Substantial decline of organ preservation fluid contamination following adoption of ischemia-free liver transplantation: a post-hoc analysis.

INTRODUCTION: Preservation fluid (PF) contaminations are common in conventional liver transplantation (CLT) and presumably originate from organ or PF exposures to the external environment in a non-strict sterile manner. Such exposures and PF contamination may be avoided in ischaemia-free liver transplantation (IFLT) because of the strict sterile surgical procedures. In this study, the authors evaluated the impact of IFLT on organ PF contamination. METHODS: A post-hoc analysis using data from the first randomized controlled trial of IFLT was performed to compare the incidence, pathogenic spectrum of PF contamination, and incidence of early recipient infection between IFLT and CLT. Multivariable logistic regression was used to explore risk factors for PF contamination. RESULTS: Of the 68 cases recruited in the trial, 64 were included in this post-hoc analysis. The incidence of culture-positive PF was 9.4% (3/32) in the IFLT group versus 78.1% (25/32) in the CLT group ( P <0.001). Three microorganisms were isolated from PF in the IFLT group, while 43 were isolated in the CLT group. The recipient infection rate within postoperative day 14 was 3.1% (1/32) in the IFLT group vs 15.6% (5/32) in the CLT group, although this difference did not reach statistical significance ( P =0.196). Multivariate analysis revealed that adopting IFLT is an independent protective factor for culture-positive PF. CONCLUSION: PF contamination is substantially decreased in IFLT, and IFLT application is an independent protective factor for PF contamination. Using rigorous sterile measures and effective antibiotic therapy during IFLT may decrease PF contamination.

Splenic Volume, an Easy-To-Use Predictor of HCC Late Recurrence for HCC Patients After Hepatectomy.

Purpose: The high recurrence rate of hepatocellular carcinoma (HCC) has a poor impact on the quality of life and survival time of patients. Especially for late recurrence, poor data are available in analysis. We aim to evaluate whether the splenic volume (SV) measured from preoperative CT images could predict late recurrence in HCC patients after hepatectomy. Patients and Methods: A cohort of 300 HCC patients hospitalized at Xiangya Hospital of Central South University between January 2015 and June 2018 was retrospectively analyzed. The SV was calculated by using automated volumetry software from preoperative CT images. A total of 300 HCC patients were separated into the early recurrence cohort (n=167), the late recurrence cohort (n=39), and the no recurrence cohort (n=94) according to whether there is a recurrence and the recurrence time. Univariate and multivariate Cox analyses were performed to identify the independent risk factors of both early and late recurrence. Results: AFP, Microvascular invasion (MVI), satellitosis, and BCLC staging were independent risk factors of HCC early recurrence. Splenic volume (HR=1.003, 95%CI:1.001-1.005, P<0.001) was the only predictor of HCC late recurrence. Based on X-tile software, 133 non-early recurrence patients were divided into two groups according to SV: low SV (<165ml, n=45) and high SV (≥165ml, n= 88). The low SV group had a significantly better RFS compared with the high SV group (P=0.015). Nomogram was built on the base of SV to get the probability of 3-year RFS, 4-year RFS, and 5-year RFS. Conclusion: In our study, we drew a conclusion that splenic volume was the only predictor of HCC late recurrence because of its association with portal hypertension and liver cirrhosis. High splenic volume often indicated a worse recurrence.

Prognostic Value of Postoperative Circulating Tumor DNA in Patients With Early- and Intermediate-Stage Hepatocellular Carcinoma.

Majority of patients with resected early- and intermediate-stage liver cancer will experience postoperative recurrence. This study aimed to investigate the application of ctDNA sequencing in the postoperative period of hepatocellular carcinoma. A total of 96 patients with liver cancer were enrolled in this study. Postoperative peripheral blood samples were collected from all patients after surgery and analyzed using hybridization capture-based next-generation sequencing. Identification of at least one somatic mutation in the peripheral blood was defined as ctDNA+. Five genetic features in tumor tissues were associated with disease-free survival (DFS) using Lasso-Cox model. The area under the receiver operating characteristic curve was 0.813 and 0.882 in training and validation cohorts, respectively. The recurrence rate in ctDNA+ and ctDNA- groups was 60.9% and 27.8%, respectively. Multivariate Cox regression analysis showed that the postoperative ctDNA was an independent prognostic predictor of DFS (HR [hazard ratio]: 6.074, 95% Cl [confidence interval]: 2.648-13.929, P<0.001) and overall survival (OS) (HR: 4.829, 95% CI: 1.508-15.466, P=0.008). Combined ctDNA with AFP improved prediction performance. The median DFS was 2.0, and 8.0 months in ctDNA+/AFP-H and ctDNA+/AFP-L groups, respectively; while ctDNA-/AFP-H and ctDNA-/AFP-L groups had not reached the median time statistically (Log-rank test, P < 0.0001). Furthermore, ctDNA- patients had better prognosis than ctDNA+ patients irrespective of tumor stage. Postoperative ctDNA sequencing has great prognostic value in patients with liver cancer. Patients with positive ctDNA should receive more intensive disease monitoring and more aggressive treatment strategies to improve the survival time.

A Nomogram Based on Preoperative Inflammatory Indices and ICG-R15 for Prediction of Liver Failure After Hepatectomy in HCC Patients.

