Esophagogastric Junction Research Articles

Effects of perioperative treatment of resectable adenocarcinoma of esophagogastric junction by immunotherapy (Adebrelimab) combined with chemotherapy (XELOX): protocol for a single-center, open-labeled study (AEGIS trial, neoadjuvant immunochemotherapy).

For resectable adenocarcinoma of the esophagogastric junction (AEG), current treatment exploration primarily focuses on perioperative chemotherapy regimens combined with PD-1/PD-L1 inhibitors, but the long-term survival benefits of still require further investigation, and the use of upfront immunotherapy is typically restricted to patients with metastatic MSI-H (M1 MSI-H) disease due to their potential responsiveness to immunological agents. Adebrelimab, as a novel PD-L1 antibody, has not yet been proven for its efficacy and safety in adenocarcinoma of the esophagogastric junction. The AEGIS study is a prospective, open-labeled, single-arm, phase II clinical trial. A total of 26 patients with AEG will be enrolled. The primary endpoint is the pathologic complete response (pCR) rate after perioperative neoadjuvant immunochemotherapy. Secondary outcomes of the study include the objective response rate (ORR), R0 resection rate, major pathological response (MPR) rate, and pCR rate in combined positive score(CPS) ≥ 5 and MSI-H populations, event-free survival (EFS), and overall survival (OS). The exploratory outcomes are the biomarkers related to therapeutic efficacy, such as PD-L1 expression, microsatellite instability (MSI), tumor mutational burden(TMB), Epstein-Barr virus(EBV) infection, and circulating tumor DNA(ctDNA). This trail aims to verify the efficacy and safety of the perioperative treatment regimen of anti-PD-L1 (Adebrelimab) combined with chemotherapy (capecitabine plus oxaliplatin, XELOX) for patients with resectable AEG. Considering the differences in chemotherapy regimen tolerance between Asian and Western populations, this study intends to evaluate the suitability of Adebrelimab combined with XELOX chemotherapy for the Asian population. ClinicalTrials.gov: NCT06482788. The trial was prospectively registered on 22 May 2024, https://clinicaltrials.gov/study/NCT06482788 .

Phase II trial of nab-paclitaxel plus ramucirumab in combination with nivolumab for unresectable advanced or recurrent gastric cancer after progression on first-line treatment including fluoropyrimidine, platinum, and anti-PD-1/PD-L1 antibody (PADDLE).

Patients with advanced gastric cancer (AGC) have poor survival after first-line treatment containing an anti-programmed death-1/ligand 1 (PD-1/PD-L1) antibody. Accumulating evidence suggests rationales for continuing immunotherapy beyond progression, synergistic effects between immune checkpoint inhibitors and angiogenesis inhibitors, and a preferable combination of steroid-free chemotherapy with immunotherapy. These rationales imply that nanoparticle albumin-bound (nab)-paclitaxel plus ramucirumab in combination with nivolumab (anti-PD-1 antibody) may enhance anti-tumor effects as second-line treatment. Therefore, we hypothesized that this triplet regimen may improve clinical outcomes in patients with AGC who experienced disease progression on first-line treatment including anti-PD-1/PD-L1 antibody. The PADDLE trial, which is sponsored by Ono Pharmaceutical, is an investigator-initiated, multicenter, open-label, single-arm, prospective phase II trial conducted at six institutions in Japan. Key eligibility criteria are as follows: (1) advanced gastric or esophagogastric junction cancer, (2) histologically confirmed diagnosis of adenocarcinoma, (3) refractory to first-line treatment including fluoropyrimidines, platinum, and an anti-PD-1/PD-L1 antibody, (4) performance status of 0-1, and (5) at least one measurable lesion. Patients are to receive nab-paclitaxel (100 mg/m2 weekly, with a 1-week rest after 3 consecutive weeks), ramucirumab (8mg/kg every 2 weeks), and nivolumab (240mg/body every 2 weeks). The primary endpoint is 6-month progression-free survival (PFS) rate. The target number of patients was set at 45 based on threshold and expected 6-month PFS rates of 35% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.95. Secondary endpoints include objective response rate, disease control rate, PFS, overall survival, duration of response, time to response, and safety. Biomarker analyses of serial blood and tumor samples are planned to clarify predictive markers and molecular mechanisms underlying treatment resistance by multifaceted analytical methods (e.g., flow cytometry, DNA sequencing [DNAseq]/RNA sequencing [RNAseq]). Recruitment started in November 2022. The PADDLE trial is expected to clarify the efficacy of nab-paclitaxel plus ramucirumab in combination with nivolumab as second-line treatment in patients with AGC refractory to first-line treatment including an anti-PD-1/PD-L1 antibody and to identify potential biomarkers for predicting clinical responses in patients with AGC undergoing this triplet regimen. jRCT2031220448.

