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Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. A nationwide database of HCC patients with PVTT who underwent liver resection with ‘curative’ intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (

Objective: Though living donor liver transplantation (LDLT) is commonly performed for pediatric patients with biliary atresia (BA), pulmonary hypertension (PH) is seldom encountered or reported previously. The aim of this study is mainly to identify the prevalence of PH in pediatric patients undergoing liver transplantation and assess whether PH significantly augment the operative risk and evaluate the outcomes in this series of patients. Design: Retrospectively cohort study. Setting: Renji hospital, Shanghai, China. Participants: This study comprised 161 pediatric patients undergoing LDLT. Interventions: Patient diagnosed of PH in preoperative examination was compared to those without PH in intra- or post- operative complications or outcomes. Measurements and Main Results: We collected clinical records of LDLT surgery for pediatric patients during the year of 2016 in our hospital. Results suggested that pediatric patients undergoing LDLT had a substantial number of PH with a prevalence of 16.1% in this study. No significant difference was identified between two groups of patients regarding intraoperative outcomes and postoperative complications and mortality. Conclusion: LDLT is a safe procedure in a selected group of BA patients with PH, however, further long-term clinical investigations and mechanical researches are needed.

Living donor liver transplantation (LDLT) in infants for congenital biliary atresia (BA) poses various challenges nowadays. We aim to investigate independent preoperative risk factors for LDLT in infants. We retrospectively analyzed medical records of infant patients who underwent LDLT surgery for BA from 1 July 2014 to 31 December 2016. Cox regression was used to explore risk factors. The Kaplan-Meier method was used to calculate the recipient and graft survival, and subgroup analysis was then applied according to the risk factors. Independent t test or Mann-Whitney U test was applied for comparison of certain factors between survival patients and death. A total of 345 infant LDLT for BA were included in the analysis. In the multivariate Cox-regression model, 3 factors were determined as independent risk factors for recipient and graft survival, there were neutrophil-lymphocyte ratio (NLR), pediatric end-stage liver disease (PELD), and recipient age. The HR (95% CI) of baseline NLR for recipient and graft survival were 1.25 (1.12-1.38) and 1.25 (1.13-1.39), with all P .0001. Kaplan-Meier curves for NLR using different cut-offs (1.5; 1, 2) suggested that higher baseline NLR was significantly associated with recipient and graft survival. The subgroup analysis indicated that for infants with elevated NLR, the recipient survival was significantly lower when their age6 months or PELD20. Our results indicate that infants with higher baseline NLR value may have lower survival rate 3 years after transplantation. Further investigations about broaden the application of pre- and post-transplant NLR to guide nutrition intervention and immunosuppression therapy are necessary.

Norepinephrine (NE) is often administered during the perioperative period of liver transplantation to address hemodynamic instability and to improve organ perfusion and oxygen supply. However, its role and safety profile have yet to be evaluated in pediatric living donor liver transplantation (LDLT). We hypothesized that intraoperative NE infusion might affect pediatric LDLT outcomes. A retrospective study of 430 pediatric patients (median [interquartile range] age, 7 [6.10] months; 189 [43.9%] female) receiving LDLT between 2014 and 2016 at Renji Hospital was conducted. We evaluated patient survival among recipients who received intraoperative NE infusion (NE group, 85 recipients) and those that did not (non-NE group, 345 recipients). The number of children aged over 24 months and weighing more than 10 kg in NE group was more than that in non-NE group. And children in NE group had longer operative time, longer anhepatic phase time and more fluid infusion. After multivariate regression analysis and propensity score regression adjusting for confounding factors to determine the influence of intraoperative NE infusion on patient survival, the NE group had a 169% more probability of dying. Although there was no difference in mean arterial pressure changes relative to the baseline between the two groups, we did observe increased heart rates in NE group compared with those of the non-NE group at anhepatic phase (P=0.025), neohepatic phase (P=0.012) and operation end phase (P=0.017) of the operation. In conclusion, intraoperative NE infusion was associated with a poorer prognosis for pediatric LDLT recipients. Therefore, we recommend the application of NE during pediatric LDLT should be carefully re-considered.

