Original Article

Aw MM, Phua KB, Ooi BC, Da Costa M, Loh DL, Mak K, Tan KC, Isaac J, Prabhakaran K, Quak SH
Correspondence: Dr Marion M Aw, paeawm@nus.edu.sg

ABSTRACT
Introduction The advent of liver transplantation has revolutionised the outcome of children with both acute liver failure and chronic end-stage liver disease. The aim of this study was to review the outcome of all paediatric liver transplants performed since the National Liver Transplant Programme began in 1990.
Methods A retrospective review of all paediatric liver transplants from 1990 to December 2004 was performed.
Results 46 liver transplants were performed in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant was 21 months (range 11 months to 14 years). The most common indication for liver transplant was biliary atresia (71.7 percent). Living-related transplants accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of patients, with a 19.6 percent incidence of acute allograft rejection within the first six months. There were nine deaths. They were related to portal vein thrombosis (three), chronic rejection (one), sepsis (two), post-transplant lymphoproliferative disease (two) and primary graft non-function (one). Overall actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent, respectively.
Conclusion Liver transplantation is an established form of intervention for end-stage liver disease and a variety of liver-related metabolic disease. Our results are comparable to those of well-established liver transplant centres.

Keywords: biliary atresia, end-stage liver disease, liver transplantation, living-related transplant, paediatric liver transplant
Singapore Med J 2006; 47(7): 595-598

Lee YM, Fernandez M, Da Costa M, Lee KH, Sutedja DS, Tai BC, Tan KC, Isaac J, Prabhakaran K, Lim SG
Correspondence: Dr Seng-Gee Lim, mdclimsg@nus.edu.sg

ABSTRACT
Introduction The Model for End-Stage Liver Disease (MELD) score is a good predictor of mortality on the liver transplant waiting list and is the current system of organ allocation in the USA. However, a higher MELD may be associated with poorer outcome post-liver transplantation. The aim of this study was to determine if MELD should be implemented as the system for organ allocation for liver transplantation in Singapore.
Methods There were 46 adult patients who underwent primary liver transplantation at the National University Hospital, Singapore from January 1996 to December 2002. We applied the MELD score to patients who were transplanted and looked for a correlation with survival post-transplant. Patients were followed-up until the most recent visit or death. Survival analysis was performed using Cox regression and Kaplan-Meier method.
Results The mean age at transplant was 52.7 (SD 2.34) years. The majority of the patients transplanted had Hepatitis B (43 percent). The median MELD score at transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There was a significant correlation between pre-transplant MELD and survival at six months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1) as well as survival for patients with and without Hepatitis B (OR 0.72, 95 percent CI 0.22-2.35).
Conclusion MELD allows livers to be allocated to the patients with the greatest medical urgency but its influence on post-transplant survival should be further clarified so that post-transplant survival is not compromised.

Keywords: hepatitis B, liver transplantation, MELD score, organ allocation
Singapore Med J 2006; 47(7): 592-594

Wai CT, Da Costa M, Sutedja D, Lee YM, Lee KH, Tan KC, Isaac J, Wee A, Prabhakaran K, Lim SG
Correspondence: Dr Seng-Gee Lim, mdclimsg@nus.edu.sg

ABSTRACT
Introduction Liver disease from chronic hepatitis B (CHB) and C (CHC) constitutes 57 percent of adult liver transplant in Singapore. Their long-term results post-transplant may be affected by recurrence of the viral illness. This study aims to evaluate the long-term results and survival in patients transplanted for CHB- and CHC-related liver disease.
Methods Patients transplanted for CHB- and CHC-related disease from 1990 until March 2004, which included decompensated cirrhosis and hepatocellular carcinoma (HCC), were reviewed and analysed.
Results 25 patients were transplanted for CHB-related liver disease, with mean follow-up of 153 +/- 25 weeks. Two- and four-year survival rates were 75 percent and 69 percent, respectively. Hepatitis B recurrence from YMDD mutants occurred in five patients, and four were treated successfully with adefovir dipivoxil, with resolution in transaminases and/or improvement in histology. One patient became non-compliant with follow-up and medications, and died 173 weeks post-transplant from reactivation of the wild-type hepatitis B virus. Nine patients were transplanted for CHC-related liver disease, with mean follow-up of 188 +/- 40 weeks, and two- and four-year survival rates of 89 percent and 76 percent, respectively. Two patients developed hepatitis C recurrence and were treated with interferon and ribavarin. One responded with sustained response but the other remained viraemic and died of HCC recurrence two years post-transplant.
Conclusion Long-term results from CHB- and CHC-related liver diseases were satisfactory and comparable to major transplant centres in the USA and Europe. Recurrence of viral hepatitis post-transplant is controllable with current antiviral therapy.