571 Delayed gastric emptying after resection of cancer of the esophagus and esophagogastric junction—an uncommon but impactful complication

571 Delayed gastric emptying after resection of cancer of the esophagus and esophagogastric junction—an uncommon but impactful complication

A phase I/II clinical trial of preoperative docetaxel/oxaliplatin/S-1 (DOS) combination therapy for esophagogastric junction adenocarcinoma.

429 Background: Esophagogastric junction (EGJ) cancer is difficult to cure with surgery alone, necessitating adjuvant chemotherapy. However, administering aggressive adjuvant chemotherapy after invasive surgery is difficult. Neoadjuvant chemotherapy, on the other hand, is expected to enhance compliance, increase the rate of curative resection, and reduce recurrence. Methods: We conducted a single center Phase I/II study to evaluate the safety and efficacy of neoadjuvant chemotherapy using docetaxel, oxaliplatin, and S-1 (DOS), followed by adjuvant chemotherapy with S-1 in patients with cT3-4aN0-3M0 adenocarcinoma of the EGJ. In Phase I, we estimated the maximum tolerated dose and dose-limiting toxicity of neoadjuvant DOS therapy and determined the recommended dose (RD). In Phase II, we assessed the safety and efficacy of the RD established in Phase I. The primary endpoint was the curative resection rate, with secondary endpoints including the 3-year overall survival rate, 3-year recurrence-free survival rate, treatment completion rate, response rate to neoadjuvant chemotherapy, pathological response, and adverse events. Neoadjuvant DOS chemotherapy was administered in three 3-week cycles. The starting dose of docetaxel was 50 mg/m², with plans to escalate it to 60 mg/m². Docetaxel and oxaliplatin (100 mg/m²) were administered on day 1, while S-1 (120 mg/body) was given orally on days 1-14. Postoperative adjuvant chemotherapy consisted of S-1 (120 mg/body), administered for 4 weeks followed by a 2-week rest period, repeated for 8 cycles. Results: Based on the 6 patients enrolled in Phase I, the RD of docetaxel was determined to be 60 mg/m². A total of 40 eligible patients, including 3 from Phase I, were enrolled in the study. Two patients discontinued protocol treatment during neoadjuvant chemotherapy due to adverse events and 1 patient discontinued due to positive peritoneal cytology. The R0 resection rate was 87.5% (35/40). Surgical procedures included esophagectomy in 18 patients, total gastrectomy in 15, and proximal gastrectomy in 4. Postoperative complications of Grade III or higher, as per the Clavien-Dindo classification, occurred in 15.0% of patients, with no surgery-related deaths. The response rates to neoadjuvant chemotherapy were 12.5% for PR, 2.5% for PD, and 85.0% for non-CR/non-PD. Pathological response rates were: Grade III in 8.1%, Grade II in 35.1% and Grade I in 56.8%. During neoadjuvant chemotherapy, Grade 3 or higher adverse events were observed, including neutropenia (82.5%), nausea (5%) and diarrhea (5%). The neoadjuvant chemotherapy completion rate was 92.5%, although 59.5% of patients required dose reductions. Conclusions: Neoadjuvant DOS therapy for esophagogastric junction cancer shows promise, achieving a high R0 resection rate and substantial pathological efficacy, with acceptable levels of adverse events. Clinical trial information: UMIN000022210.

Esophageal Motility Disorders: A Concise Review on Classification, Diagnosis, and Management.

Esophageal motility disorders (EMDs) are an underrecognized cause of dysphagia and encompass a breadth of conditions, including achalasia, esophagogastric junction outflow obstruction, absent contractility, distal esophageal spasm, hypercontractile esophagus, and ineffective esophageal motility. Whereas patients with EMDs classically present with dysphagia to both solids and liquids, other symptoms such as heartburn, noncardiac chest pain, and regurgitation may also be present. The advent and standardization of high-resolution esophageal manometry by the Chicago Classification have revolutionized the diagnosis and management of EMDs. The EMDs are broadly classified into disorders of the esophagogastric junction (achalasia, esophagogastric junction outflow obstruction) and peristalsis (absent contractility, distal esophageal spasm, hypercontractile esophagus, ineffective esophageal motility). Additional tests, such as timed barium esophagogram and EndoFLIP, can help provide adjunctive information in cases in which high-resolution esophageal manometry findings are inconclusive. Management varies widely according to the type of EMD and can range from lifestyle and dietary modifications to oral pharmacologic therapy and various endoscopic or surgical interventions. In patients with achalasia, durable management aimed at the lower esophageal sphincter should strongly be considered. This clinical review aims to provide a concise yet comprehensive summary on classification, diagnosis, and management of EMDs.

