OBJECTIVES:Type 1 gastric neuroendocrine tumors (T1g-NETs) are well-differentiated lesions with excellent survival but frequent recurrence. Tumor size is the main prognostic factor, yet optimal management for tumors >1cm remains uncertain. This study aimed to evaluate treatment strategies and outcomes in patients with T1g-NETs>1 cm. METHODS:We conducted a retrospective multicenter study including 106 adults with T1g-NETs>1 cm. Clinicopathologic and management data were collected. The primary outcome event was a composite unfavorable outcome (UO), defined as recurrence or progression, used to analyze progression-free survival as the main time-to-event outcome. Analyses included multinomial logistic regression, Cox models, and Kaplan-Meier curves (p<0.05). RESULTS:Among 106 patients (58.5% female; median age 59), median tumor size was 15mm. Most tumors were Grade 1 (61.4%) or Grade 2 (37.7%), with median Ki-67 of 2%. Endoscopic resection was performed in 76 patients (71.7%), surgery in 33 (31.1%, including 13 initially treated endoscopically), and 10 (9.4%) were surveilled. Over a median 61-month follow-up, 24 patients (22.6%) recurred, 8 (7.5%) progressed; only 2 deaths (1.9%) were tumor-related. Larger tumors were associated with UO (p=0.005), with lesions ≥24mm predicting shorter progression-free survival (HR 3.93;p<0.001). Endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (m-EMR) were associated with a significantly longer progression-free survival (p=0.004). R0 resection showed a borderline protective effect. Five-year overall survival approached 95%. CONCLUSIONS:T1g-NETs>1cm frequently recur and may exhibit aggressive potential, particularly when lesions are larger. When endoscopic resection is feasible, ESD or m-EMR should be preferred to optimize outcomes.

Anastomotic leak remains a significant source of morbidity and mortality following oesophagogastric resections. Early detection is essential in this high-risk population. C-reactive protein (CRP) is a well-established marker of post-operative complications. This study aimed to assess the association between early post-operative CRP changes and anastomotic leaks, identifying a predictive threshold in our centre. All patients undergoing oesophagogastric resection from November 2023 to November 2024 were included. Changes in CRP (delta CRP) over the first 10 post-operative days (POD) were analysed. Univariate and multivariate analyses were conducted to identify significant predictors of anastomotic leak. A predictive model was developed to determine an optimal CRP threshold. A total of 156 patients were included; 112 were male, with a median age of 66 years and BMI of 27. Open procedures accounted for 69% of cases, and the anastomotic leak rate was 9.6%. The maximum delta CRP between POD1 and POD5 was significantly associated with leaks. A delta CRP >106 mg/L in this window yielded an AUC of 0.821 (sensitivity 1.00, specificity 0.55). Between POD1 and POD3, the same threshold gave an AUC of 0.77 (sensitivity 0.93, specificity 0.59). In this single-centre study, a delta CRP >106 mg/L by POD3 serves as an early warning marker for anastomotic leak, with continued elevation by POD5 strongly predictive of leakage. CRP monitoring can guide earlier intervention and potentially improve outcomes following oesophagogastric surgery.

Boerhaave’s syndrome is a rare but potentially life-threatening rupture of the oesophagus. Despite advances in diagnosis and management, it still has a high mortality rate. While single episodes of Boerhaave’s syndrome are uncommon, recurrent spontaneous oesophageal perforations are exceedingly rare. This is a case of a 45-year-old gentleman, presenting with Boerhaave’s syndrome 3 times, over 26 months. He initially presented in April 2023 and was managed with a thoracotomy and primary repair of the oesophagus over a T-tube which failed. An attempt at disconnection was undertaken but abandoned due to a hostile chest and the patient was subsequently managed with endovac therapy. Second presentation was October 2024. He was initially managed with endovac therapy but due to the chronic chest cavity poor progress was made. A covered oesophageal stent was utilised alongside chest drainage. In April 2025, he was re-admitted with a further episode. Again, he was managed with endovac therapy and Vac Stent placement. His most recent admission has been complicated by poor functional status, ongoing respiratory issues and he has been discharged to his base hospital for prolonged tracheostomy weaning. Recurrent Boerhaave’s syndrome challenges the traditional assumption that a successfully treated oesophageal rupture is a one-time event. While the management in the repeated episodes does not necessarily differ substantially, what becomes more nuanced is the decision-making surrounding treatment. Particularly in this case, where each time the patient is in a much poorer physiological state, making the decision making even more complex.

