Oesophageal cell collection device and biomarker testing to identify high-risk Barrett's patients requiring endoscopic investigation.

BACKGROUND: Barrett's oesophagus surveillance places significant burden on endoscopy services yet is vital to detect early cancerous change. Oesophageal cell collection device (OCCD) testing was introduced across Scotland for Barrett's surveillance in response to the COVID-19 pandemic. This national pragmatic retrospective study presents the CytoSCOT programme results and evaluates whether OCCD testing is successfully identifying high-risk Barrett's patients requiring urgent endoscopy. METHODS: All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards over a 32-month period were identified. Patients who underwent endoscopy within 12 months of OCCD test were included. Individual patient records were interrogated to record clinical information and OCCD test result to categorize patients into risk groups. Endoscopic histopathology results were analysed according to risk group and segment length. Patients were deemed high risk if the OCCD test demonstrated atypia and/or p53 positivity. RESULTS: 4204 OCCD tests were performed in 3745 patients: 608 patients underwent endoscopy within 12 months and were included in this analysis. Patients with longer Barrett's segments were significantly more likely to have an abnormal OCCD test. 50/608 patients (8.2%) had high-grade dysplasia or cancer on endoscopic biopsies: this equates to 1.3% of the total group (50/3745). 46/50 patients (92.0%) were deemed high risk, triggering urgent endoscopy: this rose to 100% with insufficient tests removed. There were no cancers diagnosed within 12 months post-OCCD in the low-risk group. CONCLUSION: OCCD testing is an effective triage tool to identify high-risk patients with Barrett's oesophagus requiring further investigation with endoscopy within the real-world setting.

National adoption of an esophageal cell collection device for Barrett's esophagus surveillance: impact on delay to investigation and pathological findings.

High quality Barrett's esophagus surveillance is crucial to detect early neoplastic changes. An esophageal cell collection device (OCCD) was introduced as a triage tool for Barrett's surveillance. This study aims to evaluate whether the Scottish OCCD program (CytoSCOT) has reduced delays to Barrett's surveillance, and whether delayed surveillance negatively impacts endoscopic pathology. All patients undergoing OCCD testing for Barrett's surveillance across 11 Scottish health boards between 14/9/2020 and 13/9/2022 were identified. Patients were dichotomised into two groups (Year 1 vs. Year 2), with individual records interrogated to record demographics, recommended surveillance interval, time from last endoscopy to OCCD test, and OCCD result. Patients were deemed high-risk if the OCCD demonstrated atypia and/or p53 positivity. Further analysis was performed on patients who underwent endoscopy within 12 months of OCCD testing. A total of 3223 OCCD tests were included in the analysis (1478 in Year 1; 1745 in Year 2). In Year 1 versus Year 2, there was a longer median delay to surveillance (9 vs. 5 months; P < 0.001), increased proportion of patients with delayed surveillance (72.6% vs. 57.0%; P < 0.001), and more high-risk patients (12.0% vs. 5.3%; P < 0.001). 425/3223 patients (13.2%) were further investigated with upper gastrointestinal endoscopy, 57.9% of which were high-risk. As surveillance delay increased beyond 24 months, high-risk patients were significantly more likely to develop dysplasia or malignancy (P = 0.004). Delayed Barrett's esophagus surveillance beyond 24 months is associated with increased risk of pre-cancerous pathology. The CytoSCOT program has reduced delays in surveillance, promoting earlier detection of dysplasia and reducing burden on endoscopy services.

A Paper-Based Simulation Model for Teaching Inguinal Hernia Anatomy.

