Zane Cohen

Changing causes of mortality in patients with familial adenomatous polyposis.

Widespread use of prophylactic colectomy has resulted in a reduction in the incidence of colorectal cancer in familial adenomatous polyposis (FAP) patients. A retrospective chart review of families registered at the Steve Atanas Stavro Familial Gastrointestinal Cancer Registry in Toronto was performed to determine whether the decrease in the number of patients developing colorectal cancer implies that causes of mortality in FAP patients are shifting to that of extracolonic manifestations of FAP. Information was available on 140 deaths within 158 families and among 461 individuals with FAP. When stratified by decade, from the 1930s to the 1990s, the ratio of deaths caused by extracolonic manifestations of FAP compared with deaths caused by colorectal cancer was noted to have risen. Even though most deaths in FAP patients are still from colorectal cancer, it appears that screening policies and prophylactic colectomy have resulted in a reduction in the number of FAP patients who develop colorectal cancer. Thus, in recent decades, a greater percentage of deaths in FAP patients appears to be attributable to extracolonic manifestations of the disease.

Crohn’s Disease and Indeterminate Colitis and the Ileal Pouch-Anal Anastomosis: Outcomes and Patterns of Failure

PURPOSEThis study was designed to determine the outcome of patients with Crohn’s disease and indeterminate colitis who have an ileal pouch-anal anastomosis.METHODSBetween 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.RESULTSPouch 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.CONCLUSIONSAlthough 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.

Treatment of rectovaginal fistulas that has failed previous repair attempts

PURPOSE: The purpose of this study was to assess results of treatment of rectovaginal fistulas (excluding pouch vaginal fistulas) that have failed previous attempts at repair. METHOD: A retrospective chart review of all patients presenting with nonhealing rectovaginal fistula was performed. RESULTS: Twenty eight patients with persistent fistulas were identified. In 18 patients the fistula was classified as simple, and in 10 the fistula was complex. Fourteen fistulas were secondary to obstetric injury, five were caused by Crohns disease, and nine patients had miscellaneous etiologies for their fistulas. Of patients with persistent simple fistulas, 13 (72 percent) of the fistulas healed, 5 after advancement flaps, 5 following sphincteroplasty, and 3 after coloanal anastomoses. Of persistent complex fistulas, only four of ten (40 percent) healed, one following sphincteroplasty, one with coloanal anastomosis, and two after gracilis transposition. A total of 23 advancement flaps were done in 17 patients with five fistulas healing (29 percent). Sphincteroplasty and fistulectomy was successful in six of seven patients (86 percent). Coloanal anastomosis resulted in healing of four of six patients (67 percent) in whom it was attempted. Gracilis muscle transfer was successful in two of two patients (100 percent). CONCLUSION: Persistent rectovaginal fistula presents a difficult management problem. Choice of operation must be tailored to the underlying pathology and type of repair previously done. Advancement flap repair is generally not recommended for persistent complex fistulas or for simple fistulas that have failed a previous advancement flap repair.

Coping behavior and social support contribute independently to quality of life after surgery for inflammatory bowel disease

