Minimal residual disease (MRD) is proposed to drive early recurrence of hepatocellular carcinoma (HCC) after curative treatment, and patients with MRD may benefit from adjuvant treatment. We applied a customized targeted deep sequencing (TDS) to profile tumor genomic alterations in HCC patients undergoing liver transplantation (LT) or hepatectomy, and evaluated their associations with MRD status, recurrence risk, and adjuvant lenvatinib response across multiple independent cohorts. TDS revealed MRD-associated genomic patterns, including increased mutation burden and frequent alterations in TP53 and switch/sucrose non-fermentable (SWI/SNF) genes. Alterations in TP53 and SWI/SNF genes were consistently associated with higher early recurrence rates (48.5 % vs 30.0 %, P = 0.026 for TP53; 56.2 % vs 34.0 %, P = 0.024 for the SWI/SNF genes) and shorter recurrence-free survival (12.2 vs 34.6 months, P = 0.026 for TP53; 9.3 vs 18.6 months, P = 0.018 for the SWI/SNF genes) in the LT cohort, as well as the hepatectomy cohort. Multivariate analysis confirmed these alterations as independent risk factors for MRD. Integrative analysis demonstrated that TP53- and SWI/SNF-altered HCC represent clinically and biologically distinct phenotypes, differing in etiology, differentiation status, mutation burden, and transcriptomic subtypes: TP53 alterations correlated with an epithelial-mesenchymal transition-related subtype, while the SWI/SNF genes alterations related to a MYC-activated subtype. Notably, patients harboring TP53 alterations derived clinical benefit from adjuvant lenvatinib following curative surgery. In conclusion, TDS enables effective identification of MRD-associated genomic alterations and stratifies HCC patients who may benefit from adjuvant lenvatinib, providing a molecular basis for personalized postoperative management.

BACKGROUND:Lung metastases often occur after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and efficacy of combining hypofractionated radiotherapy (HFRT) with tyrosine kinase inhibitors (TKIs) in patients with lung metastases from HCC following OLT. METHODS:We retrospectively analyzed forty-eight patients with lung metastases post-OLT for HCC, who underwent concurrent HFRT and TKIs between July 2011 and August 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), local control rate (LCR), in-field objective response rate (ORR), and treatment-related side effects. RESULTS:The median follow-up duration was 42.3 months, with median PFS and OS of 9.9 and 32.7 months, respectively. PFS rates at 1, 2, and 3 years were 33.3%, 20.8%, and 12.5%, respectively, whereas corresponding OS rates were 91.7%, 70.8%, and 33.3%, respectively. Independent adverse factors for PFS included the presence of > 3 lung metastases, interval time from OLT to lung metastasis < 1 year, and post-HFRT lymphocyte nadir < 0.8 × 109/L. For OS, independent adverse factors included shorter PFS time, shorter intervals from OLT to lung metastasis, and post-HFRT lymphocyte nadirs < 0.8 × 109/L. The 1- and 2-year LCRs for lung metastases were 100% and 85.3%, respectively. The best in-field ORR was 95.5%, with no adverse events exceeding grade 2. Radiation pneumonitis occurred in 32 patients (66.7%), with grade 1 in 28 patients (58.3%) and grade 2 in 4 patients (8.3%). CONCLUSIONS:The combination of HFRT with TKIs is a feasible, safe, and promising approach for treating lung metastases from HCC post-OLT.

The safety of immunotherapy in patients undergoing transplant remains unclear due to rejection risks. This study assessed the safety and efficacy of programmed death-1 (PD-1) inhibitors in patients with recurrent tumors who had undergone liver transplantation, emphasizing the value of using graft programmed death-ligand 1 expression as a predictor of rejection to guide patient selection. This single-center, open-label, prospective, single-arm study was conducted from July 2019 to May 2024 at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible participants included patients with recurrent or metastatic liver cancer who had undergone liver transplantation and were unresponsive to locoregional or systemic therapies. The primary endpoints were the incidence and clinical outcomes of acute rejection. Secondary endpoints were overall survival and objective response rate. Twenty consecutive patients received PD-1 inhibitor therapy. Of these, 18 had HCC, and 2 had intrahepatic cholangiocarcinoma. Liver graft biopsies confirmed negative programmed death-ligand 1 expression in all participants before PD-1 inhibitor therapy. Three patients (15%) experienced acute rejection, with a 95% CI of 3.2%-37.9%. The 1-year and 2-year survival probabilities after PD-1 inhibitor treatment were 0.55 (95% CI: 0.33-0.77) and 0.24 (95% CI: 0.05-0.43), respectively. The median survival time after tumor recurrence was 24.6 months, exceeding the historically reported median survival time of 16.3 months. These exploratory findings suggest that, in selected recipients of liver transplant, PD-1 inhibitors may be associated with reduced rejection risk and potential survival benefit, although further validation is needed.

