Efficacy of daily abdominal self-massage for the prevention of recurrent common bile duct stones after endoscopic biliary sphincterotomy.

Recurrent common bile duct stones (CBDS) can occur after endoscopic biliary sphincterotomy (EST). Bile flow through the papilla of Vater could be improved by means of abdominal massage. We report the results of self-abdominal massage in four patients who had previously undergone cholecystectomy and experienced multiple CBDS recurrences after EST.

L-carnitine reduces hospital admissions in patients with hepatic encephalopathy.

AIM: The aim of this study was to determine whether oral L-carnitine administration reduces the blood ammonia concentration and number of hospital admissions for hepatic encephalopathy in patients with advanced cirrhosis. METHODS: Of 68 patients with hepatic encephalopathy treated with oral L-carnitine supplementation from April 2013 to March 2016, we enrolled 19 patients who had received full standard treatment. We analyzed blood ammonia concentration, number of hospital admissions, and prognosis to determine how effective L-carnitine was in achieving mid-term to long-term suppression of recurrent hepatic encephalopathy. RESULTS: Median blood ammonia concentrations at the start, 1 week, 12 weeks, 24 weeks, and 48 weeks were 159, 79, 75, and 82 µg/dL, respectively. Blood ammonia concentrations 12 week, 24 weeks, and 48 weeks after L-carnitine administration were significantly lower than those at the start (P < 0.0001, respectively). During the 3 years prior to oral L-carnitine administration, the enrolled patients were hospitalized a total of 29 times for hepatic encephalopathy. However, during the 3 years following oral L-carnitine administration, they were admitted a total of six times for hepatic encephalopathy (P < 0.001). Median survival time was 40.9 months. Child-Pugh scores before and after oral L-carnitine administration differed significantly, whereas liver reserve function, nutritional status, and muscle index did not change significantly. CONCLUSIONS: Oral L-carnitine administration is effective and free of adverse effects in patients with hyperammonemia and reduces the number of hospital admissions for hepatic encephalopathy.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Selenium deficiency is associated with insulin resistance in patients with hepatitis C virus-related chronic liver disease.

The relationship between selenium (Se) deficiency and insulin resistance has not much been established in persistent hepatitis C virus (HCV) infection, although Se deficiency is often observed in patients with liver cirrhosis. We hypothesized that the decreased serum Se levels were associated with the severity of hepatic fibrosis or insulin resistance in patients with HCV-related chronic liver disease (CLD). To test the hypothesis, 52 patients with HCV-related CLD including chronic hepatitis and liver cirrhosis were enrolled in this study. The severity of hepatic fibrosis was divided into 4 categories (F(1) through F(4)) according to the new Inuyama classification. Insulin resistance was defined by the homeostasis model for assessment of insulin resistance value. Serum Se levels significantly declined in proportion to the severity of hepatic fibrosis and were positively correlated with serum albumin (r = 0.372, P = .0065) and zinc (r = 0.403, P = .0081) concentrations. Serum Se levels were also linked to glutathione peroxidase activities in the sera of the enrolled patients (r = 0.374, P = .0148). By contrast, serum Se levels were inversely correlated with the homeostasis model for assessment of insulin resistance values (r = -0.304, P = .0338). However, serum Se levels were independent of HCV genotype and loads of HCV-RNA. These findings suggest that Se deficiency was associated with the severity of hepatic fibrosis in patients with HCV-related CLD and that Se deficiency was likely to be one of the factors contributing to insulin resistance in those patients.

Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology.

We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR), lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT), it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI, firstly reported in our department, and IVR (PELI and IVR, lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment, the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus, this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.

Successful treatment of large-size advanced hepatocellular carcinoma by transarterial chemoembolization followed by the combination therapy of percutaneous ethanol-lipiodol injection and radiofrequency ablation.

We report a case of large-size hepatocellular carcinoma (HCC) successfully treated with transarterial chemoembolization (TACE) followed by the combination therapy of percutaneous ethanol-lipiodol injection and radiofrequency ablation (PELI-RFA) and percutaneous ethanol-lipiodol injection (PELI) therapy. In the present case, the patient had a large-size advanced HCC, 7 cm in diameter, located in the S8 region of the liver. In addition, the hepatic reserve of the patient was severely poor. In order not to impair the poor hepatic reserve, we chose PELI-RFA and PELI, originally developed in our department and reported as milder treatment modalities than others. After TACE , PELI-RFA and PELI were performed several times, the HCC was totally destroyed and early enhancement shown by helical dynamic computed tomography disappeared completely after treatment. The hepatic reserve of the patient was not impaired by the series of treatments. Serum levels of tumor markers, alpha-fetoprotein and Des-gamma-carboxy prothrombin, were rapidly decreased to almost normal levels. PELI-RFA and PELI may be effective for the treatment of large-size HCC of patients with poor hepatic reserve.

