Monitoring of infliximab trough levels and anti-infliximab antibodies in inflammatory bowel diseases: A comparison of three commercially available ELISA kits.

BACKGROUND: There are many studies presenting data of biologics and several ELISA kits commercially available for monitoring infliximab serum trough levels (s-IFXt) and anti-drug antibodies (ADAb). We propose to compare technical characteristics and results of three different assays on a cohort of 35 patients under infliximab (IFX) and suffering from inflammatory bowel disease (IBD). PATIENTS AND METHODS: s-IFXt and ADAb were systematically measured with three ELISA kits: Lisa-Tracker® Duo infliximab (Theradiag®), Ridascreen® IFX Monitoring (R-Biopharm AG®) and Promonitor® IFX (Progenika Biopharma SA®). RESULTS: The main technical features that differed between kits for measuring s-IFXt were: (i) TNF coating, (ii) immune complexes revelation strategy and/or (iii) interference with other anti-TNFα agents. For kits measuring ADAb, they were revelation steps and unit of results. There was an excellent mathematical correlation of s-IFXt between assays however Bland-Altman analysis denoted (i) s-IFXt were on average 48 to 69% higher in Ridascreen® than in the other two assays, and (ii) elevated s-IFXt were higher with Promonitor® compared to Lisa-Tracker®. As a consequence, there were some substantial discrepancies between assays for classification of s-IFXt into concentration ranges. Despite unstandardized units, pairwise qualitative comparison showed a perfect agreement between the three pairs of ADAb assays. CONCLUSION: Our data show that the evaluated assays are not quantitatively interchangeable due to substantial variations in some results that could lead, for some patients, to divergent therapeutic decisions. We remind to be cautious when comparing study results issued from different kits and recommend using the same assay for the longitudinal follow-up of IBD patients.

Can papillary carcinomas be treated by endoscopic ampullectomy?

BACKGROUND: The utility of endoscopic ampullectomy versus surgical ampullectomy remains a topic of debate, particularly for the treatment of malignant tumors. The goal of this study was to prospectively establish the outcomes of endoscopic ampullectomy, with focus on carcinoma. METHODS: From February 2002 to December 2008, 61 patients underwent endoscopic ampullectomy. The ampulloma was discovered fortuitously in the majority of cases (43 patients, 70%). All patients had had an echoendoscopy revealing a T1N0 lesion without invasion of the orifice. RESULTS: Forty-three patients (70%) underwent a monobloc resection. Histological analysis revealed a low-grade dysplastic adenoma in 21 patients (35%), a high-grade dysplastic adenoma in 11 patients (18%), no dysplasia in 16 patients (26%), an adenocarcinoma in 10 patients (16%), and a well-differentiated endocrine carcinoma in 3 patients (5%). Among the ten patients with adenocarcinoma, four with adenocarcinoma of poor prognosis were treated by pancreaticoduodenectomy (PD) with R0 resection, of whom one patient had no more lesion. Two intramucosal adenocarcinomas were cured by endoscopic ampullectomy without any recurrence. Four patients received palliative care after endoscopic ampullectomy due to cephalic pancreatico-duodenectomy contraindication. For the three patients with well-differentiated endocrine carcinomas, one was treated by PD with R0 resection and two were treated solely by endoscopic ampullectomy, without recurrence. Eleven patients (18%) presented with complications. The complication rate was 30.5% for carcinomas versus 14.5% for benign tumors (p < 0.05). CONCLUSION: Endoscopic ampullectomy allows for the oncologic resection of well-differentiated intramucosal carcinomas with negative margins. The risk of complications is greater for papillary carcinomas.

Three-year outcome of local injection of autologous stromal vascular fraction cells and microfat in refractory perianal fistulas of Crohn's disease.

