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Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 15 May 2026 | Viewed by 15351

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Dr. Tania Triantafyllou

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1st Propaedeutic Surgical Department, National and Kapodistrian University of Athens, Hippokrateion General Hospital, Athens, Greece
Interests: surgery; upper GI surgery; minimally invasive and laparoscopic surgery; robotic surgery; upper GI endoscopy; impedance pH-metry; esophageal cancer; hiatal hernia repair
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Dr. Maximos Frountzas

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First Propaedeutic Department of Surgery, Hippocration General Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: gastrointestinal cancer; gastric cancer surgery; esophageal cancer surgery; pancreatic cancer surgery; oncology; nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastroesophageal junction cancer is the eighth most common malignancy and the sixth most common cause of death secondary to cancer. Even though prognosis still largely depends on disease progression, recent breakthroughs have significantly improved associated outcomes. This Special Issue will focus on the advances of the diagnostics, endoscopic resections, perioperative therapies and minimally invasive and robotic techniques in the treatment of gastroesophageal malignancy. Esophagectomy presents high morbidity and mortality rates; however, a multimodal approach in the management of postoperative complications seems to offer good results, whereas minimally invasive approaches tend to improve part of the complications. The role of chemotherapy, chemoradiotherapy and immunotherapy in the curative and palliative setting of esophageal cancer will be discussed, whereas the therapeutic approach of the oligometastatic disease shall be presented.

Dr. Tania Triantafyllou
Dr. Maximos Frountzas
Guest Editors

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Keywords

gastroesophageal cancer
endoscopic therapy
minimally invasive surgery
multimodality treatment
immunotherapy

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Published Papers (8 papers)

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Research

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21 pages, 859 KB

Open AccessArticle

Predicting the Unpredictable: Prognostic Role of Systemic Inflammatory Indices and Tumor Biology of Neoadjuvant Chemotherapy Response in Gastric and Gastroesophageal Junction Cancer—Insights from a Systematic Review and Real-World Experience

by Sibel Oyucu Orhan, Bedrettin Orhan, Yağmur Çakır, Seda Sali, Burcu Caner, Birol Ocak, Ahmet Bilgehan Şahin, Adem Deligönül, Erdem Çubukçu and Türkkan Evrensel

J. Clin. Med. 2026, 15(4), 1484; https://doi.org/10.3390/jcm15041484 - 13 Feb 2026

Viewed by 609

Abstract

Background/Objectives: Perioperative chemotherapy is the standard treatment for locally advanced gastric and gastroesophageal junction adenocarcinoma; however, substantial uncertainty remains regarding the optimal management of non-responding patients and the prognostic relevance of biological and inflammatory biomarkers. This study aimed to determine, using real-world data integrated with a comprehensive literature review, whether long-term survival is driven primarily by the choice of chemotherapy regimen or by the tumor’s intrinsic biological aggressiveness and the host’s systemic inflammatory response. Methods: A retrospective analysis was performed of 43 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. Survival outcomes were stratified by regimen (FLOT versus non-FLOT) and analyzed using Kaplan–Meier methods. The prognostic value of clinicopathological features and systemic inflammatory indices was assessed using multivariate Cox regression models to identify independent predictors of mortality. Results: Although FLOT showed a trend toward improved overall survival (OS) (median not reached vs. 18.9 months), this difference did not reach statistical significance. Univariate analysis linked lymphovascular invasion (LVI) (HR = 4.17; p = 0.003), pan-cytokeratin (panCK) (HR = 2.44; p = 0.032), and monocyte-to-lymphocyte ratio (MLR) (HR = 1.73; p = 0.027) with survival. To minimize overfitting, two multivariate models were constructed. The first confirmed LVI (HR = 7.32; p < 0.001) and panCK (HR = 4.30; p = 0.006) as independent prognostic markers. The second identified MLR (HR = 1.65; p = 0.033) and panCK (HR = 2.42; p = 0.034) as independent adverse factors. Conclusions: Our findings suggest a paradigm shift in prognostic assessment for locally advanced gastric cancer: therapeutic success appears to depend more on underlying tumor biology and the immune microenvironment than on any specific neoadjuvant regimen. High MLR and LVI serve as strong surrogate markers of a biologically aggressive, chemotherapy-resistant phenotype. Consequently, future clinical strategies should move beyond a “one-size-fits-all” chemotherapy approach and prioritize these biomarkers for risk stratification and personalization of multimodal therapy. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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17 pages, 1147 KB

