Adding anti-PD-1 or anti-VEGF therapy to chemotherapy improves survival in patients with advanced gastric cancer, yet outcomes remain poor. This Phase Ib/II trial aimed to evaluate the efficacy and safety of combining sintilimab, the bevacizumab biosimilar IBI305, and CapeOX chemotherapy as a first-line treatment for patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (GA/GEJA). In phase Ib, no dose-limiting toxicities (DLTs) that served as the primary endpoint were observed (N = 9). In phase II, the primary endpoint of the objective response rate (ORR) in the efficacy-evaluable population (N = 54) was 87.0% (95% CI: 75.1–94.6%), achieving the pre-specified target was reached. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and safety. The DCR was 98.1% (95% CI: 90.1–100.0%). At a median follow-up of 20.3 months, median PFS and DoR were 12.2 months (95% CI: 9.2–18.1) and 12.5 months (95% CI: 9.4–NE), respectively, while the median OS was not reached. A clinical benefit was observed regardless of PD-L1 CPS, Claudin-18.2 expression status, or the presence of peritoneal metastases. Treatment-related adverse events of grade ≥3 occurred in 66% of patients; the most common were neutropenia (14%), fatigue (13%), and thrombocytopenia (11%). The limitations of the study include the single-arm, non-randomized design and the modest sample size, which necessitate confirmation in larger randomized controlled trials. Nonetheless, sintilimab plus IBI305 and chemotherapy demonstrated promising antitumor activity and favorable PFS with manageable toxicity in HER2-negative advanced GA/GEJA. Trial number: NCT05640609. Previous evaluations on anti-VEGF monoclonal antibody indicate its therapeutic potential in gastric cancer treatment. Here this group reports a phase Ib/II trial combining sintilimab/bevacizumab biosimilar IBI305/CapeOX chemotherapy as the first-line treatment on 54 patients with HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma.

IntroductionUndifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive malignant soft tissue sarcoma. While most commonly arising in the extremities and trunk, primary occurrence in the stomach is exceedingly rare. Due to its rarity and nonspecific presentation, preoperative diagnosis is challenging and often established postoperatively through detailed histopathological and molecular analysis.Case presentationWe report the case of a 71-year-old female presenting with a gastric mass and anorexia, who was preoperatively misdiagnosed with gastrointestinal stromal tumor(GIST) based on clinical and imaging characteristics. Due to the massive tumor burden and anatomical complexity, the patient underwent an R0 resection combined with splenectomy. The final diagnosis of primary gastric UPS was established through an exclusionary process involving comprehensive histopathological, immunohistochemical (including negativity for CD117, CD34, DOG-1), and molecular analyses to rule out other tumors with specific lines of differentiation. Despite adjuvant doxorubicin chemotherapy, follow-up imaging revealed tumor recurrence two months postoperatively.ConclusionThis case underscores the highly aggressive biological behavior and dismal prognosis associated with primary gastric UPS. The rapid recurrence following multimodal therapy highlights the critical importance of considering UPS in the differential diagnosis of gastric soft tissue masses and emphasizes the urgent need for more effective, comprehensive therapeutic strategies.

The liver executes essential metabolic functions including energy homeostasis, lipid biosynthesis, cholesterol regulation and xenobiotic detoxification. While hepatocyte metabolic activity forms the foundation of these processes, their precise regulation is achieved through chromatin remodelling mechanisms, with the SWI/SNF complex emerging as a central epigenetic orchestrator. Accumulating evidence positions this ATP-dependent chromatin remodeler as a critical regulator of hepatic development, homeostatic maintenance and pathological transformation. Through nucleosome repositioning and histone-DNA interaction modulation, the SWI/SNF complex governs transcriptional programs controlling cellular proliferation, differentiation and metabolic adaptation. This review synthesises current understanding of SWI/SNF-mediated epigenetic regulation in hepatic biology and explores its therapeutic potential for liver disorders.

