Faculty Bibliography

BACKGROUND & AIMS: We investigated the association between the severity of primary sclerosing cholangitis (PSC) and clinical outcomes of patients with ulcerative colitis (UC) on the basis of need for colectomy. METHODS: We analyzed data from 167 patients with PSC and UC who were followed from 1985 to 2011. Patients with PSC and UC were divided into groups that received orthotopic liver transplantation (OLT) (n = 86) or did not (non-OLT, n = 81). Clinical and demographic variables were obtained, and patients were followed until they received OLT or the date of their last clinical visit. RESULTS: The OLT group had significantly more subjects with less severe symptoms of UC (59, 68.6%) than the non-OLT group (12, 14.8%; P < .001). The subjects in the OLT group had a median of 0 UC flares compared with 3 in the non-OLT group (P < .001); fewer subjects in the OLT group required use of azathioprine or mercaptopurine (1, 1.2%), compared with the non-OLT group (14, 17.3%; P = .006). More subjects in the non-OLT group required colectomies (61, 75.3%) than in the OLT group (23, 26.7%; P < .001). On the basis of Cox regression analysis, OLT for PSC independently reduces the need for colectomy (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.25-0.75; P = .003), as does a high Mayo risk score at diagnosis (HR, 0.52; 95% CI, 0.37-0.72; P < .001). Development of colon neoplasia increased the risk for colectomy (HR, 2.47; 95% CI, 1.63-3.75; P < .001). CONCLUSIONS: Severe progressive PSC that requires liver transplantation appears to reduce the disease activity of UC and the need for colectomy.

BACKGROUND: The pattern and severity of postoperative complications after colectomy and total proctocolectomy with ileoanal pouch for patients with IBD with liver cirrhosis from primary sclerosing cholangitis have not been well characterized. OBJECTIVE: This study aimed to evaluate the immediate and long-term outcomes for patients with cirrhosis from primary sclerosing cholangitis undergoing colectomy for IBD. DESIGN: This is a retrospective study. SETTING: This study was conducted at Cleveland Clinic, a tertiary medical center. PATIENTS: From 1989 to 2009, 23 patients (22 ulcerative colitis and 1 Crohn's disease) who underwent colectomy were included. RESULTS: The mean duration of primary sclerosing cholangitis before surgery was 6.8 +/- 4.9 years, and the mean duration of IBD was 18 +/- 10.7 years. All patients had cirrhosis; the mean Model for Endstage Liver Disease score was 9.3 +/- 1.6, and most patients were Child Pugh class A or early B. Eight patients were on the orthotopic liver transplantation list. Indications for colectomy were dysplasia (n = 13), failure or complications of medical therapy (n = 7), cancer (n = 2), and colonic perforation at colonoscopy (n = 1). Nineteen patients (82.6%) developed postoperative complications including bleeding (43.5%), ileus (17.4%), wound infection (8.7%), worsening liver function (34.8%), pelvic abscess (13%), and deep vein thrombosis (8.7%). Two patients, both after total proctocolectomy/IPAA, died of septic shock after pelvic abscess in the postoperative period. Two patients underwent transjugular intrahepatic portosystemic shunt procedure before total proctocolectomy/IPAA; none developed pelvic abscess or mortality. There were no differences in mortality or morbidity between patients who underwent an ileoanal pouch procedure or colectomy with ileostomy. CONCLUSIONS: Colectomy in patients with IBD complicated with cirrhotic primary sclerosing cholangitis is associated with a high early postoperative morbidity rate. Due consideration needs to be given to strategies to reduce pelvic sepsis, especially after ileoanal pouch, because this is associated with mortality.