Background Living donor liver transplantation (LDLT) in children has achieved promising outcomes during the past few decades. However, it still poses various challenges. This study aimed to analyze perioperative risk factors for postoperative death in pediatric LDLT. Methods We retrospectively analyzed medical records of pediatric patients who underwent LDLT surgery from January 1, 2014, to December 31, 2016, in our hospital. Predictors of mortality following LDLT were analyzed in 430 children. Cox regression and Kaplan-Meier curve analysis were used for covariates selection. A nomogram was developed to estimate overall survival probability. The performance of the nomogram was assessed using calibration curve, decision curve analysis, and time-dependent receiver operating characteristic curve. Results Among the 430 patients in this cohort (median [interquartile range] age, 7 [6.10] mo; 189 [43.9%] female; 391 [90.9%] biliary atresia), the overall survival was 91.4% (95% confidence interval, 89.2-94.4), and most of the death events (36/37) happened within 6 months after the surgery. Multivariate analysis indicated that the Pediatric End-stage Liver Disease score, neutrophil lymphocyte ratio, graft-to-recipient weight ratio, and intraoperative norepinephrine infusion were independent prognostic factors. A novel nomogram was developed based on these prognostic factors. The C index for the final model was 0.764 (95% confidence interval, 0.701-0.819). Decision curve analysis and time-dependent receiver operating characteristic curve suggested that this novel nomogram performed well at predicting mortality of pediatric LDLT. Conclusions We identified several perioperative risk factors for mortality of pediatric LDLT. And the newly developed nomogram can be a convenient individualized tool in estimating the prognosis of pediatric LDLT.

Background and purpose The cytokine activin C is mainly expressed in small-diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of activin C in neuropathic pain remain elusive. Experimental approach Male rats and wild-type and TRPV1 knockout mice with peripheral nerve injury - sciatic nerve axotomy and spinal nerve ligation in rats; chronic constriction injury (CCI) in mice - provided models of chronic neuropathic pain. Ipsilateral lumbar (L)4-5 DRGs were assayed for activin C expression. Chronic neuropathic pain animals were treated with intrathecal or locally pre-administered activin C or the vehicle. Nociceptive behaviours and pain-related markers in L4-5 DRGs and spinal cord were evaluated. TRPV1 channel modulation by activin C was measured. Key results Following peripheral nerve injury, expression of activin βC subunit mRNA and activin C protein was markedly up-regulated in L4-5 DRGs of animals with axotomy, SNL or CCI. [Correction added on 26 November 2020, after first online publication: The preceding sentence has been corrected in this current version.] Intrathecal activin C dose-dependently inhibited neuropathic pain in spinal nerve ligated rats. Local pre-administration of activin C decreased neuropathic pain, macrophage infiltration into ipsilateral L4-5 DRGs and microglial reaction in L4-5 spinal cords of mice with CCI. In rat DRG neurons, activin C enhanced capsaicin-induced TRPV1 currents. Pre-treatment with activin C reduced capsaicin-evoked acute hyperalgesia and normalized capsaicin-evoked persistent hypothermia in mice. Finally, the analgesic effect of activin C was abolished in TRPV1 knockout mice with CCI. Conclusion and implications Activin C inhibits neuropathic pain by modulating TRPV1 channels, revealing potential analgesic applications in chronic neuropathic pain therapy.

Physical stress is one of the most important factors affecting morphine-induced conditioned place preference (CPP). Convincing evidences demonstrate that physical stress can activate lateral habenular (LHb) neurons. However, the mechanism by which physical stress regulates morphine-induced CPP through LHb remains unclear. In this study, we examined the impact of forced swimming stress (FSS) on morphine-induced CPP in rats. We found that FSS significantly decreased the CPP scores of rats compared with the normal morphine administration rats. Meanwhile, we detected the expression of DARPP-32 phosphorylation (p-DARPP-32) in the nucleus accumbens (NAc), and CaMKII in LHb. The results show that FSS enhanced the expression of CaMΚII in LHb, while it reduced the level of p-DARPP-32 expression in the NAc. Furthermore, by microinjecting AAV-CaMKII or AAV-RNAi into LHb, we demonstrated that an overexpression of CaMKII could reduce morphine-induced CPP scores of rats, while knock-down CaMΚII could restore morphine-induced CPP scores, which were interfered by FSS. In addition, by microinjecting DiI into the ventral tegmental area (VTA) and tail of VTA (tVTA) unilaterally, and an anterograde tracing virus (AAV-CaMKII-mCherry) into LHb unilaterally, we verified the neural projections from LHb to tVTA. Taken together, our findings suggest that FSS could activate LHb neurons through CaMΚII, and inhibit morphine-induced CPP through the LHb-tVTA pathway.