Proceedings of Singapore Healthcare
Volume 19 Number 1 2010
Gastroenterology and Hepatology Issue
EDITORIAL
Novel Tests and Technology in Colorectal Care Diagnosis
Ling KL
ORIGINAL ARTICLE
Preliminary Results of Mismatch Repair Deficiency Screening via Immunohistochemical Staining in Young Asian Colorectal Cancers
Koh PK, Chew MH, Tan YS, Lim KH, Loi C, Tang CL, Eu KW
Abstract
Background: The incidence of mismatch repair (MMR) deficiency in young colorectal cancers (CRC) remains unknown in Asians. This preliminary study assessed the clinicopathological features and efficacy of screening for MMR protein deficiency in young Asian CRC patients.
Methods: From January 2006 to October 2009, patients under the age of 50 with immunohistochemical (IHC) staining for MMR proteins in resected CRC specimens were retrieved from a prospective computerised database.
Results: Eighty unrelated patients comprising predominantly 80% Chinese (n = 64), with median age of diagnosis at 41 years (range 22–50 years) had IHC performed. Twenty-three per cent (n=18) of the patients had abnormal IHC staining. Loss of staining for MLH1, MSH2 and MSH6 proteins were observed in 18%, 2% and 6% of tumours respectively. Of the 15 patients who had abnormal staining of MLH1, three had concomitant equivocal staining for MSH6. One tumour specimen had abnormal staining in all 3 proteins. Multivariate analysis revealed that family history was the only significant predictive factor for defective MMR detection (OR 8.06, 95% CI 1.69-38.35, p=0.002). However if Amsterdam criteria alone were to be used, 72% (n=12) of the cohort would have not been detected for MMR gene defects.
Conclusion: The overall burden of germline MMR deficiency in the Singapore population may be as high as 23%. Amsterdam criteria alone are insufficient to detect hereditary non-polyposis colorectal cancer (HNPCC) related patients. The use of IHC staining of at least 3 MMR proteins is a useful screening strategy for HNPCC diagnosis and routine screening of mismatch repair deficiency may be recommended for all young Asian CRC patients.
Keywords: Asian, HNPCC, immunohistochemistry, young colorectal cancers
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Different cagA and vacA Polymorphisms are Found in the Chinese versus the Malay and Indian Populations: An Analysis of Helicobacter pylori Virulence Genes in Singapore
Lui SY, Chuah SW, Goh HL, Lee KY, Lee VS, Ho B, Ling KL
Abstract
Aim: Helicobacter pylori causes peptic ulcer disease and gastric cancer. Western studies suggest that polymorphisms in the virulence factors cagA and vacA may determine the ability of bacteria to cause gastroduodenal diseases. Differences in the cagA EPIYA motifs and polymorphisms of the signal (s), middle (m) and intermediate (i) regions of vacA are thought to be important. The aim of this study was to compare the polymorphisms of cagA and vacA of H. pylori isolated from the Chinese, Malay and Indian populations living in Singapore.
Method: A total of 104 H. pylori isolates obtained from patients with dyspeptic symptoms were analysed. Of the 104 patients, 80 were Chinese, 9 Malays and 15 Indians. DNA was extracted from the isolates and the vacA allelic types and cagA EPIYA motifs were determined by polymerase chain reaction (PCR) and sequencing, respectively.
Results: Differences in the vacA and cagA polymorphisms were found between the Chinese, Malays and Indians. Significantly more non-Chinese patients carried vacA s1/m1 strains versus Chinese patients (p<0.05). All 9 Malay patients, 11/15 (73.3%) Indians and 31/80 (38.8%) Chinese patients carried H. pylori strains with the vacA s1/m1/i1. Significantly more Chinese patients carried isolates with East Asian cagA EPIYA motifs versus non-Chinese patients (p<0.05). 79/80 (98.8%) of the Chinese isolates, 2/15 (13%) of Indian isolates, and 5/9(55.6%) of Malay isolates possessed CagA with the East Asian ABD type motif.
Conclusion: Results from the current study demonstrated marked differences in the polymorphisms of vacA and CagA EPIYA motifs in strains isolated from Chinese versus non-Chinese patients. Epidemiologically, the Chinese are at the highest risk of developing gastric cancer. Work is ongoing to determine if differences found in the CagA EPIYA motifs of isolates from the Chinese patients can contribute to a subject’s risk of developing gastric cancer.
