Clinical Outcome of Patients with Raised Intraepithelial Lymphocytes with Normal Villous Architecture on Duodenal Biopsy.

INTRODUCTION: The finding of a raised intraepithelial lymphocytes (IELs) count with normal villous architecture is of sufficient clinical importance to be reported in routine duodenal biopsies. AIM: To study the clinical and demographic data of patients with isolated increased IELs on duodenal biopsy. METHODS: A single-tertiary-centre retrospective study was carried out with a review of medical records of patients with increased IELs. Patients from 2012 to 2014, >18 years with at least one biopsy from the second part of the duodenum with increased IELs; defined as >25 IELs/100 enterocytes, with preserved villous architecture were identified from our histopathology database with exclusion of patients with coeliac disease (CD).Clinical and demographic data were recorded following a chart review. CD was diagnosed by the attending physician based on the Physician Global Assessment. Data was compared between groups using a Student t test and ORs were calculated as appropriate. Statistical significance was set a priori at p < 0.05. RESULTS: Over 24 months, 6,244 patients were found to have duodenal biopsies and 114 (1.8%) had isolated increased IELs. Of the patients with increased IELs, the mean age was 50 years and 34 (30%) were male. Follow-up was available in 75 (65%) of these and CD was subsequently diagnosed in 32% (n = 24). CD was associated with the female gender (22 out of 24 vs. 39 out of 51, OR 7.5, older age 55 vs. 41 years, p < 0.04), and higher IEL count with an IEL of >40 in 11 out of 24 (46%) with CD vs. 12 out of 51 (24%) without CD, p = 0.0006. CONCLUSION: It is a non-specific but important finding, as it can have clinical implications.

Impact on direct and indirect costs of switching patients with inflammatory bowel disease from intravenous to subcutaneous infliximab (CT-P13).

BACKGROUND: We aim to compare the real-life direct and indirect costs of switching patients from intravenous to subcutaneous (SC) CT-P13, an infliximab biosimilar, in a tertiary UK Inflammatory Bowel Disease (IBD) centre. METHODS: All adult patients with IBD on standard dosing CT-P13 (5 mg/kg 8 weekly) were eligible to switch. Of 169 patients eligible to switch to SC CT-P13, 98 (58%) switched within 3 months and one moved out of area. RESULTS: Total annual intravenous cost for 168 patients was £689 507.04 (direct=£653 671.20, indirect=£35 835.84). After the switch, as-treated analysis demonstrated total annual cost for 168 patients (70 intravenous and 98 SC) was £674 922.83 (direct = £654 563, indirect = £20 359.83) resulting in £891.80 higher cost to healthcare providers. Intention to treat analysis showed a total annual cost of £665 961.01 (direct = £655 200, indirect = £10 761.01) resulting in £1528.80 higher cost to healthcare providers. However, in each scenario, the significant decrease in indirect costs resulted in lower total costs after switching to SC CT-P13. CONCLUSIONS: Our real-world analysis demonstrates switching from intravenous to SC CT-P13 is broadly cost neutral to healthcare providers. SC preparations have marginally higher direct costs, switching allows for efficient use of intravenous infusion units and reduces costs to patients.

Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease.

BACKGROUND & AIMS: The relationship between site of intestinal inflammation and primary sclerosing cholangitis (PSC) development in inflammatory bowel disease (IBD) has not been studied extensively, but may be important in understanding the pathogenesis of PSC. We aimed to determine patterns of disease distribution in IBD patients with and without PSC. METHODS: We performed a 2-part study involving the following: (1) 2754 IBD patients and (2) 82 separate PSC patients attending the Irish National Liver Transplant Unit. RESULTS: Fifty-nine of 2708 (2.2%) IBD patients had PSC. In ulcerative colitis patients, PSC incidence increased with increasing colonic involvement (P = .001) and was relatively rare in those without total colitis. Thirteen Crohn's disease patients had PSC, none with isolated small-bowel disease had PSC (P = .03). In study 2, the majority of ulcerative colitis patients with PSC had total colitis, whereas the remainder had disease extending at least to the left colon. In addition, all 10 PSC patients with Crohn's disease had colonic involvement. CONCLUSIONS: An inflamed colon, but not small bowel, is important in PSC development and it is possible that bacterial translocation and subsequent portal bacteremia is important in PSC development in IBD.

