Contralaterally-controlled functional electrical stimulation-induced muscle contraction for severe lower extremity paralysis.

[Purpose] We describe a new method of functional electrical stimulation therapy for severe hemiparesis. Conventional functional electrical stimulation of the lower legs has limited applications. It is only suitable for patients who can monitor their muscle contractions, and it has complicated equipment installation procedures. [Participant and Methods] The participant was a male in his 40s with severe motor paralysis following brain surgery. We monitored the participant's healthy side using the external assist mode of an Integrated Volitional Control Electrical Stimulation (IVES® OG Giken, Okayama, Japan) system while forcibly contracting the paralyzed side. The participant received this new functional electrical stimulation therapy five times per week. [Results] Two weeks after initiation of therapy, paralysis was noticeably improved, and motor function was maintained for approximately 1 year. [Conclusion] The outcomes of this case suggest that the addition of forced contraction therapy, mirror therapy, and repetitive exercise therapy to regular physical therapy may be beneficial. This treatment method may also be useful in postoperative patients with central motor palsy and no muscle contraction ability.

Safety and efficacy of the endoscopic delivery of capsule endoscopes in adult and pediatric patients: Multicenter Japanese study (AdvanCE-J study).

BACKGROUND AND AIM: We retrospectively determined the safety and efficacy of the endoscopic delivery (ED) of capsule endoscopes. METHODS: We enrolled 10,156 patients who underwent small bowel capsule endoscopy (SBCE), 3182 who underwent patency capsule (PC), and 1367 who underwent colon capsule endoscopy (CCE), at 11 gastroenterological and nine pediatric centers. RESULTS: Small bowel capsule endoscopies, PCs, and CCEs were endoscopically delivered to 546 (5.4%), 214 (6.7%), and 14 (1.0%) patients, respectively. Only mild complications occurred for 21.6% (167/774), including uneventful mucosal damage, bleeding, and abdominal pain. Successful ED of SBCE to the duodenum or jejunum occurred in 91.8% and 90.7% of patients aged <16 years and ≥16 years, respectively (P = 0.6661), but the total enteroscopy rate was higher in the first group (91.7%) than in the second (76.2%, P < 0.0001), for whom impossible ingestion (87.3%) was significantly more common than prolonged lodging in the stomach (64.2%, P = 0.0010). Successful PC and CCE delivery to the duodenum occurred in 84.1% and 28.6%, thereafter the patency confirmation rate and total colonoscopy rate was 100% and 61.5%, respectively. The height, weight, and age cutoff points in predicting spontaneous ingestion were 132 cm, 24.8 kg, and 9 years 2 months, respectively, in patients aged <16 years. Patients aged ≥16 years could not swallow the SBCEs mainly due to dysphagia (75.0%); those who retained it in the esophagus due to cardiac disease (28.6%), etc. and in the stomach due to diabetes mellitus (15.7%), etc. CONCLUSIONS: This large-scale study supports the safety and efficacy of ED in adult and pediatric patients. UMIN000042020.

Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study.

INTRODUCTION: Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions. RESULTS: The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child-Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5-13). The albumin-bilirubin (ALBI) score ranged from - 3.01 to - 0.45 (median - 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child-Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child-Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10-4 and 2.42 × 10-4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively. CONCLUSION: Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications. TRIAL REGISTRATION: UMIN registration no, 000038587.

Clinical Factors Associated with Missing Colorectal Polyp on Colon Capsule Endoscopy.

