No abstract

Increased LT-PA is associated with a modest reduction in colon but not rectal cancer risk; a risk reduction, which previously may have been overstated. LT-PA only interventions in public health cancer prevention strategies are unlikely to impact substantially on colorectal cancer incidences.

An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.

Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic differences, which merit further research.

The prognostic significance of identifying lymph node (LN) metastases following surgical resection for colon and rectal cancer is well recognized and is reflected in accurate staging of the disease. An established body of evidence exists, demonstrating an association between a higher total LN count and improved survival, particularly for node negative colon cancer. In node positive disease, however, the lymph node ratios may represent a better prognostic indicator, although the impact of this on clinical treatment has yet to be universally established. By extension, strategies to increase surgical node harvest and/or laboratory methods to increase LN yield seem logical and might improve cancer staging. However, debate prevails as to whether or not these extrapolations are clinically relevant, particularly when very high LN counts are sought. Current guidelines recommend a minimum of 12 nodes harvested as the standard of care, yet the evidence for such is questionable as it is unclear whether an increasing the LN count results in improved survival. Findings from modern treatments, including down-staging in rectal cancer using pre-operative chemoradiotherapy, paradoxically suggest that lower LN count, or indeed complete absence of LNs, are associated with improved survival; implying that using a specific number of LNs harvested as a measure of surgical quality is not always appropriate. The pursuit of a sufficient LN harvest represents good clinical practice; however, recent evidence shows that the exhaustive searching for very high LN yields may be unnecessary and has little influence on modern approaches to treatment.

CD105 and its ligand transforming growth factor b (TGFb) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40 -9.00) and 3.10 (range 0.90 -8.00), respectively. Kaplan -Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFb1 and TGFb3 together with the receptor -ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFb1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFb1 level was noted in patients with carcinoma over the controls. Furthermore, TGFb3 and CD105/ TGFb3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFb1 was expressed in cancer cells but TGFb3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFb1, TGFb3 and CD105/TGFb complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.

Dysplastic transformation within the ileal pouch mucosa in patients operated for ulcerative proctocolitis is rare even after a long follow-up. These results are reassuring for both patients and surgeons. There seem to be no solid grounds to support routine surveillance for dysplasia in the ileal pouch mucosa in these patients. The surveillance for neoplastic changes in the remaining muscular/epithelial cuff is a separate issue however.

Laparoscopic surgery has already begun to influence the management of diverticular disease, but the randomized controlled trials needed to support therapy decisions are largely missing.