High rates of metachronous colon cancer or dysplasia after segmental resection or subtotal colectomy in Crohn's colitis.

BACKGROUND: In ulcerative colitis, total proctocolectomy is the treatment of choice for patients with colonic dysplasia or cancer because of the high risk for metachronous neoplasia. It is unknown whether patients with Crohn's disease and colon cancer or dysplasia have a similar risk. METHODS: We retrospectively reviewed the charts of 75 patients treated at our center from 2001 to 2011 with Crohn's disease and colon cancer who underwent segmental resection or subtotal colectomy (STC). We then identified the presence or absence of subsequent colon cancer or dysplasia in these patients during the follow-up (0-19 years). RESULTS: Of the 64 patients with colon cancer, 25 had at least 1 metachronous cancer (39%). The mean time to a new cancer was 6.8 years. Eighty-five percent of patients (21/25) were undergoing annual screening colonoscopy. Of the 11 patients with dysplasia, 5 (46%) had a new dysplasia. Mean time to a new dysplastic lesion was 5.0 years. Nineteen of the 47 patients (40%) who had a segmental resection for colon cancer developed metachronous cancer and 6/17 patients (35%) with a STC had metachronous cancer. Two of the 4 patients (50%) with STC for dysplasia (50%) had a new dysplasia and 3/7 patients (43%) with segmental resection had a new dysplasia. There was no significant difference (P = 0.61) between recurrence rates in patients with segmental resection versus STC. CONCLUSIONS: The high rate of metachronous colon cancer after surgical resection suggests that total proctocolectomy should be considered. Larger studies are required to determine if the same is true for dysplasia.

Clinical presentation and outcomes of inflammatory bowel disease patients admitted to the intensive care unit.

BACKGROUND: Disease severity, immunosuppression, and malnutrition may impact morbidity and mortality of the critically ill patient with inflammatory bowel disease (IBD). The aim of this study was to identify potential predictive factors for mortality among IBD patients requiring admission to an intensive care unit (ICU). METHODS: All patients with an admitting diagnosis of ulcerative colitis or Crohn's disease presenting to the ICU at the Mount Sinai Medical Center from 2003 to 2008 were retrospectively analyzed. Data regarding IBD-specific features, medications, and surgical outcomes were collected as well as ICU-related morbidity and 30-day mortality. RESULTS: Ninety-five patients were admitted to the ICU out of a total of 6663 IBD-related hospital admissions with an overall 30-day mortality rate of 18.9%. The annual number of ICU admissions of all hospitalized IBD patients increased from 0.1% in 2003 to 2.6% of admissions in 2008. ICU-related variables associated with increased mortality included mechanical ventilation (P=0.0002), vasopressor requirement (P=0.0002), severe sepsis (P=0.0005), acute kidney injury (P=0.001), Acute Physiology and Chronic Health Evaluation II scores (P ≤ 0.0001), hypoalbuminemia (P=0.036), and thromboembolism (P=0.046). On multivariate analysis, elevated Acute Physiology and Chronic Health Evaluation II scores were the only independent predictor of mortality. CONCLUSIONS: Although the overall number of ICU admissions among IBD patients was low, the annual incidence rates of admissions are increasing. This patient subgroup had significant in-hospital morbidity and 30-day mortality. Earlier identification of potential risk factors leading to poorer outcome, particularly within the first 24 hours of ICU admission, may impact the triage and subsequent management of these critically ill patients.

Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis.

