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Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer

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A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Clinical Research in Cancer".

Deadline for manuscript submissions: 30 January 2027 | Viewed by 9254

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Editors

Dr. Liliana Streba

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Guest Editor

Department of Oncology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares Str., 200349 Craiova, Romania
Interests: medical oncology; colorectal cancer; gastric cancer; hepatocellular carcinoma; chemotherapy; immunotherapy; radiotherapy; internal medicine; palliative care

Dr. Michael Schenker

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Guest Editor

Department of Oncology, University of Medicine and Pharmacy of Craiova, 2 Petru Rares Str., 200349 Craiova, Romania
Interests: medical oncology; clinical trials; gastric cancer; pancreatic cancer; colorectal cancer; hepatocellular carcinoma; cholangiocarcinoma; neuroendocrine carcinoma; chemotherapy; immunotherapy; radiotherapy

Special Issue Information

Dear Colleagues,

This Special Issue, "Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer", aims to bridge the gap between cutting-edge laboratory research and clinical application. As gastrointestinal cancers remain a leading cause of cancer-related mortality globally, it is imperative to translate molecular and cellular findings into tangible patient outcomes. This Issue will explore key themes, including the latest advancements in understanding the molecular mechanisms of gastrointestinal tumorigenesis, the role of the microbiome in cancer progression, novel diagnostic endoscopic techniques, and the development of novel therapeutic strategies. It will also address the challenges in early detection and the integration of personalized medicine approaches in clinical settings. By fostering a multidisciplinary dialogue, this Issue seeks to highlight the importance of translational research in improving diagnostics, treatment protocols, and ultimately patient survival rates. Through comprehensive reviews, original research articles, and insightful commentary, this publication aims to serve as a valuable resource for researchers, clinicians, and healthcare professionals dedicated to combating gastrointestinal cancer.

Dr. Liliana Streba
Dr. Michael Schenker
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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

gastrointestinal cancer
tumorigenesis
microbiome
early detection
molecular mechanisms
personalized medicine
novel therapeutics
translational research
clinical application
diagnostic innovations

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Published Papers (6 papers)

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Research

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20 pages, 927 KB

Open AccessArticle

Pathological Complete Response and Residual Disease Patterns After Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: Clinical and Laboratory Associations

by Azer Gökmen and Erdoğan Şeyran

Cancers 2026, 18(18), 2983; https://doi.org/10.3390/cancers18182983 - 15 Sep 2026

Abstract

Background: Pathological response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma may differ between the primary tumor and regional lymph nodes. We evaluated pretreatment factors associated with pathological complete response (pCR) and the anatomical distribution of residual disease after esophagectomy. Methods: This retrospective single-center cohort included 100 patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. pCR was defined as ypT0N0. Associations with pCR were evaluated using logistic regression. Results: Among 99 response-evaluable patients, 59 achieved pCR (59.6%; 95% CI, 49.7–68.7%). Of 40 patients with non-pCR, residual disease involved only the primary tumor in 26 (65%), both primary and nodal compartments in 10 (25%), and only regional lymph nodes despite complete primary tumor regression in 4 (10%). Overall, 14 patients with non-pCR (35%) had residual nodal disease. In an exploratory adjusted analysis that could not account for baseline cT and cN categories, lower pretreatment lactate dehydrogenase (OR per 10 U/L increase, 0.93; 95% CI, 0.86–0.99; p = 0.026) and female sex (OR, 2.72; 95% CI, 1.02–7.24; p = 0.045) were associated with pCR. Conclusions: Response was heterogeneous across primary tumor and nodal compartments. Primary tumor regression did not invariably indicate nodal clearance, supporting compartment-specific response assessment. The lactate dehydrogenase and sex associations may reflect residual confounding by baseline disease extent and require external validation. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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18 pages, 4331 KB

Open AccessArticle

C-Reactive Protein-Based Composite Indices for Predicting Tumor Overgrowth Restenosis After Partially Covered Duodenal Stenting in Gastric Cancer: A Cohort Study

by Hyuk Lee, Young Eun Oh, Tae-Se Kim, Yang Won Min, Byung-Hoon Min and Jun Haeng Lee

Cancers 2026, 18(17), 2803; https://doi.org/10.3390/cancers18172803 - 28 Aug 2026

