This study aimed to develop a novel quantitative methodology to classify the Siewert type on multiplanar reconstructed (MPR) computed tomography (CT) and subsequently guide the diagnosis of adenocarcinoma of the esophagogastric junction.

Patients in the retrospective development and prospective validation cohort 1 were recruited from Peking University Cancer Hospital. Patients in prospective validation cohort 2 were recruited from Changzhi People's Hospital. A streamlined method determined axial/coronal CT slice numbers for the esophagogastric junction (EGJ) and tumor center; then using these slices formulated a Siewert classification system. The CT-based four-step formula for Siewert type (CT-FSFS) is: STEP 1: determining the axial level of the EGJ; STEP 2: distinguishing Type III from Type I/II; STEP 3: predicting Type III misclassified as II; STEP 4: correcting the misclassification using the deflection angle.

The CT-FSFS method demonstrated robust accuracy across all three cohorts: 89.5% in the development cohort, 91.0% in validation cohort 1 and 89.7% in validation cohort 2. In differentiating Type I/II from Type III, the formula demonstrated high specificity (96.9%) and positive predictive value (97.1%) in the development cohort.

This study presents a reproducible, quantitative Siewert classification method on MPR CT, it may aid preoperative surgical planning.

The incidence of esophagogastric junction (EGJ) adenocarcinoma has increased worldwide. As the EGJ is located at the boundary between the thoracic and abdominal cavities, the optimal surgical approach is a subject of debate and estimation of the esophageal invasion length (EIL) is an important factor in its selection.

Data from our in-house database were extracted for consecutive patients with Siewert type I, II and III EGJ adenocarcinoma (EIL ≤ 4 cm), who underwent transhiatal or transthoracic surgical resection between 2010 and 2016. The clinical records of these patients were reviewed and the accuracy of EIL estimation and its discrepancy with the pathological measurement were analyzed.

A total of 82 patients were included in the final analysis. We established that EIL was underestimated in 49 of these patients (59.8%). The mean-distance discrepancy between the preoperative and pathological diagnosis of EIL in the underestimation group was 7.0 mm. Multivariate analysis revealed that submucosal cancer spread was an independent risk factor for underestimation (P < 0.01). The mean length of submucosal cancer spread was longer for undifferentiated histologic type EGJ adenocarcinomas. (P < 0.01).

The EIL was underestimated in approximately 60% of EGJ adenocarcinomas requiring surgical treatment. Thus, careful management is necessary, especially for EGJ adenocarcinoma of the undifferentiated histologic type.

Background: The research on laparoscopic proximal gastrectomy has focused on effective methods of preventing reflux, few studies have focused on controlling the blood supply to the anastomosis site. Therefore, we introduced a modified approach to the vascular arch of the tubular stomach (TS) and conducted a preliminary examination of its safety and feasibility. Methods: Retrospective analysis of clinical data from 37 patients who underwent laparoscopic proximal gastrectomy at our center from March 2021 to June 2023, and comparison of clinical and pathological data, as well as intraoperative and short-term postoperative outcomes, between the modified TS group (n = 16) and the TS group (n = 21). Results: Compared with the TS, the modified TS had relatively longer operative times (170.63 ± 29.88 minutes versus 166.14 ± 27.49 minutes, P = .64) and anastomosis times (40.44 ± 6.60 minutes versus 36.14 ± 6.72 minutes, P = .06), and there was no significant difference in bleeding volume between the two groups (94.38 ± 75.19 mL versus 67.62 ± 44.15 mL, P = .14). There were 2 cases of postoperative anastomotic-related complications ((both of which were anastomotic bleeding) in the TS. No anastomotic-related complications were observed in the modified TS. There were a total of 6 cases in the postoperative gastroscopy modified TS, including 5 cases of LA-A and 1 case of LA-B; There are 10 cases of TS, including 7 cases of LA-A and 3 cases of LA-B. Conclusions: The modified TS during laparoscopic procedures is safe and feasible, decreasing to the maximal degree the potential blood supply disorders and bleeding risks at the anastomosis site while preventing reflux.

The objective of this study was to assess the relationship of VEGF-C and LVD with pathoclinical factors of potential prognostic value and with the survival time of gastric cancer patients.

A total of 103 radically operated patients for gastric cancer who did not undergo neoadjuvant therapy were included in this study. The minimum follow-up period after surgery was 61 months. VEGF-C and lymphatic vessels were immunohistochemically determined using antibodies, including VEGF-C (c-20) sc 1881-Goat Polyclonal IgG (Santa Cruz Biotechnology) and Podoplanin D2-40 Mouse Monoclonal Antibody (ROCHE). The relationship between VEGF-C expression in gastric adenocarcinoma cells and the density of lymphatic vessels at the periphery of the primary tumor was assessed, along with the relationships of VEGF-C and LVD with selected pathoclinical parameters of gastric cancer and prognosis.

