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

Can text-search methods of pathology reports accurately identify patients with rectal cancer in large administrative databases?

Background: The aim of this study is to derive and to validate a cohort of rectal cancer surgical patients within administrative datasets using text-search analysis of pathology reports. Materials and Methods: A text-search algorithm was developed and validated on pathology reports from 694 known rectal cancers, 1000 known colon cancers, and 1000 noncolorectal specimens. The algorithm was applied to all pathology reports available within the Ottawa Hospital Data Warehouse from 1996 to 2010. Identified pathology reports were validated as rectal cancer specimens through manual chart review. Sensitivity, specificity, and positive predictive value (PPV) of the text-search methodology were calculated. Results: In the derivation cohort of pathology reports (n = 2694), the text-search algorithm had a sensitivity and specificity of 100% and 98.6%, respectively. When this algorithm was applied to all pathology reports from 1996 to 2010 (n = 284,032), 5588 pathology reports were identified as consistent with rectal cancer. Medical record review determined that 4550 patients did not have rectal cancer, leaving a final cohort of 1038 rectal cancer patients. Sensitivity and specificity of the text-search algorithm were 100% and 98.4%, respectively. PPV of the algorithm was 18.6%. Conclusions: Text-search methodology is a feasible way to identify all rectal cancer surgery patients through administrative datasets with high sensitivity and specificity. However, in the presence of a low pretest probability, text-search methods must be combined with a validation method, such as manual chart review, to be a viable approach