PURPOSE: The purpose of this study was to examine the association between coping behavior at the time of surgery and inflammatory bowel disease-related quality of life after surgery. We also investigated the relationship between perceived social support and both coping style and postsurgical quality of life. Finally, the value of the Medical Outcomes Study Social Support Scale for preoperative screening was assessed. METHODS: Eighty-six subjects who had surgery during a 12-month period completed the Inflammatory Bowel Disease Questionnaire, the Ways of Coping, a measure of inflammatory bowel disease symptom severity, and the Medical Outcomes Study Social Support Scale. Analysis of variance was used to test an association between Ways of Coping score and membership in a high quality of life (Inflammatory Bowel Disease Questionnaire > mean) or low quality of life (Inflammatory Bowel Disease Questionnaire < mean) cohort. Comparison of group means between the high quality of life and low quality of life cohorts identified Ways of Coping behavior scales that differed between the high quality of life and low quality of life cohorts. Stepwise linear regression analysis was then used to determine the independent contribution of 1) current inflammatory bowel disease symptoms, 2) current perceived social support, and 3) identified coping behaviors (self-control, self-blame, and escape, summed as a single index named “maladaptive coping”) to postsurgical quality of life. The sensitivity, specificity, and negative predictive value of the Medical Outcomes Study Social Support Scale were assessed. RESULTS: The lower quality of life group distinguished itself by more frequent use of maladaptive coping. Regression analysis revealed that current inflammatory bowel disease-related symptoms, current perceived social support, and maladaptive coping behaviors at the time of surgery each made a highly significant independent contribution to postsurgical quality of life. The sensitivity of the Medical Outcomes Study Social Support Scale in identifying patients with poor postsurgical quality of life was 81 percent, and the specificity was 77 percent. The negative predictive value was 93 percent. CONCLUSIONS: Three coping behaviors which seem to be maladaptive (self-control, self-blame, and escape) are associated with lower quality of life after surgery for inflammatory bowel disease. These coping behaviors make a contribution to postsurgical quality of life independent of the negative effect on quality of life of inflammatory bowel disease symptoms. Perceived social support is a third factor that makes an independent contribution to postsurgical quality of life. The Medical Outcomes Study Social Support Scale has properties associated with an effective screening tool and merits further investigation as an instrument to screen presurgically for individuals at higher risk of poor subjective outcome of inflammatory bowel disease surgery.

Patients with Lynch syndrome mismatch repair gene mutations are at higher risk for not only upper tract urothelial cancer but also bladder cancer.

BACKGROUNDnLynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse.nnnOBJECTIVEnTo assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations.nnnDESIGN, SETTING, AND PARTICIPANTSnCancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnStandardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors.nnnRESULTS AND LIMITATIONSnEleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias.nnnCONCLUSIONSnLS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.

Management of advanced duodenal polyposis in familial adenomatous polyposis

Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of periampullary cancer. The aim of this study was to evaluate the roles of endoscopic and surgical therapy in the management of advanced duodenal polyposis in FAP. From 1990 to 1995, seventy-four FAP patients were enrolled in a prospective endoscopic surveillance protocol. Among these, 11 (14.8%) developed advanced duodenal polyposis and one had duodenal adenocarcinoma. Six patients underwent endoscopic resection of duodenal (n=5) or ampullary adenomas (n=1). The following operations were performed in the remaining six patients: ampullectomy in four, open polypectomy in one, and a Whipple procedure in one. There was one patient who died of acute pancreatitis following endoscopic ampullectomy. The patient with invasive duodenal cancer died of local recurrence. Small polyps were observed at the site of previous resection in all (9 of 9) patients undergoing repeat endoscopy during a mean follow-up of 18 months (range 4 to 34 months). An endoscopic and local surgical resectional approach to advanced duodenal polyposis in FAP is fraught with high recurrence rates, although recurrent polyps are small and may be amenable to retreatment in the future. Long-term follow-up is necessary to prove that deaths from duodenal or ampullary cancer are prevented with this strategy.

Outcome of patients undergoing liver transplantation for primary sclerosing cholangitis.