Keywords: cagA EPIYA motif, Helicobacter pylori, polymorphism, vacA
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REVIEW
The Role of Endoscopy in the Management of Cystic Pancreatic Lesions
Ang TL
Abstract
Pancreatic cystic lesions may be due to pseudocysts and related inflammatory fluid collections, simple cysts, cystic tumours such as serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm, as well as solid tumours with areas of cystic degeneration. The main diagnostic challenge is to distinguish premalignant and malignant cystic lesions from benign cystic lesions. Cross-sectional imaging using computer tomography and magnetic resonance imaging/ magnetic resonance cholangiopancreatography provides the initial morphological characterization. Endoscopic ultrasound (EUS) is an important tool when diagnostic doubts persist and is crucial in the assessment of invasive malignancy. EUS-guided fine needle aspiration and cyst fluid analysis has been shown to be cost-effective for risk stratifying the malignant potential of cystic tumours and the need for surgical resection. In the management of symptomatic pseudocysts and related fluid collections, endoscopic drainage has been established as the preferred technique, with efficacy similar to surgery but lower costs and morbidity.
Keywords: endosonography, pancreas, pseudocysts, tumours
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An Introduction to MR Perfusion Imaging of the Liver
Thng CH, Hartono S, Koh TS, Koh DM
Abstract
This article introduces the basic principles of magnetic resonance (MR) perfusion imaging of liver and summarized the currently available literature. Perfusion magnetic resonance imaging (MRI) is a functional imaging technique that quantifies the microcirculatory status of liver parenchyma and liver lesions such as flow, permeability, fractional intravascular volume and fractional interstitial volume. It potentially allows one to (i) detect liver metastases, (ii) assess effectiveness of anti-angiogenic therapy, (iii) assess viable tumour after therapy or ablation, and (iv) diagnose cirrhosis and assess its severity. Further work is required to establish and validate perfusion MRI as a clinical modality.
Keywords: DCE MRI, perfusion MRI, tracer kinetic modelling
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Non-alcoholic Fatty Liver Disease
Tan HH, Chang JPE
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from benign hepatic steatosis to non-alcoholic steatohepatitis with inflammation (NASH) and liver cirrhosis. NAFLD is now recognised as the hepatic manifestation of the metabolic syndrome. Simple steatosis is benign, whereas NASH can progress to cirrhosis with its resultant complications. Liver biopsy remains the gold standard in the diagnosis of NAFLD/NASH. Lifestyle and dietary modifications to achieve sustained weight loss is the cornerstone of NAFLD/NASH treatment.
Keywords: cirrhosis, fibroscan, metabolic syndrome, steatosis, steatohepatitis
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Narrow Band Imaging and Autofluorescence Imaging for the Detection and Optical Diagnosis of Colorectal Polyps
Thia KTJ, Kong CSC, Ooi CJ
Abstract
Colorectal cancer is the most common cancer in Singapore and polyps which are detected during screening colonoscopy are routinely removed. Conventional white light colonoscopy has a substantial miss-rate for polyps and limited accuracy in differentiating neoplastic from non-neoplastic polyps. Dye-based chromoendoscopy and more recent equipment-based image enhanced endoscopic techniques such as narrow-band imaging (NBI) and autofluorescence imaging (AFI) are promising tools to improve polyp detection and optical diagnosis. Current evidence suggests that NBI may not be superior compared to high definition white-light for polyp detection, but it achieves excellent accuracy in polyp characterisation, approaching that of histopathology. AFI is a wide area scanning modality which functions as a red-flag technique to improve polyp detection, although the evidence is still evolving. The ability to accurately characterise polyps with NBI and AFI will guide the management of polyps and in some cases, avoid unnecessary polypectomy and routine histopathology. This has potential to reduce associated costs and risks of polypectomy, and improves on overall efficiency of screening colonoscopy. The review will discuss the technology, current evidence and the issues relevant to the role of NBI and AFI for the detection and optical diagnosis of polyps in colorectal cancer screening.