RATIONALE:The role of nonsteroidal anti-inflammatory drugs, particularly aspirin, in the primary prevention of colorectal cancer remains controversial. The debate over aspirin use is driven by the challenge of balancing uncertain preventive benefits against the risks of adverse effects. Given the inconsistent findings from clinical trials and conflicting clinical guidelines, a rigorous and updated systematic review is necessary to clarify the evidence base. OBJECTIVES:To assess the benefits and harms of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, for preventing colorectal cancer (CRC) and colorectal adenoma (CRA) in the general population. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, and two clinical trial registers (ClinicalTrials.gov and WHO ICTRP) on 3 March 2025. ELIGIBILITY CRITERIA:We included parallel-group or factorial-design randomized controlled trials (RCTs) comparing aspirin and other NSAIDs with either no treatment or a different treatment for preventing CRC or CRA in the general population. OUTCOMES:Our critical outcomes were CRC incidence and serious adverse events (SAE). Our important outcomes included CRC mortality, CRA incidence, serious extracranial hemorrhage, and hemorrhagic stroke. When data were available, we categorized findings into prespecified follow-up intervals: 5 to < 10 years, 10 to < 15 years, and ≥ 15 years. RISK OF BIAS:We assessed the risk of bias for study outcomes as high risk, some concerns, or low risk, using the Cochrane RoB 2 tool. SYNTHESIS METHODS:We synthesized data for each outcome using random-effects meta-analysis. For time-dependent outcomes, we prioritized time-to-event data, calculating hazard ratios (HRs) with 95% confidence intervals (CIs). When these were unavailable, we used dichotomous data to calculate risk ratios (RRs). For rare outcomes, we calculated Peto odds ratios (ORs) using a fixed-effect model. We used GRADE to assess the certainty of the evidence. INCLUDED STUDIES:We included 10 RCTs involving a total of 124,837 participants. These studies compared aspirin with either placebo or no treatment for the primary prevention of CRC. Low-dose aspirin (75 to 100 mg per day) was typically used, though three studies evaluated higher doses. The studies were mostly conducted in Europe and North America. One study had sites in Australia, and there were two large studies conducted in Japan. Seven studies reported long-term results with extended observational follow-up where blinding had ceased. We did not identify any RCTs that evaluated the use of non-aspirin NSAIDs by the general population for primary CRC prevention. SYNTHESIS OF RESULTS:For the comparison of aspirin versus inactive control in the general population, we rated the certainty of the evidence as very low to high. We downgraded the certainty level for several outcomes due primarily to risk of bias and imprecision. Regarding CRC incidence, aspirin probably results in little to no difference at follow-up ≥ 5 to < 10 years (HR 1.00, 95% CI 0.81 to 1.24; 3 studies, 26,702 participants; moderate-certainty evidence) and at ≥ 10 to < 15 years (HR 0.95, 95% CI 0.77 to 1.17; 2 studies, 42,412 participants; moderate-certainty evidence). Aspirin may reduce CRC incidence slightly at follow-up ≥ 15 years (HR 0.78, 95% CI 0.67 to 0.91; 3 studies, 47,464 participants; very low-certainty evidence), but the evidence is very uncertain. Regarding CRC mortality, aspirin may increase mortality at follow-up ≥ 5 to < 10 years (HR 1.77, 95% CI 1.02 to 3.07; 1 study, 19,114 participants; low-certainty evidence), may result in little to no difference in mortality at follow-up ≥ 10 years and < 15 years (Peto OR 1.14, 95% CI 0.73 to 1.78; 1 study, 39,876 participants; low-certainty evidence), but may reduce mortality at follow-up ≥ 15 years (Peto OR 0.74, 95% CI 0.60 to 0.90; 5 studies, 53,909 participants; very low certainty evidence), but the evidence is very uncertain. Regarding CRA incidence, aspirin may result in little to no difference in CRA incidence at ≥ 5 to < 10 years of follow-up (Peto OR 0.42, 95% CI 0.10 to 1.87; 1 study, 12,546 participants; very low certainty evidence), but the evidence is very uncertain. Regarding safety, although aspirin probably results in little to no difference in overall SAE (RR 1.06, 95% CI 0.84 to 1.34; 3 studies, 16,442 participants; moderate-certainty evidence), aspirin does increase the risk of serious extracranial hemorrhage (RR 1.59, 95% CI 1.30 to 1.95; 8 studies, 97,567 participants; high-certainty evidence) and probably increases the risk of hemorrhagic stroke (Peto OR 1.40, 95% CI 1.11 to 1.77; 8 studies, 105,037 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS:It is not possible to draw definitive conclusions or outline specific implications for the routine use of aspirin for CRC primary prevention based on the current evidence. Our findings reveal complex, time-dependent preventive effects and concerns about potential harms for clinicians and patients to consider. Evidence of very low to moderate certainty shows little to no benefit for CRC or CRA incidence in the first 15 years, and low-certainty evidence suggests a potential increase in CRC mortality in the first 5 to 10 years. Very low-certainty evidence suggests potential benefits for CRC incidence and mortality after long-term follow-up (≥ 15 years), but these potential long-term benefits are derived from findings in the observational follow-up phases of RCTs, where standard intention-to-treat analyses are not robust to post-randomization confounding from factors such as treatment contamination. The uncertain and delayed potential for benefit must be weighed against a definite harm. While aspirin probably has little to no effect on overall serious adverse events (moderate-certainty evidence), it increases the risk of serious extracranial hemorrhage (high-certainty evidence) and probably increases the risk of hemorrhagic stroke (moderate-certainty evidence). In light of the mixed evidence, clinical practice should continue to center on an individualized assessment and a shared decision-making process, carefully balancing a patient's established cardiovascular risk profile against their risk of bleeding. FUNDING:This Cochrane review was funded (in part) by the China Postdoctoral Science Foundation (2024M752248) and the Postdoctoral Fellowship Program (Grade A) of China Postdoctoral Science Foundation (BX20230244). REGISTRATION:Protocol available via doi.org/10.1002/14651858.CD015266.

