Prognosis and safety of laparoscopic hepatectomy for BCLC stage 0/A hepatocellular carcinoma with clinically significant portal hypertension: a multicenter, propensity score-matched study.

BACKGROUND AND AIM: The latest Barcelona Clinic Liver Cancer (BCLC) staging system suggests considering surgery in patients with resectable BCLC stage 0/A hepatocellular carcinoma (HCC) and clinically significant portal hypertension (CSPH). This study aimed to evaluate the safety and short- and long-term outcomes of laparoscopic hepatectomy for BCLC stage 0/A HCC patients with CSPH. METHODS: We retrospectively reviewed the medical records of 647 HCC patients in BCLC stage 0/A who were treated at five centers between January 2010 and January 2019. Among these patients, 434 underwent laparoscopic hepatectomy, and 213 underwent open hepatectomy. We used Kaplan-Meier analysis to compare the overall survival (OS) rate and recurrence-free survival (RFS) rate between patients with and without CSPH before and after propensity score matching (PSM). Multivariate Cox regression analysis was performed to identify prognostic factors for BCLC stage 0/A patients, and subgroup analyses were also conducted. RESULTS: Among the 434 patients who underwent laparoscopic hepatectomy, 186 had CSPH and 248 did not. The Kaplan-Meier analysis showed that the OS and RFS rates were significantly worse in the CSPH group before and after PSM. Multivariate Cox regression analyses identified CSPH as a prognostic factor for poor OS and RFS after laparoscopic hepatectomy. However, CSPH patients treated laparoscopically had a better short- and long-term prognosis than those treated with open surgery. CONCLUSIONS: CSPH has a negative impact on the prognosis of BCLC stage 0/A HCC patients after laparoscopic hepatectomy. Laparoscopic hepatectomy is still recommended for treatment, but careful patient selection is essential.

Risk Factors of Positive Resection Margin in Hepatectomy for Resectable Ruptured Hepatocellular Carcinoma: Risk Prediction and Prognosis.

BACKGROUND AND AIM: Clinical work has revealed that hepatectomy for resectable ruptured hepatocellular carcinoma (rHCC) has a relatively high percentage of positive resection margins found in postoperative pathology. It is necessary to evaluate the risk factors associated with R1 resection in patients undergoing hepatectomy for rHCC. METHODS: A total of 408 patients with resectable rHCC originating from three centers undergoing surgery from January 2012 to January 2020 were consecutively enrolled in the study to study the prognostic impact of R1 resection using Kaplan-Meier plotting of survival curves. One center with 280 served as the training group, and the other two centers served as the validation group. Multivariate logistic regression analysis screened for variables affecting R1 and developed prediction models, and the models were tested in the validation cohort using the receiver operating characteristic curves (ROC) and calibration curves. RESULTS: The prognosis of rHCC patients with positive cut margins was worse than that of patients with R0 resection. Risk factors for R1 resection were tumor max length (OR = 2.668 [1.161-6.131]), microvascular invasion (MVI) (OR = 3.655 [1.766-7.566]), times of hepatic inflow occlusion (1/0:OR = 2.213 [1.113-4.399]; 2/0:OR = 5.723 [2.010-8.289]) and timing of hepatectomy (OR = 5.284 [2.394-9.661]), using tumor max length, times of HIO, and timing of hepatectomy to construct the nomogram, the area under the curve of the model was 0.810 (0.781-0.842) and 0.782 (0.752-0.805) in the training and validation groups, respectively, and the calibration curve of the model was basically on the 45° line. CONCLUSIONS: This study constructs a clinical model to predict R1 resection after hepatectomy for resectable rHCC, which can be used to better plan perioperative strategies for the incidence of R1 resection during hepatectomy.

A nomogram for preoperative prediction of microvascular invasion in ruptured hepatocellular carcinoma.

BACKGROUND AND AIM: Microvascular invasion (MVI) is defined as the presence of micrometastatic cancer cell emboli in hepatic vessels, including small vessels, and at present, researchers believe that is an important factor for early postoperative recurrence and survival. Here, we developed and validated a preoperative predictive model for the presence of MVI in patients with ruptured hepatocellular carcinoma (rHCC). METHODS: We retrospectively collected data for 210 rHCC patients who underwent staged hepatectomy at Wuhan Tongji Hospital, and 91 patients who underwent staged hepatectomy at Zhongshan People's Hospital between January 2010 and March 2021. Then, the former was used as the training cohort and the latter was used as the validation cohort. Logistic regression was used to screen for variables associated with MVI, and these variables were used to construct nomograms. We used R software to assess the discrimination, calibration ability, as well as clinical efficacy of nomograms. RESULTS: Multivariate logistic regression analysis identified four risk factors independently associated with MVI: max tumor length [odds ratio (OR) = 1.385; 95% confidence interval (CI), 1.072-1.790], number of tumors (OR = 2.182; 95% CI, 1.129-5.546), direct bilirubin (OR = 1.515; 95% CI, 1.189-1.930), and alpha-fetoprotein (cutoff = 400 ng/mL) (OR = 2.689; 95% CI, 3.395-13.547). Nomograms were built from the four variables and they were tested for discrimination and calibration, and the results were good. CONCLUSION: We developed and validated a preoperative predictive model for the presence of MVI in patients with ruptured HCC. This model can help clinicians identify patients at risk of MVI and make better treatment options.