BACKGROUND: Inguinal hernias remain a challenging area of learning for medical students due to its relatively complex anatomy. Modern curriculum delivery methods are conventionally limited to didactic lectures and demonstration of anatomy intraoperatively. These strategies have limitations; lectures are inherently descriptive and based on 2-dimensional models, while intraoperative teaching is often unstructured and opportunistic. METHODS: A paper-based model was developed comprising three overlapping paper panels simulating the anatomical layers of the inguinal canal which can be modified readily to further simulate various hernia pathologies and their surgical repair. These models were incorporated into a timetabled structured learning session for 3rd- and 4th-year medical students. Learners responded to fully anonymised surveys before and after the learning session. FINDINGS: A total of 45 students participated in these sessions over a period of 6 months. Pre-learning session mean ratings for the learners' confidence in their understanding of the layers of the inguinal canal, identifying indirect and direct inguinal hernias and in naming the contents of the inguinal canal were 2.5, 3.3 and 2.9, while post-learning session mean ratings were 8.0, 9.4 and 8.2, respectively. Paired samples Student's t-tests for all three questions were statistically significant (p < 0.001). The mean rating for usefulness of the session was 9.6/10. Free comments from students emphasised the models' usefulness as a visual learning aid. DISCUSSION AND CONCLUSION: Our novel, low-cost paper model was associated with an improvement in learners' perceived knowledge and understanding of inguinal canal anatomy and pathology.

Choledocholithiasis: Long-term follow-up in patients without stone clearance at first endoscopic retrograde cholangiopancreatography.

OBJECTIVES: Complete clearance during endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis is not always successful and biliary stenting is commonplace. Strategies vary between temporary stent placement (TSP) with interval ERCP or permanent stent placement (PSP) and watchful waiting for recurrent biliary obstruction (RBO). This study aimed to describe outcomes in these two groups and stent patency rates in PSP. METHODS: Patients with incomplete clearance at first ERCP for choledocholithiasis between May 2015 and December 2018 were identified. Clinical outcomes were obtained by retrospective interrogation of the case notes. Median follow-up duration was 41 months (interquartile range 29-51 mo). RESULTS: Of 1263 index ERCP, 199 (15.8%) had no stone clearance, with 53.3% receiving PSP and 46.7% undergoing TSP. The TSP group had repeat ERCP after a median of 8 weeks; 75.3% had clearance on a repeat ERCP. The PSP group was elder than the TSP group (82 y vs 72 y, P < 0.001). The rates of RBO (32.1% vs 16.1%) and emergency readmissions (32.1% vs 19.4%) were higher in the PSP group (both P < 0.05). More patients died without further biliary disease in the PSP group (39.6% vs 12.9%, P = 0.001). PSP stent patency rates at 6, 12, 24, 36, and 61 months were 87.7%, 82.1%, 75.5%, 69.8% and 67.9%, respectively. CONCLUSIONS: Though PSP had higher RBO and emergency readmissions, two-thirds of patients either died or survived without recurrent biliary disease. Stent patency decreased fastest in the first 12 months. Criteria to guide decision-making for biliary stenting remain unclear.

Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma.

OBJECTIVE: To determine the prognostic influence of residual tumor at or within 1 mm of the mobilization margins (R1Mobilization) compared with transection margins (R1Transection) following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: The prognostic strength of R1 status increases with frequency of margin positivity and is enhanced by protocol driven pathology reporting. Currently, margins are treated uniformly with tumor at or close to any margin considered of equal prognostic significance. The resection involves a mobilization phase freeing the posterior margin and anterior surface then a transection phase requiring lympho-vascular division forming the medial resection and pancreatic transection margin. The comparative assessment of the relative importance of tumor involvement of these different margins has not previously been investigated. METHODS: Retrospective analysis of 148 consecutive resections for PDAC from 1996-2007 was performed. The individual (pancreatic transection, medial, posterior, and anterior surface) margins were separately identified and analyzed by a senior pathologist. An R1 resection was defined as microscopic evidence of tumor < or = 1 mm from a resection margin. R1Mobilization tumor extension included both R1Anterior and R1Posterior cases; while R1Transection included pancreatic neck/body transection, R1Medial and adjacent transection margins. RESULTS: R1 status was confirmed in 109 patients (74%). The medial (46%) and posterior (44%) margins were most commonly involved. R1 status was found to an independent predictor of poor outcome (P < 0.001). R1Mobilization involvement only (n = 48) was associated with a significantly longer median survival of 18.9 months (95% CI, 13.7-24.8) versus 11.1 months (95% CI, 7.1-15.0) for those with R1Transection tumor involvement (n = 61) (P < 0.001). There was no significant difference in the survival of the R1Mobilization compared with R0 group (P = 0.52). CONCLUSIONS: Following pancreaticoduodenectomy for PDAC, involvement of the transection margins in contrast to mobilization margins defines a group whose outcome is significantly worse. This may impact upon the allocation of adjuvant therapy within the setting of randomized controlled trials.