The impact of nutritional status on recurrence-free survival (RFS) in patients with locally advanced oesophagogastric adenocarcinoma (LA-OGA) treated with FLOT therapy.

388 Background: Malnutrition and weight loss were reported as poor prognostic factors in operable OGA. This study examines the relationship between oncological outcomes and nutritional status in LA-OGA patients under the current standard of care, perioperative FLOT therapy. Methods: From 2017 to 2023, 423 patients who had radical resection at Royal Marsden Hospital were screened. Inclusion criteria included LA-OGA (cT2≤ and Nany or Tany and N+), at least one cycle of neoadjuvant chemotherapy (NAC), and ECOG PS 0–2. Nutritional status was assessed by body weight and prognostic nutritional index (PNI), with significant weight loss defined as a 5% loss within six months before diagnosis or during NAC. PNI was calculated as serum albumin (g/L) + 0.005 × lymphocyte count /μL, with categories of severe (<45), mild to moderate (45–49.9), and normal (≥50). The primary endpoint was 3-year recurrence-free survival (3y-RFS). Restricted mean survival time (RMST) at 36 months was calculated to analyze survival time. Multivariate analyses were performed to identify prognostic factors for RFS. The pathological response was assessed using tumour regression grade (TRG) (Mandard criteria). Results: Of the 423 patients, 210 met the inclusion criteria. Primary tumour sites were the oesophagus (52.4%), the oesophagogastric junction (18.1%), and the stomach (29.5%). The median follow-up was 26.5 months. Weight loss at baseline and after NAC, as well as PNI, did not significantly impact RFS (p=0.13, p=0.91, p=0.69, p=0.45). However, a PNI decrease from baseline was associated with significantly shorter 3y-RFS (46% vs. 69%, p<0.001), and the RMST difference was 5.46 months (p<0.001). Multivariable analyses showed ypN positivity (p<0.001), R1 resection (p<0.001), and PNI decrease (p=0.03) as negative prognostic factors for RFS. Pathological response did not differ regardless of PNI change (28.2% vs. 30.4%, p=0.75). Conclusions: A decrease of PNI is a significant poor prognostic factor for RFS in LA-OGA patients undergoing FLOT, suggesting that maintaining nutritional status during NAC could enhance survival outcomes.

A Standardized Approach to Performing and Interpreting FLIP Panometry for Esophageal Motility Disorders: The Dallas Consensus.

Functional lumen imaging probe (FLIP) Panometry provides assessment of the esophagogastric junction (EGJ) opening and esophageal body contractile activity during an endoscopic procedure and is increasing being incorporated in comprehensive esophageal motility assessments. We aimed to provide a standardized approach and vocabulary to the procedure and interpretation and update the motility classification scheme. A working group of 19 FLIP Panometry experts convened in a modified Delphi consensus process to produce and assess statements on the FLIP Panometry procedure and interpretation. Three rounds of voting were conducted on an agreement scale of 1-9 for appropriateness followed by face-to-face discussions and opportunity for revisions of statements. The "percent agreement" was proportion of votes with score ≥7 indicating level of agreement on appropriateness. A total of 40 statements were selected for final inclusion for the Dallas Consensus, including FLIP Panometry protocol, interpretation of EGJ opening and contractile response, and motility classification scheme. Key statements included: "FLIP Panometry should be interpreted in the context of the clinical presentation, the accompanying EGD findings and other relevant complementary testing". (Median response 9.0; 100% agreement). "A major motor disorder is unlikely in the setting of a "Normal" FLIP Panometry classification (Median response 9.0; 94% agreement). "Diminished or absent contractile response with reduced esophageal opening [i.e. "non-spastic obstruction] supports the diagnosis of a disorder of EGJ outflow. (Median response 8.5; 94% agreement). The standardized approach for performance and interpretation of the Dallas Consensus can facilitate use of FLIP Panometry in broad clinical settings.

A randomized phase II trial of systemic chemotherapy with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: 3-year follow-up data of the Japan Clinical Oncology Group study JCOG1301C (Trigger study).

