Stasis predisposes ileal pouch inflammation in a rat model of ileal pouch-anal anastomosis.

BACKGROUND: While restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the definitive surgical treatment for patients suffering from chronic ulcerative colitis (CUC), pouchitis still remains a major late complication. Fecal stasis has been implicated in the etiology of ileal inflammation; however, the mechanism(s) remain unclear, in part due to the lack of an animal model. Our goal was to surgically mimic the IPAA procedure in a rat to investigate the hypothesis that stasis leads to biochemical changes that predispose the ileal pouch to inflammation. MATERIALS AND METHODS: Thirty-two Sprague-Dawley rats underwent total colectomy with either straight ileorectal (IRA) or IPAA, and 11 nonoperated rats served as controls (Controls). Twenty-one d postoperatively, 48 h serial barium radiographs and 12 h charcoal transit follow-through studies were performed. Following sacrifice, ileal tissue was harvested for the measurement of myeloperoxidase activity (MPO) activity, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) mRNA levels, and histology. RESULTS: Serial barium radiographs showed stasis in the ileal pouch compared with IRA animals, and charcoal transit times that were two times longer (P ≤ 0.05) than that in the straight IRA rats. Ileal pouch MPO levels were significantly elevated in the IPAA rats compared with the straight IRA rats. ICAM-1 and VCAM-1 mRNA levels were not associated with neutrophil infiltration. CONCLUSIONS: These studies showed that ileal pouch stasis predisposes biochemical and histological evidence of ileal pouch mucosal inflammation. Studies such as this may provide the rationale for novel, adjunct therapies for the management of pouchitis in patients having undergone IPAA for CUC.

Laparoscopic gastric bypass for morbid obesity decreases bodily pain, improves physical functioning, and mental and general health in women.

INTRODUCTION: Surgery is an effective long-term therapeutic option for morbid obese patients. Although bariatric surgery's amelioration of medical ailments is well established, its nonphysical benefits have not been as well documented. METHODS: Women who had undergone laparoscopic gastric bypass between August 2003 and May 2005 were provided with an SF-36 1 month before surgery, as well as 1, 3, 6, 9, 12, 15, and 18 months after surgery. Those women who completed three surveys were included in this study. Scores were summed for each of six areas analyzed: physical function, physical role limitations, emotional role limitations, bodily pain, mental health, and general health. The results of the preoperative and the last postoperative surveys were compared using Wilcoxon's signed-rank test. RESULTS: Of 91 women considered for this study, 40 (44%) completed at least three postoperative surveys. For bodily pain, physical function, physical role limitations, mental health, and general health, median postoperative exceeded median preoperative scores (P < 0.004 for each analysis); for emotional role limitations, the median postoperative score was the same as the median preoperative score. CONCLUSIONS: In women, gastric bypass for morbid obesity decreases bodily pain and physical role limitations, and improves physical functioning as well as mental and general health. The positive impact of laparoscopic gastric bypass is thus validated by the SF-36 questionnaire.

Morbid obesity causes chronic increase of intraabdominal pressure.

Intraabdominal hypertension and the abdominal compartment syndrome are known to deleteriously affect a wide array of organ systems. We retrospectively reviewed 62 women who underwent either laparoscopic gastric bypass surgery or adjustable gastric banding. Their age, body mass index (BMI), and race were known. Their opening abdominal pressure was recorded by connecting a Verress needle to a pressure monitor. Linear regression was used to assess the contribution of age, race, and BMI to the observed variation in opening abdominal pressure. Neither variation in age or race explained the variation in opening pressure (P > .05). By contrast, variation in BMI explained 8% of the observed variation in opening pressure (P < .05). For every 1 kg/mm(2) increase in BMI, there was on average a 0.07 mm Hg increase in opening pressure. Increases in BMI are associated with increases in intraabdominal pressure.

A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus.

Ileal pouch-anal anastomosis (IPAA) is an excellent surgical option for patients with chronic ulcerative colitis (CUC) requiring colectomy; however, persistent episodes of ileal pouch inflammation, or pouchitis, may result in debilitating postoperative complications. Because considerable evidence implicates substance P (SP) as an inflammatory mediator of CUC, we investigated whether SP participates in the pathophysiology of pouchitis. With the use of a rat model of IPAA that we developed, we showed that ileal pouch MPO levels and neurokinin 1 receptor (NK-1R) protein expression by Western blot analysis were significantly elevated 28 days after IPAA surgery. In situ hybridization and immunohistochemistry showed that the increase in NK-1R protein expression was localized to the lamina propria and epithelia of pouch ileum. The intraperitoneal administration of the NK-1R antagonist (NK-1RA) CJ-12,255 for 4 days, starting on day 28, was effective in reducing MPO levels. Starting on day 28, animals with IPAA were given 5% dextran sulfate sodium (DSS) in their drinking water for 4 days, which caused histological and physical signs of clinical pouchitis concomitant with significant increases in ileal pouch MPO concentrations as well as NK-1R protein expression by Western blot analysis. In situ hybridization and immunohistochemistry showed that the increase in NK-1R protein expression was especially evident in crypt epithelia of pouch ileum. When the NK-1RA was administered 1 day before starting DSS and continued for the duration of DSS administration, the physical signs of clinical pouchitis and the rise in MPO were prevented. These data implicate SP in the pathophysiology of pouchitis and suggest that NK-1RA may be of therapeutic value in the management of clinical pouchitis.

Pouchitis in a rat model of ileal J pouch-anal anastomosis.

Endorectal ileal pouch-anal anastomosis (IPAA) has become the operation of choice for patients with chronic ulcerative colitis. Although this procedure improves the quality of life, pouchitis remains a significant postoperative complication. Because our understanding of the pathophysiology of pouchitis may, in part, be due to the lack of small animal model, our aim was to develop a model of IPAA in a rat that mimics its clinical counterpart. Colectomy, proctectomy, construction of an ileal J pouch, and ileal pouch-rectal anastomosis as a model of IPAA was performed in Sprague-Dawley and Lewis rats. Radiographic contrast studies were performed to quantitate intestinal transit. The presence of activated neutrophils was quantified by measuring mucosal myeloperoxidase (MPO) activity. Oxidative stress was quantitated by measuring urinary 8-isoprostane (8-IP) levels. Anaerobic and aerobic bacterial counts were determined on Brucella and tryptic soy agar plates, respectively. Dextran sulfate sodium (DSS) was used to exacerbate ileal J pouch inflammation. Mortality was low, and animals gained weight normally after recovery. Stasis was documented radiographically. MPO levels were elevated (p < 0.05) in the ileal J pouch 30 and 60 days after IPAA, indicating an inflammation that was associated with stasis and bacterial overgrowth. 8-IP levels were elevated by 80% compared with controls. Oral administration of 5% DSS to IPAA rats with further elevated MPO and 8-IP levels in concert with a pouchitis-like syndrome that included the physical, gross, and histologic characteristics of clinical pouchitis. An understanding of the pathophysiology of pouchitis is essential to the future development of new therapeutic modalities. This model is applicable to investigating several key etiologic mechanisms purportedly related to pouchitis.