Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) is technically demanding. We developed a quantitative indocyanine green fluorescence imaging protocol (q-ICG) to assist LDPPHR and evaluated its clinical utility. We retrospectively analyzed 72 patients who underwent LDPPHR between 2019 and 2025. Patients were divided into a q-ICG group (n = 35) and a non-q-ICG group (n = 37). Baseline characteristics and perioperative outcomes were compared between groups. Baseline characteristics were generally comparable between groups. All procedures were attempted laparoscopically, one required conversion to open surgery, and no 90-day mortality occurred. No Grade C postoperative pancreatic fistula (POPF) occurred. Compared with the non-q-ICG group, the q-ICG group had shorter operative time (P = 0.025), postoperative hospital stays (P < 0.001), and less intraoperative blood loss (P < 0.001). Bile leakage (2.9 vs. 27.0

This network meta-analysis (NMA) analyses the latest evidence to evaluate perioperative and postoperative outcomes between minimally invasive surgery (MIS), including robot-assisted (RA) and laparoscopic (LA) approaches, versus open (OA) radical surgery for hilar cholangiocarcinoma (hCCA) and subsequently rank them. A frequentist NMA was performed, and a systematic search of PubMed, Web of Science, Scopus and Cochrane Library databases. This study evaluated 8 perioperative and postoperative outcomes. Pooled relative risk (RR) and standardized mean differences (SMD) with 95

Background: Textbook outcome (TO) serves as a validated composite metric for short-term surgical quality in pancreaticoduodenectomy (PD) patients. This study developed and validated a machine learning-based model to predict the probability of TO attainment in patients with distal cholangiocarcinoma (dCCA) undergoing PD. Methods: Patients with dCCA who underwent PD at our institution between 2012 and 2020 were retrospectively analyzed. Candidate variables were first screened using least absolute shrinkage and selection operator (LASSO) regression, and the selected features were subsequently entered into multivariable logistic regression to identify independent predictors of TO. Six machine learning models were then constructed and evaluated, with their performance compared using the area under the receiver operating characteristic curve (AUC-ROC). SHapley Additive exPlanations (SHAP) analysis was used to elucidate the optimal model's decision-making process and quantify the contribution of each predictor. Results: Among the 242 patients included in the study, 177 (73.1%) achieved TO. LASSO regression followed by multivariable logistic analysis identified five independent predictors of TO: ASA classification, lymph node metastasis, perineural invasion, BMI, and operation time. Six machine learning algorithms were constructed, among which the Gradient Boosting Machine (GBM) exhibited the best discriminative performance (AUC training set: 0.951, 95% CI 0.915-0.988; test set: 0.890, 95% CI 0.800-0.980). Calibration plots and decision curve analysis further demonstrated the strong accuracy and favorable clinical utility of the GBM-based model. Conclusion: The GBM-based prediction model offers accurate preoperative probability estimates of TO attainment and serves as a valuable tool to support individualized surgical planning.

Gallbladder carcinoma (GBC) is the most common malignancy of biliary tract with a dismal prognosis. Previous studies have confirmed that oprozomib has inhibitory effects on a variety of tumors. We aim to investigate the anti-tumor effects of oprozomib on GBC and explore the potential mechanisms. In this study, we demonstrated that oprozomib had significant anti-tumor effect on SGC-996, NOZ, and GBC-SD GBC cell lines in vitro and inhibited GBC tumor growth of SGC-996 and GBC-SD cells xenograft model and exhibited no significant toxicity in vivo. Mechanistically, oprozomib induced SGC-996 and GBC-SD cells G2/M phase arrest through ERK/MAPK signaling pathway as evidenced by the decrease in the expression of CDK1 and Cdc25C, while an increase in the expression of p-ERK, p21, and p27, and apoptosis via JNK/ p38 MAPK signaling pathway as evidenced by an increase in the expression of p-JNK, c-Jun, p-c-Jun, p-p38, Cytochrome c, Cleaved Caspase-8, and Cleaved Caspase-9, while a decrease in the expression of Bcl-2. Oprozomib could induce G2/M phase arrest and apoptosis via MAPK signaling pathway. In addition, our findings provide preclinical evidence for understanding the mechanism and the development of oprozomib-based regimen as a novel potential chemotherapeutic agent against GBC in the future.

