Journal of gastrointestinal oncology最新文献

Background: Several studies have investigated the efficacy of neoadjuvant imatinib treatment (NAT) for gastrointestinal stromal tumors (GISTs); however, research on pathological regression and the prognostic factors affecting survival is limited. Thus, this study aimed to examine pathological regression and assess the prognostic factors associated with survival in GIST patients who received NAT.

Methods: The data of patients who received NAT for primary GISTs with a tumor size larger than 5.0 cm from January 2007 to December 2022 were retrospectively reviewed. Five grades of pathological regression were proposed. A survival analysis was conducted using the Kaplan-Meier method, and a Cox proportional hazards model was used to identify the independent prognostic factors.

Results: In total, 80 patients were enrolled in the study, of whom 54 (67.5%) were men and 26 (32.5%) were women. The median age of the patients was 60 (range, 39-75) years. The median duration of NAT was 7.0 (range, 0.4-23) months, and the median tumor size decreased from 9.4 to 6.2 cm. Pathological regression was found to be significantly correlated with a decrease in both tumor size (P=0.008) and tumor density (P<0.001). With a median follow-up time of 69 months, the estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 86.4% and 95.4%, respectively. The multivariate analysis identified pre-neoadjuvant tumor size [hazard ratio (HR) =5.263, 95% confidence interval (CI): 1.552-17.849, P=0.008], tumor location (HR =3.522, 95% CI: 1.161-10.683, P=0.03), mitotic count (HR =3.647, 95% CI: 1.070-12.428, P=0.04), and post-operative imatinib treatment (HR =0.124, 95% CI: 0.027-0.571, P=0.007) as independent prognostic factors.

Conclusions: Pre-neoadjuvant tumor size, tumor location, mitotic count, and post-operative imatinib treatment were identified as prognostic factors for GIST patients who received NAT. Pathological regression was associated with radiological changes in the tumor, but it was not correlated with long-term patient prognosis.

Background: While malignant neoplasms (MNs) of digestive system (MNDS) remain a leading cause of cancer mortality, evolving patterns of cause-specific deaths in the modern treatment era are poorly characterized. This study aimed to depict the trends in cause-specific mortality among MNDS patients in the U.S. from 2007 to 2021, stratified by clinical and demographic factors, with particular focus on the growing impact of non-neoplasm causes of death (CODs).

Methods: This retrospective study analyzed incidence-based mortality rates from 22 registries of the Surveillance, Epidemiology, and End Results program. Patients diagnosed with MNDS in 2000-2021 who died in 2007-2021 were included. Mortality rates were age-adjusted to the 2000 U.S. standard population. Trends of mortality rates were quantified by annual percent changes (APCs), calculated with Joinpoint regression. We stratified the cohort by tumor site, age at death, sex, race, and tumor stage. In each subgroup, mortality rates were classified by COD into MNDS, non-digestive system MNs, non-MNs, non-neoplasm diseases, and unknown COD. In the overall cohort, non-neoplasm CODs were further subclassified.

Results: From 2007 to 2021, 1,318,354 deaths occurred among MNDS patients, corresponding to an average mortality rate of 619.27 [95% confidence interval (CI): 618.2, 620.34] per 1,000,000 person-years. The overall mortality increased by 0.53% per year (95% CI: 0.40-0.67%; P<0.001), driven by the increasing non-neoplasm mortality of 3.15% per year (95% CI: 2.59-3.78%; P<0.001) despite declining MNDS-specific mortality (APC: -0.51%; 95% CI: -0.65% to -0.36%; P<0.001). Both sexes demonstrated similar mortality patterns. Colorectal MNs demonstrated a decline in MNDS-specific mortality (APC: -1.46%; 95% CI: -1.58 to -1.34%; P<0.001), but increasing non-neoplasm mortality (APC: 2.72%; 95% CI: 2.15-3.39%; P<0.001) led to overall mortality increase (APC: 0.25%; 95% CI: 0.05-0.47%; P=0.01). Meanwhile, patients with pancreatic, biliary, and anal MNs experienced mortality increases from both MNDS-specific and non-neoplasm CODs. Notably, medical complications displayed the fastest acceleration (APC, 8.58%; 95% CI: 4.97-14.17%; P<0.001) among non-neoplasm CODs. American Indian or Alaska Native was the only race with non-decreasing MNDS-specific mortality (APC: 0.63%; 95% CI: -0.56% to 1.95%; P=0.22) alongside the fastest-growing non-neoplasm mortality (APC: 4.23%; 95% CI: 3.21-5.52%; P<0.001). Localized-stage patients had the most rapid non-neoplasm mortality increase (APC: 6.42%; 95% CI: 5.60-7.43%; P<0.001) across tumor stages.

