is another great AssalamuAlaikum. initiative by our fellows to increase the awareness and augment preventive measures against viral hepatitis I am happy to furnish this issue of our beloved journal related morbidity. I hope that our fellows will take lead with some splendid articles and hope it will serve well to in making larger scale researches successful in our satisfy you. For instance, “Incidence of Gallbladder country in the coming year and our journal will be Carcinoma in Thick Walled Gallbladder in Comparison enriched by many more brilliant publications. with that of Normal Thickness – A Study of 300 Cases”- by MM Hasana, SZ Lailab, MH Mamun is a unique Thank you. study that shows that incidence of malignancy was higher (84.62%) in patients having thick walled Gall Bladder and highlighted the doctrine that all specimen should undergo histopathology after cholecystectomy. Prof. Khan Abul Kalam Azad “Hepatitis B Virus, Hepatitis C Virus Markers and Serum Editor-in-Chief Alanine Amino-Transferase Levels (ALT), in a Young Journal of BCPS