PDGRFA-mutant gastrointestinal stromal tumours (GISTs) in Eastern England: clinicopathological features and outcomes of 50 patients diagnosed between 2008-2021

Background PDGRFA-mutant gastrointestinal tumours (GISTs) comprise approximately 10% of GISTs and are mostly gastric. Targeted therapies against these tumours have historically been limited by tyrosine kinase inhibitor (TKI)-resistance. We reviewed the characteristics and outcome of all PDGRFA-mutant patients seen at our centre over the last 13 years. Methods All PDGRFA-mutant patients seen at the Cambridge University Hospitals NHS Foundation Trust GIST clinic from July 2008-July 2021 were retrospectively reviewed and followed up. Results: 50 PDGRFA-mutant GIST patients were diagnosed during the 13-year period. 60% were male. Median tumour size was 5 cm and the majority were epithelioid (44%) or mixed (36%) type. Commonest primary location was the gastric body (52%). In non-metastatic patients the low-risk modified AFIP risk group was the most common (65.2%). PDGFRA exon 18 (86%) were the most common PDGFRA mutations, most being imatinib resistant. None harboured a KIT mutation. 38% of cases had high KIT expression (immunohistochemistry), whilst 48% had patchy expression and 14% were negative. Most were positive for DOG1 (94%). CD34 was highly expressed in 48% of cases. 13% developed metastases during the 13-year follow-up period: liver (80%) being the commonest site. 76% of all patients underwent radical resection. 14% received TKI therapy. After a median follow-up of 55.1 months, 82% remained alive: 6 patients died from metastatic GIST; 3 from other causes. Median time to metastatic disease was 30.1 months, and median time from metastatic diagnosis to death was 18.5 months. Patients who presented with metastatic disease had the poorest survival outcome (p=0.001) Conclusion To date this is the largest single-centre European PDGRFA-mutant GIST cohort. Results highlight the generally indolent nature of PDGRFA-mutant disease (contrasted to the poor outcome of those who present with metastatic disease), male and gastric preponderance (unlike KIT-mutant GISTs), and variable KIT expression.

A combination of methylation and protein markers is capable of detecting gastric cancer detection by combined markers

Aim: This study aimed to validate a combination of mSEPT9, mRNF180 and CA724 for gastric cancer (GC) detection. Patients & methods: The performance of mSEPT9, mRNF180 and CA724 was examined in a prospective cohort study with 518 participants (151 with GC, 56 with atrophic gastritis, 87 with other gastrointestinal diseases and 224 with no evidence of disease). Results: mSEPT9, mRNF180 or CA724 alone detected 48.3, 37.1 and 43.1% of GC, respectively. The combination of mSEPT9 and mRNF180 detected 60.3% of GC, and the combination of all three markers detected 68.6% of GC. The detection sensitivity of mSEPT9 and mRNF180 was significantly higher for gastric body and in elder subjects. mSEPT9 was correlated with poorer GC survival. Conclusion: The combination of mSEPT9, mRNF180 and CA724 was adequately sensitive for GC detection. The blood mSEPT9 was predictive for GC prognosis.

EP.WE.718An audit of the photographic documentation of upper gastrointestinal endoscopy at Cork University Hospital

Introduction A joint statement by the British Society of Gastroenterology and the Association of Upper Gastrointestinal Surgeons in 2017 recommended that photographic documentation of relevant anatomical landmarks should be a Key Performance Indicator of oesophagogastroduodenoscopy (OGD). The aim of this study was to assess this photodocumentation standard among surgeons and gastroenterologists in a tertiary referral centre. Methods Cork University Hospital endoscopy unit records were examined for a 2-month period from 01/10/20-27/11/20. OGDs were performed by 3 consultant colorectal surgeons and 4 consultant gastroenterologists over the time period. Demographic data and photodoumentation information were obtained from the Endoraad GI reporting tool. Surgeons and gastroenterologists performances was compared using the chi-squared test. Results 104 OGDs were analysed. Fifty-three (51%) OGDs were performed in women and 51(49%) OGDs were performed by surgeons. The documentation for each site was; gastro-oesophageal junction- 68% (69/102), fundus on retroflexion- 71% (72/102), gastric body- 32% (33/102), antrum- 61% (62/102), and duodenal bulb- 35% (36/102), without significant differences (p > 0.05) for these sites between surgeons and gastroenterologists. There was more documentation of the upper oesophagus by surgeons (31% vs.12%, p = 0.030) and there was more documentation of the distal duodenum by gastroenterologists (90% vs.47%, p < 0.01). Pictures were unable to be saved in two patients due to technical failure. Discussion Photodocumentation is increasingly important from a medico-legal viewpoint. There is room for improvement in our centre, but these rates are comparable to other published series. An educational session is being planned and following this adherence to photodocumentation standards will be re-examined.