Objective: This study aimed to compare the postoperative and pathological outcomes between carboplatin, paclitaxel, radiotherapy (CROSS) and 5-FU, leucovorine, oxaliplatin and docetaxel (FLOT) in esophageal adenocarcinoma (EAC) patients from an international, multicenter cohort. Summary of Background Data: Ongoing debate exists around optimum approach to locally advanced EAC, with proponents for perioperative chemotherapy, such as FLOT, or multimodal therapy, in particular the CROSS regimen. Methods: Patients undergoing CROSS (n = 350) and FLOT (n = 368), followed by curative esophagectomy for EAC were identified from the Oesophagogastric Anastomosis Audit. Results: The 90-day mortality was higher after CROSS than FLOT (5% vs 1%, P = 0.005), even on adjusted analyses [odds ratio (OR): 3.97, confidence interval (CI)(95%): 1.34-13.67]. Postoperative mortality in CROSS were related to higher pulmonary (74% vs 60%) and cardiac complications (42% vs 20%) compared to FLOT. CROSS was associated with higher pathologic complete response (pCR) rates (18% vs 10%, P = 0.004) and margin-negative resections (93% vs 76%, P < 0.001) compared with FLOT. On adjusted analyses, CROSS was associated with higher pCR rates (OR: 2.05, CI95%: 1.26-3.34) and margin-negative resections (OR: 4.55, CI95%: 2.70-7.69) compared to FLOT. Conclusions: This study provides real-world data CROSS was associated with higher 90-day mortality than FLOT, related to cardio-pulmonary complications with CROSS. These warrant a further review into causes and mechanisms in selected patients, and at minimum suggest the need for strict radiation therapy quality assurance. Research into impact of higher pCR rates and R0 resections with CROSS compared to FLOT on long-term survival is needed.

Abstract Background Type I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs. Methods Retrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003–2019. Results Following initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11mm g-NENs. Conclusions Patients with ≤10mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2–3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Type I gastric neuroendocrine neoplasms (g-NENs) have a low risk of metastasis and a generally favourable prognosis. Patients with small type I g-NENs (≤10 mm) frequently require no treatment, whereas those with larger polyps usually undergo resection. We evaluated the safety and outcomes of endoscopic surveillance after no initial treatment in selected patients with type I g-NENs. Retrospective analysis of type I g-NEN patients across two European Neuroendocrine Tumour Society Centers of Excellence 2003–2019. Following initial assessment, 87 of 115 patients with type I g-NEN (75 with polyps ≤10 mm) received no initial treatment and underwent endoscopic surveillance. 79/87 (91%) demonstrated no clinically meaningful change in tumour size or grade over a median 62 month follow up. Only two patients developed NEN progression that required a change in management and two other patients developed gastric adenocarcinoma/high grade dysplasia; all four initially had ≥11 mm g-NENs. Patients with ≤10 mm type I g-NENs were unlikely to develop clinically significant tumour progression and in most cases, resection was not needed. The endoscopic surveillance interval could therefore potentially be safely increased to every 2–3 years in such patients. However, lifelong surveillance is still advocated due to the additional risk of developing gastric adenocarcinoma.

Background: No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer. Method: This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III-V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI95%). Results: Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI95%: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI95%: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI95%: 0.54-1.32, p = 0.5), compared to HIC. Conclusion: Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

AbstractBackgroundThe complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting.MethodsData from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups.ResultsOf 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005).ConclusionTrainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery.

BACKGROUND:Neuroendocrine tumours (NETs) of the stomach and duodenum are rare, but are increasing in incidence. Optimal management of localised, low-grade gastric and duodenal NETs remains controversial.AIMS:To systematically review recent literature that has evaluated the management of localised low-grade gastric and duodenal NETs.METHODS:A systematic literature search was conducted. Articles were screened and eligible articles fully assessed. Additional articles were identified through the included articles' reference lists.RESULTS:Several relevant retrospective case series were identified, but there was considerable heterogeneity between studies and they reported a variety of parameters. Type I gastric NETs had an excellent prognosis and conservative management approaches such as endoscopic surveillance/resection were appropriate in most cases. Many type III gastric NETs were low grade and appeared to have a better prognosis than has previously been appreciated. Endoscopic rather than surgical resection was therefore effective in some patients who had small, low-grade tumours. Duodenal NETs were more heterogenous. Endoscopic resection was generally safe and effective in patients who had small, low-grade, nonfunctional, non-ampullary tumours. However, some patients, especially those with larger or ampullary duodenal NETs, required surgical resection.CONCLUSIONS:Most type I gastric NETs behave indolently and surgical resection is only rarely indicated. Some type III gastric and duodenal NETs have a worse prognosis, but selected patients who have small, localised, nonfunctional, low-grade tumours are adequately and safely treated by endoscopic resection. Due to the complexity of this area, a multidisciplinary approach to management is strongly recommended.

