Faculty Bibliography

BACKGROUND: A proportion of UC patients with restorative proctocolectomy and IPAA develop pouch failure. Accurate risk assessment is critical for making proper evaluation and treatment. Information on factors that may reliably predict pouch failure for the patients requiring referral to a specialized care unit is minimal. AIM: We sought to develop and internally validate a nomogram for the prediction of late-onset pouch failure. METHODS: The study cohort included all eligible UC patients with restorative proctocolectomy and IPAA at the subspecialty Pouchitis Clinic from 2002 to 2009. Inclusion criteria were patients having: 1) inflammatory bowel disease; 2) ileal pouches; and 3) regular follow-up at the Pouchitis Clinic. Demographic and clinical variables were prospectively collected. Multivariable accelerated failure time regression model was developed to predict pouch failure defined as pouch excision or permanent diversion. Discrimination and calibration of the model were assessed following bootstrapping methods for correcting optimism, and the model was presented as a nomogram. RESULTS: A total of 921 patients were included for the model. The mean age for this cohort was 45.5 years old. The mean follow-up at the Pouchitis Clinic was 5.8 years. Kaplan-Meier analysis showed that the probabilities for pouch retention are 0.939, 0.916 and 0.907 at 3, 5 and 7 years, respectively. The predictor variables which were included in the nomogram were smoking, duration of the pouch, baseline pouch diagnosis, and pre- and post-op use of biologics. The concordance index was 0.824. The nomogram seemed well calibrated based on the calibration curve. CONCLUSIONS: The nomogram model appeared to predict late-onset pouch failure reasonably well with satisfactory concordance index and calibration curve. The nomogram is readily applicable for clinical practice in pouch patients.

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: 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: 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: Endoscopic management of ileal pouch strictures has not been systemically studied. The aim was to evaluate endoscopic balloon therapy of pouch strictures in inflammatory bowel disease (IBD) patients with ileal pouches and to identify risk factors for pouch failure for those patients. METHODS: Consecutive IBD patients with pouches from the Pouchitis Clinic who underwent nonfluoroscopy-guided outpatient endoscopic therapy were studied. The location, number, degree (range 0-3), and length of strictures and balloon size were documented. Efficacy and safety were evaluated with univariate and multivariate analyses. RESULTS: A total of 150 patients with pouch strictures were studied. Stricture locations were at the pouch inlet (n = 96), outlet (n = 73), afferent limb (n = 33), and pouch body (n = 2). A cumulative of 646 strictures were endoscopically dilated, with a total of 406 pouchoscopies. The median stricture score was 1 (interquartile range [IQR] 1-2); the median stricture length was 1 (IQR 0.5-1.25) cm, and the median balloon size was 20 (IQR 18-20) mm. Of 406 therapeutic endoscopies performed, there were two perforations (0.46%) and four transfusion-required bleeding (0.98%). The 5-, 10-, and 25-year pouch retention rates were 97%, 90.6%, and 85.9%, respectively. In a median follow-up of 9.6 (IQR 6-17) years, 131 patients (87.3%) were able to retain their pouches. The number of strictures and underlying diagnosis were independent risk factors for pouch failure in the Cox regression model. CONCLUSIONS: Endoscopic treatment of pouch stricture appears to be efficacious and generally safe to perform in experienced hands. Underlying diagnosis of Crohn's disease of the pouch and surgery-related strictures and multiple strictures were the risk factors for pouch failure.

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 & 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.

AIM: Evidence is lacking whether an abscess associated with anastomotic leak after an ileal pouch-anal anastomosis (IPAA) should be drained by transanal or CT-guided drainage. Therefore, the aim of this study was to compare outcomes after the two techniques for drainage. METHOD: Patients who underwent IPAA (1984-2009) and diagnosed with a pelvic abscess associated with an anastomotic leak were identified. The choice of operative or image-guided drainage was based on surgeon preference. Differences between patients undergoing transanal (group TA) and CT-guided drainage (group CT) were determined. RESULTS: Groups TA (n = 53) and CT (n = 18) had similar age (p = 0.3), gender (p = 0.3), body mass index (p = 0.6), steroid use (p = 0.4), albumin level (p = 0.9), ileostomy (p = 0.6), and follow-up time (p = 0.5). The size of the abscess was greater in group CT (p = 0.012). Two patients developed fistula at the CT-guided drainage site. Both healed after conservative treatment and drainage of associated gluteal abscess, respectively. Thirteen patients in group TA and three patients in group CT (p = 0.6) had failure of drainage and underwent surgery. The success rates for the procedures in terms of long-term pouch retention were 75.5% and 83%, respectively, for TA and CT. Groups TA and CT had similar bowel frequency (p = 0.9), incontinence (p = 0.6), urgency (p = 0.9), seepage (p = 0.6), pad usage (p = 0.1), quality of life (p = 0.9), and happiness with surgery (p = 0.9). CONCLUSIONS: There is a risk of fistula at drainage site after a CT-guided drainage of the pelvic abscess associated with anastomotic leak following IPAA. Transanal and CT-guided drainage are equally effective and result in similar long-term pouch-related outcomes.