Ulcerative Colitis: Cohen Z

Cohen Z, Senagore AJ, Dayton MT, Koruda MJ, Beck DE, Wolff BG, Fleshner PR, Thirlby RC, Ludwig KA, Larach SW, Weiss EG, Bauer JJ, Holmdahl L. · Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Dis Colon Rectum. · Pubmed #15868230 No free full text.

Abstract: INTRODUCTION: Postoperative abdominal adhesions are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Development of a bioresorbable membrane containing up to 23 percent glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers ease of handling and has been shown to provide significant postoperative adhesion prevention in animals. This study was designed to assess the safety of glycerol hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the incidence, extent, and severity of postoperative adhesion development in surgical patients. METHODS: Twelve centers enrolled 120 patients with ulcerative colitis or familial polyposis who were scheduled for a restorative proctocolectomy and ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical closure, patients were randomized to no anti-adhesion treatment (control) or treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the midline incision. At ileostomy closure, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision. RESULTS: Data were analyzed using the intent-to-treat population. Treatment with glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33 percent) with no adhesions compared with 6 of 60 adhesion-free patients (10 percent) in the no treatment control group (P = 0.002). The mean extent of postoperative adhesions to the midline incision was significantly lower among patients treated with glycerol hyaluronate/carboxymethylcellulose compared with patients in the control group (P < 0.001). The severity of postoperative adhesions to the midline incision was significantly less with glycerol hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events were similar between treatment and no treatment control groups with the exception of abscess and incisional wound complications were more frequently observed with glycerol hyaluronate/carboxymethylcellulose. CONCLUSIONS: Glycerol hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to the midline incision and adhesions between the omentum and small bowel after abdominal surgery. Safety profiles for the treatment and no treatment control groups were similar with the exception of more infection complications associated with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not predict these complications.

Scarpa M, Victor CJ, O'Connor BI, Cohen Z, McLeod RS. · Department of Surgery, Veneto Oncological Institute (IOV-IRCCS), Padova, Italy. · J Gastrointest Surg. · Pubmed #19089514 No free full text.

Abstract: OBJECTIVE: Ileal pouch anal anastomosis (IPAA) is the procedure of choice for most patients requiring surgery for ulcerative colitis and familial adenomatous polyposis because of its perceived improvement in health-related quality of life (HRQL). The aims of this cross-sectional study were to validate an English version of the Padova Inflammatory Bowel Disease Quality of Life questionnaire (PIBDQL) in patients undergoing IPAA and to investigate the pre- and postoperative predictors of long-term HRQL. MATERIALS AND METHODS: In May 2005, the English version of the PIBDQL, Short Inflammatory Bowel Disease Questionnaire, and the SF-36 were mailed to 1,379 patients who underwent IPAA at the Mount Sinai Hospital between 1982 and 2004. The test-retest reliability, internal consistency, construct validity, and discriminative ability of the English version of the PIBDQL were assessed. RESULTS: Nine hundred fifty-five patients (69%) (475 female, 480 male; mean, age 43 years) returned the questionnaires. The mean PIBDQL score was 21.1 (3.4), suggesting good quality of life. Test-retest reliability [intraclass correlation coefficient (ICC) = 0.784] and internal consistency (Cronbach's alpha = 0.83) were good. Construct validity and discriminative ability of the English version of PIBDQL were adequate. Multivariate analysis revealed that women (p < 0.01) and Crohn's disease patients (p < 0.01) had significantly worse PIBDQL scores. CONCLUSIONS: The English version PIBDQL is a reliable and valid disease-specific instrument for assessing quality of life in patients with IPAA. In this series, female gender and CD were significant predictors of worse HRQL.

Davies RJ, O'Connor BI, Victor C, MacRae HM, Cohen Z, McLeod RS. · Department of Surgery, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada. · Dis Colon Rectum. · Pubmed #18454295 No free full text.

