Liver regeneration of living donor after liver donation for transplantation: Disparity in the left and right remnant liver.

Donor safety is crucial for living donor liver transplantation (LDLT), and sufficient liver regeneration significantly affects outcomes of living donors. This study aimed to investigate clinical factors associated with liver regeneration in living donors. The study retrospectively reviewed 380 living donors who underwent liver donation at Chang Gung Memorial Hospital in Linkou. The clinical characteristics and medical parameters of donors were analyzed and compared according to liver donation graft type. There were 355 donors (93.4%) with right hemi-liver donations and 25 donors (6.6%) with left hemi-liver donations. Left hemi-liver donors had a higher body mass index (BMI) and a larger ratio of remnant liver volume (RLV) to total liver volume (TLV). However, the 2 groups showed no significant difference in the liver regeneration ratio. The type of remnant liver (P < .001), RLV/body weight (P = .027), RLV/TLV (P < .001), serum albumin on postoperative day 7 and total bilirubin levels on postoperative day 30 were the most significant factors affecting liver regeneration in living donors. In conclusion, adequate liver regeneration is essential for donor outcome after liver donation. The remnant liver could eventually regenerate to an adequate volume similar to the initial TLV before liver donation. However, the remnant left hemi-liver had a faster growth rate than the remnant right hemi-liver in donors.

Enhancement of Tumorigenicity, Spheroid Niche, and Drug Resistance of Pancreatic Cancer Cells in Three-Dimensional Culture System.

The three-dimensional (3D) cell culture technique has been applied comprehensively as a variable platform for medical research, biochemical signal pathway analysis, and evaluation of anti-tumor treatment response due to an excellent recapitulation of a tumor microenvironment (TME) in the in vitro cultured cancer cells. Pancreatic cancer (PaC) is one of the toughest malignancies with a complex TME and refractory treatment response. To comprehensively study the TME of PaC, there is an eager need to develop a 3D culture model to decompose the cellular components and their cross interactions. Herein, we establish a 3D PaC culture system with cancer stem cell (CSC) and scalability properties. To validate our model, we tested the individual PaC cell and the combined effects with cancer-associated fibroblasts (CAFs) on cancer tumorigenicity, the cellular interaction through the CXCR3/CXCL10 axis, and cellular responses reflection of anti-cancer treatments. With the help of our 3D technology, a simulated malignant spheroid with important stromal populations and TME physiochemical properties may be successfully recreated. It can be used in a wide range of preclinical research and helpful in advancing basic and translational cancer biology.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a 5-year survival rate of 6% following a diagnosis, and novel therapeutic modalities are needed. Protease-activated receptor 1 (PAR1) is abundantly overexpressed by both tumor cells and multiple stroma cell subsets in the tumor microenvironment (TME), thereby offering a suitable immunotherapy target. METHODS: A chimeric antigen receptor (CAR) strategy was applied to target PAR1 using a human anti-PAR1 scFv antibody fused to the transmembrane region with two co-stimulatory intracellular signaling domains of cluster of differentiation 28 (CD28) and CD137 (4-1BB), added to CD3ζ in tandem. RESULTS: The engineered PAR1CAR-T cells eliminated PAR1 overexpression and transforming growth factor (TGF)-ß-mediated PAR1-upregulated cancer cells by approximately 80% in vitro. The adoptive transfer of PAR1CAR-T cells was persistently enhanced and induced the specific regression of established MIA PaCa-2 cancer cells by > 80% in xenograft models. Accordingly, proinflammatory cytokines/chemokines increased in CAR-T-cell-treated mouse sera, whereas Ki67 expression in tumors decreased. Furthermore, the targeted elimination of PAR1-expressing tumors reduced matrix metalloproteinase 1 (MMP1) levels, suggesting that the blocking of the PAR1/MMP1 pathway constitutes a new therapeutic option for PDAC treatment. CONCLUSIONS: Third-generation PAR1CAR-T cells have antitumor activity in the TME, providing innovative CAR-T-cell immunotherapy against PDAC.

Converting from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Patients with Hepatitis B Following Liver Transplantation.