Conclusions: Non-neoplasm diseases have become the dominant determinant of mortality increases in MNDS patients. This paradigm change requires transforming MNDS care to address comorbidities alongside cancer treatment, particularly for high-risk subgroups.

Background: Trials on tyrosine kinase inhibitors combined with sintilimab and transarterial chemoembolization (TKIs-Sin-TACE) for the treatment of unresectable hepatocellular carcinoma (HCC) are ongoing and show promising results. However, the number of participants recruited so far has been relatively limited. This pooled analysis aims to evaluate the efficacy and safety of TKIs-Sin-TACE in patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC.

Methods: To obtain potentially eligible studies, databases such as PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched up to October 1, 2024. The Methodological Index for Non-Randomized Studies (MINORS) was used to evaluate literature quality and the levels of bias. A random-effects model was utilized to calculate the pooled rate and confidence interval (CI).

Results: This study included six studies involving a total of 336 patients with HCC at BCLC stage B/C. Regarding efficacy, the pooled objective response rate, disease control rate, integrated rates for 10-month progression-free survival, 10-month overall survival (OS), 20-month OS were 39% (95% CI: 26-55%),74% (95% CI: 60-84%),41% (95% CI: 30-54%), and 73% (95% CI: 54-86%), 30% (95% CI: 16-49%), respectively. Regarding safety, the aggregated incidence of treatment-related adverse events ≥ grade 3 was 23% (95% CI: 12-42%).

Conclusions: TKIs-Sin-TACE exhibits an efficacious and safe profile for Chinese patients with BCLC stage B/C HCC. Large-scale, global multicenter randomized-controlled trials are needed to further validate these findings.

Background: The impact of adjuvant chemotherapy (ACT) on gastric cancer (GC) patients receiving neoadjuvant chemotherapy (NACT) remains unclear. This study aims to evaluate the effect of ACT on survival in patients undergoing curative surgery after NACT.

Methods: Clinical and pathological data of GC patients treated with NACT followed by radical surgery were retrospectively collected. Patients were categorized according to ACT administration. Propensity score matching (PSM) was employed to compare the prognosis between those who received ACT and those who did not.

Results: After cohort selection and PSM, 180 patients with locally advanced GC were included: 116 in the ACT group and 64 in the no ACT group. No significant difference in overall survival (OS) was observed between the two groups (P=0.46). Subgroup analyses based on tumor invasion depth, lymph node metastasis, histological subtype, lymphovascular invasion (LVI), perineural invasion (PNI), and tumor regression grade (TRG) revealed no significant OS benefit from ACT in any subgroup. In a smaller cohort subset, among patients lacking mature tertiary lymphoid structures (mTLSs) in the tumor bed, the ACT group exhibited a higher OS rate compared with the no ACT group (P=0.006). Conversely, among patients with mTLSs, the no-ACT group demonstrated better survival (P=0.02). Likelihood ratio tests and multivariate Cox regression analysis indicated that the effect of ACT on OS depends on mTLS status. In subgroups stratified by mTLS status, ACT was identified as an independent prognostic factor.

Conclusions: For patients with locally advanced GC treated with NACT, ACT does not confer a significant survival benefit in the overall population. The presence of mTLSs following NACT serves as a strong predictive biomarker for ACT efficacy. Patients without mTLSs in the tumor bed after NACT may derive greater benefit from ACT.

Background: Advanced pancreatic adenocarcinoma (PA) remains a formidable challenge with limited therapeutic options. Gemcitabine-based regimens, often combined with novel targeted therapies, are widely employed, yet their comparative efficacy is poorly understood. This network meta-analysis (NMA) aimed to systematically evaluate the efficacy of various targeted drug combinations in previously treated patients with advanced or metastatic PA.

Methods: A systematic search of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov was conducted to retrieve relevant randomized controlled trials (RCTs) published between 2010 and 2024. Studies comparing targeted drug combinations with chemotherapy or chemotherapy alone in advanced/metastatic PA were included in the NMA. The primary outcomes of the study were overall survival (OS) and progression-free survival (PFS), which were assessed using hazard ratios (HRs) with 95% confidence intervals (CIs) and presented in a Forest plot. Surface under the cumulative ranking (SUCRA) scores were calculated to rank treatment efficacy.

