Effect of Severity of Liver Cirrhosis on Surgical Outcomes of Hepatocellular Carcinoma After Liver Resection and Microwave Coagulation

BackgroundLiver resection (LR) and percutaneous microwave coagulation therapy (PMCT) are both considered as radical treatments for small hepatocellular carcinoma (HCC). However, it is still unclear whether to select LR or PMCT in HCC patients with different degrees of liver cirrhosis. The purpose of this study was to compare the efficacy of LR and PMCT in the treatment of solitary and small HCC accompanied with different degrees of liver cirrhosis.MethodsIn this study, 230 patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function were retrospectively reviewed. Among these patients, 122 patients underwent LR, and 108 received PMCT. The short- and long-term outcomes were compared between these two procedures. Severity of liver cirrhosis was evaluated by using clinical scoring system (CSS) as previously published. Subgroup analysis based on CSS was performed to evaluate the effect of severity of liver cirrhosis on surgical outcomes after LR and PMCT.ResultsThere was no mortality within 90 days in both groups. Major complications were significantly more frequent in the LR group than in the PMCT group (18.8% vs. 4.6%, p<0.001). However, LR provided better surgical outcomes than PMCT. The 5-year overall survival (OS) rates for the LR and PMCT groups were 65.2% and 42%, respectively (p=0.006), and the corresponding disease-free survival (DFS) rates were 51.7% and 31.5%, respectively (p=0.004). Nevertheless, subgroup analysis showed that PMCT provided long-term outcomes that were similar to LR and lower surgical complications in HCC patients with CSS score≥4.ConclusionsLR may provide better OS and DFS rates than PMCT for patients with solitary HCC lesions ≤ 3 cm and Child-Pugh A liver function irrespective of liver cirrhosis. PMCT should be viewed as the optimal treatment for solitary and small HCC with severe cirrhosis.

Postoperative controlling nutritional status score is an independent risk factor of survival for patients with small hepatocellular carcinoma: a retrospective study

Background The controlling nutritional status (CONUT) score has been widely used to evaluate the nutritional and immunological status. Clinical value of postoperative CONUT (PoCONUT) score in hepatocellular carcinoma (HCC) remains unknown. This study assessed whether PoCONUT score could serve as a useful predictor of survival for patients with small HCC. Methods 547 consecutive patients with small HCC who underwent liver resection between February 2007 and December 2015 were included in this retrospective case-control study. Patients were categorized into two groups: low PoCONUT group (PoCONUT score ≤ 2, n = 382) and high PoCONUT group (PoCONUT score ≥ 3, n = 165). Propensity score matching (PSM) analysis was applied to balance the bias in baseline characteristics. A cumulative survival curve was established by the Kaplan–Meier method, and differences in OS and RFS among CONUT score groups were determined by the log rank test. Cox proportional hazard regression analysis was used to evaluate the association of PoCONUT score and overall survival (OS) and recurrence-free survival (RFS), with calculation of hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Results Cox proportional hazard regression analysis suggested that the PoCONUT score was an independent risk factor for both OS and RFS in patients with small HCC before and after PSM. Conclusions High PoCONUT score helps to predict worse OS and RFS in patients with small HCC who underwent liver resection.

Feasibility and safety of liver resection for huge hepatocellular carcinoma in cirrhotics

Background: With the current high incidence of hepatocellular carcinoma (HCC), more patients even with large and huge HCC are considered for liver resection.Methods: Medical records of consecutive adult cirrhotic patients who underwent partial hepatectomy for huge HCC (≥10 cm, huge HCC group) versus small HCC (<5 cm, small HCC group) at Sohag university hospital (January 2016 to December 2020) were analyzed. Both groups were compared regarding postoperative morbidity and risk of mortality following post hepatectomy liver failure (PHLF) as defined by the 50-50 criteria (50% mortality occurs among patients who developed increased plasma bilirubin >50 μml/l and reduced prothrombin activity <50% on postoperative day 5 (POD-5).Results: Thirty two patients were enrolled (16 per group), with median age of 56 (range 38-81) years, 22 were males. In correlation with resection of more liver segments in the huge HCC group, post hepatectomy alteration of liver functions (bilirubin rise and reduction of albumin and prothrombin concentration) was significantly pronounced among patients who had resection for huge compared with small HCC (p<0.05). Huge HCC group exhibited significantly worse postoperative complication score (p< 0.05) and needed significantly prologed periods of hospital stay (p<0.05). Concurrent persistence of PHLF and thrombocytopenia until POD-5 occurred in 3 patients (2 with huge HCC and 1 with small HCC). Among those patients, only one from huge HCC group died (mortality 6%) postoperatively.Conclusions: Liver resection provides safe and effective treatment strategy for carefully selected cirrhotic patients with huge HCC.

