Nodular Hepatocellular Carcinoma Research Articles

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization, potential conversion therapies for single huge hepatocellular carcinoma: a retrospective comparison study.

The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10cm without vascular invasion and metastasis. From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored. The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS. HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.

Efficacy of laparoscopic liver resection for small hepatocellular carcinoma located in the posterosuperior segments: A multi-institutional study using propensity score matching by the Kyushu Study Group of Liver Surgery.

Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3cm located in PS. In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. The original cohort of patients with HCC ≤3cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287ml, p<0.001), postoperative complications (0.71 vs. 8.57%, p=0.003), and postoperative hospital stay (median, 9 vs. 14days, p<0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3cm located in PS.

Usefulness of Contrast-Enhanced Ultrasound in the Differentiation between Hepatocellular Carcinoma and Benign Liver Lesions.

A differentiation between hepatocellular carcinoma (HCC) and benign liver lesions is required. The aim of the study was to perform an analysis of the time of enhancement of focal liver lesions in a contrast-enhanced ultrasound (CEUS) examination. The curves of enhancement and the homogeneity of the tumor enhancement were assessed. The study included 52 patients with diagnoses of hepatocellular adenoma (18), focal nodular hyperplasia (11) and HCC (28). The study included magnetic resonance imaging or computed tomography and a comparison of the obtained information with CEUS. In the benign lesions groups after 20-30 s, the enhancement was similar to the liver parenchyma. In the HCC group, the enhancement was slightly less intense compared to the liver parenchyma and the benign lesions. The difference of the enhancement in the arterial phase (benign lesions vs. HCC) was p = 0.0452, and the difference of enhancement in the late venous phase (benign lesions vs. HCC) was p = 0.000003. The homogeneity of the enhancement (benign lesions vs. HCC), respectively, was p = 0.001 in the arterial phase, p = 0.0003 in the portal venous phase and p = 0.00000007 in the late venous phase. Liver tumors can be classified as benign when they are homogenous in the arterial phase and don't present washout. HCC in the arterial phase is inhomogeneous and washout is observed in the venous phases. When radiological symptoms suggest malignant lesion, CEUS can be used to select the best biopsy access.

Radiologic Patterns Determine the Outcomes of Initial and Subsequent Transarterial Chemoembolization in Intermediate-Stage Hepatocellular Carcinoma

Introduction: Outcomes of transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) are diverse because of the heterogeneity of tumor burden. Radiologic pattern is one criterion for determining whether TACE is unsuitable. However, additional evidence is required. This study determined the influence of radiologic morphology on the outcomes of initial and subsequent TACE. Methods: From January 2007 to September 2021, 633 treatment-naive patients with HCC with intermediate-stage HCC undergoing TACE were retrospectively enrolled. Of these patients, 386 patients received repeated TACE. The radiological features of HCC were evaluated by two radiologists and classified into encapsulated nodular type, simple nodular type with extranodular growth, confluent multinodular type, and infiltrative type. The objective response rate (ORR) and survival rate after initial and subsequent TACE among various radiologic morphologies were compared. Results: After initial TACE, encapsulated nodular type HCC had the highest ORR (58%), followed by extranodular type (45.8%), confluent multinodular type (29%), and infiltrative type (19.5%). Notably, radiologic pattern was highly associated with tumor burden. Tumor burden and radiologic morphology were significantly associated with ORR and overall survival (OS) in the multivariate analysis. In 386 patients with subsequent TACE, encapsulated nodular type HCC had the highest ORR (48.7%), followed by extranodular type (37.3%), confluent multinodular type (26.2%), and infiltrative type (10%). In the multivariate analysis, radiologic features were significant independent predictors of ORR and OS after receiving subsequent TACE. Conclusion: Radiologic patterns determine the outcomes of initial and subsequent TACE. Systemic therapy should be considered for patients with intermediate-stage HCC with unfavorable radiologic patterns.

TACE Combined with Lenvatinib and Camrelizumab for Unresectable Multiple Nodular and Large Hepatocellular Carcinoma (>5 cm).