BACKGROUND: The risks and benefits of pouch excision and end ileostomy creation when compared to the alternative option of a permanent diversion with the pouch left in situ when restoration of intestinal continuity is not pursued for patients who develop pouch failure after IPAA have not been well characterized. OBJECTIVE: This study aimed to compare the early and long-term outcomes after permanent diversion with the pouch left in situ vs pouch excision with end ileostomy creation for pouch failure. DESIGN: This study is a retrospective review of prospectively gathered data. SETTINGS: This investigation was conducted at a tertiary center. PATIENTS: Patients with pouch failure who underwent a permanent ileostomy with the pouch left in situ and those who underwent pouch excision were included in the study. MAIN OUTCOME MEASURES: The primary outcomes measured were the perioperative outcomes and quality of life using the pouch and Short Form 12 questionnaires. RESULTS: One hundred thirty-six patients with pouch failure underwent either pouch left in situ (n = 31) or pouch excision (n = 105). Age (p = 0.72), sex (p = 0.72), ASA score (p = 0.22), BMI (p = 0.83), disease duration (p = 0.74), time to surgery for pouch failure (p = 0.053), diagnosis at pouch failure (p = 0.18), and follow-up (p = 0.76) were similar. The predominant reason for pouch failure was septic complications in 15 (48.4%) patients in the pouch left in situ group and 39 (37.1%) patients in the pouch excision group (p = 0.3). Thirty-day complications, including prolonged ileus (p = 0.59), pelvic abscess (p = 1.0), wound infection (p = 1.0), and bowel obstruction (p = 1.0), were similar. At the most recent follow-up (median, 9.9 y), quality of life (p = 0.005) and health (p = 0.008), current energy level (p = 0.026), Cleveland Global Quality of Life score (p = 0.005), and Short Form 12 mental (p = 0.004) and physical (p = 0.014) component scales were significantly higher after pouch excision than after pouch left in situ. Urinary and sexual function was similar between the groups. Anal pain (n = 4) and seepage with pad use (n = 8) were the predominant concerns of the pouch left in situ group on long-term follow-up. None of the 18 patients with pouch in situ, for whom information relating to long-term pouch surveillance was available, developed dysplasia or cancer. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: Although technically more challenging, pouch excision, rather than pouch left in situ, is the preferable option for patients who develop pouch failure and are not candidates for restoration of intestinal continuity. Because pouch left in situ was not associated with neoplasia, this option is a reasonable intermediate or long-term alternative when pouch excision is not feasible or advisable.

BACKGROUND: "Indefinite for dysplasia" (IND) on pouch mucosal biopsy is occasionally reported during routine histopathological evaluation. The natural history and implication of this histologic entity in ileal pouch-anal anastomosis (IPAA) has not been studied. AIM: The aim of this study is to characterize cumulative probability, natural history, and clinical outcome of pouch IND in a cohort of patients with inflammatory bowel disease (IBD). METHODS: All 932 patients with restorative proctocolectomy and IPAA for IBD were included. Patients with or without IND were classified into the study and control groups. Demographic, clinical, endoscopic, and histologic variables were analyzed. RESULTS: The mean duration from IBD diagnosis to colectomy and from pouch construction to data entry was 8.4 +/- 8.5 and 9.7 +/- 6.2 years, respectively. A total of 2,250 surveillance or diagnostic pouchoscopies with biopsies were performed for the cohort. Twenty-one patients (2.3%) were diagnosed with anal transitional zone and/or pouch IND, for whom subsequent pouchoscopies were performed with the mean procedure number being 3.4 +/- 2.2 per patient during a mean of follow-up of 19.3 +/- 16.1 months. One patient with IND developed low-grade dysplasia and one had high-grade dysplasia in a separate endoscopy. Cox model showed the presence of primary sclerosing cholangitis was an independent risk factor for pouch IND [hazard ratio = 6.76 (95% CI 2.56-17.88)]. Interobserver agreement (kappa score) for diagnosing pouch IND between GI pathologists ranged from 0.67 to 0.76. CONCLUSIONS: Subsequent dysplasia was uncommon in pouch patients with IND. Natural history of pouch IND warrants further long-term investigation.

BACKGROUND: Surgery in patients with inflammatory bowel disease (IBD) is often associated with complications. The aim of our study was to evaluate whether concomitant IBD was associated with an increased risk of postcholecystectomy complications. METHODS: The study group consisted of 82 consecutive IBD patients who underwent cholecystectomy from January 2001 to October 2010. The control group included 296 cholecystectomy patients without IBD who were randomly selected from the cholecystectomy database. Variables were analyzed by univariate and multivariate analyses. RESULTS: There were no significant differences in age, gender, body mass index, presence of gallstones/common bile duct stones, indication for cholecystectomy, and postoperative mortality between the study and control groups. More patients in the study group had postoperative complications than in the control group (17.1% vs. 6.8%, P = 0.005). On multivariate analysis, the presence of concomitant IBD was independently associated with an increased risk for postoperative complications (odds ratio [OR] = 4.64; 95% confidence interval [CI], 1.63-13.20, P = 0.004) after adjusting for age, the presence of cirrhosis, diabetes, body mass index, the use of corticosteroids, immunomodulators, total parental nutrition, or biologics, the presence of primary sclerosing cholangitis (PSC), acute or chronic cholecystitis, cholelithiasis, or prior abdominal surgeries, and indication for surgery (elective vs. emergent). CONCLUSIONS: IBD patients undergoing cholecystectomy have a significantly increased risk of postoperative complications. Although further studies are warranted to clarify the reason for these differences, caution should be taken to determine the need and timing of cholecystectomy in IBD patients.