A Radiomics Nomogram for Preoperative Prediction of Early Recurrence of Small Hepatocellular Carcinoma After Surgical Resection or Radiofrequency Ablation

BackgroundPatients with small hepatocellular carcinoma (HCC) (≤3 cm) still have a poor prognosis. The purpose of this study was to develop a radiomics nomogram to preoperatively predict early recurrence (ER) (≤2 years) of small HCC.MethodsThe study population included 111 patients with small HCC who underwent surgical resection (SR) or radiofrequency ablation (RFA) between September 2015 and September 2018 and were followed for at least 2 years. Radiomic features were extracted from the entire tumor by using the MaZda software. The least absolute shrinkage and selection operator (LASS0) method was applied for feature selection, and radiomics signature construction. A rad-score was then calculated. Multivariable logistic regression analysis was used to establish a prediction model including independent clinical risk factors, radiologic features and rad-score, which was ultimately presented as a radiomics nomogram. The predictive ability of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve and internal validation was performed via bootstrap resampling and 5-fold cross-validation method.ResultsA total of 53 (53/111, 47.7%) patients had confirmed ER according to the final clinical outcomes. In univariate logistic regression analysis, cirrhosis and hepatitis B infection (P=0.015 and 0.083, respectively), hepatobiliary phase hypointensity (P=0.089), Child-Pugh score (P=0.083), the preoperative platelet count (P=0.003), and rad-score (P&lt;0.001) were correlated with ER. However, after multivariate logistic regression analysis, only the preoperative platelet count and rad-score were included as predictors in the final model. The area under ROC curve (AUC) of the radiomics nomogram to predict ER of small HCC was 0.981 (95% CI: 0.957, 1.00), while the AUC verified by bootstrap is 0.980 (95% CI: 0.962, 1.00), indicating the goodness-of-fit of the final model.ConclusionsThe radiomics nomogram containing the clinical risk factors and rad-score can be used as a quantitative tool to preoperatively predict individual probability of ER of small HCC.

Stereotactic Body Radiation Therapy vs. Radiofrequency Ablation for Single Small Hepatocellular Carcinoma: A Propensity-score Matching Analysis of Their Impact on Liver Function and Clinical Outcomes

Background: Stereotactic body radiation therapy (SBRT) has high efficacy for early-stage hepatocellular carcinoma (HCC) and is expected as an accepted alternative to radiofrequency ablation (RFA). However, SBRT for HCC may cause subacute liver injury leading to negative clinical outcomes. In this study, we compared changes of liver function and prognosis after SBRT or RFA in patients with single, small HCC by using a propensity-score matching analysis.Methods: We reviewed medical records of 140 patients with single ≤3 cm HCC treated with SBRT or RFA at Kurashiki Central Hospital between January 2014 and February 2019. Changes of albumin-bilirubin (ALBI) score, local recurrence, and overall survival were compared between the propensity-score matched groups (31 patients treated with SBRT and 62 treated with RFA).Results: The ALBI score increased modestly but significantly after SBRT, while it was unchanged in the RFA group; the intergroup difference was statistically significant (p = 0.004). No local recurrence of tumor was identified in the SBRT group, whereas the cumulative recurrence incidence was 9.7% in the RFA group (p = 0.023). Overall survival was not significantly different between the two groups (hazard ratio 1.32, 95% confidence interval 0.60–2.89, p = 0.401).Conclusions: SBRT had modestly negative impact on liver function but better local control of HCC than did RFA. Although long-term follow-up of liver function is necessary with SBRT treatment especially in patients with impaired liver function, SBRT is a satisfactory alternative to RFA for treatment of single, small HCC.

Sodium Pump Na+/K+ ATPase Subunit α1 Targeted Positron Emission Tomography Imaging of Hepatocellular Carcinoma in Mouse Models

Purpose: Positron emission tomography (PET) imaging was not efficiently used in early diagnosis of hepatocellular carcinoma (HCC) due to lack of appropriate tracers. Sodium pump Na+/K+ ATPase subunit α1 (NKAα1) emerges to be a prognostic and diagnostic biomarker of HCC. Here we investigated the feasibility of 18F-ALF-NOTA-S3, a PET tracer based on an NKAα1 peptide, to detect small HCC. Methods: GEPIA database was searched to obtain the expression characteristics of NKAα1 in HCC and its relationship with the prognosis. PET/CT was performed in orthotopic, diethylnitrosamine (DEN)-induced and genetically engineered HCC mouse models to evaluate the use of 18F-ALF-NOTA-S3 to detect HCC lesions. Results: NKAα1 is overexpressed in early HCC with a high positive rate and correlates with poor survival. In orthotopic, DEN-induced and genetically engineered HCC mouse models, PET/CT imaging showed high accumulation of 18F-ALF-NOTA-S3 in the tumor. The tumor-to-liver ratios are 2.56 ± 1.02, 4.41 ± 1.09 and 4.59 ± 0.65 respectively. Upregulated NKAα1 expression in tumors were verified by immunohistochemistry. Furthermore, 18F-ALF-NOTA-S3 has the ability to detect small HCC lesions with diameters of 2-5mm. Conclusion: NKAα1 may serve as a suitable diagnostic and prognostic biomarker for HCC. 18F-ALF-NOTA-S3 shows great potential for PET imaging of HCC.