Keywords: anti-viral agents, chronic hepatitis B, chronic hepatitis C, hepatitis, lamivudine, liver transplantation
Singapore Med J 2006; 47(7): 588-591

Wai CT, Lee YM, Wang SC, Da Costa M, Isaac J, Wee A, Lim SG
Correspondence: Dr Seng-Gee Lim, mdclimsg@nus.edu.sg

ABSTRACT
Introduction The prognosis of patients with hepatocellular carcinoma (HCC) is poor. Surgical resection offers the benefit of removal of the tumour but is associated with liver decompensation and tumour recurrence, even after successful surgery. Liver transplantation offers the benefits of complete tumour removal with prevention of both decompensation and recurrence post-operation. This paper aims to review results of liver transplantation for patients with HCC in Singapore.
Methods All adult patients with HCC accepted on the waiting list for liver transplantation (based on the Milan criteria) from 1996 to 2004 in Singapore were reviewed. Patients' HCC were managed with either transarterial chemoembolisation or percutaneous radiofrequency ablation while they were on the waiting list. Post-transplant survival and factors associated with mortality were analysed by Cox regression analysis.
Results 41 patients with HCC were accepted onto the waiting list over the nine-year period. 22 underwent transplantation and 19 did not, with a one-year survival of 91 percent versus 24 percent, respectively. (p-value is less than 0.001). Mean waiting time for transplant was 39 weeks. Post-transplant HCC recurrence was 2/22 (nine percent). Among all patients, mortality was significantly related to baseline white cell counts, prothrombin time, age, alpha-foetoprotein level, Child-Pugh score, and whether patients underwent transplant.
Conclusion Despite the relatively long waiting time of a mean of 39 weeks, post-transplant recurrence of HCC was relatively low at nine percent. Liver transplant is an effective treatment for patients with a HCC, with a reasonable long-term survival.

Keywords: chronic hepatitis B, chronic hepatitis C, cirrhosis, hepatocellular carcinoma, liver transplantation
Singapore Med J 2006; 47(7): 584-587

Wai CT, Lee YM, Selamat DS, Tan KC, Tan CK, Lee HL, Kaur M, Lee KH, Aw MM, Quak SH, Isaac J, Lim SG
Correspondence: Dr Seng-Gee Lim, mdclimsg@nus.edu.sg

ABSTRACT
Introduction Liver transplantation is the accepted standard of care for patients with hepatocellular carcinoma, decompensated liver cirrhosis, and acute liver failure. Since the first liver transplant done in Singapore in 1990, results have been improving. We review the overall results of liver transplantation over the last 15 years.
Methods All transplant cases from 1990 to 2004 were reviewed retrospectively.
Results 100 liver transplants were performed over the last 15 years; four in the first five years and 96 in the subsequent ten years. Overall one- and five-year survival rates were 80 percent and 78 percent, respectively. 44 were paediatric transplants, of which biliary atresia was the commonest indication for paediatric transplant. 56 were adult transplants of which hepatocellular carcinoma and decompensated hepatitis B cirrhosis were the commonest indications for adult transplant. Infection remained the commonest cause of mortality.
Conclusion The number of transplants carried out per year was small due to the low cadaveric donation rate, but the survival of liver transplant patients was comparable to well-established liver transplant centres.

Keywords: chronic hepatitis B, cirrhosis, hepatocellular carcinoma, liver failure, liver transplantation
Singapore Med J 2006; 47(7): 580-583

Nadarajah A, Abrahan L, Lau FL, Hwang LJ, Fakir-Bolte C
Correspondence: Dr L J Hwang, lie-ju.hwang@pfizer.com