BACKGROUND:Bladder cancer (BCa) progression is driven by the tumor microenvironment, with cancer-associated fibroblasts (CAFs) playing a pivotal role. Periostin (POSTN), secreted by CAFs, is linked to tumor malignancy, but its specific role in BCa remains unclear. METHODS:This study is a secondary analysis of publicly available single-cell and bulk transcriptomic data. Single-cell RNA sequencing (scRNA-seq) data from four BCa and four control samples were analyzed to construct a transcriptomic atlas. CAFs and monocytes were subclustered, and POSTN+ CAFs were characterized using differential gene expression, GSVA, and KEGG analyses. CellChat and NicheNet assessed cell-cell communication. TCGA data were used to validate POSTN's prognostic significance. Additionally, POSTN expression was detected in transfected CAF cell lines, and scratch and invasion assays were performed using the co-culture system of CAFs and bladder cancer cells (T24). RESULTS:Nine cell clusters were identified, with monocytes and CAFs enriched in BCa. POSTN+ CAFs, significantly increased in BCa, promoted angiogenesis, migration, and invasion. CellChat revealed enhanced CAF-monocyte communication via the IL1B/IL1R1 axis, contributing to an immunosuppressive microenvironment. KLRC1+ monocytes were enriched in BCa, regulating cell cycle and angiogenesis. Pseudotime analysis showed CAFs' differentiation toward pro-tumorigenic states. TCGA analysis confirmed POSTN's upregulation and association with poor prognosis (P < 0.05). Functional assays revealed CAFs markedly enhanced T24 migration and invasion, and POSTN knockdown suppressed this CAF-induced effect (P < 0.01). CONCLUSION:POSTN+ CAFs drive BCa progression by enhancing angiogenesis, migration, and immune suppression, mediated partly by the IL1B/IL1R1 axis.

Occult peritoneal metastasis (OPM) is common in locally advanced gastric cancer, and accurate detection is critical. This prospective cohort study evaluated the diagnostic accuracy and cost of 68Ga-FAPI-04 PET/CT for detecting OPM. Methods: This single-center, prospective cohort study included patients with locally advanced gastric adenocarcinoma. All patients underwent 68Ga-FAPI-04 PET/CT before laparoscopic staging, and the diagnosis of OPM was established using laparoscopic staging combined with peritoneal washing cytology as the gold standard. The primary endpoint was the proportion of patients whose treatment intent changed based on 68Ga-FAPI-04 PET/CT results. Secondary endpoints included diagnostic accuracy and cost analysis of 68Ga-FAPI-04 PET/CT in detecting OPM. Results: In total, 109 patients were recruited between November 2022 and August 2024. 68Ga-FAPI-04 PET/CT identified OPM in 17 patients (15.6%), resulting in upstaging to stage IV, with sensitivity, specificity, and diagnostic accuracy of 75.0%, 94.6%, and 91.7%, respectively (area under the curve, 0.83; 95% CI, 0.72-0.94). Economic analysis demonstrated a net cost savings of $979.30 per patient when compared with laparoscopic staging. The combination of 68Ga-FAPI-04 PET/CT and laparoscopic staging reduced the need for laparoscopic procedures by 84% and prevented 11% of futile gastrectomies, yielding a minimal cost savings of $232.30 per patient. Conclusion: 68Ga-FAPI-04 PET/CT demonstrates high diagnostic accuracy, low cost, and the potential to reduce invasive procedures, making it a promising alternative to laparoscopic staging in patients with locally advanced gastric cancer.