VEGF-C overexpression was associated with increased LVD (Mann-Whitney U test, p = 0.03) and the Lauren intestinal type of cancer (Pearson's chi-square test, p < 0.001). Increased LVD was more often associated with cancers located beyond the cardia (Mann-Whitney U test, p = 0.04). We did not demonstrate an association of VEGF-C or LVD with OS or with prognostic features, such as pT, pN, or pTNM staging. However, in the Lauren intestinal type of cancer, VEGF-C overexpression correlated with shorter OS (log-rank, p = 0.01) and, at the level of p = 0.05 in multivariate analysis, it had an independent negative prognostic value.

Peritumoral overexpression of VEGF-C in primary gastric cancer tumors is associated with increased LVD. The Lauren intestinal type of cancer is associated with VEGF-C overexpression. The overexpression of VEGF-C in intestinal-type gastric cancer is associated with worse prognosis.

Adenocarcinoma of the esophagogastric junction (AEG) has distinct malignant features compared with other esophageal and gastric cancers. Its management is controversial and largely influenced by tumor location and esophageal involvement. Hence, understanding the clinicopathological characteristics and prognosis of AEG is essential for optimizing treatment strategies.

To evaluate the prognosis and clinicopathological features of patients with AEG, providing insights for management strategies.

This retrospective study analyzed cases with AEG admitted between January 2016 and December 2017. Patients meeting the inclusion criteria were categorized into three groups: Type E [tumors whose center was located within 5 cm above the esophagogastric junction (EGJ)]; Type Eg (tumors whose center was situated within 2 cm below the EGJ), with a 2-cm esophageal invasion; Type Ge (tumors whose center was situated within 2 cm below the EGJ, with an esophageal invasion of < 2 cm, based on tumor location and esophageal involvement. Then, clinicopathological characteristics and survival outcomes of the groups were compared to evaluate the predictive value of the American Joint Committee on Cancer/International Alliance against Cancer 8th edition gastric cancer and esophageal adenocarcinoma staging systems. Statistical analysis included survival analysis and Cox regression to assess prognostic factors.

Totally, 153 patients with AEG were included (median follow up: 41.1 months; 22, 31, and 100 patients from type E, Eg, and Ge, respectively), with significant differences in maximum tumor length, esophageal involvement length, tumor type, pathology, differentiation, depth of invasion, and lymph node metastasis between the groups (P < 0.05). Lymph node metastasis rates at stations 1, 2, 3, and 7 were lower in type E than in Eg and Ge (P < 0.05). Survival rates for type E (45.5%) were significantly lower than those for Eg (48.4%) and Ge (73.0%) (P = 0.001). Type E tumors, vascular infiltration, T3-T4 invasion depth, and lymph node metastasis, were identified as independent prognostic factors (P < 0.05). The gastric cancer staging system outperformed the esophageal adenocarcinoma system for type Ge tumors.

Clinicopathological characteristics and prognoses varied between the AEG groups, with type E demonstrating distinct features. The gastric cancer staging system more accurately predicted type Ge AEG prognosis, guiding clinical decision-making.

Upper gastrointestinal (GI) malignancies, including esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinomas, remain a major global health concern, with poor overall survival and high recurrence rate despite aggressive treatment. Patients with very early tumors (cT1a) can benefit from endoscopic therapy. However, patients with locally advanced disease require multimodal therapies that may combine surgery, radiation, and systemic therapies. This review provides a comprehensive overview of recent advancements in the treatment of locally advanced upper GI adenocarcinomas. Surgical resection remains the cornerstone of curative treatment, with perioperative chemotherapy emerging as the standard of care. While preoperative chemoradiation has demonstrated some benefits in esophageal and GEJ cancers, recent data suggest a more limited role for radiation going forward. Immunotherapy has shown some promise in both the adjuvant and perioperative settings but has yet to establish definitive survival benefit. The integration of HER2-targeted therapies into treatment regimens for HER2-positive locally advanced gastroesophageal cancers has not yielded significant improvements, underscoring the need for more effective strategies. Ongoing research focuses on better predictive biomarkers, personalized treatment approaches, and potential organ preservation strategies for patients achieving a clinical complete response. Continued advancements in treatment modalities and precision medicine are critical to improving survival for patients with locally advanced upper GI adenocarcinomas.

