Liver transplantation is the most effective radical treatment for hepatocellular carcinoma (HCC), especially for patients with HCC complicated by cirrhosis. Since most patients are in an advanced stage of unresectable state when they are present, the preoperative downstaging treatment for liver transplantation in HCC is of great significance for increasing the opportunity for surgery, reducing the dropout rate from the liver transplant waiting list, and thereby lowering the postoperative recurrence rate. Currently, immune checkpoint inhibitor (ICI)-based combination immunotherapy and targeted therapy is the most effective treatment for preoperative downstaging in liver transplantation for HCC. However, the immunoenhancing effects of ICI may increase the risk of post-transplant rejection. Therefore, it is necessary to find a "critical point" that allows ICI to effectively inhibit tumor growth during preoperative downstaging treatment without causing severe rejection after transplantation. This article reviews the latest advances in preoperative ICI treatment protocols, efficacy assessment, indications, contraindications, drug discontinuation timing, and principles of prevention and treatment of rejection in liver transplantation for HCC.

Pathologically,hepatocellular carcinoma(HCC)is prone to invade the portal vein and form portal vein tumor thrombus(PVTT).Although great advances in the treatment of HCC have been achieved in recent years,HCC patients with PVTT still have limited therapeutic options and poor prognosis.Hepatic arterial infusion chemotherapy(HAIC)is a therapeutic approach that combines local therapy with systemic antitumor effects,and a lot of studies have shown that HAIC carries certain survival benefit to patients with advanced HCC complicated by PVTT,and it is considered to be an effective local therapy for advanced HCC,especially for patients with type Vp3-4 HCC.Systemic therapy is the main treatment for advanced HCC,but the diversity of HAIC combined with targeted and immunotherapy may become a more effective treatment option for HCC with severe PVTT,and it is possible to achieve a tumor-free state through translational therapy,allowing patients with advanced HCC to survive for a longer time.This article aims to summarize the research progress in HAIC for advanced HCC complicated by PVTT.

Inherited metabolic liver disease (IMLD) is a category of liver metabolic diseases caused by genetic disorders. The pathogenesis of IMLD is complex, which primarily comprises the accumulation of harmful metabolic substrates or products caused by specific enzyme defects and energy defects or abnormal deposition caused by abnormal metabolism of glucose, fat and other substances. In recent years, liver transplantation has played an increasingly critical role in the treatment of IMLD with the development of liver transplantation. At present, IMLD has become the second most important indication after biliary atresia in pediatric liver transplantation. Currently, IMLD patients receiving liver transplantation can be divided into two categories: the first category is IMLD complicated with liver disease; Category 2 patients have a normal liver structure but are deficient in related metabolic enzymes. It can not only replace the liver with abnormal structure and function, but also provide normal enzymes required for patients' metabolism, which may improve their quality of life and even save their lives. In this article, common feasible liver transplantation for IMLD, clinical prognosis and surgical procedures of liver transplantation for IMLD were reviewed, aiming to provide reference for liver transplantation for IMLD.

Objective: To prepare an inactivated hepatitis A vaccine using a attenuated strain of hepatitis A virus (HAV) H2 and to analyze its immunizing dose, so as to provide the reference for development and production of inactivated hepatitis A vaccines. Methods: Human embryonic lung diploid cells (KMB17) were infected with attenuated HAV H2 strain to proliferate the virus, then the cells containing viruses were harvested, extracted and purified. The obtained virus concentrate was prepared into vaccine bulk and test vaccines with 1 280 EU/mL antigen content. Vaccine testing was carried out according to the inactivated hepatitis A vaccine standards specified in the Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). A total of 110 mice were randomly divided into 11 groups, including 5 dose groups (80, 160, 320, 640 and 1 280 EU/dose) of the test vaccine and the reference vaccine, as well as the adjuvant control group. Mice were immunized twice by intraperitoneal injection, their serum HAV antibodies were detected, and the geometric mean titer (GMT) and positive conversion rate of antibodies were analyzed to evaluate the immunising dose of the vaccine. Results: The antigen content and viral titer of the virus harvest solution were 5 120 EU/mL and 8.33 lgCCID50/mL, respectively. The removal rate of foreign protein reached 98.05% and the recovery rate of antigen was 66.25%. The test vaccine met the requirements of Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). The GMTs of HAV antibodies in the test vaccine and the reference vaccine dose groups after the second immunization were more than twice higher than those after the first immunization. Regardless of primary immunization or secondary immunization, the GMTs (log2) of HAV antibodies in the test vaccine groups with doses of 160 EU/dose and above were higher than those in the 80 EU/dose group (all P<0.05), while there was no statistically significant differences between the dose groups of 160 EU/dose and above (all P>0.05). The antibody positive conversion rate of 160 EU/dose and above of the test vaccine was 100.00% after the secondary immunization. Conclusions The inactivated hepatitis A vaccine of attenuated H2 strain tested in this study demonstrates strong immunogenicity in mice, suggesting its potential as a candidate vaccine. The preliminary analysis indicates an immunizing dose of 320 EU/dose for children and 640 EU/dose for adults.

