Antioxidant therapy does not reduce pain in patients with chronic pancreatitis: the ANTICIPATE study.

BACKGROUND & AIMS: We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. METHODS: We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol. RESULTS: After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, ß-carotene, and selenium were increased significantly in the antioxidant group. CONCLUSIONS: Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants.

Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn's disease.

BACKGROUND/OBJECTIVE: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn's disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed. METHODS: British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively. RESULTS: In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively). CONCLUSION: The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.

The use of thrombin injections in the management of bleeding gastric varices: a single-center experience.

BACKGROUND: There is a relative dearth of literature on the definitive endoscopic management of bleeding gastric varices. Variceal ligation with bands and detachable snares, sclerosants, cyanoacrylate glue, and thrombin injections have been used with variable success. OBJECTIVE: To report our experience with bovine thrombin injection for the treatment of bleeding gastric varices. DESIGN: A retrospective review. SETTING: Tertiary-referral hospital. PATIENTS: Forty-two cases of gastric varices were identified from our endoscopy database between July 1998 and July 2003. Thirteen patients had thrombin injection. INTERVENTION: Thrombin injection therapy for bleeding gastric varices. MAIN OUTCOME MEASUREMENTS: Control of hemorrhage, risk of rebleeding, and mortality. RESULTS: Of the 13 patients who underwent thrombin injections, hemostasis in the acute setting was successful in 92% of cases. Patients received 1 to 4 sessions of thrombin, with a mean total dose of 10.8 mL for variceal eradication. One patient continued to bleed and needed a transjugular intrahepatic portosystemic shunt as a rescue procedure. The patient with hepatocellular carcinoma died within 30 days, and 4 more patients died after a median follow-up of 22 months; none died because of bleeding. There was no rebleeding in the remaining patients at a median follow-up of 25 months. LIMITATIONS: The retrospective nature and small number. CONCLUSIONS: In our series, injection with thrombin proved to be an effective endoscopic treatment in the majority of patients with bleeding gastric varices. The overall mortality, after controlling bleeding, was 38% (5/13), subsequent to a median follow-up of 22 months.

Multicenter experience from the UK and Ireland of use of lumen-apposing metal stent for transluminal drainage of pancreatic fluid collections.

BACKGROUND AND STUDY AIMS: Pancreatic fluid collection (PFC) is a common complication of pancreatitis for which endoscopic ultrasound-guided drainage is first-line treatment. A new single-device, lumen-apposing, covered self-expanding metal stent (LAMS) has been licensed for PFC drainage. We therefore present our multicenter experience with the LAMS for PFC drainage in a multicenter prospective case series to assess success and complication rates. PATIENTS AND METHODS: All adult patients from 11 tertiary centers who had LAMS placement for PFC from July 2015 to July 2016 were included. Data including indications, technical success, clinical success, collection resolution, stent removal, early and late adverse events (AEs), mortality and recurrence at 6 months were collected. RESULTS: 116 patients, median age 52.5 years (range 16 - 80) and 67 % male, were treated with a single LAMS in each case. The indication was walled off necrosis (WON) in 70 and pseudocyst in 46. Median size of the PFC was 11 cm (5 - 21 cm) and the estimated median necrotic volume in WON was 30 % (5 % - 90 %). Stent insertion was technically successful in 115 (99.1 %) and clinically successful in 109 (94 %). Early serious AEs (SAEs): n = 7 sepsis, n = 1 stent blockage with food, n = 1 stent migration requiring laparotomy, n = 1 stent dislodgement and n = 1 bleeding requiring emboliZation. Late AEs: n = 1 buried stent and n = 1 esophageal fistula. Non-procedure-related deaths: n = 3 (2.5 %). CONCLUSION: This multicenter case series demonstrates that use of the new LAMS is feasible, effective and relatively safe in draining PFC with a technical success rate of 99 % and cumulative SAE rate of 11.2 %.

Microfluidic platform for single nucleotide polymorphism genotyping of the thiopurine S-methyltransferase gene to evaluate risk for adverse drug events.

Prospective clinical pharmacogenetic testing of the thiopurine S-methyltransferase gene remains to be realized despite the large body of evidence demonstrating clinical benefit for the patient and cost effectiveness for health care systems. We describe an entirely microchip-based method to genotype for common single nucleotide polymorphisms in the thiopurine S-methyltransferase gene that lead to serious adverse drug reactions for patients undergoing thiopurine therapy. Restriction fragment length polymorphism and allele-specific polymerase chain reaction have been adapted to a microfluidic chip-based polymerase chain reaction and capillary electrophoresis platform to genotype the common *2, *3A, and *3C functional alleles. In total, 80 patients being treated with thiopurines were genotyped, with 100% concordance between microchip and conventional methods. This is the first report of single nucleotide polymorphism detection using portable instrumentation and represents a significant step toward miniaturized for personalized treatment and automated point-of-care testing.

