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Gastroesophageal Cancer: Outcomes and Therapeutic Management
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Gastroesophageal Cancer: Outcomes and Therapeutic Management

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

Deadline for manuscript submissions: closed (30 June 2025) | Viewed by 3293

Special Issue Editor

Dr. Michael K. Gibson

E-Mail Website
Guest Editor
Division of Hematology and Oncology, Department of Internal Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Interests: translational therapeutics; gastric cancer; molecular subtypes; head and neck cancers; circulating tumor DNA; presicion medicine

Special Issue Information

Dear Colleagues,

Gastroesophageal malignancies are a diverse group of cancers affecting the stomach, gastroesophageal junction, and esophagus, and they constitute a major cause of cancer-related fatalities globally. Current FDA-approved therapies include chemotherapy, immune checkpoint inhibitors (ipilimumab, pembrolizumab, and nivolumab), anti-VEGFR2 inhibitors (ramucirumab), and HER2-targeted drugs. However, managing advanced/metastatic disease remains challenging. In the case of distant metastatic disease, the 5-year overall survival (OS) rate is only around 5%. As the innovation of immunotherapy and HER2-targeted therapy have improved the outcomes of advanced/metastatic disease, they are currently being investigated for use in earlier localized disease.

An era of personalized therapies is emerging, with newer molecular targets being evaluated, such as claudin 18.2 (CLDN18.2), Dickkopf-1 protein (DKK1), tyrosine kinase inhibitors, and fibroblast growth factor receptor-2 (FGFR2). For instance, zolbetuximab, a monoclonal antibody targeting the tight junction protein CLDN-18.2, has shown promising results among patients with HER2-negative, CLDN-18-positive gastroesophageal cancer. While most of these biomarkers require tissue biopsy, blood-based assays are rapidly evolving, with circulation cell-free DNA (cfDNA) being used to detect genetic alterations. This newer, minimally invasive technology can aid in searching for molecular drug targets, monitoring treatment failure and the emergence of drug-resistant subclones, and capturing the genetic heterogeneity of tumor cells. In summary, these studies have paved the way for precision medicine’s utility in gastroesophageal cancer, providing hope for this challenging disease. As a result, we must continue to widen our knowledge of the precision treatment of gastroesophageal malignancies in clinical practice.

Dr. Michael K. Gibson
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastroesophageal cancer
  • targeted therapy
  • circulating tumor DNA
  • precision medicine
  • immune checkpoint inhibitors
  • esophageal cancer
  • gastric cancer
  • biomarkers
  • molecular characterization

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Published Papers (4 papers)

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Research

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13 pages, 480 KiB  
Article
Surgical Timing and Outcomes in Esophageal Cancer: Insights from One- and Two-Stage Esophagectomies in a Polish Cohort
by Bartłomiej Strzelec, Piotr Paweł Chmielewski, Wojciech Kielan and Julia Rudno-Rudzińska
J. Clin. Med. 2025, 14(12), 4301; https://doi.org/10.3390/jcm14124301 - 17 Jun 2025
Viewed by 335
Abstract
Objectives: Esophagectomy is a central component of surgical treatment for esophageal cancer, with both one- and two-stage procedures frequently employed. However, these procedures are associated with a high rate of postoperative complications. This study aimed to assess the rates and types of [...] Read more.
Objectives: Esophagectomy is a central component of surgical treatment for esophageal cancer, with both one- and two-stage procedures frequently employed. However, these procedures are associated with a high rate of postoperative complications. This study aimed to assess the rates and types of complications following one- and two-stage esophagectomies, and to identify predictors of adverse outcomes in patients with esophageal cancer. Methods: We analyzed clinical data from patients undergoing one-stage (Ivor Lewis) or two-stage esophagectomies. Postoperative complications were defined as events occurring within 30 days after surgery. Variables such as patient demographics, clinical staging, histological tumor grade, and neoadjuvant chemoradiotherapy were assessed for their association with complications. Statistical analyses included logistic regression and chi-squared tests. Results: Among 61 patients, postoperative complications occurred in 24.6% of cases. The most frequent were pneumonia (22.2%), anastomotic leakage (22.2%), and hemothorax (27.8%). Significant predictors of complications included intraoperative disease staging, histological tumor grade, and the use of neoadjuvant chemoradiotherapy. The odds ratio for complications following neoadjuvant chemoradiotherapy was 8.75. The frequency of anastomotic leakage was similar in one- and two-stage procedures (30.8% vs. 26.3%, respectively). Conclusions: Postoperative complications remain a significant challenge in esophageal cancer surgery, particularly in the context of advanced disease or neoadjuvant chemoradiotherapy. These findings underscore the necessity for precise surgical planning and comprehensive postoperative care to mitigate risks and optimize patient outcomes. While postoperative risk is high, it is primarily driven by tumor characteristics and preoperative therapy. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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12 pages, 537 KiB  
Article
Induction Radiochemotherapy for Esophageal Cancer: Long-Term Outcomes from a Single-Center Study
by Bartłomiej Strzelec, Piotr Paweł Chmielewski and Renata Taboła
J. Clin. Med. 2025, 14(2), 394; https://doi.org/10.3390/jcm14020394 - 10 Jan 2025
Viewed by 1050
Abstract
Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may [...] Read more.
Background/Objectives: The management of esophageal cancer (EC) remains a significant clinical challenge, particularly in optimizing therapeutic strategies for different stages and subgroups. This study assessed the impact of preoperative radiochemotherapy (CRT) on clinical staging and identified subgroups for whom definitive CRT (dCRT) may provide a favorable alternative to surgery. Methods: Sixty-one patients with esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Pre-treatment staging included computed tomography, gastroscopy with biopsy, and comprehensive laboratory evaluations. Patients received preoperative CRT following the CROSS or dCRT protocols based on tumor stage. Surgical approaches included staged esophagectomy or single-stage Ivor Lewis procedures. Four patients declined surgery and were treated with dCRT. Postoperative outcomes were evaluated using pTNM classification. Follow-up included imaging and endoscopic surveillance. Statistical analyses assessed changes in staging and factors influencing treatment outcomes. Results: CRT significantly reduced T stage across the entire cohort (p = 0.0002), with complete pathological response (pT0N0M0) observed in 54.5% of patients following induction CRT (p = 0.0001). Male patients demonstrated a significant reduction in T stage (p = 0.0008), while a similar trend in females was not significant (p = 0.068). Among patients declining surgery, dCRT demonstrated acceptable oncologic control over a mean follow-up of 4 ± 0.79 years. Conclusions: Preoperative CRT effectively downstages EC and achieves high rates of response, especially in male patients. Therefore, dCRT may be a viable alternative in selected patients, emphasizing the need for individualized treatment strategies to optimize outcomes. These findings underscore the importance of refining multimodal approaches in EC care. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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Review

