Long-term outcomes and predictors of disabling disease in a population-based cohort of patients with incident Crohn's disease diagnosed between 1994 and 1997.

BACKGROUND: The identification of early prognostic factors during Crohn's disease (CD) remains needed for physician decision-making to minimize structural bowel damage, which this study aimed to assess in a population-based setting. METHODS: All incident cases of CD were prospectively registered from 1994 to 1997 in Brittany, a limited area of France. All charts of patients were reviewed from the diagnosis to the last clinic visit in 2015. Disabling CD course was defined according to the Saint-Antoine criteria. RESULTS: Among the 331 incident cases of CD, 272 (82%) were followed-up for a median time of 12.8 years. The cumulative probability of developing stricturing or fistulizing CD was 66% at 15 years, and 107 (39%) patients underwent surgery. The cumulative probabilities of immunosuppressant and TNF antagonist use at 15 years were 37% and 22%, respectively. The cumulative risks for disabling disease and bowel damage were 74% and 71% at 15 years, respectively. Systemic symptoms and perianal lesions at diagnosis were independently associated with a disabling disease course. Perianal disease and short disease extension were associated with the onset of bowel damage. Deep ulcers was not predictive of any outcome. CONCLUSIONS: A disabling disease course and bowel damage occurred early in the course of CD, which suggests the need for early diagnosis and early treatment, particularly for patients with systematic symptoms and perianal disease.

Altered epithelial barrier functions in the colon of patients with spina bifida.

Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1-47.2]) were compared with those of 16 HVs (age: 39.0 [31.0-46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = - 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFß1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415.

Natural History of Perianal Crohn's Disease: Long-term Follow-up of a Population-Based Cohort.

BACKGROUND AND AIMS: The natural history of perianal Crohn's disease (PCD) remains poorly described and is mainly based on retrospective studies from referral centers. The aim of this study was to assess the incidence, outcomes and predictors of the onset of PCD. METHODS: All incident cases of patients diagnosed with possible CD were prospectively registered from 1994 to 1997 in Brittany, a limited area in France. At diagnosis, the clinical features of perianal disease were recorded. All patient charts were reviewed from the diagnosis to the last clinic visit in 2015. RESULTS: Among the 272 out of 331 incident CD patients followed up, 51 (18.7%) patients had PCD at diagnosis. After a mean follow-up of 12.8 years, 93 (34%) patients developed PCD. The cumulative probabilities of perianal CD occurrence were 22%, 29%, and 32% after 1 year, 5 years, and 10 years, respectively. The cumulative probabilities of anal ulceration were 14%, and 19% after 1 year and 10 years, respectively. Extraintestinal manifestations were associated with the occurrence of anal ulceration. The cumulative probabilities of fistulizing PCD were 11%, 16%, and 19% after 1 year, 5 years, and 10 years, respectively. Extraintestinal manifestations, rectal involvement and anal ulceration were predictors of fistulizing PCD. The cumulative probability of developing anal stricture was 4% after 10 years. CONCLUSIONS: PCD is frequently observed during CD, in approximately one-third of patients. These data underline the need for targeted therapeutic research on primary perianal lesions (proctitis, anal ulceration) to avoid the onset of fistulizing perianal disease.

The reversion variant (p.Arg90Leu) at the evolutionarily adaptive p.Arg90 site in CELA3B predisposes to chronic pancreatitis.

A gain-of-function missense variant in the CELA3B gene, p.Arg90Cys (c.268C>T), has recently been reported to cause pancreatitis in an extended pedigree. Herein, we sequenced the CELA3B gene in 644 genetically unexplained French chronic pancreatitis (CP) patients (all unrelated) and 566 controls. No obvious loss-of-function variants were identified. None of the six low-frequency or common missense variants detected showed significant association with CP. Nor did the aggregate rare/very rare missense variants (n = 14) show any significant association with CP. However, p.Arg90Leu (c.269G>T), which was found in four patients but no controls, and affects the same amino acid as p.Arg90Cys, serves to revert p.Arg90 to the human elastase ancestral allele. As p.Arg90Leu has previously been shown to exert a similar functional effect to that of p.Arg90Cys, our findings not only confirm the involvement of CELA3B in the etiology of CP but also pinpoint a new evolutionarily adaptive site in the human genome.

Incidental colorectal focal 18 F-FDG uptake: a novel indication for colonoscopy.