The incidence and mortality of hepatocellular carcinoma (HCC) had increased globally over the past decades. Previous studies found that transarterial chemoembolization (TACE) combined with lenvatinib had also shown efficacy in the unresectable HCC. We aimed to evaluate the safety and efficacy of TACE combined with lenvatinib and camrelizumab to treat unresectable multiple nodular and large HCC (>5 cm). Between November 2018 and June 2021, we retrospectively recruited 82 patients with unresectable multiple nodular and large HCC (BCLC stage B or C with a single nodular diameter of >5 cm). Of the patients who had not previously been treated, 33 patients received TACE + lenvatinib + camrelizumab (group A, TLC), and 49 patients treated with TACE + lenvatinib (group B, TLB) as the initial treatment. Related efficacy and safety results were recorded and assessed. The median follow-up periods of groups A and B were 14.5 ± 7.9 months (range, 3-36) and 12.5 ± 8.2 months (range, 3-32), respectively (P = 0.799). The progression-free survival (PFS) of groups A and B was 9.4 months and 5.9 months (P < 0.01), respectively, and overall survival (OS) was significantly longer in group A (16.4 months vs 11.0 months, P < 0.01). In group A, the local response rate (LRR) and disease control rate (DCR) were 51.5% and 81.8%, respectively, which was higher than the corresponding 46.9% and 77.6% observed in group B (P = 0.233; 0.429). Patients with BCLC B stage had better PFS and OS (P < 0.05). The BCLC stage was an independent factor that affected PFS and OS. There were no massive bleeding or treatment-related deaths. In patients with unresectable multiple nodular and large HCC (single nodular diameter of >5 cm), TACE combined with target therapy and immunotherapy is safe and effective.

Tumor stiffness measurement using magnetic resonance elastography can predict recurrence and survival after curative resection of hepatocellular carcinoma

BackgroundTumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection. MethodsSeventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach. ResultsIn multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07–1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27–5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02–1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11–21.90; P < .001) than those with tumor stiffness <5.81 kPa. ConclusionPreoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.

Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients

Transarterial chemoembolization (TACE) is often used as a locoregional therapy for early hepatocellular carcinoma (HCC) when local ablation or resection are not feasible, but incomplete response and recurrence are commonly observed. In this study, we sought to determine the association between metformin administration and TACE outcomes for single nodular HCC in patients with type 2 diabetes mellitus (T2DM). The retrospective cohort analysis included 164 T2DM patients with single nodular HCC who underwent TACE as an initial treatment, and 91 were exposed to metformin before and after TACE. Propensity score (PS) matching was used to balance covariates. Logistic regression analysis was used to determine the predictors of tumor response after TACE, and Cox regression analysis assessed independent predictors of local tumor recurrence (LTR) in patients with complete response after TACE. Metformin use was associated with significantly higher objective response rate (ORR) in the overall and PS-matched cohort (79.1% vs. 60.3 and 78.7% vs. 57.5%; p = 0.008 and p = 0.029, respectively). Logistic regression analysis showed that metformin use was an independent predictor of ORR in all and PS-matched patients (odds ratio = 2.65 and 3.06; p = 0.016 and 0.034, respectively). Cox regression analysis showed metformin administration was an independent predictor for lower LTR in all and PS-matched patients (hazard ratio = 0.28 and 0.27; p = 0.001 and 0.007, respectively). Metformin administration is associated with better initial response and lower local recurrence after TACE for single nodular HCC in T2DM.

Prognostic Value of Repeat Hepatectomy for Hepatocellular Carcinoma Patients

Background/Aim: The potential for repeat hepatectomy has been increasing in hepatocellular carcinoma (HCC) patients. Patients and Methods: To assess its significance, we examined the clinical features, surgical records, and survival of 279 HCC patients who underwent hepatectomy as primary treatment. Patients were divided into three groups: single hepatectomy without HCC relapse in 97 patients (Group 1), single hepatectomy with HCC relapse in 133 patients (Group 2) and repeat hepatectomy for HCC relapse in 49 patients (Group 3). Group 3 was divided into three subgroups. Multiple, larger size (&gt;5 cm), and confluent nodular HCC. Results: Child–Pugh B patients were significantly higher in Group 2 (p&lt;0.01). The prevalence of histological vascular involvement was significantly higher in Group 2 than in the other groups (p&lt;0.01). Although Group 2 showed significantly poorer survival (p&lt;0.01), the 10-year overall survival in Groups 1 and 3 was over 70% but not different between groups. The relapse-free survival period was significantly correlated with overall survival, and patients with a cancer-free period of over 36 months showed significantly better 10-year survival rates than those with a period of less than 36 months (p&lt;0.01). Patients undergoing 3 or more repeat hepatectomies also showed good survival periods. Conclusion: Careful follow-up and proper decision-making in terms of repeat hepatectomy with multimodal treatments including novel chemotherapies upon assessment of postoperative tumor relapse are important in HCC patients to prolong survival.