BACKGROUND Taiwan has a high prevalence of hepatitis B virus (HBV) infection. HBV-related end-stage liver disease is the leading cause of liver transplantation (LT). Tenofovir alafenamide (TAF) is a recently approved agent for the treatment of chronic HBV infection that improves renal profiles compared with tenofovir disoproxil fumarate (TDF) in phase III trials. This study aimed to assess the outcomes of TAF treatment in LT recipients. MATERIAL AND METHODS This retrospective study analyzed 17 LT recipients who underwent treatment with TDF and TAF. Changes in baseline renal function were compared. RESULTS Seventeen LT recipients received TDF for ≥48 weeks and were switched to TAF. During TDF treatment, estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease [MDRD] formula) decreased significantly at weeks 24 and 48. At week 48, only 2 patients (11.8%) displayed improved renal function, whereas the other patients showed decreased eGFR ranging from 5.48% to 62.84%. After switching to TAF, the median eGFR increased by 3.01% at week 24 and decreased by 0.31% at week 48. Seven patients (47%) showed improved renal function at week 48 after TAF treatment. CONCLUSIONS Switching from TDF to TAF was associated with fewer short-term renal impairment while maintaining the antiviral efficacy in LT recipients.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Peritoneal Carcinomatosis: Additional Information Helps to Optimize Patient Selection before Surgery.

(1) Background: The prognosis of gastric cancer-associated peritoneal carcinomatosis (GCPC) is poor, with a median survival time of less than six months, and current systemic chemotherapy, including targeted therapy, is ineffective. Despite growing evidence that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for GCPC improves overall survival (OS), optimal patient selection remains unclear. We aimed to evaluate preoperative clinical factors and identify indicative factors for predicting postoperative OS in patients with GCPC undergoing CRS-HIPEC. (2) Methods: We retrospectively reviewed 44 consecutive patients with GCPC who underwent CRS-HIPEC between May 2015 and May 2021. Data on demographics and radiologic assessment were collected and analyzed. (3) Results: Elevated preoperative serum neutrophil-to-lymphocyte ratio > 4.4 (p = 0.003, HR = 3.70, 95% CI = 1.55-8.79) and number of computed tomography risks > 2 (p = 0.005, HR = 3.26, 95% CI = 1.33-7.98) were independently indicative of OS post-surgery. A strong correlation was observed between intraoperative peritoneal cancer index score and number of computed tomography risks (r = 0.534, p < 0.0001). Two patients after CRS-HIPEC ultimately achieved disease-free survival for more than 50 months. (4) Conclusions: Our experience optimizes GCPC patients' selection for CRS-HIPEC, may help to improve outcomes in the corresponding population, and prevent futile surgery in inappropriate patients.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.

Significance of Physical Status and Liver Function Reserve for Outcome of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib Treatment.

Background: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment. Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed. Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55-3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20-3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32-0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21-0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients. Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.

Elevation of Lipid Metabolites in Deceased Liver Donors Reflects Graft Suffering.

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering.

High pulse pressure predicts primary arteriovenous fistula failure within 1 year.

BACKGROUND: The arteriovenous fistula is the preferred access route for hemodialysis, although its high primary failure rate remains a clinical challenge. Multiple studies have attempted to determine the risk factors for primary arteriovenous fistula failure; however, none have identified pulse pressure as a potential predictive marker. High pulse pressure is a surrogate poor arterial compliance endpoint and leads to inferior cardiovascular outcomes. Our aim was to determine whether elevated pulse pressure indicates poor arteriovenous fistula maturation. METHODS: We retrospectively reviewed 274 patients who underwent an arteriovenous fistula index operation between September 1, 2018 and May 31, 2019. Demographic, clinical data, and operative parameters were collected and analyzed. The maximum follow-up period was 365 days. Arteriovenous fistula failure was defined as the inability to achieve functional use during the follow-up period. We identified risk factors for arteriovenous fistula failure by performing a multivariate logistic regression analysis using backward elimination procedures. RESULTS: A total of 274 patients were included in the study. The patients' average age was 61.3 ± 14.0 years, approximately half of the patients (n = 161, 58.8%) were male, and the majority had hypertension. At the end of the follow-up period, 68 (24.8%) had arteriovenous fistula failure. The proportion of patients with pulse pressure values of >60 mmHg was significantly higher in the failure group than in the maturation group (66.0% vs 80.9%; p = 0.021). A PP value of >60 mmHg (odds ratio = 2.25; 95% confidence interval = 1.14-4.42; p = 0.019) and coronary artery disease or myocardial infarction (odds ratio = 1.97; 95% confidence interval = 1.01-3.84; p = 0.045) were found to be independent risk factors for primary arteriovenous fistula failure. CONCLUSIONS: High pulse pressure is an independent risk factor for primary arteriovenous fistula failure.

Determinants of Antibody Response to SARS-CoV-2 Vaccines in Liver Transplant Recipients: The Role of Immunosuppression Reduction.