Abstract: PURPOSE: This study was designed to assess the effect of ileal pouch-anal anastomosis on sexual function and quality of life in men and women. METHODS: Sexual function of patients undergoing ileal pouch-anal anastomosis from February 2005 to June 2006 was prospectively evaluated using the International Index of Erectile Function in men and Female Sexual Function Index in women. Quality of life was assessed using the Short Inflammatory Bowel Disease Questionnaire. Preoperative scores were compared with scores at 6 and 12 months postoperatively. RESULTS: Of 110 patients eligible for inclusion, 59 (53.6 percent) agreed to participate. Male sexual function and erectile function scores remained high 12 months after surgery (mean International Index of Erectile Function score 51.7 preoperative vs. 58.3 at 12 months postoperative; P = not significant (NS)). Abnormal sexual function decreased from 33.3 percent before surgery to 22.7 percent 12 months after surgery (P = NS). Female sexual function improved 12 months after surgery (mean Female Sexual Function Index score 19.2 preoperative vs. 27 at 12 months postoperative; P = 0.031). Abnormal sexual function decreased from 73.1 percent before surgery to 25 percent 12 months after surgery (P = 0.001). Quality of life significantly improved after ileal pouch-anal anastomosis in both sexes. CONCLUSIONS: In men, ileal pouch-anal anastomosis does not have an adverse effect on sexual function, whereas sexual function in women seems to improve 12 months after surgery.

Raval MJ, Schnitzler M, O'Connor BI, Cohen Z, McLeod RS. · Department of Surgery, Samuel Lunenfeld Research Institute, Dr. Zane Cohen Digestive Diseases Clinical Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada. · Ann Surg. · Pubmed #17968167 No free full text.

Abstract: OBJECTIVE: To assess the clinical presentation, management, and outcome of leaks after the ileal pouch-anal anastomosis (IPAA) procedure. METHODS: Of 1424 IPAA procedures performed at Mount Sinai Hospital from 1981 to 2003, 141 patients experienced leaks (9.9%). Data were reviewed retrospectively from the Inflammatory Bowel Disease database and clinic and hospital charts. Statistical comparisons were performed with the chi2 test. RESULTS: There were 81 men and 60 women with a median age of 36 years (12-69). Indication for surgery was ulcerative colitis in 93% of patients. Twenty-three leaks (16.3%) originated from the pouch whereas 118 (84.1%) arose from the ileoanal anastomosis. Of ileoanal anastomosis leaks, 24.6% were associated with and 38.1% without an abscess, 12.7% were associated with a pouch-cutaneous fistula, 15.3% were associated with a pouch-vaginal fistula, and 9.3% were diagnosed radiologically. Of the 130 patients who developed symptoms, 67% had fever, 38% had abdominoperineal pain, and 6% had perineal abscess. Twenty-nine percent of those who did not have an ileostomy had increased stool frequency. Nonoperative treatment was attempted initially in 100 patients with an 80% success rate. An operative procedure was performed in 59 patients (including those who failed nonoperative treatment), including transanal repair in 34 patients with a success rate of 66%; laparotomy with direct suture repair in 7 with a success rate of 57% and combined abdominoperineal pouch reconstruction in 18 with a success rate of 72%. Overall, 119 patients (84%) have a functioning pouch. Pouch salvage after a leak increased from 67% in 1981-1984 to 88% in 2001-2003 (P = 0.0004, chi2). CONCLUSIONS: A high rate of ileal pouch salvage can be achieved after leaks associated with the IPAA procedure if management is individualized. Improved salvage rate over time is likely a reflection of increased experience with the management of complications as well as the strategy of individualized management.

Achkar JP, Dassopoulos T, Silverberg MS, Tuvlin JA, Duerr RH, Brant SR, Siminovitch K, Reddy D, Datta LW, Bayless TM, Zhang L, Barmada MM, Rioux JD, Steinhart AH, McLeod RS, Griffiths AM, Cohen Z, Yang H, Bromfield GP, Schumm P, Hanauer SB, Cho JH, Nicolae DL. · Center for Inflammatory Bowel Disease, Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, OH, USA. · Am J Gastroenterol. · Pubmed #16542294 No free full text.

Abstract: OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.

Brown CJ, Maclean AR, Cohen Z, Macrae HM, O'Connor BI, McLeod RS. · IBD Research Unit, Mount Sinai Hospital, Toronto, Ontario, Canada. · Dis Colon Rectum. · Pubmed #15937625 No free full text.

