Strategy for advanced hepatocellular carcinoma based on liver function and portal vein tumor thrombosis.

AIM: Tyrosine kinase inhibitor (TKI) therapy resulted in better prognosis for patients with hepatocellular carcinoma (HCC). However, some cases with Barcelona Clinic Liver Cancer (BCLC) stage C disease still had poor prognosis. This study aimed to investigate prognosis and characteristics of patients with HCC treated with TKI based on liver function and the extent of portal vein tumor thrombosis (PVTT). METHODS: Patients receiving TKI therapy (n = 345) were recruited retrospectively. Child-Pugh score and albumin-bilirubin (ALBI) score were used for assessment of liver function. The extent of PVTT was classified from Vp0 to Vp4. Radiotherapy or hepatic arterial infusion chemotherapy were carried out as additional therapy to TKI. The end-point for this analysis was overall survival (OS). RESULTS: A total of 291 and 54 patients received sorafenib and lenvatinib as first-line TKI therapy, respectively. The median OS of patients treated with TKI were significantly stratified by ALBI grade (grade 1, 20.1 months; grade 2a, 16.3 months; grades 2b and 3, 9.8 months; P = 0.0003). The classification of PVTT significantly stratified the prognosis of patients treated with TKI (median OS: Vp0, 18.5 months; Vp1/2, 14.4 months; Vp3/4, 5.5 months; P < 0.0001). In the ALBI 2b/3 and Vp3/4 groups, the median OS of patients treated with TKI and additional therapies was significantly longer than those treated with TKI only (9.2 months vs.. 3.6 months; P = 0.0129). CONCLUSION: Liver function and PVTT are useful for stratifying prognosis of HCC patients treated with TKI. The applicative classification could lead to appropriate therapy and better prognosis.

Three criteria for radiological response on survival in patients with hepatocellular carcinoma treated with lenvatinib.

AIM: Lenvatinib (LEN) is a newly approved, multikinase inhibitor for treating unresectable hepatocellular carcinoma. In the present study, we investigated the impact of three different criteria for evaluating radiological objective response (OR) on overall survival in real-world data. METHODS: Consent for LEN therapy was obtained from 51 patients from April 2018 to March 2019. A total of 40 patients who received a minimal cumulative duration of 4 weeks of LEN were included in the analysis. Enhanced computed tomography scan was performed at baseline and every 4-8 weeks after LEN administration. Overall survival and OR were assessed with three different evaluations, as follows: Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria. RESULTS: The average observation period for all participants after LEN introduction was 209.4 ± 77.5 days. The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria identified 10 of 40 (25.0%), 15 of 40 (37.5%), and 18of 40 (45.0%) patients with OR, respectively. The median overall survival in progressive disease evaluated by each criterion was 227 days. This result was significantly shorter than OR. Furthermore, the cumulative duration of LEN administration (>150 days) represented a significant prognostic factor (HR 0.160. 95% CI 0.039-0.646, P = 0.001). CONCLUSION: The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria were useful therapeutic evaluation methods in LEN therapy for unresectable hepatocellular carcinoma. LEN's appropriate effect evaluation and management might lead to a better prognosis.

Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after initial conventional transarterial chemoembolization.

AIM: Intermediate-stage hepatocellular carcinoma varies widely in tumor burden and liver function. This study aimed to clarify the importance of subclassification by the up-to-seven criteria in both clinical course and liver function deterioration in such patients. METHODS: We retrospectively analyzed 224 patients with Child-Pugh grade A who underwent initial transarterial chemoembolization (TACE) for hepatocellular carcinoma. Tumor downstaging to within the Milan criteria within 1 year and liver function worsening as Child-Pugh grade deterioration from A to B were analyzed. RESULTS: The median survival time was 35.8 months. Forty-five patients had no recurrence within 1 year after initial TACE. Of the 179 patients with at least one recurrence within a year, 44 (25%) achieved tumor downstaging to within the Milan criteria and showed significantly longer survival than non-downstaged ones (P = 0.02). Logistic regression univariate analysis revealed that up-to-seven criteria fulfillment was associated with tumor downstaging to within the Milan criteria (odds ratio 2.6; P = 0.007). The median deterioration time was 26.7 months. Multivariate analysis revealed that beyond the up-to-seven criteria (hazard ratio [HR] 1.9; P = 0.005) was an independent factor associated with Child-Pugh grade deterioration, along with serum albumin (HR 1.54; P = 0.01), serum bilirubin (HR 1.49; P = 0.02), and prothrombin time (HR 1.54; P = 0.04). CONCLUSIONS: The up-to-seven criteria had prognostic value and could predict non-critical recurrence and maintenance of Child-Pugh grade in patients who underwent initial conventional TACE.

