Diseases of the Esophagus最新文献

Although immune-related adverse events (irAEs) are increasingly recognized as biomarkers of response to immunotherapy in advanced cancers, their prognostic role in the neoadjuvant setting for esophageal squamous cell carcinoma (ESCC) remains unclear. This retrospective multicenter cohort study aimed to evaluate the associations between irAEs, pathological response, and 2-year survival outcomes in patients with locally advanced ESCC treated with neoadjuvant chemoimmunotherapy (NCIT) followed by esophagectomy. A total of 1076 patients with cT1bN1-3 M0 or cT2-4aN0-3 M0 ESCC who received NCIT and surgery between January 2019 and March 2023 across 26 tertiary centers in China were included. IrAEs, defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, were observed in 181 patients (16.8%), with rash/pruritus being the most common. Patients who developed irAEs completed fewer NCIT cycles and had longer treatment-to-surgery intervals, both of which were independently associated with worse disease-free survival (DFS). Although the occurrence of irAEs correlated with inferior overall survival (OS)-particularly pneumonitis and rash/pruritus-multivariable analysis revealed that irAEs were not independent predictors of either OS or DFS. The strongest independent predictors of survival were pathological nodal status (ypN3) and poor tumor regression (TRG4). In conclusion, despite being linked to prolonged treatment-to-surgery intervals, irAEs were not significantly associated with pathological response or long-term survival outcomes in this cohort of ESCC patients treated with NCIT and surgery, underscoring the importance of effective management of irAEs during neoadjuvant therapy.

Gastroesophageal reflux disease is the most frequent gastrointestinal complication of surgical repair of esophageal atresia (EA). To date, we have reported the significance of assessing the waveform pattern in multichannel intraluminal impedance-pH (MII-pH) for esophageal diseases. This study aimed to assess the relevance of MII-pH and endoscopic findings in EA. The study population of this retrospective study included 22 EA patients (median age: 3.0 years, interquartile 2-5 years) in whom MII-pH was conducted. Low baseline impedance values have been detected in patients with esophagitis and esophageal motility disorders. In the MII-pH study, low impedance influenced the difficulty of the analysis. We classified MII-pH waveforms according to the difficulty of analysis as either easy-to-analyze waveforms or difficult-to-analyze waveforms. With regard to waveform pattern, pH index, bolus exposure index, total reflux episodes, total proximal episodes, and acid proximal episodes in patients with difficult-to-analyze waveforms were significantly higher than in patients with easy-to-analyze waveforms. In addition, the baseline impedance values of distal esophagus in patients with difficult-to-analyze waveforms were significantly lower than in patients with easy-to-analyze waveforms. Four patients (26.7%) with a pH index ≥3.0% were diagnosed with nonerosive reflux disease. Endoscopic findings showed no erosions in EA patients with easy-to-analyze waveforms. Three patients with type A EA were difficult-to-analyze waveforms. The present study demonstrated that MII-pH is useful for evaluating EA. In particular, MII-pH can be used to detect nonerosive reflux disease. Evaluation of the waveform could be an indication for endoscopy.

Upper gastrointestinal malignancies bear a high morbidity and mortality burden. Curative treatment requires a multimodal approach, subjecting patients to preoperative chemotherapy or chemoradiation to downstage the tumor before resection. Various preoperative regimens exist but there is no tailor-made approach based on the tumor sensitivity for the individual patient. This predisposes a considerable subset of patients to inadequate treatment and highlights the need for personalized medicine, for which the potential of patient-derived cancer organoids (PDCOs) was investigated. PDCOs were established from pre-treatment biopsies of two gastric and four esophageal cancer patients, and compared to previously established PDCOs derived from four gastric and two esophageal resections post-neoadjuvant treatment. PDCO sensitivity, defined as area under the dose-response curve, was determined to in vitro chemotherapy (epirubicin, oxaliplatin, capecitabine and 5-fluorouracil, leucovorin, oxaliplatin, docetaxel) and chemoradiation (carboplatin, paclitaxel, radiotherapy). The PDCOs were established from 55% of the pre-treatment biopsies (derived from four of six patients), and demonstrated differential sensitivity to the treatment screens. PDCOs initiated from pre-treatment tissue were more sensitive than those derived from post-treatment tissue. In addition, drug screen sensitivity of pre-treatment PDCOs correlated well with patient response in terms of tumor regression grade. The current results provide a proof of principle and offer recommendations for a structured pipeline to more efficiently establish, validate and screen a larger cohort of pre-treatment PDCOs.