Abstract: PURPOSE: This study was designed to determine the outcome of patients with Crohn's disease and indeterminate colitis who have an ileal pouch-anal anastomosis. METHODS: Between 1982 and 2001, 1,270 patients underwent a restorative proctocolectomy at the Mount Sinai Hospital: 1,135 had ulcerative colitis, 36 had Crohn's disease, 21 had indeterminate colitis, and 78 had another diagnosis. Perioperative data were collected prospectively. Functional outcomes were assessed with a 35-question survey mailed to all patients with a functioning pouch of at least six months duration. RESULTS: Pouch complications were significantly more common in patients with Crohn's disease (64 percent) and indeterminate colitis (43 percent) compared with patients with ulcerative colitis (22 percent) (P < 0.05). Similarly, 56 percent of patients with Crohn's disease had their pouch excised or defunctioned, compared with 10 percent of patients with indeterminate colitis and 6 percent with ulcerative colitis (P < 0.01). In the subgroup of patients with a diagnosis of Crohn's disease, multivariate analysis revealed that the pathologist's initial designation of ulcerative colitis (based on the colectomy specimen) and an increasing number of pathologic, clinical, and endoscopic features of Crohn's disease were independently associated with pouch failure. The functional results in patients with Crohn's disease with a successful pouch were not significantly different from those with indeterminate colitis or ulcerative colitis. CONCLUSIONS: Although complication rates may be higher in patients with indeterminate colitis compared with ulcerative colitis, the overall pouch failure rate is similar. On the other hand, more than one-half of patients with Crohn's disease will require pouch excision or diversion. Our data suggest that it is difficult to identify patients with Crohn's disease who are likely to have a successful outcome after restorative proctocolectomy. Thus, Crohn's disease should remain a relative contraindication to restorative proctocolectomy, whereas ileal pouch-anal anastomosis is an acceptable alternative for patients with indeterminate colitis.

Johnson P, Richard C, Ravid A, Spencer L, Pinto E, Hanna M, Cohen Z, McLeod R. · IBD Research Unit, Department of Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada. · Dis Colon Rectum. · Pubmed #15164254 No free full text.

Abstract: PURPOSE: Although ulcerative colitis commonly affects young females, the impact of ulcerative colitis and its treatment on female fertility have not been well studied. The purpose of this survey was to examine the impact of ulcerative colitis and ileal pouch-anal anastomosis on female reproductive ability. METHODS: Demographic, reproductive history, and disease history information were obtained via a questionnaire mailed to females who had pelvic pouch surgery or nonoperative management for ulcerative colitis. Based on age at diagnosis, age at surgery, and marital status, 153 females who had pelvic pouch surgery and 60 females who had nonoperative management for ulcerative colitis were identified for inclusion. Patients were asked if they attempted to become pregnant, when relative to their diagnosis or surgery, and if they were successful. Married or cohabiting females aged 18 to 44 years who failed to become pregnant during 12 months of unprotected intercourse were defined as infertile. RESULTS: The infertility rate was significantly higher in females who had pelvic pouch surgery compared with females managed nonoperatively (59/153 (38.1 percent) vs. 8/60 (13.3 percent), respectively; P < 0.001). There was no difference in female fertility after diagnosis with ulcerative colitis compared with before diagnosis (odds ratio, 0.68; P = 0.23). In contrast, there was a 98 percent reduction in fertility after pelvic pouch surgery compared with before surgery (odds ratio, 0.021; P < 0.0001). By logistic regression, increasing age was the only factor associated with failure to become pregnant after surgery (odds ratio, 1.136 per additional year of age; P = 0.027). CONCLUSIONS: Females with ulcerative colitis who are managed nonoperatively have normal fertility, which suggests that ulcerative colitis and medical therapy do not decrease female reproductive ability. After pelvic pouch surgery for ulcerative colitis, female fertility is significantly decreased and this problem should be discussed routinely with patients considering this procedure.

MacLean AR, Lilly L, Cohen Z, O'Connor B, McLeod RS. · Department of Surgery, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada. · Dis Colon Rectum. · Pubmed #12907911 No free full text.

