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BACKGROUND: Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozantinib and pembrolizumab in ICI refractory or resistant mGEA. METHODS: Investigator-initiated, single-arm, single institution, and phase II study in patients with mGEA. Patients had progressed on ICI and/or had PD-L1 CPS score ≤10%. Cabozantinib dose was 40 mg p.o. daily on days 1-21 of a 21-day cycle, with pembrolizumab 200 mg i.v. on day 1. The primary endpoint was progression-free survival at 6 months (PFS-6). RESULTS: Twenty-seven patients were enrolled. Median age 58 years (24-87), female (n = 14), ECOG 0/1 = 13/14, GC/GEJ = 16/11, and non-Hispanic White/Hispanic/Asian = 12/8/7. The primary endpoint was met. After a median follow-up of 31.4 months (range 3.3-42.5), PFS-6 was 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3 months (95% CI 1.7-4.1) and 5.5 months (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). The most common grade (G) treatment-related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension, and muscle cramps (14.8% each). G3-4 TRAE were seen in n = 3 patients (hypertension, thromboembolic event, esophageal perforation; each n = 1). No G5 was observed. CONCLUSIONS: The addition of cabozantinib to pembrolizumab shows clinical benefit in ICI-resistant or refractory mGEA with a tolerable safety profile. (ClinicalTrials.gov Identifier: NCT04164979. IRB Approved: UCI 18-124, University of California Irvine IRB#20195426.).

BACKGROUND: We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC). METHODS: Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported. CONCLUSIONS: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626). CLINICAL TRIAL REGISTRATION: NCT03694522.

BackgroundOur preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib.Patients and methodsThis multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR).ResultsFifty-one patients received ramucirumab and olaparib. The RP2D was olaparib 300 mg twice daily with ramucirumab 8 mg/kg. In evaluable patients at the RP2D the ORR was 6/43 (14%) (95% CI 4.7-25.6). The median progression-free survival (PFS) was 2.8 months (95% CI 2.3-4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7-13.0). Non-statistically significant improvements in PFS and OS were observed for patients with tumours with mutations in HRD genes.ConclusionsOlaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a heavily pre-treated patient population.

Background: Although the optimal extent of lymph node dissection in esophagogastric junction cancer (EGJC) has been reported, the efficacy of mediastinal lymph node dissection remains unclear. We aimed to identify risk factors for mediastinal lymph node metastasis and its prognostic impact in patients with EGJC. Methods: A total of 100 consecutive patients who underwent curative surgery for EGJC were eligible. We examined the rates of metastasis, prognosis, and therapeutic value index at each mediastinal lymph node station. In addition, multivariate analyses were performed to identify risk factors for mediastinal lymph node metastasis. Results: The rates of upper, middle, and lower mediastinal lymph node metastases were 12.0%, 20.7%, and 13.2%, respectively. The 5-year overall survival rate was lower in patients with mediastinal lymph node metastasis than in those without mediastinal lymph node metastasis (11.1% vs. 59.2%, p < 0.01). The therapeutic value index was 0 in patients with upper/middle mediastinal lymph node metastasis, and mediastinal lymph node metastasis was an independent prognostic factor (hazard ratio 6.59, 95% confidence interval [CI] 2.48–17.9, p < 0.01). Additionally, the length of esophageal invasion and the presence of hiatal hernia were independent predictors of mediastinal lymph node metastasis (odds ratio 8.21, 95%CI 1.44–46.8, p = 0.02 and odds ratio 7.13, 95%CI 1.22–41.8, p = 0.03). Conclusion: No survival benefit of mediastinal lymph node dissection was observed. Intensive multidisciplinary treatment could be considered in patients with predicted mediastinal lymph node metastasis, such as those with longer esophageal invasion and those with hiatal hernia. [ABSTRACT FROM AUTHOR]

Background Methods Key Results Conclusion & Inferences Internationally adopted Chicago Classification (CC) criteria based on adult normative data have been used to diagnose children with esophageal motility disorders undergoing high‐resolution esophageal manometry (HREM). The aim of this study was to compare HREM parameters of children without dysphagia and children with dysphagia and normal findings according to CC.HREM metrics of 41 children (13.2 (9–18) years; 20 female) without dysphagia and 41 children (13.7 (8–18) years; 30 female) with dysphagia and normal diagnosis according to CC were compared. Analyzed data included resting and integrated relaxation pressures (IRP) of upper (UES) and lower (LES) esophageal sphincters, esophageal peristaltic contractile integrals, transition zone (TZ) gaps, distal latency (DL), and manometric esophageal length to height ratio (MELH). 95%ile normative cutoffs were calculated from the cohort without dysphagia.Proximal contractile integral (PCI), UES and LES mean resting and IRP were not significantly different between the cohorts (p > 0.3). On the contrary, distal contractile integral (DCI), TZ gap and MELH were notably different with p = 0.0002, p = 0.027, and p = 0.033 respectively. According to 95%ile normative cutoffs of DCI, TZ gap and MELH, in cohort with dysphagia 27%, 15%, and 22% of patients respectively were not normal.First study ever to compare HREM parameters of children without dysphagia to children with dysphagia. Considerable proportion of children with dysphagia may be underdiagnosed according to the adult criteria. This emphasizes the need for universally accepted child‐specific diagnostic protocols and norms. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer treatment, yet patient responses vary, highlighting the need for effective biomarkers. Common markers, such as programmed cell death ligand-1 (PD-L1), microsatellite instability/mismatch repair (MSI/MMR), tumor mutational burden, tumor-infiltrating lymphocytes, and Epstein–Barr virus, face sampling challenges and high costs. This study seeks practical, minimally invasive biomarkers to enhance patient selection and improve outcomes. Methods: This multicenter retrospective study analyzed 617 patients with advanced gastric or gastroesophageal junction cancer treated with programmed cell death protein-1 (PD-1)/PD-L1 inhibitors from January 2019 to March 2023. Clinical data and peripheral blood marker data were collected before and after treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Least absolute shrinkage and selection operator (LASSO)-Cox and LASSO logistic regression analyses identified independent factors for OS, PFS, and ORR. Predictive nomograms were validated using receiver operating characteristic (ROC) curves, areas under the curve (AUCs), C-indices, and calibration curves, with clinical utility assessed via decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: OS-related factors included treatment line, T stage, ascites, pretreatment indirect bilirubin (pre-IBIL), posttreatment CA125, CA199, CA724, and the PLR. PFS-related factors included treatment lines, T stage, metastatic sites, pre-IBIL, posttreatment globulin (GLOB), CA125, and CA199 changes. ORR-related factors included treatment line, T stage, N stage, liver metastasis, pretreatment red cell distribution width-to-platelet ratio (RPR), CA125, and CA724 changes. The nomograms showed strong predictive performance and clinical utility. Conclusions: Early treatment, lower T stage, the absence of ascites, and lower pre-IBIL, post-CA125, CA199, CA724, and PLR correlate with better OS. Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance. [ABSTRACT FROM AUTHOR]

Objectives: The endoscopic pressure study integrated system (EPSIS) represents an innovative approach for evaluating lower esophageal sphincter function by monitoring intragastric pressure using diagnostic gastroscopes. This study aimed to assess the feasibility and validity of employing ultrathin gastroscopes for EPSIS. Methods: A retrospective analysis was conducted on a database of consecutive patients who underwent EPSIS using both ultrathin and regular gastroscopes between September 2021 and October 2023. The study compared EPSIS parameters between the two gastroscope types to evaluate the correlation of key metrics. Results: Thirty patients underwent EPSIS with both ultrathin and regular gastroscopes. Significant positive correlations were observed in the pressure waveform: maximum intragastric pressure (mmHg) (ρ = 0.82, P < 0.001) and intragastric pressure gradient (mmHg/s) (ρ = 0.80, P < 0.001) when comparing the two gastroscopes. Maximum intragastric pressure (15.5 [5.3–20.3] vs. 18.5 [3.4–21.6], P < 0.001) and pressure gradient (0.16 [0.013–0.41] vs. 0.24 [0.0039–1.13], P < 0.001), (median [range]) were significantly lower with ultrathin gastroscopes. Conclusions: This study establishes that EPSIS parameters obtained with an ultrathin gastroscope exhibit a significant correlation with those obtained using a regular gastroscope, with each EPSIS parameter consistently lower. These findings support the viability of EPSIS for ultrathin gastroscopy and highlight its potential as a diagnostic tool for assessing lower esophageal sphincter function. [ABSTRACT FROM AUTHOR]

