Journal of Gastrointestinal Cancer最新文献

Purpose: Intrahepatic cholangiocarcinoma (iCCA) represents a biologically heterogeneous subgroup of biliary tract cancer (BTC) with a 5-year survival below 20%. Delayed diagnosis, intrinsic aggressiveness, and extensive intertumoral and intratumoral heterogeneity at the clinical, histopathological, and genomic level all contribute to this dismal outcome. Increasingly, treatment decisions in advanced iCCA depend on the identification of actionable molecular alterations, including FGFR2 fusions or rearrangements, IDH1 mutations, HER2 amplifications, NTRK fusions, and microsatellite instability (MSI-high) and/or mismatch repair deficiency (dMMR).

Methods: A narrative review of the current literature was conducted, focusing on (i) what molecular alterations are clinically relevant today, (ii) when molecular profiling should be performed, and (iii) how testing should be technically implemented in routine clinical practice. Results iCCA, particularly the small-duct subtype, harbors a high prevalence of therapeutically actionable molecular alterations, in contrast to extrahepatic cholangiocarcinoma and gallbladder carcinoma. Early and comprehensive molecular profiling enables access to approved targeted therapies, molecularly stratified second-line treatments, and clinical trials. Combined DNA- and RNA-based next-generation sequencing, complemented by immunohistochemistry and in situ hybridization, provides the most reliable diagnostic framework.

Conclusion: Molecular testing has become an essential component of modern iCCA management. Broad, early, and technically integrated molecular profiling-ideally performed at initial diagnosis and interpreted in an interdisciplinary (molecular) tumor board-is critical to fully realize the potential of precision oncology in BTC.

Purpose: Colorectal cancer (CRC) remains a significant health burden worldwide. Although some clinicopathological factors have been identified in stage I-III CRCs, there is a need to identify new prognostic factors. This study aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) methylation analysis in predicting the prognosis of stage I-III CRCs.

Methods: Methylation analyses were performed on 273 preoperative plasma samples from CRC patients who underwent surgery at Juntendo University Hospital between 2011 and 2019. The methylation levels of three tumor suppressor genes (CHFR, SOX11 and CDO1) were analyzed as relative methylation value (RMV).

Results: There were no significant differences in the methylation levels of each gene among different stages of CRC. However, multivariate analysis revealed that the methylation level of SOX11 was an independent prognostic factor (Hazard ratio (HR) = 2.37 (1.20-4.67), p = 0.01). Subgroup analysis of stage III CRC also showed methylation levels of SOX11 and CDO1 were independent prognostic factors (HR = 2.66 (1.16-6.07), p = 0.02 and HR = 2.51 (1.06-5.94), p = 0.04, respectively). In cases with high CHFR and CDO1-RMV, the use of postoperative adjuvant chemotherapy (POAC) was related to significantly higher RFS (p = 0.006 and p = 0.001, respectively). However, no significant effect of POAC was seen in high SOX11-RMV cases (p = 0.24).

Conclusions: This study demonstrated the clinical utility of ctDNA methylation analysis for predicting prognosis in stage I-III CRCs. Furthermore, the ctDNA methylation status might be a biomarker for identifying the patients who can benefit from POAC.

Background: Gastric cancer (GC) is considered a leading cause of cancer-related deaths. Identifying patients with poor survival outcomes and factors related to prognosis are crucial measures in patient care. In addition to the existing prognostic markers, new markers need to be introduced to overcome their limitations and improve risk stratification. In this systematic review and meta-analysis, we aim to assess the albumin-bilirubin (ALBI) grade as a novel prognostic marker in patients with GC.

Method: The PubMed, Web of Science, Embase, and Scopus databases were searched from inception to April 4, 2025. Studies investigating the prognostic value of the ALBI grade in GC were included. The prognostic efficacy was evaluated using hazard ratio (HR) with 95% confidence interval (95% CI). The meta-analysis was performed using R version 4.5.1.