BACKGROUND: Inflammatory bowel disease (IBD) is reported to be associated with autoimmune pancreatitis. The aim of the study was to investigate serum IgG4 and tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouches. METHODS: Ninety-seven consecutive persistent symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic from January to December 2010 were included in the study. Serum IgG4 was measured at the time of presentation. All patients underwent pouchoscopy with pouch biopsies immunostained for IgG4+ plasma cells. Patients with >/=10 per high-power field of IgG4+ plasma cells were considered positive for the stain. RESULTS: Twenty-eight (28.9%) patients had positive IgG4 immunostaining of pouch and/or afferent limb biopsy, while the remaining 69 patients (71.1%) were IgG4 negative. Demographic and symptoms were similar between the two groups. The median serum IgG4 in the IgG4 positive group was 21.3 (interquartile range 0-41.3) mg/dL vs. 0 (interquartile range 0-18) in the IgG4 negative group. (p=0.04). On multivariate analysis, the Pouchitis Disease Activity Index (PDAI) endoscopy score in the pouch (odds ratio [OR] 1.66, 95% confidence interval [CI]: 1.21-2.29, p=0.002) and number of concomitant autoimmune disorders (OR 3.04, 95% CI: 1.22-7.53, p=0.017) were independent risk factors for the presence of IgG4+ plasma cell infiltration. CONCLUSIONS: Increased IgG4+ plasma cells were found in 1/4 of IPAA patients with persistent symptoms. The presence of tissue infiltration of IgG4+ plasma cells appeared to be associated with chronic pouch inflammation and concurrent autoimmune disorders.

BACKGROUND AND AIM: Patients with ulcerative colitis (UC) are at an increased risk for low bone mineral density (BMD). It is unclear whether proctocolectomy with ileal pouch-anal anastomosis (IPAA) for UC alters the risk of bone loss. The aim of this study was to compare BMD in UC patients with and without IPAA. METHODS: A total of 267 patients with UC and IPAA (study group) were compared to 119 UC patients without IPAA (control group) in this cross-sectional study. The demographic and clinical variables including dual-energy X-ray absorptiometry scan results were compared. Patients were classified as having normal or low BMD, based on the criteria by the International Society for Clinical Densitometry. Univariate and multivariate analyses were performed to assess risk factors associated with low BMD. Age, gender, race, smoking status, steroid use, alcohol use, body mass index, years of absent estrogen protection, use of calcium, vitamin D supplements and disease duration were selected as covariates. RESULTS: 83 (31.1%) had low BMD in the study group vs. 18 (15.1%) in the control group (p=0.001). 2/13 (15.4%) had low BMD before surgery. The mean age of patients in the study and control groups were 44.7 +/- 14.1 vs. 52.4 +/- 17.7 years, respectively (p<0.001). The hip BMD was lower in the study group (0.93 +/- 0.17 g/cm2) than that in the control group (0.98 +/- 0.17 g/cm2) (p=0.038). Fragility fracture was documented in 23 (8.6%) patients in the study group vs. 3 (2.5%) in the control group (p=0.038) Sixty-four (24.0%) of the study group patients were using corticosteroids after surgery in contrast to 93 (78.2%) in the control group (p<0.001). On multivariable analyses, covariate adjusted factors associated with a low BMD in UC patients were advanced age [odds ratio (OR) 1.51 per 5 years; 95% confidence interval [CI], 1.34-1.71], low body mass index (OR=2.37 per 5 kg/m(2) decrease; 95% CI, 1.68-3.36), and the presence of IPAA (OR=6.02; 95% CI, 2.46-14.70). For the 13 IPAA patients who had information available, BMD before IPAA was low. After a median of 46 (Range 7-84) months after IPAA, BMD improved in 7/13 patients (53.8%), while it continued to be low in 6/13 (46.2%) patients. CONCLUSIONS: Low BMD is common in patients with UC. The risk appears to persist even after colectomy and IPAA surgery suggesting that these patients need to be monitored for bone loss.