Early radiological response evaluation with response evaluation criteria in solid tumors 1.1 stratifies survival in hepatocellular carcinoma patients treated with lenvatinib.

BACKGROUND AND AIM: Lenvatinib (LEN) has an antitumor effect with an early reduction in contrast enhancement for unresectable hepatocellular carcinoma (HCC). The aim of this study was to reveal the most useful radiological response evaluation for overall survival (OS) in patients treated with LEN. METHODS: Patients receiving LEN therapy (n = 80) were retrospectively recruited from April 2018 to January 2020. Enhanced computed tomography scans were performed at baseline and every 4-8 weeks. OS and radiological response were evaluated using response evaluation criteria in solid tumors (RECIST 1.1), modified RECIST (mRECIST), and Choi criteria. To be eligible for study, a minimal cumulative duration of LEN was 4 weeks. A total of 62 patients were included in the analysis. RESULTS: The median OS was 469 days. The RECIST 1.1, mRECIST, and Choi criteria identified 14 (22.5%), 30 (48.3%), and 33 (53.2%) patients with an objective response, respectively. In the univariate analysis, Child-Pugh class B, major vascular invasion, and high alpha-fetoprotein (>200) were statistically significant poor prognostic factors. Radiological response was a significantly better prognostic factor in each criterion (RECIST, mRECIST, and Choi). In the multivariate analysis, radiological response evaluated by RECIST (hazard ratio, 0.259; 95% confidence interval, 0.0723-0.928; P = 0.038) was an independent factor. Furthermore, only RECIST significantly stratified prognosis (P = 0.041) when limited to the first evaluation. CONCLUSION: RECIST 1.1 was useful even as early therapeutic evaluation for HCC patients treated with LEN. Understanding the characteristics of radiological response over time may contribute to improving the prognosis of patients with HCC.

Prediction of histological grade of hepatocellular carcinoma using quantitative diffusion-weighted MRI: a retrospective multivendor study.

OBJECTIVE: To evaluate the usefulness of quantitative diffusion-weighted (DW) imaging acquired by multivendor magnetic resonance units for predicting grade of hepatocellular carcinoma (HCC). METHODS: 83 patients with 100 histologically diagnosed HCCs who underwent pre-operative liver DW imaging with b = 0 and1000 s mm-2 or b = 0 and800 s mm-2 at any of six institutions were included. Two radiologists independently measured the apparent diffusion coefficient (ADC) of the lesion as well as non-ADC parameters, such as the relative contrast ratio and the contrast-to-noise ratio (CNR) between the lesion and the liver parenchyma on high b-value DW images. The diagnostic performance of the DW parameters in discriminating poorly-differentiated HCCs was compared using receiver operating characteristic (ROC) analysis. RESULTS: The areas under the receiver operating characteristic curves for the CNR (86.4% [95% confidence interval (CI) (77.2-95.6] and 83.9% [95% CI 71.2-96.6] for b = 1000 and 800 s mm-2, respectively] and the relative contrast ratio (85.3% [95% CI 75.5-94.8] and 83.5% [95% CI 70.5-96.4]) tended to be superior to the ADC [71.1% [95% CI (56.9-85.2)] and 75.7% [95% CI (55.1-96.2)]; p < 0.05 for CNR vs ADC for b = 1000 s mm-2, but not significant for other parameters) for discrimination of poorly-differentiated HCCs. CONCLUSION: All DW parameters could discriminate HCC grade. Non-ADC parameters might be more useful than the ADC for predicting poorly-differentiated HCCs. Advances in knowledge: The utility of quantitative DW parameters for predicting HCC grade was demonstrated by using multivendor MR units.

Assessment of Kupffer cells by ferumoxides-enhanced MR imaging is beneficial for diagnosis of hepatocellular carcinoma: comparison of pathological diagnosis and perfusion patterns assessed by CT hepatic arteriography and CT arterioportography.

