Jie Gao

Background: Patients with complex pancreatic cancer, including those with challenging local vascular anatomy, liver oligometastases, obstructive jaundice, gastrointestinal bleeding, or severe pain, often fall into a guideline grey zone not fully addressed by conventional stage- or resectability-based algorithms. We characterized how a multidisciplinary team (MDT)-guided surgical-window framework was implemented and the downstream clinical course following the resulting treatment decisions. Methods: We retrospectively reviewed 37 patients with complex pancreatic cancer discussed by the MDT at a tertiary academic center (Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing, China) between November 2017 and November 2020 and followed through November 30, 2022. Patients were characterized according to the realized MDT-guided pathway: a surgery-inclusive surgical-window pathway (n=20) or a non-surgical-window pathway (n=17). The analysis focused on pathway realization, disease-control patterns, functional and symptom status, and exploratory descriptive overall survival (OS), with progression-free survival (PFS) retained as a secondary descriptive time-to-event outcome. Because pathway assignment was clinically selected and incorporated evolving post-baseline information, clinical outcomes were summarized descriptively without formal between-pathway hypothesis testing. Results: Nine of 37 index MDT decisions (24.3%) involved a surgery-inclusive strategy outside standard guideline-supported surgical indications, all in highly selected patients with stage IV low-burden metastatic disease. Functional status was summarized both as composite survival-functional states and among survivors at each assessment time point, with all between-pathway differences interpreted descriptively. Conclusions: In this single-center retrospective cohort, the MDT-defined surgical-window framework provided a structured way to integrate anatomy, metastatic burden, symptoms, treatment tolerance, and feasibility of subsequent care into individualized treatment decisions. The observed downstream disease-control, functional, symptom, and survival patterns are hypothesis-generating and do not establish a causal benefit of surgery or of MDT itself. Prospective studies with baseline-defined decisions are needed to validate the clinical usefulness of this framework.

Portal vein tumor thrombus (PVTT) is a major manifestation of macrovascular invasion in hepatocellular carcinoma (HCC) and is associated with aggressive progression and heterogeneous responses to immune checkpoint inhibitor–based therapy. Current stratification relies mainly on anatomical extent, liver function, and tumor burden and does not fully capture the biology of the intravascular lesion. In this Review, we propose PVTT as an anatomically distinct, lesion-centered intravascular tumor–immune niche for hypothesis generation rather than as an established autonomous immune compartment. We distinguish PVTT-direct evidence from supportive venous-thrombus/metastatic evidence and HCC-extrapolated mechanisms. Current PVTT-direct evidence is strongest for clonal and spatial divergence and PVTT-specific stromal remodeling, including myofibroblast-like cancer-associated fibroblast accumulation, NID1-associated immune barriers, and FAP-positive fibroblast/GJA5-positive endothelial hubs. Venous-thrombus studies provide supportive evidence for macrophage-associated immune suppression, including C5aR-positive tumor-associated macrophages, whereas hypoxia–adenosine signaling, adaptive checkpoint activation, and lipid metabolic rewiring remain largely extrapolated candidate mechanisms requiring direct PVTT validation. On this basis, we organize the available evidence into literature-informed candidate resistance phenotypes and outline a translational framework integrating paired primary tumor–PVTT sampling, spatial and single-cell profiling, functional imaging, and liquid biopsy. These phenotypes are conceptual groupings rather than empirically derived or validated patient subtypes and should guide mechanistic testing and biomarker-enriched trial design rather than routine treatment assignment. Prospective PVTT-specific studies with anatomically resolved sampling, longitudinal pharmacodynamic assessment, and biomarker-by-treatment interaction analyses are required to determine whether this lesion-centered niche framework can ultimately provide clinically useful stratification.

