Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors:Where do we stand?

Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.

Portal vein arterialization in 25 liver transplant recipients:A Latin American single-center experience

BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation

BACKGROUND Hepatocellular carcinoma(HCC)is an aggressive malignant neoplasm that requires liver transplantation(LT).Despite patients with HCC being prioritized by most organ allocation systems worldwide,they still have to wait for long periods.Locoregional therapies(LRTs)are employed as bridging therapies in patients with HCC awaiting LT.Although largely used in the past,transarterial embolization(TAE)has been replaced by transarterial chemoembolization(TACE).However,the superiority of TACE over TAE has not been consistently shown in the literature.AIM To compare the outcomes of TACE and TAE in patients with HCC awaiting LT.METHODS All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included.All patients underwent LRT with either TACE or TAE.Some patients also underwent percutaneous ethanol injection(PEI),concom-itantly or in different treatment sessions.The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus.The primary outcome was waitlist dropout due to tumor progression,and the secondary outcome was the occurrence of adverse events.In the subset of patients who underwent LT,complete pathological response and post-transplant recurrence-free survival were also assessed.RESULTS Twelve(18.5%)patients in the TACE group(only TACE and TACE+PEI;n=65)and 3(7.9%)patients in the TAE group(only TAE and TAE+PEI;n=38)dropped out of the waitlist due to tumor progression(P log-rank test=0.29).Adverse events occurred in 8(12.3%)and 2(5.3%)patients in the TACE and TAE groups,respectively(P=0.316).Forty-eight(73.8%)of the 65 patients in the TACE group and 29(76.3%)of the 38 patients in the TAE group underwent LT(P=0.818).Among these patients,complete pathological response was detected in 7(14.6%)and 9(31%)patients in the TACE and TAE groups,respectively(P=0.145).Post-LT,HCC recurred in 9(18.8%)and 4(13.8%)patients in the TACE and TAE groups,respectively(P=0.756).Posttransplant recurrence-free survival was similar between the groups(P log-rank test=0.71).CONCLUSION Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC.Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.

Liver preservation prior to transplantation: Past, present, and future

Since Dr. Thomas Starzl performed the first series of successful liver transplants(LTs), important advances have been made in immunosuppression, operative techniques, and postoperative care. In 1988, Belzer's group reported the first successful LT using the University of Wisconsin preservation solution(UW).Since then, UW has replaced EuroCollins solution and allowed prolonged and safer preservation of liver, kidney, and pancreas allografts, thus contributing to the improvement of transplant outcomes. Although UW is still considered the standard of care in the United States and in several countries worldwide, a recent meta-analysis revealed similar LT outcomes among UW, Celsior solution, and the Institut Georges Lopez-1 preservation solution, which were slightly superior to those obtained with histidine-tryptophan-ketoglutarate preservation solution.Dynamic preservation has been recently developed, and liver allografts are preserved mainly through the following methods: hypothermic machine perfusion, normothermic machine perfusion, and subnormothermic machine perfusion. Their use has the potential advantage of improving clinical results in LT involving extended criteria donor allografts. Although associated with increased costs, techniques employing machine perfusion of liver allografts have been considered clinically feasible. This editorial focuses on recent advances and future perspectives in liver allograft preservation.

Liver transplantation for hepatitis B virus: Decreasing indication and changing trends