Open AccessArticle

Adjuvant Chemotherapy and Chemoradiotherapy in Gastric Cancer: Prognostic Determinants and Real-World Survival Outcomes

by Sedat Yildirim, Hatice Odabas, Seval Ay Ersoy, Seval Orman, Miray Aydogan, Ezgi Turkoglu, Goncagul Akdag, Hamit Bal, Melike Pekyurek Varan, Deniz Isik and Nedim Turan

J. Clin. Med. 2026, 15(2), 553; https://doi.org/10.3390/jcm15020553 - 9 Jan 2026

Viewed by 565

Abstract

Objective: The role of adjuvant chemoradiotherapy (CRT) following curative gastrectomy remains controversial, especially in the context of D2 dissection. This research evaluated survival indicators through an analysis of previous observational studies and it evaluated treatment outcomes between patients who underwent CRT and those who received CT as their sole therapy. Methods: The researchers performed a non-randomized retrospective cohort study which analyzed 206 patients who underwent R0–R1 resection for gastric adenocarcinoma and received either adjuvant CRT (n = 107) or CT alone (n = 99). A Kaplan–Meier analysis together with Cox regression methods were used to evaluate survival outcomes of patients. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline differences between groups at the beginning of the study. The median follow-up was 52.0 months. Results: The baseline characteristics differed markedly between groups, with CRT patients showing higher rates of T4 tumors (34.6% vs. 22.2%), N3 disease (47.7% vs. 26.3%), vascular invasion (72.9% vs. 50.5%), and R1 resection (10.3% vs. 1.0%). Unadjusted survival favored CT alone (median DFS 81.7 vs. 103.9 months; median OS 86.2 months vs. not reached). These differences lost significance after IPTW adjustment (DFS: HR 1.18, p = 0.428; OS: HR 1.24, p = 0.336). T3–T4 stage, N2–N3 nodal status, vascular invasion, and positive margins emerged as independent prognostic factors. Subgroup analyses revealed no treatment interactions (all p > 0.05). Conclusions: The research used a retrospective study design which showed substantial differences between treatment groups at the beginning of the study. The survival results that showed better outcomes for CT alone became attenuated after the researchers applied propensity score adjustment to adjust for confounding from treatment selection. The study established that advanced T–N stage, vascular invasion, and positive margins were identified as independent prognostic factors. The research results are hypothesis-generating and require randomized controlled trials to establish the exact difference in effectiveness between different treatments. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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15 pages, 855 KB

Open AccessArticle

An Opportunistic Screening Strategy for Gastric Cancer Based on Questionnaire and Sequential Serology: A Hospital-Based Cross-Sectional Study (SIGES)

