Takashi Ikehara

Risk factors for the local recurrence of hepatocellular carcinoma after single-session percutaneous radiofrequency ablation with a single electrode insertion

Radiofrequency ablation (RFA) is a new local therapy for hepatocellular carcinoma (HCC). In this study, we investigated the risk factors associated with local recurrence of HCC after single-session RFA with a single electrode insertion. From April 2003 to December 2007, we treated 138 HCC lesions by single-session RFA with a single electrode insertion using the Cool-tip RFA, RTC 2000 and RTC 3000 Systems. Risk factors for the local recurrence of these lesions and complications after RFA were analyzed. The mean size of the 138 lesions was 16.9±5.4 mm in diameter (range 7-33 mm). Local recurrence rates were 6.6 and 22.0% at 1 and 2 years, respectively, during the mean follow-up period of 16.4 months. Univariate analysis showed that tumor diameter (≥20 mm), tumor location, pre-treatment AFP-L3 fraction level and ablation pattern were significant variables. Multivariate analysis of these four variables identified only the tumor diameter as an independent risk factor for local recurrence. Complications occurred in 2.2% of the lesions (3/138). Single-session RFA is an effective treatment for HCC in that it reduces serious complications. This study demonstrated that a tumor size ≥20 mm influenced the local recurrence of single-session RFA with a single electrode insertion.

Intracellular cytokine analysis of CD4-positive T cells predictive of sustained response to interferon therapy for patients with chronic hepatitis C.

We investigated whether the measurement of serum interleukin 18 (IL-18) and intracellular cytokine analysis of peripheral blood CD4-positive T cells (ICA-CD4+ Tc) of chronic hepatitis C (CH-C) patients before and two weeks after interferon (IFN) administration are useful for predicting sustained response to IFN. Twenty-nine CH-C patients received IFN every day for two weeks and three times a week for 22 weeks. Patients were divided into two groups: responders, in whom serum HCV-RNA was undetectable at the end of the follow-up (week 48), and nonresponders, in whom any other patterns were seen. Before and two weeks after IFN administration, serum IL-18 and ICA-CD4+ Tc as described by Jung et al were measured. Serum IL-18 and the relative prevalence of IFN-γ+ and IL-4+, IFN-γ+ and IL-4− (Th-1), and IFN-γ− and IL-4+ cells in the responders were significantly increased, but only the relative prevalence of Th-1 cells in the nonresponders was increased two weeks after IFN therapy. In conclusion, ICA-CD4+ Tc and the measurement of serum IL-18 might be useful for predicting IFN therapy by comparing the results between before and two weeks after IFN

Sustained complete response of hepatocellular carcinoma with portal vein tumor thrombus following discontinuation of sorafenib: A case report.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated mortality worldwide. No effective treatment has been established for unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi-targeted tyrosine kinase inhibitor for unresectable advanced HCC that significantly improves progression-free and overall survival. However, in the two large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of complete response (CR) were reported. The present study reports the case of a 68-year-old male with hepatitis C virus-related cirrhosis and multiple recurrent HCCs, with a tumor thrombus of the third portal vein following resection. The patient received 400 mg once daily (half the standard dose) of sorafenib for two years and achieved a CR. At the most recent follow-up examination at one year after the cessation of treatment, the patient was observed to be in remission without clinical or imaging evidence of disease recurrence.

Short-Term Effects and Early Complications of Balloon-Occluded Retrograde Transvenous Obliteration for Gastric Varices