Liver transplant recipients on chronic immunosuppression show an attenuated antibody response after SARS-CoV-2 vaccination. Adjusting immunosuppressants during vaccination remains debated. We enrolled 380 liver transplant recipients receiving 2 doses of a protein subunit, mRNA, or a vector vaccine. The patients were informed to temporarily suspend immunosuppression for 2 weeks for both vaccination doses. We measured anti-live-SARS-CoV-2 spike neutralizing antibody levels at 1−2 months after the second vaccination; 83.9% of patients had humoral responses (SARS-CoV-2 NT50 ≥ 9.62 IU/mL) to 2 doses of vaccines. The mRNA (86.7%) and protein subunit vaccines (85%) yielded higher response rates than the vector vaccines (40.9%). Immunosuppression suspension during the two vaccinations yielded a higher response rate (91.5% vs. 57.7%). Only eight patients (2.1%) experienced transaminase level elevation of thrice the normal value (>110 IU/L) after the second vaccination. Most recovered spontaneously after resuming immunosuppression. Multivariate analysis revealed ABO incompatibility, white blood cell count <4000, lymphocyte count <20%, tacrolimus trough level >6.5 ng/mL, and no immunosuppression adjustment as independent risk factors to nonresponse. The mRNA and protein subunit vaccines yielded a higher response rate. Immunosuppression suspension for 2 weeks enhanced the antibody response. ABO incompatibility, leukopenia, lymphopenia, a high tacrolimus trough level, and no immunosuppression adjustment are associated with nonresponse.

Modified preoperative score to predict disease-free survival for hepatocellular carcinoma patients with surgical resections.

BACKGROUND: No prognostic models specific to hepatocellular carcinoma patients receiving surgical resection have been considered strong and convincing enough for survival prediction thus far, and there are no models including only preoperative predictors. We derived a nomogram to predict disease-free survival in a previous study. AIM: To simplify our score and compare research outcomes among other scoring systems. METHODS: We retrospectively reviewed data from 1106 patients with hepatocellular carcinoma who underwent liver resection at the Linkou Chang Gung Memorial Hospital between April 2003 and December 2012. Multivariate analyses were conducted to identify the significant survival predictors. Homogeneity, Harrell's C-index, and Akaike information criterion were compared between our score, AJCC 8th edition, Tokyo score, and Taipei Integrated Scoring System (TTV-CTP-AFP model). RESULTS: Among the 1106 patients, 731 (66.1%) had tumor recurrence at a median follow-up of 83.9 mo. Five risk factors were identified: platelet count, albumin level, indocyanine green retention rate, multiplicity, and radiologic total tumor volume. Patients were divided into three risk groups, and the 5-year survival rates were 61.7%, 39%, and 25.7%, respectively. The C-index was 0.617, which was higher than the Tokyo score (0.613) and the Taipei Integrated Scoring System (0.562) and equal to the value of the AJCC 8th edition (0.617). CONCLUSION: The modified score provides an easier method to predict survival. Appropriate treatment can be planned preoperatively by dividing patients into risk groups.

Recurrence Patterns After Hepatectomy With Very Narrow Resection Margins for Hepatocellular Carcinoma.

Background: The extent of hepatic resection In HCC depends on the remnant liver reserve or the proximity of the tumor to major vessels. In this study, we evaluated the effects of very close resection margins on postoperative recurrence. Methods: Consecutive LR for HCC between 2003 and 2009 were studied. Patients were divided into groups with very narrow (≤1 mm) or wider (>1 mm) resection margins. Propensity score matching (PSM) was used to balance demographic, surgical, and pathological factors. Results: 983 patients were included in the study. After PSM, 173 patients were analyzed in each group. 5-year tumor recurrence and survival rates were comparable. Most recurrences were multiple intrahepatic. Section margin recurrences were similar in both groups. By multivariate analysis, tumor size >5 cm was associated with a very narrow resection margin, whereas low platelet count and tumor macrovascular invasion were significant factors related to tumor recurrence. Conclusions: Patients with very narrow surgical margins showed outcomes comparable to those with wider surgical margins. Most recurrences were multiple intrahepatic and associated with the degree of portal hypertension and adverse tumor biology. Although wide surgical margins should be aimed whenever possible, a narrow tumor-free margin resection still represents an effective therapeutic strategy.

Individualized Selection Criteria Based on Tumor Burden in Future Remnant Liver for Staged Hepatectomy of Advanced CRLM: Conventional TSH or ALPPS.

Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM.

Living-Donor Liver Transplantation for Hepatocellular Carcinoma: Impact of the MELD Score and Predictive Value of NLR on Survival.

Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR). Patients and Method: This retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004−2019 in our institute. We defined a high MELD score as ≥20. Results: The MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02−1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532−0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005). Conclusions: Pre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores.