ABSTRACT
Introduction Cyclooxygenase (COX)-2 selective inhibitors are attractive candidates for treatment of ankle sprain because of their efficacy as anti-inflammatory and analgesic agents and their overall safety, including lack of effect on platelet aggregation. The objective of this study was to assess the efficacy and tolerability of celecoxib compared with diclofenac slow release (SR) in the treatment of acute ankle sprain in an Asian population.
Methods In this seven-day, multicentre, double-blind, randomised, parallel-group trial, 370 patients with first- or second-degree ankle sprain occurring at or less than 48 hours prior to the first dose of study medication were randomised to receive celecoxib 200 mg bid (189 patients) after a 400 mg loading dose or diclofenac SR 75 mg bid (181 patients). Patients were required to demonstrate moderate to severe ankle pain on weight bearing (45 mm or greater on a 100 mm visual analogue scale [VAS]) at baseline. The primary efficacy end point was the patient's assessment of ankle pain (VAS on full weight bearing) on day 4.
Results Celecoxib was as effective as diclofenac SR in improving the signs and symptoms of ankle sprain. At day 4, mean VAS scores for celecoxib and diclofenac SR had decreased to 28 mm and 30 mm, respectively. Treatment differences were not statistically significant. Incidence of upper gastrointestinal adverse events was low in both treatment groups (0.5 percent versus 2.2 percent for celecoxib and diclofenac SR, respectively).
Conclusion Celecoxib, a COX-2 selective inhibitor, is as effective as diclofenac SR in treating ankle sprains. With its platelet-sparing properties, celecoxib may offer an advantage over diclofenac SR in managing musculoskeletal injuries.

Keywords: ankle sprain, celecoxib, diclofenac SR, drug efficacy, musculoskeletal injuries
Singapore Med J 2006; 47(6): 534-542

Chee CBE, Wang YT, Teleman MD, Boudville IC, Chew SK
Correspondence: Dr Cynthia B E Chee, cynthia_chee@ttsh.com.sg

ABSTRACT
Introduction A key intervention of the Singapore Tuberculosis Elimination Programme (STEP) was the introduction in 2001 of a computerised treatment surveillance module (TSM) for the real-time monitoring of the treatment progress of the country's notified tuberculosis (TB) cases until a final outcome. We report the treatment outcome as at December 31, 2002 for the cohort of Singapore residents with new and relapsed pulmonary TB in whom treatment was commenced in 2001.
Methods Each TB notification will activate the TSM, which requires a return on the patient's treatment progress, treatment delivery mode and the treating physician's management decision at each clinic visit to the STEP Registry until an outcome is reached.
Results There were 1,354 Singapore residents with new or relapsed pulmonary TB who started treatment in 2001. Of these, 620 (45.8 percent) underwent directly-observed therapy (DOT) at their nearest polyclinic. As at December 31, 2002 , 79 percent of patients completed treatment, nine percent died (two percent from TB), nine percent interrupted treatment (they were either lost to follow-up or refused treatment), 1.8 percent were still on treatment, 0.6 percent left the country, and 0.5 percent had permanent cessation of treatment due to drug reactions. Factors associated with treatment completion were Chinese ethnicity (odds-ratio [OR] 1.5, 95 percent confidence interval [Cl] 1.1-2, p-value is 0.02), age younger than 65 years (OR 1.8, 95 percent Cl 1.3-3.0, p-value is 0.003) and the use of DOT (OR 3.1, 95 percent Cl 2.3-4.1, p-value is less than 0.05).
Conclusion The findings from the TSM's first year provide a baseline for future programme evaluation.

Keywords: directly observed therapy, pulmonary, treatment outcome, tuberculosis
Singapore Med J 2006; 47(6): 529-533

Quan WL, Chia CK, Yim HB
Correspondence: Dr Quan Wai Leong, wai_leong_quan@ttsh.com.sg

ABSTRACT
Introduction Data on safety issues and therapeutic outcomes of endoscopy in pregnancy remains limited especially in the local context. The concerns are that of safety in sedation and radiation to the foetus, effects on the pregnancy, the need for special precautions on mother and foetus during the procedure and long-term foetal outcome. We report a case series on four pregnant women to address these concerns and outline their therapeutic approaches.
Methods We reviewed four patients who underwent oral gastroduodenoscopy (OGD) or endoscopic retrograde cholangiopancreatography (ERCP) during their pregnancies. Lead aprons were used to shield the foetuses in all patients that underwent ERCP. Sedation was given when necessary, and an anaesthetist was employed in one case for close patient monitoring. Fluoroscopy was minimised and radiographs were taken only when essential.
Results The mean patient age was 27.8 years (range 23-35 years). The mean gestation was 21.5 weeks (range 14-32 weeks), with two patients each being in their second and third trimesters. The indications for ERCP were cholangitis and pancreatitis (one), choledocholithiasis on ultrasonography (two), and that for OGD was persistent vomiting (one). Two patients underwent sphincterotomy and one had a biliary stent inserted. One patient was lost to follow-up. The other three had a full-term normal delivery and all babies were healthy at birth with good birth weight and normal Apgar scores.
Conclusion Our series showed that endoscopic procedures in pregnancy are safe for both mother and foetus. However, these procedures should be restricted to cases with definite. indications and radiation exposure should be minimised with additional safety precautions such as minimal radiation exposure and the use of lead shield when applicable.