AIM: To evaluate the indication and outcome of hepatitis B virus(HBV)-related liver transplantation(LT) in the era of newer antiviral agents.METHODS: We collected data on all patients who underwent transplantation at King Faisal Specialist Hospital and Research Center.These data included demographic,perioperative and long-term postoperative follow-up data including viral serological markers,HBV DNA,and repeated liver imaging.Between January 1990 and January 2012,133 patients(106 males and 27 females) underwent LT for HBV-related cirrhosis at our center.All patients were followed up frequently during the first year following transplantation,according to our standard protocol; follow-up visits occurred every 3-6 mo thereafter.Breakthrough infection was definedas re-emergence of HBV-DNA or hepatitis B surface antigen(HBs Ag) while on treatment.Five patients transplanted prior to 1992 did not receive immediate posttransplant anti-HBV prophylaxis; all other patients were treated with HBIG and at least one nucleos(t)ide analog.RESULTS: One hundred and thirty-three patients underwent LT for HBV and were followed for a median of 82 mo(range: 1-274).The rates of post-LT survival and HBV recurrence during the follow-up period were 89% and 11%,respectively.The following factors were associated with disease recurrence: younger age(44.3 ± 16.2 years vs 51.4 ± 9.9 years,P = 0.02),positive pretransplant hepatitis B e antigen(HBe Ag)(60% vs 14%,P < 0.0001),detectable pretransplant HBV DNA(60% vs 27%,P = 0.03),positive posttransplant HBs Ag(80% vs 4%,P < 0.0001) and positive posttransplant HBe Ag(27% vs 1%,P < 0.0001).Forty-four(33%) patients had hepatocellular carcinoma(HCC).In the first(pre-2007) group,HBV was the second leading indication for LT after hepatitis C virus infection.A total of 64 transplants were performed,including 46(72%) for decompensated HBV cirrhosis,12(19%) for decompensated cirrhosis complicated by HCC and 6(10%) for compensated cirrhosis complicated by HCC.In the second group,nonalcoholic steatohepatitis surpassed HBV as the second leading indication for LT.A total of 69 HBV related transplants were performed,including 43(62%) for decompensated HBV cirrhosis,7(10%) for decompensated cirrhosis complicated by HCC and 19(27.5%) for compensated cirrhosis complicated by HCC.There was a significant(P = 0.007) increase in the number of transplants for compensated cirrhosis complicated by HCC.CONCLUSION: The use of potent anti-HBV agents has led to a changing trend in the indications for LT.HBV is currently the third leading indication for LT in this hyperendemic area.

China organ donation and transplantation update: the Hangzhou Resolution

The much-anticipated change in the practice of organ donation and transplantation in China is now underway and affirmed by an important Hangzhou Resolution promulgated at the 2013 China Transplant Congress.Support of the National Health and Family Planning Commission On October 29,2013,in a meeting of the National Health and Family Planning Commission (NHFPC)officials with Jie-Fu Huang,Head of National Organ Transplant Committee(OTC), Hai-Bo Wang,Director of China Organ Transplant Response System (COTRS)

Listeria monocytogenes following orthotopic liver transplantation:Central nervous system involvement and review of the literature

Listeria monocytogene is a well-recognized cause of bacteremia in immunocompromised individuals, including solid organ transplant recipients, but has been rarely reported following orthotopic liver transplantation. We describe a case of listeria meningitis that occurred within a week after liver transplantation. The patient developed a severe headache that mimicked tacrolimus encephalopathy, and was subsequently diagnosed with listeria meningitis by cerebrospinal fluid culture. The infection was successfully treated with three-week course of intravenous arnpicillin. Recurrent hepatitis C followed and was successfully treated with interferon alfa and ribavirin. Fourteen cases of listeriosis after orthotopic liver transplantation have been reported in the English literature. Most reported cases were successfully treated with intravenous ampicillin. There were four cases of listeria meningitis, and the mortality of them was 50%. Early detection and treatment of listeria meningitis are the key to obtaining a better prognosis.

Robotic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Analysis of surgical outcomes and long-term prognosis in a high-volume center

Background: Robotic pancreaticoduodenectomy(RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma(PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients. Methods: Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival(OS), and an online nomogram calculator was developed based on the independent prognostic factors. Results: Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 m L, the median OS was 23.6 months, and the median recurrence-free survival(RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9(CA19-9) [hazard ratio(HR) = 2.607, 95% confidence interval(CI): 1.560-4.354, P < 0.001], lymph node metastasis(HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately(HR = 3.190, 95% CI: 1.813-5.614, P < 0.001) or poorly differentiated(HR = 5.114, 95% CI: 2.839-9.212, P < 0.001), and Clavien-Dindo grade ≥ Ⅲ(HR = 1.657, 95% CI: 1.079-2.546, P = 0.021) were independent prognostic factors for OS. The concordance index(C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685(95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging(8th edition): 0.541(95% CI: 0.493-0.589)( P < 0.001). Conclusions: This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ Ⅲ were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner.