The use of various classifications to grade and differentiate appearances of digestive diseases has enhanced precision and provided better means for their clinical evaluation and comparison. Staging systems abound to classify erosive esophagitis, gastro-esophageal varices, upper gastrointestinal hemorrhage, histopathology of celiac disease, various types of gastrointestinal neoplasia, and colitis associated with Crohn's disease or ulcerative colitis. The present review serves to highlight how potential bias may become introduced when comparing clinical outcomes based on varying and continuously evolving staging systems of digestive diseases.

Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic type. Here we report such a case where comprehensive tumor profiling by next generation sequencing (NGS) as well as immunohistochemistry revealed two independent adenocarcinomas comprising what was initially diagnosed as a single adenocarcinoma of the gastroesophageal (GEJ) junction. Biopsy of the esophageal portion of the GEJ mass showed a mismatch repair deficient tumor with loss of immunoreactivity for MLH1 and PMS2, while the biopsy taken from the gastric portion of the mass revealed a separate tumor with a discordant, non-overlapping, set of molecular alterations, including an EML4::ALK fusion, as well as intact MMR. This case illustrates one way in which NGS can reveal diagnoses such as collision tumor that are wholly unexpected based on clinical and histological grounds. Such diagnoses can have important implications for patient care, particularly in cases where there is discordance for targetable molecular alterations.

The incidence of gastroesophageal cancers is rising, driven, in part, by an increasing burden of risk factors of obesity and gastroesophageal reflux. Despite efforts to address these risk factors, and a growing interest in methods of population screening, the bulk of these tumours are unresectable at diagnosis. In this setting, effective systemic treatments are paramount to improve survival and quality of life. Early and accurate identification of oncogenic drivers, such as human epidermal growth factor receptor 2 (HER2), present in 5-30% of gastroesophageal adenocarcinomas (GEAs), is integral to guide choice of therapies due to the clear predictive implications that arise from overexpression of this receptor. After trastuzumab, the first anti-HER2 agent with approved use in HER2-positive GEA, the addition of pembrolizumab to first-line trastuzumab-chemotherapy and trastuzumab deruxtecan in the refractory space have more recently changed practice. Yet, the response to these agents has been vastly different across patients with HER2-positive disease, underpinning the need for reliable biomarkers of response. Emergent data have suggested that levels of HER2 expression on tissue or liquid biopsies may predict response to first-generation HER2 therapies while HER2 heterogeneity, receptor changes, co-occurring molecular alterations and oncogenic genomic and metabolic reprogramming may be implicated in resistance. A robust knowledge of the mechanisms of resistance and response to HER2-directed therapies is necessary to inform novel strategies of HER2-targeting and guide choice combinations with other biomarker-directed therapies, to improve outcomes from a new generation of clinical trials in HER2-positive GEA. Understanding and close examination of previous failures in this space form an important part of this assessment, as does correlative biomarker and translational work pertaining to the role of HER2 and dynamic changes that result through treatment exposure. In this review, we aim to provide an overview of strategies for HER2 targeting, summarising both the successes and disappointments in this therapeutic landscape and discuss existing challenges and future perspectives on development in this highly morbid tumour type.

Radiology practices may choose to divide interpretation of concurrently acquired chest and abdominal CT examinations between two readers. Although this approach has benefits, there also are potential pitfalls that should be recognized and avoided, such as differences in contrast material timing that can cause an abdominal finding to be more conspicuous on the chest examination, and vice versa. Pathologic lesions that cross the boundary between the chest and abdomen, as well as precise delineation of that boundary, also create issues. Additionally, there can be uncertainty regarding the responsibilities as a secondary reader for the region of overlap. Example cases demonstrate these potential pitfalls, and strategies are provided for mitigating or avoiding them. These cases include pancreatic adenocarcinoma visualized only on the chest images, pulmonary embolism best seen on the abdominal images, and metastatic gastrointestinal stromal tumor invading into the chest. Mitigation strategies discussed include appropriate search pattern modification as well as the importance of establishing guidelines and facilitating ease of communication between radiologists. ©RSNA, 2025.

Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.

Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries. Formalin-fixed paraffin-embedded primary tumour endoscopic biopsy samples were collected and submitted for central morphological and immunohistochemical characterization and TP53 molecular assessment and Helicobacter pylori infection.