MR Imaging Biomarkers for the Prediction of Outcome after Radiofrequency Ablation of Hepatocellular Carcinoma: Qualitative and Quantitative Assessments of the Liver Imaging Reporting and Data System and Radiomic Features

PurposeTo assess the Liver Imaging Reporting and Data System (LI-RADS) and radiomic features in pretreatment magnetic resonance (MR) imaging for predicting progression-free survival (PFS) in patients with nodular hepatocellular carcinoma (HCC) treated with radiofrequency (RF) ablation. Material and MethodsSixty-five therapy-naïve patients with 85 nodular HCC tumors <5 cm in size were included in this Health Insurance Portability and Accountability Act–compliant, institutional review board–approved, retrospective study. All patients underwent RF ablation as first-line treatment and demonstrated complete response on the first follow-up imaging. Gadolinium-enhanced MR imaging biomarkers were analyzed for LI-RADS features by 2 board-certified radiologists or by analysis of nodular and perinodular radiomic features from 3-dimensional segmentations. A radiomic signature was calculated with the most informative features of a least absolute shrinkage and selection operator Cox regression model using leave-one-out cross-validation. The association between both LI-RADS features and radiomic signatures with PFS was assessed via the Kaplan-Meier analysis and a weighted log-rank test. ResultsThe median PFS was 19 months (95% confidence interval, 16.1–19.4) for a follow-up period of 24 months. Multifocality (P = .033); the appearance of capsular continuity, compared with an absent or discontinuous capsule (P = .012); and a higher radiomic signature based on nodular and perinodular features (P = .030) were associated with poorer PFS in early-stage HCC. The observation size, presence of arterial hyperenhancement, nonperipheral washout, and appearance of an enhancing “capsule” were not associated with PFS (P > .05). ConclusionsAlthough multifocal HCC clearly indicates a more aggressive phenotype even in early-stage disease, the continuity of an enhancing capsule and a higher radiomic signature may add value as MR imaging biomarkers for poor PFS in HCC treated with RF ablation.

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

BackgroundEarly singular nodular hepatocellular carcinoma (HCC) is an ideal surgical indication in clinical practice. However, almost half of the patients have tumor recurrence, and there is no reliable prognostic prediction tool. Besides, it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it. It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus, to improve the outcomes of these patients. The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival (RFS) and overall survival (OS) in patients with singular nodular HCC by integrating the clinical data and radiological features. MethodsWe retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital (EHBH). They all met the surgical indications and underwent radical resection. We randomly divided the patients into the training cohort (n =132) and the validation cohort (n = 79). We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS. By analyzing the receiver operating characteristic (ROC) curve, the discrimination accuracy of the models was compared with that of the traditional predictive models. ResultsOur RFS model was based on HBV-DNA score, cirrhosis, tumor diameter and tumor capsule in imaging. RFS nomogram had fine calibration and discrimination capabilities, with a C-index of 0.74 (95% CI: 0.68-0.80). The OS nomogram, based on cirrhosis, tumor diameter and tumor capsule in imaging, had fine calibration and discrimination capabilities, with a C-index of 0.81 (95% CI: 0.74-0.87). The area under the receiver operating characteristic curve (AUC) of our model was larger than that of traditional liver cancer staging system, Korea model and Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma, indicating better discrimination capability. According to the models, we fitted the linear prediction equations. These results were validated in the validation cohort. ConclusionsCompared with previous radiography model, the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC. Our models may preoperatively identify patients with high risk of recurrence. These patients may benefit from neoadjuvant therapy which may improve the patients’ outcomes.