Adding a PD-1/PD-L1 inhibitor to gemcitabine plus cisplatin (GemCis) has shown survival benefits in advanced biliary tract cancer (BTC). Dual inhibition of PD-1/PD-L1 and TIGIT may act synergistically, and further enhance antitumor effects. ZSAB-TOP was a single-arm, multicenter, phase 2 study (NCT05023109) evaluating efficacy and safety of first-line tislelizumab (a PD-1 inhibitor) plus ociperlimab (a TIGIT inhibitor) and GemCis in advanced BTC. Eligible patients received tislelizumab (200 mg) and ociperlimab (900 mg) on day 1 until unacceptable toxicity or disease progression, in combination with cisplatin (25 mg/m²) and gemcitabine (1000 mg/m²) on days 1 and 8 of a 21-day cycle for a maximum eight cycles. The primary endpoint was confirmed objective response rate (ORR) evaluated by the investigator, which was compared with a historical ORR of 25% with GemCis, with a statistical superiority setting at p ≤ 0.05. From March 8, 2022, to January 18, 2023, 45 patients were enrolled. Among the 41 patients in the efficacy analysis set, the confirmed ORR was 51.2% (95% CI 35.1–67.1), achieving the statistical superiority criteria (p = 0.0003). Patients who had TIGIT+/PD-L1+ (n = 16) tended to have a numerically greater confirmed ORR (75.0% [95% CI 47.6–92.7]). After a median follow-up of 14.6 months, median progression-free survival was 7.7 months (95% CI 6.0–9.4), with a median overall survival of 17.4 months (95% CI 11.7-not reached). Treatment-related adverse events of grade ≥3 occurred in 60.0% of patients; immune-mediated adverse events of any grade was observed in 42.2%, with the majority being grade 1 or 2. In conclusion, first-line tislelizumab and ociperlimab plus GemCis yielded clinically promising tumor response and survival outcomes in advanced BTC and were generally well tolerated without new safety signals.

BACKGROUND:The optimal conversion regimen that allows more patients with unresectable biliary tract cancer to access surgery remains unclear; there is currently no standard conversion therapy for biliary tract cancer in China, with commonly used regimens including immunotherapy-based combinations and local therapy. The ZSAB-TransGOLP study aimed to assess the efficacy and safety of tislelizumab plus lenvatinib and GEMOX (gemcitabine plus oxaliplatin) chemotherapy (GOLP) in patients with this disease. METHODS:This single-arm, phase 2 study was conducted at two centres in China. Eligible patients aged 18-70 years with previously untreated locally advanced unresectable biliary tract cancer (intrahepatic cholangiocarcinoma, perihilar bile duct cancer, and gallbladder cancer), and an Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of A, and at least 3 months' life expectancy were enrolled. Patients received 200 mg intravenous tislelizumab on day 1 and intravenous GEMOX (0·5 h of 1000 mg/m2 gemcitabine on days 1 and 8; and 2 h of 85 mg/m2 oxaliplatin on day 1) in a 21-day cycle for three cycles, and 8 mg oral lenvatinib once daily. Tumour resectability was determined by the multidisciplinary team every 3 cycles of conversion therapy; patients who were ineligible for R0 resection and did not require surgery after six cycles received maintenance therapy with tislelizumab plus lenvatinib at the same dose as used in conversion therapy until completing 1 year of treatment, disease progression, intolerable toxicity, death, consent withdrawal, or investigators' decisions. The primary endpoint was the R0 resection rate. All treated patients were evaluable for safety and primary endpoint. The trial is registered with ClinicalTrials.gov (NCT05156788) and is ongoing but closed for recruitment. FINDINGS:Between Dec 27, 2021 and July 3, 2023, 52 patients were screened, 11 were excluded for ineligiblity, and 41 patients were enrolled and received the GOLP regimen. All patients were Chinese, with median age of 58 years (IQR 54-65); 21 patients (51%) were male and 20 patients (49%) were female. Median duration of GOLP treatment was 3 cycles (IQR 3-6). 28 (68%) of 41 patients underwent surgery. At a median follow-up of 19·5 months (IQR 14·6-25·0) by data cutoff on Jan 20, 2025, the R0 resection rate was 63% (26 of 41 [95% CI 47-78]). All patients had at least one any-grade treatment-related adverse event (TRAE); grade 3-4 TRAEs occurred in 20 (49%) of 41 patients, with neutropenia (14 [34%] of 41) being most common. Serious TRAEs occurred in 4 (10%) of patients and included neutropenia (three [7%]) and decreased platelet count (one [2%]). No TRAE-related deaths occurred. INTERPRETATION:With promising efficacy and manageable safety, GOLP represents a potentially feasible and high-efficiency conversion regimen for unresectable locally advanced biliary tract cancer. FUNDING:Program of Shanghai Academic Research Leader, the Key Disease Joint Research Program of Xuhui District, Shanghai Health Commission Clinical Research Special Project, Fellowship from the China Postdoctoral Science Foundation, National Science and Technology Major Project of China, the Outstanding Resident Clinical Postdoctoral Program of Zhongshan Hospital Affiliated to Fudan University, National Natural Science Foundation of China, and the Shanghai Sailing Program.