The short-term effects of balloon-occluded retrograde transvenous obliteration (BRTO) to treat gastric varices were evaluated by using computed tomography (CT) and gastroscopy (GF). The subjects were 77 patients who underwent BRTO to treat gastric varices. The short-term effects of BRTO were investigated with regard to ascites, pleural effusion, venous thrombus, and esophageal varices by comparing the findings of CT and GF performed within one month before and after BRTO. The mean duration of followup was 960.1 days. Ascites and pleural effusion were exacerbated after BRTO in 26 (33.8%) and 31 (40.3%), respectively. A significant difference in ascites exacerbation was noted in patients with hypoalbuminemia and a high Child-Pugh score, and a significant difference in exacerbation of pleural effusion was noted in patients with hypoalbuminemia. Venous thrombus was noted in 7 patients (9.1%). Esophageal varices were exacerbated in 14 (21.2%) of the 66 patients. The 2-year survival rate was 720 days, and significant differences were noted in the Child-Pugh classification and the concomitance of hepatocellular carcinoma (HCC) on multivariate analysis of prognosis-related factors. Conclusion. The frequencies of exacerbation of ascites, pleural effusion, and esophageal varices after BRTO were high but these may not be related to survival.

Analysis of patients with tumor seeding after percutaneous radiofrequency ablation of hepatocellular carcinoma

To determine the incidence and risk factors associated with tumor seeding after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), 781 lesions from 352 patients who had undergone ultrasound (US)-guided RFA at our hospital between April 1999 and December 2005 were examined. Of these patients, 6 presented HCC lesions (6 lesions in total) and tumor seeding (7 seedings in total), which were analyzed. RFA using RITA 500 PA, the Cool-tip RFA System or the RTC 2000 System was performed. RFA sessions were repeated until complete necrosis was confirmed by imaging. Subsequently, follow-up was performed every 3-4 months by means of computed tomography (CT) and US scans. The 6 patients were retrospectively analyzed for patient characteristics, CT and histopathological findings, RFA method and complications, and clinical and imaging progress and outcome. Of the 6 lesions, 2 were in a subcapsular location at S7. Mean tumor diameter was 23.3±9 mm. Tumor biopsies indicated that 1 of the 6 lesions was well-differentiated, 4 were moderately-differentiated, and 1 was undifferentiated. The RITA 500 PA was used in 2 cases, and the Cool-tip RFA System in 4. Seeding was identified 14.6±13 months after RFA. Four of the cases with seeding were located on the abdominal wall, 2 on the thoracic wall and 1 in the Douglas pouch. Four of the patients underwent surgical resection, 1 radiation, and 1 conservative treatment for seeding. Five of the 6 patients died 12.6±9 months after seeding was detected, with the exception having undergone surgical treatment. The seeding risks identified in this study include treatment of subcapsular lesions and patient treatment over multiple sessions. The selection of the proper RFA system to avoid multiple sessions and the use of ablation technique are important for the prevention of seeding. Additionally, long-term follow-up after RFA by extensive imaging of the pelvic cavity and the thoracoabdominal wall is needed.

Comparison of percutaneous radiofrequency ablation and CyberKnife® for initial solitary hepatocellular carcinoma: A pilot study

AIM To compare therapeutic outcomes and adverse events in initial solitary hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and CyberKnife(®). METHODS Seventy three consecutive patients with initial solitary HCC treated with RFA (38 patients; RFA group) and CyberKnife(®) (35 patients; CK group) were enrolled in this study. Background factors were compared between the two groups. Local and intrahepatic distant recurrence control, and cumulative survival rates were compared between the two groups. These were determined using the Kaplan-Meier method, and the significance of differences was analyzed by log-rank test. The presence of more grade 3 on CTCAE ver. 4.0 early and late adverse events was investigated. RESULTS In background factors, age was significantly higher (P = 0.005) and the tumor diameter was significantly larger (P = 0.001) in the CK group. The 1-year local recurrence control rates were 97.4% and 97.1% in the RFA and CK groups, respectively (P = 0.71); the 1-year intrahepatic distant recurrence control rates were 85.6% and 86.1%, respectively (P = 0.91); and the 1-year cumulative survival rates were 100% and 95.2%, respectively (P = 0.075), showing no significant difference in any rate between the two groups. There were no late adverse event in the RFA group, but 11.4% in the CK group had late adverse events. In the CK group, the Child-Pugh score at 12 mo after treatment was significantly higher than that in the RFA group (P = 0.003) and significantly higher than the score before treatment (P = 0.034). CONCLUSION The occurrence of adverse events is a concern, but CyberKnife(®) treatment is likely to become an important option for local treatment of early HCC.

