Journal of gastrointestinal oncology最新文献

Background: The systemic treatment landscape for advanced hepatocellular carcinoma (HCC) has evolved from tyrosine kinase inhibitors, such as sorafenib (SOR), to immune checkpoint inhibitor-based combinations (IO). Despite these advances, there is a lack of simple, objective tools to stratify patient prognosis in clinical practice. While several laboratory parameters are known to correlate with outcomes, their combined utility across treatment types remains unclear. We aimed to evaluate the prognostic value of commonly available biomarkers and to develop a simplified score applicable to both SOR- and IO-treated patients.

Methods: This retrospective cohort study analyzed patients with advanced or intermediate-stage HCC treated with first-line systemic therapy at a single center in Brazil from 2009 to 2024. Patients were stratified into a SOR cohort and an IO cohort. Baseline variables included demographics and biochemical markers. We assessed the association between survival and three baseline biomarkers: alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, and neutrophil-to-lymphocyte ratio (NLR). A prognostic score was developed in the SOR cohort by assigning one point to each adverse factor: AFP ≥200 ng/mL, ALBI grade 2-3, and NLR ≥3. Overall survival (OS) was estimated by the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) were derived from Cox regression models.

Results: The study included 440 patients in the SOR cohort and 32 in the IO cohort. In the SOR cohort. Most patients in both cohorts were Child-Pugh A, PS 0-1 and hepatitis C was the predominant etiology. AFP ≥200 ng/mL (P<0.001), ALBI 2-3 (P<0.001), and NLR ≥3 (P<0.001) were independently associated with worse OS. Median OS in the SOR cohort was 17.4 months for patients with 0-1 points, 7.9 months for 2 points, and 4.2 months for 3 points (P<0.001). The score remained prognostic in the IO cohort, where patients with 0-1 vs. 2-3 points had significantly different OS (HR 2.2; 95% CI: 1.1-4.9; P=0.04).

Conclusions: This simplified prognostic score, based on three routine laboratory parameters, stratifies survival outcomes in HCC patients receiving either sorafenib or immunotherapy. While further validation is needed in larger and more diverse populations, this tool may support individualized clinical counseling and risk-adapted trial design.

Background: Despite being the fourth leading cause of cancer deaths globally, advanced gastric cancer (GC) lacks effective therapeutic targets. While HER2-targeted therapy benefits a subset of patients, the role of its homolog ERBB4 remains controversial in GC pathogenesis and prognosis. This study aimed to examine the expression of ERBB4 in GC and explore whether it could serve as a new target for the biological therapy of GC.

Methods: Sequencing and clinical data on the ERBB4 gene in GC (tumor) tissues and adjacent non-cancerous (normal) tissues were downloaded from The Cancer Genome Atlas (TCGA) database. A differential expression analysis of the collected ERBB4 gene expression data was conducted. The ERBB4 expression profile in GC was obtained from the Human Protein Atlas (HPA) database. The association between ERBB4 expression and GC prognosis was analyzed using the Kaplan-Meier plotter. The relationship between ERBB4 gene methylation and stomach adenocarcinoma (STAD) was examined online by MEXPRESS visualization in TCGA database. The correlation between ERBB4 messenger RNA (mRNA) expression and methylation/copy number variations (CNVs) was also examined by Spearman correlation analysis. ERBB4 expression microarray data were obtained from the Kaplan-Meier plotter database, and the ERBB4 expression survival curve was plotted. A Cox regression model was established to conduct univariate and multivariate analyses of the risk factors affecting patient prognosis.

Results: Compared with adjacent non-cancerous tissues, ERBB4 mRNA and protein expression were significantly down-regulated in GC tissues. The mRNA expression level of the ERBB4 gene was affected by age, the sample type, and the risk of recurrence in GC patients. The abnormal amplification of ERBB4 was not correlated with its mRNA expression level. Additionally, there was a negative correlation between the methylation level and the mRNA expression of the ERBB4 gene. The Kaplan-Meier survival analysis revealed that patients with high ERBB4 expression had poor overall survival (OS) and progression-free survival (PFS) compared with those with low ERBB4 expression. The multivariate Cox regression analysis showed that ERBB4 was an independent prognostic factor for a poor prognosis in GC, but was not related to PFS.

Conclusions: ERBB4 is an independent prognostic factor for OS and may serve as a novel target for molecular therapy in GC.

Background: Gastric carcinoma ranks as one of the most prevalent gastrointestinal malignancies globally, with heterogeneous clinical-biological behavior significantly affecting prognosis and treatment outcomes. In advanced stages, systemic chemotherapy remains the cornerstone of treatment, but associated toxicities often limit their duration. Maintenance therapy with fluoropyrimidines has shown promise in improving survival and quality of life in colorectal and other cancers. However, its role in advanced gastric cancer, particularly in the Mexican population, remains underexplored. This study aimed to evaluate the survival benefit and toxicity profile of maintenance therapy with fluoropyrimidines in this population.