It is important to predict response of esophageal squamous cell carcinoma (ESCC) to neoadjuvant immunochemotherapy for treatment decision-making. This study aimed to explore whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived parameters and MR signal intensity can predict the response. About 82 consecutive ESCC patients undergoing pretherapeutic DCE-MRI, T2WI, and T1WI followed by neoadjuvant immunochemotherapy were prospectively enrolled, among which patients from Institution 1 were randomly stratified into training (n = 52) and internal validation (n = 15) cohorts, and those from Institution 2 were assigned to external validation cohort (n = 15). Ktrans, Kep, and Ve of ESCC and their standard deviation (SD) were generated based on DCE-MRI, mean, and SD of MR signal intensity on T1WI and T2WI were also obtained, and coefficient of variation of these parameters were calculated. In training cohort, all parameters were statistically compared between responders and non-responders. Predictive effectiveness of individual parameters with statistical difference, and the parameters based logistic regression models were evaluated using area under the receiver operating characteristic curve (AUC) in three cohorts. Mean and SD of Kep (Kep_Mean and Kep_SD, respectively) and T2WI signal intensity (T2WI_Mean and T2WI_SD, respectively) in responders were higher than in non-responders (all P-values <0.05), among which, Kep_Mean could best predict the responsiveness with AUCs of 0.858, 0.768, and 0.870; and the model (T2WI_Mean + T2WI_SD + Kep_Mean + Kep_SD) demonstrated superior predictive performance (AUCs: 0.928, 0.911, and 0.907) in training, internal and external validation cohorts, respectively. Combination of mean and SD of Kep, and T2WI signal intensity could well predict immunochemotherapy responsiveness of ESCC.

The pHoenix score was recently developed to reduce the proportion of inconclusive diagnoses associated with using total acid exposure time (AET) alone. The aim of this study was to compare the discriminative performance of the pHoenix score to total AET and DeMeester score (DMS) in patients undergoing 24-hour transnasal pH-monitoring (24-h pH). This cross-sectional study included consecutive patients (2017-2024) undergoing 24-h pH for suspected gastroesophageal reflux disease. Exclusions criteria were prior foregut/bariatric procedures, outflow obstruction disorders and inadequate pH-studies (<18 hours). The pHoenix score calculation was (%upright AET × 0.991) + (% supine AET × 1.286), with thresholds: <7.06 (normal), 7.06-8.45 (borderline), >8.45 (pathological). Total AET thresholds were: <4% (normal), 4-6% (borderline), and >6% (pathological). The DMS (pathological if >14.72) was the reference standard. Of 500 patients (50% females, median age 51 years, median BMI 24.65 kg/m2), 213 (43%) had pathological DMS. The pHoenix score and total AET identified a similar proportion of normal cases (54% vs. 56.2%, P > 0.99), but different pathological (40.4% vs. 30%, P < 0.01) and borderline diagnoses (5.6% vs. 13.8%, P < 0.01; with a 59% reduction with the pHoenix score). The pHoenix model showed strong performance (pseudo R2:0.877; Akaike information criterion = 83.57). Sensitivity/specificity were high at both 7.06 (99.1%/93.4%) and 8.45 (93.9%/99.3%) cutoffs. The AUC was 0.995 (95% CI: 0.987-1) for the pHoenix score, and 0.992 (95% CI: 0.987-0.997) for total AET. The pHoenix score, while maintaining a high diagnostic accuracy, offers a refined classification of acid exposure weighting supine/upright AET, thus reducing borderline diagnoses and potential need for further testing.