BACKGROUND: There are a number of reports that demonstrate the high diagnostic accuracy of colon capsule endoscopy (CCE) for polyp detection. However, some colorectal polyps are missed on CCE, and the clinical factors influencing those missed polyps are still unknown. OBJECTIVE: The aim of this study was to elucidate the clinical factors related to missing colorectal polyp on CCE by using per-polyp analysis. METHODS: We performed a retrospective multi-center study of 53 consecutive patients who underwent both CCE and colonoscopy (CS) within 3 months from January 2014 to -December 2017. Of those patients, we analyzed 151 polyps detected on CCE, and 149 polyps detected on CS diagnosed as neoplasm according to histopathological result. RESULTS: The capsule excretion rate was 81%. One hundred three polyps were detected on both CS and CCE, 46 polyps (31%) were missed on CCE, and 48 polyps were considered false positive on CCE when CS result was considered as the gold standard. Per-polyp sensitivity and positive predictive value on CCE were 69.1 and 68%. On multiple logistic analysis, only the segmental transit time on CCE was identified as the independent factor influencing missed polyp on CCE. CONCLUSIONS: The clinical factor related to missing colorectal polyp on CCE was the segmental transit time.

Multicenter feasibility study of bowel preparation with castor oil for colon capsule endoscopy.

BACKGROUND AND AIM: Extensive use of laxatives and incomplete excretion rates are problematic for colon capsule endoscopy (CCE). The aim of the present study was to determine the effectiveness of castor oil as a booster. METHODS: At four Japanese hospitals, 319 examinees undergoing CCE were enrolled retrospectively. Before and after the introduction of castor oil, other preparation reagents were unchanged. RESULTS: Of 319 examinees who underwent CCE, 152 and 167 examinees took regimens with castor oil (between November 2013 and June 2016) and without castor oil (between October 2015 and September 2017), respectively. Capsule excretion rates within its battery life in the groups with and without castor oil were 97% and 81%, respectively (P < 0.0001). Multivariate analysis showed that ages younger than 65 years (adjusted odds ratio [OR], 3.00; P = 0.0048), male gender (adjusted OR, 3.20; P = 0.0051), and use of castor oil (adjusted OR, 6.29; P = 0.0003) were predictors of capsule excretion within its battery life. Small bowel transit time was shorter and total volume of lavage and fluid intake was lower with castor oil than without (P = 0.0154 and 0.0013, respectively). Overall adequate cleansing level ratios with and without castor oil were 74% and 83%, respectively (P = 0.0713). Per-examinee sensitivity for polyps ≥6 mm with and without castor oil was 83% and 85%, respectively, with specificities of 80% and 78%, respectively. CONCLUSION: Bowel preparation with castor oil was effective for improving capsule excretion rate and reducing liquid loading.

Usefulness of Real-Time 4D Ultrasonography during Radiofrequency Ablation in a Case of Hepatocellular Carcinoma.

We report a case of hepatocellular carcinoma (HCC) with chronic hepatitis C virus infection successfully treated with percutaneous radiofrequency ablation (RFA) under live four-dimensional (4D) echo guidance. A 65-year-old Japanese man had a HCC nodule in the liver S5 region 2.0 cm in diameter. We performed real-time 4D ultrasonography during RFA therapy with a LeVeen needle electrode. The echo guidance facilitated an accurate approach for the needle puncture. The guidance was also useful for confirming whether an adequate safety margin for the nodule had been obtained. Thus real-time 4D ultrasonography echo technique appears to provide safe guidance of RFA needles via accurate targeting of HCC nodules, thereby allowing real-time visualization when combined with echo contrast. Furthermore the position of the needle in a still image was confirmed in every area using a multiview procedure.

Usefulness of radiofrequency ablation with micro-convex probe for hepatocellular carcinoma.

BACKGROUND/AIMS: It was aimed to assess whether a micro-convex probe is superior to the present conventional probe for ultrasonography from the points of safety and efficacy during percutaneous radiofrequency ablation therapy for hepatocellular carcinoma. METHODOLOGY: Twenty-one patients with 23 hepatocellular carcinoma lesions who had one or 2 lesions, each 4 cm or less in diameter, and liver function of Child-Pugh class A or B were enrolled. All the patients except for 2 patients were seropositive for hepatitis C virus. Radiofrequency ablation was carried out under a real-time US guidance. The cooled-tip electrodes used were single and clustered. RESULTS: It was possible to perform safe and accurate percutaneous radiofrequency ablation procedure using micro-convex probes for the treatment of all hepatocellular carcinoma nodules. It was also possible to treat hepatocellular carcinoma located in the right subphrenic region without artificial pleural effusion under intercostal ultrasonography guide. Improved clustered needles were successfully applied to treat the nodules more than 3 cm in diameter with less resistance for penetration compared with the conventional needle. The findings of advanced dynamic flow image on ultrasonography to assess the therapeutic efficacy indicated the consistency with those of dynamic CT which was done 3 to 5 days later radiofrequency ablation. Major complication of radiofrequency ablation procedure was noted in none. CONCLUSIONS: These results suggest that micro-convex probe with clustered tips is superior to conventional probe for ultrasonography from the points of safety and efficacy during radiofrequency ablation for hepatocellular carcinoma nodule located in the right subphrenic region and for larger sized nodule more than 3 cm.