Result: The meta-analysis included 3,459 patients in the univariate analysis for overall survival (OS) and 2,503 in the multivariate analysis. A higher ALBI grade was associated with worse OS in both univariate (HR = 3.05; 95%CI, 1.74-5.33; P ˂ 0.0001) and multivariate analyses (HR = 1.89; 95%CI, 1.30-2.76; P = 0.0010). A meta-analysis of 888 patients also showed that a higher ALBI grade was associated with worse recurrence-free survival/disease-free survival (RFS/DFS) in both univariate (HR = 2.23; 95%CI, 1.74-2.85; P ˂ 0.0001) and multivariate analyses (HR = 1.86; 95%CI, 1.42-2.43; P ˂ 0.0001).

Conclusion: A higher ALBI grade is associated with worse OS and RFS/DFS. This novel marker could be used to complement the existing prognostic markers and enhance survival prediction in patients with GC.

Background: Cannabis use is increasing globally, with a parallel rise in Cannabis Use Disorder (CUD). Chronic pancreatitis (CP), a progressive inflammatory condition, is associated with acute pancreatitis (AP) flares and an elevated risk of pancreatic cancer (PC). Although cannabis is often used for pain management in CP, its impact on PC risk and AP flare frequency is unclear.

Methods: We conducted a retrospective cohort study using TriNetX to identify adults with CP, stratified by CUD status. Patients with pre-existing PC were excluded. Propensity score matching (1:1) was applied for demographics, behavioral factors, and comorbidities. The primary outcome was PC incidence; the secondary was AP flare frequency. Hazard ratios (HR) were calculated using Cox proportional hazards regression. Sensitivity analysis adjusted for opioid use disorder.

Results: Before matching, the CUD cohort (n = 10,864) had higher rates of alcohol and nicotine use than controls (n = 42,160). After matching, 6,858 patients per group remained with balanced covariates (SMD < 0.1). Mean follow-up was shorter in the CUD cohort (736 ± 422 vs. 896 ± 368 days). CUD was associated with a significantly reduced risk of PC (67 vs. 274 cases; HR: 0.263, 95% CI: 0.202-0.344; p < 0.001) but a modest increase in AP flare risk (HR: 1.102, 95% CI: 1.043-1.166; p = 0.001). Results were consistent in the sensitivity analysis.

Conclusions: Among patients with CP, CUD was associated with lower rates of PC detection during available follow-up, but a slightly increased risk of AP flares. These findings warrant further prospective and mechanistic studies to clarify cannabis's role in pancreatic disease.

Background: This study evaluated the efficacy and safety of a regimen consisting of sintilimab, nanoparticle polymeric micellar paclitaxel (NPMP) and S-1 in HER2-negative advanced gastric cancer (AGC).

Method: In this real-world study, patients with HER2-negative AGC received first-line sintilimab plus NPMP and S-1. The primary endpoint was overall survival (OS) and progression free survival (PFS), while objective response rate (ORR), disease control rate (DCR), and safety were evaluated as secondary endpoints.

Results: Among 33 enrolled patients, 14 patients (42.4%) achieved partial response (PR), 17 (51.5%) maintained stable disease (SD), 2 (6.1%) showed progressive disease (PD). ORR and DCR were 42.4% and 93.9%. Median OS reached 15.4 months (95%CI: 13.0-17.6), median PFS was 7.8 months (95%CI: 5.8-9.3). Subgroup analysis revealed significant differences in OS and PFS according to PD-L1 expression and cycles of treatment. Observed adverse events (AEs) were fatigue (60.6%), leukopenia (54.5%),anemia (51.5%),thrombocytopenia (36.4%),nausea (30.3%) and vomiting (15.1%). Most toxicities were manageable and predominantly grade 1-2.

Conclusions: The combination of sintilimab, NPMP and S-1 demonstrates promising antitumor effects and controllable toxicity as first-line treatment in patients with HER2-negative with AGC.

Purpose: The REGARD trial resulted in insurance approval for ramucirumab monotherapy; however, it did not include Japanese patients. Subsequent phase II trials and retrospective studies have examined Japanese cohorts, but reports identifying prognostic factors remain limited.

Methods: A total of 27 patients across six institutions received ramucirumab monotherapy as a second-line treatment for gastric cancer between September 2017 and December 2019.