A total of 259 patients were included in the study: 137 (53%) from LATAM and 122 (47%) from Europe. Significant biological differences were detected between European and LATAM patients. Low representation of chromosomal instability (CIN) and HER2 positive cases were found in LATAM. MUC6 and PD-L1 were more frequently overexpressed in European cases, showing a significant correlation across the entire study population, with this association being especially pronounced in MMRdeficient cases. Both TP53 mutation by next-generation sequencing and p53 immunohistochemical aberrant pattern were linked with features associated with chromosomal instability. No regional differences were observed in H. pylori prevalence or abundance, indicating that the afore mentioned variations cannot be attributed to this factor.

Our findings underscore a need for region-specific approaches in gastroesophageal cancer diagnosis and treatment. MUC6 emerges as a putative immune regulator that needs further investigation. Research tailored to the unique biological profiles in different global regions is crucial to effectively address the observed disparities.

Background: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the esophago-gastric junction (EGJ) are rare aggressive malignant neoplasms, with, currently, limited evidence regarding the appropriate therapeutic approach. Methods: Herein, we report multimodal treatment management of a patient with oligometastatic MiNEN of EGJ (Siewert III), discuss the lessons learnt, and provide a review of the literature. Results: A 69-year-old female was diagnosed with a locally advanced EGJ tumor and three liver metastases (cT4, cN+, M1). Although the initial histology from biopsy revealed adenocarcinoma, the histopathology of a lymph node biopsy from staging laparoscopy revealed infiltration of neuroendocrine carcinoma cells. Thus, the diagnosis of a mixed neuroendocrine adenocarcinoma was set, and systemic chemotherapy with etoposide and cisplatin was initiated. A major clinical response led to conversion surgical resection of the primary tumor and metastases, followed by adjuvant therapy with immunotherapy. The patient is free of disease at the 3-year follow-up. A review of the literature on similar cases of EGJ or gastric MiNENs revealed a limited number of cases. Out of the 39 patients, 20 of them (51.3%) suffered from advanced-stage disease. The MiNEN diagnosis typically occurred after surgical resection. Systemic chemotherapy against the neuroendocrine component demonstrated significant response rates, while in cases in which conversion surgery was offered, prolongation of survival was demonstrated. Conclusions: Our case and the existing literature on MiNENs of EGJ underline the need for a personalized treatment approach following thorough interpretation of comprehensive pretherapeutic staging. Conversion radical surgery with curative intent could be considered in cases of major or complete clinical response to induction chemotherapy with potentially favorable outcomes.

The surgery of adenocarcinoma of the esophagogastric junction (AEG) is a complex procedure that increases postoperative morbidity compared to distal gastric cancer. In this study, we included thoracic anatomical parameters of patients for the first time to investigate their impact on the postoperative outcomes of transabdominal gastrectomy for Siewert type II/III AEG.

All patients with Siewert type II or III AEG of our institution who underwent transabdominal proximal or total gastrectomy from January 2015 to December 2022 were included in this study. We measured thoracic anatomical parameters on the level of the lower edge of the sternum using preoperative computer tomography. The anteroposterior diameter of the thorax was measured as the distance from the posterior edge of the sternum to the anterior edge of the spine, while the transverse diameter was the maximum distance between the ribs on both sides. Patients' data and postoperative details were retrospectively collected. Correlation between thoracic anatomical parameters with postoperative complications were analyzed.

Overall, 647 patients were eligible for this study. The incidence of postoperative complications was 28.1%, with postoperative pulmonary complications occurring in 24.7%. In multivariate analysis, anteroposterior thoracic diameter > 10.2 cm was an independent risk factor for postoperative complications (OR = 1.891, 95% CI: 1.137-3.146, p = 0.014), transverse thoracic diameter > 23.3 cm was an independent risk factor for postoperative pulmonary complications (OR = 2.243, 95% CI: 1.234-4.079, p = 0.004). In open group, transverse thoracic diameter over 23.3 cm correlated independently with postoperative complications (OR = 2.451, 95% CI: 1.219-4.927, p = 0.012) and postoperative pulmonary complications (OR = 2.988, 95% CI: 1.407-6.347, p = 0.004). However, this correction was not significant in laparoscopy-assisted group.

Thoracic size is an independent risk factor affecting the postoperative outcomes of transabdominal gastrectomy for Siewert type II and III AEG. Patients with larger thoracic cage are at a higher risk of postoperative complications, particularly pulmonary complications. For those patients, laparoscopic surgery may be a viable option.