by Wen Xiang, Zhuo-Yu Li, Yan Huang and Xin-Zu Chen

J. Clin. Med. 2026, 15(1), 24; https://doi.org/10.3390/jcm15010024 - 19 Dec 2025

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Abstract

Objectives: In the absence of massive screening programs, it is imperative to develop and validate a candidate selection strategy for opportunistic endoscopic screening (OES) targeting the early detection of gastric cancer. Methods: A hospital-based cross-sectional study was conducted, enrolling both health check-up controls and gastric cancer patients. Data collection included two components: (1) a questionnaire including demography, self-reported comorbidities, and family history of cancers; (2) serology including hemoglobin, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Associations between potential variables and gastric cancer risk were assessed and the predictive efficacy of these risk factors was quantified. Sequentially, risk stratification scoring systems were constructed and their cost-effectiveness profiles were evaluated. Results: A total of 58,218 participants were included in the analysis, among whom 619 (1.1%) were gastric cancer patients. Multivariate analyses identified male, age >40 years, family history of gastric cancer, comorbidities of upper digestive tract benign diseases (UDTBDs), anemia, and elevated serum CEA and/or CA19-9 as independent risk factors of increasing gastric cancer risk. Cost-effectiveness analysis demonstrated that individuals, especially those symptomatic, presenting any of following conditions should be recommended for OES: (1) age ≥50 years, (2) family history of gastric cancer, and/or (3) comorbid UDTBDs. Elsewise, unclear anemia and/or elevated serum CEA and/or CA19-9 presenting among males and/or persons 41–50 years of age should be considered for OES. Notably, this selection strategy achieved a detection rate comparable to that of alternative protocols while yielding superior cost-effectiveness outcomes. Conclusions: The integrated strategy combining questionnaire and sequential serology represents an effective and cost-effective approach to identifying high-risk candidates for gastric cancer OES. Further investigations are warranted to develop more precise and tailored screening and surveillance protocols, with the aim of optimizing both detection rates and cost-effectiveness in clinical practice. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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12 pages, 1107 KB

Open AccessArticle

Stenting Versus Endoscopic Vacuum Therapy for Anastomotic Leakage After Esophago-Gastric Surgery

by Carlo Galdino Riva, Stefano Siboni, Matteo Capuzzo, Francesca Senzani, Lorenzo Cusmai, Daniele Bernardi, Pamela Milito, Andrea Lovece, Eleonora Vico, Marco Sozzi and Emanuele Luigi Giuseppe Asti

J. Clin. Med. 2025, 14(19), 7075; https://doi.org/10.3390/jcm14197075 - 7 Oct 2025

Cited by 2 | Viewed by 1505

Abstract

Background: Anastomotic leakage (AL) is a major complication after esophago-gastric surgery, with incidence rates of 11–21% and mortality up to 14%. Early intervention is essential to reduce morbidity. Endoscopic treatments have advanced, with self-expandable metal stents (SEMSs) as the traditional standard (success ~90%), but they carry risks like migration, stenosis, and need for drainage. Endoscopic vacuum therapy (EVT), applying negative pressure to drain secretions and promote healing, has shown success rates of 66–100%. Limited comparative data exists from small retrospective studies. This study compares SEMS and EVT for safety and efficacy in AL management. Methods: A retrospective case–control study from a prospective database at our institution was performed (March 2012–2025). We included patients with AL post-esophageal/gastric surgery treated endoscopically (SEMS or EVT). We excluded patients treated with conservative or surgical management. Demographics, comorbidities, oncology, surgery type, leak details, treatments, and outcomes were collected. Primary outcome was complete healing of the leak, while secondary outcomes were time to success, number of procedures needed, hospital stay, complications, mortality. Results: From 592 resections, we extracted 68 AL (11.5%), 45 of which met the inclusion criteria (22 SEMS, 23 EVT). Groups were similar demographically, but SEMS had more respiratory issues (43% vs. 8.7%, p = 0.018). SEMS were used more after esophagectomy (86.4% vs. 56.5%, p = 0.004); EVT was performed mostly after gastrectomy (34.7% vs. 9.1%, p = 0.009). Success rate was 86.4% for SEMS vs. 95.6% for EVT (p = 1.000). Complications were significantly lower in EVT (8.3% vs. 50%, p = 0.001; SEMS: 36.4% migrations, 18.2% stenoses). Leak onset time, modality of diagnosis, and leak size were comparable among the groups. Need for jejunostomy was higher in EVT (43.5% vs. 9.1%, p = 0.015), while chest drains in SEMS (63.7% vs. 13.1%, p < 0.001). Hospital stays (33–38 days, p = 0.864) and mortality (22.7% vs. 8.7%, p = 0.225) were similar. No differences were observed in terms of long-term mortality (log-rank p = 0.815). Conclusions: SEMS and EVT are both effective for AL after esophago-gastric surgery. EVT offers fewer complications and shorter treatment, so it is favored especially for esophago-jejunal leaks. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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12 pages, 328 KB