Objective To discuss the perioperative blood transfusion strategy of patients with hereditary coagulation fac-tor deficiency through the perioperative blood coagulation management of a patient with coagulation factor Ⅺ deficiency and hemangioma of knee joint.Methods Coagulation factor activity test and gene test were used to confirm the patients with co-agulation factor Ⅺ antecedent deficiency.Perioperative bleeding risk assessment,thromboela-stogram(TEG)and coagula-tion factors detection were performed to detect the coagulation status of the patients.400 mL fresh frozen plasma was trans-fused before surgery and first day after surgery,200 mL daily for 3 days thereafter.Results The level of APTT was con-trolled from 97.1 s before operation to 36.9 s after operation.There was no obvious bleeding during operation,and the wound healed well after operation.Conclusion In the situation of lack of commercial coagulation factors,transfusion of blood products such as fresh frozen plasma can significantly improve the coagulation function and reduce the risk of intraoperative bleeding in patients with hereditary coagulation factor deficiency during perioperative period.

A 62-year-old man with hepatocellular carcinoma began to take tyrosine kinase inhibitor(TKI)lenvatinib orally.After taking the medicine for a week,the patient developed watery diarrhea 2 to 3 times a day.The patient received the first dose of tislelizumab.After 20 days,the patient's diarrhea worsened,nearly 40 times a day.Lenvatinib was discontinued and the second dose of tislelizumab was received,while the diarrhea was not significantly relieved.Treatments were given upon the symptoms and diarrhea was alleviated so that lenvatinib was restarted,diarrhea aggravated again and the drug was discontinued.Acute colitis complicated with colon erosion was diagnosed by colonoscopy which was presumed to be immure-associated colitis caused by programmed cell death protein 1(PD-1).The patient was admitted to hospital for liver transplantation.After the administration of immunosuppressive drugs against graft rejection,the diarrhea gradually cleared.Diarrhea caused by anti-PD-1 antibody is usually mild.In this case,mild diarrhea caused by TKI developed rapidly into severe colitis after the first dose of anti-PD-1 antibody.Mechanism of the increasing rate of adverse effect caused by the combined use of TKI and anti-PD-1 antibodies worth further discussion.

OBJECTIVE: To analyze the accuracy of prosthesis size selection in Naton robot-assisted medial unicondyle knee arthroplasty by comparing the actual prosthesis size used during operation and the preoperative planning. METHODS: The clinical data of 100 patients (110 knees) who underwent Naton robot-assisted medial unicondylar knee arthroplasty between June 2023 and July 2024 was retrospectively analyzed, including 47 knees on left side and 63 knees on right side. There were 37 males (40 knees) and 63 females (70 knees) with a mean age of 65.4 years (range, 59-71 years). Body mass index was 22.2-28.6 kg/m ² (mean, 25.4 kg/m ²). The disease duration ranged from 1 to 8 years (mean, 3.4 years). Preoperative planning was performed by Naton robotic surgical system based on lower limb CT data. The final prosthesis size after osteotomy was recorded and compared with the preoperative plan to analyse whether it was consistent with the preoperative plan, as well as the situation of knee flexion and extension gaps (<0.5 mm, >2.0 mm) corresponding to the different models of prostheses. RESULTS: During operation, 5 patients (5 knees) were treated with traditional UKA due to mechanical arm failure, software obstacles, significant bone amputation bias, or loose reference frame, and were excluded from the final analysis. The remaining 95 patients (105 knees) successfully received Naton robot-assisted surgery, and no related complications occurred. The prosthesis size was consistent with the preoperative plan in 101 knees (96.2%) on the femur side, 100 knees (95.2%) on the tibia side, and 97 knees (92.4%) on both femur and tibia sides. The prosthesis size was inconsistent in 3 cases (2.86%) on the femur side alone, 4 cases (3.81%) on the tibial side alone, and 1 case (0.95%) on both femur and tibial sides. Among the prostheses with different models, the flexion and extension gaps were less than 0.5 mm in 3 knees, the flexion gap was less than 0.5 mm and the extension gap was more than 2.0 mm in 3 knees, and the flexion gap was more than 2.0 mm and the extension gap was less than 0.5 mm in 2 knees. CONCLUSION The accuracy of prosthesis size selection for Naton robot-assisted medial unicondylar knee arthroplasty is relatively high.
Humans ; Arthroplasty, Replacement, Knee/instrumentation* ; Female ; Male ; Middle Aged ; Aged ; Knee Prosthesis ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Prosthesis Design ; Knee Joint/surgery* ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular

Posttransplant diabetes mellitus(PTDM)is a prevalent metabolic disorder after solid organ transplantation. As a major risk factor for cardiovascular disease and even death, PTDM shares the same characteristics with T2DM(obesity & insulin resistance, etc.). Immunosuppressants is also a predisposing factor for transplantation.Screening, prevention and management of PTDM should be performed pre-transplantation, peri-operation and during stable period post-transplantation. In recent years, several novel blood glucose monitoring techniques and anti-diabetic agents have been developed for a more precise treatment of PTDM. In the near future, a multi-disciplinary team should be formulated for optimizing the management of PTDM and improving the outcomes of solid organ transplantation recipients.

