Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.

Unravelling the pathogenesis of inflammatory bowel disease

High serum procalcitonin concentrations in patients with sepsis and infection.

Epidemiology and Natural History of Inflammatory Bowel Diseases

Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)60750-8.pdf

Inflammatory bowel disease: cause and immunobiology

OBJECTIVE: The aim of this randomized multicenter trial was to assess the rate of symptomatic anastomotic leakage in patients operated on with low anterior resection for rectal cancer and who were ...

Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer : A randomized multicenter trial

Objective. Surgical technique and peri-operative management of rectal carcinoma have developed substantially in the last decades. Despite this, morbidity and mortality after anterior resection of the rectum are still important problems. The aim of this study was to identify risk factors for anastomotic leakage in anterior resection and to assess the role of a temporary stoma and the need for urgent re-operations in relation to anastomotic leakage.Patients and methods. In a nine-year period, from 1987 to 1995, a total of 6833 patients underwent elective anterior resection of the rectum in Sweden. A random sample of 432 of these patients was analysed (sample size 6.3%). The associations between death and 10 patient-and surgery-related variables were studied by univariate and multivariate analysis. Data were obtained by review of the hospital files from all patients.Results. The incidence of symptomatic clinically evident anastomotic leakage was 12% (53/432). The 30-day mortality was 2.1% (140/6833). The rate of mortality associated with leakage was 7.5%. A temporary stoma was initially fashioned in 17% (72/432) of the patients, and 15% (11/72) with a temporary stoma had a clinical leakage, compared with 12% (42/360) without a temporary stoma, not significant. Multivariate analysis showed that low anastomosis (≤ 6 cm), pre-operative radiation, presence of intra-opcrative adverse events and male gender were independent risk factors for leakage. The risk for permanent stoma after leakage was 25%. Females with stoma leaked in 3% compared to men with stoma who leaked in 29%. The median hospital stay for patients Arithout leakage was 10 days (range 5-61 days) and for patients with leakage 22 days (3-110 days).Conclusion. In this population based study, 12% of the patients had symptomatic anastomotic leakage after anterior resection of the rectum. Postoperative 30-day mortality was 2.1%. Low anastomosis, pre-operative radiation, presence of intra-operative adverse events and male gender were independent risk factors for symptomatic anastomotic leakage in the multivariate analysis. There was no difference in the use of temporary stoma in patients with or without anastomotic leakage.

Risk factors for anastomotic leakage after anterior resection of the rectum

Forty two Crohn's disease patients were followed up after ileocolic resection with regard to symptoms and endoscopic appearance of the ileocolic anastomosis. Twenty eight patients resected because of colonic neoplasm served as controls. In all the Crohn's disease patients the ileal resection margin was disease free macroscopically at operation. In addition, intraoperative ileoscopy was performed in 13 and no sign of residual inflammation in the neoterminal ileum was seen. Endoscopy soon after surgery often showed preanastomotic ileal ulceration before symptoms appeared, whereas no anastomotic lesions were observed in the controls. Thus, 22 of 30 Crohn's disease patients examined had ulceration of the anastomotic area after three months, but only 10 had developed symptoms indicating relapse (73 v 33%). Corresponding figures in the 30 patients examined after one year were 93 v 37%, and in 14 patients after three years they were 100 and 86% respectively. The inflammatory lesions in all cases were preanastomotic, in the neoterminal ileum, and showed time related progression from aphthae to larger ulcers and stricture. The study suggests that endoscopically observed inflammatory lesions that appear soon after ileocolic resection for Crohn's disease signify new inflammation and not residual, persistent disease or incomplete anastomotic healing. The data further suggest that despite clinical remission after apparently radical intestinal resection, the bowel is permanently inflamed in Crohn's disease.

https://gut.bmj.com/content/gutjnl/33/3/331.full.pdf

Natural course of Crohn's disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms.

ObjectiveThe authors compared clinical bowel function and complications of a low anterior resection with either a straight or colonic J pouch anastomosis.Summary Background DataUrgency and frequent bowel movements after rectal resection with a low anastomosis have been related to the loss of rectal

Randomized comparison of straight and colonic J pouch anastomosis after low anterior resection.

Early results after rectal cancer surgery in a defined population were compared before and after the introduction of total mesorectal excision. In the first period (1984–1986) 211 cases of rectal cancer were diagnosed and in the second (1990–1992) 230. Of these, 134 patients in the first period (group 1) had anterior resection or abdominoperineal excision which was considered curative. In the second period 128 curative anterior resections and abdominoperineal excisions were performed by a limited number of surgeons familiar with total mesorectal excision (group 2). No differences between the groups were found in stage distribution, rate of curative operations, postoperative complications or postoperative mortality. Local recurrence had developed in 19 patients in group 1 and in eight in group 2, 1 year after the end of the study periods (P = 0·03). Local radicality was in doubt in 13 patients in group 1 and in eight in group 2. In the remaining 121 and 120 patients, 13 and four local recurrences respectively were present (P = 0·03). Actuarial analysis showed a significant reduction in local recurrence rate (P = 0·03) and an increase in crude survival (P = 0·03) at 4 years in group 2 compared with group 1. Total mesorectal excision reduces the local recurrence rate after excision of rectal cancer.

Rune Sjödahl

Papers

Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer : A randomized multicenter trial

Risk factors for anastomotic leakage after anterior resection of the rectum

Natural course of Crohn's disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms.

Randomized comparison of straight and colonic J pouch anastomosis after low anterior resection.

Local recurrence following total mesorectal excision for rectal cancer.