Open AccessArticle

Addressing Anastomotic Leak After Esophagectomy: Insights from a Specialized Unit

by Alexandra Triantafyllou, Evgenia Mela, Charalampos Theodoropoulos, Andreas Panagiotis Theodorou, Eleni Kitsou, Konstantinos Saliaris, Sofia Katsila, Konstantinos Kakounis, Tania Triantafyllou and Dimitrios Theodorou

J. Clin. Med. 2025, 14(11), 3694; https://doi.org/10.3390/jcm14113694 - 25 May 2025

Cited by 2 | Viewed by 4684

Abstract

Background/Objectives: Anastomotic leakage is one of the most frightening and potentially fatal complications after esophagectomy. The collaboration between the surgical team, interventional gastroenterologists, and radiologists has the potential to improve the hospital stay, as well as morbidity and mortality. The aim of this study is to present our experience and evaluate the results of the multimodal management of anastomotic leak following esophagectomy in our unit. Methods: This is a retrospective study analyzing a single referral center’s prospectively maintained database of all patients diagnosed with anastomotic leak between March 2019 and March 2025 using the definition of the Esophageal Complications Consensus Group. The treatment pathways and the patient outcomes are presented. The primary endpoint was 90-day mortality and in-hospital mortality. Results: A total of 241 esophageal resections were performed between March 2019 and March 2025. Lymphadenectomy of the mediastinum was performed in 88.4% of the patients. Cervical and intrathoracic anastomosis were performed in 143 (59.3%) and 98 (40.7%) cases, respectively. Twenty-nine patients (12%) with a mean age of 59.1 years developed anastomotic leak. Anastomotic leak occurred in 14.3% of intrathoracic anastomoses and 10.5% of cervical anastomoses. The median day of leak diagnosis was the sixth postoperative day. Leak management involved conservative strategies, wound exploration, endoscopic stent placement or vacuum therapy, drainage of effusions under radiologic guidance, and reoperation. The 90-day and in-hospital mortality rate was 3.4%. No cases of conduit necrosis or mediastinitis were reported. Endoscopic management was employed in 18 patients (62.1%) as a first- or second-line treatment, while reoperation was required in 6 patients (20.7%). The median interval from diagnosis to anastomosis healing was 21 days and the median duration of hospital stay 32 days. The management was successful in 27 patients (93.1%) except for 1 who developed tracheoesophageal fistula and 1 who died due to hemorrhagic complication of anticoagulant treatment. Conclusions: Anastomotic leak after esophagectomy is considered a complex, diversified, and morbid clinical entity. The evolving potential of multidisciplinary management encompassing surgical and interventional radiological and endoscopic treatment addresses the mortality rates and heralds a new era of minimizing morbidity. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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10 pages, 197 KB

Open AccessArticle

Post-Esophagectomy Dumping Syndrome: Assessing Quality of Life of Long-Term Survivors

by Dionysios Dellaportas, Ioannis Margaris, Eleftherios Tsalavoutas, Zoi Gkiafi, Anastasia Pikouli, Despoina Myoteri, Nikolaos Pararas, Panagis M Lykoudis, Constantinos Nastos and Emmanuel Pikoulis