A Case of Sclerosing Angiomatoid Nodular Transformation of the Spleen: Correlations Between Contrast-enhanced Ultrasonography and Histopathologic Findings

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized benign vascular lesion of the spleen. Detection of SANT as an incidentaloma has increased due to improvements in imaging techniques. However, a definitive diagnosis of SANT on CT or MRI remains difficult. We report the use of contrast‐enhanced ultrasonography with Sonazoid in a case of SANT in a 50‐year‐old woman, with gross and microscopic pathologic correlations.

Arrival time parametric imaging using Sonazoid-enhanced ultrasonography is useful for the detection of spoke-wheel patterns of focal nodular hyperplasia smaller than 3 cm

It is considered difficult to make a definitive diagnosis of focal nodular hyperplasia (FNH) of <3 cm when using conventional diagnostic imaging modalities. Typical FNH imaging findings are: i) central scar formation, ii) nutrient vessels extending radially from the center and iii) the presence of Kupffer cells. In a clinical setting, identification of a spoke-wheel pattern formed by nutrient vessels extending radially is a key feature in the diagnosis of FNH. In this study, we investigated the detection rate of spoke-wheel patterns of FNH <3 cm using arrival time parametric imaging (At-PI) technology with Sonazoid-enhanced ultrasonography (US). Five patients with FNH <3 cm who had undergone Sonazoid-enhanced US at the Toho University Omori Medical Center between February 2008 and March 2009 were included in the study. The mean tumor diameter was 20.2±7.2 mm. Lesions were enhanced with 0.5 ml Sonazoid US contrast agent and a video of the procedure was saved and used for At-PI analysis of contrast agent dynamics in FNH. Three ultrasonographic specialists examined the images and made a diagnosis of FNH based on the findings of spoke-wheel patterns. Similarly, micro-flow imaging (MFI) was performed to evaluate the contrast agent dynamics in FNH. Using MFI, FNH was diagnosed in 3 of the 5 cases by the three specialists, whereas At-PI enabled the identification of spoke-wheel patterns in all 5 cases. At-PI using Sonazoid-enhanced US is superior for detecting spoke-wheel patterns of FNH <3 cm.

Characteristics of hepatic insulin‐sensitive nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high‐HIS, mid‐HIS, low‐HIS), as assessed by the hyperinsulinemic‐euglycemic clamp studies using stable isotope. Hepatic insulin sensitivity of the high‐HIS group was identical to that of the non‐NAFLD lean control (clamped percent suppression of endogenous glucose production, 91.1% ± 5.2% versus 91.0% ± 8.5%, respectively) and was significantly higher than that of the low‐HIS group (66.6% ± 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular lipid content), hepatic histopathology, and expression levels of various genes by using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma metabolites by metabolomics analysis, putative biomarkers, and lifestyles were assessed and compared between the high‐HIS and low‐HIS groups. Among these, adipose tissue insulin sensitivity assessed by clamped percent suppression of free fatty acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites, such as citric acid and cis‐aconitic acid, were significantly higher in the high‐HIS group compared to the low‐HIS group. In contrast, there were no differences in adiposity, including intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (28.3% ± 16.1% versus 20.4% ± 9.9%, respectively), hepatic histopathology, other putative biomarkers, and lifestyles. Conclusion: High levels of adipose tissue insulin sensitivity, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are unique characteristics that define patients with hepatic insulin‐sensitive NAFLD regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634–647)

Evaluation of Hemodynamics in Focal Steatosis and Focal Spared Lesion of the Liver Using Contrast-Enhanced Ultrasonography with Sonazoid

We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyperenhancement, isoenhancement, and hypoenhancement) in the vascular phase and the presence or absence of a hypoechoic area in the postvascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was isoenhancement in 19 and hypoenhancement in 5. Hypoechoic areas were noted in the postvascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was isoenhancement in 18 and hyperenhancement in 5. No hypoechoic areas were noted in the postvascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in nondiffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.