Original Article

Chin CWD, Loh KS, Tan KSL
Correspondence: Dr Tan K S Luke, enttanl@nus.edu.sg

ABSTRACT
Introduction Elective hemithyroidectomy is a common operation with a low complication rate. The aim of this study was to conduct an audit on the safety and efficacy of ambulatory hemithyroidectomy in carefully-selected patients.
Methods This is a cohort study of 114 patients who were scheduled to have either ambulatory (50 patients) or inpatient (64 patients) hemithyroidectomy over a two-year period. Selection for day case surgery was based on pre-established criteria and patient preference. Preoperative patient characteristics, indications for surgery, operative characteristics, histological diagnoses and surgical complications are compared.
Results Of the 50 patients selected for day case surgery, 45 (90 percent) were discharged on the day of surgery. The complication rates of the two groups were similar. Two patients required admission for wound complications and the other three were admitted for non-medical reasons.
Conclusion The overall complication rate was low. There were no differences in the rate of complications between ambulatory and inpatient hemithyroidectomies. Ambulatory hemithyroidectomy can be performed safely for a select group of patients in the setting of appropriate facility and management protocol.

Keywords: ambulatory surgery, day surgery, outpatient surgery, postoperative haemorrhage, thyroidectomy
Singapore Med J 2007; 48(8): 720–724

Kumarasamy V, Chua SK, Hassan Z, Wahab AHA, Chem YK, Mohamad M, Chua KB
Correspondence: Dr Chua Kaw Bing, chuakawbing@yahoo.com.sg

ABSTRACT
Introduction The aim of this report is to establish an accurate diagnosis of acute dengue virus infection early, in order to provide timely information for the management of patients and early public health control of dengue outbreak.
Methods 224 serum samples from patients with a clinical diagnosis of acute dengue infection, which were subsequently confirmed by laboratory tests, were used to evaluate the performance of a commercially-available dengue NS1 antigen-capture ELISA kit.
Results The dengue NS1 antigen-capture ELISA gave an overall sensitivity rate of 93.3 percent (209/224). The sensitivity rate was significantly higher in acute primary dengue (97.4 percent) than in acute secondary dengue (68.8 percent). In comparison, the virus isolation gave an overall positive isolation rate of 64.7 percent, with a positive rate of 70.8 percent and 28.1 percent, for acute primary dengue and acute secondary dengue, respectively. Molecular detection of dengue RNA by RT-PCR gave an overall positive detection rate of 63.4 percent, with a positive rate of 62.5 percent and 68.8 percent, for acute primary dengue and acute secondary dengue, respectively. Of the 224 acute serum samples from patients with laboratory-confirmed acute dengue infection, dengue IgM was detected in 88 specimens, comprising 68 acute primary dengue specimens and 20 acute secondary dengue specimens. NS1 antigen-capture ELISA kit gave an overall sensitivity rate of 88.6 percent in the presence of anti-dengue IgM and 96.3 percent in the absence of anti-dengue IgM.
Conclusion Of the 224 acute serum samples, the sample ages of 166 acute serum samples are known. The positive detection rate of dengue NS1 antigen-capture ELISA, on the whole, was higher than the other three established diagnostic test methods for laboratory diagnosis of acute dengue infection.

Keywords: dengue virus, NS1 antigen-capture ELISA
Singapore Med J 2007; 48(7): 669–673

Yong YK, Thayan R, Chong HT, Tan CT, Sekaran SD
Correspondence: Dr S D Sekaran, shamalamy@yahoo.com