Preoperative transcatheter arterial chemoembolization and prognosis of patients with solitary large hepatocellular carcinomas (≥5 cm): Multicenter retrospective study.

OBJECTIVES: Large hepatocellular carcinoma (LHCC) is prone to short-term recurrence and poor long-term survival after hepatectomy, and there is still a lack of effective neoadjuvant treatments to improve recurrence-free survival (RFS) and overall survival (OS). We retrospectively analyzed the efficacy of preoperative transcatheter arterial chemoembolization (TACE) in solitary LHCC (≥5 cm). MATERIALS AND METHODS: A multicenter medical database was used to analyze preoperative TACE's effects on RFS, OS, and perioperative complications in patients with solitary LHCC who received surgical treatment from January 2005 to December 2015. The patients were divided into Group A (5.0-9.9 cm) and Group B (≥10 cm), with 10 cm as the critical value, and the effect of preoperative TACE on RFS, OS and perioperative complications was assessed in each subgroup. RESULTS: In the overall population, patients with preoperative TACE had better RFS and OS than those without preoperative TACE. However, after stratifying the patients into the two HCC groups, preoperative TACE only improved the survival outcomes of patients with Group B (≥10 cm). Multivariate Cox-regression analysis showed that lack of preoperative TACE was an independent risk factor for RFS and OS in the overall population and in Group B but not in Group A. CONCLUSIONS: Preoperative TACE is beneficial for patients with solitary HCC (≥10 cm).

Circulating Tumor Cells as an Indicator of Treatment Options for Hepatocellular Carcinoma Less Than or Equal to 3†cm in Size: A Multi-Center, Retrospective Study.

Background: The status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC. Methods: This study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR). Results: There was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patients. Conclusions: The CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.

Preoperatively staging liver fibrosis using noninvasive method in hepatitis B virus-infected hepatocellular carcinoma patients.

BACKGROUND: Advanced liver fibrosis can result in serious complications (even patient's death) after partial hepatectomy. Preoperatively percutaneous liver biopsy is an invasive and expensive method to assess liver fibrosis. We aim to establish a noninvasive model, on the basis of preoperative biomarkers, to predict liver fibrosis in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection. METHODS: The HBV-infected liver cancer patients who had received hepatectomy were retrospectively and prospectively enrolled in this study. Univariate analysis was used to compare the variables of the patients with mild to moderate liver fibrosis and with severe liver fibrosis. The significant factors were selected into binary logistic regression analysis. Factors determined to be significant were used to establish a noninvasive model. Then the diagnostic accuracy of this novel model was examined based on sensitivity, specificity and area under the receiver-operating characteristic curve (AUC). RESULTS: This study included 2,176 HBV-infected HCC patients who had undergone partial hepatectomy (1,682 retrospective subjects and 494 prospective subjects). Regression analysis indicated that total bilirubin and prothrombin time had positive correlation with liver fibrosis. It also demonstrated that blood platelet count and fibrinogen had negative correlation with liver fibrosis. The AUC values of the model based on these four factors for predicting significant fibrosis, advanced fibrosis and cirrhosis were 0.79-0.83, 0.83-0.85 and 0.85-0.88, respectively. CONCLUSION: The results showed that this novel preoperative model was an excellent noninvasive method for assessing liver fibrosis in HBV-infected HCC patients.

Chemokines and Their Receptors: Potential Therapeutic Targets for Bone Cancer Pain.

Bone cancer pain (BCP) is still an intractable problem currently because the analgesic pharmacological intervention remains insufficient. Thus, the development of novel therapeutic target is critical for the treatment of BCP. Emerging evidence demonstrated that some chemokines and their receptors contribute to the induction and maintenance of BCP. In this article, we reviewed the current evidence for the role of different chemokines and their receptors (e.g. CXCL12/CXCR4, CXCL1/CXCR2, CCL2/CCR2, CCL5/CCR5, CX3CL1/CX3CR1 and CXCL10/CXCR3) in mediating BCP. By extensively understanding the involvement of chemokines and their receptors in BCP, novel therapeutic targets may be revealed for the treatment of BCP.