393 Background: We previously reported better objective and pathological response with the addition of trastuzumab to preoperative chemotherapy in the randomized phase II trial comparing the efficacy of systemic chemotherapy with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis. Here, we report 3-year follow-up data. Methods: Eligible patients with HER2-positive gastric cancer having extensive lymph node metastasis were randomized to receive preoperative chemotherapy with S-1/cisplatin (SP: S-1 80–120 mg/body on days 1–14, and cisplatin 60 mg/m2 on day 1, q21 days, 3-4 courses) in arm A or SP plus trastuzumab (first course 8 mg/kg followed by 6 mg/kg, day 1 on each course) in arm B. After gastrectomy, adjuvant chemotherapy with S-1 was added for 1 year in both arms. The primary endpoint was overall survival (OS), and the sample size was planned to be 130 patients in total, expecting a 10% increase in the 3-year OS (70% vs 80%) with a 1-sided alpha of 0.2, a power of 0.75. Results: The study was terminated in March 2021 due to slow patient accrual. In total, 46 patients were randomized to either arm A (22 patients) or arm B (24 patients). Patient characteristics were well balanced between the arms. Planned preoperative chemotherapy was completed in 20 patients (90.9%) in arm A and in 23 patients (95.8%) in arm B. Objective response rate tended to be higher in arm B (66.7% [16/24]) than in arm A (36.4% [8/22], p=0.08), and R0 resection was achieved in 20 patients (90.9%) in arm A and 22 patients (91.7%) in arm B. The adjuvant chemotherapy was completed in 54.6% (12/22) in arm A and in 54.2% (13/24) in arm B. With the median observation period of 4.1 years, the 3-year OS was 68.2% in arm A and was 78.9% in arm B with a hazard ratio of 0.698 (95% confidence interval (CI), 0.221-2.209). The 3-year progression-free survival of arm A and arm B was 39.3% and 62.3%, respectively, with a hazard ration of 0.562 (95% CI, 0.229-1.377). Conclusions: Preoperative chemotherapy with SP plus trastuzumab was feasible, and tended to improve the objective response rate, OS and progression-free survival. An integrated analysis with other clinical trials evaluating perioperative trastuzumab is being planned. Clinical trial information: s031180006.

Impact of prior nivolumab use on the efficacy of second-line taxane-based chemotherapy in advanced gastric or esophagogastric junction adenocarcinoma.

352 Background: Taxane-based chemotherapy remains the standard second-line treatment after first-line treatment including anti-PD-1 antibody therapy for patients with advanced gastric or esophagogastric junction adenocarcinoma (GA/EGA). The CheckMate 649 trial suggested that prior use of nivolumab in the first-line setting was associated with longer progression-free survival (PFS) with subsequent treatment. However, there have been few reports on the difference in efficacy of taxane-based chemotherapy as second-line treatment with or without prior nivolumab use in the real-world setting. Methods: We retrospectively reviewed the medical records of patients with advanced GA/EGA who received solvent-based paclitaxel or nanoparticle albumin–bound (nab)-paclitaxel chemotherapy regimens as second-line treatment after first-line platinum-based chemotherapy between January 2018 and August 2024. We divided the patients into two groups: those who received nivolumab with the first-line chemotherapy (Nivo group) and those who did not (non-Nivo group). PFS and overall survival (OS) were estimated using the Kaplan–Meier method and compared between the two groups using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated by univariate and multivariate Cox regression analysis. Results: A total of 115 patients were included: 27 patients in the Nivo group and 88 in the non-Nivo group. Patient backgrounds did not differ significantly in terms of age (median 67/67 years), sex (male 59%/57%), performance status (PS; ≥2 11%/15%), site of primary tumor (EGA 11%/9%), number of metastatic sites (≥3 33%/18%), and ramucirumab use (yes 82%/82%). For the taxane regimens, nab-paclitaxel-based treatment was significantly more common in the non-Nivo group (11.1% /55.7%, p<0.001). There was a tendency toward longer PFS in the Nivo group compared with the non-Nivo group (median 4.2 months [95%CI 2.8-6.0] vs. 2.3 months [95%CI 2.0-3.0], HR 0.65 [95%CI 0.40-1.03]; p=0.067.) The objective response rate was numerically higher in the Nivo group compared with the non-Nivo group (29.4% vs. 17.6%, p=0.315). OS was not significantly different between the Nivo and non-Nivo groups (median 9.6 months [95%CI 4.9-NA] vs. 6.6 months [95%CI 5.5-10.8], HR 0.92 [95%CI 0.52-1.64]; p=0.785). In the non-Nivo group, 64 patients (73%) received subsequent chemotherapy, and 63 patients (72%) received nivolumab. Multivariate analysis identified prior use of nivolumab was a favorable prognostic factor for PFS (HR 0.55 [95%CI 0.31-0.97]; p=0.039). However, prior use of nivolumab did not show a significant benefit for OS (HR 1.09 [95% CI: 0.56-2.13]; p = 0.802). Conclusions: Prior use of nivolumab in first-line platinum-based chemotherapy had a positive impact on PFS with taxane-based second-line chemotherapy in advanced GA/EGA.

EORTC-1203 GITC "INNOVATION": Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy of HER-2 positive stomach cancer: Overall survival results.