Introduction: Duodenal neuroendocrine tumours (d-NETs) are rare but are increasing in incidence. Current ENETS guidelines advocate resection of all localized d-NETs. However, “watch and wait” may be appropriate for some localized, small, grade 1, non-functioning, non-ampullary d-NETs. We evaluated whether patients with such d-NETs who chose “watch and wait” involving regular endoscopic surveillance had equivalent disease-related outcomes to patients undergoing endoscopic or surgical resection. Methods: Retrospective review of patients with histologically confirmed d-NETs at Liverpool ENETS Centre of Excellence 2007–2020. Results: Sixty-nine patients were diagnosed with d-NET of which 50 were sporadic, non-functioning, non-ampullary tumours. Patient treatment groups were similar in terms of age, gender, and tumour location and grade, but unsurprisingly, larger tumours (median diameter 17 mm [p < 0.0001]) were found in the surgically treated group. Five patients underwent surgical resection with no evidence of tumour recurrence or disease-related death. Twelve patients underwent endoscopic resection (ER), with 1 local recurrence detected during follow-up. Thirty patients (28 with d-NETs ≤10 mm) underwent “watch and wait” with resection only if tumours increased in size. The d-NETs in 28/30 patients remained stable or decreased in size over a median 27 months (IQR: 15–48, R: 3–98). In 7 patients, the d-NET was completely removed by avulsion during diagnostic biopsy and was not seen at subsequent endoscopies. Only 2 patients showed increased d-NET size during surveillance, of whom only one was fit for ER. No NET-related deaths were documented during follow-up. Conclusions: All of the localized, ≤10 mm, grade 1, non-functioning, non-ampullary d-NETs in this cohort behaved indolently with very low risks of progression and no tumour-related deaths. “Watch and wait,” therefore, appears to be a safe alternative management strategy for selected d-NETs.

BACKGROUND & AIMS:In patients with autoimmune atrophic gastritis and achlorhydria, hypergastrinemia is associated with the development of type 1 gastric neuroendocrine tumors (gNETs). Twelve months of treatment with netazepide (YF476), an antagonist of the cholecystokinin B receptor (CCKBR or CCK2R), eradicated some type 1 gNETs in patients. We investigated the mechanisms by which netazepide induced gNET regression using gene expression profiling.METHODS:We obtained serum samples and gastric corpus biopsy specimens from 8 patients with hypergastrinemia and type 1 gNETs enrolled in a phase 2 trial of netazepide. Control samples were obtained from 10 patients without gastric cancer. We used amplified and biotinylated sense-strand DNA targets from total RNA and Affymetrix (Thermofisher Scientific, UK) Human Gene 2.0 ST microarrays to identify differentially expressed genes in stomach tissues from patients with type 1 gNETs before, during, and after netazepide treatment. Findings were validated in a human AGSGR gastric adenocarcinoma cell line that stably expresses human CCK2R, primary mouse gastroids, transgenic hypergastrinemic INS-GAS mice, and patient samples.RESULTS:Levels of pappalysin 2 (PAPPA2) messenger RNA were reduced significantly in gNET tissues from patients receiving netazepide therapy compared with tissues collected before therapy. PAPPA2 is a metalloproteinase that increases the bioavailability of insulin-like growth factor (IGF) by cleaving IGF binding proteins (IGFBPs). PAPPA2 expression was increased in the gastric corpus of patients with type 1 gNETs, and immunohistochemistry showed localization in the same vicinity as CCK2R-expressing enterochromaffin-like cells. Up-regulation of PAPPA2 also was found in the stomachs of INS-GAS mice. Gastrin increased PAPPA2 expression with time and in a dose-dependent manner in gastric AGSGR cells and mouse gastroids by activating CCK2R. Knockdown of PAPPA2 in AGSGR cells with small interfering RNAs significantly decreased their migratory response and tissue remodeling in response to gastrin. Gastrin altered the expression and cleavage of IGFBP3 and IGFBP5.CONCLUSIONS:In an analysis of human gNETS and mice, we found that gastrin up-regulates the expression of gastric PAPPA2. Increased PAPPA2 alters IGF bioavailability, cell migration, and tissue remodeling, which are involved in type 1 gNET development. These effects are inhibited by netazepide.

