Ariane Vienne

Usefulness of co-treatment with immunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy

Background and aims Concomitant use of immunosuppressants (IS) with scheduled infliximab (IFX) maintenance therapy for Crohns disease (CD) or ulcerative colitis (UC) is debated. The aim of this study was to assess whether IS co-treatment is useful in patients with inflammatory bowel disease (IBD) on scheduled IFX infusions. Methods 121 consecutive patients with IBD (23 UC, 98 CD) treated by IFX and who received at least 6 months of IS co-treatment (azathioprine (AZA) or methotrexate (MTX)) were studied. In each patient, the IFX treatment duration was divided into semesters which were independently analysed regarding IBD activity. Results Semesters with IS (n=265) and without IS (n=319) were analysed. IBD flares, perianal complications and switch to adalimumab were less frequently observed in semesters with IS than in those without IS (respectively: 19.3% vs 32.0%, p=0.003; 4.1% vs 11.8%, p=0.03; 1.1% vs 5.3%, p=0.006). Maximal C-reactive protein (CRP) level and IFX dose/kg observed during the semesters were lower in semesters with IS. Within semesters with IS, IBD flares and perianal complications were less frequently observed in semesters with AZA than in those with MTX. In multivariate analysis, IS co-treatment was associated with a decreased risk of IBD flare (OR 0.52; 95% CI 0.35 to 0.79) Conclusion In patients with IBD receiving IFX maintenance therapy, IS co-treatment is associated with reduced IBD activity, IFX dose and switch to adalimumab. In this setting, co-treatment with AZA seems to be more effective than co-treatment with MTX. Benefit of such a combination treatment has to be balanced with potential risks, notably infections and cancers.

Prediction of drainage effectiveness during endoscopic stenting of malignant hilar strictures: the role of liver volume assessment.

BACKGROUND The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral stenting. OBJECTIVE To identify useful criteria for predicting successful endoscopic drainage. DESIGN AND SETTING Retrospective 2-center study in the greater Paris area in France. PATIENTS A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. INTERVENTIONS The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. MAIN OUTCOME MEASUREMENTS The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. RESULTS The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). LIMITATIONS Heterogeneous population and volume assessment methodology to improve in further prospective studies. CONCLUSION Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.

Risk Factors for Neoplasia in Inflammatory Bowel Disease Patients With Pancolitis

OBJECTIVES:Colorectal cancer (CRC), developing from dysplastic lesions, is the main long-term complication of pancolitis. The aims of the present study were to assess the risks for neoplasia and advanced neoplasia (AN), respectively, in ulcerative colitis (UC) and Crohns disease (CD) patients with pancolitis, and to search for protective and risk factors for colorectal neoplasia.METHODS:A total of 855 inflammatory bowel disease (IBD) patients with longstanding pancolitis (276 UC, 56 IBD unclassified (IBDu), and 523 CD) had pathological examination of a proctocolectomy specimen (n=255) or multiple biopsy samples from a surveillance colonoscopy (n=600) after median disease duration of 115 months. Risk factors for low-grade dysplasia (LGD) and AN, respectively, were searched for in the whole group of patients and in a case–control comparison after matching for IBD phenotype.RESULTS:A total of 75 patients eventually developed colorectal neoplasia: 14 adenomas, 28 nonadenomatous LGD, and 33 ANs. The 25-year cumulative risks for neoplasia and AN, respectively, were 32.8±5.7% and 25.9±5.7% in UC and IBDu vs. 12.1±2.7% and 3.9±2.0% in CD (P<0.0001). In CD, patients with UC-like endoscopic appearance (n=126) had an increased risk for AN compared with those with discrete lesions (at 25 years, 10.6±7.2 vs. 1.5±0.9%). In the case–control comparison, factors associated with an increased risk of AN were primary sclerosing cholangitis (hazard ratio (HR) 4.72 (1.54–14.52)) and family history of CRC (HR 3.37 (1.02–11.14)), whereas previous segmental colectomy was protective (HR 0.25 (0.07–0.88)).CONCLUSIONS:The risk of AN in longstanding pancolitis is higher in UC or IBDu than in CD. In CD, this risk is significantly increased in patients with UC-like endoscopic lesions. The surveillance program should focus on these latter patients.

Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort

Aliment Pharmacol Ther 2011; 34: 188–195

Early experience with a novel hemostatic powder used to treat upper GI bleeding related to malignancies or after therapeutic interventions (with videos)

Upper GI bleeding is a common clinical condition associated with considerable morbidity and mortality. Conventional treatment modalities, such as injection and thermal and mechanical therapies used alone or in combination, typically achieve hemostasis in more than 90% of cases. However, treatment of recurrent bleeding (necessary in 10%-30%) introduces additional limitations and adverse events. Epinephrine injection is associated with high rates of recurrent bleeding, and thermal therapies can cause tissue injury. Mechanical methods can be technically challenging and require specialized endoscopic expertise. These conventional modalities also can be challenging during treatment of diffuse, widespread bleeding. Peptic ulcer disease is the most common type of nonvariceal upper GI bleeding. However, bleeding also can occur as a consequence of therapeutic endoscopic interventions and from malignancies. In the latter, bleeding can be induced by tumor necrosis or chemotherapy and is typically diffuse and widespread. Even though conventional treatments can be effective as first-line therapies, hemostasis is often difficult to achieve and maintain

Current Smoking, Not Duration of Remission, Delays Crohn's Disease Relapse Following Azathioprine Withdrawal

To the Editor: Whereas azathioprine (AZA) is an efficient maintenance treatment in Crohn’s disease (CD), there is increasing evidence that most of the risks of AZA use rely on prolonged exposure. However, CD relapses when AZA is stopped within 5 years following its initiation. We tested whether the risk of relapse remains high after a longer use of AZA. Among the 4035 patients with CD evaluated in our tertiary center, medical files from 47 patients who stopped AZA for personal convenience during remission and after a minimum of 3.5 years of treatment were retrospectively analyzed. Clinical and follow-up data were compared to those of a control group composed of CD patients matched 2 on 1 for AZA initiation date and who continued with AZA beyond the withdrawal date of the case (94 patients). Both patients groups were similar regarding gender, age at AZA initiation, elapsed time between CD diagnosis and AZA initiation, CD phenotype (Montréal Classification), and smoking habits. As expected, patients from the AZA withdrawal group had an earlier relapse compared to the controls (57.3% versus 17.6% relapse rate at 2 years and 73.3% versus 44.4% relapse rate at 5 years, respectively; P < 0.001). More important, in the AZA withdrawal group, late withdrawal (after: 98.4 5.7 months; [72.0–164.0]) led to a similar relapse rate than early withdrawal (after: 58.7 1.6 months; [41.0–69.7]) with relapse rates of 61% versus 54% at 2 years and 68% versus 78% at 5 years, respectively (P 1⁄4 0.89). In the AZA withdrawal group, factors independently associated with relapse (obtained using a Cox model) were: male gender (odds ratio [OR] 1⁄4 2.42; P 1⁄4 0.02) and absence of smoking (OR 1⁄4 2.78; P 1⁄4 0.006). The relapse rates increased significantly with none, 1, or 2 of those predictive factors (Fig. 1; P 1⁄4 0.006). Interestingly, in a previous study in CD, male gender was also associated with a higher risk of relapse after 6-mercaptopurine withdrawal. The paradoxical protective effect of smoking after AZA withdrawal was also demonstrated in a recent GETAID study that included different patients from ours. There is no clear explanation about this effect and in many other CD settings, such as postoperative situation, tobacco use has been associated with a higher relapse rate. Moreover, the effect of current smoking was clearly harmful in our whole cohort of CD patients. One can hypothesize that the AZA effect is more prolonged in smokers than in nonsmokers, possibly because of a synergistic immunosuppressive action of tobacco and AZA. Another explanation could be that the selection of the patients in our study (as well as in the study from Treton et al) was skewed as we selected patients in whom AZA was highly effective, for a yet unknown reason, despite tobacco use. In conclusion, AZA withdrawal exposes patients to a high relapse rate regardless of the treatment duration, even when it is above 6 years. Nonsmoking male patients seem to be more exposed to relapse. These data are in favor of an extended AZA maintenance therapy, and particularly in nonsmoking males. On the other hand, transient AZA interruption could be attempted in selected smoking females.

Pancreatoscopy-guided intracorporeal laser lithotripsy for difficult pancreatic duct stones: a case series with prospective follow-up (with video)

Pancreatic stones develop in patients with chronic pancreatitis, with as many as 90% of alcoholic chronic pancreatitis patients bearing ductal stones during long-term follow-up. 1 Main pancreatic duct calculi can lead to an outflow obstruction with increased parenchymal pressure, upstream dilation (ie, toward the tail of the pancreas), and ischemia. Untreated stones can also trigger bouts of acute pancreatitis sometimes associated with life-threatening adverse events. Pain is the predominant symptom in most patients with obstructive chronic pancreatitis, often alleviated only by narcotics and inducing anorexia, malabsorption, and weight loss. It is only with main pancreatic duct decompression from impacted stones that such adverse events can be avoided. 2,3 Small stones can be extracted by using various endoscopic techniques during ERCP, such as pancreatic sphincterotomy with balloon or basket sweeping, pancreatic duct stricture dilation, or stent placement. Larger and impacted stones typically require lithotripsy or surgery. Endoscopic lithotripsy options include (1) mechanical lithotripsy, for which data are scarce but suggest that this procedure may carry an increased risk of adverse events when compared with lithotripsy for biliary stones 2 ; (2) extracorporeal shock wave lithotripsy (ESWL), which overcomes the problem of size by fragmenting calculi and reducing the stone burden, thus facilitating endoscopic duct clearance 3 ; (3) contact lithotripsy by using pancreatoscopy with a mother-baby endoscope system. 4 Directcontact lithotripsy of biliopancreatic stones can be achieved by means of electrohydraulic lithotripsy (EHL) or pulseddye laser, both of which must be done under direct vision. Scant clinical outcome data are available regarding the application of these methods for pancreatic duct stone fragmentation. 5 Our aim was to evaluate the endoscopic treatment at our center by intracorporeal laser lithotripsy (ILL) with a single-operator mini-endoscope (SpyGlass; Boston Scientific, Natick, Mass) during ERCP, for its performance, feasibility, and safety in the treatment of difficult main pancreatic duct stones.