LBA331 Background: 10-20% of GC are HER-2 positive. The role of perioperative anti-HER2-directed treatment is yet undefined. Methods: This randomized, open-label phase II-trial investigates the benefit of perioperative chemotherapy (CT) alone or in combination with either T or T and P for HER-2+ gastric (GC) and esophagogastric junction cancer (EGJC). 172 patients (pts) with centrally confirmed, positive HER-2 status and resectable GC or EGJC (UICC TNM stages Ib-III) were included. Pts were randomized in a 1:2:2 ratio to: Arm A (CT alone) (35 pts); Arm B (CT+ T [8mg/kg, followed by 6mg every 3 weeks]) (67 pts); Arm C (CT + T+ P [840mg every 3 weeks]) (70 pts). CT was initially cisplatin (80 mg/m 2 d1) and capecitabine (2 x 1000 mg/m 2 /d d1) for 3 cycles before and after surgery. After publication of FLOT-4 (Al-Batran, Lancet 2019), the protocol was amended. CT changed to four cycles FLOT, with FOLFOX or CAPOX as alternative for pts ineligible for FLOT. In arm B and C, T and P were continued beyond CT at the same dose for a total of 17 cycles. Out of 172 pts randomized, 161 fulfilled all key eligibility criteria and started their allocated treatment (per protocol population). Centrally determined major pathological response rates (mpRR) were 33.3%, 53.3% and 37.9% in Arm A: B: C after amending the protocol while, in contrast, they were 8.3%, 16.7% and 12.5% before (ASCO 2024, abstract 4057). Here, we present progression-free-(PFS) and overall survival (OS) after a median follow-up of 4.3 years. Results: In Arm A: B: C, 63.6%, 64.7%, 50.4% and 51.9%, 61.0%, 47.9% of pts were progression-free at 3 and 5 years. As compared to CT alone, HRs for PFS versus CT+T were 0.88 (90% CI, 0.51 to 1.53) and for CT+T+P 1.40 (90% CI, 0.82 to 2.37). Survival rates at 3 and 5 years in arm A: B: C were 75.6%, 76.9%, 65.2% and 60.5%, 67.5% and 62.6 %. As compared to CT alone, HRs for OS for CT+T and CT+T+P were 0.89 (95% CI, 0.42 to 1.88)) and 1.29 (95% CI, 0.62 to 2.66). For results before and after amendment see table. Conclusions: Non-significant advantages in terms of PFS and OS were observed for the addition of T to CT before, but not after the amendment. CT+T+P was detrimental. These results reflect the challenge of using mpRR as surrogate for survival in the perioperative treatment of GC. Clinical trial information: NCT 02205047 . PFS and OS results before and after amendment. Before amendment: Arm PFS (%) at 3 Years (95% CI) Hazard Ratio (95% CI) OS (%) at 3 Years (95% CI) Hazard Ratio (95% CI) CT(N=14) 57.1(28.4, 78.0) 1.00 78.6(47.3, 92.5) 1.00 CT+T(N=26) 64.2(42.5, 79.5) 0.64(0.24, 1.72) 83.6(62.0, 93.5) 0.77(0.25, 2.44) CT+T+P(N=28) 50.4(30.1, 67.6) 1.18(0.48, 2.93) 68.3(46.3, 82.8) 1.28(0.44, 3.75) After amendment: CT(N=19) 68.4(42.8, 84.4) 1.00 73.3(47.2, 87.9) 1.00 CT+T(N=38) 65.0(47.5, 78.0) 1.12(0.46, 2.75) 72.2(54.3, 84.0) 0.99(0.37, 2.69) CT+T+P(N=36) 50.4 (32.9, 65.7) 1.62(0.67, 3.90) 62.2(42.6, 76.8) 1.30(0.49, 3.48)

The Esophageal Response to Distension on Functional Lumen Imaging Probe Panometry Is Minimally Changed by Conscious Sedation in Healthy Asymptomatic Subjects.

Functional lumen imaging probe (FLIP) Panometry has demonstrated utility in the assessment of esophageal motility as a complement to existing methodologies like high-resolution manometry. However, as FLIP is typically performed with sedation during routine endoscopy, there is potential for impact of sedation agents on esophageal motility. We aim to examine the effects of conscious sedation with midazolam and fentanyl on FLIP Panometry metrics and classification. A cross-over study was conducted on 12 healthy, asymptomatic volunteers that completed FLIP while sedated with intravenous fentanyl and midazolam and while awake on a separate day. FLIP was performed in the same manner in both conditions with transoral placement of the FLIP and stepwise FLIP filling. During awake FLIP, subjects also rated the presence and intensity of esophageal perception. In both experimental conditions, all subjects demonstrated normal motility. The esophagogastric junction distensibility index was lower (median [interquartile range]: 5.8 [5.15-6.85] vs 8.9 [7.68-9.38] mm2/mmHg; P = 0.025), and the FLIP pressure was higher (46.5 [38.125-52.5] vs 33 [26-36.8] mmHg; P = 0.010) in the sedated condition compared to the awake condition. Maximum esophagogastric junction diameter and body distensibility plateau were no different between conditions (P = 0.999 and P = 0.098, respectively). Perception of esophageal sensation during awake FLIP was reported in 7/12 (58%) subjects. While numeric differences in FLIP Panometry metrics were observed between sedated and awake FLIP in healthy subjects, these differences did not change the FLIP Panometry diagnosis. Sedated FLIP offers a well-tolerated method to assess esophageal motility during endoscopy.

