Predictive criteria of response to endoscopic treatment for severe strictures in primary sclerosing cholangitis.

BACKGROUND: The aim of this study was to identify predictive criteria of improvement after endoscopic treatment (ET) for severe strictures of extrahepatic bile ducts in patients with primary sclerosing cholangitis (PSC). METHODS: PSC patients who had at least one ET for severe stricture were included. Features of magnetic resonance cholangiography (MRC), performed before ET, were evaluated according to a standard model of interpretation, and a radiologic qualitative score of probability of improvement after ET was built. Score 3 (likely) was given in case of severe common bile duct (CBD) stricture with marked dilatation without severe strictures of upstream ducts, Score 1 (unlikely) was given in case of severe multiple strictures of secondary ducts without biliary dilatation and Score 2 (undeterminate) was given to an intermediate pattern. The response to ET was assessed at 2 months (T2-response) from the last ET and at 12 months (T12-response) from inclusion. RESULTS: Thirty-one patients were included. All had severe stricture (reduction ≥ 75% of the diameter) of CBD and 50% had severe stricture of right and/or left hepatic duct (LHD) at MRC before ET. According to the qualitative score, 16 patients had Score 3, 7 had Score 1 and 9 had Score 2. T12-response was obtained in 50% of patients. In univariate analysis, short LHD strictures, bilirubin, transaminases, pruritus and Score 3 were associated with T12-response. Increased bilirubin and transaminases were independent predictive factors of T12-response (HR 24, 95% CI: 3.4-170.4, P = 0.001 and 23.8, 95% CI: 3.4-169.4, P = 0.002, respectively). CONCLUSION: MRC, together with biochemical features, may contribute to identify the PSC patients who are likely to be improved after ET for severe strictures of extrahepatic bile ducts.

No Superiority of Stents vs Balloon Dilatation for Dominant Strictures in Patients With Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Dominant strictures occur in approximately 50% of patients with primary sclerosing cholangitis (PSC). Short-term stents have been reported to produce longer resolution of dominant strictures than single-balloon dilatation. We performed a prospective study to compare the efficacy and safety of balloon dilatation vs short-term stents in patients with non-end-stage PSC. METHODS: We performed an open-label trial of patients with PSC undergoing therapeutic endoscopic retrograde cholangiopancreatography (ERCP) at 9 tertiary-care centers in Europe, from July 2011 through April 2016. Patients found to have a dominant stricture during ERCP were randomly assigned to groups that underwent balloon dilatation (n = 31) or stent placement for a maximum of 2 weeks (n = 34); patients were followed for 24 months. The primary outcome was the cumulative recurrence-free patency of the primary dominant strictures. RESULTS: Study recruitment was terminated after a planned interim analysis because of futility and differences in treatment-related serious adverse events (SAEs) between groups. The cumulative recurrence-free rate did not differ significantly between groups (0.34 for the stent group and 0.30 for the balloon dilatation group at 24 months; P = 1.0). Most patients in both groups had reductions in symptoms at 3 months after the procedure. There were 17 treatment-related SAEs: post-ERCP pancreatitis in 9 patients and bacterial cholangitis in 4 patients. SAEs occurred in 15 patients in the stent group (45%) and in only 2 patients in the balloon dilatation group (6.7%) (odds ratio, 11.7; 95% confidence interval, 2.4-57.2; P = .001). CONCLUSIONS: In a multicenter randomized trial of patients with PSC and a dominant stricture, short-term stents were not superior to balloon dilatation and were associated with a significantly higher occurrence of treatment-related SAEs. Balloon dilatation should be the initial treatment of choice for dominant strictures in patients with PSC. This may be particularly relevant to patients with an intact papilla. ClinicalTrials.gov no. NCT01398917.

Surveillance of Duodenal Polyposis in Familial Adenomatous Polyposis: Should the Spigelman Score Be Modified?