Helicobacter pylori and nonmalignant diseases.

Research published over the past year has documented the continued decline of Helicobacter pylori-related peptic ulcer disease and increased recognition of non-H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer complications and associated mortality remain stubbornly high. The role of H. pylori in functional dyspepsia is unclear, with some authors considering H. pylori-associated nonulcer dyspepsia a distinct organic entity. There is increasing acceptance of an inverse relationship between H. pylori and gastroesophageal reflux disease (GERD), but little understanding of how GERD might be more common/severe in H. pylori-negative subjects. Research has focused on factors such as different H. pylori phenotypes, weight gain after H. pylori eradication, and effects on hormones such as ghrelin that control appetite.

First UK experience of endoscopic vacuum therapy for the management of oesophageal perforations and postoperative leaks.

Oesophageal perforations and anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a promising novel treatment that promotes healing and avoids sepsis. There are no data reporting its use in the UK. We report the first British experience of EVT in two elderly frail patients. Two patients were treated in our institution with EVT using Eso-SPONGE®. One patient had spontaneous oesophageal perforation and the other had anastomotic leakage post-Merendino oesophageal reconstruction (oesophagogastric continuity with jejunal interposition anastomosis). Both patients were over 65 years of age. One patient had 13 endoscopic Eso-SPONGE® exchanges over 8 weeks, while the other one had 6 exchanges over 4 weeks. Complete resolution of oesophageal leakage was achieved in both cases. EVT should be considered in the management of patients with oesophageal perforations and postoperative leaks. This novel therapeutic intervention has the potential to significantly reduce morbidity and mortality in these patients.

A Case of Primary Gastric Melanoma Exhibiting a Rare BRAF V600R Mutation.

INTRODUCTION: Malignant melanoma of the gastrointestinal tract is usually a metastasis from a cutaneous source. Primary gastric melanoma is an extremely rare clinical entity, with few reported cases worldwide. It is often advanced at time of diagnosis and is associated with a dismal outcome. BACKGROUND: A 76 year old gentleman presenteded with a one month history of fatigue and exertional dyspnoea. Laboratory investigations indicated an anaemia, with a haemoglobin level of 11.0g/dl. Subsequent gastroscopy visualised a large, atypical, crater-like ulcerated lesion distal to the cardia in the proximal stomach.Provisional histology was suggestive of a poorly differentiated adenocarcinoma but subsequent cyto-morphology and immunophenotyping were consistent with melanoma, with positive S100 protein, HMB45 and Melan A. Further molecular genetic testing revealed a V600R mutation in the BRAF gene, which is the first primary gastric melanoma with this mutation to be reported in the literature. Given the rarity of the findings, an extensive secondary work-up was undertaken, which concluded the diagnosis primary gastric melanoma. DISCUSSION: Primary gastric melanoma is a rare disease that can present similarly to other upper gastrointesinal lesions, with weight loss, abdominal pain, malena, and anaemia. Given its rarity, the pathogenesis is poorly understood. Lesions are often endoscopically atypical. Important points to note would include the absence of a primary lesion, as supported by a full skin examination and PET-CT findings, which can help to delineate the limitation to the stomach, thus helping to inform subsequent management. LEARNING POINTS: Primary gastric melanoma (PGM) is a rare clinical entity.Work-up including skin and ophthalmic examination is important to exclude a primary cutaneous source, as this helps dictate both prognosis and subsequent management, including whether surgical resection is advisable.Immunophenotyping and genetic testing inform management but, despite advances in therapy, the prognosis of PGM and other mucosal melanomas remains poor.