Neutrophil-to-lymphocyte-ratio-based perioperative prognosis prediction model on early mortality after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to treat peritoneal surface malignancy (PSM) has gained a positive result compared with palliative chemotherapy alone in several cancer types. However, its postoperative care could be challenging. We aimed to develop a predicting model on early mortality. METHODS: We retrospectively reviewed 132 PSM patients who had received CRS-HIPEC. The optimal cut-off value of the neutrophil-to-lymphocyte ratio (NLR) was determined as 4.4 by using the receiver operating characteristic curve analysis with an area under the curve (AUC) of 0.75. The impact of NLR on survival was elucidated by comparing the pre-operative low (NLR≤ 4.4, n = 101) and high (NLR> 4.4, n = 31) groups using the Kaplan-Meier method. The significant variables selected in multivariate analysis on early mortality were used in prediction model development. RESULTS: Multivariate analysis showed that incomplete CRS, major postoperative complications, higher pre-operative NLR, and dynamic NLR changes were significant predictors of early mortality. Our perioperative prediction of prognosis (triple P) model contained four independent risks, and the AUC after classification was 0.860 (95% confidence interval [CI]: 0.773-0.947). External validation confirmed positive discrimination ability (AUC: 0.808, 95% CI: 0.666-0.950). CONCLUSION: In conclusion, our triple P model provides great determination in outcomes prediction and it is easily obtained, reliable, and applicable in routine practice.

Reconstruction of Separated Intrahepatic Ducts Using the Cystic and Common Hepatic Ducts in Right-Lobe Living-Donor Liver Transplantation: Experiences of Surgical Techniques, Biliary Complications, and Outcomes in a Single Institution.

BACKGROUND Duct-to-duct biliary reconstruction has been increasingly used in living-donor liver transplantation. Information regarding dual duct-to-duct biliary anastomoses is limited. We present the largest case series to date on the use of the cystic and common hepatic ducts as dual-ductal anastomosis, along with long-term follow-up results. MATERIAL AND METHODS In this study, 740 patients underwent right-lobe living-donor liver transplantation; 56 of them were documented as dual-ductal anastomoses. We analyzed recipient and donor characteristics, surgical procedures, appearance of biliary complications, corresponding interventions, and long-term biliary outcomes. RESULTS Cystic and common hepatic ducts were utilized in 56 cases of dual-ductal biliary reconstruction, which we categorized into 2 types: A (78.6%), in which the right anterior intrahepatic duct was anastomosed to the common hepatic duct and the right posterior intrahepatic duct to the cystic duct; and B (21.4%), which was the reverse of A. After a median follow-up period of 46.4 months, 23 patients (41.1%) experienced complications, including biliary leakage and biliary stricture. However, after aggressive intervention (patent biliary anastomosis in most of them), 50 of 56 patients (89.3%) had patent biliary anastomosis and restored normal liver function at the end of follow-up. A small graft (graft-to-recipient weight ratio <0.9%) was the only predictor of biliary complications after multivariate analysis. CONCLUSIONS Dual-ductal biliary reconstruction in adult right-lobe living-donor liver transplantation is challenging but feasible. Our findings support the use of the cystic duct for reconstruction in selected patients. Good long-term results can be achieved with adequate management of patients with biliary complications.

Preferred Treatment with Curative Intent for Left Lateral Segment Early Hepatocellular Carcinoma under the Era of Minimal Invasive Surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. METHODS: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. RESULTS: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1-60.9 months) and 17.6 (range: 2.4-94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

Quick preparation of ABO-incompatible living donor liver transplantation for acute liver failure.

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.

Clinical Relevance of Isoagglutinin Rebound in Adult ABO-Incompatible Living Donor Liver Transplantation.

ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) can be performed successfully. However, anti-ABO isoagglutinin rebound may cause antibody-mediated rejection (AMR) and graft loss. The risk threshold of isoagglutinin rebound is still not defined. 76 ABO-I LDLT recipients were divided into group A (n = 56) with low isoagglutinin titers (<1:256), and group B (n = 20) with high isoagglutinin titers (≥1:256), at initial assessment for liver transplantation. The last 12 patients in group B received a modified desensitization regimen by adding bortezomib to deplete plasma cells. Six (10.7%) patients in group A and 10 (50.0%) patients in group B had postoperative isoagglutinin rebound (p < 0.001). Three patients (5.54%) in group A and two patients (10%) in group B developed clinical AMR (p = 0.602). The cutoff value of postoperative isoagglutinin rebound to cause clinical AMR was ≥1:1024. Among the 12 patients in group B with bortezomib administration, isoagglutinin rebounded up to 1:128 only, and no clinical AMR occurred. In conclusion, the patients with high isoagglutinin titers had a higher rate of postoperative isoagglutinin rebound. Isoagglutinin rebound ≥1:1024 is risky for developing clinical AMR. Adding bortezomib into the desensitization regimen may mitigate isoagglutinin rebound, and avoid clinical AMR.