BACKGROUND AND STUDY AIMS: The relevance of incidental colorectal focal 18 F-FDG PET/CT uptake is debatable. All patients who were referred for colonoscopy because of incidental colonic focal FDG uptake were included in this retrospective study. PATIENTS AND METHODS: PET/CT imaging characteristics were reviewed by a nuclear physician who was blinded to endoscopic and histopathological findings to determine the location of FDG uptake sites and to measure the maximum standardized uptake values (SUVmax) and metabolic volume (MV). Endoscopic findings were categorized as malignant lesions (ML), high-risk polyps (HRP), low-risk polyps (LRP) or other non-neoplastic lesions (NNL). RESULTS: Seventy patients with 84 foci of FDG uptake were included. The proportions of true-positive (lesions found at colonoscopy at the same location) and false-positive (no lesion at colonoscopy) PET/CT findings were 65.5 % (n = 55) and 34.5 % (n = 29). Median SUVmax values did not differ between true-positive and false-positive findings ( P  = 0.27). Median MV30 values differed significantly between true-positive (5.5 cm 3 , [3.3 - 10.9 cm 3 ]) and false-positive (9.7 cm 3 , [5.2 - 40.8 cm 3 ]) findings ( P  = 0.015). Among the 55 true-positive FDG uptake sites, there were 14 (25.5 %) malignant lesions, 30 (54.5 %) HRP, 4 (7.3 %) LRP, and 7 (12.7 %) NNL. Median MV30 values differed significantly between advanced neoplasia (5.0 cm 3 , [2.9 - 9.7 cm 3 ]) and other endoscopic findings (9.4 cm 3 , [5.2 - 39.8 cm 3 ]) ( P  = 0.001); the AUROC was 0.71. By per-colonic segment analysis, the distribution of true-positive, false-negative, false-positive, and true-negative FDG PET/CT findings was as follows: 21.5 %, 14.2 %, 11.5 %, and 52.8 %, respectively. CONCLUSION: Our study demonstrates that follow-up complete colonoscopy is mandatory in all patients with incidental colorectal focal 18 F-FDG PET/CT uptake.

Core needle versus standard needle for endoscopic ultrasound-guided biopsy of solid pancreatic masses: a randomized crossover study.

BACKGROUND AND STUDY AIMS: A new core biopsy needle for endoscopic ultrasound (EUS)-guided sampling has recently been developed. The aim of this prospective multicenter study was to compare this needle with a standard needle in patients with solid pancreatic masses. PATIENTS AND METHODS: Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included. Each patient had two passes with a standard 22G needle and a single pass with a 22G core needle performed in a randomized order. Samples from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists. The primary endpoint was the accuracy of the detection of malignancy. The reference standard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning, endoscopic or surgical guidance, and/or by clinical follow-up with repeated imaging examinations for at least 12 months. The secondary endpoints were the rate of technical failure and the quality of the cytohistological samples obtained. RESULTS: Of the 80 patients included (49 men; mean age 67.1 ±â€Š11.1), 87.5 % had final malignant diagnoses (adenocarcinoma n = 62, 77.5 %). There was no difference between the needles in diagnostic accuracy (standard needle 92.5 % vs. core needle 90 %; P = 0.68) or technical failure. Both pathologists found the overall sample quality significantly better for the standard needle (expert 1, P = 0.009; expert 2, P = 0.002). CONCLUSIONS: The diagnostic accuracy of EUS sampling for solid pancreatic masses using standard and core needles seems comparable but with a better overall histological sample quality for the former. ClinicalTrial.gov identifier: NCT01479803.

Long-term results of pneumatic dilatation for relapsing symptoms of achalasia after Heller myotomy.

BACKGROUND: The aim of this study was to assess the efficacy and safety of pneumatic dilatation (PD) to treat symptom recurrence after Heller myotomy (HM). METHODS: Consecutive patients receiving PD for relapsing symptoms following prior HM were included in this retrospective single-center study. Eckardt score ≤3 and/or ∆ Eckardt (difference between Eckardt score before and after dilatation) ≥3 defined the success of initial dilatation. Patients who maintained response longer than 2 months after initial dilatation were defined as short-term responders. Relapsers were offered further on-demand dilatation. Remission was defined as an Eckardt score ≤3 at the study endpoint. Kaplan-Meier survival curves were used to determine relapse rates. KEY RESULTS: Eighteen patients (11 women, seven men) were included from January 2004 to January 2013. Ten patients had type I achalasia, and seven had type III, according to the Chicago classification. Thirty-nine PDs were performed (1.5 [1-2.25] per patient). All patients had short-term responses. The remission rate at the endpoint, after a median follow-up of 33 months, was 78%, but 44% were treated with on-demand PD during the follow-up interval. The proportions of patients without relapse and subsequent PD were 72% at 12 months, 65% at 24 and 36 months, and 49% at 48 months. No factors predictive of long-term response, particularly the type of achalasia, could be identified in this series. There were no perforations. CONCLUSIONS & INFERENCES: In treating symptom recurrence following HM, PD was safe and effective over the long term when combined with subsequent PD.

