How do we improve outcomes for gastric cancer?

Although the incidence of gastric cancer is decreasing globally, it remains the second leading cause of cancer death, accounting for 600,000 deaths annually worldwide. It is particularly common in Asia and especially in China, Japan and Korea. In Singapore, it is the fourth commonest cancer in men, who have a 1:50 lifetime risk of developing gastric cancer. Gastric cancer traditionally carries a poor prognosis because of late presentation at an advanced stage of disease. If diagnosed at an early stage, it is a curable disease. Four strategies will systematically help to improve outcomes for gastric cancer: (i) early detection by screening of high-risk groups; (ii) clarification of the hypothesis that Helicobacter pylori eradication in endemic areas with a high incidence of gastric cancer is an effective primary prevention strategy; (iii) improvement of treatment by well-designed clinical trials, coupled with molecular characterization of tumors; and (iv) improving our biological understanding of gastric carcinogenesis.     

Irinotecan-induced mucositis manifesting as diarrhoea corresponds with an amended intestinal flora and mucin profile

Chemotherapy-induced diarrhoea is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy. Irinotecan is linked with severe mucositis and diarrhoea, the mechanisms of which remain poorly understood. Bacterial β-glucuronidase is thought to be involved in the metabolism of irinotecan, implicating the intestinal flora. Intestinal mucins may also be implicated in the development of chemotherapy-induced diarrhoea. Rats were treated with 200 mg/kg of irinotecan and killed at 96, 120 and 144 h. The rats were monitored for diarrhoea. Pathology and immunohistochemical staining was performed. The samples were cultured and faecal DNA was analysed using real-time polymerase chain reaction. Severe diarrhoea was observed from 72 to 96 h. A decrease in body mass was also observed after treatment. Significant changes in goblet cell numbers (both complete and cavitated cells) were observed in the small and large intestines. Changes in MUC gene expression were observed in the small intestine only. Modifications were observed to the intestinal flora profile, especially Escherichia coli , and an increase in the expression of β-glucuronidase was detected. In conclusion, irinotecan-induced diarrhoea may be caused by an increase in some β-glucuronidase-producing bacteria, especially E. coli , exacerbating the toxicity of active metabolites. Accelerated mucous secretion and mucin release may also contribute to the delayed onset of diarrhoea.     

Chemotherapy-induced mucositis: the role of gastrointestinal microflora and mucins in the luminal environment

Collectively, mucositis refers to the damage caused to the mucous membranes of the body following cytotoxic cancer therapy. Diarrhea is one such manifestation of mucositis and is a common side effect of chemotherapy that remains poorly understood. It affects the entire gastrointestinal tract. The exact number of patients affected by diarrhea as a result of treatment is uncertain, although it is believed that approximately 10% of patients with advanced cancer will be affected. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhea, has not been well defined, and the underlying mechanisms of the condition have yet to be established. The majority of the literature concerning diarrhea is based on clinical observations, with little basic research. However, from the research conducted, it is likely that the intestinal microflora play a role in the development of chemotherapy-induced diarrhea. This review will examine in detail what is known about the mechanisms of chemotherapy-induced diarrhea and will explore the potentially important relationship among intestinal microflora, the luminal environment, and the subsequent development of chemotherapy-induced diarrhea.     

Xenobiotic and folate pathway gene polymorphisms and risk of childhood acute lymphoblastic leukaemia in Javanese children

Xenobiotic and folate metabolic pathways are important for the maintenance of genetic stability and may influence susceptibility to the development of childhood acute lymphoblastic leukaemia (ALL). In this study, we investigated 10 polymorphisms in 6 genes (GSTM1‐present/null, GSTT1‐present/null, GSTP1 1578A > G, NQO1 609C > T, MTHFR 677C > T, MTHFR 1298A > C, MTHFD1 1958G > A, 3′‐TYMS 1494 6bp‐deletion/insertion, 5′‐TYMS 28bp‐tandem repeats, and SLC19A1 80G > A) in a cohort of 185 Javanese children with ALL and 177 healthy controls. In ALL patients, none of the polymorphisms demonstrated a statistically significant association with ALL after correcting for multiple comparisons. Gender‐stratified analysis showed that in girls, GSTT1‐null genotype was associated with increased ALL risk (OR = 2.20; p = 0.027), while GSTP1 1578AG genotype was associated with reduced risk (OR = 0.43; p = 0.031). Strong linkage disequilibrium between the MTHFR 677C > T and 1298A > C polymorphisms was observed (D′ = 1.0; r² = 0.072). The haplotypes 677C‐1298C and 677T‐1298A were associated with a reduced risk of ALL (OR = 0.68 and 0.64, respectively; gender‐adjusted global p = 0.028). Classification and regression tree (CART) analysis was employed to identify potential high‐order gene‐gene interactions and cluster subjects into susceptibility groups. SLC19A1 80G > A emerged as the predominant polymorphism associated with risk of ALL. Individuals simultaneously carrying MTHFR 1298AA, 3'‐TYMS 6bp deletion(s) and SLC19A1 80A‐allele(s) were at higher disease risk (OR = 2.21; p < 0.001). On the contrary, simultaneous possession of MTHFR 1298CC, 3'‐TYMS 6bp homozygosity and SLC19A1 80A‐allele(s) conferred lower risk (OR = 0.25; p = 0.004). Carriage of NQO1 609C‐allele amongst SLC19A1 80GG genotype was associated with lower risk (OR = 0.47; p = 0.003). In conclusion, our study has demonstrated the importance of gender and gene‐gene interaction within the xenobiotic and folate pathways in modulating childhood ALL susceptibility. Copyright © 2010 John Wiley & Sons, Ltd.     

Cerebral Tuberculoma

SUMMARY Intracranial tuberculoma has become a rarity. It remains a curable lesion that responds well to medical therapy. Although diagnosis in developed countries is often made only postoperatively, early and effective treatment can be instituted if a high index of suspicion is maintained and diagnostic criteria are looked for. A case is presented which illustrates the difficulties in reaching a diagnosis, and a review of the literature is given.