Hepatocellular Carcinoma 11 and a Half Years after the Resolution of Chronic Hepatitis C Virus Infection Successfully Treated with Interferon.

A 41-year-old Japanese man had received successful interferon (IFN) therapy against chronic hepatitis C in 1994. Since then, serum hepatitis C virus (HCV) RNA had been negative, and aminotransferase levels had been continuously normal. He had abstained from alcohol. However, his serum aminotransferase levels showed slight elevation as his body weight increased gradually. He was diagnosed as having fatty liver and diabetes mellitus. In January 2006, 11 and a half years after the resolution of HCV infection, he was found to have a hepatic nodule 4.0 cm in diameter at liver S4/8 region by plain abdominal CT at an annual follow-up examination. He was diagnosed as having hepatocellular carcinoma (HCC) by angiography. The tumor was curatively resected and its histological diagnosis was moderately differentiated HCC. Noncancerous lesion of the liver revealed fibrosis of stage F2 and mild inflammation of grade A1 with mild steatosis. This case suggests that all patients with chronic HCV infection should be followed as long as possible for the potential development of HCC even after clearance of the virus.

Deficiency of forkhead box P3 and cytotoxic T-lymphocyte-associated antigen-4 gene expressions and impaired suppressor function of CD4(+)CD25(+) T cells in patients with autoimmune hepatitis.

AIM: Recently, forkhead box P3 (Foxp3), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR), and CD28 were identified as the key molecules that control the development and activation of CD4+CD25+ regulatory T cells (T-reg). We investigated the expression pattern of these molecules on T-reg, and investigated the ability of T-reg to produce cytokines in patients with autoimmune hepatitis (AIH). METHODS: Fifteen patients with AIH and nine healthy patients were included. To determine the frequency of T-reg, a two-color flow cytometry analysis was performed. T-reg were isolated using immunomagnetic beads, and the mRNA levels of Foxp3, CTLA-4, GITR, and CD28 were quantified by real-time polymerase chain reaction (PCR). The ability of T-reg to produce interferon-gamma, interleukin (IL)-10, transforming growth factor-beta, and tumor necrosis factor-alpha after stimulation by OKT3 was evaluated by measuring the levels of mRNA in T-reg by real-time PCR. RESULTS: The frequency of T-reg was increased in AIH. The mRNA levels of Foxp3 and CTLA-4 were significantly lower in AIH. The ability of T-reg to produce IL-10 was impaired in AIH. CONCLUSION: We speculate that the inferiority of the Foxp3 and CTLA-4 gene expressions on T-reg results in the impaired suppressor function of T-reg, and eventually in the breakdown of self-tolerance.

Expression of Toll-like receptors in chronic hepatitis C virus infection.