Perianal fistulas in Crohn's disease are frequent and disabling, with a major impact on patients' quality of life. Cell-based therapy using mesenchymal stem cells represents new hope for these patients, but long-term efficacy remains challenging. In a pilot study, including patients with refractory complex perianal fistulas, autologous adipose-derived stromal vascular fraction (ADSVF) combined with microfat achieved combined remission in 60% of cases, with a good safety profile at 1 year. The purpose of this study is to assess whether these results were maintained at longer term. The safety and efficacy data of the ten patients were evaluated retrospectively 3 years after injection on the basis of clinical and radiological data. MRI were analysed according to the MAGNIFI-CD score. No adverse event was attributed to the experimental stem-cell treatment. Combined remission was achieved in 7 patients (70%) and associated with a significant improvement in the MAGNIFI-CD MRI score. In conclusion, the safety and efficacy of ADSVF and microfat injection in Crohn's disease fistulas were maintained at 3 years, demonstrating that this innovative strategy is effective in producing a long-lasting healing effect. The ongoing multicentre randomized placebo-controlled trial (NCT04010526) will be helpful to define the place for this approach in the current therapeutic arsenal.

Preoperative infliximab treatment and postoperative complications after laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis: a case-matched study.

BACKGROUND: Infliximab offers promising new therapeutic options for treatment of moderate to severe ulcerative colitis. However, several studies suggest that it increases postoperative complication rates for patients who later require a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). This study aimed to assess the postoperative course of patients after laparoscopic IPAA, comparing those who had and those who had not received infliximab before surgery. METHODS: The authors identified patients from their institution's IPAA database, finding 13 patients who had received preoperative infliximab treatment. Using age, gender, and type of procedure (2 or 3 stages) as criteria, they matched these cases with infliximab-naive patients drawn from the same database. The differences in perioperative data between the two groups were analyzed. Complications and their severity were assessed using the Strasberg classification. RESULTS: No significant difference was found between patients treated with and those treated without infliximab for each variable studied, namely, mean operative time (353 vs. 355 min), complication rate (23 vs. 38%), and mean hospital stay (22 vs. 25 days). CONCLUSION: The study findings showed no adverse impact from previous infliximab therapy on the laparoscopic IPAA postoperative course.

Cuffitis: is an endoscopic approach possible?

Background Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the reference surgical treatment for patients with ulcerative colitis (UC) refractory to medical treatment. One of the complications is leaving a strip of rectal mucosa which can be a cause of persistent inflammation or cuffitis. The objective of our study is to present an endoscopic approach for the treatment of cuffitis. Methods This retrospective study included three patients who suffered from cuffitis after a proctocolectomy with IPAA for UC refractory to medical treatment. An endoscopic resection of the cuffitis was performed by the same operator. Two different techniques were used: hybrid endoscopic submucosal dissection (ESD) for one patient and mucosectomy with cap and resection for the two others. Results The endoscopic treatment was performed successfully in all three patients. The only complication observed was rectal bleeding which did not require endoscopic revision. The three patients are now asymptomatic. Conclusion Endoscopic treatment of cuffitis appears to be an interesting approach with few complications in the short term and good clinical efficacy.

Sacral nerve stimulation can improve continence in patients with Crohn's disease with internal and external anal sphincter disruption.

PURPOSE: Sacral nerve stimulation is a technique commonly used for the treatment of idiopathic incontinence. This study was designed to assess the efficiency of sacral nerve stimulation as a means of treating fecal incontinence in patients with Crohn's disease with disrupted internal and external anal sphincters. METHODS: Five patients (3 women) with fecal incontinence suffering from Crohn's disease-related anoperineal lesions were treated by applying three weeks of sacral nerve stimulation and then by permanent sacral nerve stimulation implantation. Endoanal ultrasonography showed that all of these patients had disrupted external and internal anal sphincters. RESULTS: Continence was improved in all treated patients. The median follow-up time was 14 (range, 3-36) months. At the end of the follow-up period, the median Wexner's score significantly improved from 15 to 6 and the median number of daily stools decreased from 7 to 2. The patients' quality of life also increased significantly. CONCLUSIONS: Sacral nerve stimulation improves fecal continence in patients suffering from Crohn's anoperineal lesions with internal and external anal sphincters disruption.

Is endoscopic sphincterotomy avoidable in patients with sphincter of Oddi dysfunction?