Background:This is an updated component network meta-analysis to evaluate efficacy and safety of various therapeutic approaches and their combinations for small hepatocellular carcinoma (SHCC) following PRISMA 2020 guideline. Methods:We screened two previously published meta-analyses on this topic, and searched PubMed, Embase, and the Cochrane Library from 1 January 2021 to 12 March 2026 for randomized controlled trials (RCTs) focusing on treatments of SHCC. We compared the efficacy and safety of surgical resection (SR), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolization (TACE), radiotherapy (RT), and their combinations. Outcomes were overall survival (OS), recurrence-free survival (RFS), and the rate of complications. Standard network meta-analysis (NMA), component NMA were performed, adding subgroup analysis, network meta-regression, and meta-regression between outcomes for sensitive analysis. This study is registered in PROSPERO (CRD420251132447). Findings:We included 41 RCTs involving 5804 patients. RFA + 125I [OS: Hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81; RFS: HR 0.51, 95% CI 0.32-0.81], TACE + RFA (OS: HR 0.66, 95% CI 0.52-0.85; RFS: HR 0.70, 95% CI 0.57-0.86), TACE + SR (OS: HR 0.30, 95% CI 0.16-0.58; RFS: HR 0.37, 95% CI 0.23-0.59) and SR (OS: HR 0.83, 95% CI 0.71-0.98; RFS: HR 0.82, 95% CI 0.71-0.94) had better OS and RFS than RFA; MWA had better RFS (HR 0.75, 95% CI 0.60-0.93), while TACE + RT might worsen RFS (HR 3.53, 95% CI 1.29-9.62). SR yielded more complications (RR 1.52, 95% CI 1.14-2.03). Better liver function (Child-Pugh A) was negatively correlated with HR of RFS (-0.16, 95% CI -0.28 to -0.04). Interpretation:SR remains the foundational treatment for SHCC, and TACE + SR exhibits superior efficacy in SHCC patients. RFA + 125I serves as a potential alternative in patients with unresectable tumors, and most locoregional treatments show effects comparable to SR for SHCC. Liver function may negatively affect relative efficacy of treatments. Funding:This study is funded by 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, SCU; 1.3.5 project for Artificial Intelligence West China Hospital, SCU; National Natural Science Foundation of China for Young Scientists Fund; Sichuan Science and Technology Program; (Qilu) Clinical Research of Sichuan Anticancer Association.