The impact of thrombocytopenia on prognosis of HBV-related small hepatocellular carcinoma: a propensity score matching analysis

Background Thrombocytopenia was reported both detrimental and advantageous to hepatocellular carcinoma (HCC). However, there is little evidence showing clearly the clinical value of preoperative thrombocytopenia on the surgical outcome of patients with small HCC. This retrospective study aimed at elucidating the correlation between preoperative thrombocytopenia and surgical outcome of small HCC patients within Milan criteria treated with liver resection. Methods Data of hepatitis B virus (HBV)-related small HCC patients were retrospectively analyzed, and we performed the propensity score matching (PSM) analysis to overcome the imbalance of clinicopathological features. Patients enrolled were subsequently categorized into two groups according to preoperative platelet counts: thrombocytopenia group and non-thrombocytopenia group. Survival outcomes of the patients in both groups were described with the Kaplan-Meier method, and the difference was compared with a log-rank test. Cox regression analysis was applied to identify the risk factors of surgical outcome. Results After PSM, the estimated 1-, 3-, and 5-year overall survival (OS) rates for small HCC patients in the thrombocytopenia group were 94.5%, 77.0%, and 57.6%, and 95.0%, 79.6%, and 68.0%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.042). And the 1-, 3-, and 5-year estimated recurrence-free survival (RFS) rates for small HCC patients in the thrombocytopenia group were 70.4%, 51.0%, and 42.1%, and 83.8%, 63.7%, and 46.7%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.035). Multivariate analysis indicated preoperative thrombocytopenia was a significant prognosticator of poor RFS (hazard ratio (HR) = 1.388, 95% confidence interval (CI) 1.028~1.874, P = 0.033). Conclusion Preoperative thrombocytopenia had an undesirable impact on the recurrence of small HCC patients treated with liver resection.

TACE Combined with HIFU Versus Surgical Resection for Single Hepatocellular Carcinoma with Child-Pugh B Cirrhosis in Overall Survival and Progression-Free Survival: A Retrospective Study

Objective: To compare the effectiveness, safety and survival outcome of transcatheter arterial chemoembolization (TACE) combined with high-intensity focused ultrasound (HIFU) versus surgical resection for treating single hepatocellular carcinoma (HCC) with Child-Pugh B cirrhosis. Methods: A hospital-based retrospective study with 146 patients diagnosed with single HCC with Child-Pugh B cirrhosis from July 2010 to July 2018 was conducted in a tertiary teaching hospital. A total of 49 patients underwent TACE combined with HIFU (the combined group), and 97 patients underwent surgical resection (the resection group). Of them, 22 patients undergoing TACE combined with HIFU and 45 patients undergoing surgical resection had small HCC (tumor diameter ≤3 cm). The overall survival (OS) time, progression-free survival (PFS) time and postoperative complications were compared between the two groups. Results: In the single HCC tumor cohort, there was no significant difference in OS between the two groups [hazard ratio (HR) = 0.6379; 95% confidence interval (95% CI) = 0.3737 to 1.089; P = .0995], while the resection group showed an obvious superiority to the combined group regarding PFS (HR = 0.3545; 95% CI = 0.2176-0.5775; P < .0001). The 1-year, 3-year and 5-year recurrence rates were 30.9%, 55.7%, 86.6% in the resection group and 53.1%, 77.6%, 89.8% in the combined group, respectively. In the small HCC tumor cohort, there was also no difference in OS between the two groups (HR = 0.8808; 95% CI = 0.3295-2.355; P = .06396), while the resection group showed an obvious superiority to the combined group regarding PFS (HR = 0.4273; 95% CI = 0.1927-0.9473; P = .0363). The 1-year, 3-year and 5-year recurrence rates were 28.9%, 53.3%, 93.3% in the resection group and 40.9%, 68.2%, 81.8% in the combined group, respectively. Furthermore, the incidence of complications of the combined group was 38.8%, which was significantly less than the 56.7% of the resection group ( P = .041), and the duration of general anesthesia in the combined group was shorter than that in the resection group ( P = .001). Therein, there was no difference in the incidence of grade I complications (Clavien-Dindo classification) between the two groups ( P = .866). Conclusion: For patients with single or single small HCCs, TACE combined with HIFU may not be inferior to surgical resection in terms of the long-term survival rate, while surgical resection still has a definite advantage in terms of delaying recurrence. In addition, the combination of TACE and HIFU has higher safety than surgical resection.