Results: In total, 13 RCTs, comprising 4,665 patients and evaluating 13 targeted drug combinations, were included in the NMA. While no statistically significant improvements in OS or PFS were observed for most targeted drug combinations compared with gemcitabine monotherapy, epidermal growth factor receptor (EGFR)-targeted agents, particularly nimotuzumab, demonstrated a significant survival benefit in specific subgroups. Similarly, indirect comparisons among targeted therapies revealed no significant differences. The SUCRA rankings identified gemcitabine plus nimotuzumab (Gem-Nimot; 98%) as having the highest probability of ranking first for OS, followed by gemcitabine plus masitinib (Gem-Masit; 80%), gemcitabine plus erlotinib (Gem-Erlot; 70%), and gemcitabine plus sorafenib (Gem-Soraf; 23%). For PFS, Gem-Nimot (98%) ranked highest, followed by Gem-Erlot (73%), gemcitabine plus rigosertib (Gem-Rigos; 57%), and gemcitabine plus sunitinib (Gem-Sunit; 8%).

Conclusions: This NMA combining network and forest plot results showed that Gem-Nimot provided significant survival benefits in advanced PA. EGFR-targeted combinations demonstrated a significant advantage in both OS and PFS compared with gemcitabine alone, indicating that EGFR inhibition may provide real clinical benefits.

Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment for advanced or metastatic esophageal adenocarcinoma (EAC)/gastroesophageal junction adenocarcinoma (GEJC). The aim is to explore the safety and efficacy of ICI and a potential biomarker.

Methods: As of August 2025, we comprehensively reviewed the literature on clinical randomized controlled trials (RCTs) by searching keywords, such as "esophageal adenocarcinoma", "gastroesophageal junction cancer", or "immunotherapy" across multiple databases (including Embase, Cochrane, Scopus, PubMed, Web of Science and the Clinical Trial Registries, as well as abstracts from the American Society of Clinical Oncology, European Society of Medical Oncology and other international tumor conferences). Two authors independently screened the studies, extracted the relevant data, and used RevMan 5.3 software and related evaluation tools for the statistical analysis and risk and quality evaluations, respectively. The primary outcomes of the study were overall survival (OS) and progression-free survival (PFS), which were estimated by calculating the hazard ratio (HR) and confidence interval (CI). The secondary outcomes were the objective response rate (ORR), and incidence of adverse events (AEs).

Results: In total, seven studies, comprising 7,043 patients with advanced EAC/GEJC, were included in the meta-analysis. We compared the efficacy of immunotherapy combined with chemotherapy, and chemotherapy alone. Immunotherapy combined with chemotherapy significantly improved the survival rate of the patients, significantly prolonging their OS (HR =0.80, 95% CI: 0.76-0.85, P<0.001; I²=0%). The PFS (HR =0.75, 95% CI: 0.71-0.80, P<0.001; I²=0%) and ORR of these patients also improved significantly. The incidence of AEs was higher in the immunotherapy combined with chemotherapy patients than the chemotherapy alone patients, but the overall range was controllable. The magnitude of the treatment benefit from immunotherapy combined with chemotherapy was positively correlated with the combined positive score (CPS), with greater efficacy observed in patients with higher CPS levels.

Conclusions: Immunotherapy combined with chemotherapy significantly improved the survival benefit of patients with advanced EAC/GEJC, better controlled disease progression, and had controllable AEs.

Background: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with diabetes mellitus (DM), and their prognosis remains particularly poor. Metformin, a widely used antidiabetic agent, has demonstrated anti-tumor effects through multiple mechanisms and has been associated with improved outcomes in various malignancies. In this study, we investigated retrospectively survival outcomes and intra-tumoral infiltration patterns of various immune cells in diabetic patients who underwent curative resection of PDAC, comparing those who received metformin with those who did not.

Methods: A total of 65 diabetic patients who underwent curative resection for invasive PDAC were retrospectively analyzed. Among them, 17 patients received metformin, while 48 did not. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups. Following propensity score matching, tumor-infiltrating CD3(+) and CD8(+) T cells were assessed by immunohistochemistry (IHC), and their densities were compared between metformin users and non-users.

