Peter J. Wahab

A Conservative and Minimally Invasive Approach to Necrotizing Pancreatitis Improves Outcome

BACKGROUND & AIMS Treatment of patients with necrotizing pancreatitis has become more conservative and less invasive, but there are few data from prospective studies to support the efficacy of this change. We performed a prospective multicenter study of treatment outcomes among patients with necrotizing pancreatitis. METHODS We collected data from 639 consecutive patients with necrotizing pancreatitis, from 2004 to 2008, treated at 21 Dutch hospitals. Data were analyzed for disease severity, interventions (radiologic, endoscopic, surgical), and outcome. RESULTS Overall mortality was 15% (n=93). Organ failure occurred in 240 patients (38%), with 35% mortality. Treatment was conservative in 397 patients (62%), with 7% mortality. An intervention was performed in 242 patients (38%), with 27% mortality; this included early emergency laparotomy in 32 patients (5%), with 78% mortality. Patients with longer times between admission and intervention had lower mortality: 0 to 14 days, 56%; 14 to 29 days, 26%; and >29 days, 15% (P<.001). A total of 208 patients (33%) received interventions for infected necrosis, with 19% mortality. Catheter drainage was most often performed as the first intervention (63% of cases), without additional necrosectomy in 35% of patients. Primary catheter drainage had fewer complications than primary necrosectomy (42% vs 64%, P=.003). Patients with pancreatic parenchymal necrosis (n=324), compared with patients with only peripancreatic necrosis (n=315), had a higher risk of organ failure (50% vs 24%, P<.001) and mortality (20% vs 9%, P<.001). CONCLUSIONS Approximately 62% of patients with necrotizing pancreatitis can be treated without an intervention and with low mortality. In patients with infected necrosis, delayed intervention and catheter drainage as first treatment improves outcome.

Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis

Objectives:To determine the relation between intestinal barrier dysfunction, bacterial translocation, and clinical outcome in patients with predicted severe acute pancreatitis and the influence of probiotics on these processes. Summary of Background data:Randomized, placebo-controlled, multicenter trial on probiotic prophylaxis (Ecologic 641) in patients with predicted severe acute pancreatitis (PROPATRIA). Methods:Excretion of intestinal fatty acid binding protein (IFABP, a parameter for enterocyte damage), recovery of polyethylene glycols (PEGs, a parameter for intestinal permeability), and excretion of nitric oxide (NOx, a parameter for bacterial translocation) were assessed in urine of 141 patients collected 24 to 48 h after start of probiotic or placebo treatment and 7 days thereafter. Results:IFABP concentrations in the first 72 hours were higher in patients who developed bacteremia (P = 0.03), infected necrosis (P = 0.01), and organ failure (P = 0.008). PEG recovery was higher in patients who developed bacteremia (PEG 4000, P = 0.001), organ failure (PEG 4000, P < 0.0001), or died (PEG 4000, P = 0.009). Probiotic prophylaxis was associated with an increase in IFABP (median 362 vs. 199 pg/mL; P = 0.02), most evidently in patients with organ failure (P = 0.001), and did not influence intestinal permeability. Overall, probiotics decreased NOx (P = 0.05) but, in patients with organ failure, increased NOx (P = 0.001). Conclusions:Bacteremia, infected necrosis, organ failure, and mortality were all associated with intestinal barrier dysfunction early in the course of acute pancreatitis. Overall, prophylaxis with this specific combination of probiotic strains reduced bacterial translocation, but was associated with increased bacterial translocation and enterocyte damage in patients with organ failure.

Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: A randomized trial

BACKGROUND Self-expandable metal stents deployed across the gastroesophageal junction predispose to gastroesophageal reflux. The efficacy of a stent with an antireflux mechanism in preventing gastroesophageal reflux was assessed. METHODS Thirty patients with carcinoma of the distal esophagus or of the gastric cardia were randomized to receive either a stent with a windsock-type antireflux valve (FerX-Ella) (n = 15) or a standard open stent (n = 15) of the same design minus the valve. Gastroesophageal reflux was assessed by using standardized questionnaires and by 24-hour pH monitoring 14 days after treatment. RESULTS Technical problems occurred during stent placement in 3 patients: migration (n = 2) and a problem with the introducing system (n = 1). Dysphagia improved from a median score of 3 (liquids only) to 1 (eat some solid food) in the antireflux group and from 3 to 0 (solid foods) in the open stent group ( p > 0.20). Reflux symptoms were reported by 3/12 patients (25%) with an antireflux stent and by 2/14 (14%) with an open stent. In 11 patients, 24-hour pH monitoring was obtained, and increased esophageal acid exposure (normal: <4%) was present with both types of stent: median 24-hour reflux time (9 patients) with the antireflux stent was 23% vs. 10% in (2 patients) with the open stent ( p = NS). Major complications occurred in 3 patients (20%) in each group and included bleeding (n = 3), severe pain (n = 2), and aspiration pneumonia (n = 1). The main cause of recurrent dysphagia was stent migration, which occurred in 7 of the 30 patients (23%). CONCLUSIONS The FerX-Ella antireflux stent provided relief of dysphagia caused by malignancy of the distal esophagus and gastric cardia. However, the antireflux valve failed to prevent gastroesophageal reflux.

Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: A prospective multicenter study

Summary Background Data:The role of early endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) remains controversial. Previous studies have included only a relatively small number of patients with predicted severe ABP. We investigated the clinical effects of early ERCP in these patients. Methods:We performed a prospective, observational multicenter study in 8 university medical centers and 7 major teaching hospitals. One hundred fifty-three patients with predicted severe ABP without cholangitis enrolled in a randomized multicenter trial on probiotic prophylaxis in acute pancreatitis were prospectively followed. Conservative treatment or ERCP within 72 hours after symptom onset (at discretion of the treating physician) were compared for complications and mortality. Patients without and with cholestasis (bilirubin: >2.3 mg/dL [40 &mgr;mol/L] and/or dilated common bile duct) were analyzed separately. Results:Of the 153 patients, 81 (53%) underwent ERCP and 72 (47%) conservative treatment. Groups were highly comparable at baseline. Seventy-eight patients (51%) had cholestasis. In patients with cholestasis, ERCP (52/78 patients: 67%), as compared with conservative treatment, was associated with fewer complications (25% vs. 54%, P = 0.020, multivariate adjusted odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.13–0.99, P= 0.049). This included fewer patients with >30% pancreatic necrosis (8% vs. 31%, P = 0.010). Mortality was nonsignificantly lower after ERCP (6% vs. 15%, P = 0.213, multivariate adjusted OR: 0.44, 95% CI: 0.08–2.28, P = 0.330). In patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49–3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19–3.12, P = 0.734). Conclusions:Early ERCP is associated with fewer complications in predicted severe ABP if cholestasis is present.

Safety experience with the duodenal-jejunal bypass liner: an endoscopic treatment for diabetes and obesity

BACKGROUND The duodenal-jejunal bypass liner (DJBL) is a new, device-based endoscopic treatment for type 2 diabetes mellitus (T2DM) and obesity. OBJECTIVE To report serious safety events of subjects treated with the DJBL while offering a simple guideline to mitigate risk. DESIGN Single-center observational study. SETTING Tertiary referral center. PATIENTS For commercial use, patients were eligible for implantation of the DJBL when they met the following criteria: age 18 to 65 years, body mass index 28 to 45 kg/m(2), T2DM, and negative serum Helicobacter pylori test. INTERVENTIONS Endoscopic implantation of the DJBL. MAIN OUTCOME MEASUREMENTS Adverse events, serious adverse events, early explantation. RESULTS Between October 2007 and January 2014, 152 of 165 planned implantations (92%) and 94 explantations were performed in our center. Significant weight loss and improvement in T2DM and other cardiovascular parameters were achieved. Early removal of the device occurred because of persistent GI symptoms in 16 patients (11%). Serious adverse events were observed in a subset of patients: 7 GI bleeds, 5 of which required early removal; 2 cases of pancreatitis; 1 case of hepatic abscess; and 1 obstruction of the sleeve. Explantation resulted in an esophageal tear in 2 cases. LIMITATIONS Single-center study. CONCLUSION The DJBL improves glycemic control while causing weight loss. The safety profile of the DJBL demonstrates a reasonable tolerability profile. However, serious safety adverse events can occur. Patient selection, expert use of the device at placement and removal, and the supportive care of an experienced multidisciplinary team are key for safe and effective use of the DJBL.

Intragastric band erosion: Experiences with gastrointestinal endoscopic removal

AIM To remove the migrated bands using a gastrointestinal endoscopic approach. Little is published on complications that can occur. METHODS From June 2006 to June 2010, eight patients developed intragastric band migration. Two patients had received their AGB in a different hospital, the remaining six were operated by the same surgeon. In all patients gastrointestinal endoscopic removal of the band was attempted by two individual gastroenterologists. Clinical signs of band migration were: persisted nausea, abdominal pain, weight gain, recurrent infection of the port and tubing system and hematemesis. RESULTS In four patients removal was performed without complications. In two patients extracting the cleaved gastric band into the stomach appeared impossible. The two remaining patients presented with acute hematemesis and melena. One of these patients was readmitted with hematemesis. The other patient started bleeding during the gastroscopy and was converted to a laparoscopy in which one of the branches of the left gastric artery was oversewn. CONCLUSION Band migration after gastric banding can be life threatening. Gastrointestinal endoscopic removal is a feasible technique that holds the promise of fast reconvalescence.

Naive T cells in the gut of newly diagnosed, untreated adult patients with inflammatory bowel disease.