Background The benefits of the use of interventional therapy and neoadjuvant chemotherapy [1] to improve post-operative outcomes and potentially reduce the rate of recurrence during a laparoscopic extended cholecystectomy with extended left hemi-hepatectomy (left lobe & S5) for a T3N1M0 (Stage IIIb) Gallbladder Cancer (GBC). Patient and method This 58-year-old female patient, diagnosed with stage IIIb GBC and left portal vein tumor thrombus (PVTT) underwent multiple cycles of transarterial chemoembolization (TACE), hepatic arterial infusion of chemotherapy (HAIC) (Chen et al., 2021) [2] and neoadjuvant systemic anti-cancer chemotherapy (SACT) prior to surgery. Tumor downstaging, left liver lobe atrophy and reduced tumor levels (especially of AFP and CA19-9) all led to safer surgical parameters for this late-staged tumor resection, that allowed for improved FLR after neoadjuvant locoregional therapies and SACT. More details on tumor size changes and other information are provided in the supplementary video file (Supplementary_Video1). Laparoscopic extended cholecystectomy with extended left hemi-hepatectomy was performed with regional lymph node skeletonization via en-bloc technique that extended from the enlarged LNs surrounding the portal vein, to the common hepatic artery. The extent of lymphadenectomy is individualized according to tumor staging and per-operative imaging findings. For late-stage GBC, extended lymphadenectomy is suggested considering the presence of skip lesions and therefore is a routine peri-operative decision that our surgical team makes given the circumstance on a case-to-case basis. Samples from gallbladder, cystic duct, liver and various regional lymph nodes were collected and sent for pathology. Results This minimally invasive extended cholecystectomy with extended left hemi-hepatectomy (LHH) was successfully completed in the duration of 260 minutes with estimated blood loss of 150ml. The frozen section sample of the cystic duct stump was found to be negative. The patient's post-operative pathology results confirmed adenocarcinoma of gallbladder tissue with G2-G3 histological grading, positive perineural and lymphovascular invasion. The liver bed sample was also confirmed for infiltration. However, only the portal vein lymph nodes were found positive for metastases amongst all the lymph node samples, thereby confirming a pT3N1M0 TNM staging for this patient. The immunohistochemical results of the specimens showed: CK7(+), CK19(+), CK20(−), CDX2(+), CEA(+), MLH1(+), MSH2(+), MSH6(+), PMS2 (+), Ki-67(MIB-1)(+), HER2 (−), p53 (+). The patient was discharged Day 5 after surgery with a prescription of 1g oral capecitabine (twice a day, biweekly with one week off). The post operative 6 month and one year CT scans and MRI scans were consistent with normal post-surgical changes, and the patient didn't succumb to any complications (Supplementary_Video1 showcases the technique used for this surgery). Conclusions The use of tri-modal therapy of HAIC and TACE with neoadjuvant SACT (Lin et al., 2024) [3] showed a positive effect on the tumor by downstaging the cancer, thereby reducing the size of the tumor and in turn reducing the risk of surgery by maintaining a healthy FLR. Furthermore, adequate liver resection of Liver segments 2,3,4 and 5 lead to a lower recurrence rate. This surgical technique demonstrated the feasibility of Laparoscopic surgery for stage IIIb GBC with Liver infiltration and LN metastasis.

Cholangiocarcinoma (CCA) is a highly aggressive, molecularly heterogeneous biliary tract malignancy and the second most common primary liver cancer, and it has an increasing global incidence and persistently poor prognosis. Recent updates of international guidelines, including those from the NCCN, ESMO, EASL, CSCO, BSG, and Japanese societies, along with rapid advances in precision oncology, have substantially changed the clinical management of CCA. This review systematically compares current global guidelines, highlighting both areas of consensus and regional differences in epidemiology, risk factors, screening strategies, diagnostic approaches, pathological and molecular classification, staging systems, surgical indications, systemic therapy, and multidisciplinary management. This review also summarizes recent advances in molecular diagnostics, including next-generation sequencing, liquid biopsy, circulating tumor DNA, extracellular vesicles, artificial intelligence-assisted imaging, radiomics, and emerging prognostic biomarkers. The evolving roles of immune checkpoint inhibitors, molecularly targeted therapies against FGFR2, IDH1, HER2, BRAF, NTRK, and MSI-H/dMMR, liver transplantation, locoregional treatment, and conversion (translational) therapy are also discussed. Finally, this review addresses current challenges, including drug resistance, limited access to molecular testing, regional disparities in healthcare resources, and the lack of universally accepted screening strategies. By integrating updated guideline recommendations with the latest clinical evidence, this review provides a comprehensive reference for evidence-based clinical decision-making and future translational research in CCA.