BACKGROUND: Toll-like receptors (TLRs) are involved in innate immunity. Certain viruses interact with TLRs and mediate antiviral effects as well as immune responses. The aim of this study was to investigate the effect of TLRs on pathogenesis in hepatitis C virus (HCV)-infected patients. METHODS: Peripheral blood mononuclear cells (PBMC) and CD14+ (monocytes) or CD14- cells from 25 patients with chronic liver disease and 15 healthy subjects were studied for expression of TLRs 2-9 and cytokines of extracted RNA using real-time PCR. Then TLR expression was examined in HepG2 cells transfected with entire or parts (core-NS3, NS3-NS5B) of the HCV open reading frame. TLR expression was calculated as the relative mRNA levels. RESULTS: Expression of TLRs 4, 7 and 8 in CD14+ cells of PBMC was increased in patients. Levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12 p35 for PBMC were also increased in patients. When PBMC were incubated with HCV core protein, enhancement of TLR2 expression and suppression of TLR4 and TLR7 were noted in patients. Similar alteration of TLRs expression was observed in controls. Among HepG2 transfectants, only TLR3 expression was changed; it was suppressed in entire gene transfectant and enhanced in core-NS3 transfectant. Expression of some proteins related to the TLR signaling pathway was suppressed in the entire gene transfectant. CONCLUSIONS: The results suggest a correlation between expression levels of TLRs and cytokines, and chronic HCV infection. TLR3 recognizes double-stranded RNA and induces type 1 interferon synthesis. Collectively, suppressed expression of TLR3 in cells transfected with entire HCV may be responsible for continuous HCV infection, although a part of the HCV gene enhances its expression.

Usefulness of live 3D echocardiography during radiofrequency ablation in a case of hepatocellular carcinoma.

We report a case of hepatocellular carcinoma (HCC) with chronic hepatitis C virus (HCV) infection, which was successfully treated with percutaneous radiofrequency ablation (RFA) under live three-dimensional (3D) echocardiography guidance. Recently, it was reported that live 3D echocardiography was able to enhance the efficacy of catheter-based endomyocardial injection since the 3D images made it possible to observe the target from multiple directions so that it guided more accurately. A 63-year-old Japanese man had an HCC nodule of 3.0 cm in diameter at the S8 region of the liver. Here we applied live 3D echocardiography during RFA therapy with a LeVeen needle electrode. The echocardiography guidance allowed for easier and accurate approach for needle puncture. The guidance was also effective to confirm whether an enough safety margin for the nodule was obtained. Thus, live 3D echocardiography appears to safely guide RFA needles by accurate targeting for HCC nodule, providing real-time visualization when combined with echocardiography contrast.

Noninvasive assessment of liver disease - measurement of hepatic fibrosis using tissue strain imaging.

The development of hepatic fibrosis in patients with liver disease is associated with an increased risk of liver cancer. Assessing the degree of hepatic fibrosis is therefore one of the most important factors in treatment planning. Liver biopsy is commonly performed to assess hepatic fibrosis, but this method is associated with complications such as hemorrhage. Recently, a number of studies on the noninvasive assessment of hepatic fibrosis have appeared in the literature. The present study was conducted to determine whether an easily performed myocardial examination technique can also be applied to the assessment of hepatic fibrosis. The statistical software Minitab, which performs hypothesis testing based on the P value, was used for statistical analysis. The mean strain values were 0.26 in the normal adult group, 0.155 in the chronic hepatitis group, and 0.058 in the cirrhosis group. Statistically significant differences were observed between the groups. The results of the present study suggest that noninvasive tissue strain imaging may become the method of choice for assessing hepatic fibrosis in routine clinical practice.

Effect of vitamin K2 on the recurrence in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Vitamin K2 (VK2) appears to have a potent inhibitory activity for cell growth including HCC cells. We investigated whether VK2 could reduce incidence of tumor recurrence after treatment of HCC. Forty-five patients with cured or possibly cured HCC were randomly selected, assigning patients to treatment (n=21) or control group (n=24) with randomization list. METHODOLOGY: For the treatment group, forty-five mg of Glakay was given orally every day after therapy for HCC. No patients complained of adverse effects. Abdominal ultrasonography and dynamic CT were performed at 3-month intervals. Recurrence was confirmed by abdominal angiography. RESULTS: Recurrence of HCC occurred in 7 cases (33.3%) for the treatment group and 12 cases (50.0%) for the control group during mean observation periods of 19.5 and 16.5 months, respectively. Administration of VK2 was not an independent variable for the recurrence on univariate analysis. Cumulative incidence of HCC recurrence did not differ between the two groups, and the cumulative survival rate tended to be high in treatment group (p =0.054). Cox regression analysis revealed that serum albumin concentration alone was an independent factor affecting the recurrence. CONCLUSIONS: These findings suggest that VK2 does not appear to prevent recurrence of HCC after curative treatment. Our study is preliminary and large-scale trials are needed to determine whether VK2 is of benefit to decrease the recurrence of HCC.