BACKGROUND: Duodenal polyposis is a manifestation of adenomatous polyposis that predisposes to duodenal or ampullary adenocarcinoma. Duodenal polyposis is monitored by upper GI endoscopies and may require iterative resections and prophylactic radical surgical treatment when malignancy is threatening. OBJECTIVE: The purpose of this study was to evaluate severity scoring for surveillance and treatment in a large series of duodenal polyposis. DESIGN: From 1982 to 2014, every patient surveyed by upper GI endoscopies for duodenal polyposis was included. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: We performed 1912 upper GI endoscopies in 437 patients (median = 3; interquartile range, 2-6 endoscopies). MAIN OUTCOME MEASURES: Conservative treatment was performed in 103 patients (159 endoscopic and 17 surgical resections), whereas radical surgical treatment (Whipple procedure or duodenectomy) was required in 52 (median age, 47.5 y; range, 43.0-57.3 y) because of high-grade dysplasia or unresectable lesions. RESULTS: Genes involved were APC (n = 274; 62.7%) and MUTYH (n = 21; 4.8%). First upper GI endoscopies (median age, 32 y; range, 21-44 y) revealed duodenal polyposis in 190 (43.5%). Rates of low-grade dysplasia, high-grade dysplasia, and duodenal or ampulary adenocarcinoma at 5 years were 65% (range, 61.7%-66.9%), 12.1% (range, 10.3%-13.9%), and 2.4% (range, 1.5%-3.3%), whereas 10-year rates were 75.8% (range, 73.1%-78.5%), 20.8% (range, 18.2%-23.4%), and 5.4% (range, 3.8%-7.0%). The rate of ampullary abnormalities rose during surveillance from 18.3% at the first upper GI endoscopies to 47.4% at the fourth. Predictive factors for high-grade dysplasia were age at first upper GI endoscopy, type and age of colorectal surgery, Spigelman score, presence of an ampullary abnormality, and number of endoscopic treatments. In multivariate analysis, only age at first upper GI endoscopy and presence of an ampullary abnormality were independent predictive factors. Histologic analysis after radical surgical treatment showed high-grade dysplasia in 30 patients and duodenal or ampulary adenocarcinoma in 11 (4 patients had lymph node involvement). LIMITATIONS: The study was limited by its retrospective analysis of a prospective database. CONCLUSIONS: More than 20% of patients developed high-grade dysplasia with duodenal polyposis after 10 years. Iterative endoscopic resections allowed extended control, but surgery remained necessary in 12% of the patients and happened too late in many cases; 20% of those operated had developed duodenal or ampulary adenocarcinoma, whereas 8% exhibited malignancy with lymph node involvement. The trigger for prophylactic surgery required a more accurate predictive score leading to closer endoscopic surveillance. Modifying the Spigelman score by accounting for ampullary abnormalities should be considered as a means to increase compliance with closer endoscopic follow-up in high-risk patients. See Video Abstract at http://links.lww.com/DCR/A430.

Prevalence and risk factors for adenomas in the ileal pouch and the afferent loop after restorative proctocolectomy for patients with familial adenomatous polyposis.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the treatment of choice in familial adenomatous polyposis (FAP) to prevent the risk of colorectal cancer. However, it currently is recognized that adenomas may develop in the ileal pouch. The risk of adenoma occurring in the afferent ileal loop above the pouch is less clearly identified. This study aimed to evaluate the difference in prevalence of adenomas between the ileal pouch and the afferent ileum after IPAA in FAP. METHODS: The study analyzed 442 endoscopies performed between 2003 and 2008 for 139 FAP patients. The patients had undergone an IPAA in 118 cases, an ileorectal anastomosis in 13 cases, or an ileostomy in 8 cases. RESULTS: Among the 118 IPAA patients, 57 (48.3 %) had pouch adenomas a median of 15 years after surgery. The risk factors for pouch adenomas were delay since pouch construction [odds ratio (OR), 1.11; p = 0.016] and presence of advanced duodenal adenomas (OR, 4.35; p = 0.011). Seven patients had pouch adenomas with high-grade dysplasia. Only nine patients had afferent ileal loop adenomas (6.5 %). The only significant risk factor for ileal adenomas was the presence of pouch adenomas (OR, 2.16; p = 0.007). CONCLUSION: After restorative proctocolectomy in FAP, adenoma recurrence is frequent in the pouch, with a higher risk for patients with advanced duodenal adenomas and an increasing risk over time, whereas adenomas are rarely found in the afferent ileal loop. This finding may help to propose redo ileal pouch anal anastomosis if required.