AbstractPURPOSE: The purpose of this study was to determine thenoutcome of patients with inflammatory bowel disease whonunderwent liver transplantation for primary sclerosingncholangitis. METHODS: All patients who underwent liverntransplantation for primary sclerosing cholangitis at ourninstitution were identified. A review of patients’ hospitalnand office charts was performed; all patients were thenncontacted, and a detailed survey was administered by telephone.nRESULTS: Sixty-nine patients were identified. Therenwere 53 males (76.8 percent) and 16 females, with a meannage of 45.3 (± 13.3) years. Fifty-two (75.4 percent) of the 69npatients had documented inflammatory bowel disease; ofnthese, 40 had ulcerative colitis (76.9 percent), 11 hadnCrohn’s disease, and 1 had indeterminate colitis. Thirty-onenpatients (60 percent) were diagnosed with inflammatorynbowel disease before primary sclerosing cholangitis, with anmean interval to diagnosis of primary sclerosing cholangitisnof 10.8 (± 10.3) years. Seven patients had both diagnosesnmade at roughly the same time, and 14 patients initiallynwere diagnosed with primary sclerosing cholangitis andnsubsequently were found to have inflammatory bowel disease,nwith a mean interval of 5.2 (± 4.4) years; 5 (35.7npercent) of those 14 patients were only diagnosed withninflammatory bowel disease after their liver transplant. Thenmean time from diagnosis of primary sclerosing cholangitisnto liver transplantation was 6.1 (± 4.9) years. Since theirntransplant, 30.8 percent of patients rated their colitis asnworse, 38.5 percent felt it was unchanged, and 30.8 percentnfelt that their colitis was better controlled. Eight (15.4npercent) of the 52 patients with inflammatory bowel diseasendenied having any knowledge of an increased risk ofncolorectal neoplasia. Four patients have required colectomynfor colorectal neoplasia after liver transplantation, at a meannof 4.7 years after transplantation. Of the patients with inflammatorynbowel disease, 42 (80.1 percent) had at least 1nposttransplant surveillance colonoscopy. Eight of the remainingnten patients had a colectomy, leaving only twonpatients (3.8 percent) who had not been surveyed. However,nonly 32 (61.5 percent) of the patients with inflammatorynbowel disease have been on a surveillance regimen thatnwould approximately conform to current screening recommendations.nCONCLUSIONS: The activity of inflammatorynbowel disease after transplantation is highly variable. Patientsnappeared to lack knowledge of their increased risk forncolorectal neoplasia. Colorectal cancer is an uncommon butnimportant complication in patients after liver transplantationnfor primary sclerosing cholangitis, and ongoing surveillancenis required. Patients may require education to increasentheir awareness of the cancer risk and compliance withnsurveillance.

Sepsis is a Major Predictor of Failure After Ileal Pouch-Anal Anastomosis

PURPOSE: This study aimed to determine the risk of ileal pouch-anal anastomosis failure and factors predictive of failure overall and in patients with septic complications. METHODS: Patients were identified through a prospectively maintained patient registry. All patients registered in the Mount Sinai Hospital Inflammatory Bowel Disease database who had an ileal pouch-anal anastomosis for more than 12 months were included in the study. Pouch failure was defined as ileal pouch-anal anastomosis excision or permanent diversion. Cox proportional hazard models with death as a competing risk were created, modeling time to failure as the outcome of interest for all patients and for the subgroup of patients with septic complications. RESULTS: The study included 1,554 patients. One hundred six patients experienced an ileal pouch-anal anastomosis failure (6.8%), 49 (46.2%) of these failures were caused by septic complications. Independent predictors of failure included Crohn’s disease (hazard ratio 7.5, 95% confidence interval [4.7, 12.0]) and postoperative sepsis (hazard ratio 6.6, 95% confidence interval [4.4, 9.8]). In the subgroup of patients with failure due to postoperative septic complications, independent predictors of failure were Crohn’s disease (hazard ratio 2.7, 95% confidence interval [1.3, 5.7]) and presence of a pouch fistula (hazard ratio 2.6, 95% confidence interval [1.3, 5.2]). CONCLUSION: Septic complications are the most common cause of ileal pouch-anal anastomosis failure. Careful patient selection and the prevention of septic complications may decrease the risk of this failure.

Favorable pathologic and long-term outcomes from the conventional approach to abdominoperineal resection.