Derivation and validation of a preoperative prognostic model for resectable pancreatic ductal adenocarcinoma

Background: The prognosis of patients with pancreatic ductal adenocarcinoma(PDAC) remains poor even after radical pancreaticoduodenectomy(PD). The study aimed to develop and validate a novel preoperative prognostic model to accurately predict the long-term survival of patients with PDAC.Methods: Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation cohort.Results: Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low-and high-risk groups with distinctly different long-term survival in the training cohort [median overall survival(OS)32.1 vs. 17.5 months;median recurrence-free survival(RFS) 19.3 vs. 10.0 months, both P < 0.001] and the validation cohort(median OS 28.3 vs. 19.0 months;median RFS 17.5 vs. 11.2 months, both P < 0.001).Time-dependent receiver operating characteristic and decision curve analyses revealed that the model provided higher diagnostic accuracy and superior net benefit compared to other staging systems.Conclusions: This study constructed and validated a novel preoperative prognostic model that can accurately and conveniently predict the long-term survival of patients with resectable PDAC of pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.

Expanding indications for liver transplantation in the era of liver transplant oncology

Despite numerous advances and emerging data,liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications.In an era of persistent organ shortage and increasing organ demand,allocation of liver grafts must be considered carefully.While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation,tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes.As more studies seeking to expand the oncologic indications for liver transplantation are emerging,it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes.In addition,time from diagnosis to transplantation appears to correlate with survival,as stable disease over time portends better outcomes post-operatively.Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques.While tumor size and stage are important prognostic predictors for most malignancies,patient and tumor selection protocols are necessary.As the fields of medical and surgical oncology continue to evolve,it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively.Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms.Current data evaluating liver transplantation for expanded oncologic indications such as:expanded criteria hepatocellular carcinoma,intrahepatic cholangiocarcinoma,mixed tumors,and liver limited metastatic colorectal carcinomas,incorporate multi-modal therapies and evaluation of tumor treatment response.While further investigation is necessary,initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.

Biliary fistula and late recurrence of liver hydatid cyst:Role of cystobiliary communication:A prospective multicenter study

BACKGROUND Hydatid cyst disease(HCD)is common in certain locations.Surgery is associated with postoperative biliary fistula(POBF)and recurrence.The primary aim of this study was to identify whether occult cysto-biliary communication(CBC)can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase(ALP)levels in predicting POBF and recurrent HCD.AIM To identify whether occult CBC can predict recurrent HCD.The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD.METHODS From September 2010 to September 2016,a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty.Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence.RESULTS There was a highly statistically significant association(P≤0.001)between cystic fluid biochemical indices and the development of biliary complications(of 16 patients with POBF,15 patients had high cyst fluid bilirubin and ALP levels),where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications.There was a highly statistically significant association(P≤0.001)between biliary complications,biochemical indices,and the occurrence of recurrent HCD(of 30 patients with recurrent HCD,15 patients had high cyst fluid bilirubin and ALP;all 16 patients who had POBF later developed recurrent HCD),where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts,respectively.CONCLUSION Occult CBC can predict recurrent HCD.Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.

A narrative review of the current and future role of robotic surgery in liver surgery and transplantation

Background:Minimally invasive surgery(MIS)is the technique of choice in selected patients for the treatment of liver tumors.The robotic approach is considered today the natural evolution of MIS.The application of the robotic technique in liver transplantation(LT)has been recently evaluated,especially in the living donation.The aim of this paper is to review the current role of the MIS and robotic donor hepatectomy in the literature and to evaluate the possible future implication in the transplant field.Methods:We conducted a narrative review using PubMed and Google Scholar for reports published so far,using the following keywords:minimally invasive liver surgery,laparoscopic liver surgery,robotic liver surgery,robotic living donation,laparoscopic donor hepatectomy and robotic donor hepatectomy.Results:Several advantages have been claimed in favor of robotic surgery:three-dimensional(3-D)imaging with stable and high-definition view;a more rapid learning curve than the laparoscopic one;the lack of hand tremors and the freedom of movements.Compared to open surgery,the benefits showed in the studies evaluating the robotic approach in the living donation are:less postoperative pain,the shorter period before returning to normal activity despite sustaining longer operation time.Furthermore,the 3-D and magnification view makes the technique excellent in distinguishing the right plane of transection,vascular and biliary anatomy,associated with high precision of the movements and a better bleeding control(essential for donor safety)and lower rate of vascular injury.Conclusions:The current literature does not fully support the superiority of the robotic approach versus laparoscopic or open method in living donor hepatectomy.Robotic donor hepatectomy performed by teams with high expertise and in properly selected living donors is safe and feasible.However,further data are necessary to evaluate properly the role of robotic surgery in the field of living donation.