Background:Bladder cancer (BCa) represents the most common malignancy of the urinary system, characterized by a high recurrence rate, with approximately 61% of patients experiencing recurrence within 1 year post-surgery. Current monitoring methods, such as cystoscopy and urine cytology, are constrained by low sensitivity and patient discomfort. This study employed multi-omics data to investigate the role of OLFML3 in BCa recurrence, with the aim of enhancing the accuracy of recurrence prediction and improving clinical management. Methods:This study utilized RNA sequencing (RNA-seq) data and clinical information from The Cancer Genome Atlas (TCGA) to analyze patients with BCa, stratifying them into relapse and non-relapse groups. Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with 1-year BCa recurrence. Subsequently, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to select eight prognostic genes, and a risk model was developed and validated in both TCGA and Gene Expression Omnibus (GEO) datasets. Additionally, single-cell RNA sequencing (scRNA-seq) data from Guangdong Provincial Second People's Hospital were analyzed to evaluate gene expression across high and low tumor stromal BCa subtypes and explore the relationship between the expression of these eight genes and clinical features. A deep learning model based on the ResNet50 architecture was developed to predict OLFML3 expression in hematoxylin and eosin-stained images. Statistical analysis was performed using R software (version 4.4.2), with significance set at P<0.05. Results:WGCNA identified gene modules associated with BCa recurrence, with the red module exhibiting a significantly positive correlation with recurrence status. Through univariate and LASSO Cox regression analyses, we selected eight prognosis-related genes. Kaplan-Meier survival analysis demonstrated that these genes effectively differentiated between high- and low-risk groups, with statistically significant survival differences observed in both TCGA and GEO datasets. Further Kaplan-Meier survival analysis of each of the eight genes indicated that high OLFML3 expression was associated with lower survival rates. scRNA-seq revealed differential expression of OLFML3 between high and low tumor stromal subtypes, suggesting that OLFML3 may be a key gene associated with 1-year BCa recurrence. High OLFML3 expression also correlated with BCa invasiveness, grade, and stage. Using a deep learning model based on BCa pathological features, we constructed a random forest (RF) model that successfully predicted high and low OLFML3 expression levels, providing novel insights for the clinical prognosis of BCa recurrence within 1 year. Conclusions:Multi-omics approaches effectively identified the OLFML3 gene as a critical factor potentially associated with 1-year BCa recurrence. Furthermore, a deep learning model based on pathological features was developed to predict OLFML3 expression. Further research is warranted to elucidate its role in BCa recurrence within 1 year.

Liver transplantation represents a complex surgical procedure and serves as a curative treatment for patients presenting an acute or chronic end-stage liver disease, or carefully selected liver malignancy. A significant gap still exists between the number of available donor organs and potential recipients. The use of an otherwise-wasted resected liver lobe from patients with benign liver tumors is a new, albeit small, option to alleviate the allograft shortage. This review provides evidence that resected liver lobes may be used successfully in liver transplantation.