Effect of Anti-reflux Mucosal Ablation on Esophageal Motility in Patients With Gastroesophageal Reflux Disease: A Study Based on High-resolution Impedance Manometry.

Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral (16.42 ± 16.93 mmHg·cm to 31.95 ± 21.25 mmHg·cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg·s·cm to 1198.8 ± 811.74 mmHg·s·cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed.

Marantic endocarditis in patients with malignant disease and stroke: a prospective, observational study.

Abstract Background Non-bacterial thrombotic "marantic" endocarditis (NBTE) is characterized by sterile platelet–fibrin vegetations on normal cardiac valves in patients with malignant disease. Common complications of the disease include cerebrovascular or systemic thromboembolism. Systematic prospective data on this disease is missing. We sought to prospectively investigate prevalence and outcome of marantic endocarditis in patients with active malignancy who present with stroke. Methods At our tertiary university center, we prospectively included all patients from 12/2023 to 06/2024 who were admitted with stroke and had active malignant disease. All patients received transthoracic and, if indicated and tolerated, transesophageal echocardiography. Comprehensive interdisciplinary work-up of neurology, infectious diseases, hematology/oncology, and cardiology was performed. Results For this preliminary analysis, a total of 8 patients were included. The median age was 62 years, 6 were female. The underlying malignant diseases included carcinoma of the ovaries in two patients, and melanoma, lung carcinoma, breast carcinoma, oropharynx carcinoma, pancreatic carcinoma, carcinoma of the esophagogastric junction, acute myeloid leukemia, and carcinoma of the thyroid gland in one patient each. Three patients (37.5%) had NBTE: one involving the mitral valve, one involving the aortic valve, and one involving both the mitral and aortic valves. At the time of stroke, one of these patients was receiving anticoagulation therapy with apixaban, one with prophylactic doses of enoxaparin. Two of the patients with NBTE were switched to anticoagulation with low-molecular-weight heparin (LMWH) after the diagnosis of NBTE and one of them continued the anticoagulation therapy with apixaban. One patient was switched to rivaroxaban after the resolution of the lesions and showed a re-occurrence in the follow-up visit. Conclusion NBTE is common in patients who have active malignant disease and present with stroke which therefore must be included in the list of likely differential diagnoses. Consistent with previously published case reports, we observed another case where NBTE lesions resolved under LMWH therapy and originated and even reoccurred under NOAK therapy.

Clinical characteristics and esophageal motility in patients with gastric cardia submucosal tumors and associated changes after endoscopic resection.

This study aimed to investigate the clinical characteristics and esophageal motility of patients with gastric cardia submucosal tumors (SMTs) and the associated changes after endoscopic resection based on high-resolution impedance manometry (HRIM). From our electronic database, we identified patients who underwent pre-operative evaluation of gastric cardia SMTs between 2015 and 2023. All patients completed standardized symptom questionnaires and underwent endoscopic ultrasonography and HRIM. Endoscopic resection via submucosal dissection or submucosal tunnel endoscopic resection was performed, followed by esophagogastroduodenoscopy and HRIM three months later. Esophageal motility on HRIM was compared based on the updated Chicago Classification v4.0. Thirty patients (mean age, 47.4 ± 12.8years; male, 50%) were analyzed. Most patients were asymptomatic (43.3%), while others presented with epigastralgia, regurgitation, chest pain, or dysphagia. On endoscopic ultrasonography, the average tumor size was 16.7 ± 4.5mm (range, 10.0-30.0mm), and most tumors originated from the fourth layer (80%). On HRIM, eight patients (26.7%) had abnormal esophageal motility, including five with ineffective esophageal motility (IEM) and three with esophagogastric junction outflow obstruction. Complete resection was achieved in 25 of the 27 patients (92.6%) who underwent endoscopic treatment. Pathology revealed leiomyomas (96%) and gastrointestinal stromal tumors (4%). No significant differences in symptom profiles or HRIM parameters were observed after tumor resection. Three patients with pre-operative IEM exhibited normal motility at the follow-up HRIM. Up to 26.7% of patients with gastric cardia SMTs had abnormal esophageal motility on HRIM. Endoscopic resection of these SMTs was effective and safe and appeared to improve esophageal motility in patients with IEM.

Macranthoside B Suppresses the Growth of Adenocarcinoma of Esophagogastric Junction by Regulating Iron Homeostasis and Ferroptosis through NRF2 Inhibition.