The Dallas Donation after Circulatory Death Transplantation Summit:expanding donation after circulatory death procedures through process improvement,broader utilization,and innovation

Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential.There is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation.We convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and gastroenterologists.The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers.We divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD outcomes.For each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD.There is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.

Thrombocytopenia after liver transplantation:should we care?

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation(LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes.

Feasibility and safety of sorafenib treatment in hepatocellular carcinoma patients with spontaneous rupture

AIM: To report the outcome of patients with ruptured hepatocellular carcinoma (HCC) treated at a single center during a 5-year period.

Notch1 downregulation combined with interleukin-24 inhibits invasion and migration of hepatocellular carcinoma cells

AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin(IL)-24 in hepatocellular carcinoma(HCC) cells.METHODS: γ-secretase inhibitors(GSIs) were used to down-regulate Notch1.Hep G2 and SMMC7721 cells were seeded in 96-well plates and treated with GSI-I or/and IL-24 for 48 h.Cell viability was measured by MTT assay.The cellular and nuclear morphology was observed under a fluorescence microscope.To further verify the apoptotic phenotype,cell cultures were also analyzed by flow cytometry with Annexin V-FITC/propidium iodide staining.The expression of Notch1,SNAIL1,SNAIL2,E-cadherin,IL-24,XIAP and VEGF was detected by Western blot.The invasion and migration capacities of HCC cells were detected by wound healing assays.Notch1 and Snail were downregulated by RNA interference,and the target proteins were analyzed by Western blot.To investigate the mechanism of apoptosis,we analyzed Hep G2 cells treated with si Notch1 or si CON plus IL-24 or not for 48h by caspase-3/7 activity luminescent assay.RESULTS: GSI-I at a dose of 2.5 μmol/L for 24 h caused a reduction in cell viability of about 38% in Hep G2 cells.The addition of 50 ng/m L IL-24 in combination with 1 or 2.5 μmol/L GSI-I reduced cell viability of about 30% and 15%,respectively.Treatment with IL-24 alone did not induce any cytotoxic effect.In SMMC7721 cells with the addition of IL-24 to GSI-I(2.5 μmol/L),the reduction of cell viability was only about 25%.Following GSI-I/IL-24 combined treatment for 6 h,the apoptotic rate of Hep G2 cells was 47.2%,while no significant effect was observed in cells treated with the compounds employed separately.Decreased expression of Notch1 and its associated proteins SNAIL1 and SNAIL2 was detected in Hep G2 cells.Increased E-cadherin protein expression was noted in the presence of IL-24 and GSI-I.Furthermore,the increased GSI-I and IL-24 in Hep G2 cell was associated with downregulation of MMP-2,XIAP and VEGF.In the absence of treatment,Hep G2 cells could migrate into the scratched space in 24 h.With IL-24 or GSI-I treatment,the wound was still open after 24 h.And the distance of the wound closure strongly correlated with the concentrations of IL-24 and GSI-I.Treatment of Notch-1 silenced Hep G2 cells with 50 ng/m L IL-24 alone for 48 h induced cytotoxic effects very similar to those observed in non-silenced cells treated with GSI-I/IL-24 combination.Caspase-3/7 activity was increased in the presence of si Notch1 plus IL-24 treatment.CONCLUSION: Down-regulation of Notch1 by GSI-I or si RNA combined with IL-24 can sensitize apoptosis and decrease the invasion and migration capabilities of Hep G2 cells.

Risk factor for ischemic-type biliary lesion after ABO-incompatible living donor liver transplantation