BACKGROUND & AIMS: In patients with severe corticosteroid-refractory ulcerative colitis, cyclosporine or infliximab may be added in an effort to induce remission. If the patient then fails either of these drugs, it is unknown whether success can be achieved by using the other agent. The aim of this study was to assess outcomes of using cyclosporine after failure of infliximab, and vice versa. METHODS: We retrospectively reviewed the charts of 19 patients with corticosteroid-refractory ulcerative colitis who received either infliximab after failed cyclosporine or cyclosporine after failed infliximab. Acute salvage therapy was defined as having received the alternate drug within 4 weeks of discontinuing the first agent. RESULTS: Ten patients received infliximab after failing cyclosporine; 9 patients received cyclosporine after failing infliximab. Four patients (40%) in the infliximab-salvage group achieved remission, as did 3 (33%) in the cyclosporine-salvage group. Remission lasted a mean of 10.4 months (range, 4.4-17.03 mo) and 28.5 months (range, 5.0-41.5 mo), respectively. Severe adverse events included one patient who developed sepsis and died after receiving infliximab salvage. One patient who received cyclosporine salvage developed herpetic esophagitis, and another patient who received cyclosporine salvage developed pancreatitis and bacteremia. CONCLUSIONS: In patients with severe corticosteroid-refractory ulcerative colitis who fail treatment with either cyclosporine or infliximab, remission rates using acute salvage therapy by crossing over to the other drug occur in approximately one third of patients and have limited duration. Serious adverse events occurred in 16%, including 1 death, suggesting that the risks of acute salvage therapy may outweigh the benefits.

Pouch-ouch.

PURPOSE OF REVIEW: For patients who require colectomy, the ileal pouch anal anastomosis operation has alleviated the need for permanent ileostomy and has improved associated self-esteem issues. The most common complication of this surgery, however, is pouchitis. This review highlights the most recent research in the pathophysiology, risk factors, diagnosis and management of pouchitis, and pouch surveillance for neoplasia in patients who had ulcerative colitis. RECENT FINDINGS: Markers of inflammation, including fecal lactoferrin and mucosal cytokines, have been reported as useful in differentiating between irritable pouch syndrome and pouchitis. Numerous risk factors for the development of pouchitis have been identified. They include the presence of perinuclear antinuclear cytoplasmic antibodies, steroid use prior to colectomy, dysplasia as the indication for colectomy, the presence of extraintestinal manifestations, and an elevated platelet count. Therapy for acute pouchitis remains a short course of antibiotics. For chronic pouchitis, studies found success with rifaximin, tinidazole, and oral budesonide. Cancer in the residual rectal mucosa, in the ileal mucosa, and in pouch polyps occurs frequently enough to warrant surveillance. SUMMARY: Risk factors for the development of pouchitis should be discussed with patients. Less invasive diagnostic strategies have been proposed and antibiotics are still the mainstay of therapy.

Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn's disease.

BACKGROUND & AIMS: The effect of infliximab infused at scheduled intervals on antibody formation, preinfusion trough serum concentrations of infliximab, and their clinical significance was evaluated in patients with Crohn's disease. METHODS: Antibodies to infliximab and trough serum infliximab were measured in 105 patients with Crohn's disease treated with 5 mg/kg infliximab for induction followed by maintenance episodic re-treatment (n = 23) or scheduled therapy at 6- to 8-week intervals (n = 82). RESULTS: After a median of 14 infusions (range, 2-45), 21% of patients had detectable antibodies, 25% were antibody negative, and 54% were antibody inconclusive. Antibody formation was higher after episodic compared with scheduled treatment (39% vs 16%; P = .036) and was associated with a higher rate of infusion reactions (50% vs 21%; P = .018). Ninety patients continued maintenance scheduled therapy beyond 12 months including 12 converted episodic patients, with a median follow-up of 23 months (range, 16-68 months). The rate of clinical remission was higher for patients with a detectable trough serum infliximab compared with patients in whom serum infliximab was undetectable, including those without antibodies (82% vs 6%; P < .001). A detectable trough serum infliximab was also associated with a lower C-reactive protein (2.0 vs 11.8 mug/L; P < .001) and a higher rate of endoscopic improvement (88% vs 33%; P < .001). Concurrent immunomodulators did not alter outcomes. CONCLUSIONS: For Crohn's disease patients treated with scheduled maintenance infusions of infliximab, the trough serum concentration of infliximab predicts clinical outcome. Factors in addition to antibody formation, likely pharmacokinetic, modulate serum infliximab and thus the response to infliximab therapy.