Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Survival effects of postoperative adjuvant TACE in early-HCC patients with microvascular invasion: A multicenter propensity score matching.

Background: The presence of microvascular invasion (MVI) significantly worsens the surgical outcome of hepatocellular carcinoma (HCC). The purpose of this research was to investigate the survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with MVI after hepatectomy. Methods: A retrospective analysis was conducted on 1372 HCC patients who underwent curative liver resection in four medical institutions. In order to minimize confounding factors and selection bias between groups, Propensity Score Matching (PSM) (1:1) was performed to ensure balanced clinical characteristics. Results: A total of 1056 patients were enrolled after PSM, including 672 patients with MVI and 384 patients without MVI. Adjuvant TACE improves DFS (Median, 36 months vs 14 months, p < 0.001) and OS (Median, NA vs 32 months, p < 0.001) in patients harboring MVI, but not in those (all p > 0.05) lacking MVI. In different different CNLC stages, adjuvant TACE improved DFS (CNLC stage I, Median, 37 vs 15 months; CNLC stage II, Median, 25 vs 11 months, p < 0.001) and OS (CNLC stage I, Median, NA vs 32 months, p < 0.001; CNLC stage II, Median, NA vs 26 months, p = 0.002) in patients who carried MVI, but not in those (CNLC stage I-II, all p > 0.05) who lacked MVI. Conclusions: Adjuvant TACE may be a potentially effective treatment option for improving survival outcomes in early-HCC patients harboring MVI, but not in those lacking MVI.

Development and Validation of a Nomogram for Predicting Postoperative Early Relapse and Survival in Hepatocellular Carcinoma.

BACKGROUND: Early relapse after hepatectomy presents a significant challenge in the treatment of hepatocellular carcinoma (HCC). The aim of this study was to construct and validate a novel nomogram model for predicting early relapse and survival after hepatectomy for HCC. PATIENTS AND METHODS: We conducted a large-scale, multicenter retrospective analysis of 1,505 patients with surgically treated HCC from 4 medical centers. All patients were randomly divided into either the training cohort (n=1,053) or the validation cohort (n=452) in a 7:3 ratio. A machine learning-based nomogram model for prediction of HCC was established by integrating multiple risk factors that influence early relapse and survival, which were identified from preoperative clinical data and postoperative pathologic characteristics of the patients. RESULTS: The median time to early relapse was 7 months, whereas the median time from early relapse to death was only 19 months. The concordance indexes of the postoperative nomogram for predicting disease-free survival and overall survival were 0.741 and 0.739, respectively, with well-calibrated curves demonstrating good consistency between predicted and observed outcomes. Moreover, the accuracy and predictive performance of the postoperative nomograms were significantly superior to those of the preoperative nomogram and the other 7 HCC staging systems. The patients in the intermediate- and high-risk groups of the model had significantly higher probabilities of early and critical recurrence (P<.001), whereas those in the low-risk group had higher probabilities of late and local recurrence (P<.001). CONCLUSIONS: This postoperative nomogram model can better predict early recurrence and survival and can serve as a useful tool to guide clinical treatment decisions for patients with HCC.

Efficacy of adjuvant TACE on the prognosis of patients with HCC after hepatectomy: a multicenter propensity score matching from China.

