Yoshitaka Takuma

Measurement of Spleen Stiffness by Acoustic Radiation Force Impulse Imaging Identifies Cirrhotic Patients With Esophageal Varices

BACKGROUND & AIMS We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination. METHODS In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices. RESULTS Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%). CONCLUSIONS Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.

Clinical trial: oral zinc in hepatic encephalopathy

Aliment Pharmacol Ther 2010; 32: 1080–1090

Prophylactic balloon-occluded retrograde transvenous obliteration for gastric varices in compensated cirrhosis.

BACKGROUND & AIMS Because gastric variceal bleeding is associated with a high mortality rate, its prophylaxis is expected to improve survival. We investigated the effectiveness of balloon-occluded retrograde transvenous obliteration (B-RTO) for the treatment of gastric fundal varices. METHODS A prospective nonrandomized study was conducted. Prophylactic B-RTO was performed in 17 patients (B-RTO group), whereas the remaining 17 patients received no specific treatment (control). The nonbleeding rate, cumulative survival rate, and prognostic values of the patients were assessed. RESULTS The respective nonbleeding rates at 1, 3, and 5 years were 100%, 100%, and 83% in the B-RTO group and 81%, 59%, and 39% in the control. The respective cumulative survival rates at 1, 3, and 5 years were 94%, 85%, and 39% in the B-RTO group and 71%, 41%, and 22% in the control. Both the nonbleeding rate and the cumulative survival rate of the B-RTO group were significantly higher than those of the control (P = .01 and .04, respectively). B-RTO was determined by multivariate analysis to be a significant factor for low bleeding rate (relative risk, 0.06; 95% confidence interval [CI], 0.004-0.79), whereas B-RTO (0.11; 95% CI, 0.03-0.44) and Child-Pugh class A (0.10; 95% CI, 0.03-0.39) were the significant factors for a low mortality rate, and the presence of hepatocellular carcinoma (5.68; 95% CI, 1.49-21.7) was the significant factor for a high mortality rate. CONCLUSIONS Prophylactic B-RTO is effective in preventing gastric variceal rupture and consequently improves patient survival.

Comparison of Combined Transcatheter Arterial Chemoembolization and Radiofrequency Ablation with Surgical Resection by Using Propensity Score Matching in Patients with Hepatocellular Carcinoma within Milan Criteria

PURPOSE To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching. RESULTS After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively). CONCLUSION TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible.

Portal Hypertension in Patients with Liver Cirrhosis: Diagnostic Accuracy of Spleen Stiffness.

PURPOSE To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of β-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. RESULTS The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). CONCLUSION SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis.

Telomerase reverse transcriptase gene amplification in hepatocellular carcinoma.

Background and Aim:  Telomerase activation is essential for the immortality of cancer cells. The expression of telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex, regulates telomerase activity in human cancers. Amplification of the hTERT gene, located at chromosome 5p, is thought to be a potential genetic event contributing to telomerase activation in sporadic tumors.

Hepatic steatosis correlates with the postoperative recurrence of hepatitis C virus‐associated hepatocellular carcinoma

Background: Hepatic steatosis is a prominent feature of chronic hepatitis C. Hepatic steatosis was reported recently to be a risk factor for hepatitis C virus (HCV)‐associated hepatocellular carcinoma (HCC).

Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria.

Background and Aim:  The prognosis of cryptogenic cirrhosis‐associated hepatocellular carcinoma (CC‐HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC‐HCC.

Real-time image fusion for successful percutaneous radiofrequency ablation of hepatocellular carcinoma.

Percutaneous radiofrequency ablation (RFA) is an established nonsurgical curative treatment for hepatocellular carcinoma (HCC). Because of its efficiency and safety, sonography is the most commonly used imaging modality when performing RFA. However, the presence of HCC nodules that are inconspicuous when using conventional sonography is a major drawback of RFA and limits its feasibility as a treatment for HCC. However, a new technology has been developed that synthesizes high‐resolution multiplanar reconstruction images using 3‐dimensional data and is combined with a position‐tracking system using magnetic navigation. With this technology, real‐time sonograms can be fused with corresponding computed tomographic, magnetic resonance imaging, or even sonographic volume data; this process is known as real‐time image fusion. In this article, we describe this novel imaging method as a useful tool for successful RFA treatment of HCC.

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21–2.81), and OS (HR, 1.95; 95% CI, 1.21–3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30–3.06) and OS (HR, 1.94; 95% CI, 1.19–3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.