Temporary placement of fully covered self-expandable metal stents for the treatment of benign biliary strictures.

Background Endoscopic treatment of benign biliary strictures (BBS) can be challenging. Objective To evaluate the efficacy of fully covered self-expandable metal stents (FCSEMS) in BBS. Methods Ninety-two consecutive patients with BBS (chronic pancreatitis (n = 42), anastomotic after liver transplantation (n = 36), and post biliary surgical procedure (n = 14)) were included. FCSEMS were placed across strictures for 6 months before endoscopic extraction. Early success rate was defined as the absence of biliary stricture or as a minimal residual anomaly on post-stent removal endoscopic retrograde cholangiopancreatography (ERCP). Secondary outcomes were the final success and stricture recurrence rates as well as procedure-related morbidity. Results Stenting was successful in all patients. Stenting associated complications were minor and occurred in 22 (23.9%) patients. Migration occurred in 23 (25%) patients. Stent extraction was successful in all but two patients with proximal stent migration. ERCP after the 6 months stenting showed an early success in 84.9% patients (chronic pancreatitis patients: 94.7%, liver transplant: 87.9%, post-surgical: 61.5%) (p = 0.01). Final success was observed in 57/73 (78.1%) patients with a median follow-up of 12 ± 3.56 months. Recurrence of biliary stricture occurred in 16/73 (21.9%) patients. Conclusions FCSEMS placement is efficient for patients with BBS, in particular for chronic pancreatitis patients. Stent extraction after 6 months indwelling, although generally feasible, may fail in a few cases.

Duodenal duplication cyst: a rare cause of recurrent pancreatitis

We report the case of a 54-year-old man with a medical history of recurrent pancreatitis who was referred to our department for a novel episode of epigastric pain. A blood test confirmed the diagnosis of acute pancreatitis, and a biliary origin was suspected because of abnormal liver test results and dilatation of the biliary ducts as shown by US. A CT scan confirmed the bile duct dilatation and showed a voluminous cystic lesion of 40 30 mm developed from the duodenal wall (Fig. 1). Upper GI endoscopy identified a submucosal pedunculated lesion likely originating from the papilla area and completely obstructing its lumen. The cystic characteristics of the lesion were confirmed by EUS, but neither the typical

Long-term follow-up after endoscopic resection for superficial esophageal squamous cell carcinoma: a multicenter Western study

BACKGROUND  Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are the first-line treatments for superficial esophageal squamous cell carcinoma (SCC). This study aimed to compare long-term clinical outcome and oncological clearance between EMR and ESD for the treatment of superficial esophageal SCC. METHODS  We conducted a retrospective multicenter study in five French tertiary care hospitals. Patients treated by EMR or ESD for histologically proven superficial esophageal SCC were included consecutively. RESULTS  Resection was performed for 148 tumors (80 EMR, 68 ESD) in 132 patients. The curative resection rate was 21.3 % in the EMR group and 73.5 % in the ESD group (P < 0.001). The recurrence rate was 23.7 % in the EMR group and 2.9 % in the ESD group (P = 0.002). The 5-year recurrence-free survival rate was 73.4 % in the EMR group and 95.2 % in the ESD group (P = 0.002). Independent factors for cancer recurrence were resection by EMR (hazard ratio [HR] 16.89, P = 0.01), tumor infiltration depth ≥ m3 (HR 3.28, P = 0.02), no complementary treatment by chemoradiotherapy (HR 7.04, P = 0.04), and no curative resection (HR 11.75, P = 0.01). Risk of metastasis strongly increased in patients with tumor infiltration depth ≥ m3, and without complementary chemoradiotherapy (P = 0.02). CONCLUSION  Endoscopic resection of superficial esophageal SCC was safe and efficient. Because it was associated with an increased recurrence-free survival rate, ESD should be preferred over EMR. For tumors with infiltration depths ≥ m3, chemoradiotherapy reduced the risk of nodal or distal metastasis.