BACKGROUND: The survival benefit of adjuvant transarterial chemoembolization (TACE) in patients with hepatectomy for hepatocellular carcinoma (HCC) after hepatectomy remains controversial. We aimed to investigate the survival efficacy of adjuvant TACE after hepatectomy for HCC. METHODS: 1491 patients with HCC who underwent hepatectomy between January 2018 and September 2021 at four medical centers in China were retrospectively analyzed, including 782 patients who received adjuvant TACE and 709 patients who did not receive adjuvant TACE. Propensity score matching (PSM) (1:1) was performed to minimize selection bias, which balanced the clinical characteristics of the two groups. RESULTS: A total of 1254 patients were enrolled after PSM, including 627 patients who received adjuvant TACE and 627 patients who did not receive adjuvant TACE. Patients who received adjuvant TACE had higher disease-free survival (DFS, 1- ,2-, and 3-year: 78%-68%-62% vs. 69%-57%-50%, p < 0.001) and overall survival (OS, 1- ,2-, and 3-year: 96%-88%-80% vs. 90%-77%-66%, p < 0.001) than those who did not receive adjuvant TACE (Median DFS was 39 months). Among the different levels of risk factors affecting prognosis [AFP, Lymphocyte-to-monocyte ratio, Maximum tumor diameter, Number of tumors, Child-Pugh classification, Liver cirrhosis, Vascular invasion (imaging), Microvascular invasion, Satellite nodules, Differentiation, Chinese liver cancer stage II-IIIa], the majority of patients who received adjuvant TACE had higher DFS or OS than those who did not receive adjuvant TACE. More patients who received adjuvant TACE accepted subsequent antitumor therapy such as liver transplantation, re-hepatectomy and local ablation after tumor recurrence, while more patients who did not receive adjuvant TACE accepted subsequent antitumor therapy with TACE after tumor recurrence (All p < 0.05). CONCLUSIONS: Adjuvant TACE may be a potential way to monitor early tumor recurrence and improve postoperative survival in patients with HCC.

A Blumgart Anastomosis-Based Half-Invagination Pancreaticoenterostomy with Better Applicability to Laparoscopy and Lower Incidence of Pancreatic Leakage.

Background: The Blumgart anastomosis (BA) is one of the safest anastomoses for pancreatic stump reconstruction. The incidence of postoperative pancreatic fistula (POPF) and postoperative complications is low. However, how to make laparoscopic pancreaticoenterostomy easier and safer is still a topic to be discussed. Methods: The data of patients who underwent laparoscopic pancreaticoduodenectomy (PD) from April 2014 to December 2019 were analyzed retrospectively. Results: Half-invagination anastomosis was performed in 20 cases (HI group), and the Cattell-Warren anastomosis was carried out in 26 cases (CW group). The amount of intraoperative bleeding, operation time, and postoperative catheterization time in the HI group was significantly less than those in the CW group. Besides, the number of patients at the Clavien-Dindo grade III and above in the HI group was significantly less than that in the control group. Moreover, the incidence of POPF in the HI group was significantly lower than that in the CW group. Furthermore, fistula risk score (FRS) analysis showed that there was no high-risk group, and the highest risk in the medium-risk group was pancreatic leakage. In addition, the incidence of pancreatic leakage in the HI group and CW group was 7.7% and 46.67%, respectively, while the incidence of pancreatic leakage in the HI group was significantly lower than that in the CW group. Conclusions: The half-invagination pancreaticoenterostomy based on the Blumgart anastomosis should have good applicability under laparoscopy and could effectively reduce the incidence of postoperative pancreatic leakage.

Postoperative adjuvant transarterial chemoembolisation improves survival of hepatocellular carcinoma patients with microvascular invasion: A multicenter retrospective cohort.

BACKGROUND: We aimed to investigate the efficacy of postoperative adjuvant transarterial chemoembolisation (PA-TACE) in patients with hepatocellular carcinoma (HCC) complicated by microvascular invasion (MVI). METHODS: A retrospective analysis of 1505 patients with HCC who underwent hepatectomy at four medical centers, including 782 patients who received PA-TACE and 723 patients who did not receive adjuvant PA-TACE, has been conducted. Propensity score matching (PSM) (1:1) was performed on the data to minimise selection bias, which resulted in a balanced clinical profile between groups. RESULTS: After PSM, 620 patients who received PA-TACE and 620 patients who did not receive PA-TACE were included. Disease-free survival (DFS, 1-, 2-, and 3-year: 88%-68%-61% vs. 70%-58%-51%, p < 0.001) and overall survival (OS, 1-, 2-, and 3-year: 96%-89%-82% vs. 89%-77%-67%, p < 0.001) were significantly higher in patients who received PA-TACE than in those who did not. Patients with MVI who received PA-TACE had significantly higher DFS (1-, 2-, and 3-year: 68%-57%-48% vs. 46%-31%-27%, p < 0.001) and OS (1-, 2-, and 3-year: 96%-84%-77% vs. 79%-58%-40%, p < 0.001) than those who did not receive PA-TACE. Among the six different liver cancer stages, MVI-negative patients did not have significant survival outcomes from PA-TACE (p > 0.05), whereas MVI-positive patients achieved higher DFS and OS from it (p < 0.05). Liver dysfunction, fever, and nausea/vomiting were the most common adverse events in patients receiving PA-TACE. There was no significant difference in grade 3 or 4 adverse events between the groups (p > 0.05). CONCLUSIONS: Postoperative adjuvant transarterial chemoembolisation has a good safety profile and may be a potentially beneficial treatment modality for survival outcomes in patients with HCC, especially those with concomitant MVI.