Four-dimensional ultrasonography for therapeutic radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND/AIMS: We examined whether four-dimensional real-time flow imaging on ultrasonography (US) is valuable to display the accurate position of percutaneous radiofrequency ablation (RFA) needle in the nodule of hepatocellular carcinoma (HCC). METHODOLOGY: Ten patients with 12 HCC nodules were studied; nine were infected with hepatitis C virus (HCV) and one was diagnosed as non-B non-C. Diagnosis was done by helical dynamic CT and/or celiac angiography. Tumor vascularities in the early arterial and post-vascular phases after injection of a microbubble contrast agent were assessed by real-time US scanning of coded harmonic imaging and intermittent interval-delay scanning with a wide-band power Doppler technology. Percutaneous RFA was performed with four-dimensional real-time flow imaging under US to display the accurate position of cool-tip needle. RESULTS: It was possible to obtain accurate position of the needle during RFA procedure in all 12 nodules. The needle was confirmed to be inserted into the center of the tumor nodule by various angles. The simultaneous study before RFA therapy showed the inflow of arterial blood and tumor staining in all nodules at early arterial phase of coded harmonic angio on contrast-enhanced US scan. Posttreatment study to evaluate the therapeutic efficacy showed no blood flow at both early vascular and post-vascular phases. No residual blood flow was noted on early phase of CT scan with adequate safety margin. There was no discrepancy in the finding at early phase between contrast-enhanced US and dynamic CT. CONCLUSIONS: It appeared that four-dimensional real-time US provided more perceptible information on the spatial relationship between RFA needle and the target lesion, and resulted in accurate therapeutic efficacy for percutaneous RFA procedure.

Alteration of serum cytokine balances among different phases of chronic hepatitis B virus infection.

To understand the pathogenesis of chronic hepatitis B virus (HBV) infection, we examined the serum levels of IL-10, TNF-alpha IL-12 p70, and IL-12 p40 in 77 patients chronically infected with HBV and 19 controls. The patients were classified into four groups: asymptomatic carriers (ASC), patients with chronic hepatitis (CH), patients with liver cirrhosis (LC), and patients with hepatocellular carcinomas (HCC). The cytokine values among these groups were compared and their relations to clinical parameters were investigated. All these cytokine values were higher in the patient groups than in controls. IL-10 and TNF-alpha became higher in accordance with the progress of the disease phases, from ASC to LC, and lowest when the patients had HCC. IL-12 p40 was also lowest in HCC, however, the group with highest levels was CH. IL-12 p70 was unchanged among ASC, CH, and LC, but were raised in HCC. Serial analyses for the cytokine values in the same patients showed the similar tendencies. Regression analysis showed the significant correlations between ALT and IL-10. Serum cytokine values well reflected the pathological differences of the individual disease phases, and may become useful indices to understand the pathogenesis of chronic HBV infection.

A case of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) using 4D real-time ultrasound system.

The patient was a 62-year-old man. The anamnesis revealed an alcoholic liver disease. The patient was admitted to the department of otolaryngology in our hospital with sudden deafness in March 2003. The liver damage was pointed out due to the laboratory data on admission. A liver tumor was identified on the subsequently performed CT scan and the patient was referred to another department at another ward for detailed examinations. Based on the results of contrast echography, CT findings and angiography a HCC was diagnosed and RFA was performed. The conventional B-mode ultrasound examination sometimes presented unclear cross-sectional images of the tumor at the target area, and so additional treatment had to be given from time to time. Simultaneously with the puncturing multi-slice imaging could be obtained, allowing exact and definite performance of the RFA using a 4D real-time ultrasound system. Additionally, ultrasound examination with contrast media was conducted to help determine the efficacy of treatment.