Aims: Nivolumab is approved as adjuvant treatment in subjects with resected oesophageal or gastroesophageal junction cancer (EC/GEJC) based on results from the pivotal CheckMate 577 trial. We present a model‐based clinical pharmacology profiling and benefit–risk assessment of nivolumab as adjuvant treatment in subjects with resected EC/GEJC supporting a less frequent dosing regimen. Methods: Population pharmacokinetic (popPK) analysis was conducted to characterize nivolumab pharmacokinetics (PK) using clinical data from 1493 subjects from seven monotherapy clinical studies across multiple solid tumours. The exposure‐response (E‐R) analyses included data from 756 patients from CheckMate 577. E‐R relationships for efficacy and safety were characterized by evaluating the relationship between nivolumab exposure and disease‐free survival (DFS) for efficacy; and time to first occurrence of Grade ≥2 immune‐mediated adverse events (Gr2 + IMAEs) for safety. Results: Nivolumab exposure was found to be associated with both DFS and risk of Gr2 + IMAEs. However, the hazard ratios (HRs) (95% confidence interval [CI]) at the 5th and 95th percentiles of nivolumab exposure were similar for DFS and Gr2 + IMAEs, indicating flat E‐R relationships within the exposure range produced by the studied regimen. Model‐predicted probability of DFS and Gr2 + IMAEs were similar between the two regimens of 240 mg every 2 weeks or 480 mg every 4 weeks for 16 weeks followed by 480 mg Q4W up to 1 year. Conclusions: The analyses demonstrated a flat E‐R relationship over the range of exposures produced by the studied regimen and supported the approval of an alternative dosing regimen with less frequent dosing in patients with adjuvant EC/GEJC. [ABSTRACT FROM AUTHOR]

Background Aims/Methods Results Conclusions Gastro‐esophageal reflux disease (GERD) is the most common cause for noncardiac chest pain (NCCP), with an estimated prevalence rate ranging between 30% and 60%. Heartburn and NCCP may share common mechanisms.To assess whether particular patterns of impedance‐pH variables characterize patients with dominant heartburn, regurgitation, or NCCP and their ability to predict proton pump inhibitor (PPI) response for each symptom, GERD patients, evaluated with high‐resolution manometry (HRM) and impedance‐pH, were included.In total, 109 NCCP, 68 heartburn, and 64 regurgitation patients were included. Pathological reflux episodes were observed in 28%, 19%, and 56% (p < 0.001). Pathological mean nocturnal baseline impedance (MNBI) values were observed in 55%, 53%, and 34% (p < 0.05). Hypomotility was more frequent in NCCP compared to heartburn patients (p < 0.05). When comparing NCCP with heartburn, hypomotility was associated with NCCP perception (OR: 2.34, 95% CI: 1.23–4.43; p < 0.01). When comparing NCCP with regurgitation, >80 refluxes and type 2/3 esophagogastric junction (EGJ) were associated with regurgitation perception (OR: 0.31, 95% CI: 0.16–0.59; p < 0.001, and OR: 0.5, 95% CI: 0.27–0.93; p < 0.05), while pathological MNBI was associated with NCCP perception (OR: 2.34, 95% CI: 1.23–4.43; p < 0.01). 45.5% NCCP patients, 45.6% with heartburn, and 36% with regurgitation responded to PPIs (p < 0.05). At multivariate analysis, pathological MNBI or PSPW index were associated with PPI responsiveness in patients with NCCP or heartburn, while in patients with regurgitation, pathological MNBI was associated with PPI responsiveness and a reflux number >80 to PPI refractoriness.We highlight the usefulness of an accurate clinical and functional evaluation of GERD patients, allowing to discriminate particular characteristics in patients with dominant heartburn, NCCP, or regurgitation, which may benefit of distinct therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited. Methods: ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur–gimeracil–oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints—centrally assessed progression-free survival (PFS) and overall survival (OS)—and landmark analyses of OS among patients alive using 3-year follow-up data. Results: At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55–0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75–1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy. Conclusion: This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer. Trial registration: NCT02746796 [ABSTRACT FROM AUTHOR]

Background: Surgical bariatric interventions, while highly effective, can be associated with post‐operative esophageal symptoms, gastroesophageal reflux disease and esophageal dysmotility. Whether pre‐operative physiology impacts this risk is unknown, in part because expected values on esophageal manometry in patients with obesity are not well understood. This study seeks to establish normative values on esophageal high resolution manometry (HRM) and the prevalence of esophageal dysmotility in the asymptomatic patient with obesity. Methods: This retrospective study included adult patients with body mass index (BMI) ≥35 kg m−2 without esophageal symptoms undergoing preoperative bariatric surgical evaluation, including HRM, at a single tertiary care center between February, 2019 and February, 2020. Results: Of 104 asymptomatic patients with obesity, HRM identified normal esophageal motility in 94 (90.4%) with the remaining 10 having ineffective esophageal motility (3.8%), manometric esophagogastric junction outflow obstruction (3.8%), distal esophageal spasm (1.0%), and hypercontractile esophagus (1.0%). Mean of median lower esophageal sphincter integrated relaxation pressure (LES IRP) was 10.6 mmHg supine (95th percentile 21.5 mmHg) and 8.5 mmHg upright (95th percentile 21.3 mmHg). 86% of patients had intragastric pressure above 8 mmHg. Mean of mean distal contractile integral (DCI) was 2261.6 mmHg cm s−1 (95th percentile 5889.5 mmHg cm s−1). Conclusion: The vast majority of asymptomatic patients with obesity had normal manometry. LES IRP and DCI were higher than that observed in non‐obese cohorts. Additionally, BMI correlated to increased intragastric pressure. These data suggest that normative values in patients with obesity should be adjusted to prevent overdiagnosis of EGJOO or hypercontractile esophagus. [ABSTRACT FROM AUTHOR]

Background: Functional lumen imaging probe (FLIP) panometry assesses esophageal motility in response to controlled volumetric distension. This study aimed to describe the physiomechanical states of the lower esophageal sphincter (LES) in response to serial filling/emptying regimes for esophageal motility disorders. Methods: Fourty‐five patients with absent contractile response on FLIP and diagnoses of normal motility (n = 6), ineffective esophageal motility (IEM; n = 8), scleroderma (SSc; n = 10), or nonspastic achalasia (n = 21) were included, as were 20 patient controls with normal motility on FLIP and manometry. LES diameter and pressure were measured after stepwise FLIP filling at 60 mL, 70 mL, and emptying to 60 mL with relative changes used to define physiomechanical states. Key Results: Passive dilatation after FLIP filling occurred in 63/65 (97%) patients among all diagnoses. After FLIP emptying, passive shortening occurred in 12/14 (86%) normal motility/IEM, 10/10 (100%) SSc, 9/21(43%) achalasia, and 16/20 (80%) controls, with auxotonic relaxation seen in 2/14 (14%) normal motility/IEM, 12/21 (57%) achalasia, and 4/20 (20%) controls. After achalasia treatment (LES myotomy), 21/21 (100%) achalasia had passive shortening after FLIP emptying. Conclusions & Inferences: Physiomechanical states of the LES can be determined via response to FLIP filling and emptying regimes. While passive shortening was the general response to FLIP emptying, auxotonic relaxation was observed in achalasia, which was disrupted by LES myotomy. Further investigation is warranted into the clinical impact on diagnosis and treatment of esophageal motility disorders. [ABSTRACT FROM AUTHOR]