This prospective, nonrandomized, open-label phase 2 trial (Chinese Clinical Trial Registry, ChiCTR2200061906) aimed to evaluate the effectiveness of adding the PD-1 antibody tislelizumab to perioperative chemotherapy in patients with locally advanced gastroesophageal junction adenocarcinoma (GEJA). This study enrolled patients with GEJA clinically staged as cT3-4aNanyM0 or cT1-2N+M0 from October 2022 to June 2023. Eligible patients were administered three preoperative and five postoperative 3-week cycles of treatment with PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. Thirty-two patients were enrolled. The median age was 60 years (range: 28-74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 93.8% (30/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. The R0 resection rate was 96.9% (31/32). MPR, pathological complete response (pCR) of primary tumors and ypT0N0 rates were 50.0% (16/32, 95% CI: 31.9-68.1%), 28.1% (9/32, 95% CI: 13.7-46.7%) and 25.0% (8/32, 95% CI: 11.5-43.4%), respectively. The surgical morbidity rate was 15.6% (5/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment periods, the rate of treatment-related grade 3-4 adverse events was 31.2% (10/32). At the date of 7th Jan 2025, 8 (25.0%) patients occurred recurrence. Therefore, perioperative tislelizumab plus chemotherapy demonstrated significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJA.

Gastric cancer is a leading cause of cancer and cancer-related mortality worldwide, especially in East Asia. It is often diagnosed at an advanced stage, which carries a poor prognosis. Patients with advanced gastric cancer typically receive systemic therapy and best supportive care. For patients with locally advanced gastric cancer, a combination of systemic therapy and surgical resection is recommended, while surgical resection-alone is recommended for patients with early-stage localized tumors. Surgical resection, including total gastrectomy, distal gastrectomy, and proximal gastrectomy, is recommended for resection of localized tumors based on tumor location. Herein, the authors provide an overview of open gastrectomy resection and reconstruction techniques.

The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. Eligibility criteria included a primary tumor with a clinical stage of cT1 cN+, cT2-4a cN+, or cT2-4a cN0 disease, in which T indicates the size and extent of the tumor (higher numbers indicate a more advanced tumor), and N indicates the presence (N+) or absence (N0) of cancer spread to the lymph nodes, without evidence of metastatic spread. The primary end point was overall survival.

From February 2016 through April 2020, we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group. With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group (hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P = 0.01). Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group (hazard ratio for disease progression or death, 0.66; 95% CI, 0.51 to 0.85). Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. Serious adverse events were observed in 98 of 207 patients (47.3%) in the FLOT group and in 82 of 196 patients (41.8%) in the preoperative-chemoradiotherapy group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group.

Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy. (Funded by the German Research Foundation; ESOPEC ClinicalTrials.gov number, NCT02509286.).

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area. Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version. Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

To explore whether neoadjuvant Sintilimab is suitable for patients with gastroesophageal junction (GEJ) adenocarcinoma, we designed this study to evaluate the short-term efficacy and safety of neoadjuvant Sintilimab in combination with chemotherapy for resectable GEJ adenocarcinoma.

We retrospectively collected data on patients with GEJ adenocarcinoma who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at Jining First People's Hospital between October 2020 and October 2023. The primary endpoint was complete pathological response (pCR) rate; secondary endpoints: major pathological response (MPR) rate, neoadjuvant therapy-related adverse events (AES), the safety of surgery, Postoperative Complications, and overall survival (OS).

24 eligible patients were enrolled in the study and achieved a pCR rate of 16.7%. The treatment-related AES was manageable. The median time interval between the end of neoadjuvant therapy and surgery was 35 days (28-81 days), R0 resection rate was 100%. The most common postoperative complications in the study were pneumonia (n = 11, 45.8%). Median follow-up was 13.5(interquartile range: 8.00, 25.50) months, Kaplan-Meier survival analysis showed median OS was not reached.

It was safe and effective for resectable GEJ adenocarcinoma to undergo neoadjuvant Sintilimab combined with chemotherapy followed by surgery, and long-term efficacy needs to be confirmed by further follow-up.