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Abstract

Background/Objectives: Partially covered duodenal stents rapidly relieve malignant gastric outlet obstruction, but tumor overgrowth restenosis limits durability. We compared six preprocedural inflammatory, nutritional, and immune indices for predicting this outcome in patients with gastric cancer. Methods: We retrospectively analyzed 68 consecutive patients from a prospectively maintained cohort. The primary endpoint was endoscopically or radiologically confirmed tumor overgrowth restenosis. Discrimination was assessed using receiver operating characteristic curves (pairwise DeLong tests with Bonferroni correction) and time-dependent areas under the curve (AUCs) accounting for death as a competing risk. Multivariable cause-specific Cox models were restricted to preprocedural covariates; post-stenting chemotherapy or radiotherapy was examined in time-dependent sensitivity analyses. Results: Technical and clinical success rates were 100% and 94.1%. Seventeen patients (25.0%) developed restenosis at a median of 66 days. The C-reactive protein–albumin–lymphocyte (CALLY) index showed the highest AUC (0.859), followed by the C-reactive protein-to-albumin ratio (CAR; 0.822) and neutrophil-to-lymphocyte ratio (0.774); these three indices did not differ significantly. At an exploratory, internally derived cutoff of ≤0.110, CALLY had 76.5% sensitivity and 84.3% specificity and remained associated with restenosis after adjustment for stenosis site and stent length (adjusted hazard ratio, 12.30; 95% confidence interval, 3.89–38.83; C-index, 0.836), with consistent results in continuous, time-dependent, and tumor-covariate-adjusted analyses. The 180-day cumulative incidence was 52.4% with low CALLY versus 4.3% with high CALLY. Conclusions: C-reactive protein-based indices showed the highest numerical discrimination, although pairwise differences among CALLY, CAR, and NLR were not statistically significant. CALLY is a promising exploratory biomarker for restenosis risk stratification, but its cutoff should not guide clinical decisions until externally validated. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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16 pages, 18739 KB

Open AccessArticle

Deep Learning-Based Computer-Aided Detection and Diagnosis System for Malignant Biliary Stricture (With Video)

by Qingyu Tang, Sanping Zhou, Zizhan Tang, Kangpeng Li, Zejian Huang, Lei Zhang, Dapeng Bian, Qiushi Feng, Qi Li, Hao Sun, Jie Tao, Le Wang, Zhimin Geng and Chen Chen

Cancers 2026, 18(15), 2410; https://doi.org/10.3390/cancers18152410 - 26 Jul 2026

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Abstract

Background/Objectives: Malignant biliary stricture (MBS) remains difficult to diagnose accurately despite digital single-operator cholangioscopy (DSOC). We developed a deep learning (DL)-based computer-aided detection (CADe) and diagnosis (CADx) system for DSOC-based MBS assessment. Methods: This retrospective multicenter study included 149 patients from one center for model development and internal validation and 25 patients from two independent centers for external evaluation. CADe used a You Only Look Once version 11 (YOLOv11) architecture to localize irregular mucosa, abnormal vasculature, and nodular protrusions defined by the Carlos Robles-Medranda and Mendoza criteria. CADx used a Residual Network-18 classifier with gradient-weighted class activation mapping for interpretability. Results: CADe achieved a mean average precision at 50% intersection-over-union of 91.2%, with a precision of 92.0% and recall of 87.0%. CADx achieved a frame-level area under the receiver operating characteristic curve (AUC) of 0.960 in internal validation and 0.843 in external validation. External frame-level sensitivity was 52.0% and specificity was 95.2%. For the patient-level external endpoint, sensitivity was 85.7%, specificity was 94.4%, accuracy was 92.0%, and AUC was 0.881. Conclusions: The two-stage system combines localization of predefined cholangioscopic features with interpretable diagnostic classification. The small external cohort and marked reduction in frame-level sensitivity preclude firm conclusions regarding generalizability; prospective multicenter and live-procedure evaluation is required. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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19 pages, 15521 KB

Open AccessArticle

Small Bowel Tumors: A 7-Year Study in a Tertiary Care Hospital

by Sergiu Marian Cazacu, Dan Cârțu, Mihai Popescu, Liliana Streba, Bogdan Silviu Ungureanu, Vlad Florin Iovănescu, Mihai Cimpoeru, Cecil Sorin Mirea, Valeriu Marian Surlin, Stelian Mogoantă and Mirela Marinela Florescu

Cancers 2025, 17(9), 1465; https://doi.org/10.3390/cancers17091465 - 27 Apr 2025

Cited by 5 | Viewed by 5266

Abstract

(1) Background: Tumors of the small bowel represent 3–6% of gastrointestinal neoplasms and 3–6% of GI malignancies. The difficulties regarding the diagnosis are associated with larger tumors at the moment of the diagnosis and with advanced forms of malignant tumors, associated with a dismal prognosis. (2) Methods: We performed an observational, retrospective, cohort study that included patients with small bowel tumors admitted to the Craiova County Emergency Clinic Hospital between 1 January 2017 and 31 December 2023. The data were collected from the analysis of the patient’s discharge documents from the Hippocrates computer system of the hospital and the evaluation of endoscopy databases. Patients under 16 years of age, those with no pathological confirmation of the malignancy, and those with insufficient data were excluded. (3) Results: A total of 80 cases of small bowel tumors were diagnosed; 72.5% were malignant, of which 10.3% were metastases. The most frequent primary malignant small bowel tumor was adenocarcinoma; two squamous cell carcinomas were noted. CT scans and upper digestive endoscopy represent the most frequent imaging methods for the diagnosis. The prognosis for malignant tumors was poor, with a 41% 5-year survival rate. (4) Conclusions: Small bowel tumors are rarely encountered, with 72.5% being malignant, and were diagnosed at large dimensions and in advanced stages for malignant tumors, with a dismal prognosis. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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Review