AIM: Endoscopic sphincterotomy is an efficient means of treating sphincter of Oddi dysfunction (SOD), but it is associated with a morbidity rate of 20%. The aim of this study was to assess how frequently endoscopic sphincterotomy was performed to treat SOD in a group of patients with a 1-year history of medical management. METHODS: A total of 59 patients, who had been cholecystectomized 9.3 years previously on average, were included in this study and they all underwent biliary scintigraphy. Medical treatment was prescribed for 1 year. Endoscopic sphincterotomy was proposed for patients whose medical treatment had been unsuccessful. RESULTS: Eleven patients were rated group 1 on the Milwaukee classification scale, 34 group 2 and 14 group 3. The hile-duodenum transit time (HDTT) was lengthened in 32 patients. The medical treatment was efficient or fairly efficient in 45% of the group 1 patients, 67% of the group 2 patients, and 71.4% of the group 3 patients (P=0.29). Only 14 patients out of the 21 whose medical treatment was unsuccessful agreed to undergo endoscopic sphincterotomy. HDTT was lengthened in 11 of the 14 patients undergoing endoscopic sphincterotomy and in 21 of the 45 non-endoscopic sphincterotomy patients (P=0.03). Twelve of the 14 patients who underwent endoscopic sphincterotomy were cured. CONCLUSION: In this prospective series of patients with a 1-year history of medical management, only 23% of the patients with suspected SOD underwent endoscopic sphincterotomy although 54% had an abnormally long HDTT.

First clinical case report of local microinjection of autologous fat and adipose-derived stromal vascular fraction for perianal fistula in Crohn's disease.

Mesenchymal stem cell therapy is a promising treatment for perianal Crohn's fistulas refractory to conventional therapy, which are an extremely morbid complication and a true therapeutic challenge. Autologous adipose-derived stromal vascular fraction (ADSVF) is an easily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. Here, we describe a case involving a patient with severe perianal Crohn's fistulas refractory to the best medical and surgical practices who received local treatment with ADSVF and microfat. This patient was first examined under anesthesia with drainage via seton placement; 1 week later, on a single day, he underwent adipose tissue extraction, ADSVF and microfat preparation, and the local injection of 14 ml of microfat and approximately 20 million viable ADSVF cells into the soft tissue around the fistulas. No serious adverse events were observed. At the first endpoint at 12 weeks, the fistula had clinically healed with complete re-epithelialization of all external openings; no fistula tract was detected on magnetic resonance imaging, confirming this finding. This good clinical outcome was sustained at 48 weeks and was associated with a reduction in the severity of perianal disease and an improvement in quality of life. The current case highlights the therapeutic potential of a new cellular treatment for Crohn's patients with refractory perianal fistulas based on the innovative hypothesis that the combined action of ADSVF in association with the trophic characteristics of a microfat graft could be beneficial for this condition. TRIAL REGISTRATION: EudraCT number 201325, NCT02520843 . Registered on 5 August 2015.

[Endoscopic management of biliary and pancreatic ascariasis in Viet-Nam. Report of a series of 91 cases]. / Traitement endoscopique de l'ascaridiose bilio-pancréatique au Viet-Nam. A propos de 91 cas.

AIM: Ascariasis is the most widespread helminthiasis in the world. Biliary and pancreatic involvement, frequently encountered in endemic areas, is a serious public health problem. Surgical management is often required. The purpose of our work was to assess the feasibility of emergency endoscopic treatment of biliary and pancreatic ascariasis in the Viet Duc hospital (Hanoi, Vietnam), and to evaluate outcome. METHODS: A prospective study conducted over a 3-year period included 91 patients with biliary and pancreatic ascariasis. Diagnosis was based on clinical findings and abdominal ultrasound and was confirmed by endoscopic procedures. RESULTS: The 91 patients, 21 males and 70 females, mean age 41 +/- 17 years, underwent endoscopic procedures to retrieve the worm. The procedure was successful in 89 patients (97.8%). Mild pancreatitis occurred in four patients who underwent biliary sphincterotomy. The mean hospital stay was 3.1 days. CONCLUSION: Endoscopic management of ascariasis is feasible, with a very low morbidity and a high rate of success. With this treatment, hospital stay is greatly shortened.

Serum measurements of pancreatitis associated protein in active Crohn's disease with ileal location.