Background and Objectives: The Esophageal Adenocarcinoma Study Group Europe (EACSGE) recently proposed a granular histologic classification of esophageal-esophago-gastric junctional adenocarcinomas (EA-EGJAs) based on the study of naïve surgically resected specimens that, when combined with the pTNM stage, is an efficient indicator of prognosis, molecular events, and response to treatment. In this study, we compared histologic classes of endoscopic biopsies taken before surgical resection with those of the surgical specimen, to evaluate the potential of the EACSGE classification at the initial diagnostic workup. Methods: A total of 106 EA-EGJA cases with available endoscopic biopsies and matched surgical resection specimens were retrieved from five Italian institutions. Histologic classification was performed on all specimens to identify well-differentiated glandular adenocarcinoma (WD-GAC), poorly differentiated glandular adenocarcinoma (PD-GAC), mucinous muconodular carcinoma (MMC), infiltrative mucinous carcinoma (IMC), diffuse desmoplastic carcinoma, diffuse anaplastic carcinoma (DAC), and mixed subtypes. Related risk subgroups (low-risk versus high-risk) were also assessed. The correlations of histologic classes and risk subgroups between diagnostic biopsies and surgical resection specimens were explored with Spearman's correlation test. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, true positives, true negatives, false positives, and false negatives were also calculated. Results: A strong positive correlation between biopsies and surgical specimens occurred for both histologic classes (coefficient: 0.75, p < 0.001) and risk subgroups (coefficient: 0.65, p < 0.001). The highest sensitivities and specificities were observed for MMC, IMC, and DAC (100% and 99% for all), followed by WD-GAC (sensitivity 91%, specificity 79%) and PD-GAC (sensitivity 722%, specificity 86%). The low-risk and high-risk groups presented a sensitivity and specificity of 89% and 76% (low-risk) and 76% and 89% (high-risk). Conclusions: The EACSGE histologic classification of EA-EGJAs and associated prognostic subgroups can be reliably assessed on pre-operative diagnostic biopsies. Further studies on larger and more representative cohorts of EA-EGJAs will allow us to validate our findings and confirm if the EA-EGJA biopsy histomorphology and clinical TNM staging will be as efficient as the surgical specimen histomorphology and pTNM in predicting patient prognoses and tailoring personalized therapeutic approaches.

Introduction: Performing a tandem endoscopy and colonoscopy in selected individuals has advantages, such as the early detection of benign and/or precancerous foregut diseases; it is efficient, and it may allow added therapies. It may also have disadvantages, such as generating anxiety from false-positive screening, possible harm from further testing, and unproven cost-effectiveness. Aims: We aimed to examine the prevalence of foregut endoscopic and histologic abnormalities in subjects referred for screening/surveillance colonoscopy who also underwent a tandem endoscopy. We wanted to (1) assess implications for cancer detection, intervention, and surveillance of precancerous foregut abnormalities, (2) identify benign foregut lesions, and (3) generate data on the utilities of this tandem approach. Patients and Methods: A retrospective cohort study of consecutive subjects referred for screening or surveillance colonoscopy who also underwent an endoscopy. Based on national screening guidelines, responses to prompting questions, personal or family history, or other risk factors, subjects were assigned to tandem endoscopy with biopsies (modified Seattle and Sydney protocols), under one anesthesia. Results: Of the 1004 patients referred for colonoscopy, 317 (32%) underwent tandem endoscopy. There were 214 women and 103 men. There were 237 Whites, 16 Asians, 40 Blacks, and 24 Hispanics. Median age was 59 (range 19-85). At endoscopy, we identified actionable benign (45%) peptic, inflammatory, and H. pylori-related abnormalities, and premalignant findings (i.e., intestinal metaplasia, 27%, dysplasia, 2%, and cancer 0.9%), comparable to the premalignant (40.3%) and malignant (0.6%) colonoscopy yield. Conclusions: When implemented based on national screening guidelines, tandem EGD and colonoscopy combines Barrett's esophagus and gastric cancer screening in one examination, and it has a high yield in a diverse US population.

In submucosal invasive adenocarcinoma of the esophagogastric junction (pT1b-SM AEG), the extent of tumor submucosal (SM) invasion is measured using the vertical depth of SM invasion with the muscularis mucosa. This study aimed to investigate whether tumor thickness and depth of invasion without accounting for muscularis mucosa were superior to the vertical depth of SM invasion as metastasis predictors. We enrolled patients with pT1b-SM AEG who underwent endoscopic resection or surgical resection (SR) at our institution between January 2011 and September 2019 and were followed up for ≥2 years. The relationship between metastasis and clinicopathological factors was examined. Metastasis was defined as pathologically confirmed lymph node metastasis in the surgical specimen or recurrence during follow-up. This study included 57 patients (44 men; median age, 72 years). Endoscopic resection and SR were performed in 16 and 41 patients, respectively. Nine patients were diagnosed with metastasis: five who underwent SR showed pathologically confirmed lymph node metastasis in the surgical specimens, and four experienced recurrences during a median follow-up of 48 months. Univariate analyses showed that tumor thickness was significantly associated with metastasis (P = 0.021), and the vertical depth of SM invasion (P = 0.48) and depth of invasion (P = 0.38) were not. Furthermore, in multivariate analysis, tumor thickness ≥2800 μm (odds ratio, 38.70; P = 0.013) was a significant predictor for metastasis. Tumor thickness may be a more convenient and useful predictor of metastasis in patients with pT1b-SM AEG than the vertical depth of SM invasion.