Comparison of the Value of Color Doppler Ultrasound and Multislice Spiral CT in the Differential Diagnosis of Benign and Malignant Nodules in the Liver.

Objective This study aimed to explore the value of color Doppler ultrasound and multislice spiral CT (MSCT) in the differential diagnosis of benign and malignant nodules in the liver. Methods The clinical imaging data of 102 patients with nodular hepatocellular carcinoma (hepatocellular carcinoma group) and 50 patients with focal nodular hyperplasia (FNH) of the liver (FNH group) admitted to our hospital were collected, and their color Doppler ultrasound and MSCT imaging features were retrospectively analyzed to explore the value of their clinical application in the differential diagnosis of benign and malignant nodules in the liver. Results The sensitivity, accuracy, and negative predictive value of MSCT in the diagnosis of nodular liver cancer were 94.12%, 92.76%, and 88.24%, respectively, which were significantly higher than those of color Doppler ultrasound 79.41%, 84.21%, and 69.12%, and the difference was statistically significant (P < 0.05). Conclusion In conclusion, the value of MSCT in the differential diagnosis of benign and malignant liver nodules was significantly better than color Doppler ultrasound.

Long-term outcome of percutaneous radiofrequency ablation for periportal hepatocellular carcinoma: tumor recurrence or progression, survival and clinical significance

Background/aimRecent studies have suggested that periportal location of percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered as one of the independent risk factors for local tumor progression (LTP). However, the long-term therapeutic outcomes of percutaneous RFA as the first-line therapy for single periportal HCCand corresponding impacts on tumor recurrence or progression are still unclear.Materials and methodsFrom February 2011 to October 2020, a total of 233 patients with single nodular HCC ≤ 5 cm who underwent RFA ± transarterial chemoembolization (TACE) as first-line therapy was enrolled and analyzed, including 56 patients in the periportal group and 177 patients in the nonperiportal group. The long-term therapeutic outcomes between the two groups were compared, risk factors of tumor recurrence or progression were evaluated.ResultsThe LTP rates at 1, 3, and 5 years were significantly higher in the periportal group than those in the nonperiportal group (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year overall survival (OS) rates in the periportal group were significantly worse than those in the nonperiportal group (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P<0.0001). In the subgroup of single HCC ≤ 3 cm, patients with periportal HCC showed significantly worse LTP P = 0.0006) and OS (P<0.0001) after RFA than patients with single nonperiportal HCC; The univariate and multivariate analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. Furthermore, patients with single periportal HCC had significantly higher risk for IDR(P = 0.0012), PVTT(P<0.0001) and extrahepatic recurrence(P = 0.0010) after RFA than those patients with single nonperiportal HCC. .ConclusionThe long-term therapeutic outcomes of RFA as the first-line therapy for single periportal HCC were worse than those for single nonperiportal HCC, an increased higher risk of tumor recurrence or progression after RFA was significantly associated with periportal HCC.

Prospect of lenvatinib for unresectable hepatocellular carcinoma in the new era of systemic chemotherapy.

The phase III clinical trial of the novel molecular targeted agent (MTA) lenvatinib for patients with advanced hepatocellular carcinoma (HCC) (REFLECT trial) found that lenvatinib was non-inferior to sorafenib in overall survival. Recently, the efficacy of multiple MTAs, including lenvatinib, in practice has been reported, and therapeutic strategies for Barcelona Clinic Liver Cancer (BCLC) intermediate stage HCC are undergoing major changes. Based on these results, lenvatinib could be recommended for patients with transcatheter arterial chemoembolization (TACE)-refractory, ALBI grade 1, within the up-to-seven criteria in the BCLC intermediate stage. Lenvatinib provides a more favorable outcome than TACE, even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A. When patients meet the definitions of TACE-refractory or TACE-unsuitable, switching to systemic chemotherapy, including lenvatinib, is for favorable for preserving liver function. If initial treatment, including MTA, has a significant therapeutic effect and downstaging of HCC is obtained, additional TACE or surgical resection should be considered. Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug. Furthermore, a significant therapeutic effect is expected in tumors with more than 50% liver involvement or main portal vein invasion, which have traditionally been considered to have a poor prognosis in patients. This suggests that at the start of lenvatinib treatment, HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.

