Alterations in enteric calcitonin gene-related peptide in patients with colonic diverticular disease: CGRP in diverticular disease.

Diverticular disease (DD) is one of the most prevalent diseases of the large bowel. Lately, imbalance of neuro-muscular transmission has been recognized as a major etiological factor for DD. Neuronal calcitonin gene-related peptide (CGRP) is a potent gastrointestinal smooth muscle relaxant shown to have a widespread effect within the alimentary tract. Nevertheless, CGRPergic innervation of the enteric ganglia has never been considered in the context of motility impairment observed in DD patients. Changes in CGRP and calcitonin receptor-like receptor (CRLR) abundance within enteric ganglia were investigated in sigmoid samples from symptomatic and asymptomatic DD patients using quantitative fluorescence microscopy. CGRP effect on gastrointestinal smooth muscle was investigated using organ bath technique. We found CGRP levels within the enteric ganglia to be declined by up to 52% in symptomatic DD patients. Conversely, CRLR within the enteric ganglia was upregulated by 41% in symptomatic DD. Longitudinal smooth muscle displayed an elevated (+10.5%) relaxant effect to the exogenous application of CGRP in colonic strips from symptomatic DD patients. Samples from asymptomatic DD patients consistently showed intermediate values across different experiments. In conclusion, the present study demonstrates that CGRPergic signaling is subject to alteration in DD. Our results suggest that a hypersensitization mechanism to gradually decreasing levels of CGRP-IR nerve fibers takes place during DD progression. Alterations to CGRPergic signaling in DD disease may have implications for physiological abnormalities associated with colonic DD.

Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery.

AIM: The aim of this study was to compare the downstaging achieved after long-course chemoradiotherapy (chRT) and short-term radiotherapy (sRT) followed by delayed surgery. METHOD: A randomized controlled trial was carried out. Eighty-three patients with resectable stage II and III rectal adenocarcinoma were randomized to receive long-course chemoradiotherapy (46) and short-term radiotherapy (5×5 Gy) (37). Surgery was performed 6 weeks after preoperative treatment in both groups. RESULTS: The R0 resection rate was 91.3% in the chRT and 86.5% in the sRT group (P=0.734). Sphincter preservation rates were 69.6%vs 70.3% (P=0.342) and postoperative complication rates were 26.1%vs 40.5% (P=0.221). There were more patients with early pT stage [pT0 (complete pathological response) pT1] in the chRT group [21.8%vs 2.7% (P=0.03)] and more patients with pT3 disease in the sRT group [75.7%vs 52.2% (P=0.036)]. There were no differences in pN stage and lymphatic or vascular invasion in either group. Pathological downstaging (stage 0 and I) was observed in eight (21.6%) patients in the sRT group and in 18 (39.1%) in the chRT group (P=0.07). Tumours were smaller after preoperative ChRT (2.5 cm vs 3.3 cm; P=0.04). CONCLUSION: Long-course preoperative chemoradiation resulted in greater statistically significant tumour downsizing and downstaging compared with short-term radiation, but there was no difference in the R0 resection rates. Similar postoperative morbidity was observed in each group.

Morbidity predicting factors of penetrating colon injuries.

THE AIM: To analyze patients suffering from penetrating colon injuries management, clinical outcomes and factors, which predict higher morbidity and complications rate. METHODS: this was a retrospective analysis of prospectively collected data from patients with injured colon from 1995 to 2008. Age, time till operation, systolic blood pressure, part of injured colon, fecal contamination, PATI were registered. Monovariate and multivariate logistic regression was performed to determine higher morbidity predictive factors. RESULTS: 61 patients had penetrating colon injuries. Major fecal contamination of the peritoneal cavity and systolic blood pressure lower than 90 mmHg are independent factors determining the fecal diversion operation. Primary repair group analysis establish that major fecal contamination and systolic blood pressure lower than 90 mmHg OR = 4.2 and 0.96 were significant risk factors, which have contributed to the development of postoperative complications. And systolic blood pressure lower than 90 mmHg and PATI 20 predict OR = 0.05 and 2.61 higher morbidity. CONCLUSIONS: Fecal contamination of the peritoneal cavity and hypotension were determined to be crucial in choice of performing fecal diversion or primary repair. But the same criteria and PATI predict higher rate of postoperative complications and higher morbidity.