The appropriate extent of resection for esophagogastric junction cancer and the method of surgical approach remain controversial. This study aimed to assess the safety and outcomes of the parachute technique, which is an open transhiatal reconstruction method that facilitates stable reconstruction.

The surgical outcomes of 20 consecutive patients who underwent open lower- esophagogastrectomy for EGJ cancer at Kitasato University Hospital from June 2019 to July 2023 were retrospectively reviewed.

The esophagus was transected, and a purse-string suture was placed at the stump. Then, a fixing string was placed. Hence, the mucosa, muscular layer, and adventitia, including the string of the purse-string suture, were not displaced. By placing approximately 10 stay sutures around the whole esophageal stump, the esophageal stump can be opened to the maximum diameter. Then, insert the anvil head into the esophagus lumen while laying it sideways, and it can be put on smoothly without stress.

In total, there were 17 and 3, male and female patients, respectively. The median esophageal invasion length was 12.5 (0-30) mm. One patient presented with cStage I EGJ cancer, four with cStage II, 14 with cStage III, and one with cStage IV. In terms of postoperative complications, three (15%) patients developed grade II intra-abdominal fluid correction according to the Clavien-Dindo classification. However, none of the patients presented with anastomotic leakage.

The parachute technique can be a safe and effective reconstruction technique as it does not cause anastomotic leakage.

The safety of proximal gastrectomy (PG) for the treatment of advanced Siewert II adenocarcinoma of the esophagogastric junction (AEG) remains debatable. In this study, we aim to evaluate the oncological safety of PG and the metastasis rate of key distal lymph node dissection, which is typically excluded in PG.

This study retrospective collected advanced Siewert II AEG patients who underwent gastrectomy at the First Medical Center of the General Hospital of the People's Liberation Army (PLA) from January 2014 to December 2019. A total of 421 patients were enrolled, including 237 PG and 184 total gastrectomy (TG). Propensity score matching (PSM) in a 1:1 ratio was performed to reduce the influence of confounding variables.

After PSM, 153 cases were matched in each group. The TG group had longer operation time, more lymph node detection and longer postoperative hospitalization time than the PG group (Both P < 0.05). The postoperative complications of the two groups were not statistically significant (P > 0.05). For long-term complications, the incidence of reflux esophagitis and anastomotic stenosis were significantly higher in the PG group than in the TG group (Both P < 0.05), but dumpling syndrome and anemia were significantly lower in the PG group compared to the TG group (Both P < 0.05). The 3-year overall survival (OS) and disease-free survival (DFS) between the two groups were no statistically significant difference (OS: 77.4% and 80.9%, P = 0.223; DFS: 69.7% and 76.1%, P = 0.063). Distal lymph node metastasis rates for No.4d, 5, and 6 were all less than 5%, and the therapeutic value index were also relatively low, with values of 1.09%, 3.26%, and 1.45%, respectively. In addition, the distal No.4d, 5, or No.6 lymph node metastasis rates were significantly higher in patients with tumor size ≥ 4 cm and T4 stage (14.29% and 23.40%) than in patients with tumor size < 4 cm and T2-3 (2.78% and 5.11%) (Both P < 0.05). The results of subgroup survival analysis showed that for patients with tumor size ≥ 4 cm or T4 stage, the TG group had better DFS compared with the PG group (HR 0.618, 0.387-0.987, P = 0.044), while no significant survival benefits were observed in other subgroups.

In summary, for Siewert II AEG with tumor size < 4 cm and T2-3 stage, PG may be a reasonable choice with comparable oncological efficacy to TG. But for higher survival benefits, TG remains gold standard particularly for patients with tumor size ≥ 4 cm or T4 stage.

Serum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection.

Consecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS).

Among 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (p = 0.002) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (p = 0.005) in multivariable analysis. The ROC curve of FAR (AUC = 0.744) outperformed fibrinogen (AUC = 0.738) and albumin (AUC = 0.378) in predicting OS for AEG patients.

The FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively.

The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population.

Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year.

A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1-3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1 cm, 0.026 (0.011-0.054)%/year for 1-3 cm, and 0.58 (0.042-2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively.

By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE.

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.

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.

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.

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.

Analyze the pattern of lymph node metastasis in Siewert II adenocarcinoma of the esophagogastric junction (AEG) and provide a basis for the principles of surgical access.