Background: Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER), VEGFR-2, KIT, and MET. SAFFRON-104 (NCT03941873) was a multicohort phase Ib/II study investigating sitravatinib with/without tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody, in patients with advanced hepatocellular carcinoma (HCC) or gastric cancer/gastroesophageal junction cancer (GC/GEJC). Methods: Eligible patients had histologically/cytologically confirmed advanced HCC or GC/GEJC. Phase I determined the recommended phase II dose (RP2D) of sitravatinib with/without tislelizumab. Phase II evaluated sitravatinib monotherapy in patients with pretreated HCC, and sitravatinib plus tislelizumab in anti-PD-(L)1–naïve or –treated HCC and anti-PD-(L)1–naïve GC/GEJC. Primary endpoints were safety/tolerability (phase I) and objective response rate (ORR) (phase II). Results: At data cutoff (March 31, 2023), 111 patients were enrolled; 102 were efficacy-evaluable (median study follow-up 9.1 months [range: 0.7–36.9]). The RP2D of sitravatinib was determined as 120 mg orally once daily. In patients receiving sitravatinib monotherapy and sitravatinib in combination with tislelizumab, grade ≥ 3 treatment-related adverse events occurred in 14 (51.9%) and 42 (50.0%) patients, respectively. The ORR was 25% (95% confidence interval [CI]: 8.7–49.1) in patients with pretreated HCC receiving sitravatinib monotherapy. In patients receiving sitravatinib with tislelizumab, the ORR was 11.5% (95% CI 2.4–30.2) with anti-PD-(L)1–naïve HCC, 9.5% (95% CI 1.2–30.4) with anti-PD-(L)1–treated HCC, and 16.1% (95% CI 5.5–33.7) in patients with anti-PD-(L)1–naïve GC/GEJC. Conclusions: Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric tumors in dogs, although uncommon, present considerable diagnostic and treatment challenges, often diagnosed late in the disease course, resulting in poor prognosis. Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) and positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) offer promising approaches in human medicine for intraoperative tumor detection and metastasis assessment. This case report presents a novel application of ICG-guided surgery and 18F-FDG PET/CT in a canine gastric tumor. A 13-year-old Maltese dog with an abdominal mass underwent 18F-FDG PET/computed tomography (CT) for tumor localization and metastatic evaluation. PET/CT scans revealed a gastric mass near the esophagogastric junction and demonstrated mean and maximum standardized uptake values (SUVs) of 4.596 and 6.234, respectively, for the abdominal mass. Subsequent surgery incorporated ICG for NIR fluorescence-guided imaging, aiding in precise tumor localization and margin assessment. The excised mass was identified as a low-grade leiomyosarcoma on histopathology. The dog underwent PET/CT imaging six months postoperatively following the excision of the mass, which confirmed the absence of recurrence or residual lesions during follow-up. NIR fluorescence imaging using ICG demonstrated efficacy in real-time tumor visualization and margin assessment, a technique not previously reported in veterinary literature. The PET/CT findings complemented the diagnosis and provided valuable insights into metastasis. The absence of recurrence or complications in postoperative follow-up underscores the potential of these imaging modalities in enhancing surgical precision and improving prognosis in canine gastric tumors. [ABSTRACT FROM AUTHOR]

Background: Achalasia is characterized as an esophageal motility disorder with incomplete relaxation of the lower esophageal sphincter. Achalasia can be associated with abnormal peristalsis and symptoms of dysphagia, acid reflux, and chest pain. The exact pathophysiology of achalasia remains unclear, but it is hypothesized to be due to degeneration of the myenteric plexus. Case presentation: In this case, a 46-year-old Hispanic man presented to the emergency room with a 12-year history of progressive discomfort with swallowing solids and liquids. Due to many years of incomplete follow-up care and lack of understanding of the course of his disease, this patient's symptoms escalated to complete intolerance of oral intake and significant weight loss. He was diagnosed with achalasia during his hospital stay and treated successfully with laparoscopic Heller myotomy. Conclusions: This case discussion illustrates the importance of follow-up care and patient education so that diagnosis and treatment of achalasia are not delayed. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to analyze the independent risk factors for intraoperative bleeding in Siewert II adenocarcinoma of the esophagogastric junction (AEG) using two minimally invasive surgical approaches, namely, the laparoscopy-assisted abdominal trans-hiatal (LTH) method and transthoraciclaparoscopic esophagectomy (TLE). Methods: The clinical data of 100 patients with SiewertII AEG admitted to our hospital from October 2017 to October 2020 were retrospectively analyzed. According to the type of surgery, the patients were divided into LTH approach group and TLE approach group. The differences between the clinical characteristics of the patients in different groups and the differences in the intraoperative bleeding and prognosis between different surgical procedures were analyzed and compared using the t-test and chi-squared test. Multiple linear regression was used to identify the independent risk factors affecting the amount of intraoperative bleeding in patients. Results: The results of this study showed that patients in the LTH group had significantly less intraoperative bleeding and operative time and significantly better postoperative recovery than the TLE group. The results of multivariate linear regression showed that the combined trans-thoracic-abdominal approach (P=0.000), advanced age (P=0.014), larger BMI (P=0.000), and larger tumor diameter (P=0.001) were the independent risk factors influencing the increase in intraoperative bleeding. Conclusion: In addition to the conventional factors that affect intraoperative bleeding, such as the patient's general condition, operation time, and tumor size, LTH surgery is another way to avoid intraoperative bleeding for Siewert type II AEG patients and can significantly improve postoperative recovery. [ABSTRACT FROM AUTHOR]

Background/Aims Chicago classification version 4.0 enhances the diagnosis of esophageal motility disorders using position change and provocative tests such as multiple rapid swallows and a rapid drink challenge. This study investigates the diagnostic role of the rapid drink challenge based on Chicago classification 4.0 using a functional luminal imaging probe to estimate the cutoff value. Methods This study included 570 patients who underwent esophageal manometry with a rapid drink challenge between January 2019 and October 2022. The diagnostic flow was analyzed according to Chicago classification 4.0. Results Ninety-nine patients (38, achalasia; 11, esophagogastric junction outflow obstruction; 7, ineffective esophageal motility; 1, hypercontractile esophagus; and 42, normal esophageal function) failed the rapid drink challenge. Among the 453 participants, 50 and 86 were diagnosed with achalasia and esophagogastric junction outflow obstruction, respectively, using Chicago classification 4.0. In 249/453 (55.0%) patients initially diagnosed with esophagogastric junction outflow obstruction using Chicago classification 3.0, the diagnosis was changed to achalasia (n = 28), hypercontractile esophagus (n = 7), ineffective esophageal motility (n = 7), or normal esophageal function (n = 121) using Chicago classification 4.0. Rapid drink challenge-integrated relaxation pressure’s diagnostic cutoff value was 19 mmHg. Nine patients had diagnoses changed after the rapid drink challenge, including 3 with panesophageal pressurization. Conclusions Chicago classification 4.0 increased the diagnostic yield of the rapid drink challenge by 2.0% (9/453 patients). However, the rapid drink challenge had a failure rate of 17.9% (99/552 patients). Given the relatively low diagnostic yield and high failure rate of the rapid drink challenge, we recommend adopting an individualized approach to manometry [ABSTRACT FROM AUTHOR]

Background/Aims Activation of the cold receptor, transient receptor potential melastatin 8 (TRPM8) by menthol inhibits esophageal secondary peristalsis in healthy adults. Ineffective esophageal motility (IEM) is common. This study is to evaluate the effects of acute infusion of menthol on esophageal peristalsis in patients with IEM. Methods Twenty patients with IEM (males 11, mean age 36) were studied for esophageal peristalsis using high-resolution manometry. All participant had primary peristalsis performed with 10 water swallows and secondary peristalsis generated with 10 rapid air injections of 20 mL via mid-esophageal infusion port. Two different sessions by randomly performing acute administration of placebo or menthol (3 mM) were used for testing their effects on esophageal peristalsis. Results Menthol infusion had no effects on distal contractile integral (P = 0.471), distal latency (P = 0.58), or complete peristalsis (P = 0.251). Menthol infusion did not change basal lower esophageal sphincter pressure (P = 0.321), esophagogastric junction contractile integral (P = 0.758), or integrated relaxation pressure (P = 0.375) of primary peristalsis, but reduced upper esophageal sphincter pressure (P = 0.037). Infusion of menthol significantly reduced the frequency of secondary peristalsis for air injects of 20 mL (P = 0.002), but did not affect distal contractile integral of secondary peristalsis for air injections of 20 mL. Conclusion This work has suggested that activation of TRPM8 by menthol can attenuate mechanosensitivity of secondary peristalsis in response to rapid air distension regardless of the presence of IEM. [ABSTRACT FROM AUTHOR]