Abstract: PURPOSE: The purpose of this study was to determine the outcome of patients with inflammatory bowel disease who underwent liver transplantation for primary sclerosing cholangitis. METHODS: All patients who underwent liver transplantation for primary sclerosing cholangitis at our institution were identified. A review of patients' hospital and office charts was performed; all patients were then contacted, and a detailed survey was administered by telephone. RESULTS: Sixty-nine patients were identified. There were 53 males (76.8 percent) and 16 females, with a mean age of 45.3 (+/- 13.3) years. Fifty-two (75.4 percent) of the 69 patients had documented inflammatory bowel disease; of these, 40 had ulcerative colitis (76.9 percent), 11 had Crohn's disease, and 1 had indeterminate colitis. Thirty-one patients (60 percent) were diagnosed with inflammatory bowel disease before primary sclerosing cholangitis, with a mean interval to diagnosis of primary sclerosing cholangitis of 10.8 (+/- 10.3) years. Seven patients had both diagnoses made at roughly the same time, and 14 patients initially were diagnosed with primary sclerosing cholangitis and subsequently were found to have inflammatory bowel disease, with a mean interval of 5.2 (+/- 4.4) years; 5 (35.7 percent) of those 14 patients were only diagnosed with inflammatory bowel disease after their liver transplant. The mean time from diagnosis of primary sclerosing cholangitis to liver transplantation was 6.1 (+/- 4.9) years. Since their transplant, 30.8 percent of patients rated their colitis as worse, 38.5 percent felt it was unchanged, and 30.8 percent felt that their colitis was better controlled. Eight (15.4 percent) of the 52 patients with inflammatory bowel disease denied having any knowledge of an increased risk of colorectal neoplasia. Four patients have required colectomy for colorectal neoplasia after liver transplantation, at a mean of 4.7 years after transplantation. Of the patients with inflammatory bowel disease, 42 (80.1 percent) had at least 1 posttransplant surveillance colonoscopy. Eight of the remaining ten patients had a colectomy, leaving only two patients (3.8 percent) who had not been surveyed. However, only 32 (61.5 percent) of the patients with inflammatory bowel disease have been on a surveillance regimen that would approximately conform to current screening recommendations. CONCLUSIONS: The activity of inflammatory bowel disease after transplantation is highly variable. Patients appeared to lack knowledge of their increased risk for colorectal neoplasia. Colorectal cancer is an uncommon but important complication in patients after liver transplantation for primary sclerosing cholangitis, and ongoing surveillance is required. Patients may require education to increase their awareness of the cancer risk and compliance with surveillance.

Evans JP, Steinhart AH, Cohen Z, McLeod RS. · Division of General Surgery, Department of Surgery, Mount Sinai Hospital, University of Toronto, Ontario, Canada. · J Gastrointest Surg. · Pubmed #12763417 No free full text.

Abstract: This paper examines the safety and feasibility of providing short-term, in-home total parenteral nutrition (TPN) for patients with inflammatory bowel disease (IBD) for whom the alternative is prolonged hospitalization or early surgery. The records of all patients with IBD who were receiving temporary home TPN between June 1996 and July 2000 were reviewed. A quality-of-life phone interview was conducted at the time of review. Fifteen patients (11 men and 4 women) were identified whose average age was 35 years. The underlying diagnosis was Crohn's disease in 10 and ulcerative colitis in five. The indications for home TPN were complex internal fistulas and resolving sepsis in two, postoperative septic complications (anastomotic leak/enterocutaneous fistula) in five, high-output proximal stomas in four, prolonged ileus/partial obstruction in three, and spontaneous enterocutaneous fistula in one. The average duration of home TPN was 75 days (range 7 to 240 days). Two patients (13%) failed home TPN (1 with uncontrolled sepsis; 1 with dehydration) and were readmitted to the hospital. Home TPN was discontinued in one patient whose enterocutaneous fistula failed to heal with nonoperative treatment. Home TPN was successful in 12 patients (80%): eight (53%) who underwent planned definitive surgery and four (27%) whose conditions resolved without surgery. Complications of home TPN were line sepsis and pulmonary aspergillosis in one patient. All patients preferred home TPN to further hospitalization and reported good or excellent quality of life at home. Home TPN is a safe alternative to prolonged hospitalization or early surgery in patients with complicated IBD.