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45 pages, 1494 KB

Open AccessReview

Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications

by Dami Aiyejuto, Ananya Luthria, Thompson Hui and Anitha Kota Shenoy

Cancers 2026, 18(16), 2569; https://doi.org/10.3390/cancers18162569 - 10 Aug 2026

Cited by 1 | Viewed by 629

Abstract

Colorectal cancer (CRC) remains a major cause of cancer-related mortality, with recurrence and treatment resistance as persistent challenges. Increasing evidence supports the cancer stem cell (CSC) model in CRC, in which a subpopulation of self-renewing colorectal cancer stem cells (CCSCs) sustains tumor growth, metastasis, and therapy resistance. CCSCs are increasingly recognized as key drivers of tumor progression, therapeutic resistance, and relapse, and are increasingly being investigated not only as therapeutic targets but also as biomarkers with diagnostic and prognostic relevance in CRC. Multiple signaling pathways regulate CCSC maintenance and aggressive behavior, including Wnt/β-catenin, Notch, Hedgehog, PI3K/AKT, MAPK/ERK, NF-κB, and TGF-β signaling. These pathways form the basis of therapeutic strategies aimed at modulating stemness-associated pathways, with several CSC-focused agents and pathway inhibitors currently under translational and clinical investigation. In parallel, CCSC surface markers and molecular signatures are being explored as putative tools for early detection, minimal residual disease monitoring, and outcome prediction. However, successful translation of CSC-directed approaches into effective and safe clinical applications remains difficult. Tumor heterogeneity, CSC plasticity, compensatory signaling mechanisms, and the shared regulatory networks between malignant and normal intestinal stem cells pose substantial barriers. In this review, we summarize the molecular mechanisms underlying CCSC biology, discuss their diagnostic and prognostic implications. We also focus on clinical trials that apply CCSC-directed therapeutic, biomarker, and prevention strategies in CRC., Finally, we emphasize the lessons learned and the translational challenges, including the need for rigorously validated, CCSC-specific biomarkers, that continue to shape the development of these therapeutic and biomarker strategies. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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14 pages, 282 KB

Open AccessReview

The Role of Organ Sparing Approaches After Total Neoadjuvant Treatment in Rectal Cancer

by Gianluca Rizzo, Vincenzo Tondolo, Luca Emanuele Amodio, Federica Marzi, Camilla Marandola, Donato Paolo Pafundi, Giuseppe De Rito and Claudio Coco

Cancers 2026, 18(1), 55; https://doi.org/10.3390/cancers18010055 - 24 Dec 2025

Cited by 2 | Viewed by 1918

Abstract

Organ-preserving strategies have gained increasing relevance in the management of rectal cancer, driven by the improved ability of neoadjuvant therapies to induce major and complete tumor regression. The introduction of Total Neoadjuvant Therapy (TNT), delivered through induction and/or consolidation chemotherapy combined with radiotherapy, has substantially increased both pathological and clinical complete response rates. This progress has renewed interest in non-operative management—namely Watch-and-Wait (W&W)—and in local excision (LE) as potential alternatives to total mesorectal excision (TME). However, the W&W strategy raises important oncologic concerns, including a non-negligible rate of local regrowth—consistently reported at approximately 20–30%—which is associated with inferior distant metastasis-free survival and overall survival. These limitations underscore the inherent uncertainty in reliably defining a true clinical complete response. Within this context, LE may serve as a valuable diagnostic and therapeutic modality by confirming the pathological response, improving local control through removal of residual resistant tumor clones, and enabling more accurate stratification of patients suitable for organ preservation versus those requiring completion TME. Overall, while TNT has expanded the therapeutic opportunities for rectal preservation, LE appears to play a critical role in reducing the discordance between clinical and pathological assessment, thereby offering a more oncologically secure pathway toward organ preservation. This narrative review discusses the current role, benefits, and limitations of organ-preserving approaches after TNT in both locally advanced and early rectal cancer. Full article

(This article belongs to the Special Issue Advances in Clinical Therapy and Prognosis of Gastrointestinal Cancer)

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