CDX2 Protein as a Surrogate Marker of Gastric Mucosal Atrophy

The aim of the study is to develop an approach to assess the severity of the gastric mucosa (GM) atrophy based on the immunohistochemical (IHC) technique to improve diagnostic quality of the stage of chronic gastritis (CG) and to implement predictive assessment of risk factors of gastric cancer development.Material and methods. The study included 155 cases of CG selected in accordance with Operational Link for Gastritis Assessment (OLGA)-system (2 samples of antral gastric mucosa (GM), 1 sample of angular GM and 2 samples of corpus GM). All biopsy samples were examined using histological and IHC (CDX2) techniques. An expression semi-quantitative index was developed to characterize CDX2. The results obtained were statistically processed using the Mann-Whitney and Kruskal-Wallis tests, the Spearman correlation coefficient, and the construction of logistic regression models.Results. It was found that the value of the CDX2 index assessed within the GM biopsy samples positively correlates with the gradation of atrophy (r=0.665 (p<0.001)). A positive correlation remains between the CDX2sum index, calculated by summing the CDX2 index values at each of the GM points, and the stage of chronic gastritis according to the OLGA classification (r=0.70 (p<0.01)). When assessing the contribution of changes at each point of biopsy sampling and retrospective correlation of the CDX2 index at two points of the GM and the stage of chronic gastritis, the greatest correlation was found for points 3 (stomach angle) and 5 (greater curvature of the gastric body), at three points – for points 1 (greater curvature antrum), 3 and 5 (r=0.592 (p<0.01)). Logistic regression models were built to predict the stage of chronic gastritis based on the CDX2 index in the specified combinations of points. The following model was chosen as the optimal one: to take biopsies at three points (1, 3, 5) and assess their CDX2 index, with sensitivity equal 80.4%, specificity equal 82.8% and diagnostic accuracy equal 83.9%.Conclusion. The CDX2 semi-quantitative index can be used to evaluate GM atrophy. The performed regression analysis demonstrates its predictive role. The constructed regression model based on the CDX2 semi-quantitative index calculation at two/three points of GM allows increasing predictive value of biopsy investigations and accuracy of stratified assessment of the gastric adenocarcinoma risk development in patients with CG.

Successful revision surgery for very late-onset stomal obstruction following Gomez gastroplasty: a case report

Background Gomez gastroplasty, which was developed in the 1970s as one of the gastric restrictive surgeries for severe obesity, partitions the stomach using a stapler from the lesser towards the greater curvature at the upper gastric body, leaving a small channel. This procedure is no longer performed due to poor outcomes, but surgeons can encounter late-onset complications even decades after the surgery. Here, we report a case of very late-onset stomal obstruction following Gomez gastroplasty which was successfully treated by revision surgery. Case presentation A 58-year-old man was referred to our institution with sudden-onset nausea and vomiting. He underwent weight loss surgery in the USA in 1979, but the details of the surgery were unclear. Esophagogastroduodenoscopy demonstrated a stoma at the greater curvature of the upper gastric body, and fluoroscopy showed retention of contrast medium in the fundus and poor outflow through the stoma. Abdominal computed tomography revealed a staple line partitioning the stomach. Considering these preoperative investigation findings and the period during which the surgery was performed, the patient was diagnosed with very late-onset stomal obstruction following Gomez gastroplasty. Supporting the preoperative diagnosis, the surgical findings revealed a staple line extending from the lesser towards the greater curvature of the upper gastric body and a channel reinforced by a running seromuscular suture on the greater curvature. Moreover, gastric torsion caused by the enlarged proximal gastric pouch was found. Re-gastroplasty involving wedge resection of the original channel was performed followed by construction of a new channel. Postoperative course was uneventful, and the patient no longer had symptoms of stomal obstruction after revision surgery. Conclusions Re-gastroplasty was safe and feasible for very late-onset stomal obstruction following Gomez gastroplasty. Accurate preoperative diagnosis based on the patient’s interview and the investigation findings was important for surgical planning. A careful follow-up is required to prevent excessive weight regain after revision surgery.