Silverberg MS, Mirea L, Bull SB, Murphy JE, Steinhart AH, Greenberg GR, McLeod RS, Cohen Z, Wade JA, Siminovitch KA. · Department of Medicine, University of Toronto, Toronto, Ontario, Canada. · Inflamm Bowel Dis. · Pubmed #12656131 No free full text.

Abstract: The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population- and family-based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB1*0103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case-control analysis of non-Jewish IBD-affected individuals. This association was apparent among both Crohn's disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non-Jewish IBD population by results of family-based association analysis using the transmission disequilibrium test. HLA DQB1*0501 was also associated with IBD (OR = 1.64, p = 0.02) in the non-Jewish population. but statistically significant association of this allele with disease was not detected for Crohn's disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non-Jewish IBD families, IBD was as strongly associated with the DRB1*0103 DQB1*0501 haplotype as with the DRB1*0103 allele alone. The carrier frequency of the DRB1*0103 allele was found to be 10-fold higher in Crohn's disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB1*0103 allele with both Crohn's disease and ulcerative colitis and with large intestine-restricted disease in non-Jewish IBD patients and therefore identify HLA DRB1*0103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.

Ravid A, Richard CS, Spencer LM, O'Connor BI, Kennedy ED, MacRae HM, Cohen Z, McLeod RS. · IBD Research Unit and Samuel Lunenfeld Research Institute, Division of General Surgery and Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Dis Colon Rectum. · Pubmed #12394423 No free full text.

Abstract: PURPOSE: This study was designed to evaluate the pregnancies, method of delivery, and functional results of females with chronic ulcerative colitis who have an ileal pouch-anal anastomosis. METHODS: A mailed questionnaire was sent to all females with an ileal pouch-anal anastomosis for chronic ulcerative colitis. Information on the pregnancy, method of delivery, and outcome was collected. Those females who had a successful pregnancy and delivery were contacted by telephone to clarify results and determine pouch functional results. Other clinical information was obtained from the Mount Sinai Hospital Inflammatory Bowel Disease database. RESULTS: Thirty-eight subjects had 67 pregnancies. Of these, 29 subjects had 49 deliveries. There were 25 vaginal deliveries and 24 cesarean sections. There were two pouch-related complications during the pregnancies and four pouch-related complications postpartum. All were treated nonoperatively. Stool frequency and day and night incontinence were increased during pregnancy in most subjects, but after delivery, prepregnancy function was restored in 24 (83 percent) of them. Five subjects (17 percent) had some degree of permanent deterioration in pouch function. Of these, three had vaginal deliveries, and two had cesarean sections. Multiple births and birth weight were not found to adversely affect subsequent pouch function. CONCLUSION: Pregnancy is safe in females with ileal pouch-anal anastomosis. Functional results are altered almost exclusively during the third trimester, but pouch function promptly returns to prepregnancy status in most females. A small proportion of females have long-term disturbances in function, but these are not related to the method of delivery. Thus, the method of delivery should be dictated by obstetric considerations.

MacLean AR, O'Connor B, Parkes R, Cohen Z, McLeod RS. · Inflammatory Bowel Disease Research Unit, Department of Surgery, Department of Health, Health Policy, Management, and Evaluation, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada. · Dis Colon Rectum. · Pubmed #12130874 No free full text.

Abstract: PURPOSE: Salvage procedures for failed ileal pouch-anal anastomoses frequently require total reconstruction with a combined abdominal and perineal approach. The aim of this study was to determine the indications for surgery and the outcomes in this group of patients. METHODS: All patients who underwent combined abdominal and perineal ileal pouch-anal anastomosis reconstruction at the Mount Sinai Hospital between 1982 and 2000 were reviewed. Data were collected prospectively in the inflammatory bowel disease database. RESULTS: Sixty-three reconstructive procedures were performed in 57 patients, with a mean age of 33.9 (+/-10.4) years at the time of reconstruction. There were 14 males. The mean follow-up was 69.1 months. The initial indication for ileal pouch-anal anastomosis was ulcerative colitis in 98 percent. The primary indication for reconstruction was pouch-vaginal fistula in 21 patients, long outlet in 14, pelvic sepsis in 14, ileoanal anastomotic stricture in 5, pouch-perineal fistula in 2, and chronic pouchitis in 1. The mean operative time was four hours (+/-1.1), the average blood loss was 500 mL (+/-400), and the average length of stay was 10.3 days (+/-4.6). All patients had a diverting ileostomy. Forty-two (73.6 percent) of the patients have a functioning pouch. Seven (12.3 percent) patients have had their pouch excised. The ileostomy has not yet been closed in 8 (14 percent) patients; 3 of these patients are awaiting closure, whereas the remaining 5 have a permanently defunctioning ileostomy. Eighty-nine percent have ten or fewer bowel movements per day. No patients are incontinent of stool during the day, whereas two patients are incontinent at night. Seventeen percent complain of frequent urgency. Despite this, more than 80 percent rate their physical and psychological health as good to excellent. CONCLUSION: Reconstructive pouch surgery has a high success rate in experienced hands. The functional results in those whose pouch is in use are good.