Neurofibromatosis type 1 (NF1), an autosomal dominant disorder resulting from mutations in the NF1 tumor suppressor gene, predisposes affected individuals to diverse benign and malignant neoplasms. We herein report a rare case of a 61-year-old female NF1 patient presenting with a unique combination of four synchronous or metachronous tumors: a duodenal ampullary neuroendocrine tumor (NET, Grade 2), a high-risk gastrointestinal stromal tumor (GIST) of the small intestine, a previously resected gastric leiomyoma, and cutaneous neurofibromas. Preoperative evaluation included endoscopy, endoscopic ultrasound, contrast-enhanced CT, and MRI, which localized the lesions and assessed their morphological features. The patient underwent pancreaticoduodenectomy and partial small bowel resection, achieving complete tumor resection. Genetic testing identified a germline NF1 mutation (p.Y2182*). No adjuvant therapy was administered due to the absence of residual disease and actionable mutations. This case highlights the broad tumor spectrum in NF1 and underscores the importance of comprehensive imaging, multidisciplinary management, and genetic testing for optimal outcomes.

Surgery remains curative for esophageal gastrointestinal stromal tumors (GISTs), while debates persist between minimally invasive enucleation and radical esophagectomy. Limited evidence from case reports and small cohorts necessitates a systematic evaluation to guide clinical decisions. This review showed that enucleation may be considered for small and low-mitotic-index esophageal GISTs with benign tendency. Despite higher R1 and tumor rupture rates, survival outcomes were comparable to esophagectomy. Enucleation, including endoscopic enucleation, was safe and effective in selected cases.

Endoscopic papillectomy (EP) is an established treatment for ampullary tumors. This study aimed to analyze recurrence patterns and risk factors in a large cohort with long-term follow-up. Patients who underwent EP for ampullary tumors at a large tertiary center from January 2010 to June 2025 were retrospectively reviewed. Cumulative recurrence rates were estimated using Kaplan–Meier analysis, and Gaussian kernel density estimation was employed to explore dynamic recurrence patterns. Cox proportional hazards model was used to identify risk factors for recurrence. Sensitivity analysis was conducted in a subgroup with at least a 5-year follow-up. A total of 262 patients were enrolled, with an endoscopic treatment success rate of 85.1

