Background: The aim of this study was to assess the validity of the 7^th edition of the American Joint Committee on Cancer (AJCC) TNM system (TNM-7) for patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Methods: Partial hepatectomies performed for 879 patients from 1993 to 2005 were retrospectively reviewed. Clinicopathological factors, surgical outcome, overall survival (OS), and disease-free survival (DFS) were analyzed to evaluate the predictive value of the TNM-7 staging system. Results: According to the TNM-7 system, differences in five-year survival between stages I, II, and III were statistically significant. Subgroup analysis of stage III patients revealed that the difference between stages II and IIIA was not significant (OS, p = 0.246; DFS, p = 0.105). Further stratification of stages IIIA, IIIB and IIIC also did not reveal significant differences. Cox proportional hazard models of stage III analyses identified additional clinicopathological factors affecting patient survival: lack of tumor encapsulation, aspartate aminotransferase (AST) values > 68 U/L, and blood loss > 500 mL affected DFS whereas lack of tumor encapsulation, AST values > 68 U/L, blood loss > 500 mL, and serum α-fetoprotein (AFP) values > 200 ng/mL were independent factors impairing OS. Stage III factors including tumor thrombus, satellite lesions, and tumor rupture did not appear to influence survival in the stage III subgroup. Conclusions: In terms of 5-year survival rates, the TNM-7 system is capable of stratifying post-hepatectomy HCC patients into stages I, II, and III but is unable to stratify stage III patients into stages IIIA, IIIB and IIIC. Lack of tumor encapsulation, AST values > 68 U/L, blood loss > 500 mL, and AFP values > 200 ng/mL are independent prognostic factors affecting long-term survival.

Murine full-thickness skin transplantation is a well-established model to study rejection in an alloimmune setting. Here, we provide a...

PURPOSE: Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors. PATIENTS AND METHODS: The IMbrave150 study's atezo-bev group was analyzed. PR or SD per RECIST v1.1 lasting more than 6 months was defined as durable. For histologic analysis, a comparable real-world group of patients from Japan and Taiwan who had undergone resection of residual tumors after atezo-bev was investigated. RESULTS: In the IMbrave150 study, 56 (77.8%) of the 72 PRs and 41 (28.5%) of the 144 SDs were considered durable. The median overall survival was not estimable for patients with durable PR and 23.7 months for those with durable SD. The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world setting, a total of 38 tumors were resected from 32 patients (23 PRs and nine SDs) receiving atezo-bev. Pathologic complete responses (PCRs) were more frequent in PR tumors than SD tumors (57.7% v 16.7%, P = .034). PCR rate correlated with time from atezo-bev initiation to resection and was 55.6% (5 of 9) for PR tumors resected beyond 8 months after starting atezo-bev, a time practically corresponding to the durable PR definition used for IMbrave150. We found no reliable radiologic features to predict PCR of the residual tumors. CONCLUSION: Durable PR patients from the atezo-bev group showed a favorable outcome, which may be partly explained by the high rate of PCR lesions. Early recognition of PCR lesions may help subsequent treatment decision.

Immune checkpoint inhibitors (ICI) have been applied to treat advanced stage hepatocellular carcinoma (HCC) and obtain promising effects. However, tumor response to treatment was unpredictable. A predicting biomarker of objective response or disease-control is an unmet need for patient selection. In this study, 45 advanced HCC patients who failed to sorafenib treatment and received nivolumab, 3 mg/kg bi-weekly, were included. Tumor responses to nivolumab treatment were assessed by the modified response evaluation criteria in solid tumors (mRECIST) criteria. Tumor responses were correlated to clinical characteristics to find out response predictors. In this small series, the prevalence of extrahepatic nodal metastasis, distant metastasis, and portal vein thrombus among the patients were 22.2% (n = 10), 48.9% (n = 22), and 42.2% (n = 19), respectively. The pre-treatment tumor size was 7.2 ± 4.2 cm in maximal diameter, and the calculated total tumor volume was 619.0 ± 831.1 cm³. Among 45 patients, 3 patients had partial response (PR), 11 had stable disease (SD), and the other 31 had progression of disease. By correlating clinical data to the patients with PR and SD, serum neutrophil-to-lymphocyte ratio (NLR) (hazard ratio (HR) = 2.04) and patient-generated subjective global assessment (PG-SGA) score (HR = 2.30) were the independent factors in multivariate analysis. By receiver operating characteristic curve analysis, pre-treatment NLR ≤ 2.5 and PG-SGA score < 4 were the cutoff points to predict tumor response to ICI treatment. In conclusion, biomarkers to predict tumor response for HCC are still lacking in this costly ICI therapy. In this study, NLR ≤ 2.5 and PG-SGA score < 4 indicated disease-control, and can be applied as biomarkers to select the right patients to receive this costly therapy.

Microvascular invasion (MVI) is a significant risk factor for the recurrence of hepatocellular carcinoma, but it is a histological feature that needs to be confirmed after hepatectomy or liver transplantation. The preoperative prediction of MVI can optimize the treatment plan of HCC, but an easy and widely applicable model is still lacking. The aim of our study was to predict the risk of MVI using objective preoperative factors. We retrospectively collected 1153 patients who underwent liver resection for HCC, and MVI was found to be associated with significantly poor disease-free survival. The patients were randomly split in a 3:1 ratio into training (n = 864) and validation (n = 289) datasets. The multivariate analysis of the training dataset found preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We built a risk score model with cutoff points of TTV at 30, 60, and 300 cm³ and AFP at 160 and 2000 ng/mL, and the model stratified the risk of MVI into low risk (14.1%), intermediate risk (36.4%), and high risk (60.5%). The validation of the risk score model with the validation dataset showed moderate performance (the concordance statistic: 0.731). The model comprised simple and objective preoperative factors with good applicability, which can help to guide treatment plans for HCC and future study design.

Background: Organ demand for liver transplantation (LT) is constantly increasing. Split liver transplantation (SPLT) is an ideal option for increasing the number of available liver grafts for transplantation and ameliorating organ shortage to a certain degree. However, SPLT for two adult recipients is still not broadly applied. Methods: We retrospectively analyzed the outcomes of SPLT for adult recipients at a single center. All donor, recipient, and transplantation factors were thoroughly investigated to clarify factors affecting patient outcomes after LT. Results: One hundred consecutive adult SPLTs were performed during the study period. Early mortality and 1-year mortality occurred in 21 and 31 recipients, respectively. On multivariate analysis, graft weight (p = 0.036, odds ratio = 0.99, 95% confidence interval = 0.98–0.99) was the independent risk factor associated with early mortality; however, no factor was significantly related to 1-year mortality. On receiver operating characteristic curve analysis, a graft weight of 580 g was identified the cutoff for stratifying outcomes. Recipients transplanted with a graft weighing ≥580 g had significantly better outcome as compared with other recipients (p = 0.001). Moreover, SPLT remarkably provided a better survival benefit for recipients than those on the LT wait-list (p < 0.0001). Conclusions: Given the considerable incidence of wait-list mortality, SPLT for two adult recipients should be encouraged whenever possible to increase the donor pool and benefit patients awaiting LT. Nonetheless, caution should be taken with a smaller graft weight owing to the risk of early graft loss.