A conscious mouse model of gastric ileus using clinically relevant endpoints

BACKGROUND: Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. METHODS: Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. RESULTS: Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. CONCLUSION: Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of stomach function appears to be simultaneous to colonic recovery

Association Between Postoperative Complications and Clinical Cancer Outcomes

ABSTRACT Introduction. The treatment for a majority of solid organ tumors is surgical resection; 10-20 % of patients suffer a perioperative complication. Perioperative complications may contribute to cancer recurrence. This study examined the relationship between postoperative complications and risk-adjusted patient overall survival. Methods. Data from 2003 to 2009 were linked from our clinical cancer registry, the National Surgery Quality Improvement Project (NSQIP), and medical records. Patients who had tumor extirpation for cure were included. The NSQIP was used to identify complications. Patients with a complication were matched to patients without a complication. v 2 tests and Cox proportional hazard regression models were used. Results. A total of 415 patients were included for survival analysis. The hazard ratio (HR) for mortality associated with having a complication was 2.17. The HR for mortality after 200 days postoperatively was 2.47. Infectious complications were associated with the highest association with increased mortality (HR = 3.56). Noninfectious complications were not associated with an increased risk of mortality. Conclusions. This study investigated the relationship of surgical infectious complications in cancer patients with long-term survival for patients who had a number of different types of cancer. After taking into account the site, histology, and stage of the cancer, we found that patients with infectious complications had earlier death. The primary treatment for the majority of solid organ tumors remains surgical tumor extirpation. The complex nature of these surgeries leads to a high rate of perioperative complications, occurring in 5-30 % of all cases