Duodenal duplication cyst with profound elevation of intracystic carbohydrate antigen (CA 19-9) and carcinoembryonic antigen (CEA): a rare but important differential in the diagnosis of cystic tumours of the pancreas.

CONTEXT: Enteric duplication cysts are rare lesions of uncertain incidence and natural history. Pre-operative confirmation of diagnosis can be difficult. This case reports an adult duodenal duplication cyst presenting with grossly elevated intra-lesional levels of tumour markers. CASE REPORT: A 57-year-old female was found to have a complex cystic lesion of the head of the pancreas. Intra-lesional fluid analysis revealed a grossly elevated CA 19-9 and CEA. Resection was undertaken under the assumption that this was a cystic tumour. Macroscopic examination after opening the duodenum revealed a villous, circumferential tumour in the proximal duodenum measuring 4 cm in length. A cystic lesion was present in the medial wall of the tumour and did not communicate with the duodenal lumen. Microscopically, the tumour comprised Brunner's gland hyperplasia with associated mucosal thickening. The wall of the underlying cystic lesion was comprised of muscularis formed by the outer muscle coat of the duodenal wall. The final diagnosis was of a duodenal duplication cyst. There was no evidence of dysplasia or malignancy. CONCLUSION: This is the first report of a duodenal duplication cyst having elevated intra-cyst fluid levels of amylase, carbohydrate antigen CA 19-9 and carcinoembryonic antigen (CEA). Although rare, this is an important differential diagnosis in the management of cystic tumours of the pancreas.

Gastric amyloidosis presenting with severe weight loss.

A previously well 59-year-old lady with 70 kg weight loss and chronic diarrhoea over a 28-month period presented following collapse and subsequent diagnosis of pulmonary embolism. Previous investigations for this weight loss included normal gastroscopy and colonoscopy, CT and MRI abdomen, barium follow through and octreotide scan. She underwent echocardiogram which revealed myocardial speckling and asymmetrical left ventricular hypertrophy. Repeat oesophago-gastro-duodenoscopy and colonoscopy for rectal bleeding was performed. Colonoscopy revealed intramucosal haematomas and electron microscopy (EM) of the gastric biopsies confirmed amyloid deposition. Amyloidosis of the gastrointestinal (GI) tract and heart were confirmed on serum amyloid protein scan. GI amyloid is rare and symptoms include weight loss, diarrhoea, GI bleeding and gut dysmotility.1 GI amyloidosis should be considered as a diagnosis and sought when other common causes have been excluded. The greatest yield is by Congo red staining or EM of rectal specimens.

Quality of life assessment in patients with chronic pancreatitis receiving antioxidant therapy.

AIM: To undertake a baseline study comparing quality of life (QoL) in patients with chronic pancreatitis (CP) on Antox to those with CP, matched for disease duration, who were not on this medication. METHODS: CP was defined according to the Zurich classification. Sixty eight consecutive patients with CP who were taking Antox (antioxidants) were compared with 69 consecutive control CP patients not on Antox. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core questions 30 and Pancreatic Modification (28 questions) were used to assess QoL. Out of a total of 137 patients 28 in each group were matched for disease duration (within 12 mo). Median disease duration was 8 (1-22) years in the Antox group and 7 (1-23) years in the Non-Antox cohort (P = NS, Mann-Whitney U-test). Other parameters (age, gender, etiology, endocrine and exocrine insufficiency) were similar between groups. RESULTS: Median visual analogue pain score in the Antox group was 3 (0-8) compared with 6 (0-8) in the Non-Antox group (P < 0.01). Perceptions of cognitive, emotional, social, physical and role function were impaired in the Non-Antox group compared to Antox patients (P < 0.0001, P = 0.0007, P = 0.0032 and P < 0.005 and P < 0.001, respectively). Analgesics and opiate usage was significantly lower in the Antox group (P < 0.01). Overall physical health and global QoL was better in the Antox group (P < 0.0001, 95% CI: 1.5-3). CONCLUSION: Contemporary quality of life assessments show that after correction for disease duration and cigarette smoking, patients with CP taking antox had better scores than non-antox controls.