MacLean AR, Cohen Z, MacRae HM, O'Connor BI, Mukraj D, Kennedy ED, Parkes R, McLeod RS. · IBD Research Unit, Department of Surgery, Mount Sinai Hospital and University of Toronto, Canada. · Ann Surg. · Pubmed #11807359 links to  free full text

Abstract: OBJECTIVE: To determine the incidence of small bowel obstruction (SBO), to identify risk factors for its development, and to determine the most common sites of adhesions causing SBO in patients undergoing ileal pouch-anal anastomosis (IPAA). METHODS: All patients undergoing IPAA at Mount Sinai Hospital were included. Data were obtained from the institution's database, patient charts, and a mailed questionnaire. SBO was based on clinical, radiologic, and surgical findings. Early SBO was defined as a hospital stay greater than 10 or 14 days because of delayed bowel function, or need for reoperation or readmission for SBO within 30 days. All patients readmitted after 30 days with a discharge diagnosis of SBO were considered to have late SBO. RESULTS: Between 1981 and 1999, 1,178 patients underwent IPAA (664 men, 514 women; mean age 40.7 years). A total of 351 episodes of SBO were documented in 272 (23%) patients during a mean follow-up of 8.7 years (mean 1.29 episodes/patient). Fifty-four patients had more than one SBO. One hundred fifty-four (44%) of the SBOs occurred in the first 30 days; 197 (56%) were late SBOs. The cumulative risk of SBO was 8.7% at 30 days, 18.1% at 1 year, 26.7% at 5 years, and 31.4% at 10 years. The need for surgery for SBO was 0.8% at 30 days, 2.7% at 1 year, 6.7% at 5 years, and 7.5% at 10 years. In patients requiring laparotomy, the obstruction was most commonly due to pelvic adhesions (32%), followed by adhesions at the ileostomy closure site (21%). A multivariate analysis showed that when only late SBOs were considered, performance of a diverting ileostomy and pouch reconstruction both led to a significantly higher risk of SBO. CONCLUSIONS: The risk of SBO after IPAA is high, although most do not require surgical intervention. Thus, strategies that reduce the risk of adhesions are warranted in this group of patients to improve patient outcome and decrease healthcare costs.

Silverberg MS, Daly MJ, Moskovitz DN, Rioux JD, McLeod RS, Cohen Z, Greenberg GR, Hudson TJ, Siminovitch KA, Steinhart AH. · Department of Medicine, Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Canada. · Gut. · Pubmed #11709510 links to  free full text