Background/Aims Pharyngeal pump, esophageal peristalsis, and phrenic ampulla emptying play important roles in the propulsion of bolus from the mouth to the stomach. There is limited information available on the mechanism of normal and abnormal phrenic ampulla emptying. The goal of our study is to describe the relationship between bolus flow and esophageal pressure profiles during the phrenic ampulla emptying in normal subjects and patient with phrenic ampulla dysfunction. Methods Pressure (using topography) and bolus flow (using changes in impedance) relationship through the esophagus and phrenic ampulla were determined in 15 normal subjects and 15 patients with retrograde escape of bolus from the phrenic ampulla into esophagus during primary peristalsis. Results During the phrenic ampulla phase, 2 high pressure peaks (proximal, related to lower esophageal sphincter and distal, related to crural diaphragm) were observed in normal subjects and patients during the phrenic ampulla emptying phase. The proximal was always higher than the distal one in normal subjects; in contrast, reverse was the case in patients with the retrograde escape of bolus from the phrenic ampulla into the esophagus. Conclusions We propose that a strong after-contraction of the lower esophageal sphincter plays an important role in the normal phrenic ampullary emptying. A defective lower esophageal after-contraction, along with high crural diaphragm pressure are responsible for the phrenic ampulla emptying dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to identify the temporal and spatial parameters of videofluoroscopic swallowing study (VFSS) that could predict the recovery of swallowing function in subacute stroke patients. Methods: We included 102 patients who were admitted to the Department of Rehabilitation Medicine between 2019 and 2022. Patients were classified into good and poor prognosis groups according to whether they had restored prestroke swallowing function or were able to consume sufficient nutrition via oral feeding to meet their body's needs. Univariate and multivariate regression analyses were used to identify the predictors. Calibration and discrimination were tested using the Hosmer–Lemeshow test and area under the curve (AUC), respectively. Results: Of the 102 included patients, 51 had a good prognosis for swallowing function within 6 months of onset. The final multivariate regression model included three significant factors: laryngeal closure duration (LCD) (OR: 0.998; 95% CI: 0.996–0.999; p < 0.05), maximum width of the upper esophageal sphincter opening (MWUESO) (OR: 1.251; 95% CI: 1.073–1.458; p < 0.05), and pharyngeal residual grade (PRG) (p < 0.05). The shorter LCD and larger MWUESO were positive predictors of good swallowing function outcomes, while higher PRG was a negative predictor of good outcomes. The AUC for PRG, MWUESO, and LCD were 0.767 (p < 0.05), 0.738 (p < 0.05), and 0.681 (p < 0.05), respectively. Conclusion: Identifying prognostic factors for the recovery of swallowing function in patients with poststroke dysphagia is essential for developing treatment strategies. The findings of this study may provide an important reference for developing appropriate therapeutic interventions to promote the recovery of swallowing function in stroke patients. [ABSTRACT FROM AUTHOR]

Background: The herbal preparation, STW5‐II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5‐II on esophago‐gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut–brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. Methods: STW5‐II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double‐blind, randomized fashion, on two separate occasions, separated by 3–7 days, to evaluate effects on (i) esophago‐gastric junction pressures following a standardized meal using solid‐state high‐resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high‐resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). Key Results: STW5‐II increased maximum intrabag volume (ml; STW5‐II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago‐gastric junction, pyloric, or duodenal pressures. Conclusions & Inferences: STW5‐II has marked region‐specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia. [ABSTRACT FROM AUTHOR]

Objectives: Esophageal high-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders, but it may be poorly tolerated and unsuccessful. We sought to evaluate a protocol for sedation and endoscopy-assisted (SEA) HRM in patients who previously failed standard HRM and assess patient perspectives towards it. Methods: Adult patients who previously failed HRM were prospectively enrolled. Under propofol sedation, an upper endoscopy was performed during which the HRM catheter was advanced under endoscopic visualization. If the catheter did not reach the stomach on its own, the endoscope itself or a snare was used to help it traverse the esophagogastric junction (EGJ). Results: Thirty patients participated (mean age 67.8, 70% female). The technical success of SEA-HRM was 100%. Twenty-two (73.3%) were diagnosed with a motility disorder including thirteen (43.3%) with achalasia. Eighteen (60%) had previously failed HRM due to discomfort/intolerance, while twelve (40%) failed due to catheter coiling in the esophagus. Subjects in the coiling group were more likely to need endoscopic assistance to traverse the EGJ (91.7% vs. 27.7%, p = 0.001) and have a motility disorder (100.0% vs. 55.6%, p = 0.010), including achalasia (75.0% vs. 22.2%, p = 0.004), compared to the discomfort/intolerance group. All patients preferred SEA-HRM and rated it higher than standard HRM (9.5 ± 1.3 vs. 1.9 ± 2.1, p = <0.001, on a scale of 1–10). Conclusions: SEA-HRM is a highly successful and well-tolerated option in patients who previously failed standard HRM. This should be the recommended approach in cases of failed HRM rather than secondary tests of esophageal motility. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Peroral endoscopic myotomy (POEM) may result in a distended distal esophagus, referred to as a blownout myotomy (BOM), the relevance of which is uncertain. The aim of this study was to investigate the prevalence, risk factors, and associated symptoms of BOM after achalasia treatment. METHODS: A data set of the locally treated patients in a randomized controlled trial comparing POEM with pneumatic dilation (PD) was analyzed. A BOM is defined as a >50% increase in esophageal diameter at its widest point in the distal esophagus between the lower esophageal sphincter and 5 cm above. RESULTS: Seventy-four patients were treated in our center, and 5-year follow-up data were available in 55 patients (32 patients [58%] randomized to POEM, 23 [42%] PD). In the group initially treated with POEM, the incidence of BOMincreased from 11.5%(4/38) at 3 months, to 21.1% (8/38) at 1 year, 27.8% (10/36) at 2 years, and 31.3%(10/32) at 5 years. None of the patients treated with PD alone developed a BOM. Patients who developed a BOM had a higher total Eckardt score and Eckardt regurgitation component compared with patients who underwent POEM without BOM development (3 [2.75-3.25] vs 2 [1.75-3], P 5 0.032, and 1 [0.75-1] vs 0 [0-1], P 5 0.041). POEM patients with a BOM more often report reflux symptoms (85% [11/13] vs 46% [2/16], P 50.023) and had a higher acid exposure time (24.5% [8-47] vs 6% [1.2-18.7], P 5 0.027). DISCUSSION: Thirty percent of the patients treated with POEM develop a BOM, which is associated with a higher acid exposure, more reflux symptoms, and symptoms of regurgitation. [ABSTRACT FROM AUTHOR]

High-resolution esophageal manometry [HRM] has become the gold standard for the evaluation of esophageal motility disorders. It is unclear whether there are HRM differences in diagnostic outcome based on regional or geographic distribution. The diagnostic outcome of HRM in a diverse geographical population of Mexico was compared and determined if there is variability in diagnostic results among referral centers. Consecutive patients referred for HRM during 2016–2020 were included. Four major referral centers in Mexico participated in the study: northeastern, southeastern, and central (Mexico City, two centers). All studies were interpreted by experienced investigators using Chicago Classification 3 and the same technology. A total of 2293 consecutive patients were included. More abnormal studies were found in the center (61.3%) versus south (45.8%) or north (45.2%) P  < 0.001. Higher prevalence of achalasia was noted in the south (21.5%) versus center (12.4%) versus north (9.5%) P  < 0.001. Hypercontractile disorders were more common in the north (11.0%) versus the south (5.2%) or the center (3.6%) P.001. A higher frequency of weak peristalsis occurred in the center (76.8%) versus the north (74.2%) or the south (69.2%) P  < 0.033. Gastroesophageal junction obstruction was diagnosed in (7.2%) in the center versus the (5.3%) in the north and (4.2%) in the south p.141 (ns). This is the first study to address the diagnostic outcome of HRM in diverse geographical regions of Mexico. We identified several significant diagnostic differences across geographical centers. Our study provides the basis for further analysis of the causes contributing to these differences. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ. Methods: Patients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified. Results: One hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors. Conclusions: Histologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study. [ABSTRACT FROM AUTHOR]