Vonoprazan-Associated Gastric Mucosal Redness in Non-Helicobacter pylori-Infected and Helicobacter pylori-Eradicated Stomach

Vonoprazan-associated gastric mucosal redness is rare, and its endoscopic and pathological features remain poorly described. We report 4 cases of vonoprazan-associated gastric mucosal redness, that is, 2 cases each in non-<i>Helicobacter pylori</i>-infected and -eradicated stomach. In all cases, esophagogastroduodenoscopy demonstrated spotty and linear redness newly appearing in the greater curvature of the gastric body after initiation of vonoprazan but disappearing after its discontinuation. A tissue biopsy taken from the gastric mucosa with redness revealed various pathological findings and included inflammatory cell infiltration, parietal cell protrusions, oxyntic gland dilatations, congestion, focal hemorrhage with congestion beneath the basement membrane, and vacuolar degeneration of parietal cells. To our knowledge, this is the second report describing the endoscopic and pathological features of vonoprazan-associated gastric mucosal redness.

Dieulafoy's Lesion in the Gaster Secondary to the Resection of Lung Cancer: A Rare Case Report Presentation

Background: Dieulafoy’s lesion is a dilated, aberrant, submucosal vessel that erodes the overlying epithelium without obvious ulceration. Dieulafoy's lesion is a rare disease, meanwhile the lesion secondary to resection of lung cancer is even extremely rare. It is most commonly located in the lesser curvature of the stomach but rarely occurrences in extragastric sites have also been reported. To summarize the key points in the diagnosis and treatments of this disease, we present a clinical case of acute gastrointestinal bleeding due to Dieulafoy's lesion in the gaster secondary to resection of lung cancer.Case presentation: An 58-year-old woman presented with a clinical condition of haematemesis and haematochezia associated with anaemia and haemodynamic instability, needing blood transfusion. After many changes of body position, when the patient was in prone position, we finally found jet bleeding on the gastric body near the great curvature of gastric fundus under gastroscopy, and then we performed successfully with hemostatic clip placement. Hospitalization occurred without further com plications. There was no recurrence after 18 months follow-up.Conclusion: It is essential to be aware of this lesion as a possible cause of gastrointestinal bleeding and especially thoracic postoperative acute gastrointestinal appears. Timely and effective endoscopy can improve the diagnosis rate of these lesions and reduce the related mortality. At the same time, we need to pay attention to the patients with the risk factors in the perioperative period to reduce the incidence of Dieulafoy's lesion.

Metastatic gastric adenocarcinoma associated with hypertrophic gastropathy resembling Ménétrier's disease in an adult Labrador Retriever dog

We describe a case of hypertrophic gastropathy (Ménétrier’s like disease) with metastatic gastric adenocarcinoma in a seven-year-old intact female Labrador Retriever dog. The animal suddenly presented with emesis and died. Gross lesions included a marked diffuse thickening of the gastric mucosa and an ulcerated transmural neoplastic mass in the gastric body. Gastric body and fundus were affected by foveolar hyperplasia with loss of chief and parietal cells replaced by mucous cells and marked dilatation of gastric glands. An area of gastric adenocarcinoma with submucosal lymphatic vessels invasion was also present and metastases were observed in the gastric lymph nodes, small intestine, pancreas, lung and liver. Due to its similarity with other gastric proliferative disorders, including this condition in the list of differentials is a necessary step in the diagnostic investigation of canine gastropathies.

A Rare Case of Nsaid Induced Gastric Body Diaphragmatic-Like Stricture

Protein-losing gastroenteropathy is a rare syndrome of protein loss from the gastrointestinal system. It manifests with hypoproteinemic edema, which may be due to either lymphatic leakage due to increased interstitial pressure or leakage of protein-rich fluids due to intestinal disorders. Our case describes a 65-year-old female with life-threatening protein-losing enteropathy (PLE) requiring multiple transfers to intensive care unit for vasopressor support. In this rare instance, her extensive initial workup did not reveal any etiology for PLE, but she was later found to have underlying Crohn’s colitis. Protein-losing enteropathy is an underdiagnosed complication of inflammatory bowel disease and must be considered while treating patients with colitis.