The peri-operative period surrounding esophagectomy is challenging for patients to navigate. In this study, we describe the implementation of a digital health pathway to provide peri-operative education and track patient reported outcomes (PRO) after esophagectomy. This single-center study involved adults who underwent esophagectomy between 2021 and 2024. Educational emails, PRO surveys, and quality of life (QOL) questionnaires were delivered via a mobile health (mHealth) platform (CareSense; MedTrak Inc). Pathway data were combined with outcome data. Primary outcome was the rate of post-operative complications. Secondary outcomes included enrollment rate, PRO, and QOL scores. Fisher's exact test, Pearson Chi-square test, Kruskal-Wallis test, and logistic regressions were utilized for statistical analyses. Of 168 eligible patients, 136 (80.9%) enrolled in the pathway. There were no significant differences in demographic characteristics between patients who enrolled and those who did not. Enrollment was not associated with post-operative complication rate. Patients activated the pathway a median of 26 days (19-36) before their operation. They received a median of 23 emails (22, 30), 14 surveys, and 6 questionnaires; only 8 patients did not complete any of the daily surveys (5.9%). Median pre-operative anxiety score was 51 (43-56) after peri-operative education, indicating little to no anxiety. Median score change in global QOL at the 2-year time-point was +17 (0, 21). The majority of eligible patients enrolled in the pathway and patient satisfaction was high. There were no differences in post-operative complications based on enrollment. Enrolled patients had low pre-operative anxiety following peri-operative education and clinically significant QOL improvement at 2 years.

Barrett's esophagus (BE) is a premalignant condition. Societal guidelines standardize its management to prevent progression to adenocarcinoma, yet adherence varies substantially between gastroenterologists. This study aimed to assess and compare the accuracy of large language models in delivering guideline-based recommendations for managing BE. We evaluated 107 cases of patients with BE, each case included all available esophagogastroscopy and pathology reports. Two experts provided recommendations according to the European Society of Gastrointestinal Endoscopy, focusing on three aspects: (i) pathology confirmation by a second pathologist; (ii) next action-and (iii) the interval until next endoscopy. Gemini 2.0 and o3-mini-high were evaluated. Training with prompt engineering and testing were performed on 23 and 84 cases respectively. Gold standard was defined as the consensus recommendations provided by the experts. Accuracies were calculated using bootstrapping, and McNemar's test was employed for large language models comparison. Both large language models demonstrated high to near perfect accuracy across all three fields as compared to expert recommendations, without significant differences between the two models for all parameters. Agreement between the two large language models was high in all three fields. Large language models demonstrated high accuracy in assessing real-world presentations of BE and providing guideline-based recommendations for patient management.

Diagnosing gastroesophageal reflux disease (GERD) remains challenging in patients with inconclusive endoscopic findings or acid exposure time. Mean nocturnal baseline impedance (MNBI) is a diagnostic metric to delineate pathological GERD. This study evaluates MNBI in relation to GERD phenotypes, antisecretory medication use, symptomatology, and other covariates to validate its integration into recommendations in light of Lyon consensus updates. We conducted a retrospective analysis of 550 patients who underwent esophagogastroduodenoscopy and 24-hour pH-impedance testing. A multivariate linear model inferred the association between medication status and MNBI, adjusting for covariates. Interaction terms determined moderation of patient medication status on MNBI by other clinical covariates. Medication status significantly influenced MNBI, independent of covariates. Medicated patients had mean MNBI 0.52 kΩ greater (95% CI: 0.27-7.8, P < 0.001) than non-medicated patients. MNBI was 0.78 kΩ lower (95% CI: -1.2 to -0.41, P < 0.001) in patients with erosive disease and 1.0 kΩ lower (95% CI: -1.5 to -0.5, P < 0.001) in those with Barrett's esophagus. Additionally, MNBI decreased by 0.02 kΩ for every one-unit body mass index increase (95% CI: -0.04 to -0.01, P = 0.006). This study validates lower MNBI as a potential surrogate marker for GERD, particularly in more erosive presentations. Increased MNBI in medicated patients highlights antisecretory therapy as a potential confounding factor, reinforming the need for off-therapy testing. The study is strengthened by its large population, though limited by retrospectivity. The findings support both MNBI as a valuable diagnostic tool in GERD assessment and the need to further standardize MNBI cutoffs.