Abstract: BACKGROUND: Linkage data have now identified several inflammatory bowel disease (IBD) susceptibility loci but these data have not been consistently replicated in independent studies. One potential explanation for this is the possibility that patients enrolled in such studies may have been erroneously classified with respect to their diagnosis. AIMS: To determine the rate and type of misclassification in a large population of individuals referred for participation in an IBD genetics study and to examine the effect of diagnostic misclassification on the power to detect linkage. METHODS: The medical records of 1096 patients entered into an IBD genetics programme were reviewed using standardised diagnostic criteria. The original patient reported diagnoses were changed, if necessary, based on review, and the reasons for the change in diagnosis were recorded. To evaluate the effect of misclassification on linkage results, simulations were created with Gensim and analysed using Genehunter to evaluate a model for IBD inheritance. RESULTS: Sixty eight of 1096 (6.2%) individuals had a change in diagnosis from that originally reported. The majority of changes were patients with either Crohn's disease or ulcerative colitis who were determined not to have IBD at all. The principal reasons for changes to the original diagnosis were discordance between the patients' subjective reports of diagnosis and actual clinical history, endoscopic, or pathological results; a change in disease pattern over time; and insufficient information available to confirm the original diagnosis. A 10% misclassification rate resulted in 28.4% and 40.2% loss of power to detect a true linkage when using a statistical model for a presumed IBD locus with lambda(s) values of 1.8 and 1.3, respectively. CONCLUSIONS: Diagnostic misclassification occurs in patients enrolled in IBD genetic studies and frequently involves assigning the diagnosis of IBD to non-affected individuals. Even low rates of diagnostic misclassification can lead to significant loss of power to detect a true linkage, particularly for loci with modest effects as are likely to be found in IBD.

Thompson-Fawcett MW, Marcus V, Redston M, Cohen Z, McLeod RS. · Department of Surgery, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto M5G 1X5 Canada. · Gastroenterology. · Pubmed #11487537 No free full text.

Abstract: BACKGROUND & AIMS: Recent reports have suggested the mucosa of an ileal reservoir could be at risk of neoplasia. Risk factors may include the age of the pouch, chronic pouchitis, and previous colonic neoplasia. This study examined a group of such patients to determine the risk of dysplasia. METHODS: From a cohort of 1221 patients with ileal pouches, 171 patients with possible risk factors were selected. Successful contact was made with 138 patients who were invited for endoscopy and multiple biopsies. Biopsy specimens were stained with H&E and p53, scored for inflammatory changes including villous atrophy, and analyzed by flow cytometry. RESULTS: One hundred six patients took part and fell into 1 or more of the following clinical categories: chronic pouchitis (n = 34), pelvic pouch for > or =12 years (n = 42); Kock pouch for > or =14 years (n = 29), and neoplasia in colectomy specimen (n = 11). Thirty-three patients had severe villous atrophy. One patient of 106 (95% confidence interval, 0.9% +/- 1.6%) with a long-standing pouch had low-grade dysplasia that was multifocal. DNA analysis by flow cytometry showed aneuploidy in this patient and 2 others. CONCLUSIONS: These data suggest that the development of dysplasia in ileal pouches performed for ulcerative colitis is probably a rare event within 15-20 years of pouch surgery.

Silverberg MS, Clelland C, Murphy JE, Steinhart AH, McLeod RS, Greenberg GR, Cohen Z, Siminovitch KA. · Department of Medicine, University of Toronto, Mount Sinai Hospital Inflammatory Bowel Disease Centre and Samuel Lunenfeld Research Institute, Canada. · Hum Genet. · Pubmed #11354631 No free full text.

Abstract: Colorectal cancer (CRC) occurs with an increased incidence in individuals with chronic inflammatory bowel disease (IBD) of the colon. Recent data suggest that a family history of colorectal cancer is an independent risk factor for CRC in IBD, an observation that implies that genetic factors are relevant to the development of CRC in this context. Among the genetic defects associated with CRC, the APC I1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps. These findings, together with the increased incidence of IBD in AJ, prompted the current analysis of the contribution of the APC I1307K variant of CRC in AJ IBD patients. APC I1307K carrier frequencies were determined in 306 AJ individuals affected with IBD and 308 of their unaffected relatives ascertained from a family collection obtained for the identification of IBD susceptibility genes. Prevalence of the I1307K variant was not significantly different among individuals with IBD, Crohn's disease, ulcerative colitis, and unaffected relatives (6.9%, 7.6%, 4.7%, and 6.2%, respectively), and the mutation was detected in only one of five IBD-affected individuals with a diagnosis of CRC. These results reveal that IBD patients of AJ origin carry the APC I1307K variant at the same rate as individuals within the general AJ population. Lack of an increased APC I1307K carrier rate suggests that this mutation does not account for the increased CRC susceptibility associated with IBD.

Thompson-Fawcett MW, Richard CS, O'Connor BI, Cohen Z, McLeod RS. · Department of Surgery, Mt. Sinai Hospital, University of Toronto, Ontario, Canada. · Dis Colon Rectum. · Pubmed #11089582 No free full text.