Acute liver failure caused by Amanita verna: a case series and review of the literature.

BACKGROUND: Amanita verna is one of the most harmful wild fungi in China. Amanita verna poisoning occurs every year, and the mortality is as high as 50%. However, its clinical manifestations are complex and diverse. CASE PRESENTATION: In March 2019, three patients took a large amount of Amanita, and one of them received liver transplantation in Zhongshan hospital, Sun Yat-sen University. All patients had vomiting and diarrhea 8-12 h after eating wild mushrooms (Amanita). The patients were initially diagnosed with Amanita poisoning. One case (case 3) was complicated and diagnosed as mushroom poisoning (fatal Amanita), toxic hepatitis, acute liver failure, toxic encephalopathy, hemorrhagic colitis, toxic myocarditis, disseminated intravascular coagulation (DIC) and pregnancy. The general clinical data of all patients were recorded, who received early treatment such as hemodialysis, artificial liver plasma exchange, hormone shock and anti-infection. One case (case 1) recovered smoothly after liver transplantation, and the indexes of liver, kidney, coagulation function and infection were improved. The other two cases died of intracerebral hemorrhage. CONCLUSION: Liver transplantation is an effective method for the treatment of acute liver failure caused by mushroom poisoning and can improve the survival rate of patients with toxic liver failure.

Survival analysis between laparoscopic and open hepatectomy for hepatocellular carcinoma: a meta-analysis based on reconstructed time-to-event data.

BACKGROUND/PURPOSE OF THE STUDY: Laparoscopic hepatectomy (LH) has been widely used in the treatment of hepatocellular carcinoma (HCC). It is generally believed that the long-term outcomes of LH are not inferior to open hepatectomy (OH). However, the quality of evidence is low. The purpose of this study was to reconstruct time-to-event data for meta-analysis based on Kaplan-Meier curves from propensity-score matched studies and compare survival rates following LH and OH for hepatocellular carcinoma. METHODS: All published propensity-score matched studies reported in English that compared LH and OH for hepatocellular carcinoma with Kaplan-Meier curves were screened. Patients' survival information was reconstructed with the aid of a computer vision program. Different models (fixed-effects model for two-stage survival analysis and Cox regression for one-stage survival analysis) were performed for sensitivity analysis. In addition to the primary meta-analysis, two specific subgroup analyses were performed on patients by types of resection, cirrhosis status. RESULTS: Time-to-event data were extracted from 45 propensity-score matched studies (N = 8905). According to the time-to-event data and the reconstructed Kaplan-Meier curves, the cumulative overall survival rate was 49.0% and 50.9% in the LH and OH cohorts, respectively, a log-rank test did not demonstrate statistical significance (p > 0.05). The cumulative recurrence-free survival (RFS) probability was both close to 0.0%. The median RFS time was 49.1 (95% CI 46.1 ~ 51.7) and 44.3 (95% CI 41 ~ 46.1) months. The difference in disease status was statistically significant by the Log-rank test (p < 0.05). Using the random-effects model of two-stage analysis, the minor hepatectomy subgroup (HR = 1.32, 95% CI [1.09, 1.55], I2 = 6.2%, p = 0.383) and the shared fragile model of one-stage analysis (HR = 1.44 95% CI [1.23, 1.69], p < 0.001) suggested that LH could significantly prolong RFS of patients compared with OH. This result was consistent with sensitivity analysis using different models. CONCLUSION: This study was the first reconstructed time-to-event data based on a high-quality propensity-score matching study to compare the survival outcomes of LH and OH in the treatment of HCC. Results suggested that LH can improve RFS in patients with HCC undergoing minor hepatectomy and may also benefit long-term RFS in overall patients.