The clinical data of 112 Siewert type II AEG patients admitted to the Fifth Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2020 to 2022 were retrospectively collected. The probability of lymph node metastasis in each site and the clearance rate of lymph nodes in each site by different surgical approaches were analyzed.

The lymph node metastasis rates in the middle and upper mediastinum group, the lower mediastinum group, the upper perigastric + supra pancreatic group, and the lower perigastric + hepatoduodenal group were 0.0%, 5.4%, 61.6%, and 17.1%, (P < 0.001). The number of lymph nodes cleared in the middle and upper mediastinum group was 0.00, 0.00, 4.00 in the transabdominal approach (TA), left thoracic approach (LT), and Ivor-Lewis (IL) group, (P < 0.001); The number of lymph nodes cleared in the lower mediastinal group was 0.00, 2.00, 2.00, (P < 0.001); The number of lymph node dissection in the perigastric + hepatoduodenal group was 3.00, 0.00, and 8.00, (P < 0.001). The overall complication rates were 25.7%, 12.5%, and 36.4%, (P = 0.058).

Siewert II AEG has the highest rate of lymph node metastasis in the upper perigastric + supra-pancreatic region, followed by the lower perigastric + hepatoduodenal, lower mediastinal, middle, and upper mediastinal regions. Ivor-Lewis can be used for both thoracic and abdominal lymph node dissection and does not increase the incidence of postoperative complications.

Oesophagogastric junction carcinoma is now being increasingly regarded as a distinct site of neoplasia, separate from its adjacent sites. Recent advances in multimodal treatment approaches, including endoscopic procedures, oesophagectomy with three-field lymph node dissection, and definitive chemoradiotherapy, have significantly improved overall patient survival rates. Despite these advancements, the recurrence rate remains around 50% within one to three years following initial surgery. A major challenge in management arises when the resected surgical margins are involved with cancer. We present a 55-year-old man who experienced progressive dysphagia and, upon further assessment, was noted to have a Siewert III oesophagogastric junction adenocarcinoma. He underwent neoadjuvant chemotherapy before undergoing total gastrectomy with D2 lymphadenectomy with a Roux-en-Y reconstruction. Histopathological examination of the resected specimen revealed a positive proximal margin involvement. After optimization, he then underwent a salvage three-field McKeown oesophagectomy with colonic conduit reconstruction and adjuvant chemotherapy. Salvage surgery can be considered for patients with locoregional recurrence after definitive chemoradiotherapy or surgery. Other options include salvage chemoradiotherapy. Our case outlines the importance of proper patient selection for salvage surgery and highlights the choices of conduit in patients undergoing total esophagectomy post gastrectomy.  In conclusion, managing proximal margin involvement of cardioesophageal junction adenocarcinoma remains a complex and multifaceted challenge, necessitating a tailored, multidisciplinary approach. The decision-making process must consider the patient's functional status, previous treatments, and specific anatomical considerations.

Esophagectomy is associated with significant mortality. A better understanding of the causes leading to death may help to reduce mortality. A root cause analysis of mortality after esophagectomy was performed.

Root cause analysis was retrospectively applied by an independent expert panel of 4 upper gastrointestinal surgeons and 1 anesthesiologist-intensivist to patients included in the French national multicenter prospective cohort FREGAT between August 2014 and September 2019 who underwent an esophagectomy for cancer and died within 90 days of surgery. A cause-and-effect diagram was used to determine the root causes related to death. Death was classified as potentially preventable or non-preventable.

Among the 1,040 patients included in the FREGAT cohort, 70 (6.7%) patients (male: 81%, median age 68 [62-72] years) from 17 centers were included. Death was potentially preventable in 37 patients (53%). Root causes independently associated with preventable death were inappropriate indication (odds ratio 35.16 [2.50-494.39]; P = .008), patient characteristics (odds ratio 5.15 [1.19-22.35]; P = .029), unexpected intraoperative findings (odds ratio 18.99 [1.07-335.55]; P = .045), and delay in diagnosis of a complication (odds ratio 98.10 [6.24-1,541.04]; P = .001). Delay in treatment of a complication was found only in preventable deaths (28 [76%] vs 0; P < .001). National guidelines were less frequently followed (16 [43%] vs 22 [67%]; P = .050) in preventable deaths. The only independent risk factor of preventable death was center volume <26 esophagectomies per year (odds ratio 4.71 [1.55-14.33]; P = .006).

More than one-half of deaths after esophagectomy were potentially preventable. Better patient selection, early diagnosis, and adequate management of complications through centralization could reduce mortality.