In this paper we present a large-area interactive mixed reality system where multiple users can experience an event simultaneously. Through the combination of a number of innovative methods, the system can tackle common problems that are inherent in most existing mixed reality solutions, such as robustness against lighting conditions, static occlusion, illumination correction, registration and tracking etc. Most importantly, with our proposed experience server, a shared event among multiple users is seamless. The experience server tracks every user's position and experience state and presents a unique viewpoint of the event to multiple users simultaneously. The effectiveness of the system is demonstrated through an example application at a heritage site, where we perform user testing through multiple focus groups.

e16220 Background: The combination of Sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar improved progression-free survival and overall survival in unresectable or advanced HCC as compared with sorafenib in ORIENT-32 study and was approved as first-line treatment for unresectable HCC in China. We assessed the efficacy and safety of the combination therapy as conversion therapy for potentially resectable intermediate-stage HCC. Methods: Treatment-naïve patients (pts) with potentially resectable intermediate stage (BCLC stage B) HCC were enrolled in this phase II trial (NCT04843943). Eligible pts received sintilimab (200 mg, IV, D1) and bev (15 mg/kg, IV, D1) per 3 weeks. Tumor response and resectability were assessed every 6 weeks per RECIST v1.1. Pts with evaluations of partial response (PR) or at least two consecutive stable disease (SD) and eligible for R0 resection were referred for hepatectomy, then continued with sintilimab/bev for at most 12 months. Primary endpoints were event-free survival (EFS) (time from study enrollment to tumor progression, disease recurrence after surgery, or death from any cause) and treatment safety. Secondary endpoints included R0 resection rate, pathologic response, objective response rate (ORR), and disease control rate (DCR). Results: At data cutoff on Feb 7, 2023, 30 pts with BCLC-B stage HCC were enrolled. Of them, 25 pts (83.3%) were up-to-7 criteria out. The median follow-up time was 15.3 months (interquartile range [IQR] 13.8-17.6). ORR and DCR were 26.7% and 90.0% (8 PR and 19 SD). 17 pts (56.7%) met the pre-designated criteria for hepatectomy and received liver resection, including 7 pts were evaluated as PR and 10 as SD before surgery. The median time from initiation of sintilimab/bev to liver resection was 4.3 months (IQR 2.3-5.6). No postoperative mortality was observed. 2 pts had a pathological complete response. Median EFS was 13.8 months (95%CI, 10.3-17.3), and the 6-month and 12-month EFS rates were 76% and 60%, respectively. 3 pts died, and OS data was not mature. Most treatment-related AEs (TRAE) were grade 1-2, and grade 3/4 TRAEs occurred in 7 pts (23.3%). 9 serious adverse events occurred, and 3 of them were treatment associated. Conclusions: For pts with potentially resectable intermediate-stage HCC, sintilimab/bev in combination with liver resection was safe and may improve long-term survival. Clinical trial information: NCT04843943 .

Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m 2 ) on Days 1 and 8 and oxaliplatin (85 mg/m 2 ) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825). Trial registration Clinical trials : NCT03951597.

PDF file - 73K, Supplemental Figure S1: The relationship of SBP1 Expression level and Prognosis. The expression levels of SBP1 in 323 HCC tissues were divided by a 4-point scale (0 - +++) system based on the number of positive cells and the intensity of staining. Kapl

Abstract Background P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co‐test for detecting high‐grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high‐throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. Methods P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A‐knockout) standards. Since 2018, 24 100‐women (HPV‐positive/‐negative, Pap‐normal/‐abnormal) have been enrolled nationwide for two‐tier validation work. In cross‐sectional studies, age‐ and viral genotype‐dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut‐offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2‐year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV‐positive Pap‐normal, Pap‐abnormal biopsy‐negative and biopsy‐confirmed LSIL. Results P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A‐positive ratio was 13.9 ± 1.8% among HPV‐negative NILM women and peaked at the ages of 40–49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV‐negative: 17.7 ± 5.0–21.4 ± 7.2%; HPV‐positive: 18.0 ± 5.2–20.0 ± 9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV‐combined double‐cut‐off‐ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co‐test. The p16INK4A‐abnormal situation was an independent HSIL+ risk factor for 2‐year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3–7.2). Conclusions FCM‐based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk‐stratification‐based interventions.