Long-Term Outcomes of Transarterial Radioembolization for Large Single Hepatocellular Carcinoma: A Comparison to Resection

The surgical treatment for large hepatocellular carcinoma (HCC) remains controversial because of a high risk of recurrence after resection. This study aimed to compare long-term outcomes of transarterial radioembolization (TARE) with resection for patients with large HCC. Methods: This retrospective cohort study included 557 patients who were initially treated with either resection (n = 500) or TARE (n = 57) for large (≥5 cm), single nodular HCC at 2 tertiary centers in Korea. Patients with major portal vein tumor thrombosis or extrahepatic metastasis were excluded. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), time to intrahepatic progression (TTIP), and safety. Results: The resection group was younger (median, 60 vs. 69 y) and had a smaller tumor size (median, 7.0 vs. 10.0 cm) (all P < 0.05). After baseline characteristics were balanced using inverse-probability-of-treatment weighting, the OS (hazard ratio [HR], 0.98; 95% CI, 0.40-2.43; P = 0.97), TTP (HR, 1.10; 95% CI, 0.55-2.20; P = 0.80), and TTIP (HR, 1.45; 95% CI, 0.72-2.93; P = 0.30) of the TARE group was comparable to the resection group. TARE was not an independent risk for OS (adjusted HR, 1.04; 95% CI, 0.42-2.59; P = 0.93), TTP (adjusted HR, 0.98; 95% CI, 0.50-1.95; P = 0.96), or TTIP (adjusted HR, 1.30; 95% CI, 0.65-2.58; P = 0.46). The TARE group had a shorter hospital stay and fewer adverse events than the resection group. Conclusion: Compared with surgical resection for large single nodular HCC, TARE showed a comparable OS, TTP, and TTIP and a better safety profile.

Chemoembolization for Single Large Hepatocellular Carcinoma with Preserved Liver Function: Analysis of Factors Predicting Clinical Outcomes in a 302 Patient Cohort.

The purpose of this study was to define the role of transcatheter arterial chemoembolization (TACE) in patients with a single large hepatocellular carcinoma (HCC) and define the patient groups benefiting from TACE. Treatment-naïve patients with preserved liver function who received TACE as the first-line treatment for single large (>5 cm) HCC without macrovascular invasion and extrahepatic metastasis between 2007 and 2019 were retrospectively analyzed. Overall survival, progression-free survival, radiologic tumor response, complications, and predictors of survival were analyzed using multivariate analysis, and then a pretreatment risk-prediction model was created using the four predictive factors of tumor size, tumor type, ALBI grade, and ECOG performance status. Patients with scores of 0 (n = 54), 1–2 (n = 170), and 3–6 (n = 78) according to the model were classified as low-, intermediate-, and high-risk, respectively. The corresponding median OS values were 141, 55, and 28 months, respectively. The percentage of major complications increased as tumor size increased (4–21%). Asymptomatic, nodular HCC patients with a tumor size of 5–7 cm and ALBI grade 1 benefited the most from TACE. By contrast, the value of TACE in the treatment of single huge HCC (>10 cm) with high complication rates remains unclear.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma: Virtual Tumor Absorbed Dose as a Predictor of Complete Response.

To evaluate the impact of virtual tumor absorbed dose (vTAD) on tumor response in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 radioembolization. The institutional review board approved this retrospective single center study, which comprised 100 patients with nodular HCC who underwent yttrium-90 radioembolization between November 2015 and December 2019. The vTAD was calculated assuming that all infused microspheres were distributed only in the tumor. The ability of mean absorbed dose (mAD) and vTAD in predicting complete response were evaluated by receiver operating characteristic (ROC) curve analyses. The mAD was 263.9 Gy ± 125.8, and the mean vTAD was 2005.8 Gy ± 2348.9. In terms of tumor response, 63 patients had complete response, 25 partial response, and 12 stable disease. For predicting complete response, ROC curve analyses revealed that the area under the curve (AUC) value of the vTAD was significantly higher (p<0.001) than that of the mAD. Multivariate analysis revealed that Child-Pugh class A5, unilobar disease, and vTAD (>952 Gy) were significant factors in predicting complete response. High vTAD (>952 Gy) plays a significant role in complete response in patients with nodular HCC.