Background: Patients with colorectal cancer deemed to be high-risk may be denied an elective laparoscopic resection due to subjective reasons. A comparison of the 30-day outcomes in true functional high-risk patients who underwent either open or laparoscopic colorectal resection was undertaken. Materials and Methods: A retrospective cohort of all functional high-risk patients as assessed by cardiopulmonary exercise test between July 2015 and April 2018 were identified. Anaerobic threshold of <11 mL/kg/minute was used as a physiologic indicator to determine a high-risk patient. Adherence to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) was ensured. P values were computed via two-sided Fisher's exact test, and the exact Mann-Whitney U-test. Forest plots for relative risks with 95% confidence intervals were displayed on a log scale. Results: One hundred forty-six patients were identified as high-risk. Outcomes demonstrated a trend to laparoscopic benefit in all Clavien-Dindo grades of postoperative complications, but especially in severe complications of grades 3-4 (3.5% versus 10.2%). Readmissions demonstrated a trend to laparoscopic surgery benefit (7% versus 11.8%), as did mortality (1.7% versus 3.4%). The rate of surgery-site complications was higher after open surgery (42.1% versus 22.4%, P = .0201). Wound infections were observed more frequently after open surgery (12.5% versus 1.72%, P = .0280). The estimated risk of all-grade complications was significantly higher after open anterior rectal resection (63.0% versus 29.6%, P = .0281) and there was significantly shorter stay after laparoscopic right colectomy (5 v. 7 days, P = .0490). Conclusions: Laparoscopic approach for colorectal resections in high-risk patients is safe and beneficial compared to open surgery, especially in patients undergoing laparoscopic resection of the rectum and right colon.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Objective The aim of this study was to assess the nutritional status of patients presenting with small bowel obstruction (SBO), along with associated nutritional interventions and clinical outcomes. Design Prospective cohort study. Setting 131 UK hospitals with acute surgical services. Participants 2069 adult patients with a diagnosis of SBO were included in this study. The mean age was 67.0 years and 54.7% were female. Primary and secondary outcome measures Primary outcome was in-hospital mortality. Secondary outcomes recorded included: major complications (composite of in-hospital mortality, reoperation, unplanned intensive care admission and 30-day readmission), complications arising from surgery (anastomotic leak, wound dehiscence), infection (pneumonia, surgical site infection, intra-abdominal infection, urinary tract infection, venous catheter infection), cardiac complications, venous thromboembolism and delirium. Results Postoperative adhesions were the most common cause of SBO (49.1%). Early surgery (<24 hours postadmission) took place in 30.0% of patients, 22.0% underwent delayed operation and 47.9% were managed non-operatively. Malnutrition as stratified by Nutritional Risk Index was common, with 35.7% at moderate risk and 5.7% at severe risk of malnutrition. Dietitian review occurred in just 36.4% and 55.9% of the moderate and severe risk groups. In the low risk group, 30.3% received nutritional intervention compared with 40.7% in moderate risk group and 62.7% in severe risk group. In comparison to the low risk group, patients who were at severe or moderate risk of malnutrition had 4.2 and 2.4 times higher unadjusted risk of in-hospital mortality, respectively. Propensity-matched analysis found no difference in outcomes based on use or timing of parenteral nutrition. Conclusions Malnutrition on admission is associated with worse outcomes in patients with SBO, and marked variation in management of malnutrition was observed. Future trials should focus on identifying effective and cost-effective nutritional interventions in SBO.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The Enhanced Recovery After Surgery program (ERAS), has become the basis of perioperative management after colorectal surgery, vascular, thoracic, and more recently the radical cystectomy. The aim of this study is to show our initial experience using an ERAS protocol.A total of 47 laparoscopic radical cystectomies (LRC) were compared in this study. For retrospective data analysis, the patients were divided into two groups: Group A included patients who underwent LRC before the ERAS protocol was implemented; and Group B included patients who underwent LRC after the ERAS protocol was implemented.Hospital stay was significantly shorter (p = 0,04) in Group B with a median of 11.73 days versus 17.53 days in Group A. The paralytic ileus is the most common complication in both groups, and only two complications seem to be lower between groups; central vein catheter infection in Group A was 14.2% versus 5.2% in Group B and paralytic ileus in Group A was 35.7% versus 21.0% in Group B. There was no statistical difference between groups in the appearance of minor or major complications.The combination of minimally invasive surgery and an ERAS protocol is a feasible multidisciplinary challenge and is useful in the recovery of patients undergoing LRC.