Background Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed.Methods Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence.Results Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2-100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers.Conclusions ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

PDF file - 130K, Univariate analyses of factors associated with survival and recurrence in cohort 2

The combination treatment using sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar improved PFS and OS in unresectable or advanced HCC as compared with sorafenib in ORIENT-32 study and was approved as first-line treatment for unresectable HCC in China. We assessed the efficacy and safety of the combination therapy as conversion therapy for potentially resectable intermediate stage HCC. Treatment-naïve patients (pts) with potentially resectable intermediate stage (BCLC stage B) HCC were enrolled in this phase II trial (NCT04843943). Eligible pts received sintilimab (200 mg, IV, D1) and bev (15 mg/kg, IV, D1) per 3 weeks. Tumor response and resectability were assessed every 6 weeks per RECIST v1.1. Pts with evaluations of PR or at least two SD and eligible for R0 resection were referred for hepatectomy, then continued with sintilimab/bev for at most 12 months. Primary endpoints were event-free survival (EFS) and treatment safety. Key secondary endpoints included R0 resection rate, pathologic response, objective response rate (ORR), and disease control rate (DCR). At data cutoff on April 26, 2022, 30 pts with BCLC-B stage HCC were enrolled. Of them, 25 pts (83.3%) were up-to-7 criteria out. The median follow-up time was 7.0 months (range 3.2–13.1). All pts completed at least one imaging evaluation. ORR and DCR were 23.3% and 90% (7 PR and 20 SD). 13 pts (43.3%) met the pre-designated criteria for hepatectomy and received liver resection, including 5 were evaluated as PR and 8 as SD before surgery. The median time from initiation of sintilimab/bev to liver resection was 4.1 months (range 2.0-5.7). No postoperative mortality was observed. 1 patient had a pathological complete response. Median EFS data was still not mature. There is no tumor recurrence in patients with hepatectomy for now. Most treatment-related AEs (TRAE) were grade 1-2, Grade 3 TRAEs occurred in 6 pts. 3 serious adverse events occurred, and 1 was treatment associated (rash). Systemic therapy using Sintilimab/bev as conversion therapy for intermediate-stage HCC was well tolerated and effective. Longer follow up are required to further evaluate the efficacy and safety.

Tumor recurrence and metastasis after liver transplantation (LT) remains one of the most important factors that affect the outcome of LT for hepatocellular carcinoma (HCC). The diagnosis and treatment strategies in the era of precision medicine, including utilizing multi-omics, high-throughput gene sequencing analysis, big data and artificial intelligence to select the biomarkers which can accurately predict the prognosis after LT, evaluating the immune status comprehensively, inducing immune tolerance, providing effective prevention for patients at a high risk of recurrence with sensitive antitumor drugs and attaching importance to individualized treatment for recurrence and metastasis, may further improve the outcome of LT. Combined with experience and review of relevant research articles, the authors elaborate perioperative diagnosis and treatment strategies of LT for HCC, aiming to promote the application of precision medicine in the field of LT.

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.

Objective To summarize the therapeutic efficacy of liver transplantation in patients with intrahepatic cholangiocarcinoma（ICC） and to analyze the prognostic risk factors. Methods The clinicopathological data of 46pathological confirmed ICC patients who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from April 2001 to February 2022 were analyzed retrospectively. The survival and recurrence of the patients were followed up. Kaplan Meier method was employed to analyze the overall survival（OS） rate and relapse-free survival（RFS） rate of patients, and Cox regression model was used to evaluate the risk factors affecting the prognosis. Results The median overall survival time of patients with ICC after liver transplantation was 19 months, and the 1, 3, 5-year OS rates were 64.4%, 30.2%, 20.7%, respectively. The median RFS time was 10 months, and the 1, 3 and 5-year RFS rates were 45.8%, 20.8%,10.4%, respectively. The results of multivariate analysis revealed that the level of preoperative carbohydrate antigen19-9（CA19-9）（P = 0.026） was an independent risk factor for the overall survival time of patients, and local extrahepatic structures due to direct ICC invasion（P = 0.019） was an independent risk factor for tumor recurrence and metastasis. Conclusion The prognosis of liver transplantation for intrahepatic cholangiocarcinoma is poor. The high level of preoperative CA19-9 is an independent risk factor for short postoperative survival of recipients, and direct tumor invasion of extrahepatic tissues is an independent risk factor for high recurrence rate after liver transplantation.