ABSTRACT
Introduction Dengue fever and dengue haemorrhagic fever currently rank highly among the newly-emerging infectious diseases, and are considered to be the most important arboviral disease worldwide. The definitive diagnosis is culture analysis, but practical considerations limit its use. Also, the period for viral detection is limited. Within a day or two after fever subsides, rising levels of antibodies interfere with viral cultures. An alternative to this quandary is the use of viral RNA detection assays. In our laboratory, a reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed using a set of degenerate primers.
Methods This multiplex RT-PCR assay was evaluated with 280 samples collected during the year 2003. These groups include prototype dengue virus (serotypes 1-4), acute serum from which the dengue virus was isolated, seronegative acute samples (culture negative) but whose convalescent samples seroconverted, and sera positive for other microbial diseases. This assay was then modified into a real-time SYBR Green RT-PCR assay. Sensitivity and specificity of both assays were compared.
Results The multiplex RT-PCR assay was able to detect 134 samples whereas SYBR Green RT-PCR assay was able to detect 178 out of 306 samples. Both assays were 100 percent specific. Further analysis of 53 samples showed that the virus could be amplified at IgM positive/negative values of up to 4.2, and up to six days after onset of fever. The viral detection rate was inversely proportional to the day of fever onset as well as IgM values.
Conclusion The sensitivity and specificity of the conventional multiplex RT-PCR assay are 98.18 percent and 100 percent, respectively, and for the real-time SYBR Green assay, 99.09 percent and 100 percent, respectively. The melting curve analysis allows all four dengue serotypes to be discriminated based on distinct melting temperature value. The accuracy and speed of this multiplex RTPCR assay makes it a suitable test for the diagnosis of dengue and for epidemiological surveillance.

Keywords: conventional multiplex RT-PCR, dengue virus, melt curve analysis, real-time SYBR Green RT-PCR
Singapore Med J 2007; 48(7): 662–668

Ong G, Rasidah N, Wan S, Cutter J
Correspondence: Dr Gary Ong, gary_ong@moh.gov.sg

ABSTRACT
Introduction Indigenous cases of measles continue to occur in Singapore despite the implementation of a two-dose mumps, measles and rubella (MMR) vaccination policy in 1998. We investigated a measles outbreak that took place in a primary school from April 17 to May 6, 2004 to identify all cases, evaluate vaccine efficacy (VE) and implement outbreak control measures.
Methods A case of measles was defined as anyone having generalised rash and fever with or without cough, coryza or conjunctivitis during the outbreak period, and who had either laboratory-confirmed acute measles infection or was epidemiologically linked to a patient with laboratory-confirmed measles infection. Vaccination status was obtained from the studentos health booklet and confirmed with the National Immunisation Registry. Attack rates in unvaccinated (ARU) and vaccinated (ARV) students were calculated and VE was evaluated using the formula: VE (percent) = [(ARU-ARV) / ARU] x 100 percent.
Results Nine students, aged between eight and 14 years, from five classes in primary three and primary six, were epidemiologically linked to have measles. None of them had received the second dose of the MMR vaccine. 93 percent of students in the affected classes (n = 184) had prior documented evidence of receiving at least one dose of MMR vaccination, as compared to 96.5 percent for the entire school enrolment (n = 1,309). The attack rate was 1.2 percent in the vaccinated group and 53.8 percent in the unvaccinated group. The VE for the primary dose of MMR in the affected classes was 97.8 percent.
Conclusion It is important to achieve a high coverage for the primary dose of MMR vaccine in order to prevent any potential outbreaks prior to receiving the booster dose.

Keywords: measles, measles outbreak, vaccine efficacy, vaccination coverage
Singapore Med J 2007; 48(7): 656–661

Lim CM, Lim J, Loh KS, Tan LKS
Correspondence: Dr Lim Chwee Ming, limchweeming@yahoo.com.sg

ABSTRACT
Introduction This study aims to retrospectively review our early experience with free tissue transfer in the reconstruction of head and neck defects following extirpation of head and neck cancers in a tertiary hospital in Singapore.
Methods A total of 25 patients underwent free tissue transfer between June 1998 and Oct 2003. An overall descriptive analysis was carried out by looking at the following outcome measures: length of hospitalisation, duration of intensive care unit (ICU) stay, readmission for complication, and failure rate.
Results There were 21 men and four women in our study cohort, with their age ranging from 28 to 89 (mean 59.8) years. The mean length of stay was 12.6 (SD 7.3) days and mean stay in ICU was 1.6 days. Two patients (8.0 percent) were readmitted within a 30-day period after discharge for flap-related complications. Six patients (24 percent) developed flap-related complications. Two patients developed pharyngocutaneous fistula, three patients developed flap venous congestion and one patient developed minor donor site haematoma. Salvage anastomotic revision was performed in all the three congested flaps. One of the flaps was successfully revived, while the other two flaps were lost. Hence, our flap success rate was 92 percent (23/25).
Conclusion Our early experience shows that free tissue transfer is a safe surgical option in the reconstruction of head and neck defects. Our success rate is 92 percent. We believe that subsequent results would continue to improve with advances in technical skill and experience.