Background:The phenotype of the T-cell subpopulations and their related cytokine networks in the gastrointestinal mucosa of patients with inflammatory bowel disease can potentially be used as a predictive value for clinical course and response to therapy. Here, we analyzed T-cell subpopulations in newly diagnosed, untreated adult patients and correlated them with clinical presentation. Methods:Mucosal biopsies from duodenum, ileum, and colon mucosa of patients with Crohns disease and ulcerative colitis and controls were obtained. The simple endoscopy score in Crohns disease and the full Mayo score in ulcerative colitis were used to score disease activity. Mucosa-infiltrating T cells were characterized by flow cytometric immunophenotyping and were stimulated to assess cytokine secretion. Results:Based on the expression of the maturation and activation markers CD45RA and CD27, we identified 4 different profiles. Profile A contained mainly CD45RA+CD27+ naive T cells; profile B contained mainly CD45RA−CD27+ central memory T cells; profile C contained mainly CD45RA−CD27− effector memory T cells; and profile D consisted of similar percentages of these aforementioned subpopulations. Profile A was only observed in the ileum/colon of patients with inflammatory bowel disease, associated with upper gastrointestinal location and perianal disease in Crohns disease and expressed more tumor necrosis factor &agr; and less interferon &ggr;. In contrast, profile D was restricted to controls. There was no correlation between the different T-cell profiles and endoscopic disease activity. Conclusions:Newly diagnosed patients with inflammatory bowel disease display different T-cell maturation profiles in the gut mucosa, corresponding to distinct cytokine responses. Follow-up studies are needed to determine whether the profiles associate with clinical course and response to therapy.

Contrast Enhanced Abdominal Ultrasound in the Assessment of Ileal Inflammation in Crohn's Disease: A Comparison with MR Enterography.

Background and Aims To prospectively examine the feasibility and accuracy of Contrast Enhanced Ultrasound (CEUS) in the assessment of Crohn’s disease (CD) activity in the terminal ileum in comparison to Magnetic Resonance Enterography (MRE), using endoscopy as a reference standard. Methods 105 consecutive patients with alleged clinically active CD were assessed by MRE and CEUS. CEUS of the terminal ileum was performed using an intravenous microbubble contrast enhancer. Accuracy values of CEUS and MRE for the presence of active terminal ileitis were evaluated using the Receiver Operating Characteristic method, using endoscopic findings as a reference standard. Sensitivity and specificity values of MRE and CEUS were compared by the McNemar test. Results CEUS was feasible in 98% of patients, MRE in all. Optimal diagnostic accuracy in CEUS was obtained at a peak intensity value of 10%, showing 100% sensitivity, 92% specificity and an accuracy of 99% in demonstrating ileal mucosal inflammation. For MRE, overall sensitivity, specificity and accuracy were, 87%, 100%, and 88%, respectively. CEUS and MRE were highly correlated in assessing length and wall thickness of the terminal ileum. CEUS identified 11 of 16 MRE-detected strictures, but no fistulae. Conclusion The accuracy of CEUS is comparable to that of MRE in the assessment of active, uncomplicated terminal ileal CD and therefore a valuable bedside alternative to MRE in the follow-up of these patients.

Prevalence of Upper Gastrointestinal Lesions at Primary Diagnosis in Adults with Inflammatory Bowel Disease.

Background:The prevalence of upper gastrointestinal (GI) involvement in adult inflammatory bowel disease has mostly been studied in patients with long-standing disease. The aim of this study was to prospectively evaluate the prevalence of upper GI involvement in a consecutive series of newly diagnosed, treatment-naive adult patients with inflammatory bowel disease, irrespective of upper GI tract symptoms. Methods:Consecutive patients with suspected inflammatory bowel disease underwent combined ileocolonoscopy and upper endoscopy with biopsies. Patients diagnosed with either Crohns disease (CD) or ulcerative colitis (UC), denying use of nonsteroidal anti-inflammatory drug, were included in the study. Helicobacter pylori infection was diagnosed histologically and positive patients were excluded from the analysis. Endoscopic and histologic lesions in the stomach and duodenum were recorded. Upper GI location (+L4) was defined as a combination of endoscopic and histological lesions. Results:A total of 152 patients (108 CD and 44 UC) were analyzed. Endoscopic lesions were only seen in patients with CD (60 of 108, 55%). Histological lesions were present in both patients with CD and patients with UC: focally enhanced gastritis in 58 CD (54%) and 10 UC (23%), granulomas in 30 CD (28%). Upper GI disease location was diagnosed in 44 patients with CD (41%) and no patients with UC. Upper GI tract symptoms were reported in 14 of 44 patients (32%) with upper GI location. Conclusions:A high prevalence of upper GI involvement was observed in newly diagnosed patients with CD, with a majority of the patients being asymptomatic. Focally enhanced gastritis was common in both patients with CD and patients with UC, whereas granulomatous inflammation was restricted to patients with CD.

On naivety of T cells in inflammatory bowel disease: a review.

Abstract:Little is known about different phases of T-cell maturation in gut mucosa. Based on current knowledge about the migratory pathways of naive and memory T cells, it is believed that access to peripheral, nonlymphoid tissues is restricted to memory T cells. Surprisingly, there is increasing evidence of high numbers of naive T cells in the chronically inflamed gut tissue of patients with inflammatory bowel disease. This could partially be explained by new formation of ectopic lymphoid organs. Ongoing recruitment of naive T cells at inflammatory sites might play a role in the immunopathogenesis of inflammatory bowel disease.