J. Clin. Med. 2025, 14(10), 3587; https://doi.org/10.3390/jcm14103587 - 21 May 2025

Cited by 2 | Viewed by 2294

Abstract

Background/Objectives: Survival rates for esophageal cancer patients have markedly improved. Inevitably, attention has been drawn to functional and quality-of-life problems. The aim of the current study was to investigate the prevalence of dumping syndrome in patients following esophageal resection and its correlation with postoperative quality of life. Methods: This cross-sectional study involved disease-free patients who underwent a potentially curative resection for esophageal or gastroesophageal junction carcinoma between January 2019 and January 2024 in a single academic institution. Patients were asked to fill in two questionnaires: the Dumping Syndrome Rating Scale (DSRS) and the QLQ-OG25. A Composite Dumping Syndrome Index (CDSI) was calculated by adding the summary severity and frequency scores for each patient. Results: During the study period, 42 patients underwent esophagectomy for malignant esophageal or junctional tumors. In total, 14 eligible patients responded to the questionnaires at a mean time of 19.7 (±20.8) months following their operation. Three patients (21%) reported having at least quite severe problems related to at least two dumping symptoms. Six patients (43%) reported that they avoid certain foods in order to alleviate related problems. A high CDSI score was associated with significantly increased OG25 scores for dysphagia, eating restriction, odynophagia, pain and discomfort, and reflux (p < 0.05). Conclusions: Early dumping syndrome can occur in a significant proportion of patients following esophagectomy and may adversely affect quality of life. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

21 pages, 8861 KB

Open AccessFeature PaperArticle

Oligometastatic Mixed Neuroendocrine Adenocarcinoma of the Esophago-Gastric Junction: A Case of Successful Multidisciplinary Management, the Lessons Learnt and Review of the Literature

by Anastasia Sotiropoulou, Maria Avgoustidou, Vassilis Milionis, Ioannis Papadimitriou, Chrysovalantis Vergadis, Dimitrios Schizas, Nikolaos Arkadopoulos and Orestis Lyros

J. Clin. Med. 2025, 14(5), 1503; https://doi.org/10.3390/jcm14051503 - 24 Feb 2025

Viewed by 1508

Abstract

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. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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Review

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20 pages, 453 KB

Open AccessReview

Current Role of Artificial Intelligence in the Management of Esophageal Cancer

by Evgenia Mela, Dimitrios Tsapralis, Dimitrios Papaconstantinou, Panagiotis Sakarellos, Chrysovalantis Vergadis, Michail E. Klontzas, Ioannis Rouvelas, Antonios Tzortzakakis and Dimitrios Schizas

J. Clin. Med. 2025, 14(6), 1845; https://doi.org/10.3390/jcm14061845 - 9 Mar 2025

Cited by 6 | Viewed by 2653

Abstract

Background/Objectives: Esophageal cancer (EC) represents a major global contributor to cancer-related mortality. The advent of artificial intelligence (AI), including machine learning, deep learning, and radiomics, holds promise for enhancing treatment decisions and predicting outcomes. The aim of this review is to present an overview of the current landscape and future perspectives of AI in the management of EC. Methods: A literature search was performed on MEDLINE using the following keywords: “Artificial Intelligence”, “Esophageal cancer”, “Barrett’s esophagus”, “Esophageal Adenocarcinoma”, and “Esophageal Squamous cell carcinoma”. All titles and abstracts were screened; the results included 41 studies. Results: Over the past five years, the number of studies focusing on the application of AI to the treatment and prognosis of EC has surged, leveraging increasingly larger datasets with external validation. The simultaneous incorporation in AI models of clinical factors and features from several imaging modalities displays improved predictive performance, which may enhance patient outcomes, based on direct personalized therapeutic options. However, clinicians and researchers must address existing limitations, conduct randomized controlled trials, and consider the ethical and legal aspects that arise to establish AI as a standard decision-support tool. Conclusions: AI applications may result in substantial advances in EC management, heralding a new era. Considering the complexity of EC as a clinical entity, the evolving potential of AI is anticipated to ameliorate patients’ quality of life and survival rates. Full article

(This article belongs to the Special Issue Gastroesophageal Cancer: Advances in Clinical Diagnosis and Management)

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