Efficacy of combination therapies of percutaneous or laparoscopic ethanol-lipiodol injection and radiofrequency ablation.

Percutaneous radiofrequency ablation (RFA) is able to destroy hepatocellular carcinoma (HCC) in a few sessions without major complications. We have previously shown that not only the combined use of percutaneous ethanol injection and RFA (PEI-RFA) but also injection of mixture of ethanol and lipiodol (PELIT) was useful for the treatment of HCC. In the present study, we further developed the combined use of PELIT and RFA through percutaneous or laparoscopic approach (PELI-RFA or LELI-RFA) and evaluated its usefulness. Nineteen nodules in 18 cases were treated with PELI-RFA or LELI-RFA. In the cases treated with LELI-RFA, no bleeding and no spilling milky fluid containing tumor cells were observed from the surface of ablated tumors. In the cases sufficiently treated with PELI-RFA or LELI-RFA, the mixture of ethanol and lipiodol was accumulated in the entire region of the tumor and low-density area was observed around the lipiodol deposit by computed tomography (CT). These delineations of coagulated area were helpful to evaluate the precise area of safety margin around the tumor treated with PELI-RFA or LELI-RFA. Furthermore, the total volume of coagulated necrosis significantly and positively correlated with the product of energy requirement for ablation and the volume of ethanol injected by PELI-RFA or LELI-RFA. Among the cases treated with PELI-RFA or LELI-RFA, local recurrence emerged only in one case in whom enough safety margin could not be achieved by PELI-RFA. Therefore, it is critical to evaluate whether enough safety margin could be obtained with RFA therapy, and PELI-RFA and LELI-RFA are helpful in visualizing the safety margin area.

Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma.

Radiofrequency ablation (RFA) therapy is of great significance in the treatment of hepatocellular carcinoma (HCC) or metastatic liver tumors. RFA is able to achieve widely coagulated necrosis in a few sessions without major complications. However, HCC cases exist that are resistant to RFA therapy for several reasons. In the present study, we performed injection of the mixture of ethanol and lipiodol (percutaneous ethanol-lipiodol injection therapy: PELIT) for HCCs that lacked clear visuality of the entire shape of the tumor by ultrasonography (US) or computed tomography (CT), or that were difficult to treat with RFA alone due to their locations in the liver or due to severe liver dysfunction of the patients. Local recurrence rates of HCC treated with PELIT were shown to be low in patients followed up for at least 4 months. In all patients treated with PELIT, lipiodol was accumulated in the entire region of the tumor after several trials of PELIT and the accumulation was kept for many months. The biopsy examination from the tumor treated with PELIT showed that HCC cells were totally destroyed by the PELIT. Although RFA therapy serves as a central role for the treatment of HCCs, PELIT, considered to be milder therapy, is likely to be important as a supportive treatment for HCCs and useful for the treatment of HCCs that are difficult to treat with RFA.

Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and the opposing effect of L-arginine.

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a newly identified endothelial cell surface major receptor for oxidatively modified low-density lipoprotein. Progression of arthrosclerosis in the donor organ after organ transplantation is a major problem. We hypothesized that ischemia-reperfusion induces LOX-1. After 1 h ischemia of bilateral kidneys plus 3, 6, or 12 h reperfusion, we first revealed that LOX-1 mRNA expression was increased in renal cortex and medulla at 6 h after reperfusion, which was decreased by L-arginine supplement. Plasma nitric oxide (NO) end-product nitrite plus nitrate and inducible nitric oxide synthase (NOS) expression were increased after reperfusion of 6 h. However, NOS substrate L-arginine did not augment but markedly decreased plasma NO end product, because L-arginine supplement suppressed inducible NOS expression in kidney. We hypothesized that available L-arginine is depleted by ischemia-reperfusion, leading to inducible NOS induction. Ischemia decreased L-arginine levels in kidney and L-arginine supplement increased NO end products in renal cortex in the earliest phase of reperfusion. These results disclosed for the first time that a deficiency in L-arginine by ischemia reperfusion causes uncoupling of constitutive NOS, which induces inducible NOS and LOX-1, implying why L-arginine is effective for stroke or transplantation in preventing atherosclerotic progress.