Changes in natural killer T cells subsets during therapy in type C hepatitis and hepatocellular carcinoma.

Natural killer T (NKT) cells share features of both classical T cells and NK cells. NKT are heterogenous populations, and recognize glycolipids associated with CD1d molecule. We investigated Th1/Th2 cytokine production as well as frequency and phenotype of circulating NKT cells in 14 healthy subjects and in patients during therapy with type C chronic hepatitis (CH; 14 cases) and hepatocellular carcinoma (HCC; 13 cases). Peripheral blood mononuclear cells (PBMC) were obtained before and 2 weeks later interferon (IFN)/ribavirin and radiofrequency ablation therapy for CH and HCC, respectively. PBMC were cultured for 10 days with alpha-galactosylceramide (alpha-GalCer) and interleukin-2 (IL-2). Frequencies and IFN-gamma/IL-4 production of NKT cells were analyzed using flow cytometry. Intrahepatic lymphocytes were analyzed in seven CH patients with liver biopsy specimen. Prevalence of circulating Valpha24+CD3+ T cells was 0.9+/-0.9% of PBMC for controls and increased to 8.5+/-8.9% (p<0.001) in response to alpha-GalCel. Similar frequency and expansion were noted in CH. The frequency increased during therapy. The prevalence in HCC tended to be high compared to controls and response to alpha-GalCel was well. Although frequency of Valpha24+Vbeta11+CD3+ T cells was low in all groups, the distribution pattern was similar to Valpha24+Vbeta11-CD3+ T cells. Prevalence of CD56+CD3+ T cells was low independent of therapy in CH (2-3%) compared to 5.0+/-4.0% of controls, although response to alpha-GalCel was not impaired. IFN-gamma production of Valpha24+CD3+ T cells did not differ among groups, but became greater after treatment in contrast to lowered IL-4 production. Frequencies of NKT populations were higher in liver than in peripheral blood. Our study suggests that CD1d-reactive T cells have distinct distribution in different populations and therapy for patients alters cytokine response of NKT cells.

Advanced dynamic flow imaging with contrast-enhanced ultrasonography for the evaluation of tumor vascularity in liver tumors.

To examine the usefulness of advanced dynamic flow imaging in diagnosing hepatic tumor and in assessing therapeutic effects in patients with hepatocellular carcinoma (HCC) and metastatic hepatic tumor, we performed contrast-enhanced ultrasonography (US) with Levovist, a microbubble contrast agent. Twenty-two patients of 35 HCC nodules infected with hepatitis C virus (HCV) and six patients with metastatic liver nodules were studied. They were diagnosed as having HCC or metastasis with helical dynamic computed tomography (CT) and/or celiac angiography. Tumor vascularities in the early arterial and postvascular phases were assessed by real-time scanning of advanced dynamic flow imaging and intermittent interval-delay scanning of contrast pulse subtraction imaging with a wide-band power Doppler technology. All patients showed hypervascular enhancement of HCC on contrast-enhanced US and/or dynamic CT. The advanced dynamic flow could be obtained as vascular and perfusion images of hepatic tumors. Tumor vascularities, including tumor vessels and parenchymal flow, were able to demonstrate in 27 of 29 nodules including 17 patients with 27 HCC nodules and 2 patients with 2 metastatic nodules before radiofrequency ablation (RFA) treatment by the advanced dynamic flow on contrast-enhanced harmonic US. Two nodules gave insufficient dynamic flow which were located approximately 12 cm in depth from the body surface. The advanced dynamic flow, which was done 7-10 days after RFA, indicated disappearance of the tumor vessels in 27 of visible 27 nodules. The study on early phase of helical dynamic CT revealed the same results as noted in early vascular phase of dynamic flow US. No major complication of RFA procedure was noted. The results indicated that contrast-enhanced advanced dynamic flow imaging on US clearly depicted intratumoral vascularity in real time and thus it is useful to diagnose and assess therapeutic efficacy in patients with HCC and metastatic liver tumor.