Background Contemporary evidence highlights a paucity of systematic research addressing the prognostic implications of total targeted therapy duration in the neoadjuvant setting. Parallel to this, the optimal timeframe for preoperative therapy remains a subject of unresolved debate in clinical practice. In this study, we estimated the impact of total targeted therapy duration on prognosis in patients with gastrointestinal stromal tumors (GIST) undergoing neoadjuvant imatinib therapy. Methods In this nationwide study, we retrospectively analyzed the clinical data from 186 GIST patients receiving neoadjuvant imatinib therapy from January 2010 to December 2021. Clinical data including baseline characteristics, treatment pattern, treatment outcome, adverse events and survival status were collected. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Cox regression analysis was used to analyze the prognostic factors of PFS and OS. Results Among 186 patients, 149 (80.1%) were aged ≤65 years and 110 (59.1%) were male. Regarding neoadjuvant imatinib treatment duration, 59 patients (31.7%) had less than 6 months, 97 (52.2%) patients had 6 to 12 months, and 30 (16.1%) patients had more than 12 months. Multivariate Cox regression analysis indicated that residual mitotic index (>5/50 HPF: HR = 5.80, 95% CI: 2.56-13.15, P < 0.001), non-R0 resection (HR = 11.50, 95% CI: 4.71-28.08, P < 0.001), and adjuvant imatinib therapy (HR = 0.23, 95% CI: 0.07-0.74, P = 0.014) were independent prognostic factors for PFS, while residual mitotic index (>5/50 HPF: HR = 4.40, 95% CI: 1.29-15.06, P = 0.018), multivisceral resection (HR = 4.07, 95% CI: 1.09-15.19, P = 0.037), and adjuvant imatinib therapy (HR = 0.04, 95% CI: 0.01-0.17, P < 0.001) were independent prognostic factors for OS. Maximally selected log-rank analysis identified 35 months and 45 months as the optimal cut-offs for adjuvant and total targeted therapy durations, respectively. No significant difference was found in PFS and OS among patients with different neoadjuvant imatinib therapy durations (P = 0.233, P = 0.326). Conclusions Prolonged adjuvant and total targeted therapy durations correlate with improved survival in GIST patients receiving neoadjuvant imatinib, whereas neoadjuvant imatinib duration alone does not independently affect long-term outcomes. Additionally, a low residual mitotic index remains a robust histopathological predictor of favorable prognosis.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, with recurrence risk primarily determined by tumor size, mitotic index, site, and genetic profile. While most recurrences occur within 5 years post-resection, late recurrences (>10 years) are rare, posing diagnostic and therapeutic challenges. We report a unique case of hepatic metastasis from a jejunal GIST 24 years after initial curative resection of a very low-risk tumor (1.5 cm, ≤5 mitoses/50 HPF). The patient underwent jejunal GIST resection in November 2000, no KIT/PDGFRA mutational testing or adjuvant therapy was performed at the time. He remained recurrence-free for 24 years based on periodic abdominal imaging. In June 2024, abdominal ultrasound revealed a liver nodule (2.9×1.8 cm), confirmed by MRI/CT as a suspicious hepatic lesion. Laparoscopic right-sided complex hepatectomy was performed, and histopathology with immunohistochemistry (DOG1+/CD117+) and molecular testing (KIT exon 11 deletion) confirmed metastatic GIST. Adjuvant imatinib (400 mg/day) was initiated, with no recurrence at 18-month follow-up. This case challenges the assumption that very low-risk GISTs confer negligible long-term risk, highlighting their potential for extremely delayed metastasis. It underscores the need for lifelong vigilance, even in low-risk patients, and emphasizes the critical roles of advanced imaging, immunohistochemistry, and molecular diagnostics in diagnosing late metastases. Individualized follow-up strategies and consideration of long-term surveillance for selected low-risk GISTs warrant reevaluation in the era of molecular-targeted therapy.

Dysregulation of Speckle-type POZ protein (SPOP) and cargo receptor p62/SQSTM1 impairs homologous recombination (HR)-mediated DNA repair by destabilizing RAD51 and FLNA, yet their mechanistic interplay in genomic stability and oncogenesis remains unclear. In this study, we found that the interaction between SPOP and p62/SQSTM1 is obviously enhanced in nucleus in response to DNA damage. Moreover, the nuclear ubiquitination of p62/SQSTM1 at lysine 7 by SPOP led to its degradation, resulting in upregulation of RAD51 and FLNA, RAD51 foci formation, and HR efficiency. In addition, patients-derived p62/SQSTM1 mutations in SPOP-binding consensus (SBC) motif (S276Y/S277G/S277I) increased radiotherapy sensitivity in vitro and in vivo, which attributes to HR deficiency caused by increased degradation of RAD51 and FLNA proteins, and decreased RAD51 and γ-H2AX foci formation. Our finding provides insight into the regulation of HR by SPOP and p62/SQSTM1, and disrupting the interaction between SPOP, p62/SQSTM1 and nuclear ubiquitination may be a potential approach for overcoming radiotherapy resistance in cancer.

Tissue stromal cells are composed of numerous cell types with phenotypical and functional heterogeneity. Apart from providing structural support, they are emerging as key orchestrators of both activation and repression of immune responses in tissue microenvironment. The underlying mechanisms by which stromal cells contribute to immunomodulation are multifaceted, in which the chemokine-mediated interactions with immune cells have drawn great attention. The distinct stromal cell subpopulations can change the chemokine secretion profiles to regulate the recruitment and activation of immune cells in the onset and progression of inflammation. Elucidation of the mechanisms of the homeostatic and pathogenic stromal-immune cell interactions via chemokines can assist in the identification of novel therapeutic targets for modulating inflammatory diseases and enhancing the efficacy of cancer immunotherapy. Therefore, the current review highlights the updated understanding of the stromal-immune interactions via chemokines in inflammation, as well as potential therapeutic avenues to target at the intercellular crosstalk for inflammatory disorders and cancer.