Removal of transanastomotic pancreatic stent tubes after pancreaticoduodenectomy: a new role for double-balloon enteroscopy.

BACKGROUND: Endoscopic interventions are usually very challenging in patients with anatomic changes caused by earlier GI surgery. The recent development of the double-balloon enteroscopy (DBE) system creates an opportunity to reach the biliary tract and the pancreatic duct in postsurgical conditions. OBJECTIVE: To report a further application of DBE in surgical patients; namely, extraction of pancreatic stents placed in pancreaticojejunal anastomosis during pancreaticoduodenectomy. DESIGN: Two case reports. SETTING: A single-center experience in a tertiary-care unit. PATIENTS AND INTERVENTIONS: Two patients who underwent Whipple resection with Roux-en-Y reconstruction presented with migration of pancreatic stent tubes inserted in pancreaticojejunal anastomoses. Stents had migrated to the end of the afferent limb and were causing abdominal pain. Because extraction failed by using conventional endoscopy, we used the DBE system. MAIN OUTCOME MEASURES: Successful extraction of the stents. RESULTS: Stents were successfully removed in both patients with no complications. After 1 year of follow-up, the patients remained free of painful symptoms. LIMITATIONS: Small volume case series. CONCLUSIONS: Double-balloon enteroscopy is a reliable way to investigate and treat patients with postsurgical altered anatomy. Here, we report the successful removal of pancreatic stents migrating into the jejunal loop through pancreaticojejunal anastomosis.

Type 1 and 2 gastric carcinoid tumors: long-term follow-up of the efficacy of treatment with a slow-release somatostatin analogue.

Little is known about the long-term results of treating gastric carcinoid tumors with a slow-release somatostatin analogue. We report three patients with type 1 and 2 gastric carcinoid tumors who were treated in the above mentioned way and followed for 27-50 months. In all cases, alternative endoscopic or surgical management was considered but deemed inappropriate. Treatment with a slow-release somatostatin analogue was begun in light of a favorable recent report. The result was regression or complete disappearance of macroscopic fundal tumors. No side-effects were reported and, most notably, none of the patients developed gallstones. This small study may help define the optimal duration, dose, and administration interval of the treatment. Slow-release somatostatin analogue is a safe and efficacious treatment for type 1 and 2 gastric carcinoid tumors, and can be used when tumors are growing rapidly. Slow-release somatostatin analogue represents an alternative to repeated endoscopic treatment or high-risk surgery.

[Posttraumatic pancreatic fistula: successful endoscopic stent placement]. / Fistule pancréatique post-traumatique: succès du traitement endoscopique par endoprothèse.

INTRODUCTION: The risk of complications and the severity of pancreatic trauma depend on the status of the main pancreatic duct. Endoscopic retrograde pancreatography (ERCP) has emerged as the technique of reference for assessing pancreatic ductal anatomy, and it also permits therapeutic intervention by the endoscopic placement of an endoprosthesis. CASE: We report a pancreatic fistula attributable to posttraumatic rupture of the main duct, undiagnosed before ERCP and successfully treated by endoscopic stent placement. DISCUSSION: ERCP has emerged as a tool for both diagnosis and treatment. Major traumatic pancreatic duct disruptions can be diagnosed more easily and managed successfully by endoscopic stent placement, thereby avoiding surgical morbidity. ERCP is impractical in emergency settings for many reasons. Magnetic resonance pancreatography may be useful for establishing the type and extent of pancreatic lesions and for selecting patients for endoscopic treatment.

[Subcutaneous emphysema, pneumomediastinum, pneumoperitoneum and retropneumoperitoneum following a colonoscopy with mucosectomy]. / Emphysème sous-cutané, pneumomédiastin, pneumopéritoine et rétropneumopéritoine dans les suites d'une coloscopie avec mucosectomie.

The occurrence of associated intraperitoneal and retroperitoneal colonic perforation is uncommon after colonoscopy. We report a case of this complication revealed by subcutaneous emphysema, pneumomediastinum, pneumoperitoneum and retro-pneumoperitoneum after colonic mucosectomy.