Results: Patients in the metformin group showed significantly prolonged RFS [hazard ratio (HR) =0.42, P=0.03] and OS (HR =0.421, P=0.03) compared to those in the non-metformin group. Multivariate analysis identified metformin use as an independent prognostic factor for both RFS (HR =0.40, P=0.02) and OS (HR =0.21, P=0.02). The survival benefit of metformin was particularly evident in patients who underwent upfront surgery, whereas not significant in those who received neoadjuvant therapy. Immunohistochemical analysis revealed a significantly higher density of CD8(+) T cells (650.7 vs. 269.9/mm², P<0.001) with an increased CD8/CD3 ratio in resected tumors from metformin-treated patients compared to non-users (58.9% vs. 44.8%, P<0.001). This trend was kept in patients who underwent upfront surgery, while less pronounced in patients treated with neoadjuvant therapy.

Conclusions: Metformin may enhance the infiltration of cytotoxic CD8(+) T cells into the tumor microenvironment and improve the prognosis of diabetic patients with PDAC, particularly in those undergoing upfront surgical resection.

Background: Patient selection is one of the key factors influencing prognosis after liver transplantation (LT), and a number of selection criteria have been proposed and broadly applied. The benefit of LT is debatable when patients exceed these criteria in light of liver worldwide donor shortage. This study aims to identify key prognostic indicators predicting patients undergoing LT beyond Hanzhou criteria, to guide LT candidate selection.

Methods: The clinical data and pathological findings of patients who underwent LT in the Liver Transplantation Center of General Hospital of Southern Theater Command from September 2003 to August 2017 were collected for retrospective analysis, only patients exceeding the Hangzhou criteria were enrolled. Patients were followed up until December 1, 2023; disease-free survival (DFS) and overall survival (OS) was analyzed; and predictive models of DFS and OS were constructed and validated.

Results: A total of 161 patients were included in the analysis. A tumor diameter ≥6 cm [hazard ratio (HR) =2.01; P=0.01], alpha fetoprotein (AFP) levels >1,000 ng/mL (HR =2.68; P<0.001), lack of metformin administration (HR =2.98; P=0.008), operative blood loss >2,000 mL (HR =1.75; P=0.01), and female donor gender (HR =3.71; P=0.004) were independent risk factors for lower DFS, while a tumor diameter ≥6 cm (HR =2.05; P=0.001), AFP level >1,000 ng/mL (HR =1.54; P=0.04), and female donor gender (HR =4.45; P<0.001) were independent predictors of worse OS. Patients with a preoperative AFP level ≤1,000 ng/mL or a history of metformin administration had a significantly better prognosis after LT.

Conclusions: For patients exceeding the Hangzhou criteria, those with an AFP level ≤1,000 ng/mL can still achieve acceptable long-term prognosis after LT. Administration of metformin has a strong positive association with longer recurrence-free survival. The patient criteria for selection for LT can be tentatively expanded.

Background: Anastomotic leak after reversal of an ostomy is a significant complication in rectal cancer patients. The effects of neoadjuvant chemoradiotherapy (NCRT) on outcomes following stoma reversal are not well established. The aim of our study was to evaluate the effect of NCRT on outcomes in rectal cancer patients following stoma reversal.

Methods: We performed a [2005-2012] retrospective cohort analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), including adult (≥18 years) rectal cancer patients who had elective stoma reversal. Patients were stratified into those who received NCRT and those who did not. Primary outcomes were anastomotic leak and major complications. Secondary outcomes were mortality and length of stay (LOS). Regression analysis was performed confounding variables.

Results: We identified a total of 461 patients of which 259 received NCRT while 202 did not. The mean age was 52±10 years, and 28% had an American Society of Anesthesiologists (ASA) class III-IV. Overall, the rate of anastomotic leak was 6.8%. Major complications were seen in 5.6% of patients with the most common complication being organ space infection (3.2%). There was no difference between the two groups regarding anastomotic leak (7.9% vs. 6.2%, P=0.22), major complications (5.1% vs. 6.4%, P=0.17), LOS {5 [3-5] vs. 4 [4-5] days, P=0.12}, or mortality (1.9% vs. 2.4%, P=0.26). On regression analysis, after adjusting for confounding variables, NCRT was not associated with anastomotic leaks [overall survival: odds ratio (OR) =1.03; 90% confidence interval (CI): 0.86-1.07], major complications (OR =1.97; 90% CI: 0.79-1.99), or mortality (OR =1.04; 90% CI: 0.59-1.12).

Conclusions: Our findings suggested that NCRT for rectal cancer does not increase morbidity following stoma closure. Stoma closure is safe and should not be withheld based on NCRT.