RATIONALE:Gastric cancer with peritoneal metastasis carries a poor prognosis and is considered incurable. Intraperitoneal chemotherapy (IPC) has been explored for preventing and treating peritoneal metastasis, but clinical trials show conflicting results and guidelines provide inconsistent recommendations. A comprehensive evaluation of intraperitoneal chemotherapy effects in gastric cancer is needed. OBJECTIVES:To evaluate the benefits and harms of IPC in gastric cancer for: (1) prophylactic IPC plus radical surgery versus radical surgery alone in people at high risk of peritoneal metastasis; and (2) therapeutic IPC plus cytoreductive surgery (CRS) versus CRS alone in people with confirmed peritoneal metastasis. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, two Chinese databases, three trials registries, and gray literature sources. We also checked references and contacted study authors. The latest search was conducted on 12 June 2025. ELIGIBILITY CRITERIA:We included parallel randomized controlled trials (RCTs) comparing IPC with no IPC for prophylactic and therapeutic use. We excluded studies without postoperative systemic chemotherapy. We assessed trial trustworthiness using the trustworthiness of randomized controlled trials (TRACT) checklist. OUTCOMES:Our outcomes were overall survival, serious adverse events (SAEs), surrogate endpoints for overall survival including disease-free survival (DFS) for prophylactic IPC and progression-free survival (PFS) for therapeutic IPC, quality of life (QOL), total adverse events (AEs), anastomotic leakage, and intra-abdominal abscess. RISK OF BIAS:We assessed the risk of bias (RoB) for outcomes reported in the summary of findings tables using the Cochrane RoB 2 tool. SYNTHESIS METHODS:We synthesized results for each outcome using meta-analysis, by calculating hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) for survival outcomes and dichotomous outcomes. Where meta-analysis was not possible, we summarized results narratively. We used GRADE to assess evidence certainty. INCLUDED STUDIES:We identified nine parallel RCTs involving 829 participants that met eligibility criteria. Seven studies (656 participants) evaluated prophylactic IPC and two studies (173 participants) evaluated therapeutic IPC. Among the included studies, seven studies were conducted in China. Follow-up ranged from 0.2 months to 83.5 months. We assessed most outcomes to have some concerns or a high risk of bias. SYNTHESIS OF RESULTS:We are very uncertain about all results due to very low certainty evidence, downgraded for risk of bias, indirectness, and imprecision for each outcome. Comparison 1: prophylactic IPC plus radical surgery versus radical surgery alone in participants at high risk of peritoneal metastasis Six trials investigated hyperthermic intraperitoneal chemotherapy (HIPEC) effects; one examined normothermic intraperitoneal chemotherapy (NIPEC). No studies reported QOL, SAEs, or total AEs. IPC may increase overall survival (HR 0.66, 95% CI 0.48 to 0.91; 6 studies, 522 participants; very low-certainty evidence) but may have little to no effect on DFS (HR 0.85, 95% CI 0.40 to 1.82; 1 study, 134 participants; very low-certainty evidence). IPC may make little to no difference to anastomotic leakage (RR 1.68, 95% CI 0.43 to 6.58; 4 studies, 366 participants; very low-certainty evidence) and intra-abdominal abscess (RR 2.04, 95% CI 0.19 to 21.80; 1 study, 105 participants; very low-certainty evidence). Comparison 2: therapeutic IPC plus CRS versus CRS alone in participants with confirmed peritoneal metastasis Two trials investigated HIPEC effects. No studies reported on the incidence of total AEs or intra-abdominal abscess. IPC may increase overall survival (HR 0.52, 95% CI 0.28 to 0.96; 2 studies, 173 participants; very low-certainty evidence). IPC may make little to no difference to SAEs (RR 1.25, 95% CI 0.37 to 4.26; 1 study, 68 participants; very low-certainty evidence) and anastomotic leakage (RR 0.90, 95% CI 0.15 to 5.49; 2 studies, 126 participants; very low-certainty evidence). One study with 105 participants (follow-up ranging from 0.2 months to 65.4 months) suggests that IPC may increase median PFS from 3.5 months (95% CI 3.0 to 7.0) to 7.1 months (95% CI 3.7 to 10.5); P = 0.047; very low-certainty evidence. However, IPC may result in little to no difference in QOL measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the EORTC Quality of Life Questionnaire-Stomach module (QLQ-STO22) (P = 0.102 for QLQ-C30 global health status; 1 study, unclear number of participants; very low-certainty evidence). AUTHORS' CONCLUSIONS:Current evidence for IPC is limited. Very low-certainty evidence suggests prophylactic and therapeutic IPC (primarily HIPEC) may improve survival and may have little to no effect on anastomotic leakage. Prophylactic IPC may have little to no effect on tumor recurrence and intra-abdominal abscess. Therapeutic IPC may have little to no effect on SAEs; limited evidence indicates IPC may delay tumor progression and may make little to no difference to QOL. These results are highly uncertain and require cautious interpretation. Therefore, it is not possible to draw definitive conclusions or outline specific implications for the routine use of IPC in individuals with gastric cancer based on the current evidence. Further high-quality, long-term RCTs - particularly involving non-Asian populations - are needed, along with more comprehensive data on safety and QOL. Additionally, a considerable number of studies are still ongoing, meaning effect estimates and conclusions may change when these findings become available. FUNDING:This Cochrane review was funded (in part) by the foundation of the National Natural Science Foundation of China (No. 82472926), the Foundation of Science & Technology Department of Sichuan Province (2023YFS0060; 23ZDYF2812), the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYJC21006; 2023HXFH005), and the Postdoctor Research Fund of West China Hospital, Sichuan University (2025HXBH063). REGISTRATION:Protocol (2009) available via doi.org/10.1002/14651858.CD008157 Updated protocol (2023) available via doi.org/10.1002/14651858.CD015698.