OBJECTIVE: To establish a nomogram based on inflammatory indices and ICG-R15 for predicting post-hepatectomy liver failure (PHLF) among patients with resectable hepatocellular carcinoma (HCC). METHODS: A retrospective cohort of 407 patients with HCC hospitalized at Xiangya Hospital of Central South University between January 2015 and December 2020, and 81 patients with HCC hospitalized at the Second Xiangya Hospital of Central South University between January 2019 and January 2020 were included in the study. Totally 488 HCC patients were divided into the training cohort (n=378) and the validation cohort (n=110) by random sampling. Univariate and multivariate analysis was performed to identify the independent risk factors. Through combining these independent risk factors, a nomogram was established for the prediction of PHLF. The accuracy of the nomogram was evaluated and compared with traditional models, like CP score (Child-Pugh), MELD score (Model of End-Stage Liver Disease), and ALBI score (albumin-bilirubin) by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Cirrhosis (OR=2.203, 95%CI:1.070-3.824, P=0.030), prothrombin time (PT) (OR=1.886, 95%CI: 1.107-3.211, P=0.020), tumor size (OR=1.107, 95%CI: 1.022-1.200, P=0.013), ICG-R15% (OR=1.141, 95%CI: 1.070-1.216, P<0.001), blood loss (OR=2.415, 95%CI: 1.306-4.468, P=0.005) and AST-to-platelet ratio index (APRI) (OR=4.652, 95%CI: 1.432-15.112, P=0.011) were independent risk factors of PHLF. Nomogram was built with well-fitted calibration curves on the of these 6 factors. Comparing with CP score (C-index=0.582, 95%CI, 0.523-0.640), ALBI score (C-index=0.670, 95%CI, 0.615-0.725) and MELD score (C-ibasedndex=0.661, 95%CI, 0.606-0.716), the nomogram showed a better predictive value, with a C-index of 0.845 (95%CI, 0.806-0.884). The results were consistent in the validation cohort. DCA confirmed the conclusion as well. CONCLUSION: A novel nomogram was established to predict PHLF in HCC patients. The nomogram showed a strong predictive efficiency and would be a convenient tool for us to facilitate clinical decisions.

The prognostic value of postoperative circulating cell-free DNA in operable hepatocellular carcinoma.

BACKGROUND: Tumor biomarkers are eagerly needed in monitoring the recurrence of operable hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) is a promising noninvasive molecular biomarker for HCC. The current study aimed to evaluate the clinical significance of the postoperative cfDNA in operable HCC. METHODS: This study enrolled 82 HCC patients from January 2018 to June 2019. All patients underwent liver surgery and were pathologically diagnosed with HCC. Postoperative blood samples were collected from each patient. A fluorometric dsDNA assay was used to measure the concentration of cfDNA. We explore the correlation between cfDNA and recurrence. Kaplan-Meier's curves were used to evaluate the recurrence-free survival (RFS). Univariate and multivariate Cox regression analyses were used for assessing the relative clinical variables in predicting recurrence. RESULTS: Of the 82 HCC patients, 72 (87%) patients are male and the average age was 52.7 ± 12.8 years. The cfDNA-low and cfDNA-high groups had median recurrence times of 19.5 months and 14.0 months, respectively (p = .023). Multivariate analysis showed that postoperative cfDNA, tumour number and microvascular invasion (p < .050) were independent risk factors for recurrence in operable HCC. CONCLUSIONS: Postoperative cfDNA is still a promising marker to predict prognosis in postoperative HCC patients although prospective and large multicenter clinical study is needed to further validate the relationship between cfDNA and HCC recurrence.

Nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

OBJECTIVE: To establish nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). METHODS: A cohort of 422 patients with HCC or ICC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent differential factors. Through combining these independent differential factors, a nomogram was established for differential diagnosis between ICC and HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). The results were validated using a prospective study on 98 consecutive patients operated on from January 2019 to November 2019 at the same institution. RESULTS: Sex (OR = 9.001, 95% CI: 3.268-24.792, P < .001), hepatitis (OR = 0.323, 95% CI: 0.121-0.860, P = .024), alpha-fetoprotein (AFP) (OR = 0.997, 95% CI: 0.995-1.000, P = .046), carbohydrate antigen 19-9 (CA199) (OR = 1.016, 95% CI: 1.007-1.025, P < .001), and aspartate transaminase-to-neutrophil ratio index (ANRI) (OR = 0.904, 95% CI: 0.843-0.969, P = .004) were the independent differential factors for ICC. Nomogram was established with well-fitted calibration curves through incorporating these 5 factors. Comparing model 1 including gender, hepatitis, AFP, and CA199 (C index = 0.903, 95% CI: 0.849-0.957) and model 2 enrolling AFP and CA199 (C index = 0.850, 95% CI: 0.791-0.908), the nomogram showed a better discrimination between ICC and HCC, with a C index of 0.920 (95% CI, 0.872-0.968). The results were consistent in the validation cohort. DCA also confirmed the conclusion. CONCLUSION: A nomogram was established for the differential diagnosis between ICC and HCC preoperatively, and better therapeutic choice would be made if it was applied in clinical practice.