Background Early recurrence (ER) after curative-intent resection for gallbladder carcinoma (GBC) is clinically important but lacks a consistent definition. Fixed 6- or 12-month cutoffs are commonly used, however, recurrence timing is strongly stage dependent, which can systematically misclassify ER and compromise cross-study comparability. Methods We conducted a retrospective cohort study of patients undergoing curative-intent resection for GBC with complete recurrence and pathology data. Among recurred patients, ER was defined within each AJCC stage using the prespecified stage-specific median time to recurrence (mTTR) (ER versus LR: TTR≤mTTR vs TTR>mTTR). The primary outcome was survival after recurrence (SAR), evaluated within stage. Sensitivity analyses included bootstrap assessment of stage-specific cut-point stability, RMST contrasts at prespecified horizons, and time-varying effects to address non-proportional hazards. Results Of 537 screened patients, 507 met eligibility criteria. AJCC stage distribution was I (n=42), IIA (n=55), IIB (n=108), IIIA (n=131), IIIB (n=87), and IVA (n=84). Recurrence occurred in 320/507 (63.1%) patients. In recurred patients, mTTR decreased monotonically with stage (30.4 months in stage I; 14.2, 11.3, 10.4, 7.9, and 6.5 months in stages IIA, IIB, IIIA, IIIB, and IVA), demonstrating fundamentally distinct stage-specific recurrence kinetics. Fixed calendar cutoffs yielded marked stage heterogeneity in the fraction labeled “early”: for TTR≤12 months, 0.0%, 17.4%, 61.8%, 95.1%, 98.6%, and 100.0% across stages I–IVA; for TTR≤6 months, 0.0%, 0.0%, 3.6%, 4.9%, 12.5%, and 34.7%. Under the stage-adapted mTTR definition, ER (vs LR) was associated with significantly shorter SAR in stages IIA (P=0.00519), IIB (P=0.0149), IIIA (P=0.00243), and IIIB (P<0.001), but no in stage I (P=0.208) or IVA (P=0.101). ER (vs LR) was also enriched for adverse pathologic features within stage, most prominently in stage III-IVA disease, including higher perineural invasion (stage IIIA: 52% vs 15%; P<0.001; IIIB: 50% vs 25%; P=0.028; IVA: 90% vs 33%; P<0.001), vascular invasion (IIIA: 52% vs 13%; P<0.001; IIIB: 67% vs 19%; P<0.001; IVA: 95% vs 31%; P<0.001), and tumor necrosis (IIIA: 62% vs 38%; P=0.035; IIIB: 97% vs 36%; P<0.001; IVA: 85% vs 47%; P<0.001). Conclusions ER in GBC is not a fixed calendar time but a stage-dependent, time-varying phenotype. A stage-adapted ER framework based on within-stage TTR improves interpretability and identifies a high-risk subgroup with shorter SAR and enrichment of adverse pathology. External validation is warranted to confirm transportability across treatment eras and surveillance patterns.

BACKGROUND:In 2020, immunotherapy entered first-line care for hepatocellular carcinoma (HCC). It remained uncertain whether population-level survival improved thereafter and whether adding immunotherapy to chemotherapy in routine practice was associated with additional benefit. METHODS:A population-based SEER analysis was performed among HCC diagnosed in 2018-2022. Comparative analyses were performed between cases in the immunotherapy era (IEC) versus cases in the pre-immunotherapy era (PIEC). A prespecified chemotherapy subset compared chemotherapy + immunotherapy with chemotherapy alone. Competing-risks methods (Gray's test; Fine-Gray) were applied with cancer-related death (CRD) as the event. RESULTS:In total, 12056 patients were included (PIEC 7291; IEC 4765). After matching (n = 8796), better survival was observed in IEC versus PIEC (HR 0.905, 95% CI 0.846-0.968; P = 0.004). In the matched cohort, a lower CRD risk was also observed for IEC (sHR 0.807, 95% CI 0.750-0.868; P = 7.33 × 10-9) with a matched-strata Gray's P = 0.0105. In the chemotherapy subset (n = 3381; PSM n = 1884), the addition of immunotherapy was not associated with a statistically significant OS advantage after adjustment (HR 0.917; P = 0.166) or after matching (HR 0.914; P = 0.218), a pattern that remained consistent in the non-surgical subgroup (matched HR 0.885; P = 0.106). The matched CRD comparison was not significant (Gray's P = 0.96), whereas an unmatched Fine-Gray model suggested a protective association (sHR 0.803, 95% CI 0.701-0.919; P ≈ 0.001). CONCLUSIONS:Diagnosis in the post-approval immunotherapy era was associated with modestly improved OS and lower CRD at the population level. However, because this was an era-based rather than regimen-level comparison, the observed association cannot be attributed solely to immunotherapy uptake.