Incidence and Clinical Features of Hepatitis C Virus-associated Hepatocellular Carcinoma Patients without Liver Cirrhosis in Hepatitis B Virus-endemic Area.

Hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is rarely observed in patients without liver cirrhosis (LC). We evaluated the incidence and clinical feature of HCV-associated HCC patients with or without LC. The medical records of 1,516 patients diagnosed as having primary HCC at our hospital between January 2005 and December 2017 were retrospectively reviewed. Of these, 154 (10.2%) HCV-associated HCC patients were analyzed. LC was diagnosed histologically or clinically. Seventeen (11.0%) of the 154 patients had non-cirrhotic HCC, and all were of Child-Turcotte-Pugh (CTP) class A, Among the 17 patients, 88.2% were male, all had nodular type HCC, and only 2 (11.8%) were under HCC surveillance. Median overall survival (OS) of HCV-associated HCC patients with and without LC was 15 months and 37 months, respectively. Cumulative OS rates were not different between non-cirrhotic patients and cirrhotic patients with CTP class A (P=0.229). Cumulative OS rates were significantly higher in non-cirrhotic patients than in cirrhotic patients of CTP class B (P<0.001) or C (P<0.001). Multivariate analyses showed serum AST (hazard ratio [HR] 1.01, P=0.003) and AFP levels (HR 1.01, P=0.016), antiviral therapy (HR 0.25, P=0.022), and LC of CTP class B (HR, 5.24, P=0.006) or C (HR 21.79, P<0.001) were significantly associated with prognosis in HCV-associated HCC patients. HCC in a non-cirrhotic liver was found in 11% of HCV-associated HCC patients. OSs of HCV-associated HCC patients were better in those of CTP A, regardless of LC than in those with LC of CTP class B or C.

Laparoscopic Liver Resection versus Percutaneous Radiofrequency Ablation for Small Single Nodular Hepatocellular Carcinoma: Comparison of Treatment Outcomes

Background: Treatment outcomes of laparoscopic liver resection (LLR) and percutaneous radiofrequency ablation (p-RFA) for small single hepatocellular carcinomas (HCCs) have not yet been fully compared. The aim of this study was to compare LLR and p-RFA as first-line treatment options in patients with single nodular HCCs ≤3 cm. Methods: From January 2014 to December 2016, a total of 566 patients with single nodular HCC ≤3 cm treated by either LLR (n = 251) or p-RFA (n = 315) were included. The recurrence-free survival (RFS) and cumulative incidence of local tumor progression (LTP) were estimated using Kaplan-Meier methods and compared using the log-rank test. Treatment outcome of 2 treatment modalities was compared in the subgroup of patients according to the tumor location. Results: There were no significant differences in overall survival between LLR and p-RFA (p = 0.160); however, 3-year RFS was demonstrated to be significantly higher after LLR (74.4%) than after p-RFA (66.0%) (p = 0.013), owing to its significantly lower cumulative incidence of LTP (2.1% at 3 years after LLR vs. 10.0% after p-RFA, p < 0.001). The complication rate of p-RFA was significantly lower than that of LLR (5.1 vs. 10.0%, p = 0.026). LLR also provided significantly better local tumor control than p-RFA for subscapular tumors (3-year LTP rates: 1.9 vs. 8.8%, p = 0.012), perivascular tumors (3-year LTP rates: 0.0 vs. 17.2%, p = 0.007), and tumors located in anteroinfero-lateral liver portions (3-year LTP rates: 0.0 vs. 10.7%, p < 0.001). However, there were no significant differences in LTP rates between LLR and p-RFA for non-subcapsular and non-perivascular tumors (p = 0.482) and for tumors in postero-superior liver portions (p = 0.380). Conclusions: LLR can provide significantly better local tumor control than p-RFA for small single HCCs in subcapsular, perivascular, and anteroinferolateral liver portions and thus may be the preferred treatment option for these tumors.

Tumor Stiffness Measurements on MR Elastography for Single Nodular Hepatocellular Carcinomas Can Predict Tumor Recurrence After Hepatic Resection.