Keywords: autofluorescence, chromoendoscopy, colorectal polyp, optical diagnosis, narrow band imaging
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Molecular Genetics of Gastric Adenocarcinoma
Eng AKH, Kon OL
Abstract
Gastric carcinoma is the second leading cause of cancer deaths in the world. Its aetiology is closely linked to the bacterial pathogen Helicobacter pylori which is believed to induce a state of chronic inflammation that predisposes to a cascade of molecular and cellular alterations leading to carcinogenesis. Although the exact process of gastric carcinogenesis has yet to be elucidated fully, the interaction of the genetic factors with environmental factors is likely to be a significant consideration. Numerous genes and molecular pathways have been discovered to be associated with gastric adenocarcinoma and more importantly, it is now becoming possible to use some of these as means of prognostication and targeted therapy. This review will outline our current understanding of the aetiology and molecular genetics of gastric adenocarcinoma and its current clinical applications.
Keywords: aetiology, cancer, carcinogenesis, Helicobacter, stomach
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Innovative Proven Clinical Research Strategies for Participant Recruitment and Retention
Tong SC, Tin AS, Lim JFY
Abstract
The ability to successfully recruit and retain research participants is an important precursor to conducting a successful clinical trial. With respect to participant recruitment, we discuss potential strategies used in well-known and successful research studies to reach out to the targeted populations, including public education on the importance of clinical trials and the use of new media in reaching out to a wider population. The measures used by research studies to engage their participants and their healthcare providers to optimise participant retention are also examined. We conclude by discussing how these strategies may be adapted for use in Singapore.
Keywords: clinical research, recruitment, retention
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CASE REPORT
Allergic Eosinophilic Gastroenterocolitis: Review of the Nutritional Management
Han WM, Tan N, Chiang WC, Chu HP
Abstract
The immunopathologies of food allergies can involve Immunoglobulin E (IgE), or non-IgE, or have a mixed IgE and non-IgE response. In the past decade, food allergy manifestations have evolved and there have been increased reports of the latter two presentations. A case report of a young child with allergic eosinophilic gastroenterocolitis, with a mixed immune reaction is described. The nutritional management of the condition is reviewed.
Keywords: allergy, attributes, elimination diet, eosinophilic, gastroenterocolitis, immunoglobulin E (IgE)
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Necrotising Fasciitis in the Elderly: A Double Delay
Cheah KL, Surrun SK
Abstract
Necrotising fasciitis is an uncommon and rapidly progressive infection of the subcutaneous tissues and fascia which results in necrosis. Without prompt and aggressive surgical intervention, it inevitably leads to severe sepsis and multiorgan failure with a high mortality rate. In general, the diagnosis of infection in the elderly is often difficult, regardless of the type of infection. We report a case of necrotising fasciitis in a 95-year-old lady. The patient presented with bowel and urinary symptoms as well as left leg pain suggestive of sciatica. There was no sign of cellulitis and intravenous antibiotic was started for a presumed urinary tract infection. The diagnosis of necrotising fasciitis was made only much later when crepitus was noted in her leg and radiological studies confirmed gas in the soft tissues. The patient and her family declined surgery and she subsequently died from septicaemia. This condition posed a diagnostic dilemma in the absence of fever, sudden onset of severe pain, and cutaneous findings. In order to reduce morbidity and mortality a high degree of suspicion is required to reach an early diagnosis for prompt surgical intervention.
Keywords: diagnostic delay, necrotising soft tissue infection, subcutaneous fat
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IMAGING
An Uncommon Cause of Abdominal Pain and Vomiting in a 55-year-old Woman
Chang JPE, Cheng LTE, Low ASC
Abstract
Abdominal pain is a symptom that is commonly encountered in clinical practice. Evaluation of abdominal pain involves the exclusion of a myriad of possible diagnosis. This case illustrates an uncommon cause of abdominal pain and vomiting in a 55-year-old female with diagnostic radiological features.
Keywords: hernia, obstruction, paraduodenal, small bowel
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LABORATORY INSIGHTS
Liver Function Tests (LFTs)
Yap CYF, Aw TC
Abstract
Each liver function test by itself is neither highly sensitive nor specific but when interpreted together may provide the clinician with useful information about the patient’s liver, and may also indicate other health issues such as malnutrition and bone disease.
Keywords: albumin, ALP, ALT, AST, bilirubin, hepatocellular injury, liver function tests
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STATISTICS
Three Myths about Biostatisticians
Tan SB