Expert Opinion on Laparoscopic Surgery for Colorectal Cancer Parallels Evidence from a Cumulative Meta-Analysis of Randomized Controlled Trials

PMID: 22532846 [PubMed - indexed for MEDLINE] PMCID: PMC3332109 Free PMC ArticlePeer reviewedPublisher PD

Biological actions of glucagon-like peptide-2

grantor: University of TorontoIn the following set of studies, we demonstrate for the first time that exogenous administration of a human degradation resistant analog, h[Gly2]-GLP-2, attenuated intestinal damage in rodent models of small and large intestinal injury, and following the administration of chemotherapy in both non-tumour and tumour bearing mice. Several novel concepts have emerged from these experiments regarding the biology of GLP-2 'in-vivo': (i) In the experimental models that examined the effect of different GLP-2 treatment regimens on animal survival and intestinal growth parameters, the administration of GLP-2 as a pretreatment regimen was more effective then administration of GLP-2 concomitantly with or following the onset of intestinal injury. (ii) In addition to enhancing cellular proliferation within the small and large intestinal crypts, GLP-2 inhibited apoptotic cell death in a position-dependent manner within the crypt cell compartment and in heterologous cells expressing the GLP-2 receptor (BHK-GLP-2R cells). (iii) GLP-2 treatment attenuated the systemic dissemination of intestinal bacterial flora commonly observed following intestinal epithelial injury. (iv) GLP-2 treatment reduced intestinal proinflammatory TH1 and macrophage-derived cytokine levels, reduced neutrophil infiltration following the onset of intestinal inflammation, and attenuated chemotherapy and indomethacin-induced leukopenia. (v) Circulating levels of the GLP-2 degrading enzyme dipeptidyl peptidase IV (DPP-IV) were reduced in human patients with both Crohn's disease and ulcerative colitis. Changes in circulating DPP-IV activity, resulting in increased levels of biologically active GLP-2, emphasize the importance of endogenous GLP-2 clearance as part of the normal intestinal adaptive response to injury. Taken together, the experimental studies presented in this thesis have contributed novel insights into the actions of GLP-2 at the molecular, cellular, and whole organism level in the setting of intestinal disease. While many unanswered questions remain, the present set of studies raise the possibility of utilizing GLP-2 in the treatment of several human conditions, including inflammatory bowel diseases and chemotherapy-induced enteritis, and provide a scientific rationale for future human experimentation.Ph.D

Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors

In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption

Complications of Enterocutaneous Fistulas and Their Management

Complications related to enterocutaneous fistulas are common and include sepsis, malnutrition, and fluid or electrolyte abnormalities. Intestinal failure is one of the most feared complications of enterocutaneous fistula management and results in significant patient morbidity and mortality. The authors review emerging trends in the medical and surgical management of patients with intestinal failure