AIM: To evaluate the risk factors for ischemic-type biliary lesion(ITBL) after ABO-incompatible(ABO-I) adult living donor liver transplantation(ALDLT).METHODS: Among 141 ALDLTs performed in our hospital between 2008 and 2014, 27(19%) were ABO-I ALDLT and 114 were ABO-identical/compatible ALDLT. In this study, we extensively analyzed the clinico-pathological data of the 27 ABO-I recipients to determine the risk factors for ITBL after ABO-I ALDLT. All ABO-I ALDLT recipients underwent an identical B-cell depletion protocol with preoperative rituximab, plasma exchange(PE), and operative splenectomy. The median follow-up period after transplantation was 26 mo. The clinical outcomes of the 27 ABO-I ALDLT recipients were compared with those of 114 ABO-identical/compatible ALDLT recipients.RESULTS: ITBL occurred in four recipients(14.8%) between 45 and 112 d after ABO-I ALDLT. The overall survival rates were not different between ABO-I ALDLT and ABO-identical/compatible ALDLT(P = 0.303). Among the ABO-I ALDLT recipients, there was no difference between patients with ITBL and those without ITBL in terms of B-cell and T-cell count, serum isoagglutinin titers, number of PEs, operative time and transfusion, use of graft infusion therapy, or number of remnant B-cell follicles and plasma cells in the spleen. However, the perioperative NK cell counts in the blood of patients with ITBL were significantly higher than those in the patients without ITBL(P < 0.05). Preoperative NK cell count > 150/μL and postoperative NK cell count > 120/μL were associated with greater relative risks(RR) for development of ITBL(RR = 20 and 14.3, respectively, P < 0.05). CONCLUSION: High NK cell counts in a transplant recipient's blood are associated with ITBL after ABO-I ALDLT. Further research is needed to elucidate the molecular mechanism of NK cell involvement in the development of ITBL.

Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide.Sarcomatoid HCC,which contains poorly differentiated carcinomatous and sarcomatous components,is a rare histological subtype of HCC that differs from conventional HCC.It is highly aggressive and has a poor prognosis.Its clinicopathological characteristics,surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated.AIM To examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC.METHODS In total,196 patients[41 sarcomatoid HCC and 155 high-grade(Edmondson-Steiner grade III or IV)HCC]who underwent surgical resection between 2007 and 2017 were retrospectively reviewed.The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC.The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated.RESULTS Sarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom,adjacent organ invasion and lymph node metastasis than high-grade HCC(all P<0.05).Compared with high-grade HCC patients,sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC(44.4%vs 72.7%,P=0.001)and elevated serum alpha-fetoprotein levels(>20 ng/mL;36.6%vs 78.7%,P<0.001).The sarcomatoid group had a significantly shorter median recurrence-free survival(5.6 mo vs 16.4 mo,log-rank P<0.0001)and overall survival(10.5 mo vs 48.1 mo,log-rank P<0.0001)than the high-grade group.After controlling for confounding factors,the sarcomatoid subtype was identified as an independent predictor of poor prognosis.Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components.CONCLUSION Sarcomatoid HCC was associated with a more advanced stage,atypical dynamic imaging,lower serum alpha-fetoprotein levels and a worse prognosis.The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.

Possible benefit of splenectomy in liver transplantation for autoimmune hepatitis

Liver transplantation for autoimmune hepatitis(AIH) is usually successful with excellent long-term outcomes,but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy.Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.

Prediction of rat liver transplantation outcomes using energy metabolites measured by microdialysis

Background: Warm ischemia jeopardizes graft quality and recipient survival in donation after cardiac death(DCD) transplantation. Currently, there is no system to objectively evaluate the liver quality from DCD. The present study tried to use energy metabolites to evaluate the donor liver quality. Methods: We divided 195 Sprague-Dawley rats into five groups: the control( n = 39), warm ischemic time(WIT) 15 min( n = 39), WIT 30 min( n = 39), WIT 45 min( n = 39), and WIT 60 min( n = 39) groups. Three rats from each group were randomly selected for pretransplant histologic evaluation of warm ischemiarelated damage. The remaining 36 rats were randomly divided into donors and recipients of 18 liver transplantations, and were subjected to postoperative liver function and survival analyses. Between cardiac arrest and cold storage, liver energy metabolites including glucose, lactate, pyruvate, and glycerol were measured by microdialysis. The lactate to pyruvate ratio(LPR) was calculated. Results: The changes in preoperative pathology with warm ischemia were inconspicuous, but the trends in postoperative pathology and aminotransferase levels were consistent with preoperative energy metabolite measurements. The 30-day survival rates of the control and WIT 15, 30, 45, and 60 min groups were 100%, 81.82%, 76.92%, 58.33%, and 25.00%, respectively. The areas under the receiver operating characteristic curves of glucose, lactate, glycerol, and LPR were 0.87, 0.88, 0.88, and 0.92, respectively. Conclusion: Glucose, lactate, glycerol, and LPR are predictors of graft quality and survival outcomes in DCD transplantation.