Severe duodenal involvement in familial adenomatous polyposis treated by pylorus-preserving pancreaticoduodenectomy.

PURPOSE: Pancreaticoduodenectomy is an alternative to pancreas-sparing duodenectomy for radical treatment of duodenal lesions. The aims of this study were to assess the results of pylorus-preserving pancreaticoduodenectomy (PPPD) for severe duodenal polyposis in familial adenomatous polyposis in terms of morbidity, long-term influence on functional results, the recurrence rate of cancer or jejunal polyps, and survival. METHODS: All patients operated on for a PPPD between 1992 and 2009 were included. Clinical data, endoscopic findings, and pathologic examinations were evaluated. RESULTS: A total of 19 patients underwent PPPD for severe duodenal polyposis (17 Spigelman IV, 1 Spigelman III, and 1 invasive carcinoma). Postoperative mortality was nil. The postoperative morbidity rate was 42%, including 4 pancreatic fistulae (21%) and 2 delayed gastric emptying (11%). Pathologic examination found 7 invasive carcinomas, of which only 1 was known before resection. One third of patients operated on without a preoperative diagnosis of malignancy already had an invasive duodenal carcinoma. After a mean follow-up of 58 months, 16 patients were alive. Thirteen patients underwent endoscopic follow-up, and new adenomas were found in 4 (31%). All were treated successfully during the same endoscopic procedure. PPPD did not modify the functional result after coloproctectomy. CONCLUSIONS: PPPD remains a safe and efficient therapeutic option for severe duodenal polyposis in familial adenomatous polyposis patients.

Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study.

Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cirrhosis (PBC). The long-term administration of UDCA might indirectly favor colon carcinogenesis by increasing the fecal excretion of secondary bile acids or, in contrast, it might inhibit colon carcinogenesis, as demonstrated in animal models. In patients with PBC, we examined the effect of prolonged UDCA administration on the prevalence and recurrence of colorectal adenoma and on the proliferation of colon epithelial cells. One hundred fourteen patients (103 women, 11 men; mean age, 55 years) with PBC, were enrolled in a colonoscopic surveillance program. The prevalence of colon adenoma was compared in patients already treated with UDCA (mean duration 46 months) at the time of colonoscopy (treated group, n = 52) and in patients undergoing colonoscopy just prior to treatment initiation (untreated group, n = 62). The recurrence of adenoma following removal (mean follow-up, 35 months) was compared between UDCA-treated patients and appropriate age- and gender-matched controls (2/1) selected from a cohort of 205 patients undergoing polypectomy. Epithelial cell proliferation was assessed using anti-Ki67 antibodies on colon biopsies from both treated and untreated patients. Treated and untreated patients displayed similar demographic characteristics. The prevalence of colorectal adenomas was 13% in the treated group versus 24% in the untreated group (P =.16). The colon epithelial cell proliferation index was significantly lower in treated patients than in untreated patients (P =.001). Following removal of the adenoma, the probability of recurrence was significantly lower in patients treated with UDCA than in controls (7% vs. 28% at 3 years, P =.04). In conclusion, this study suggests that, in patients with PBC, the prolonged administration of UDCA (1) is not associated with an increased prevalence of colorectal adenomas, and (2) significantly decreases the probability of colorectal adenoma recurrence following removal. These results are strengthened by the significant reduction in colon epithelial cell proliferation seen in patients treated with UDCA.