Keywords: free tissue transfer, head and neck cancers, reconstructive surgery
Singapore Med J 2007; 48(7): 652–655

Manikandan P, Vidjaya Letchoumy P, Prathiba D, Nagini S
Correspondence: Dr Siddavaram Nagini, s_nagini@yahoo.com; snlab@sancharnet.in

ABSTRACT
Introduction This study was designed to evaluate the chemopreventive effects of ethanolic Ocimum sanctum (OS) leaf extract on cell proliferation, apoptosis and angiogenesis during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis.
Methods The rats were divided into four groups of ten each. Rats in group one were given MNNG (150 mg/kg body weight) by intragastric intubation three times, with a two-week interval between treatments. Rats in group two were administered MNNG as in group one, and in addition, they received intragastric intubation of ethanolic OS extract (300 mg/kg body weight) three times per week, starting on the day following the first exposure to MNNG. The intubation of ethanolic OS extract continued until the end of the experimental period. Rats in group three were given ethanolic OS leaf extract only. Group four served as controls. All the rats were killed after an experimental period of 26 weeks.
Results Intragastric administration of MNNG-induced well-differentiated squamous cell carcinomas that showed increased cell proliferation, and angiogenesis with evasion of apoptosis, as revealed by the upregulation of proliferating cell nuclear antigen (PCNA), glutathione S-transferase-pi (GST-pi), Bcl-2, cytokeratin (CK) and vascular endothelial growth factor (VEGF) and with downregulation of Bax, cytochrome C and caspase 3 protein expression. Administration of ethanolic OS leaf extract reduced the incidence of MNNG-induced gastric carcinomas. This was accompanied by decreased expression of PCNA, GST-pi, Bcl-2, CK and VEGF, and overexpression of Bax, cytochrome C, and caspase 3.
Conclusion This study provides evidence that, in MNNG-induced gastric carcinogenesis, the key proteins involved in the proliferation, invasion, angiogenesis and apoptosis, are viable molecular targets for chemoprevention using ethanolic OS leaf extract.

Keywords: apoptosis, cell proliferation, chemoprevention, gastric cancer, N-methyl-N’-nitro-N-nitrosoguanidine, Ocimum sanctum
Singapore Med J 2007; 48(7): 645–651

Sreedharan S, Pang CE, Chan GSW, Soo KC, Lim DTH
Correspondence: Dr Sreedharan S, sreedharan.sechachalam@singhealth.com.sg

ABSTRACT
Introduction Common modes of presentation of follicular thyroid carcinoma include a solitary thyroid nodule and cervical lymphadenopathy. We report four patients who presented with axial skeletal metastases rather than the usual neck lumps. 
Methods A review of a database of 389 cases of thyroid cancer, managed by our department from 1990 to 2003, was perfomed. Based on each patient's presenting clinical feature, patients for the case series were selected.
Results Four of the 389 patients presented with axial skeletal metastases - three were in the scalp while the fourth was in the sacral region. The histology of all four cases was that of follicular thyroid carcinoma. Despite widespread metastases at presentation, the overall survival rates of these patients remained relatively good.
Conclusion Patients presenting with lesions suspicious of secondary malignancy in the axial skeleton should be clinically evaluated for thyroid cancer. This is especially important if the patient belongs to a high risk age group and has highly vascular lesions.

Keywords: axial skeletal metastasis, follicular thyroid carcinoma, papillary thyroid carcinoma, sacral metastasis, scalp metastasis, thyroid carcinoma
Singapore Med J 2007; 48(7): 640–644