Methods: This retrospective study analyzed data from 190 patients with metastatic adenocarcinoma of the esophago-gastric junction and stomach treated between 2018 and 2023 at the Oncology Hospital, National Medical Center Century XXI. Patients with at least stable disease after induction chemotherapy based on fluoropyrimidines and platinum salts or camptothecins were included. Maintenance therapy with fluoropyrimidines (capecitabine or 5-fluorouracil) was evaluated. Progression-free survival (PFS), overall survival (OS), and toxicity profiles were assessed. Survival estimates were generated using the Kaplan-Meier method, and multivariate analyses employed Cox proportional hazards models, with significance set at P<0.05.

Results: The median follow-up was 17.4 months. Median PFS was 11.4 months [95% confidence interval (CI): 10.38-12.55], and median OS was 17.0 months (95% CI: 13.8-20.2). Patients with G1 tumors showed significantly longer PFS (22.8 months) compared to G3 tumors [10.8 months; hazard ratio (HR) =1.41, P<0.001]. Maintenance therapy with capecitabine was predominant (75.8%), with a median of six cycles administered. Common adverse events included neuropathy (52.6%), hand-foot syndrome (47.4%), and fatigue (43.7%). Grades 3-4 toxicities were rare, with hand-foot syndrome (7.4%) and fatigue (5.3%) being the most reported.

Conclusions: Maintenance therapy with fluoropyrimidines demonstrates a favorable survival benefit and manageable toxicity profile in advanced esophago-gastric adenocarcinoma. Despite limitations, including the study's retrospective design and the absence of direct comparisons with non-maintenance groups, these findings align with international studies, suggesting that fluoropyrimidines offer an effective strategy to prolong the benefits of first-line treatment in gastric cancer. Further studies incorporating human epidermal growth factor receptor 2 (HER2) and immune checkpoint inhibitors are warranted to enhance therapeutic personalization.

Background: The causal relationship between immune cell phenotypes and esophageal cancer (EC) has not yet been fully elucidated. Further, the potential mediating role of metabolites in the relationship between immune cell phenotypes and EC remains largely unexplored. This study investigated the genetic mechanisms underlying the effects of immune cells on EC, and examined the mediating effects of metabolites.

Methods: This study adopted a bidirectional two-sample Mendelian randomization (MR) approach to assess the causal relationship between immune cell phenotypes and EC. A reverse MR analysis was performed to eliminate potential reverse causation bias. Additionally, a two-step MR analysis and multivariable Mendelian randomization (MVMR) analysis were conducted to investigate potential metabolite mediators between immune cells and EC.

Results: First, the bidirectional two-sample univariable MR analysis revealed statistically significant causal associations between 22 immune cell phenotypes and EC. A subsequent MRMR analysis was conducted to evaluate the independent causal effects of these phenotypes on EC, and revealed persistent significant correlations for three specific subtypes: CD38⁺ CD20^- B cells, CD33⁺ CD14⁺ monocytes, and CD45⁺ CD33⁺ HLA^-DR⁺ CD14dim cells. Finally, MVMR combined with a mediation analysis revealed that the aspartate to citrate ratio mediated 10.6% of the total effect between the CD33⁺CD14⁺ monocytes and EC.

Conclusions: This study provides genetic evidence supporting the causal roles of specific immune cell phenotypes, particularly CD38⁺CD20^- B cells, CD33⁺CD14⁺ monocytes, and CD45⁺CD33⁺HLA-DR⁺CD14dim myeloid cells, in promoting EC risk. Furthermore, we identified the aspartate to citrate ratio as a significant metabolic mediator in the pathway linking monocyte activity to esophageal carcinogenesis. These findings unveil a novel immunometabolic axis and highlight potential therapeutic targets for intervening in EC development.

Background: STRIP2 is a key regulator of cytoskeletal dynamics, yet its precise role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to elucidate the mechanistic function of STRIP2 in HCC progression.

Methods: STRIP2 expression was analyzed using public databases. The prognostic significance and predictive value of STRIP2 were assessed through Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox regression, and nomogram models. Enrichment analysis was performed to explore STRIP2-related signaling pathways. Immune infiltration analysis was conducted to examine the relationship between STRIP2 and the tumor immune microenvironment. Tumor Immune Dysfunction and Exclusion (TIDE) scores and drug sensitivity analyses were used to evaluate the therapeutic relevance of STRIP2. Finally, immunohistochemistry (IHC) and immunofluorescence (IF) staining were performed to validate STRIP2 expression and its prognostic significance in a clinical cohort, while its functional role in HCC cells was investigated through knockout experiments.