Background Purpose Dysphagia is one of the most common complaints that gastroenterologists encounter in the outpatient setting. To evaluate this common complaint, patients are often sent for a barium esophagram, a test that is widely available, inexpensive, and easy to perform. This simple test provides a reliable method to evaluate esophageal anatomy and structural abnormalities.This narrative reviews the history of the development and validation of the timed‐barium esophagram (TBE), along with its strengths and limitations, and discusses its use in the pre‐ and posttreatment assessment of patients with achalasia, esophagogastric junction outflow obstruction (EGJOO), and esophageal strictures. Providing excellent anatomic detail of the esophagus and an accurate assessment of esophageal emptying, over time, the TBE has become part of the standard workup in our Swallowing Center for patients with dysphagia. [ABSTRACT FROM AUTHOR]

Introduction: Vogt-Koyanagi-Harada (VKH) disease is a multisystem syndrome characterized by uveitis and exudative retinal detachments in the absence of ocular trauma or surgery. Neurological and cutaneous manifestations can also occur. Prior case reports have associated immune checkpoint inhibitors with a VKH-like disease. Case Presentation: A 64-year-old woman presented with 3 months of epigastric pain, and subsequent endoscopy showed a large mass in the gastroesophageal junction. Staging imaging showed an FDG-avid para-aortic node, making the disease stage IV, and she was treated with systemic therapy with FOLFOX. Molecular profiling showed HER2 amplification and PDL1 positivity, so trastuzumab and pembrolizumab were added. PET and esophagogastroduodenoscopy with biopsies showed a complete radiologic and pathologic response to treatment. Chemotherapy was stopped, and she continued on trastuzumab and pembrolizumab maintenance. After about 18 months of treatment with pembrolizumab, she presented with painful blurry vision in both eyes. Ophthalmologic evaluation showed panuveitis, serous retinal detachment, bilateral uveal edema, and secondary angle closure, consistent with VKH-like uveitis. She was treated with local and systemic corticosteroids. Pembrolizumab was assessed as the most likely causative agent and was discontinued. Her ophthalmologic exam improved, and her visual acuity returned to baseline. She continues on trastuzumab maintenance, and most recent imaging shows no evidence of disease. Conclusion: Oncologists should be aware of VKH-like disease as a possible immune-related adverse event and seek urgent ophthalmologic consultation when such symptoms arise. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion The gastroesophageal junction (GEJ) consists of various anatomical components that together form a barrier to prevent reflux of gastric content. This study introduces a novel phase concept to dynamically evaluate the antireflux barrier (ARB) during endoscopy and analyzes its functionality.We reviewed previously the recorded endoscopic videos of subjects who underwent the endoscopic pressure study integrated system (EPSIS) from February to April 2024 for indications other than gastroesophageal reflux disease symptoms. This device was used as an auxiliary tool to measure intragastric pressure (IGP) during endoscopy with a retroflex view. The ARB dynamic was divided into three phases: Phase I (gastric phase), Phase II (lower esophageal sphincter phase), and Phase III (esophageal clearance phase). We evaluated the morphological changes in the ARB during insufflation using EPSIS.The median age of the 30 subjects was 58 years (interquartile range [IQR] 46.5–68.8), including 20 men and 10 women. Endoscopic findings and IGPs were recorded during the three phases. In Phase I, at low IGP (median 6.75 mmHg), the gastroesophageal flap valve and longitudinal folds were observed in 80% of cases. In Phase II, at moderate IGP (median 11.8 mmHg), the scope holding sign was observed in 86.7%. In Phase III, at high IGP (median 19 mmHg) inducing belching, peristalsis was observed in 80% of cases with median recovery time of 5 s.The phase concept provides a valuable framework for understanding the antireflux mechanism. Further research is needed to validate these findings in GEJ disorders and explore correlations with other modalities. [ABSTRACT FROM AUTHOR]

Background: The Chinese Society of Clinical Oncology (CSCO) has recommended sintilimab plus chemotherapy (SINT + Chemo) as a standard first-line therapy for advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), based on the proven effectiveness and safety in the ORINT-16 trail. Its cost-effectiveness, however, remains to be evaluated. Methods: We established a partitioned survival approach (PartSA) model with a 10-year time horizon to determine whether SINT + Chemo (vs. chemotherapy) was more cost-effective as a first-line treatment for unresectable advanced or metastatic GC/GEJC. Survival data was generated from the ORIENT-16 trail. Cost calculation was limited to direct medical costs. Database of Hunan Public Resources Trading Service Platform was used as the source for obtaining drug prices. Other cost and utility values were gathered from established literature. Incremental cost-effectiveness ratio (ICER) was the primary output. Additionally, we conducted sensitivity analysis, subgroup analysis, and scenario analysis. Results: In the base-case analysis, group SINT + Chemo showed an increase in utility value by 0.32 quality-adjusted life-years (QALYs) at an extra cost of $7988.43, resulting in an ICER of $25239.29/QALY, below the Chinese cost-effective willingness-to-pay (WTP) threshold of $38223.34. Upon further subgroup analysis according to patients' programmed death 1 ligand (PD-L1) combined positive score (CPS), the ICERs were $26341.01/QALY for patients highly expressing PD-L1 (CPS ≥5) and $17658.26/QALY for patients lowly expressing PD-L1 (CPS <5). Based on the sensitivity analysis, we found the PFS utility was the parameter that had the most significant impact on the model's outcomes. Moreover, in scenario analysis, the results remained consistent despite variations in the model's time frame. Conclusion: In China, SINT + Chemo is a more cost-effective option (vs. chemotherapy) as a first-line therapy for unresectable advanced or metastatic GC/GEJC, irrespective of PD-L1 expression levels. [ABSTRACT FROM AUTHOR]

Purpose: The differences in tumor behavior between adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagogastric junction (EGJ) have yet to be well investigated. The purpose of this study was to gain insights that can contribute to tailored treatments and follow-up strategies by analyzing the correlation between histological subtypes and oncological outcomes. Methods: A retrospective analysis was used to determine the characteristics of the histological subtypes of EGJ cancer by comparing the appearance of postoperative recurrence. A total of 102 consecutive patients with pathological stage IIA to IVA EGJ cancer, who underwent R0 surgery in our department from 2004 to 2020, were enrolled. The recurrence pattern, timing, survival, and potential prognostic factors were compared. Results: After a median follow-up time of 70.1 months, the AC group demonstrated comparable lymph node failure-free survival (P = 0.291) and significantly worse non-lymphogenous recurrence-free survival (P = 0.035) than did the SCC group. A significantly longer period from surgery to recurrence was also observed in the AC group (P = 0.029). Multivariate analysis indicated that histological subtype (P = 0.015, 95% CI 1.24–7.28) was significantly correlated with the incidence of non-lymphogenous recurrence. Conclusions: The pattern and timing of postoperative recurrence were significantly different between the histological subtypes of EGJ cancer. Compared with EGJ SCC, EGJ AC may have a greater tendency toward non-lymphogenous progression and a greater propensity for longer surgery-to-recurrence periods. [ABSTRACT FROM AUTHOR]