BACKGROUND AND AIMS: Pancreatitis-associated protein (PAP) is a pancreatic stress protein also expressed in the ileum but not in the colon. Its serum concentration is increased in patients with small bowel inflammation due to untreated celiac disease. We searched to determine whether PAP could be a serum marker for ileal location of active Crohn's disease (CD). METHODS: A multicenter prospective study was conducted, including 54 healthy controls and 124 patients with CD of whom 38 had quiescent ileal or ileocolonic disease (group A), 45 had active ileal or ileocolonic disease (group B), 18 had quiescent colon-only CD (group C), and 28 had active colonic disease (group D). Active disease was defined by a Crohn's disease activity index > 150 and serum C-reactive protein (CRP) > 10 mg/mL. Location of lesions was assessed by endoscopy. PAP was assayed in serum, the upper threshold for normal values being 50 ng/mL. RESULTS: In group B, 27 patients (60%) had elevated serum PAP, compared to one in group A (2.5%), one in group C (5.3%), three in group D (10.7%) and none in the control group (P<0.01). By contrast, serum levels of C-reactive protein did not differ between patients with active CD and either ileal location (group B) or pure colonic location (group D) (38 +/-10.5 vs 41.6 +/- 6.4 mg/mL, NS). Within group B, serum PAP concentration was correlated with none of the epidemiological, clinical or biological data available. Increased serum level of PAP diagnosed ileal location in active CD with a sensitivity of 60%, a specificity of 94%, a positive predictive value of 84% and a negative predictive value of 81%. CONCLUSION: Elevated serum PAP (> 50 ng/mL ) is significantly associated with disease activity and ileal location

Targeting tissular immune response improves diagnostic performance of anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease.

Antibodies against Saccharomyces cerevisiae (ASCA) and Escherichia coli outer membrane porin C (anti-OmpC) are known to be detectable in the serum of patients with Crohn's disease (CD) but display a very poor sensitivity for the disease especially in forms with isolated colonic involvement. In this study we aimed at evaluating performances of these markers in supernatant of cultured colonic biopsies. Patients with colonic CD (n =  67), ulcerative colitis (UC) (n = 35) and control individuals (n = 37) were prospectively recruited for colonoscopy pinch biopsies and blood sampling. Serum and supernatant of culture tissues were analyzed for ASCA and anti-OmpC. Direct immunofluorescence was also performed on colonic tissues for total IgA detection. We detected for the first time ASCA IgA/IgG and anti-OmpC IgA in cultured colonic tissue supernatants. For both markers, sensitivities for diagnosing CD were better in supernatants (ASCA: 53.7%, anti-OmpC: 28.4%) than in serum (ASCA: 31.3%, anti-OmpC: 22.4%). Combination of results from a panel of these tests gave the greatest sensitivity ever described for CD diagnosis in colonic forms (70.2%). In this study, we described, for the first time, ASCA in supernatant of colonic tissue cultures. This assaying approach in CD diagnosis should be taken into consideration in the future especially in CD forms with isolated colonic involvement.

The usefulness of factor XIII levels in Crohn's disease.

BACKGROUND AND AIMS: The assessment of inflammatory activity in Crohn's disease (CD) is challenging, and no specific laboratory marker is currently available. Several studies have reported decreased serum factor XIII levels in CD patients as a function of disease activity. We aimed to determine whether the factor XIII level could be a marker for the evolution of CD. METHODS: In this prospective, single-centre trial, 129 patients were included and categorised into two groups: functional bowel disorders (FBDs, n=42) and CD (n=86). The CD group was divided into two subgroups depending on disease activity, as defined by the Crohn's Disease Activity Index score: active disease (CDa, n=41) and disease remission (CDb, n=45). The factor XIII levels were evaluated for each patient. Serial factor XIII levels were evaluated in the patients within the CDa subgroup. RESULTS: The factor XIII levels were significantly different between the FBD (117.69%) and CD (101.89%) groups (p=0.009) but there was no significant difference between the CDa and CDb subgroups (99.04% vs 104.65%, p>0.05), and the levels did not vary during follow-up for the patients in the CDa subgroup. By multivariate analysis, factor XIII levels did not correlate with the time course of disease evolution, CRP, serum fibrin levels, platelet count, disease distribution within the bowel, or the presence of a fistulising form of CD. CONCLUSIONS: Our results confirm that factor XIII levels are decreased in CD patients but cannot be recommended as a marker for the disease activity.