Tertiary lymphoid structures (TLS) have evolved from descriptive histological findings into candidate biomarkers and targetable immune niches in solid tumors. In intrahepatic cholangiocarcinoma (ICC), however, similar lymphoid architectures may have different biological implications depending on their relationship to tumor nests, immune circuitry, and suppressive stroma. We define a “TLS topotype” as the multidimensional state of an individual TLS-centered region, including the TLS core, its perilesional neighborhood, and the nearest tumor–stroma interface. This state integrates anatomic topology and tumor accessibility, structural maturity, putative effector circuitry, and suppressive context; treatment-induced plasticity is considered separately through longitudinal assessment. Because heterogeneous TLS may coexist within one tumor, the whole tumor is represented by a “topotype landscape” based on compartment-specific TLS density and the distribution of TLS-level states rather than a single label. Direct human ICC evidence supports compartment-resolved associations between TLS distribution and outcome and identifies suppressive B-cell, Treg, myeloid, and stromal programs. These observations establish spatial TLS organization as prognostically relevant, but do not validate the framework or demonstrate treatment-specific prediction. By contrast, TLS-resident TCF7-positive stem-like CD8 T-cell maintenance, coordinated B-cell–dendritic-cell–T-cell circuitry, and ICI-specific predictive value remain unproven in ICC and should be considered hypothesis-generating. The framework therefore distinguishes candidate circuit-competent, tumor-accessible TLS states from stromally excluded or suppressive-neighborhood states while allowing mixed profiles. Multiplex pathology and spatial transcriptomics may define these states, whereas radiomics, liquid biopsy, and pretreatment biopsy provide complementary but incomplete information. Biopsy can characterize only TLS states captured in sampled tissue, and radiomics currently estimates whole-lesion TLS probability rather than functional topology. Marker expression or spatial colocalization alone does not establish functional productivity, which requires evidence of tumor-antigen presentation or specificity, local lymphocyte renewal or clonal expansion, functional perturbation, or a spatially linked treatment response. By separating TLS-level state, tumor-level landscape, and patient-level trial stratum, this review provides a framework for biomarker development, therapeutic reprogramming, prospective validation, and longitudinal monitoring in ICC. No TLS topotype has yet been validated to predict differential benefit from immune checkpoint inhibition in ICC.

Background: Pyogenic liver abscess caused by migration of an ingested toothpick through occult gastrointestinal perforation is rare and may be missed. Case presentation: A 47-year-old woman presented with 2 weeks of fever and epigastric pain. Laboratory tests revealed leukocytosis (13.3 × 10^9/L) and elevated C-reactive protein (45.4 mg/L) with normal procalcitonin (0.03 ng/mL). Non-contrast CT demonstrated an abscess-like lesion in the left hepatic lobe with an intralesional linear hyperdense focus, suggesting a foreign body. After empirical broad-spectrum antibiotics, laparoscopic left lateral sectionectomy with gastric perforation repair was performed. An intact toothpick was retrieved from the abscess cavity, confirming the etiology. The postoperative course was uneventful. This case highlights the diagnostic value of a linear hyperdense focus within a left-lobe hepatic abscess on CT for suspecting foreign body migration and guiding timely source control. Conclusion: A linear hyperdense focus within a hepatic abscess on CT should raise suspicion for migrated gastrointestinal foreign body. Definitive cure requires prompt source control, including foreign body removal and repair of the perforation tract.

Introduction: Although the transcatheter arterial chemoembolization (TACE) combined with sintilimab and bevacizumab improves outcomes in unresectable HCC (uHCC), predictive tools are lacking. This study developed and validated a prognostic model for triple therapy efficacy. Methods: A multicenter study enrolled uHCC patients receiving TACE-sintilimab-bevacizumab. Overall survival (OS) was the primary endpoint; a Cox model was developed and validated. Results: This study enrolled 147 patients (training cohort: n = 92; validation cohort: n = 55). The optimal cutoff value for the fibrin degradation product-to-cholinesterase ratio*1000 (FCR) was determined as 0.8. Univariate and multivariate Cox regression analyses identified FCR, AST, AFP, and PVTT as independent OS predictors. These variables were integrated to establish the FAAP scoring system, which demonstrated robust discriminative performance with AUC of 0.804 (95% CI: 0.703-0.893) and 0.799 (95% CI: 0.67-0.911) in the training and validation cohorts, respectively. Patients were stratified into three risk groups based on FAAP scores: low (FAAP < 0.7), intermediate (0.7 ≤ FAAP < 2.2), and high (FAAP ≥ 2.2). Kaplan-Meier analyses revealed significant prognostic stratification for both OS and progression-free survival (PFS) across groups. Subgroup analyses confirmed the prognostic relevance of FAAP scores in key clinical subsets, including age, gender, extrahepatic metastasis status, viral hepatitis etiology, PVTT presence, and Child-Pugh stage. Conclusions: The FAAP scoring system effectively predicted survival outcomes in HCC patients receiving TACE-sintilimab-bevacizumab therapy, which suggests its clinical utility for prognostic prediction. Further large prospective studies are required for external validation.

Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality, with liver transplantation (LT) offering curative potential for patients in the early stages. While immune checkpoint inhibitors (ICIs) are effective in managing tumor progression, concerns about graft rejection persist. This study investigates how peri-LT ICIs administration affects rejection rates and survival outcomes in HCC patients. This global study analyzed 386 HCC patients receiving Peri-LT ICIs therapy, integrating data from a systematic literature review and institutional registries. The risk of graft rejection and survival outcomes were assessed using logistic and Cox regression, along with restricted cubic splines modeling dose-response dynamics. Overall graft rejection rates did not significantly differ between Pre-LT (17.5%) and Post-LT (22.1%) ICI users (P = 0.351); however, Post-LT use was associated with higher rates of graft loss/dysfunction (47.1% vs. 25.9%, P < 0.05) and rejection-related mortality (47.1% vs. 18.5%, P < 0.05). In Pre-LT patients, washout periods >30 days (OR = 0.36, 95% CI: 0.18-0.72, P = 0.004) and >1.5 half-life counts (OR = 0.24, 95% CI: 0.12-0.50, P < 0.001) were associated with reduced rejection risk. Post-LT, high PD-L1 expression on graft tissue correlated with increased rejection risk (P < 0.001). Graft rejection following Pre-LT ICIs was linked to poorer overall survival (HR = 5.17, 95% CI: 2.21-12.24, P < 0.001). With careful management, peri-LT ICIs may be considered for HCC patients. Optimizing washout periods and monitoring graft PD-L1 expression may improve transplant outcomes.

Mucinous cystic neoplasm of the liver (MCN-L) is a rare benign tumor accounting for less than 5% of all liver cysts, with MCN-L in the hilar region being exceptionally uncommon and often misdiagnosed due to its complex presentation. A 48-year-old woman presented with obstructive jaundice following initial laparoscopic drainage of hepatic cysts, where pathology initially indicated benign cystic lesions. Months later, imaging revealed an enlarged cystic lesion in the left liver lobe with intrahepatic bile duct dilation. Further evaluations, including ultrasound, enhanced CT, and MRI, confirmed a large cystic lesion compressing the intrahepatic bile ducts. After a multidisciplinary discussion, hepatic cyst puncture and drainage were performed, temporarily alleviating jaundice. However, she returned with yellowish-brown drainage fluid and worsening jaundice, prompting cyst wall resection. Postoperative pathology confirmed MCN-L. Three months later, jaundice subsided, and a hepatic resection of segment 4 was performed, with pathology confirming low-grade MCN-L. At a 12-month follow-up, the patient showed no abnormalities. This case highlights the diagnostic and therapeutic challenges of MCN-L in the hilar region, as it can easily be mistaken for other liver cystic lesions on imaging. Pathologic examination is essential for definitive diagnosis, and early radical surgical resection is critical to improve prognosis and reduce the risk of malignancy and recurrence.