Lau WY, Lai ECH
Correspondence: Prof Lau Wan Yee, josephlau@cuhk.edu.hk

ABSTRACT
Introduction Nearly 50 percent of patients who have colorectal carcinoma will develop liver metastases, which is frequently the cause of death. Liver resection is the only curative treatment for patients with colorectal metastases confined to the liver. However, liver resection can be performed in only ten percent of patients. A strategy to improve resectability and outcome of patients with colorectal liver metastases is needed.
Methods The progress and outcome of patients, who had colorectal liver metastases and underwent liver resection in a tertiary surgical centre between January 1998 and December 2002, were retrospectively studied.
Results During the five-year study period, 42 patients with colorectal liver metastasis underwent hepatic resection. 36 patients received primary liver resection. Six patients with initially unresectable disease received salvage surgery after tumour downstaging with systemic chemotherapy. Five of the 42 patients needed repeat liver resection for recurrent colorectal liver metastases. The hospital mortality rate was 2.1 percent. 11.9 percent of patients had major postoperative complications. The median survival was 49 months. The one-, three- and five-year overall survival rates after resection were 91 percent, 54 percent, and 37 percent, respectively; and the recurrence rate was 76 percent. The five-year survival rate with salvage surgery after tumour downstaging was 34 percent, and the corresponding figure, after repeat liver resection, for recurrent liver metastases was 27 percent.
Conclusion Hepatic resection for colorectal metastases confined to the liver resulted in reasonably good long-term survival, with acceptably low operative mortality and morbidity. Our results were compatible with the international standard of liver resection for colorectal liver metastases.

Keywords: colonic cancer, colorectal liver metastasis, colorectal neoplasms, hepatectomy, tumour downstaging
Singapore Med J 2007; 48(7): 635–639

Lee LK, Tan EL, Gopala K, Sam CK
Correspondence: Mr Lee Lin Kiat, linkiatlee@gmail.com

ABSTRACT
Introduction Nasopharyngeal carcinoma (NPC) is the second most common cancer among Malaysian Chinese males. We determined the frequencies of 17 human leukocyte antigens (HLA), HLA-A and HLA-B, alleles in 88 Malaysian Chinese with NPC.
Methods Using polymerase chain reaction sequence-specific primers, the frequencies of 17 HLA-A and HLA-B alleles were analysed. They were A1, A2, A11, A31, A32, A33, B8, B13, B27, B38, B39, B44, B46, B55, B58, B61 and B71.
Results Three of the 17 alleles were detected in NPC patients. They were A1 (0.6 percent), A2 (56.3 percent) and A11 (43.2 percent). Three of the 17 alleles were detected in age- and sex-matched healthy individuals. They were A2 (50.0 percent), A11 (50.0 percent) and B27 (4.7 percent). The A2 and A11 alleles were evenly distributed in both groups, while A1 was only found in one NPC patient and B27 exclusively in healthy individuals.
Conclusion We conclude that A1 is very rare, and A2, A11, A31, A32, A33, B8, B13, B38, B39, B44, B46, B55, B58, B61 and B71 alleles have no associations with the occurrence of NPC in Malaysia, while allele B27 is negatively associated.

Keywords: human leukocyte antigen, nasopharyngeal carcinoma, polymerase chain reaction sequence-specific primers
Singapore Med J 2007; 48(7): 632–634

Liam CK, Pang YK, Poosparajah S
Correspondence: Prof Chong-Kin Liam, liamck@ummc.edu.my

ABSTRACT
Introduction This study aims to determine whether the diagnostic yield of flexible bronchoscopy sampling procedures in patients with lung cancer was dependent on tumour location.
Methods A retrospective analysis was conducted on the diagnostic yield of bronchial washing (BW), endobronchial biopsy (EBB), bronchial brushing (BB), bronchoalveolar lavage (BAL), blind brushing (B) and transbronchial biopsy (TBB) specimens obtained at fibre-optic bronchoscopy for patients with lung cancer.
Results Of 503 patients who underwent fibre-optic bronchoscopy examination, BW, EBB, BB, BAL, B and TBB were performed on 254, 325, 67, 155, 70 and 54 patients, respectively. For patients with bronchoscopically-visible tumours, BW, EBB and BB yielded diagnostic specimens for lung cancer in 28.3 percent, 77.5 percent and 53.7 percent of patients, respectively. For patients whose tumours were not visible bronchoscopically, BAL, B and TBB yielded diagnostic specimens for lung cancer in 35.5 percent, 22.9 percent and 31.5 percent of patients, respectively. EBB was less likely to be diagnostic in patients with tumours in the middle or lingular lobe bronchi. The diagnostic yields of all the other sampling techniques were not influenced by the location of the bronchoscopically-visible or non-visible tumours.
Conclusion The diagnostic yields of bronchoscopic sampling procedures were dependent on tumour visibility during bronchoscopy and location of bronchoscopically-visible tumours.

Keywords: bronchial brushing, broncho-alveolar lavage, bronchoscopy, endo-bronchial biopsy, lung cancer, transbronchial biopsy
Singapore Med J 2007; 48(7): 625–631