Objective:To compare the prognoses of salvage liver transplantation fulfilling the Criteria of Milan, University of California San Francisco(UCSF)and Hangzhou.Methods:Clinical data were retrospectively reviewed for 256 patients with recurrent hepatocellular carcinoma(HCC)undergoing donation after citizen death(DCD)liver transplantation(LT)from January 2015 to October 2019.They were divided into two groups of primary(PLT, n=175)and salvage(SLT, n=81). General profiles, tumor pathological characteristics and postoperative complications of two groups were compared by T-test, rank-sum or χ2 test.Kaplan-Meier method and Log rank test were employed for comparing overall survival rate(OS)and recurrence-free survival rate(RFS)between two groups.In SLT group, 31 cases fulfilled Milan criteria, 45 cases UCSF criteria and 69 cases Hangzhou criteria.OS/RFS of three groups were compared.According to there was downstaging or bridging treatment pre-LT, SLT group was divided into downstaging group(n=32)and non-downstaging group(n=49). OS/RFS of two groups were compared.According to the Rescit1.1 criteria, downstaging group were divided into remission group(n=14)and non-remission group(n=18)and OS/RFS of two groups were compared. Results:The operative durations of PLT and SLT groups were(439.5±74.9)and(475.1±83.4)min respectively.There was significant inter-group difference( P<0.05); However, no significant inter-group difference existed in amount of intraoperative bleeding, blood transfusion, postoperative hospital stay or incidence of postoperative complications(all P>0.05). No significant difference existed in OS/RFS between PLT and SLT groups( P>0.05). No significant difference existed in OS at 1/3/5 years post-SLT among Milan, UCSF and Hangzhou criteria groups(all P>0.05); However, RFS in Milan criteria group at 1/3/5 years post-SLT were 93.5%, 81.7% and 81.7% respectively.They were significantly higher than 68.9%, 59.7% and 59.7% in UCSF criteria group and 78.3%, 58.8% and 55.5% in Hangzhou criteria group(all P<0.05). For patients on downstaging therapy, OS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 73% and 73% respectively, which was significantly higher than 83.3%, 49.4% and 0 in non-Remission group( P=0.042). RFS in the Remission group at 1, 3 and 5 years post-SLT were 100%, 62.5% and 46.9% respectively, which was significantly higher than 52.9%, 0 and 0 in no-Remission group( P=0.001). Conclusions:The survival outcome of SLT recipients is similar to that of PLT recipients.The overall survival of SLT recipients shows no significant difference between Milan, UCSF and Hangzhou criteria.However, SLT recipients fulfilling Milan criteria have the longest recurrence-free time.The prognosis of patients with remission after preoperative descending treatment is superior to that of patients without remission.

Objective:To explore the effect of pre-transplant immunotherapy on the prognosis of transplant recipients with hepatocellular carcinoma(HCC).Methods:From June 2018 to September 2021, retrospective analysis was conducted for clinical data of 19 HCC-liver transplant recipients receiving pre-transplant immunotherapy in affiliated Huashan Hospital of Fudan University. Pre-transplant immunotherapy regimen, adverse reactions, post-transplant acute rejection, tumor recurrence and metastasis and other complications were recorded. According to the preoperative tumor imaging and the changes of alpha-fetoprotein level, tumor change during recipient waiting period was judged by the mRECIST standard. According to whether or not there was partial tumor remission, they were divided into two groups of non-remission( n=13)and remission( n=6). Postoperative conditions of two groups were compared. Kaplan-Meier method was used for calculating the survival rate of recipients after transplantation and survival curve and Log-rank test utilized for comparing the recurrence-free and overall survival rates of recipients at 1 and 2 years post-operation. Results:A total of 19 liver transplant recipients received immunotherapy plus targeted and transcatheter arterial chemoembolization(TACE) before transplant. In non-remission group, tumor was stable( n=9)and progressive( n=4); 6 cases in remission group had tumor partial remission. Two recipients in non-remission group were pathologically confirmed by liver biopsy to have acute rejection(2/19, 10.5%)and both recovered after glucocorticoid + rATG and glucocorticoid therapy. In non-remission group, 2 patients died from septic shock post-operation. Among 3 patients of tumor recurrence and metastasis post-operation, 2 cases survived with tumor and 1 died after tumor recurrence and metastasis. In remission group( n=6), none had postoperative tumor recurrence and metastasis. The recurrence-free survival rates of non-remission group recipients at 1 and 2 years post-operation were 76.9% and 76.9% and recurrence-free survival rates in remission group were 100% and 100% respectively and inter-group difference in RFS was not statistically significant( χ2=1.468, P=0.226). The overall survival rates of recipients in non-remission group at 1 and 2 years post-operation were 76.9% and 76.9% respectively. And recipients in remission group were 100% and 100% respectively and no statistically significant inter-group difference existed in OS( χ2=1.292, P=0.256). Conclusions:Without a significantly higher risk of acute rejection after transplant, immunotherapy may be an effective option for bridging treatment before liver transplantation for HCC. And it remains necessary to expand the sample size for verifications and supports.