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16 pages, 1146 KiB  
Review
Wnt Signaling and Circular RNAs in Esophageal and Gastric Cancers: Opportunities for Early Detection and Targeted Therapy
by Piotr Paweł Chmielewski, Bartłomiej Strzelec and Julia Rudno-Rudzińska
J. Clin. Med. 2025, 14(13), 4805; https://doi.org/10.3390/jcm14134805 - 7 Jul 2025
Viewed by 349
Abstract
Aberrant activation of Wnt/β-catenin signaling, frequently caused by oncogenic mutations, plays a crucial role in the development, progression, and therapy resistance of gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Concurrently, circular RNAs (circRNAs), produced by back-splicing of precursor mRNAs (pre-mRNAs), have emerged as [...] Read more.
Aberrant activation of Wnt/β-catenin signaling, frequently caused by oncogenic mutations, plays a crucial role in the development, progression, and therapy resistance of gastric, esophageal, hepatic, pancreatic, and colorectal cancers. Concurrently, circular RNAs (circRNAs), produced by back-splicing of precursor mRNAs (pre-mRNAs), have emerged as critical modulators of this pathway. Accumulating evidence indicates that specific circRNAs regulate Wnt/β-catenin signaling by sponging microRNAs, interacting with RNA-binding proteins, modulating protein function, and altering the expression of pathway components. Some circRNAs are also subject to feedback regulation by Wnt signaling itself. Clinically, tumor-associated circRNAs are present in body fluids and correlate with disease stage, metastatic burden, and patient survival, underscoring their potential as early and minimally invasive biomarkers. Moreover, targeting oncogenic circRNAs has shown promise in preclinical models of Wnt-driven gastrointestinal malignancies. In this review, we summarize the current understanding of the interplay between circRNAs and Wnt/β-catenin signaling in gastric and esophageal cancers. We discuss the translational challenges and emerging opportunities for biomarker development and targeted therapy. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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18 pages, 1930 KiB  
Review
Gastroesophageal Neuroendocrine Tumors: Outcomes and Management
by Christine Son, Joshua Kalapala, Jeff Leya, Michelle Marion Popadiuk, Mohammed K. Atieh, Daniel Havlichek III, Lawrence Feldman, Paul Roach and Promila Banerjee
J. Clin. Med. 2025, 14(7), 2148; https://doi.org/10.3390/jcm14072148 - 21 Mar 2025
Viewed by 1051
Abstract
Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our [...] Read more.
Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes. Methods: A total of 61 GI NET cases were identified from our institution from 2019–2024. In total, twenty-seven review papers, ten population-based/multicenter/outcome studies, six case reports, and one case series were reviewed for the literature review. Results: The incidence of GI NETs at our institution was higher than the known epidemiology of GI NETs. Small intestine NETs were one of the most common sites of GEP-NETs at our institution, with only one of nineteen cases being grade 3 poorly differentiated neuroendocrine carcinoma. All cases of colonic and rectal NETs had good clinical outcomes consistent with findings from the literature. Most of the gastric NETs were type 1 and had benign courses of disease, except for one case with an intermediate grade and metastatic liver lesions. One case of esophageal neuroendocrine carcinoma (E-NEC) showed a complete response to chemotherapy despite a significant tumor burden on presentation and high-grade pathology, while another case of ENEC had recurrent disease despite systemic therapy. Conclusions: While the role of surgery or endoscopic resection is limited to localized tumors, combined treatment with chemoradiation can significantly improve patient outcomes, especially in high-grade, poorly differentiated tumors. Further studies are needed to establish systemic (i.e., chemotherapy and radiation) treatment strategies for poorly differentiated GI NETs. Full article
(This article belongs to the Special Issue Gastroesophageal Cancer: Outcomes and Therapeutic Management)
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