Macranthoside B (MB) is a saponin compound extracted from hon-eysuckle that has been reported to exhibit significant medicinal values, particularly anti-tumor activities. This study aimed to evaluate the anticancer efficacy of MB in treating adenocarci-noma of the esophagogastric junction (AEG) and elucidate its underlying mechanisms. Three AEG cell lines and normal gastric epithelial cells were used to assess the an-ticancer activity of MB in vitro. A series of experiments, including RNA sequencing (RNA-seq) analysis, transmission electron microscopy (TEM), immunofluorescence, and western blot assay, were conducted to validate the molecular mechanisms by which MB may mediate these physiological changes. Finally, we used shRNA assays to silence the key gene driving these changes and examined the expression of molecules involved in the affected pathways. MB exhibited significant anti-AEG cell activity with IC50 values ranging from 9.5 to 12.7 μM. RNA-seq results indicated that MB treatment in AEG cells significantly altered mRNA levels of autophagy- and ferroptosis-related genes. Further experiments revealed that MB treatment led to the up-regulation of lipid reactive oxygen species (Lip-ROS), oxidative stress-related pathway genes, and LC3B-labeled autophagic vesicles in AEG cells. Moreover, MB mediated NCOA4-dependent ferritinophagy, disrupting iron homeostasis and causing subsequent ferroptosis. We further confirmed that the intrinsic connection between autophagy and ferroptosis was due to the inhibition of NRF2 by MB. The inhibition of NRF2 by MB triggered transcriptional repression of its downstream effector molecules HERC2 and VAMP8, thus stabilizing NCOA4. This study demonstrated MB to inhibit AEG cell growth by regulating iron ho-meostasis and inducing ferroptosis through the inhibition of NRF2, providing a basis for the development of novel drugs for AEG treatment.

Minimum resection length to ensure a pathologically negative distal margin and a larger remnant stomach for esophagogastric junction cancer.

Ensuring a pathologically negative distal margin (DM) and preserving a larger remnant stomach is important for proximal gastrectomy (PG) in patients with esophagogastric junction (EGJ) cancer. However, the minimum DM length for ensuring negative margins has not been identified. We enrolled patients undergoing PG or total gastrectomy for EGJ cancer. A parameter ΔDM, representing the pathological extension distally beyond the gross tumor boundary, was evaluated. The maximum ΔDM, which indicates the minimum length ensuring a pathologically negative DM, was determined in all patients. Subgroup analyses were performed according to factors associated with ΔDM > 10mm. The possible incidences of pathologically positive DM based on gross DM length were also calculated. Among 253 eligible patients, the maximum ΔDM was 55mm. Growth and pathological types were significantly associated with ΔDM > 10mm. In subgroup analyses, the maximum ΔDM was 30/20/55mm for the superficial/expansive/infiltrative growth types, and 55/40mm for the differentiated/undifferentiated types. In the infiltrative growth type alone, the maximum ΔDM remained 55/40mm for the differentiated/undifferentiated types. However, even if the gross DM length was reduced to 30mm, the possible incidence of pathologically positive DM only increased to 2.6% in the infiltrative differentiated type. We recommend a minimum DM length of 30/20/55mm for the superficial/expansive/ infiltrative growth types. Specifically in the infiltrative growth type, we alternatively recommend 30/40mm for the differentiated/undifferentiated types, with a mandatory intraoperative frozen section analysis. Mini-abstract This study proposes a distal margin length for safe resection of esophagogastric junction cancer, ensuring pathologically negative margins while preserving a larger remnant stomach, based on growth and pathological types.

Study on the metastatic mechanism of LINC00115 in adenocarcinoma of the Esophagogastric junction.

Adenocarcinoma of the esophagogastric junction (AEG) is a common and deadly cancer, and an in-depth investigation of its molecular mechanisms of metastasis is crucial for discovering new therapeutic targets. This study explores the role of the long non-coding RNA (lncRNA) LINC00115 in AEG metastasis and its underlying mechanisms. Through the analysis of 108 pairs of AEG cancer tissues and matched adjacent tissues, we found a significant upregulation of LINC00115 in AEG tissues, closely associated with TNM staging and lymph node metastasis. Utilizing cell counting kit-8 (CCK-8) assays, colony formation experiments, wound healing assays, flow cytometry for apoptosis and cell cycle analysis, and Transwell assays, we have confirmed that LINC00115 significantly promotes proliferation, migration, and invasion of AEG cells in vitro. Animal experiments further validate the role of LINC00115 in promoting tumor growth and metastasis in vivo. Additionally, our nuclear-cytoplasmic fractionation experiments and RNA fluorescence in situ hybridization (FISH) reveal that LINC00115, along with its interacting protein KH-Type splicing regulatory protein (KHSRP), predominantly localizes to the cell nucleus. By conducting RNA pull-down assays and mass spectrometry (MS) analysis, we have identified a direct interaction between LINC00115 and KHSRP protein and further determined their binding sites through catRAPID and ENCORI databases. This study provides evidence of LINC00115 as a novel biomarker and potential therapeutic target for AEG and offers a fresh perspective on understanding the molecular mechanisms of AEG metastasis.

