Journal of Gastrointestinal Cancer最新文献

Purpose: Colorectal cancer (CRC) is the third leading cancer-type worldwide and is exhibiting an increasing incidence in developing countries including India. Aberrant activation of Wnt-signalling and Mismatch-Repair inactivation causing microsatellite instability are the two major CRC drivers. CpG island methylator phenotype, the third driver, exhibits extensive overlap with MSI. The mechanisms driving CRC in India are poorly understood. We attempted to characterize sporadic CRC caused by MSI and its complex interplay with other CRC drivers in patients from Telangana, India.

Methods: To determine the MSI status of our cohort, we analysed the instability statuses of five canonical microsatellites, expression statuses of major MMR genes, and the mutation statuses of the MLH1 and MSH2 genes. Detection of H3K36me3 was performed to assess for defects in MMR-complex recruitment. The methylation statuses of a panel of CIMP markers, in addition to the nuclear-stabilization statuses of β-catenin and p53 were also assessed to identify the involvement of other pathways.

Results: Among 230 CRC patients, a majority of whom were males, ≥ 50 years old and harbouring late stage tumours in the rectum, low frequency of loss of major MMR genes was observed in MSI + tumors. MSH2 loss was detected in 16% of MSI + samples, a frequency significantly higher than previously reported. Causal genetic aberrations were undetected in 57% of MSI + tumors suggesting novel/non-canonical drivers.

Conclusions: A majority of MSI + samples exhibited proficient expression of the four major MMR genes. The results highlight the importance of studying geographically-distinct populations to expand our understanding of CRC origins.

Prognosis for patients with unresectable intrahepatic cholangiocarcinoma (iCC) remains poor despite advances in systemic therapy. This review delineates the indications and outcomes for hepatic artery infusion pump (HAIP) therapy in patients with liver-limited iCC based on retrospective reviews and single-arm studies. Early results have shown favorable outcomes when incorporating HAIP in the management strategy, including impressive 3-year survival rates ranging from 31 to 40%. Randomized controlled trials will be vital in defining the role of HAIP in current treatment regimens (e.g. first-line vs. second-line). As data continue to accumulate, we emphasize the importance of patient selection within the context of comprehensive multidisciplinary evaluation. Finally, we discuss promising new therapeutic strategies for HAIP as applied to patients with cholangiocarcinoma, including the introduction of novel agents, and approaches to mitigating dose-limiting toxicities, and thereby maximizing therapeutic benefit.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor survival, driven in part by early metastatic spread. Conventional imaging lacks sufficient precision to predict metastasis accurately. Machine learning (ML)-based radiomics, integrating quantitative imaging features from modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET), may enhance prognostic accuracy.

Objective: To systematically review the diagnostic accuracy and clinical utility of ML-based radiomics models for predicting metastasis in PDAC.

Methods: A systematic search of PubMed, Embase, Scopus, Web of Science, and Cochrane Library was conducted according to PRISMA 2020 guidelines (PROSPERO: CRD420251109941). Eligible studies applied ML-based radiomics to MRI, PET, or combined MRI/PET for metastasis prediction in histologically or clinically confirmed PDAC. Data were extracted on study design, patient characteristics, imaging protocols, feature selection, ML algorithms, performance metrics, and validation strategies. Methodological quality was assessed using QUADAS-2. Certainty of evidence was graded using the GRADE framework.

Results: Seven studies met inclusion criteria and were included in the Systematic Review. MRI-based models were the most common, with one multimodal PET/MRI study. Risk of bias was moderate overall, primarily due to retrospective designs and variable reference standards. GRADE certainty was low for pooled diagnostic accuracy and very low for PET/MRI evidence due to imprecision and suspected publication bias.

Conclusions: ML-based radiomics demonstrates promising accuracy for metastasis prediction in PDAC, particularly with MRI and PET/MRI modalities. Integration with clinical biomarkers further enhances predictive value. However, methodological limitations and low certainty of evidence warrant prospective, multicenter validation with standardized protocols before clinical adoption.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Early detection of precancerous lesions such as adenomas and polyps is vital for prevention, yet standard colonoscopy may miss up to 26% of adenomas. Artificial intelligence (AI)-assisted colonoscopy has emerged as a promising tool to enhance lesion detection. This meta-analysis provides an updated synthesis of randomized controlled trials (RCTs) evaluating the diagnostic performance of AI-assisted versus standard colonoscopy.

Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Cochrane, Web of Science, and Scopus identified 38 RCTs including 29,745 participants. Pooled risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses by geographical region and AI manufacturer were performed to explore heterogeneity. Certainty of evidence was rated using the GRADE approach, and publication bias was assessed through funnel plots and Egger's test.

Results: AI-assisted colonoscopy significantly improved adenoma detection rate (ADR: RR = 1.19, 95% CI 1.14-1.25) and polyp detection rate (PDR: RR = 1.19, 95% CI 1.13-1.25), while reducing adenoma miss rate (AMR: RR = 0.52, 95% CI 0.38-0.72) and polyp miss rate (PMR: RR = 0.53, 95% CI 0.33-0.88). The mean number of adenomas per colonoscopy increased (MD = 0.20, 95% CI 0.14-0.25). AI modestly prolonged withdrawal time (MD = 0.46 min, 95% CI 0.26-0.66). No significant difference was observed for carcinoma detection (RR = 1.12) or advanced adenoma miss rate (RR = 0.67). Sessile serrated lesion detection showed a nonsignificant trend toward improvement (RR = 1.13), becoming significant after outlier exclusion (RR = 1.23). Subgroup analyses revealed higher ADR improvement in East Asian studies and with specific AI systems (e.g., Wision AI). Egger's test suggested minor small-study effects for ADR and withdrawal time.

Conclusions: AI-assisted colonoscopy substantially enhances adenoma and polyp detection while reducing miss rates. However, its benefit for carcinoma and sessile serrated lesion detection remains uncertain. Further standardized RCTs with long-term follow-up are warranted to confirm its role in colorectal cancer screening.

Objective: The development of treatments for advanced gastric cancer (AGC) has made significant advances over the past decade. Although clinical trials for novel drugs targeting HER2-positive AGC are ongoing, current clinical management still faces challenges. Therefore, further comparison of the effectiveness of such combination therapies is needed.

Methods: comprehensive search was conducted in the PubMed, Embase, and Cochrane databases, with the search cut-off date set to May 2025. Outcomes were evaluated using indicators such as progression-free survival (PFS) and overall survival (OS).

Results: Our study included only randomized controlled trials comparing combination regimens of targeted and/or immunotherapy, involving 3,231 patients across eight different interventions.The network meta-analysis revealed that no treatment regimen demonstrated a statistically significant improvement in OS or PFS. However, a trend toward improved PFS was observed with HLX22 plus HLX02 and chemotherapy compared to trastuzumab-based chemotherapy, although the difference was not statistically significant (MD=-0.94, 95% CI: -5.26-3.37). Pembrolizumab in combination with trastuzumab and chemotherapy significantly improved the objective response rate (ORR).Cumulative ranking probabilities indicated that trastuzumab plus chemotherapy may be associated with the longest PFS, while chemotherapy alone ranked highest in OS, though all confidence intervals included the null value.

Conclusion: No first-line regimen significantly improved OS or PFS in HER2-positive advanced gastric cancer. However, HLX22-based and immune-combination strategies show potential clinical value-particularly in enhancing ORR-and merit further investigation.

Background: The impact of neoadjuvant chemotherapy (NAC) on perioperative and functional outcomes for patients undergoing laparoscopic radical resection for rectal cancer remains incompletely understood. This study aimed to compare surgical, biochemical, functional, and immunologic outcomes between patients receiving NAC and those undergoing surgery alone.

Methods: In this retrospective cohort study, 231 patients who underwent laparoscopic radical resection for rectal cancer between January 2020 and January 2025 were analyzed. Patients were assigned to either the NAC group (n = 112, mFOLFOX6 regimen) or the non-NAC group (n = 115) based on preoperative chemotherapy status. Baseline characteristics, surgical and recovery parameters, serum tumor biomarkers (CEA, CA19-9, AFP), anorectal dynamics, and immune cell subsets (CD3+, CD4+, CD4+/CD8+) were measured at specified time points. Postoperative complications and adverse reactions were recorded.

Results: Baseline demographic and clinical characteristics were similar between groups. The NAC group demonstrated a higher rate of anus preservation (54.46% vs. 39.13%; P = 0.021), shorter postoperative recovery times, and reduced hospital stay compared to the non-NAC group (all P < 0.05). At 7 days and 6 months postoperatively, the NAC group had significantly lower levels of CEA, CA19-9, and AFP (all P < 0.05). Anorectal dynamic assessment showed improved functional recovery in the NAC group at 7 days postoperatively. However, the NAC group exhibited a greater reduction in peripheral CD3+, CD4+, and CD4+/CD8 + levels postoperatively (P < 0.05) and higher rates of leukopenia (8.04% vs. 0.87%; P = 0.021) and neutropenia (7.14% vs. 0.87%; P = 0.037). Major postoperative complication rates did not differ significantly between groups.