Background and aim:Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver malignancy with limited prognostic tools to guide treatment strategies. This study aimed to develop and validate a preoperative prognostic model combining tumor burden score (TBS), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9), termed the TCCA model, to predict outcomes in patients with ICC undergoing hepatectomy. Methods:Patients who underwent curative resection for ICC between 2014 and 2020 were retrospectively identified from a multi-institutional database. The impact of the TCCA model on overall survival (OS) and recurrence-free survival (RFS) was evaluated in training and validation cohorts. Predictive performance was evaluated using the area under the Receiver Operating Characteristic curve (AUC), the Akaike Information Criterion (AIC), and the C-index. Results:A total of 849 patients were included. Lower TCCA scores were associated with better median OS (score 0: 59.7 months; score 1: 31.3 months; score 2: 19.4 months; score 3: 11.5 months, respectively) and median RFS (28.8; 15.4; 9.7; 8.1 months, respectively). The TCCA model performed well in both the training cohort (AUC: 0.697 for OS and 0.649 for RFS) and the validation cohort (AUC: 0.672 for OS and 0.632 for RFS), outperforming the 8th edition TNM system and other models, with the highest C-index (0.734) and lowest AIC (3840). Subgroup analyses demonstrated that the TCCA model maintained good discriminative ability among patients with negative CEA or CA19-9 levels. Conclusion:The TCCA model accurately stratifies ICC patients for OS and RFS after resection. It provides a simple and practical tool for preoperative risk assessment, supporting individualized surgical decision-making and individualized patient counseling.

Biliary tract cancer (BTC) is a rare but highly lethal form of cancer and is frequently diagnosed at a late stage, thus limiting treatment options and prognosis. Although there have been great strides in the field of oncology, there are still a number of obstacles that stand in the way of improving patient care. Unfortunately, early diagnosis is still challenging due to the absence of sensitive biomarkers and effective screening strategies. Limited therapeutic options are also available, in which a small number of patients with molecular changes (IDH1/2, FGFR2, EGFR, HER2) benefit from FDA-approved targeted therapies. Despite the advent of less invasive and image-guided surgery, low resectability rates and important technical difficulties limit the use of surgery as the only potentially curative treatment. This review is dedicated to discussing the barriers to the effective translation of recent scientific advances into routine BTC management, including both translation and implementation. Issues of delayed diagnosis, limited tissue sampling for molecular analysis, limited availability of biomarker-driven therapies, and complex choice of surgery and local treatments are critical. Other barriers are weak multidisciplinary team (MDT) coordination, low rates of clinical trial participation, and lack of focus on patient-reported outcomes and quality of life. Existing preclinical models such as patient-derived xenografts (PDX) and patient-derived organoids (PDO) are unable to fully represent the molecular diversity of BTC and therefore are not useful for precision medicine. The molecular testing, adaptable clinical trial designs, multidisciplinary collaboration, and more patient-centered supportive care approaches will be needed to improve BTC outcomes.