To investigate the clinical significance of the radiographic assessment of Kupffer cells and hemodynamics in the diagnosis of hepatocellular nodules, both magnetic resonance (MR) imaging enhanced by ferumoxides and CT hepatic arteriography (CTHA)/CT arterioportography (CTAP) were undertaken for 118 patients with 158 primary nodular hepatocellular lesions. The radiographic findings were analyzed in the context of the pathological diagnosis. Among nodules presumed to be pre- or early HCC by CTHA/CTAP, all 13 hyperintense nodules identified by MR imaging (MRI) were found pathologically to be hepatocellular carcinoma (HCC). In contrast, in 14 hypointense nodules, no advanced (moderately or poorly differentiated) HCC was pathologically identified and none of these progressed to advanced HCC during the follow up period (mean: 24 months). Instead, 78% of these cases were pathologically confirmed as dysplastic nodules. For the 16 lesions undetectable by CTHA/CTAP, four of eight (50%) hypointense nodules turned out to be dysplastic nodules and one hyperintense lesion was HCC. Signal intensity by ferumoxides-enhanced MRI showed a strong correlation with the increase or decrease of Kupffer cells assessed by immunohistochemistry. Assessment of Kupffer cells by ferumoxides-enhanced MRI is beneficial for the accurate diagnosis of primary hepatocellular nodules that are considered borderline or early stage HCC by their hemodynamic profile.

A case of primary leiomyoma of the liver in a patient without evidence of immunosuppression.

A 31-year-old Japanese male was admitted to our hospital for investigation of an asymptomatic nodular lesion of the liver detected by abdominal ultrasonography (US) during a routine medical examination. Computed tomography (CT) revealed a single, hypovascular mass 35 mm in diameter, within the left lobe of the liver. The tumor demonstrated hypointensity on T1-weighted, and hyperintensity on T2-weighted magnetic resonance (MR) imaging. Hematological and biochemical investigations were normal. There were no abnormalities of the gastrointestinal or urinary tracts. A left lateral segmentectomy of the liver was performed. Pathological examination of the nodule revealed a primary leiomyoma of the liver, with positive immunohistochemical staining for vimentin and desmin antigens. Primary leiomyoma of the liver is rare, with the majority of cases associated with immunodeficiency disorders. This patient had no evidence of any underlying disease. Primary leiomyoma of the liver should be considered when a nodular lesion is found in a patient without evidence of viral hepatitis.

A case with primary aldosteronism due to unilateral multiple adrenocortical micronodules.

A 46-year-old male with long-term treatment-resistant hypertension and past history of cerebral hemorrhage was found to have suppressed plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) with aldosterone/renin ratio of 25.3. Furosemide plus upright test did not stimulate PRA, but computed tomography scan of the abdomen revealed no abnormal lesions in either adrenal gland. Selective adrenal venous sampling (SAVS) showed that PAC in the left and the right adrenal vein were 1000 ng/dl and 230 ng/dl, respectively, which increased to 1500 ng/dl and 620 ng/dl, respectively, after ACTH stimulation. Diagnosis of primary aldosteronism due to hypersecretion of aldosterone from the left adrenal gland was made, and laparoscopic left adrenalectomy was performed. Pathological examination of the 'apparently normal' adrenal tissue resected revealed the presence of poorly encapsulated multiple adrenocortical micronodules which showed positive immunoreactivity for 3beta-hydroxysteroid dehydrogenase by immunohistochemical study, but negative immunoreactivity in the hyperplastic zona glomerulosa consistent with paradoxical hyperplasia associated with primary aldosteronism. Postoperatively, PRA was normalized and his high blood pressure was well controlled with lower doses of antihypertensive drugs than those used before surgery. The clinicopathological features of our case are consistent with the diagnosis of unilateral multiple adrenocortical micronodules (UMN), a new subset of primary aldosteronism, in which SAVS proved to be a useful diagnostic tool for its localization.

Computed tomography-guided transarterial chemoembolization as the initial therapy for hepatocellular carcinoma: experience of 75 cases in a single institute.

We present the survival rates of 75 nonruptured hepatocellular carcinoma cases initially treated with computed tomography-guided transarterial chemoembolization in a single institute. The 1-, 3-, and 5-year survival rates were 93.9%, 74.7%, and 47.4% in 50 Child's A cases; 75.0%, 43.6%, and 6.8% in 20 Child's B cases; and 60.0%, 40.0%, 0.0% in 5 Child's C cases, respectively. The 1-, 3-, and 5-year survival rates of the 38 estimated resectable hepatocellular carcinoma cases (Child's A, tumors limited in a single lobe) were 94.7%, 82.0%, and 44.6%, respectively. The 1-, 3-, and 5-year survival rates of the 41 cases with estimated indication for percutaneous ethanol injection therapy (tumors less than 3 cm in diameter and three or fewer in number) were 96.8%, 84.6%, and 55.5% in 31 Child's A cases; and 90.0%, 46.7%, and 0% in 10 Child's B cases, respectively. In conclusion, computed tomography-guided transarterial chemoembolization is an excellent primary therapy for hepatocellular carcinoma.