BACKGROUND: The aim of this study was to develop a novel prognostic model that captures complex interplay among clinical and histologic factors to predict survival of patients with colorectal cancer after a radical potentially curative resection. STUDY DESIGN: Survival data of 2,505 colon cancer and 2,430 rectal cancer patients undergoing radical colorectal resection between 1969 and 2007 were analyzed by random forest technology. The effect of TNM and non-TNM factors such as histologic grade, lymph node ratio (number positive/number resected), type of operation, neoadjuvant and adjuvant treatment, American Society of Anesthesiologists (ASA) class, and age in staging and prognosis were evaluated. A forest of 1,000 random survival trees was grown using log-rank splitting. Competing risk-adjusted random survival forest methods were used to maximize survival prediction and produce importance measures of the predictor variables. RESULTS: Competing risk-adjusted 5-year survival after resection of colon and rectal cancer was dominated by pT stage (ie, tumor infiltration depth) and lymph node ratio. Increased lymph node ratio was associated with worse survival within the same pT stage for both colon and rectal cancer patients. Whereas survival for colon cancer was affected by ASA grade, the type of resection and neoadjuvant therapy had a strong effect on rectal cancer survival. A similar pattern in predicted survival rates was observed for patients with fewer than 12 lymph nodes examined. Our model suggests that lymph node ratio remains a significant predictor of survival in this group. CONCLUSIONS: A novel data-driven methodology predicts the survival times of patients with colorectal cancer and identifies patterns of cancer characteristics. The methods lead to stage groupings that could redefine the composition of TNM in a simple and orderly way. The higher predictive power of lymph node ratio as compared with traditional pN lymph node stage has specific implications and may address the important question of accuracy of staging in patients when fewer than 12 nodes are identified in the resection specimen.

BACKGROUND: We hypothesized that patients with primary sclerosing cholangitis (PSC) may have a higher risk for prepouch ileitis in the setting of ileal pouch-anal anastomosis (IPAA). The aim of this study was to compare endoscopic and histologic inflammation in the afferent limb (prepouch ileum) and pouch between IPAA patients with and without PSC. METHODS: In all, 39 consecutive inflammatory bowel disease (IBD) and IPAA patients with PSC (study group) were identified and 91 IBD and IPAA patients without PSC (control group) were randomly selected with a 1:2 ratio. Demographic, clinical, endoscopic, and histologic variables were analyzed. RESULTS: There were no significant differences in age, gender, and nonsteroidal antiinflammatory drug use between the study and control groups. Twelve (30.8%) patients in the IPAA-PSC group had coexisting autoimmune disorders, in contrast to five (5.5%) patients in the IPAA control group (P < 0.001). More patients in the study group had endoscopic inflammation as demonstrated by the higher Pouchitis Disease Activity Index (PDAI) endoscopic scores of the afferent limb and pouch body than those in the control group (P = 0.02 and P < 0.001, respectively). In addition, more patients with PSC had higher PDAI histologic scores of the afferent limb than those without PSC (P < 0.001). Multivariate analysis showed higher PDAI endoscopy and histology subscores were associated with risk for PSC, with odds ratio 1.34 (95% confidence interval [CI]: 1.34, 3.79) and 1.61 (95% CI: 1.00, 2.58), respectively. CONCLUSIONS: Concurrent PSC appears to be associated with a significant prepouch ileitis on endoscopy and histology in patients with IPAA. Pouch patients with long segment of ileitis should be evaluated for PSC.

BACKGROUND & AIMS: There has been controversy over the significance of active inflammation of the terminal ileum (also known as backwash ileitis) in patients with ulcerative colitis (UC) and idiopathic inflammatory bowel disease of indeterminate type for diagnosis and pouch construction. We investigated the impact of backwash ileitis on pouch outcome after restorative proctocolectomy with ileoanal pouch anastomosis. METHODS: Data from patients with backwash ileitis (n = 132) were compared with those from 132 matched controls without ileal inflammation for age, sex, and type of proctocolectomies with ileal pouch construction (1- or 2-stage). We evaluated terminal ileal sections from original colectomies of 2213 patients with either UC or idiopathic inflammatory bowel disease of indeterminate type, collected during a 21-year period, for extent and severity of chronic and active ileitis. Clinical pouch outcomes were assessed through a longitudinally maintained clinical outcome database that systematically catalogued all short-term and long-term pouch complications, including pouchitis, sepsis, impaired long-term pouch survival, and conversion to Crohn's disease. RESULTS: Regardless of severity or extent, backwash ileitis was not correlated with any clinical outcome examined, short-term or long-term. CONCLUSIONS: Ileal inflammation is not a contraindication for restorative proctocolectomy with ileal pouch construction in patients with UC or idiopathic inflammatory bowel disease of indeterminate type. Ileal inflammation with pancolitis is not a useful criterion for classifying otherwise typical UC as colitis of indeterminate type, because pouch outcomes are not affected.