Achalasia is a rare and complex esophageal disease of unknown etiology characterized by difficulty in swallowing due to the lack of opening of the lower esophageal sphincter and the absence of esophageal peristalsis. Recent advancements in technology for analyzing DNA, RNA and biomolecules in high-throughput techniques are offering new opportunities to better understand the etiology and the pathogenetic mechanisms underlying achalasia. Through this narrative review of the scientific literature, we aim to provide a comprehensive assessment of the state-of-the-art knowledge on omics of achalasia, with particular attention to those considered relevant to the pathogenesis of the disease. The notion and importance of the multi-omics approach, its limitations and future directions are also introduced, and it is highlighted how the integration of single omics data will lead to new insights into the development of achalasia and offer clinical tools which will allow early diagnosis and better patient management. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the short-term clinical efficacy of modified Kamikawa anastomosis and double tract anastomosis after laparoscopic proximal gastrectomy. Methods: A retrospective analysis was carried out by collecting the clinical and pathological data of 42 patients who underwent laparoscopic proximal gastrectomy after admission in our centre from May 2020 to October 2022. Among the 42 enrolled patients, 22 underwent modified Kamikawa anastomosis (modified Kamikawa group), and the other 20 underwent double tract anastomosis (double tract group). Outcome measures included intraoperative condition, postoperative recovery, postoperative quality of life, postoperative nutritional status and gastroesophageal reflux. The patients were followed up using outpatient examination and telephone interviews to identify their nutritional status, reflux esophagitis and anastomotic status. Results: (1) Intraoperative condition: Compared with the double tract group, the modified Kamikawa group had significantly prolonged time for operation and digestive tract reconstruction. However, no statistically significant difference in intraoperative blood loss was found between the two groups. (2) Postoperative recovery: Compared with the double tract group, the modified Kamikawa group had a significantly shorter time for the first postoperative intake of fluids, drainage tube placement and postoperative hospital stay. No statistically significant difference in the time to first postoperative anal exhaust and postoperative complications was found between the two groups. (3) Postoperative quality of life: Compared with the double tract group, the modified Kamikawa group showed better quality of life at 12 months after surgery. (4) Postoperative nutritional status and gastroesophageal reflux: No statistically significant difference in hemoglobin, total serum albumin, albumin, body mass index, MUST score, PG-SGA score, grading of reflux esophagitis using the Los Angeles classification system and GERD score was found between the two groups at 6 and 12 months after surgery. All patients did not experience anastomotic stenosis and tumour recurrence or metastasis. Conclusions: Modified Kamikawa anastomosis is a safe and feasible treatment in laparoscopic proximal gastrectomy, which can ensure good postoperative antireflux effect and nutritional status. It has the advantage of better postoperative recorvery and quality of life compared with double tract anastomosis. [ABSTRACT FROM AUTHOR]

Background: Mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) is a rare malignant gastrointestinal tumor. The prognosis of patients with MiNEN is poor because of the high frequency of recurrence and metastases. We report a case of esophagogastric junction MiNEN (EGJ-MiNEN) with a long-term recurrence-free survival of 5.5 years. Case presentation: A 58-year-old male patient underwent thoracoscopic esophagectomy for esophagogastric junction adenocarcinoma. The patient's postoperative course was uneventful. R0 resection was achieved, and the pathological diagnosis of the surgical specimen was pT3N2M0 Stage IIIA (according to the Japanese Classification of Gastric Cancer, 4th edition). Based on the pathology results, the patient was treated with postoperative adjuvant therapy with oral S-1. The patient maintained recurrence-free survival for 5.5 years postoperatively. However, 6 years postoperatively, the patient visited our department with cachexia. Computed tomography (CT) revealed a large amount of ascites and pleural effusion. He rapidly developed a poor circulatory and respiratory status and died 16 days after admission. An autopsy revealed severe bloody ascites and pleural effusion, as well as numerous nodules on the pleura and mesentery. Immunohistochemistry of the nodules revealed positivity for chromogranin A, Synaptophysin A, neural cell adhesion molecule (NCAM or CD56), and insulinoma-associated protein 1 (INSM1). The specimen showed a mixture of adenocarcinoma and neuroendocrine cell carcinoma and was diagnosed as MiNEN. Retrospective immunostaining of the surgical specimen showed similar results, and we diagnosed the patient with recurrence of EGJ-MiNEN. Conclusion: MiNEN has a poor prognosis; however, in some cases, long-term recurrence-free survival is achieved with radical resection and adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Esophagogastric junction outflow obstruction (EGJOO) is a heterogenous disorder in which the correct management strategy is unclear. We assessed whether functional lumen imaging probe (FLIP) topography data could select EGJOO, which would benefit from lower esophageal sphincter Botulinum toxin (Botox) injection. Methods: This was a single‐center prospective study of adult patients meeting Chicago Classification (CC) v3.0 criteria for EGJOO. We assessed differences in pretreatment physiologic measurements on high‐resolution manometry (HRM) and FLIP and other relevant clinical variables in predicting Botox response (>50% in BEDQ at 2 months). Key Results: Sixty‐nine patients were included (ages 33–90, 73.9% female). Of these, 42 (61%) were Botox responders. Majority of physiologic measures on HRM and FLIP and esophageal emptying were not different based on Botox response. However, a spastic‐reactive (SR) FLIP contractile response (CR) pattern predicted a Botox response with OR 25.6 (CI 2.9–229.6) when compared to antegrade FLIP CR; and OR for impaired‐disordered/absent CR was 22.5 (CI 2.5–206.7). Logistic regression model using backward elimination (p value = 0.0001, AUC 0.79) showed that a SRCR or IDCR/absent response and the upright IRP predicted Botox response. Response rates in tiered diagnostic groups were: (i) CCv3.0 EGJOO (60.9%), (ii) CCv4.0 EGJOO (73.1%), (iii) CCv4.0 + FLIP REO (80%), (iv) CCv4.0, FLIP REO, and abnormal FLIP CR (84.2%), and (v) CCv4.0, FLIP REO, and SR FLIP CR (90%). Conclusions and Inferences: FLIP helps identify patients with EGJOO who are likely to response to LES Botox therapy. An abnormal FLIP contractile response pattern is the single‐most important predictor of a Botox response. [ABSTRACT FROM AUTHOR]

Background and Purpose: Measurement of gastro‐intestinal motility is increasingly performed under general anesthesia during endoscopic or surgical procedures. The aim of the present study was to review the impact of different anesthetic agents on digestive motility measurements in humans. Methods: This systematic review was performed using the Medline‐Pubmed and Web of Science databases. All articles published until October 2023 were screened by identification of key words. Studies were reviewed if patients had an assessment of digestive motility using conventional perfused manometry, high‐resolution manometry, electronic barostat or functional lumen impedance planimetry with the use of inhaled or intravenous anesthetic anesthetic agents (propofol, ketamine, halogens, nitrous oxide, opioids, and neuromuscular blockades). Results: Four hundred and eighty‐eight unique citations were identified, of which 42 studies met the inclusion criteria and were included in the present review. The impact of anesthetics was mostly studied in patients who underwent esophageal manometry. There was a heterogeneity in both the dose and timing of administration of anesthetics among the studies. Remifentanil analgesia was the most studied anesthetic drug in the literature, showing a decrease in both distal latency and lower esophageal sphincter pressure after its administration, but the impact on Chicago classification was not studied. Inhaled anesthetics administration elicited a decrease in lower esophageal sphincter pressure, but contradictory findings were shown on esophageal motility following propofol or neuromuscular blocking agents administration. Conclusion: Studies of the impact of anesthetics on digestive motility remain scarce in the literature, although some agents have been reported to profoundly affect gastro‐intestinal motility. [ABSTRACT FROM AUTHOR]

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett's esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR. [ABSTRACT FROM AUTHOR]