Alternative splicing (AS) is crucial for tumor cells as it regulates protein expression and produces various protein isoforms, which can have diverse or even opposing roles in tumor growth and metastasis. Despite its significance, the role of AS and related splicing factors, particularly splicing-related messenger ribonucleoproteins (mRNPs), in hepatocarcinogenesis, is poorly understood. High-throughput transcriptome sequencing of HCC patients revealed that the spliceosome pathway might play a significant role in HCC development. Through the combined analysis of the three gene clusters, the splicing factor RBM39 was identified, which was highly expressed in HCC tumor tissues with prognostic value. Functional studies showed that silencing RBM39 inhibited cell proliferation, migration, and invasion via the integrin pathway. By performing RNA immunoprecipitation sequencing (RIP-seq), we found that RBM39 combined to RFX1 pre-mRNA and regulated alternative splicing of exon 2. Mechanistically, the exon 2 skipping in RFX1, influenced by high RBM39 expression in HCC cells, led to the production of an N-terminal truncated RFX1, which lost the transcriptional repression ability on oncogenic collagen genes. High RBM39 expression enhances the malignant capabilities of HCC cells by regulating the alternative splicing of RFX1 and subsequently activating the FAK/PI3K/AKT signaling pathway.

BACKGROUND:In a bridging study of INTRIGUE, second-line ripretinib demonstrated comparable progression-free survival (PFS) and favorable safety versus sunitinib in Chinese patients with advanced gastrointestinal stromal tumor. Overall survival (OS) was highly immature at the time of primary analysis. This updated analysis assessed long-term OS of ripretinib versus sunitinib. METHODS:This phase 2, multicenter, randomized, open-label study in China enrolled patients with gastrointestinal stromal tumor previously treated with imatinib, randomized (1:1) to ripretinib 150 mg once daily by continuous dosing in 42-day cycles or sunitinib 50 mg once daily in 42-day cycles (four weeks on/two weeks off). The updated analysis assessed OS and PFS on third-line therapy in all-patient intention-to-treat and KIT exon 11-mutated intention-to-treat (Ex11 ITT) populations. RESULTS:Of 108 patients randomized, 54 received ripretinib and 54 sunitinib; 70 had a primary KIT exon 11 mutation (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT). By December 30, 2024, in all-patient intention-to-treat population, median OS was 43.3 months with ripretinib and 29.9 months with sunitinib (hazard ratio, 0.681; 95% CI, 0.411-1.126; nominal p = .134). In the Ex11 ITT population, median OS was 43.3 months with ripretinib and 28.6 months with sunitinib (hazard ratio, 0.552; 95% CI, 0.291-1.047; nominal p = .065). PFS on third-line therapy was comparable between treatment arms in both populations. CONCLUSIONS:After two additional years of follow-up, ripretinib showed a trend toward clinically meaningful OS benefit versus sunitinib in the Ex11 ITT population. Second-line ripretinib does not appear to affect third-line treatment efficacy.