Clinical and functional factors influencing the outcome of laparoscopic Nissen fundoplication.

Laparoscopic Nissen fundoplication (LNF) is the gold standard of antireflux surgery. Up to 30% of patients experience symptoms after surgery, with insufficient information available. The main objective is to evaluate epidemiological, clinical, and functional factors associated with symptoms after LNP. a retrospective case-control study including 79 operated patients (2015-2024). We assessed the relationship between epidemiological data, functional tests, and imaging study results with the occurrence of symptoms after LNF. 24 asymptomatic and 55 symptomatic patients were included. Functional and imaging tests were normal in the majority of asymptomatic patients. IRP-4s (95th percentile) in asymptomatic patients is 20.4 mmHg. Female gender (OR 4, 95%CI; 1.1-14), preoperative dysphagia (OR 8.2, 95%CI: 1.4-47.6), and IRP-4s (OR 1.2, 95%CI: 1-1.3) are independent factors for postoperative dysphagia. Type-III esophagogastric junction morphology on high-resolution manometry (OR 6.1, 95%CI: 2.1-18.1) is independently associated with GERD symptoms. AET showed a trend toward being an independent factor but did not reach statistical significance (OR 1.1, 95%CI:1-1.3). Hiatal hernia in the esophagogram was associated with reintervention (OR 5.5, 95%CI: 1.6-19.1). Asymptomatic patients mostly have normal functional tests after LNF, although IRP-4s normal value (95th percentile) is higher than proposed in the Chicago Classification. Preoperative dysphagia and female gender are independent factors for postoperative dysphagia, which should be considered in the preoperative assessment. Functional and imaging tests are essential in evaluating patients with postoperative symptoms. Dysphagia is associated with higher IRP while GERD symptoms are related to type-III-EGJ on HRM. Similarly, a hiatal hernia on the esophagogram is associated with reintervention.

The Effect of Postoperative Sepsis on 1-Year Mortality and Cancer Recurrence Following Transhiatal Esophagectomy for Esophageal-Gastric Junction Adenocarcinomas: A Retrospective Observational Study.

Transhiatal esophagectomy (THE) is used for specific gastroesophageal junction adenocarcinomas. THE is a high-risk surgical procedure. We aimed to assess the impact of postoperative sepsis (sepsis or septic shock) on the 1-year mortality after THE and to determine the risk factors associated with these outcomes. Secondly, we aimed to assess the impact of postoperative sepsis and other risk factors on 1-year cancer recurrence. A retrospective, observational study was undertaken at the Paoli-Calmettes Institute, Marseille, from January 2012 to March 2022. Of 118 patients, 24.6% (n = 29) presented with postoperative sepsis. Their 1-year mortality was 11% (n = 13), and their 1-year cancer recurrence was 23.7% (n = 28). In the multivariate analysis, independent factors for 1-year mortality were the following: postoperative sepsis (OR: 7.22 (1.11-47); p = 0.038), number of lymph nodes removed (OR: 0. 78 (0.64-0.95); p = 0.011), recurrence at one year (OR: 9.22 (1.66-51.1); p = 0.011), mediastinitis (OR: 17.7 (1.43-220); p = 0.025) and intraoperative driving pressure (OR: 1.77 (1.17-2.68); p = 0.015). For postoperative sepsis, independent factors were low-dose vasopressors (OR: 0.26; 95% CI: 0.07-0.95; p = 0.049), a cervical abscess (OR: 5.33; 95% CI: 1.5-18.9; p = 0.01), bacterial pneumonia (OR: 11.1; 95% CI: 2.99-41.0; p < 0.001) and a high SOFA score on day 1 (OR: 2.65; 95% CI: 1.36-5.19; p = 0.04). For 1-year cancer recurrence, independent factors were the number of lymph nodes removed (sHR: 0.87; 95% CI: 0.79-0.96; p = 0.005), pTNM stages of III or IV (sHR: 8.29; 95% CI: 2.71-25.32; p < 0.001) and postoperative sepsis (sHR: 6.54; 95% CI: 1.70-25.13; p = 0.005). Our study indicates that after THE, postoperative sepsis influences survival and cancer recurrence. We identified the associated risk factors, suggesting an early diagnosis might decrease mortality and recurrence.

A case of esophagogastric junction obstruction due to octopus ingestion

A case of esophagogastric junction obstruction due to octopus ingestion