Abstract: PURPOSE: Despite high patient satisfaction with a pelvic pouch, patients experience some bowel dysfunction. Patients whose indication for surgery is neoplasia may have near-normal preoperative bowel function. We hypothesized that these patients would be less accepting of a poorer functional status after surgery, reflected in a poorer measure of quality of life. METHOD: Sixteen patients who had dysplasia or cancer as the primary indication for surgery were compared with a matched control group whose indication for surgery was failed medical therapy. Quality of life was assessed using one disease-specific instrument, the Inflammatory Bowel Disease Questionnaire, two generic quality-of-life instruments, the Sickness Impact Profile and the Short Form 36, and two utility assessments. RESULTS: The groups were well matched with no significant differences in functional outcome. Quality-of-life scores were high in both groups and there were no significant differences in overall quality of life between the two groups using all five instruments. There was evidence of a response shift phenomenon in the failed medical therapy control group. CONCLUSION: Quality of life of patients who have a pelvic pouch for colitis-associated neoplasia is excellent and the same as that of patients who have a pouch for failure of medical therapy.

Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, McLeod RS, Griffiths AM, Green T, Brettin TS, Stone V, Bull SB, Bitton A, Williams CN, Greenberg GR, Cohen Z, Lander ES, Hudson TJ, Siminovitch KA. · Whitehead Institute/Massachusetts Institute of Technology, Center for Genome Research, Cambridge, MA 02139, USA. · Am J Hum Genet. · Pubmed #10777714 links to  free full text

Abstract: The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.

Soravia C, O'Connor BI, Berk T, McLeod RS, Cohen Z. · Department of Surgery and the Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital, University of Toronto, Canada. · Dis Colon Rectum. · Pubmed #10411437 No free full text.

Abstract: PURPOSE: The aim of this study was to review the functional outcome in 20 patients with familial adenomatous polyposis and ulcerative colitis who were converted from ileorectal anastomosis to ileal pouch-anal anastomosis. METHODS: From 1985 to 1997, 12 patients with familial adenomatous polyposis (5 males; mean age, 39.1 years) and 8 patients with ulcerative colitis (5 males; mean age, 36.7 years) underwent conversion from ileorectal anastomosis to ileal pouch-anal anastomosis. Clinical and operative data were analyzed retrospectively. Functional results were obtained by telephone interview in 16 patients (94 percent) after pouch construction. Four patients were not interviewed (2 were deceased, 1 was lost to follow-up, and 1 was not reachable). RESULTS: Indications for conversion were uncontrollable rectal polyps (10 patients) and colonic cancer found in the pathology specimen after ileorectal anastomosis in patients with familial adenomatous polyposis (2 patients), intractable proctitis (5 patients), colonic cancer found in the pathology specimen of patients with ulcerative colitis after ileorectal anastomosis (2 patients), and rectal dysplasia (1 patients). Mean follow-up time was 5 (range, 1-11) years. Ileal pouch-anal anastomosis was handsewn in 14 patients, and the remaining cases were double-stapled in 4 patients with ulcerative colitis. No intraoperative difficulties were reported in 13 cases; technical problems were related to adhesions (3 cases), difficult rectal dissection (2 cases), and stapler-related difficulties (2 cases). Postoperative complications after ileal pouch-anal anastomosis included small-bowel obstruction (4 patients) and ileal pouch-anal anastomosis leak (1 patient). Patients with ileorectal anastomosis vs. those with ileal pouch-anal anastomosis had a better functional outcome with regard to nighttime continence (14 (88 percent) vs. 6 (38 percent) patients) and average bowel movements (<6/day; 12 (75 percent) vs. 4 (25 percent) patients). Complete daytime continence, 15 (94 percent) vs. 10 (62 percent) patients, was similar in the two groups. Physical and emotional well-being were similarly rated as very good to excellent. CONCLUSIONS: In patients with familial adenomatous polyposis and ulcerative colitis with ileorectal anastomosis, conversion to ileal pouch-anal anastomosis may be required. In view of the risk of rectal cancer or intractable proctitis, patients seem to accept the conversion in spite of poorer bowel function.