Palliative stenting for oesophagogastric cancer: tumour and host factors and prognosis.

OBJECTIVES: Palliative self-expandable metallic stent (SEMS) insertion is common in patients not suitable for resection of oesophagogastric (OG) cancer. Factors which may determine survival, however, are not clear. The present study examined the relationship between tumour and host factors, including the systemic inflammatory response and survival of patients undergoing palliative SEMS insertion. METHODS: Patients with a diagnosis of OG cancer who were considered suitable for palliative SEMS only without systemic therapy were identified. Patient characteristics including Eastern Cooperative Oncology Group performance status, radiological stage and modified Glasgow Prognostic Score (mGPS: 0-C-reactive protein (CRP) ≤10 mg/L; 1-CRP >10 mg/L; 2-CRP >10 mg/L; albumin <35 g/L) were recorded prospectively. The relationship between such characteristics and 3-month survival was examined. RESULTS: 203 patients were included in the final analysis. All patients died during follow-up, with median survival from diagnosis 75 days (IQR 47-157). 78% of patients were systemically inflamed (mGPS >1). On multivariate analysis, only poor performance status (HR 1.23, p=0.025), metastatic disease (HR 2.27, p<0.001) and mGPS (HR 1.25, p=0.021) were associated with shorter survival. The combination of performance status and mGPS stratified 3-month survival of patients without metastatic disease from 88% to 20% (p<0.001) and patients with metastases from 43% to 6% (p=0.059). Similar results were observed when analysis was restricted to patients with oesophageal and junctional cancer (M0: 83%-20%, p=0.008; M1: 33%-8%, p=0.082). CONCLUSION: Performance status, metastatic disease and mGPS are independent predictors of survival in patients with OG cancer undergoing palliative SEMS insertion. These routinely available markers provide a rational system on which to base decisions regarding prognosis and treatment.

Chronic inflammation and pancreatic cancer.

There is a proven association between carcinoma of the pancreas and both the sporadic and hereditary forms of chronic pancreatitis. In chronic pancreatitis the standardised incidence ratio for development of pancreatic cancer is 14-18 and is further increased by cigarette smoking. Underlying mechanisms are unclear but current theories point to the progressive accumulation of genetic mutations as a consequence of repeated DNA damage and cell regeneration in an environment favouring proliferation and neovascularisation. In patients who develop pancreatic cancer, there is interest in the role of the inflammatory response in the development of cancer cachexia and in determining prognosis. Furthermore, markers of a systemic inflammatory response have prognostic significance in both advanced, inoperable pancreatic cancer and in patients undergoing resection. Further understanding of the details of the relationship between inflammation, carcinogenesis and cancer prognosis may lead to new therapeutic possibilities as part of multi-modality management of this difficult disease.

The role of stents in the palliation of oesophageal cancer.

Oesophageal cancer is the 13th most common cancer in the UK and very few patients are suitable for radical treatment. Almost all of the remaining patients suitable for palliative treatment only have some degree of dysphagia requiring treatment. Self-expanding metal stents are currently the most common means of improving swallowing. This review discusses when we should stent patients, what type of stent we should use and how it can be carried out as well as illustrating the problems that can occur immediately after stent insertion and longer term problems.

Iron-induced gastric ulceration with radiological and endoscopic appearance of carcinoma.