BackgroundFrail elderly patients undergoing hepatobiliary-pancreatic (HBP) surgery face a substantially elevated risk of postoperative pulmonary complications (PPCs), which are associated with increased mortality, extended morbidity, and greater healthcare costs. Although the “I Cough” pulmonary rehabilitation program is a well-established preventive strategy for PPCs, its clinical effectiveness is often limited by suboptimal patient adherence. This randomized controlled trial was therefore conducted to determine whether a nurse-led intensive pulmonary rehabilitation exercises (IPREs) program could improve compliance and reduce the occurrence of PPCs in this highly susceptible population.MethodsA total of 160 participants were randomly assigned to two groups. Eighty patients in the intervention (IPREs) group received IPREs, whereas 80 patients in the control group underwent conventional self-pulmonary rehabilitation training. The incidences of PPCs and other postoperative outcomes were compared between the two groups.ResultsThe median compliance rate with pulmonary rehabilitation exercises was significantly higher in the IPREs group than in the control group (100.00% [IQR 83.33–100.00%] vs. 33.33% [IQR 33.33–66.67%]; P < 0.001). The incidence of PPCs was significantly lower in the IPREs group (22.50% vs. 38.75%; OR 0.459, 95% CI 0.230–0.926; P = 0.026), with notably reduced rates of pneumonia and atelectasis (P < 0.05). The overall rate of major complications was also reduced in the IPREs group (12.50% vs. 25.00%; OR 0.429, 95% CI 0.186–0.989; P = 0.043). Additionally, the median postoperative hospital stay was shorter in the IPREs group (6 days [IQR 5–8] vs. 8 days [IQR 6–9]; P = 0.035).ConclusionsThe nurse-led intensive pulmonary rehabilitation program significantly improved compliance with pulmonary rehabilitation exercises, reduced the incidence of PPCs, and shortened postoperative hospitalization in frail elderly patients undergoing HBP surgery.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2000040021.

Background:Bronchogenic cyst is a rare congenital developmental abnormality of the anterior bowel. Peri-pancreatic bronchogenic cyst (PBC) is extremely rare, when only a few cases reported worldwide. Diagnosis of PBC is difficult due to the lack of specific clinical features and symptoms, laboratory and imaging findings. Currently, the diagnosis of PBC mainly relies on the comprehensive judgment of multidisciplinary collaboration, combined with clinical manifestations, imaging features and pathological verification. Most bronchogenic cysts are benign and the long-term survival rate after complete resection is close to 100%. Case presentation:A 21-year-old male with a pancreatic mass was admitted to our hospital. CT scan showed a low-density cystic shadow about 3.6 × 3.5 cm2 on the pancreatic body, with clear boundaries, no enhancement, and no dilation of the main pancreatic duct. The patient underwent open distal pancreatectomy. Postoperative histopathological findings allowed for a definitive diagnosis of PBC. There was no recurrence for two years postoperatively. Conclusion:In this study, we reported a rare case of PBC. At present, radical surgical resection remains the most effective treatment for bronchogenic cyst with mass effects, infection, bleeding, rupture, or larger than 3 cm in diameter. Further research on the diagnosis and treatment strategies of PBC is required.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive cancers, typically diagnosed at an advanced stage due to its subtle and often absent early symptoms. Despite representing only 3% of new cancer cases, it is projected to become the second leading cause of cancer-related deaths by 2030. Currently, early diagnosis remains a significant challenge, and survival rates remain poor due to the lack of effective screening tools. METHODS:We conducted a comprehensive literature review to explore the most recent advances in PDAC detection, focusing on novel biomarkers, liquid biopsies, artificial intelligence (AI)-enhanced imaging, and non-invasive surveillance strategies. We examined the role of circulating tumor DNA (ctDNA), microRNAs, and volatile organic compounds (VOCs) as diagnostic tools, alongside the integration of advanced imaging modalities like MRI, EUS, and MRCP in high-risk individuals, including those with hereditary cancer syndromes. RESULTS:Emerging technologies, such as AI-driven imaging and liquid biopsy, have shown promising improvements in detecting PDAC at earlier, potentially resectable stages. Surveillance strategies for high-risk populations, including BRCA1/2 mutation carriers and individuals with Lynch syndrome, have demonstrated increased detection of Stage I PDAC, offering a significant opportunity for curative intervention. AI and machine learning techniques are also enhancing the sensitivity and specificity of imaging, providing a new frontier in early-stage diagnosis. CONCLUSION:The integration of molecular diagnostics, advanced imaging technologies, and AI may enable a paradigm shift in PDAC detection, transitioning from late to early-stage diagnosis and potentially improving survival rates. However, further clinical validation and standardization of these technologies are essential to ensure their widespread clinical adoption. The future of PDAC detection lies in a multimodal, personalized approach, optimizing diagnostic accuracy and early intervention for high-risk individuals.