Results: The median age of 27 patients was 74 years (range: 36-90). Eighteen patients were male, and ten had intestinal-type gastric cancer. Metastases were observed in 6 patients in the liver, 3 in the lung, 18 in lymph nodes, and 14 in the peritoneum. Third-line chemotherapy was administered to 6 patients. The response rate was 3.7%, and the disease control rate was 18.5%. The median progression-free survival was 2.1 months, and the median overall survival was 3.0 months. Of the 27 patients, 6 received third-line treatment and 4 received nivolumab alone. Overall survival did not differ significantly between patients who received third-line treatment and those who did not. The median progression-free survival showed no significant differences based on tumor markers (carcinoembryonic antigen and CA19-9), age, histology, or metastases in the lung, lymph nodes, or peritoneum. In contrast, liver metastases were associated with poorer progression-free survival (HR:4.735 (95% CI: 1.508-14.86) and overall survival HR:2.906 (95% CI: 1.031-8.189).

Conclusions: Ramucirumab monotherapy is selected for patients with poor general condition, but it is suggested to have a poor prognosis, particularly in cases with liver metastases.

Purpose: Gastrointestinal (GI) cancers significantly contribute to the global cancer burden, yet their epidemiological trends among adolescents and young adults (AYAs: aged 15-39 years) remain understudied. This study provides the first comprehensive analysis of global burden, temporal trends (1990-2021), and projections to 2045 for GI cancers in AYAs.

Methods: Using the Global Burden of Disease (GBD) 2021 dataset, we analyzed age-standardized incidence rates (ASIR), death rates (ASDR), disability-adjusted life-years (DALYs), and estimated annual percentage changes (EAPC). Bayesian age-period-cohort modeling was employed for projections to 2045.

Results: In 2021, there were 156,033 new GI cancer cases, 84,623 deaths, and 4.9 million DALYs among AYAs globally. From 1990 to 2021, ASIR for colorectal and gallbladder cancers increased (EAPCs:0.55[95%CI:0.44, 0.67] and 0.13[0.05, 0.20], respectively), while ASIR for other GI cancers declined (e.g., stomach cancer:-2.75 [- 2.94, - 2.57]). East Asia bore the highest burden. Projections suggest a stabilization of overall ASIR and ASDR by 2045, though liver and gallbladder cancers are expected to rise.

Conclusions: The burden of GI cancers among AYAs remains substantial and is projected to persist, highlighting the need for targeted early-detection strategies and age-specific prevention programs, especially in high-risk regions.

Background: Oligometastasisdisease (OMD) is an intermediate stage between localised disease and widespread metastasis. No standard OMD definition exists for gallbladder cancer (GBC). This review examines OMD definitions in GBC, treatment challenges, current strategies like systemic therapy, immunotherapy, surgery, loco-regional therapy, emerging approaches, and future directions for GBC patients with OMD.

Materials and methods: A literature review of GBC and oligometastasiswas conducted using PubMed and Google Scholar through July 2025.

Results: Metastatic GBC has a poor prognosis; however, a combination of systemic and immunotherapy can slightly improve survival, ranging from 11.3 to 12.7 months. OMD is a subgroup of patients (with 1-3 liver metastases, para-aortic lymph nodes, metastasis limited to adherent omentum, and/or up to three peritoneal deposits) who experience better survival with consolidative treatment, including neoadjuvant therapy followed by curative resection (such as minor hepatectomy, para-aortic lymphadenectomy) and adjuvant therapy. Reported survival rates at 1, 3, and 5 years range from 20 to 64.0%, 5.7-17%, and 0-23%. Risk factors like extensive hepatic lobectomy and portal vein resection in cholestatic liver increase morbidity and mortality. Elevated preoperative tumour markers (CEA, CA 19 - 9) are associated with poorer survival.

Conclusion: There is no standard definition of OMD in GBC. Our review emphasises the need to develop a standardised definition of OMD in GBC and for multidisciplinary evaluation and well-designed clinical trials to expand therapeutic options and to optimise patient outcomes.