Phaik-Leng Cheah

Ethnicity and H. Pylori as risk factors for gastric cancer in Malaysia: a prospective case control study.

OBJECTIVE:To determine the risk factors for gastric cancer (GCA), with particular emphasis on ethnicity in our multiracial population.METHODS:A prospective case control study with ratio of cancer:controls of 1:2. Diagnosis of H. pylori was made by serology using the ELISA technique. Dietary intake was assessed by dietary recall over the preceding 6 months.RESULTS:Eighty-seven cases of GCA were enrolled. The cancers were predominantly distal in location and of the intestinal type. Risk factors identified following multiple logistic regression analysis were: Chinese race (OR 10.23 [2.87–36.47]), H. pylori (OR 2.54 [1.16–5.58]), low level of education (OR 9.81 [2.03–47.46]), smoking (OR 2.52 [1.23–5.15]), and high intake of salted fish and vegetables (OR 5.18 [1.35–20.00]) were identified as significant independent risk factors for GCA, while high intake of fresh fruits and vegetables was protective for GCA (OR 0.15 [0.04–0.64]). Chili intake was not a significant protective factor following multivariate analysis.CONCLUSIONS:Chinese race was a strong independent predictor of GCA. H. pylori was an important predictor of GCA with a 2.5-fold greater risk in our patients. Despite a high prevalence of H. pylori, the prevalence of GCA among Indians was low and this paradox can be appropriately called the “Indian enigma.”

Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8+CD56+ (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαβ over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8+ cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

Evaluation of a new biopsy urease test: Pronto Dry, for the diagnosis of Helicobacter pylori infection.

Background The gastric biopsy urease test is the most frequently used test for the diagnosis of Helicobacter pylori infection in routine gastrointestinal endoscopy practice. In Malaysia up to recently, only one commercial biopsy urease test was available: the CLO test (Ballard Medical Products, Draper, Utah, USA). Large endoscopy units use their own ‘homemade’ unbuffered ultra rapid urease test for diagnosis of H. pylori infection. Objective To compare the accuracy and reaction time of a new biopsy urease test, Pronto Dry (Medical Instruments Corporation, Solothurn, Switzerland) and the CLO test in the diagnosis of H. pylori infection. Methods Consecutive patients presenting with dyspepsia to the endoscopy unit, University of Malaya Medical Centre were recruited for the study. Patients who were previously treated for H. pylori infection or who had received antibiotics, proton pump inhibitors or bismuth compounds in the preceding 4 weeks were excluded. H. pylori diagnosis was made based on the ultra rapid urease test and histological examination of gastric biopsies. Four antral and four corpus biopsies were taken for this purpose from all patients. A diagnosis of H. pylori infection was made when both the ultra rapid urease test and histology were positive in either the antral or corpus biopsies. A negative diagnosis of H. pylori was made when both tests from antral and corpus biopsies were all negative. Another four antral and four corpus biopsies (two each) were taken for the Pronto Dry and CLO tests. The Pronto Dry and CLO tests were stored and performed according to the manufacturers instruction. Results Two hundred and eight patients were recruited in the study. Eighty-six of the patients were males and 122 were females. The mean age was 46.3 years with a range of 15–82 years. The results for both the Pronto Dry and the CLO tests were completely concordant with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 98.1%, 100%, 100%, 98.1% and 99%, respectively. The Pronto Dry test showed a faster reaction time to positive compared with the CLO test, with 96.2% positive reaction by 30 min versus 70.8% and 100% positive reaction time by 55 min versus 83%. The colorimetric change was also more distinct with the Pronto Dry test compared with the CLO test. Conclusions Both the Pronto Dry and the CLO tests were highly accurate for the diagnosis of H. pylori infection. The Pronto Dry test showed a quicker positive reaction time and the positive colour change was more distinct.

Clinical Predictors of Non-diabetic Renal Disease and Role of Renal Biopsy in Diabetic Patients with Renal Involvement: A Single Centre Review

Background: Type 2 diabetes mellitus (T2DM) is reportedly the leading cause of end-stage renal disease (ESRD) worldwide. However, non-diabetic renal diseases (NDRD) are not uncommon among T2DM patients with renal involvement. Our study aimed to examine the prevalence of NDRD in T2DM and clinical markers for diabetic nephropathy (DN) and NDRD and to determine the role of renal biopsy in T2DM patients and its impact on clinical practice. Methods: We conducted a retrospective analysis of T2DM patients in whom renal biopsies were performed from January 2004 to March 2008 (n = 110). Results: Biopsy results were divided into three groups: group I/pure DN (62.7%), group II/isolated NDRD (18.2%), and group III/mixed lesions (19.1%). The causes of NDRD in decreasing order of frequency were acute interstitial nephritis, glomerulonephritides, hypertensive renal disease, and acute tubular necrosis. Significant clinical markers for DN are presence of diabetic retinopathy and longer duration of diabetes. For NDRD, useful clinical markers include the presence of acute renal failure and microscopic hematuria. In the DN subgroup, Indians had significantly shorter duration of diabetes on biopsy compared with Malays and Chinese. Conclusions: NDRD is prevalent in T2DM patients, and given its potentially treatable nature, renal biopsy should be considered in T2DM patients with nephropathy, especially in those with atypical features.

Non-alcoholic fatty liver disease in Malaysia: a demographic, anthropometric, metabolic and histological study.

BACKGROUND AND OBJECTIVES:  Nonalcoholic fatty liver disease (NAFLD) is increasing rapidly in the Asia–Pacific region. There has been a paucity of studies from the region. The aims of this study were to define the demographic, anthropometric, metabolic and histological characteristics of patients with NAFLD in our local population and to determine independent predictors of severe liver fibrosis.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene.

Genetic polymorphism has been implicated as a factor for the occurrence of non‐alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin‐like phospholipase domain‐containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.

Childhood primary hepatocellular carcinoma and hepatitis B virus infection.

In the 7‐year period between 1980 and 1987, six cases of childhood primary hepatocellular carcinoma (PHC) were confirmed histologically in our institution. Hepatitis B surface antigen (HBsAg) seropositivity was confirmed in five of the cases, and tissue HBsAg was shown in four of these using the Shikatas orcein stain. An associated maternal HBsAg seropositivity was shown in two of the seropositive children. The youngest seropositive patient who developed PHC was 7 years old. The mother of this patient was also seropositive. These observations support a causal relation between childhood Hepatitis B virus infection and PHC. The importance of vertical or perinatal transmission of HBV in the causation of childhood PHC and the prophylactic role of childhood vaccination is emphasized. Attention is also drawn to the relative short malignant transformation time seen in some of these patients.

Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma

Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma

Comparison of two 1-week low-dose omeprazole triple therapies--optimal treatment for Helicobacter pylori infection?

To determine and compare the efficacy and tolerability of two 1‐week regimen comprising omeprazole, clarithromycin and amoxycillin or metronidazole in the eradication of Helicobacter pylori, and to determine the influence of bacterial resistance to metronidazole and clarithromycin on the outcome of treatment.