Results: STRIP2 expression was found to be significantly upregulated in HCC tissues based on public database analysis, enrichment and immune infiltration analyses indicated that high STRIP2 expression was linked to an immunosuppressive tumor microenvironment, characterized by increased Th2 cell infiltration and reduced CD8⁺ T-cell activity. Mechanistically, STRIP2 may regulate ion channel activity to mediate cytoskeletal remodeling and cell adhesion, thereby enhancing HCC cell migration and invasion. Additionally, elevated STRIP2 expression was associated with reduced sensitivity to immunotherapy, as indicated by higher TIDE scores. Immunohistochemical and IF staining demonstrated that STRIP2 is predominantly localized in the cytoplasm of HCC cells. In clinical cohort analysis, STRIP2 overexpression was associated with poor prognosis in HCC patients. Cox regression analyses confirmed that it was an independent prognostic factor for HCC. Functional experiments further revealed that STRIP2 knockout significantly inhibited HCC cell proliferation, migration, and invasion.

Conclusions: STRIP2 functions as a tumor-promoting factor in HCC, facilitating tumor progression, immune evasion, and therapy resistance. STRIP2 may serve as a novel biomarker and a promising target for precision treatment in HCC.

Background: Early gastric cancer (EGC) represents a critical subgroup, with a significantly better prognosis compared to advanced-stage disease. However, even among patients with EGC, there are substantial variations in survival outcomes. This study aims to investigate the prognostic factors associated with overall survival (OS) in patients with EGC.

Methods: The clinicopathological data of 1,340 patients diagnosed with EGC who underwent surgery in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were collected, with those with incomplete data excluded. Potential predictors, including age, gender, race, the number of lymph nodes resected, lymph node metastasis (LNM), submucosal invasion, and tumor size were assessed. OS was measured from diagnosis to death or last follow-up. The X-tile program was used to identify the optimal cutoff value of tumor size. Univariate and multivariate Cox proportional hazards regression was used to explore the possible risk factors of EGC Subgroup analyses were performed on the independent prognostic factors of the patients.

Results: The optimal cutoff value for tumor diameter in EGC was determined to be 20 mm using X-tile software. There were 741 patients with a tumor diameter of ≤20 mm [small-size tumors (SST)] and 599 patients with a tumor diameter of >20 mm [large-size tumors (LST)]. The 5-year survival rates of the two groups were 64.9% and 52.8%, respectively, with statistical significance (P<0.001). The Cox proportional hazards regression model indicated that age (P<0.001), gender (P<0.001), race (P<0.001), the number of lymph nodes resected (P=0.003), LNM (P<0.001), submucosal invasion (P=0.002), and tumor size (P<0.001) were independent prognostic factors affecting survival. Further stratified analysis indicated that the survival rate of patients with LST was significantly lower than that of those with SST in patients without LNM (P<0.001). In patients aged ≥60 years, LST was independently associated with worse OS [hazard ratio (HR) =1.505; 95% confidence interval (CI): 1.210-1.871; P<0.001].

Conclusions: Age, gender, race, the number of dissected lymph nodes, LNM, invasion depth, and tumor size are independent factors affecting the prognosis of EGC patients. There are also differences in risk factors affecting prognosis among different age groups and different gender groups. The optimal cut-off point for tumor size was 20 mm, which can exert a significant impact on the prognosis of EGC patients without LNM or those aged ≥60 years. These findings can provide guidance for clinical decision-making. Identifying high-risk patients with different clinical characteristics can offer certain evidence-based support for the precise treatment of patients with EGC, thereby improving the overall patient management.

Background: Gastric cancer (GC) patients with peritoneal metastasis (PM) have a poor prognosis. Little is known about factors for successful conversion therapy in GC with PM. This study aimed to identify early predictive factors associated with R0 resection in GC patients with PM undergoing conversion therapy.

Methods: We retrospectively analyzed 108 patients diagnosed with PM via laparoscopic exploration and treated systemically at The First Affiliated Hospital of Xi'an Jiaotong University (2019-2023). Prognostic outcomes were evaluated using Kaplan-Meier analysis, and logistic regression was employed to identify factors influencing conversion therapy success.

Results: In total, 108 patients with PM were included in the study, 21 of whom underwent R0 resection after conversion therapy (R0 resection rate, 19.4%). Patients in the conversion surgery (CS) group had a significantly longer median overall survival than those in the non-CS group (P<0.001). Multivariate analysis revealed that elevated carbohydrate antigen 125 (CA125) levels [odds ratio (OR): 5.449, 95% confidence interval (CI): 1.425-20.830; P=0.01] were a risk factor for the failure of conversion therapy in GC patients with PM. Treatment with a programmed death 1 (PD-1) inhibitor (OR: 0.285, 95% CI: 0.099-0.820, P=0.02) was a protective factor against the failure of conversion therapy in GC patients with PM.