Background/Objective: Multiple system atrophy (MSA) is often associated with dysphagia and esophageal dysmotility (ED). However, ED in patients with MSA is poorly understood. To assess the relationship between ED, dysphagia, and other clinical findings in such patients and investigate the details of ED in MSA using high-resolution manometry (HRM). Methods: Patients from The University of Tokyo Hospital with MSA who underwent swallowing examinations, esophagography, and HRM between 2017 and 2022 were enrolled. A retrospective chart review of patients' backgrounds, swallowing function, and esophageal motility was performed. ED was evaluated using the Chicago Classification version 4.0. Results: Seventy-four patients with MSA were identified. The median age was 64 years, 48 patients (65%) were male, and the cerebellar variant type was predominant (69%). Abnormal upper esophageal sphincter (UES) resting pressure was observed in 34 patients (46%) and intraesophageal stasis in 65 (88%). High-severity MSA was a risk factor for developing dysphagia, vocal fold movement impairment, and abnormal UES function (p < 0.05). However, no overt clinical risk factors for ED were identified. Various types of ED were detected using HRM, and ineffective esophageal motility was the most frequent disorder. Conclusions: ED is a common occurrence in patients with MSA. Although a high-severity MSA may be a risk factor for developing dysphagia and vocal fold motion impairment, ED can occur regardless of clinical severity. Since ED is rarely detected based on subjective symptoms, careful evaluation of esophageal motility by esophagography or HRM is warranted in patients with MSA. [ABSTRACT FROM AUTHOR]

Background: Limited data exist for global prevalence of claudin 18 isoform 2 (CLDN18.2) positivity and association of CLDN18.2 status with clinical and tumor characteristics in patients with locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. We report prevalence of CLDN18.2 positivity (phase 3; SPOTLIGHT, NCT03504397; GLOW, NCT03653507) and concordance of CLDN18.2 status between a subset of pair-matched tumor samples (phase 2, ILUSTRO, NCT03505320; phase 1, NCT03528629) from clinical studies of zolbetuximab. Methods: Tumor samples from patients with LA unresectable or mG/GEJ adenocarcinoma were tested for CLDN18.2 status by immunohistochemistry. Human epidermal growth factor receptor 2 (HER2) expression was tested per central or local assessment. Results: Across SPOTLIGHT and GLOW, the prevalence of CLDN18.2 positivity (≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 38.4%. Prevalence was similar in gastric versus GEJ adenocarcinoma samples and regardless of collection method (biopsy versus resection) or collection site (primary versus metastatic). CLDN18.2 positivity was most prevalent in patients with diffuse-type tumors. In ILUSTRO and the phase 1 study, concordance of CLDN18.2 positivity was 61.1% between archival (i.e., any time before treatment) and baseline (i.e., ≤ 3 months before first treatment) samples, and concordance of any CLDN18 staining (≥ 1% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 88.9%. Conclusions: CLDN18.2 was a highly prevalent biomarker in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 positivity remained relatively stable over time in many patients. Biomarker testing for CLDN18.2 should be considered in standard clinical practice in these patients. [ABSTRACT FROM AUTHOR]

Background: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. Methods: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. Results: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8–17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6–10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29–0.87); median OS (95% CI) was 24.7 months (13.8–33.1) vs 12.9 months (9.3–21.4), respectively (HR 0.56, 95% CI 0.32–0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. Conclusion: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6. [ABSTRACT FROM AUTHOR]

Surgery for cancer of the esophagus or gastro-esophageal junction can be performed with a variety of minimally invasive and open approaches. The left thoracoabdominal esophagectomy (LTE) is an open technique that gives an opportunity to operate in the chest and abdomen with excellent exposure of the gastro-esophageal junction through a single incision, and there is currently no equivalent minimally invasive technique available. The aim of this multi-institutional review was to study a large contemporary international study cohort of patients treated with LTE. An international multicenter cohort study was performed including all patients treated with LTE at six high-volume centers for gastro-esophageal cancer surgery between 2012 and 2022. Patient data were prospectively collected in each participating centers' institutional database. Information about patient, tumor, and treatment details were collected. The study cohort included a total of 793 patients treated with LTE during the study period. The most frequently observed complications were pneumonia in 185/727 (25.5%) patients and atrial fibrillation in 91/727 (12.5%). Anastomotic leak occurred in 35/727 (4.8%) patients; no patient suffered from conduit necrosis. Thirty-day mortality occurred in 15/785 (1.9%) patients and 90-day mortality in 39/785 (5.0%) patients. Factors with statistically significant association with survival were American Society for Anesthesiologists-score, tumor location, tumor stage, and tumor free resection margins. Neoadjuvant therapy was not associated with increased survival compared to surgery alone but neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy showed statistically significant improved survival with hazard ratio 0.60 (95% confidence intervals:0.44–0.80, P  = 0.001) in a multivariable adjusted model. This study demonstrates that LTE can be applied in selected patients with results that are comparable to other large studies of open and minimally invasive surgery for esophageal or gastro-esophageal cancer at high-volume centers. [ABSTRACT FROM AUTHOR]

Molecularly targeted therapy for receptor tyrosine kinases (RTKs) has faced limitations in gastric and gastroesophageal junction (G/GEJ) cancer except for HER2-targeted agents, possibly due to inappropriate assay selection that has hindered identification of sensitive patients, in addition to coexisting genetic abnormalities as well as intratumoral heterogeneity. Immunohistochemistry of RTKs has, thus, proved largely unsuccessful for patient selection, and detection of RTK gene amplification as a true oncogenic driver is problematic given the small numbers of affected individuals. FGFR2 amplification is associated with poor prognosis in G/GEJ cancer, and immunohistochemistry of the FGFR2b protein isoform has proved effective for the detection of such FGFR2-dependent tumors. Phase III and Ib/III trials of the FGFR2-targeted antibody bemarituzumab for G/GEJ cancer overexpressing FGFR2b are ongoing based on the promising result in a phase II trial, especially in cases with an FGFR2b positivity of ≥ 10%. Challenges to EGFR- and MET-targeted therapies are being tackled with antibody–drug conjugates (ADCs) and bispecific antibodies. CLDN18.2 is expressed in some G/GEJ tumors but lacks oncogenic driver potential, and the CLDN18.2-targeted antibody zolbetuximab prolonged the survival of CLDN18.2-positive G/GEJ cancer patients in phase III trials. Antibody–drug conjugates and ADCs that target CLDN18.2 are also being pursued for treatment of such patients. Similarly, targeting of nondriver molecules such as DKK1, TROP2, and CEACAM5 is under investigation in early-stage clinical trials. This shift in focus from target molecules with driver potential to markers for precise drug delivery should increase the number of possible targets in G/GEJ cancer. [ABSTRACT FROM AUTHOR]

Benign and malignant diseases of the upper gastrointestinal tract show gender-specific differences. The frequent gastroesophageal reflux disease is a prime example: men have an erosive reflux disease more often than women and are also younger at the time of onset. The rate of progression to a metaplastic Barrett's esophagus is also higher in men. In the case of achalasia, there are indications that surgical treatment by laparoscopic Heller's myotomy and semifundoplication 180° according to Dor leads to a markedly better improvement in the symptoms in women compared to men, although they showed a more pronounced dilation of the tubular esophagus. The female hormone status influences the localization and histopathology of adenocarcinoma of the esophagogastric junction and gastric carcinoma. Premenopausal and postmenopausal carcinomas differ significantly in women. In addition, high microsatellite instability (MSI high) is more frequent in women and is associated with a generally significantly better prognosis. The MSI high gastric carcinomas of women show better survival than MSI high carcinomas of men. The future inclusion of gender-specific aspects in studies of the upper gastrointestinal tract is desirable in order to generate adequate data and to enable differentiated treatment stratification in the future. [ABSTRACT FROM AUTHOR]