Introduction: Liver disease remains a significant global health concern. In China, the number of patients with liver cirrhosis is estimated to reach 7 million. In addition to the high risk of death, cirrhosis leads to several severe complications. Patients with cirrhosis have significantly longer hospital stays and higher total hospital costs than those without cirrhosis. We aimed to investigate the predictors of readmission among patients with cirrhosis in China.Materials and methods: We conducted a retrospective study to evaluate adult patients with cirrhosis. Data on various sociodemographic, clinical, and hospitalization characteristics were collected. We defined the primary endpoint as the first liver-related readmission occurring within 30–90 days of initial hospitalization. Adult patients with cirrhosis admitted to our hospital between January 2009 and December 2022 were included. Differences between groups were analyzed using Student’s t-test and chi-square test. Logistic and multiple linear regression analyses were performed to identify predictors associated with readmission and the length of the first hospitalization.Results: In total, 1,285 patients were diagnosed with cirrhosis. Among these patients, 767 (59.7%) were males, and the mean age was 58.9 ± 12.3 years. Seventy-two (5.6%) and 154 (12.0%) patients were readmitted within 30 and 90 days, respectively. Compared with those who were not readmitted, patients readmitted at 30-day and 90-day had a higher proportion of males, ascites, spontaneous bacterial peritonitis, electrolyte abnormalities, higher Child-Pugh–Turcotte scores, longer initial hospital stays, and higher initial hospitalization costs. Logistic regression analysis indicated that hepatic encephalopathy, spontaneous bacterial peritonitis, diabetes, and ascites were predictors of 30- and 90-day readmission. Hypertension and spontaneous bacterial peritonitis were significant predictors of the length of the first hospitalization.Conclusion: Patients with cirrhosis presenting with hepatic encephalopathy, ascites, and spontaneous bacterial peritonitis may have a higher risk of rehospitalization.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with a poor prognosis, predominantly CA19-9 positive. High CA19-9 levels correlate with increased aggressiveness and worse outcomes. This study employs multi-omics analysis to reveal molecular features and identify therapeutic targets of CA19-9 positive ICC, aiming to support individualized treatment. Data from seven clinical cohorts, two whole-exome sequencing cohorts, six RNA sequencing/microarray cohorts, one proteomic cohort, 20 single-cell RNA sequencing samples, and one spatial transcriptome sample were analyzed. Key findings were validated on tissue microarrays from 52 ICC samples. CA19-9 positive ICC exhibited poorer OS (median 24.1 v.s. 51.5 months) and RFS (median 11.7 v.s. 28.2 months) compared to negative group (all P < 0.05). Genomic analysis revealed a higher KRAS mutation frequency in the positive group and a greater prevalence of IDH1/2 mutations in the negative group (all P < 0.05). Transcriptomic analysis indicated upregulated glycolysis pathways in CA19-9 positive ICC. Single-cell analysis identified specific glycolysis-related cell subclusters associated with poor prognosis, including Epi_SLC2A1, CAF_VEGFA, and Mph_SPP1. Higher hypoxia in the CA19-9 positive group led to metabolic reprogramming and promoted these cells’ formation. These cells formed interactive communities promoting epithelial-mesenchymal transition (EMT) and angiogenesis. Drug sensitivity analysis identified six potential therapeutic drugs. This study systematically elucidated the clinical, genomic, transcriptomic, and immune features of CA19-9 positive ICC. It reveals glycolysis-associated cellular communities and their cancer-promoting mechanisms, enhancing our understanding of ICC and laying the groundwork for individualized therapeutic strategies.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) has two main histological subtypes: large and small duct‐type iCCA, which are characterized by different clinicopathological features. This study was conducted with the purpose of expanding our understanding of their differences in molecular features and immune microenvironment.Methods: We selected 132 patients who underwent radical surgery at our department between 2015 and 2021 for clinical and survival analyses. Whole‐exome sequencing was performed to analyse mutational landscapes. Bulk RNA sequencing and single‐cell RNA sequencing data were used for pathway enrichment and immune infiltration analyses based on differentially expressed genes. The function of PPP1R1B was analysed both in vitro and in vivo and the gene mechanism was further investigated.Results: We found that large duct‐type iCCA had worse overall survival and recurrence‐free survival rates than small duct‐type iCCA. Mutations in ARID1A, DOT1L and ELF3 usually occur in large duct‐type iCCA, whereas mutations in IDH1 and BAP1 occur in small duct‐type iCCA. Among the differentially expressed genes, we found that PPP1R1B was highly expressed in large duct‐type iCCA tumour tissues. Expression of PPP1R1B promoted cell proliferation, migration and invasion and indicated a worse prognosis. A combination of USF2 with the promoter of PPP1R1B can enhance gene expression in iCCA, which may further affect the expression of genes such as AHNAK, C4BPA and activating the PI3K/AKT pathway.Conclusions: Our findings extend our understanding of large and small duct‐type iCCA. In addition, PPP1R1B may serve as a potential marker and therapeutic target for large duct‐type iCCA.