Conclusions: Achieving R0 resection through conversion therapy can significantly improve the prognosis of GC patients with PM. For patients with no significant elevation of CA125, it is advisable to consider implementing an aggressive first-line regimen in conjunction with a PD-1 inhibitor for the purpose of conversion therapy.

Rectal cancer is one of the most widespread malignant tumors in the world, with the common treatment methods being surgery, chemotherapy, and radiotherapy. Due to its minimally invasive nature and associated rapid postoperative recovery, laparoscopic radical surgery has become one of the preferred options for treating rectal cancer. With the continuous advancement of surgical techniques and the integration of advanced technologies, especially the application of indocyanine green (ICG) fluorescence technology, the precision and efficiency of surgeries have been greatly improved, fundamentally changing the approach to complex operations. One of the most innovative advancements is the use of ICG fluorescence navigation, particularly in laparoscopic colorectal cancer surgery. This technology leverages the properties of ICG, a near-infrared fluorescent dye, to enhance the visualization of key anatomical structures during surgery. The application of ICG fluorescence technology in laparoscopic rectal cancer surgery is a significant breakthrough, providing surgeons with a novel approach for improving intraoperative decision-making. This study aimed to examine the clinical application of ICG fluorescence imaging technology in laparoscopic rectal cancer surgery. A patient with rectal cancer was selected, and ICG was injected before surgery. During the procedure, a laparoscopic fluorescence imaging system was used to observe fluorescence signals from the tumor and lymph node areas in real time. The fluorescence imaging results were compared with those of conventional imaging to assess the role of this technology in tumor resection and lymph node dissection. Postoperative pathological examination was conducted to verify the accuracy of the imaging results, and postoperative follow-up was carried out to further determine the clinical value of ICG fluorescence imaging in rectal cancer surgery. In addition, we developed a case report guide containing 13 components: title, keywords, abstract, introduction, patient information, clinical findings, timeline, diagnostic evaluation, treatment intervention, follow-up, results, discussion, patient perspectives, and informed consent. Considering our findings, we believe that ICG fluorescence navigation technology will play an increasingly important role in the surgical treatment of rectal cancer.

Background: Colorectal cancer (CRC) is a major cause of cancer-related mortality in Japan, and while first- and second-line regimens have improved outcomes, the optimal third-line strategy remains unclear. Modified regimens based on Narrative Evidence-Based Medicine (NEBM) and Minimally Effective Cytotoxic Dose (MECD) theory have shown promise in maintaining survival with fewer adverse events (AEs) in Japanese patients. This study aimed to retrospectively evaluate the survival outcomes, efficacy, and safety of third-line chemotherapy following standardized earlier treatments in stage IV CRC.

Methods: This study retrospectively evaluated 37 patients, 12 with advanced recurrence following primary tumor resection and 25 with unresectable tumors with distant metastases, who had received at least three courses of chemotherapy (175 courses). The 12- and 36-month progression-free survival (PFS) and overall survival (OS) rates, along with median survival time (MST), were assessed. The number of courses (median), objective response rate (ORR), clinical benefit rate (CBR), and AEs were also examined. In addition, the 60-month (60M)-OS and MST were calculated from the initiation of first-line chemotherapy to assess the long-term efficacy of multidisciplinary treatment in advanced recurrent CRC.

Results: The 12-month (12M)-PFS and 12M-OS were 18.9% (MST 4.1 months) and 52.9% (MST not reached), respectively. The 36-month (36M)-PFS and 36M-OS rates were 5.4 % (MST 4.1 months) and 13.9% (MST 13.3 months), respectively. Meanwhile, the 60M-OS rate was 27.8%, with an MST of 39.9 months. The median number of courses was 7.0 (4.0-9.0), with an ORR and CBR of 10.8% and 37.8%, respectively. AEs were mostly grade 1, while hematological side effects tended to be grade 2, but improved after adjusting the dose and dosing interval. Only two patients (5.4%) required granulocyte colony-stimulating factors. Grade 3 AEs included leukopenia (n=2, 5.4%), neutropenia (n=6, 16.2%), thrombocytopenia (n=2, 5.4%), and allergic reaction (n=1, 3.0%). After three courses, grade 3 hematological AEs included neutropenia (n=6, 16.2%), thrombocytopenia (n=2, 5.4%), and anemia (n=2, 5.4%).

Conclusions: This study demonstrates that third-line chemotherapy incorporating oral anticancer drug and bevacizumab (B-mab) following standardized treatment is a safe and effective option for Japanese patients with stage IV CRC. The regimen was associated with a manageable safety profile and encouraging long-term outcomes and may contribute to improved quality of life and quality-adjusted life years prior to transition to best supportive care.