Usefulness of contrast-enhanced ultrasonography with dynamic flow imaging to evaluate therapeutic effects for hepatocellular carcinoma.

BACKGROUND/AIMS: To examine the usefulness of dynamic flow imaging in identifying the therapeutic effects for hepatocellular carcinoma, we performed contrast-enhanced ultrasonography with Levovist. METHODOLOGY: Tumor vascularity of 48 hepatocellular carcinoma nodules in 27 patients infected with hepatitis C virus was assessed before and after radiofrequency ablation therapy by dynamic flow imaging with a wide-band power Doppler technology. RESULTS: All patients showed hypervascular enhancement of hepatocellular carcinoma on contrast-enhanced ultrasonography and/or dynamic computed tomography. The dynamic flow was obtained as vascular and perfusion images of hepatic tumors. The diameters of tumors were 1.1-2.0 cm in 12 nodules, 2.1-3.0 cm in 28, and 3.1-5.0 cm in 8, respectively. We were able to assess the tumor vascularities in 45 of 48 nodules before radiofrequency ablation by the dynamic flow. Three nodules showed insufficient dynamic flow which was located approximately 9 cm in depth from the body surface. The dynamic flow study for the therapeutic efficacy indicated that the tumor vessels disappeared in 43 of the 45 visible nodules. The tumor vascularities were noted in the remaining 2 nodules, and they were successfully retreated by radiofrequency ablation. The frequencies detecting positive enhancement in pretreatment and post-treatment were almost equivalent between vascular phase of dynamic flow on ultrasonography and early phase on helical dynamic computed tomography, although 5 nodules gave different findings; 2 were positive only on ultrasonography, and 3 were positive only on computed tomography. A major complication of radiofrequency ablation procedure was noted in only one case associated with intestinal edema, but it was cured by medical treatment. CONCLUSIONS: The results indicated that contrast-enhanced dynamic flow imaging on ultrasonography is a reliable tool to evaluate intratumoral vascularity both before and after radiofrequency ablation treatment in patients with hepatocellular carcinoma.

Mechanisms of increased insulin resistance in non-cirrhotic patients with chronic hepatitis C virus infection.

BACKGROUND AND AIM: Evidence showing a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C virus (HCV) infection has been accumulating. However, the reason why chronic HCV infection promotes DM remains unknown. In the present study, the authors focused on non-cirrhotic and non-diabetic patients with chronic HCV infection and evaluated the factors responsible for increases in insulin resistance. METHODS: Fifty-six patients diagnosed with HCV-related chronic liver disease were included. Biochemical information including body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase, cholinesterase, triglyceride, total cholesterol, hemoglobin, platelet count, glycosylated hemoglobin, immunoreactive insulin (IRI), and serum levels of tumor necrosis factor (TNF)-alpha and HCV-RNA were determined using venous blood samples obtained from each patient after overnight fasting. Homeostasis model assessment of insulin resistance (HOMA-IR), a simple and convenient measure of insulin resistance, was also calculated. The relationship between the stage of liver fibrosis and HOMA-IR, and the clinical factors responsible for the increase in HOMA-IR in non-diabetic patients was investigated. RESULTS: Homeostasis model assessment of insulin resistance and IRI levels increased parallel with the progression of fibrosis. Among the non-diabetic patients with mild to moderate liver fibrosis, BMI, serum levels of AST and TNF-alpha were related with HOMA-IR (BMI: r = 0.395, P = 0.041; AST: r = 0.465, P = 0.014; TNF-alpha: r = 0.396, P = 0.040). In contrast, HOMA-IR related to TNF-alpha (r = 0.526, P = 0.013) in non-diabetic patients with advanced liver fibrosis. CONCLUSION: Collectively, hepatic fibrosis and inflammation appear to play key roles in the increase in insulin resistance in patients with chronic HCV infection.