Regional differences in outcomes of nonvariceal upper gastrointestinal bleeding in Saskatchewan.

BACKGROUND: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is associated with significant mortality. OBJECTIVE: To examine several factors that may impact the mortality and 30-day rebleed rates of patients presenting with NVUGIB. METHODS: A retrospective study of the charts of patients admitted to hospital in either the Saskatoon Health Region (SHR) or Regina Qu'Appelle Health Region (RQHR) (Saskatchewan) in 2008 and 2009 was performed. Mortality and 30-day rebleed end points were stratified according to age, sex, day of admission, patient status, health region, specialty of the endoscopist and time to endoscopy. Logistic regression modelling was performed, controlling for the Charlson comorbidity index, age and sex as covariates. RESULTS: The overall mortality rate observed was 12.2% (n=44), while the overall 30-day rebleed rate was 20.3% (n=80). Inpatient status at the time of the rebleeding event was associated with a significantly increased risk of both mortality and rebleed, while having endoscopy performed in the RQHR versus SHR was associated with a significantly decreased risk of rebleed. A larger proportion of endoscopies were performed both within 24 h and by a gastroenterologist in the RQHR. CONCLUSION: Saskatchewan has relatively high rates of mortality and 30-day rebleeding among patients with NVUGIB compared with published rates. The improved outcomes observed in the RQHR, when compared with the SHR, may be related to the employ of a formal call-back endoscopy team for the treatment of NVUGIB.

Src family kinase members have a common response to histone deacetylase inhibitors in human colon cancer cells.

Histone deacetylase inhibitors (HDIs) induce cell cycle arrest, differentiation and/or apoptosis in numerous cancer cell types and have shown promise in clinical trials. These agents are particularly novel, given their ability to selectively influence gene expression. Previously, we demonstrated that the HDIs butyrate and trichostatin A (TSA) directly repress c-Src proto-oncogene expression in many cancer cell lines. Activation and/or overexpression of c-Src have been frequently observed in numerous malignancies, especially of the colon. Therefore, our observation was particularly interesting since butyrate is a naturally abundant component of the large intestine and has been suggested to be a cancer-preventive agent. However, c-Src is not the only Src family kinase (SFK) member to be implicated in the development of human cancers, including those of the colon. Therefore, the relative expression levels of known SFKs were examined in a panel of human colon cancer cell lines. We found a surprisingly diverse expression pattern but noted that most cell lines expressed relatively high levels of at least 2 SFKs. When the effects of butyrate and TSA were examined in representative cell lines, the expression of all SFKs was repressed in a dose- and time-dependent manner. Further, detailed examination of Lck, Yes and Lyn demonstrated that this repression had a direct effect on transcription and was independent of new protein synthesis. These results mirror our earlier data obtained with c-Src and suggest that SFKs are a major target of HDIs and likely account in part for the anticancer effects of these promising new drugs.