Keywords: conscious sedation, digestive system, endoscopy, pregnancy, radiation safety
Singapore Med J 2006; 47(6): 525-528

Tan YSL, Hong CY, Chong PN, Tan ESL, Lew YJ, Lin RTP
Correspondence: Dr Yvette S L Tan, yvette_tan@nhgp.com.sg

ABSTRACT
Introduction This study aims to study whether knowledge that upper respiratory tract infection (URTI) resolves on its own is associated with more appropriate antibiotic cognition and treatment-seeking behaviour in adult patients seeking consultation for upper respiratory tract symptoms in all nine polyclinics of the National Healthcare Group in Singapore.
Methods A prospective study of 595 adult patients who attended for URTI symptoms of less than seven days duration was performed. We collected data using an interviewer-administered structured questionnaire eliciting the participant's personal and demographical data, his knowledge about URTI, past experience with URTI and treatment-seeking behaviour for this current episode of URTI. These variables were then regressed against the variable "URTI resolves on its own", adjusting for "antibiotics relieve URTI faster", "antibiotic used unnecessarily for URTI", "recovery faster with antibiotics" for antibiotic cognition; and "number of days with URTI", "first line of action: self-medicate", "reason for attendance: felt unwell", "reason for attendance: get well faster" and "used prescribed medication before current visit" for health-seeking behaviour.
Results More than one-third of patients believed that URTI resolved on its own. Subjects who believed that URTI resolved on its own were not significantly different in terms of gender, ethnic group, educational status, age, knowledge of germs as causal, and number of days sick before attendance. However, such patients were 1.68 times (confidence interval [CI] 1.17, 2.41) more likely to agree that, nowadays, antibiotics are used unnecessarily for "flu", and 2.07 times (CI 1.32, 3.24) more likely to self-medicate. They were 0.51 (CI 0.35, 0.76) times more likely to be dependant on prescribed medication.
Conclusion Knowledge that URTI resolves on its own is associated with more appropriate antibiotic cognition and health-seeking behaviour.

Keywords: antibiotics, health-seeking behaviour, respiratory tract infection, upper respiratory tract infection
Singapore Med J 2006; 47(6): 518-524

Shamim SM, Shamim MS, Jaffary SA, Faruqui N, Hameed K, Shamim M
Correspondence: Dr Shahzad M Shamim, shahzad.shamim@aku.edu

ABSTRACT
Introduction The study was conducted to identify and document the various aspects of elective inguinal hernia repair performed by general surgeons working in the different university hospitals of Karachi, Pakistan.
Methods This questionnaire-based survey, carried out over a two-year period, involved 84 general surgeons of Karachi. The respondents were divided into groups and comparative analysis was carried out.
Results 65 respondents (77.4 percent) were male and 19 (22.6 percent) were female. Mean years and standard deviation since post graduation were 7.7 and 7.3 years, respectively. 60 respondents (71.4 percent) reported the routine use of prophylactic antibiotics in all inguinal hernia repairs. 34 respondents (40.5 percent) quoted "spinal anaesthesia" as their preferred type of anaesthesia, 46 respondents (54.8 percent) chose to perform the procedure as a day case, and 49 respondents (58.3 percent) reported mesh repair as their preferred type of repair. 60 respondents (71.4 percent) did not recommend the laparoscopic approach to hernia repair. Surgeons associated with private hospitals were found more likely to choose mesh as their preferred method of inguinal hernia repair (p-value is 0.007), but less likely to use prophylactic antibiotics (p-value is 0.05) and respondents with more than ten years of postgraduate experience were found more likely to perform hernia repairs on an inpatient basis (p-value is 0.045).
Conclusion Various aspects of management of inguinal hernias are still determined by the preference of the operating surgeon. Day case management of hernia repairs, routine use of prophylactic antibiotics, use of mesh and open repair of hernias were the practice of the majority of surgeons, although differences were noted in specific groups of surgeons.

Keywords: herniorrhaphy, inguinal hernia, mesh repair, open hernia repair
Singapore Med J 2006; 47(6): 512-517