Tumor stiffness (TS), measured by magnetic resonance elastography (MRE), could be associated with tumor mechanical properties and tumor grade. To determine whether TS obtained using MRE is associated with survival in patients with single nodular hepatocellular carcinoma (HCC) after hepatic resection (HR). Retrospective. In all, 95 patients with pathologically confirmed HCCs. 1.5T/3D spin-echo echo-planar imaging MRE. TS values of the whole tumor (TS-WT) and of a solid portion of the tumor (TS-SP) after excluding the necrotic area were measured on stiffness maps. Known imaging prognostic factors of HCC were also analyzed. After surgery, pathologic findings were evaluated from resected pathology specimens. Fisher's exact test and the Mann-Whitney U-test were performed to determine the significance of differences according to the tumor grade. Overall survival (OS) / recurrence-free survival (RFS) analyses were performed using Kaplan-Meier analyses and Cox multivariable models. The average TS-WT was 2.14 ± 0.74 kPa, and the average TS-SP was 2.51 ± 1.07 kPa. The cumulative incidence of RFS was 73.1%, 63.1%, and 57.3% at 1, 3, and 5 years, respectively. The TS-WT, TS-SP, and tumor size (≥5 cm) were significant prognostic factors for RFS (P < 0.001; P < 0.001; P = 0.017, respectively). The estimated overall 1-, 3-, and 5-year survival rates were 95.7%, 86.9%, and 80.8%, respectively. The alpha-fetoprotein changes, platelets, tumor size (≥5 cm), and vascular invasion in pathology were significant predictive factors for overall survival (all P < 0.05). Tumor necrosis, TS-WT, TS-SP, and vascular invasion in pathology were significantly correlated with poorly differentiated HCC (all P < 0.05). The TS-WT, TW-SP, and tumor size (≥5 cm) were significant predictive factors of RFS after HR in patients with HCC. Level of Evidence Technical Efficacy Stage 5 J. MAGN. RESON. IMAGING 2021;53:587-596.

How Should We Assign Large Infiltrative Hepatocellular Carcinomas for Staging?

Simple SummaryThe outcome of hepatocellular carcinoma (HCC) patient varies depending on tumor burden and liver function. The BCLC staging system is based on these two factors while AJCC staging system is based on tumor burden only. However, the outcome of HCC does not solely depend on these two factors, but also the aggressiveness of tumor behavior represented by tumor morphology. The morphology of HCC can be divided into three types; nodular, multinodular confluent and infiltrative type. The infiltrative type is known to be associated with poor prognosis and should be staged differently from other tumors. This study revealed that large infiltrative type HCC (≥4 cm) was associated with worse survival especially in early AJCC T-stages (T1b/2) and BCLC stages (A/B). In addition, reassignment of large infiltrative tumor to T3 and T4 and to BCLC B and C increased the discriminatory ability of each staging system.Infiltrative gross morphology of hepatocellular carcinoma (HCC) is known to be associated with poor prognosis, but this is not considered for staging. A total of 774 HCC patients who underwent curative liver resection were retrospectively reviewed and the prognostic significance of infiltrative type HCC was assessed using the American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) staging systems. Seventy-four patients (9.6%) had infiltrative HCCs with a higher proportion of multifocal tumors, larger tumors, vessel invasion, increased tumor marker levels, and advanced T-stages than those with nodular HCC (all, p < 0.01). Infiltrative morphology was independently associated with lower overall survival (OS), but its impact was significant when the tumor size was ≥ 4 cm (p < 0.001). Under current AJCC and BCLC staging criteria, these large infiltrative HCCs were associated with significantly worse OS in early AJCC T-stages (T1b/T2, p < 0.001) and BCLC stage A/B (both, p < 0.01) but not in late AJCC (T3/T4) and BCLC C. The reassignment of this subtype to T3 and T4 increased the discriminatory ability of AJCC T-staging with lower AIC values (3090 and 3088 vs. 3109) and higher c-index (0.69 and 0.69 vs. 0.67), respectively (both, p < 0.001). Similarly, the reassignment of large infiltrative HCC to BCLC stages B and C also improved the prognostic performance. Large infiltrative HCCs should be assigned to more advanced stages in current staging systems for their prognostic impact.