Erosive injury of the upper gastrointestinal tract resulting from therapeutic oral iron supplements is an uncommon phenomenon. We present a case of a large gastric ulcer with clinical, endoscopic and radiological features suggestive of malignancy, which resolved completely on cessation of iron therapy.

Pneumomediastinum following Ecstasy (methylenedioxymetamphetamine, MDMA) ingestion in two people at the same 'rave'.

Ecstasy is a class A controlled drug often consumed by the young population for recreational purposes. Documented complications of its use include hyperpyrexia, disseminated intravascular coagulation (DIC), renal failure and rhabdomyolysis. We report on two patients who developed pneumomediastinum after Ecstasy abuse. Both patients obtained and consumed the drug at the same establishment and presented to the same hospital within half an hour. The possible pathogenesis of this complication are discussed and the literature reviewed. Pneumomediastinum should be recognized as a possible complication of Ecstasy use. Conservative management is appropriate.

Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer.

BACKGROUND/AIMS: Patients with pancreatic cancer have one of the poorest survival rates and selection of patients for active treatment remains problematical. The present study assesses the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with inoperable pancreatic cancer. METHODS: The GPS was constructed as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) were allocated a score of 2. Patients in whom only 1 or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. RESULTS: One hundred and eighty-seven patients were studied and 49 (26%) underwent an operative palliative bypass procedure. At the end of follow-up, 181 (97%) patients died, 17% of patients were alive at 12 months. On univariate analysis, age (p < 0.01), TNM stage (p < 0.001) and the GPS (p < 0.001) were significant predictors of survival. On multivariate survival analysis, stratified for bypass procedure, age (hazard ratio 1.53, 95%CI 1.12-2.10, p = 0.008), TNM stage (hazard ratio 1.70, 95%CI 1.33-2.18, p < 0.001) and the GPS (hazard ratio 1.72, 95%CI 1.40-2.11, p < 0.001) remained independent significant predictors of survival. CONCLUSION: At diagnosis, the presence of a systemic inflammatory response (as measured by the GPS) appears to be a useful indicator of poor outcome, independent of TNM stage, in patients with inoperable pancreatic cancer.

Potential value of contrast-enhanced intraoperative ultrasonography during partial hepatectomy for metastases: an essential investigation before resection?

OBJECTIVE: The aim of the study was to assess the clinical value of contrast-enhanced intraoperative ultrasound (CE-IOUS) as a novel tool in the hepatic staging of patients undergoing liver resection. METHODS: Sixty patients scheduled to undergo liver resection for metastatic disease were studied. Preoperative staging with contrast-enhanced CT and/or MR scans was performed within 2 to 6 weeks of operation. Following exploration, intraoperative ultrasound (IOUS) was performed using an HDI-5000 scanner (Philips) and a finger-probe with pulse inversion harmonic (PIH) capability. CE-IOUS in the PIH mode was performed in a standardized protocol (low MI: 0.02-0.04) after intravenous injection of 3-4 mL of SonoVue (Bracco spa, Milan); all detected lesions on precontrast and postcontrast scans were counted and mapped. Any alteration in surgical management was documented following CE-IOUS compared with IOUS. RESULTS: Three patients were excluded due to disseminated disease on exploration. CE-IOUS was significantly more sensitive than CT/MR and IOUS in detecting liver metastases (96.1% versus 76.7% and 81.5%, respectively) (P<0.05); it altered surgical management in 29.8% (17 of 57) of cases, due to 1) additional metastases in 19.3% (11 of 57), 2) less metastases in 3.5% (2 of 57), 3) benign lesions wrongly diagnosed as metastasis on IOUS/CT in 5.3% (3 of 57), and 4) vascular proximity in 1.8% (1 of 57). Management was unchanged in 70.2% (40 of 57) despite additional lesions detected in 3.5% (2 of 57) and benign lesion wrongly diagnosed on IOUS and CT as metastasis in 1.8% (1 of 57). CE-IOUS altered combined IOUS/CT/MR staging in 35.1%. CONCLUSION: These preliminary results suggest CE-IOUS is an essential tool prior to liver resection for metastases.