BACKGROUND: Suboptimal oncologic outcomes from abdominoperineal resection have been related to high rates of circumferential margin involvement. The extralevator approach has gained popularity as a means of reducing circumferential margin involvement, but it remains unknown whether comparable outcomes are achievable with a conventional approach to abdominoperineal resection. OBJECTIVE: This study aimed to determine the rate of circumferential margin involvement, to identify factors predictive for a positive circumferential margin, and to relate these findings to long-term outcomes. DESIGN: This is a retrospective analysis of a prospective clinical database. SETTINGS: This study was conducted at a single center, Mount Sinai Hospital, Toronto. PATIENTS: Patients were included who underwent abdominoperineal resection for low rectal adenocarcinoma between 1997 and 2006. MAIN OUTCOME MEASURES: The main outcome measures included the rate of circumferential margin involvement, local recurrence, and disease-free survival. RESULTS: A total of 115 patients underwent abdominoperineal resection for primary adenocarcinoma of the rectum. A positive circumferential margin was demonstrated in 18 patients (15.7%). Intraoperative perforations occurred in 7 patients (6.1%). Tumors located anteriorly had a higher rate of circumferential margin involvement (31.6%) compared with lateral (13%), posterior (10%), and circumferential tumors (0%) (P = .024). This finding was reflected by a reduced median distance to the circumferential margin in anterior tumors. Curative resections (n = 108) were followed up for a median of 55.5 months. The 5-year local recurrence rate was 10.6% and the 5-year disease-free survival was 67.4%. Cox regression analysis revealed that circumferential margin involvement was an independent predictor for local recurrence; and T-category, N-category, and circumferential margin involvement for disease-free survival. LIMITATIONS: This study was limited by its sample size and the number of outcome events. CONCLUSIONS: The conventional approach to abdominoperineal resection can produce oncologic outcomes comparable to the extralevator approach. However, the rate of circumferential margin involvement is higher than in restorative procedures and may be related to difficulties in obtaining adequate clearance in anterior tumors.

Long-term outcome of colectomy and ileorectal anastomosis for Crohn's colitis.

BACKGROUND: Ileorectal anastomosis is an important surgical option for patients with Crohns colitis with relative rectal sparing. OBJECTIVE: This study aimed to audit outcomes of ileorectal anastomosis for Crohns and factors associated with proctectomy and reoperation. DESIGN: This retrospective study involved a chart review and contacting patients. SETTINGS: Patients with Crohns colitis who had an ileorectal anastomosis were identified from the Mount Sinai Hospital Inflammatory Bowel Disease Database. PATIENTS: Demographics, operative and perioperative outcomes, and reoperative data were collected. MAIN OUTCOME MEASURES: Five- and 10-year Kaplan-Meier survival estimates and 95% confidence intervals were calculated for survival from proctectomy and Crohns-related revisional surgery. Cox proportional hazards models were used to model the hazards of proctectomy and Crohns-related revision on the clinical characteristics of patients. RESULTS: Eighty-one patients had an ileorectal anastomosis for Crohns disease from 1982 to 2010. The most common indications for surgery were failed medical management (60/81, 74.1%) and a stricture causing obstruction (14/81, 17.3%). Seventy-seven percent (n = 62) had a 1-stage procedure, whereas 23% (n = 19) had a 2-stage procedure (colectomy followed by ileorectal anastomosis). The overall anastomotic leak rate was 7.4% (n = 6). Fifty-six patients had a functioning ileorectal anastomosis at the time of follow-up. At 5 and 10 years, 87% (95% CI: 75.5–93.3) and 72.2% (95% CI: 55.8–83.4) of individuals had a functioning ileorectal anastomosis. Eighteen patients required proctectomy for poor symptom control, whereas 11 patients required a small-bowel resection plus redo-ileorectal anastomosis. The mean time to proctectomy from the original ileorectal anastomosis was 88.3 months (SD = 62.1). Smoking was associated with both proctectomy (HR 3.93 (95% CI: 1.46–10.55)) and reoperative surgery (HR 2.12 (95% CI: 0.96–4.72)). LIMITATIONS: This study was retrospective. CONCLUSIONS: Ileorectal anastomosis is an appropriate operation for selected patients with Crohns colitis with sparing of the rectum. However, patients must be counseled that the reoperation rate and/or proctectomy rate is approximately 30%.