Chance and challenge of associating liver partition and portal vein ligation for staged hepatectomy.

BACKGROUND: The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was first performed in 2007. The critical patient selection, timing to perform the second stage operation, and minimally invasive technique are three key factors for patient outcomes. The aim of this review is to summarize published data on these three aspects. DATA SOURCES: Studies were identified by searching PubMed for articles published from January 2007 to October 2018, using the keywords "associating liver partition and portal vein ligation for staged hepatectomy" or "ALPPS" or "in situ split". Studies on colorectal liver metastasis (CRLM), perihilar cholangiocarcinoma (PHC), and hepatocellular carcinoma (HCC) indicated for ALPPS, cutoff values to determine the timing of stage 2, as well as modifications of ALPPS were included. RESULTS: The mortality of ALPPS for CRLM is declining, for PHC is high. In patients with HCC, essential hypertrophy makes the ALPPS safer. However, the degrees of fibrosis affect the hypertrophy. The future liver remnant volume is still the gold standard to start the second stage. Hepatobiliary scintigraphy plays an important role in quantitatively assessing liver function, whereas cutoff values need to be further calibrated. Less-invasive ALPPS modifications have increased and led to a decreased mortality. CONCLUSIONS: ALLPS improved the CRLM outcomes; ALPPS is feasible in patients with PHC after failure of portal vein embolization; ALPPS may be an option for HCC patients with major vascular invasion and thrombosis. The simplified and less-invasive ALPPS is the trend.

Preoperative mean corpuscular hemoglobin affecting long-term outcomes of hepatectomized patients with hepatocellular carcinoma.

Pretreatment anemia has been reported to be associated with survival in several solid tumor types. In terms of survival, only limited data on the hemoglobin (HGB) level in hepatocellular carcinoma (HCC) have been published and no data on mean corpuscular hemoglobin (MCH) level in HCC is available. The present study sought to examine the role of HGB and MCH levels in predicting long-term survival of patients with HCC who undergo resection. A retrospective study of 399 consecutive patients (1987-1994) who underwent hepatic resection for HCC in Sun Yat-Sen University Cancer Centre was performed. Serum HGB and MCH levels were examined preoperatively, and their prognostic capabilities were evaluated by Cox's proportional hazard model. Among the whole cohort, the HGB level appeared to be positively correlated with the MCH level (P<0.001). Survival analysis revealed that low levels of HGB (P=0.007) and MCH (P<0.001) were correlated with shorter overall survival (OS). Multivariate analysis revealed that MCH level was independently associated with OS (P<0.001), however, not HGB (P=0.278). In addition, 129 patients with large HCC (≥10 cm) tended to have a poorer OS (P<0.001) when compared with patients with smaller HCC. On subanalysis of patients with large HCC, MCH level also retained its stratified significance (P=0.001). Along with common clinicopathological variables, these results suggested that MCH, however, not HGB, may be useful in assessing prognosis for patients with HCC who undergo hepatectomy, particularly in identifying patients with large HCC who are most likely benefit from resection.

MicroRNA301 is a potential diagnostic biomarker for hepatocellular cancer.

We explored microRNA301 diagnosis value in hepatocellular cancer (HCC), attempting to provide novel insights for early detection, effective prevention, and timely treatment. 42 patients with HCC and 38 controls composed of 9 liver cirrhosis (LC), 9 chronic hepatitis B (CHB) and 20 healthy individuals were investigated in the study. Serum microRNA301 expression levels were detected using fluorescent quantitative polymerase chain reaction (FQ-PCR) technology. ROC curve was performed to evaluate diagnosis value of microRNA301. Meanwhile, the correlations of microRNA301 levels with clinical characteristics were also analyzed. Significantly up-regulated expression of serum microRNA301 was seen in HCC patients compared with the controls (P<0.05). We also noted that level changes of microRNA301 were associated with differentiation, alpha fetoprotein (AFP), portal vein-emboli and HasAg (P<0.05), rather than age, gender and tumor size. Based on the area under ROC curve of 0.880, the critical value of microRNA301 was 2.3530 and the sensitivity and specificity were 88.1% and 70.3%, respectively. The results of this study revealed that microRNA301 might function as a potential diagnostic biomarker for HCC.