The Rapunzel syndrome: a hard-to-swallow tale.

INTRODUCTION: Rapunzel syndrome is a rare entity comprising of a large gastroduodenal trichobezoar due to trichotillomania. Its treatment is often surgical. CASE REPORT: A 27-year-old patient was investigated after an upper gastro-intestinal tract obstruction. Computed tomography and endoscopy showed a large gastric trichobezoar with a duodenojejunal tail. Conservative treatments failed to remove the bezoar. We performed a short laparotomy which allowed the removal of the bezoar through a longitudinal gastrotomy. Postoperative course was uneventful.

Large endoscopic mucosal resection for colorectal tumors exceeding 4 cm.

AIM: To evaluate the feasibility and the outcome of endoscopic mucosal resection (EMR) for large colorectal tumors exceeding 4 cm (LCRT) undergoing piecemeal resection. METHODS: From January 2005 to April 2008, 146 digestive tumors larger than 2 cm were removed with the EMR technique in our department. Of these, 34 tumors were larger than 4 cm and piecemeal resection was carried out on 26 colorectal tumors. The mean age of the patients was 71 years. The mean follow-up duration was 12 mo. RESULTS: LCRTs were located in the rectum, left colon, transverse colon and right colon in 58%, 15%, 4% and 23% of cases, respectively. All were sessile tumors larger than 4 cm with a mean size of 4.9 cm (4-10 cm). According to the Paris classification, 34% of the tumors were type Is, 58% type IIa, 4% type IIb and 4% type IIc. Pathological examination showed tubulous adenoma in 31%, tubulo-villous adenoma in 27%, villous adenoma in 42%, high-grade dysplasia in 38%, in situ carcinoma in 19% of the cases and mucosal carcinoma (m2) in 8% of the cases. The two cases (7.7%) of procedural bleeding that occurred were managed endoscopically and one small perforation was treated with clips. During follow-up, recurrence of the tumor occurred in three patients (12%), three of whom received endoscopic treatment. CONCLUSION: EMR for tumors larger than 4 cm is a safe and effective procedure that could compete with endoscopic submucosal dissection, despite providing incomplete histological assessment.

Clinical usefulness of a treatment algorithm for pancreatic pseudocysts.

BACKGROUND: Endoscopic procedures have become a first-line approach to the treatment of pancreatic pseudocysts. OBJECTIVE: Our purpose was to determine the results of a therapeutic algorithm including EUS-assisted drainage, transpapillary drainage, and conventional endoscopic drainage in terms of (1) feasibility and efficacy of the endoscopic procedure and (2) morbidity. DESIGN: Prospective study with a treatment algorithm drawn up before the endoscopic procedure, including either conventional endoscopic transmural drainage (CTMD), conventional transpapillary drainage (CTPD), or EUS-guided transmural drainage (EUS-GTD). PATIENTS: A total of 50 patients, including 15 women and 35 men with a mean age of 51 years, were included in this prospective study. RESULTS: The mean size of the pseudocysts was 8.2 cm (range 3-12 cm). A total of 29 pseudocysts did not bulge into the digestive wall (58%); 24 (48%) neither bulged nor communicated with the pancreatic duct. EUS-GTD was performed on 28 patients (56%), CTMD on 13 patients (26%), and CTPD on 8 patients (16%), and endoscopic procedures failed in 1 patient. Technical feasibility was 98% (49/50), and clinical success was achieved in 90% of the cases and disappearance of the pseudocysts in 96% of the cases without significant differences among the 3 groups. The morbidity rate was 18% (9 cases). Five superinfections occurred in the EUS-GTD group and 1 in the CTMD group. One death occurred from late bleeding in the CTMD group. LIMITATION: Randomization of patients in this prospective study was not possible because of the different characteristics of the pseudocysts. CONCLUSION: With this algorithm, clinical success was achieved in 45 (90%) of the cases and disappearance of the pseudocysts in 48 (96%) of the cases with a reasonable morbidity rate. In half of the cases, EUS is required for treating pancreatic pseudocyst.