Achalasia is a rare esophageal motility disorder characterized by nonrelaxation of the lower esophageal sphincter. Laparoscopic Heller myotomy (LHM) is the gold standard treatment for achalasia. Peroral endoscopic myotomy (POEM), a less invasive treatment, is performed extensively, and the selection of the intervention method remains debatable to date. In addition to the availability of extensive studies on short‐term outcomes, recent studies on the long‐term outcomes of LHM and POEM have shown similar clinical success after 5 y of follow‐up. However, gastroesophageal reflux disease (GERD) was more common in patients who had undergone POEM than in those who had undergone LHM. Moreover, existing studies have compared treatment outcomes in various disease states. Some studies have suggested that POEM is superior to LHM for patients with type III achalasia because POEM allows for a longer myotomy. Research on treatment for sigmoid types is currently in progress. However, the long‐term results comparing LHD and POEM are insufficient, and the best treatment remains controversial. Further research is needed, and treatment options should be discussed with patients and tailored to their individual needs and pathologies. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma of the esophagogastric junction (AEG) has risen significantly worldwide in recent decades. Eastern and western countries report differences in disease characteristics and treatment strategies. However, the Southeast Asian AEG data remains extremely limited. Objective: To demonstrate the clinicopathological characteristics and surgical treatment outcomes of AEG in Thai patients. Materials and Methods: The authors conducted retrospective review of 106 AEG patients who underwent curative resection at a university hospital in Thailand between 1998 and 2020. All patients were classified by the Siewert classification. The clinicopathological characteristics, operative outcomes, and survival outcomes were reported and compared between each subtype. The chi-square test was utilized to compare categorical variables, whereas, the one-way ANOVA test was used to analyze continuous data. Survival outcomes were calculated using the Kaplan-Meier method, and the log-rank test was employed to compare the variables that impact survival. Results: Of 106 patients, 13 patients (12.3%) were classified as Siewert type 1, 56 patients (52.8%) as Siewert type 2, and 37 patients (34.9%) as Siewert type 3 tumors. Most type 1 patients (76.9%) underwent Ivor-Lewis esophagectomy, whereas 60.7% and 81.1% of type 2 and type 3 patients, respectively, received extended gastrectomy. The overall 30-day mortality was 1.9%. The cohort revealed a 5-year survival rate of 25.4%, with a median survival of 17 months. Multivariate analysis showed that poor survival was significantly associated to age older than 65 years (HR 2.54, 95% CI 1.51 to 4.28), higher pN stage (HR 2.63, 95% CI 1.48 to 4.67), and higher histologic grade (HR 2.06, 95% CI 1.25 to 3.39). Conclusion: The present study is the first study on AEG in Thailand, showing increasing number comparable to those in Western countries. A greater proportion of AEG cases in Thailand were classified as Siewert types 2 and 3. The survival prognosis was still unfavorable and requires improvement in upcoming instances. [ABSTRACT FROM AUTHOR]

Introduction: Many preterm present somatic symptoms including aerodigestive and cardiorespiratory manifestations, in combination with irritability and/or distress, which are often attributed to gastroesophageal reflux (GER), albeit for unclear reasons. Areas Covered: We searched in PubMed, Google Scholar, and MEDLINE for guidelines, reviews, and randomized controlled trials up to March 2024. Expert opinion: The diagnosis of GER-disease (GERD) in preterm is challenging because manifestations are atypical and diagnostic investigations difficult and not devoid of risk for adverse events. In case of vomiting or regurgitation, GER as a consequence of anatomical or metabolic conditions should be considered. Although many preterm infants are treated with proton pump inhibitors, this is seldom needed. Low-quality evidence for alginates is available, but needs further evaluation. There is a need for an effective and safe prokinetic favoring esophageal clearance, increasing lower esophageal sphincter pressure and stimulating gastric emptying. Non-drug treatment such as feeding adaptations (volume, duration, and composition) and positional changes are insufficiently applied. Thickened formula is not indicated in preterm babies. In case none of the above recommendations did result in sufficient improvement, and if documentation of acid GER is not possible, a 2–4 week trial of a proton pump inhibitor is acceptable. [ABSTRACT FROM AUTHOR]

Background and Objectives: The threshold for ineffective esophageal motility (IEM) diagnosis was changed in Chicago v4.0. Our aim was to determine IEM prevalence using the new criteria and the differences between patients with definite IEM versus "inconclusive diagnosis". Materials and Methods: We retrospectively selected IEM and fragmented peristalsis (FP) patients from the high-resolution esophageal manometries (HREMs) database. Clinical, demographic data and manometric parameters were recorded. Results: Of 348 HREMs analyzed using Chicago v3.0, 12.3% of patients had IEM and 0.86% had FP. Using Chicago v4.0, 8.9% of patients had IEM (IEM-4 group). We compared them with the remaining 16 with an inconclusive diagnosis of IEM (borderline group). Dysphagia (77% vs. 44%, Z-test = 2.3, p = 0.02) and weight loss were more commonly observed in IEM-4 compared to the borderline group. The reflux symptoms were more prevalent in the borderline group (87.5% vs. 70.9%, p = 0.2). Type 2 or 3 esophagogastric junction morphology was more prevalent in the borderline group (81.2%) vs. 64.5% in IEM-4 (p = 0.23). Distal contractile integral (DCI) was lower in IEM-4 vs. the borderline group, and resting lower esophageal sphincter (LES) pressure and mean integrated relaxation pressure (IRP) were similar. The number of ineffective swallows and failed swallows was higher in IEM-4 compared to the borderline group. Conclusions: Using Chicago v4.0, less than 10% of patients had a definite diagnosis of IEM. The dominant symptom was dysphagia. Only DCI and the number of failed and inefficient swallows were different between definite IEM patients and borderline cases. [ABSTRACT FROM AUTHOR]

Objectives The incidence of adenocarcinomas of the esophagogastric junction (EGJ) and cardia has been gradually increasing in the East. Cancers of the EGJ and gastric cardia have poor prognoses. This study aimed to investigate lymph node metastasis (LNM) rates, their predictive factors, and determine the long-term outcomes of patients with Siewert type II/III early gastric cancer (EGC). Methods Between January 2014 and June 2022, a total of 573 patients with gastric cancer, including 130 with Siewert type II/III EGC, underwent total gastrectomies at the Kosin University Gospel Hospital. Factors associated with LNM were analyzed using a logistic regression model. Results Of the 130 patients with Siewert type II/III EGC, 10 (7.7%) demonstrated LNM (LNM-positive group). Macroscopically elevated lesions (I+IIa) (60.0% vs. 16.7%; p=0.009) and lymphovascular invasion (70.0% vs. 5.8%; p

Abstract Purpose The differences in tumor behavior between adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagogastric junction (EGJ) have yet to be well investigated. The purpose of this study was to gain insights that can contribute to tailored treatments and follow-up strategies by analyzing the correlation between histological subtypes and oncological outcomes. Methods A retrospective analysis was used to determine the characteristics of the histological subtypes of EGJ cancer by comparing the appearance of postoperative recurrence. A total of 102 consecutive patients with pathological stage IIA to IVA EGJ cancer, who underwent R0 surgery in our department from 2004 to 2020, were enrolled. The recurrence pattern, timing, survival, and potential prognostic factors were compared. Results After a median follow-up time of 70.1 months, the AC group demonstrated comparable lymph node failure-free survival (P = 0.291) and significantly worse non-lymphogenous recurrence-free survival (P = 0.035) than did the SCC group. A significantly longer period from surgery to recurrence was also observed in the AC group (P = 0.029). Multivariate analysis indicated that histological subtype (P = 0.015, 95% CI 1.24–7.28) was significantly correlated with the incidence of non-lymphogenous recurrence. Conclusions The pattern and timing of postoperative recurrence were significantly different between the histological subtypes of EGJ cancer. Compared with EGJ SCC, EGJ AC may have a greater tendency toward non-lymphogenous progression and a greater propensity for longer surgery-to-recurrence periods.

BACKGROUND: The Eckardt score (ES) is used to assess symptom response to Per-Oral Endoscopic Myotomy (POEM), but reliable methods to assess physiologic success are needed. Functional lumen imaging probe (FLIP) panometry has a potential role in post-POEM follow-up to predict long-term outcomes. The aim of this study was to assess the correlation between clinical success and FLIP parameters following POEM to determine if short interval FLIP could predict long-term outcomes. METHODS: This was a prospective study of adult patients who underwent POEM with short interval follow-up FLIP between 11/2017 and 3/2020. Clinical success was defined as post-procedure ES ≤ 3. Physiologic success was based on an esophago-gastric junction distensibility index (EGJ-DI) > 2.8 mm2/mmHg on FLIP. RESULTS: 47 patients (55% female, mean age 55 years) were included in the study. Clinical success after POEM was seen in 45 (96%) patients (mean ES 6.5 ± 2.2 pre and 0.83 ± 1.0 post-POEM, p