BACKGROUND:Cholangiocarcinoma (CCA) comprises heterogeneous malignancies arising at different anatomical locations: Intrahepatic cholangiocarcinoma (IHCC), perihilar cholangiocarcinoma (PHCC), and distal cholangiocarcinoma (DCC). These subtypes exhibit distinct clinical behaviors, treatment approaches, and outcomes. Despite advances in surgical and adjuvant therapies, the prognostic implications of tumor location remain unclear and inconsistently reported. Understanding these variations is essential for personalized management and staging refinement. We hypothesized that the anatomical subtype of CCA significantly influences prognostic outcomes and pathological features. AIM:To compare prognostic outcomes and clinicopathological characteristics among IHCC, PHCC, and DCC based on current evidence. METHODS:A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. PubMed, EMBASE, and the Cochrane Library were searched, yielding 11 eligible retrospective comparative studies involving 14484 patients (IHCC: 6260; PHCC: 6895; DCC: 1329). Outcomes assessed included overall survival (OS), lymph node metastasis, neural invasion, and vascular invasion. Statistical analyses were performed using RevMan 5.3 and Stata 13.0. RESULTS:DCC demonstrated the most favorable prognosis among all subtypes. Despite the highest lymph node metastasis rate (DCC: 56.9%), it was associated with better OS than PHCC and IHCC. Vascular invasion was more prevalent in IHCC (OR = 1.66, 95%CI: 1.22-2.28, P = 0.001). OS comparisons showed no significant difference between PHCC and IHCC (HR = 1.02, P = 0.88), while DCC showed consistent trends toward better survival against both. CONCLUSION:Anatomical subtype is a significant prognostic factor in CCA. DCC patients experience superior outcomes despite aggressive lymphatic spread, suggesting better resectability and surgical outcomes. These insights underscore the need for subtype-specific management strategies and future prospective validation.

Objectives:Hepatocellular carcinoma (HCC) is among the most frequently occurring malignant tumors of the digestive tract and is associated with an increased mortality rate worldwide. This study aimed to develop and validate a prognostic model based on immunogenic cell death (ICD)-related genes to predict patient survival and guide individualized treatment strategies for HCC. Methods:ICD-related genes were identified from the GeneCards database using a relevance score threshold of >10. A combination of least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis was used to screen prognostic genes and construct a risk score model. Immune cell infiltration was evaluated through single-sample gene set enrichment analysis (ssGSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithms. Associations between risk groups and the tumor microenvironment (TME), N6-methyladenosine (m6A) regulators, and immune checkpoint expression were analyzed. Drug sensitivity was predicted based on the risk stratification. The reliability of the model was validated in internal cohorts and further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results:A six-gene signature (CFHR3, G6PD, IGHM, KPNA2, PON1, and SERPINE1) was identified and used to calculate the risk scores. This study found that high-risk patients exhibited significantly poorer overall survival in both the training and validation datasets. The nomogram integrating the risk score and clinical factors showed strong predictive performance. High-risk patients demonstrated reduced immune cell infiltration, altered expression of immune checkpoints and immunosuppressive factors, and a distinct m6A modification pattern, suggesting a higher likelihood of immune escape. This study also revealed that the risk model effectively predicted sensitivity to multiple anticancer drugs. Conclusion:This study developed a robust ICD-related six-gene prognostic model for HCC that can accurately stratify patient risk, reflect the tumor immune landscape, and provide guidance for immunotherapy and personalized treatment strategies.