Conclusion: Neoadjuvant chemotherapy prior to laparoscopic radical resection for rectal cancer was associated with improved anus preservation, enhanced postoperative recovery, and greater biochemical and functional benefits without increasing major complication rates, although it was linked to higher hematologic adverse events and postoperative declines in immune cell counts.

Trial registration: Not applicable.

Background: Approximately 35% of patients do not receive adjuvant chemotherapy (AC) after surgery for stage III colorectal cancer (CRC). We aimed to investigate the association between receipt of AC and sociodemographic and treatment factors.

Methods: A retrospective case-control analysis of patients with stage III CRC who underwent radical resection was performed using data from the SEER registry (2010-2020). The main exposure was socioeconomic determinants, and the main outcome was receipt of AC. Multivariable binary logistic regression analyses were used to assess independent predictors of AC receipt.

Results: A total of 81,720 patients (52.4% male; median age, 65 years) were included. Overall, 70.6% of tumors were colonic and 29.4% rectal. 41.7% of patients did not receive AC. Independent socioeconomic determinants of AC receipt were age < 50 years (OR: 2.36, p < 0.001), male sex (OR: 0.931, p = 0.002), Black race (OR: 1.12, p = 0.002), Hispanic ethnicity (OR: 1.13, p < 0.001), household income <$50,000 (OR: 1.16, p = 0.001), non-metropolitan residence (OR: 1.09, p = 0.035), and unmarried status (single-OR: 0.778, p < 0.001, divorced-OR: 0.87, p < 0.001, widowed-OR: 0.313, p < 0.001). Tumor characteristics associated with AC receipt included tumor location and size, perineural invasion, number of positive lymph nodes, and CEA levels. Neoadjuvant chemotherapy (OR: 0.37, 95%CI: 0.28-0.48) and neoadjuvant radiation therapy (OR: 0.42, 95%CI: 0.38-0.46) were associated with lower odds of receiving AC in patients with colon and rectal cancer, respectively.

Conclusions: Receipt of AC was less likely among elderly males and those who received neoadjuvant treatments. Black and Hispanic patients and patients with low household income were more likely to receive AC.

Background: Mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI-H) colorectal cancers demonstrate exceptional responsiveness to immune checkpoint inhibitors; however, evidence for the efficacy of neoadjuvant immunotherapy remains limited. This review consolidates all prospective trials evaluating neoadjuvant immune checkpoint blockade in non-metastatic dMMR/MSI-H colorectal cancer.

Methods: This systematic review followed the PRISMA guidelines and was registered with the PROSPERO database (CRD420251074066). A comprehensive search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov was conducted until May 2025. Prospective interventional studies involving neoadjuvant immunotherapy in adults with stage II-III dMMR/MSI-H colorectal adenocarcinoma were included in this review. The primary outcomes were pathological complete response (pCR), major pathological response (MPR), and clinical complete response (cCR). The risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions tool.

Results: Eight prospective phase 2 trials encompassing 352 patients with stage II-III dMMR/MSI-H colorectal cancer were included. The pCR rates ranged from 41 to 90%, with the highest responses in patients with colon cancer receiving dual checkpoint blockade (nivolumab plus ipilimumab: 90% pCR, 95% MPR). In rectal cancer, 100% of patients receiving dostarlimab (n = 16) and 46% of those in the camrelizumab plus apatinib group (n = 24/52) achieved cCR with organ preservation. MPR was observed in 80-95% of the studies. Grade ≥ 3 adverse events occurred in 3-34% of patients, with no treatment-related deaths reported. At the median follow-up (8-26 months), disease-free survival exceeded 98% in most cohorts. Watch-and-wait strategies are durable, with no local regrowth in patients with complete clinical response (cCR).

Conclusions: Neoadjuvant immune checkpoint inhibition demonstrates high pathological and clinical response rates in dMMR/MSI-H colorectal cancer, with organ preservation achievable in selected rectal cancer patients. Neoadjuvant immunotherapy may become an alternative to surgery as the primary treatment for MSI-H/dMMR colorectal cancer if long-term quality of life is superior and toxicity and cost are competitive with standard surgical approaches. However, longer follow-up, predictive biomarkers, and randomized comparisons with upfront surgery are required before its routine clinical use.