Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab.

Background: Sequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4ß7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting. Methods: Patients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period. Results: Second-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001). Conclusion: Compared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Histo-MRI map study protocol: a prospective cohort study mapping MRI to histology for biomarker validation and prediction of prostate cancer.

INTRODUCTION: Multiparametric MRI (mpMRI) is now widely used to risk stratify men with a suspicion of prostate cancer and identify suspicious regions for biopsy. However, the technique has modest specificity and a high false-positive rate, especially in men with mpMRI scored as indeterminate (3/5) or likely (4/5) to have clinically significant cancer (csPCa) (Gleason ≥3+4). Advanced MRI techniques have emerged which seek to improve this characterisation and could predict biopsy results non-invasively. Before these techniques are translated clinically, robust histological and clinical validation is required. METHODS AND ANALYSIS: This study aims to clinically validate two advanced MRI techniques in a prospectively recruited cohort of men suspected of prostate cancer. Histological analysis of men undergoing biopsy or prostatectomy will be used for biological validation of biomarkers derived from Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours and Luminal Water imaging. In particular, prostatectomy specimens will be processed using three-dimension printed patient-specific moulds to allow for accurate MRI and histology mapping. The index tests will be compared with the histological reference standard to derive false positive rate and true positive rate for men with mpMRI scores which are indeterminate (3/5) or likely (4/5) to have clinically significant prostate cancer (csPCa). Histopathological validation from both biopsy and prostatectomy samples will provide the best ground truth in validating promising MRI techniques which could predict biopsy results and help avoid unnecessary biopsies in men suspected of prostate cancer. ETHICS AND DISSEMINATION: Ethical approval was granted by the London-Queen Square Research Ethics Committee (19/LO/1803) on 23 January 2020. Results from the study will be presented at conferences and submitted to peer-reviewed journals for publication. Results will also be available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT04792138.

Achalasia leading to diagnosis of adenocarcinoma of the oesophagus.

A 50-year-old male with a 7 month history of progressive dysphagia to solids then subsequently to liquids. He underwent a diagnostic gastroscopy which was normal. A further barium swallow suggested achalasia. He was referred to a tertiary centre, where he underwent pH and manometry studies which confirmed a diagnosis of achalasia. He was referred for a laparoscopic cardiomyotomy, and at surgery there was a suspected tumour at the gastro-oesophageal junction. A follow-up endoscopy with biopsies was normal. Following this, a positron emission tomography scan showed T3 distal oesophageal cancer with no nodal involvement or distal metastasis. An attempt at oesophagectomy was performed, but at operation there was locally advanced carcinoma infiltrating the coeliac axis. He is currently undergoing palliative chemotherapy.

The setting up and running of a cross-county out-of-hours gastrointestinal bleed service: a possible blueprint for the future.

OBJECTIVE: Acute upper gastrointestinal bleeding (AUGIB) results in 25 000 hospital admissions annually. Patients admitted at weekends with AUGIB have increased mortality, and guidelines advise out-of-hours endoscopy. We present retrospective data from our service involving the interhospital transfer of patients. DESIGN: We pooled resources of two neighbouring general hospitals, just north of London. Emergency endoscopy is performed at the start of the list followed by elective endoscopy in the endoscopy unit on Saturday and Sunday mornings. From Friday evening to Sunday morning, patients admitted to Queen Elizabeth II Hospital (QEII) are medically stabilised and transferred to Lister Hospital by ambulance. RESULTS: 240 endoscopies were performed out of hours from December 2007 to March 2011. Of these, 54 patients were transferred: nine had emergency endoscopy at QEII as they were medically unstable; eight of the patients transferred required therapeutic intervention for active bleeding. The mean pre-endoscopy Rockall score of those transferred was 2.5. We examined the records of 51 of the 54 patients transferred. There were three deaths within 30 days after endoscopy not associated with the transfer process. 19 (37%) patients had reduced hospitalisation after having their endoscopy at the weekend. CONCLUSIONS: The introduction of the out-of-hours endoscopy service in our trust has had multiple benefits, including patients consistently receiving timely emergency endoscopy, significantly reduced disruption to emergency operating theatres, and participation of endoscopy nurses ensures a better and safer experience for patients, and better endoscopy decontamination. We suggest our model is safe and feasible for other small units wishing to set up their own out-of-hours endoscopy service to adopt.

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease.

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.

Intussusception of the appendix secondary to endometriosis: a case report.

INTRODUCTION: Intussusception of the appendix is an extremely rare condition that ranges from partial invagination of the appendix to involvement of the entire colon. Endometriosis is an exceptionally rare cause of appendiceal intussusception and only very few cases have been reported in the literature to date. CASE PRESENTATION: A 40 year-old woman presented to clinic with a long history of lower abdominal pain, loose motions and painful, heavy periods. Subsequent colonoscopy revealed submucosal endometriotic nodules in the sigmoid as well as a polyp thought to be arising from the appendix, which had inverted itself. She was referred to a colorectal surgeon because the polyp could not be removed endoscopically despite several attempts. At laparotomy, the appendix had intussuscepted but it was possible to reduce it and therefore a simple appendicectomy was carried out. On histology, there were widespread endometrial deposits within the wall of the appendix and this was thought to be the basis for the intussusception. CONCLUSION: Histological evidence of the lead point is of crucial importance in cases of appendiceal intussusception, in order to exclude an underlying neoplastic process. Consequently, surgical resection is necessary either through an open or a laparoscopic approach. Gastrointestinal endometriosis should be considered as a cause of appendiceal intussusception in post-menarchal women with episodic symptoms and proven disease.