Transcatheter arterial infusion chemotherapy with cisplatin in combination with transcatheter arterial chemoembolization decreases intrahepatic distant recurrence of unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: This study investigated the efficacy of transcatheter arterial infusion (TAI) chemotherapy with cisplatin combined with transcatheter arterial chemoembolization (TACE). The goal was to prevent intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC), compared with TACE alone, in patients with unresectable HCC. METHODS: We conducted a historical cohort study, which involved 68 unresectable HCC patients. The study was performed on 44 and 24 consecutive patients who underwent TAI using cisplatin combined with TACE using epirubicin and TACE using epirubicin alone, respectively. We performed a propensity score analysis to identify the independent risk factors associated with IDR, and constructed propensity score-adjusted survival curves. RESULTS: After propensity score-adjusting, the adjusted cumulative IDR rates at 1 and 3 years were 76.8 and 76.8% in TACE alone group, and 21.3 and 73.1% in TACE with TAI group, respectively. TACE alone group had a significantly higher IDR rate in comparison with TACE with TAI group (P = 0.0073). Combined with TAI was associated with preventing IDR after propensity score-adjusting (hazard ratio [HR] 0.40, 95% confidence intervals [CI] 0.17-0.91, P = 0.028). Combined with TAI (HR 0.26, 95% CI 0.10-0.68, P = 0.0056) and Stage ≥III (HR 2.98, 95% CI 1.25-7.12, P = 0.014) were independent IDR predictors after adjusting for significant risk factors with propensity score. CONCLUSIONS: We demonstrated that cisplatin TAI accompanied with TACE decreased IDR compared with TACE alone. Our findings suggest that cisplatin TAI might contribute to a longer progression-free period in unresectable HCC patients treated with TACE.

Probe-based confocal laser endomicroscopy for the diagnosis of pancreatic ductal structures.

BACKGROUND AND AIM: The image-based diagnosis of pancreatic diseases can be difficult and requires pathological evaluation. Probe-based confocal laser endomicroscopy (pCLE) enables real-time observation of the microscopic tissue pattern of lesion and may be a useful assistance for the diagnosis. This study aimed to evaluate the feasibility and utility of pCLE for the diagnosis of pancreatic diseases. METHODS: Thirty patients who underwent endoscopic retrograde cholangiopancreatography with pCLE for the evaluation of indeterminate pancreatic diseases from June 2015 to October 2018 were included in this study. The pCLE findings were interpreted according to the Miami Classification. RESULTS: Among a total of 30 patients, 12, 10, 4, and 4 patients received the definitive diagnoses of pancreatic ductal adenocarcinoma (PDAC), main duct intrapapillary mucinous neoplasm, autoimmune pancreatitis, and chronic pancreatitis, respectively. The diagnostic accuracy of pCLE for PDAC and pancreatitis (96.7% and 93.3%, respectively) was higher than that of cytology (76.7% and 63.3%, respectively) (P = 0.0227 and 0.0048, respectively). The sensitivity of pCLE for PDAC was significantly higher (91.7%) than that of cytology (41.7%) (P = 0.0094). Moreover, the specificity of pCLE for pancreatitis was significantly higher than that of cytology (90.9% vs 50%; P = 0.0029). However, the diagnostic accuracies of pCLE and cytology for main duct intrapapillary mucinous neoplasm did not differ significantly (96.7% and 86.7%, respectively). CONCLUSIONS: Probe-based confocal laser endomicroscopy may be effective for the diagnosis of pancreatic diseases as adjunct modality. It requires technical learning and further evaluation of its usefulness.

Acceptance of the Deltoid Muscle Injection of Aripiprazole Long-acting Injectable in the Patients with Schizophrenia.

OBJECTIVE: To improve poor medication adherence in schizophrenic patients, long-acting injectable (LAI) antipsychotics are used. However, it has not yet become common in Japan. Recently, aripiprazole LAI was approved for alternative injection into the deltoid muscle in addition to the gluteal muscle. The acceptance for the proposal to switch from gluteal to deltoid injections of aripiprazole LAI was investigated. METHODS: The subjects were 32 outpatients with schizophrenia who had continuously received aripiprazole LAI administration into the gluteal muscle for ≥ 6 months. In the patients who had continued deltoid injection for 3 months after switching, the changes in the pain and shame in comparison with gluteal injections were evaluated. RESULTS: Switching to the deltoid injection was chosen by 17 out of 32 patients. Three months later, 9 patients were still receiving deltoid injections with highly rated satisfaction. The main reasons for switching to deltoid injections included the pain and shame associated with gluteal injections. The main reason for returning to the gluteal injection was the pain experienced from the injection in the deltoid. RESULTS: The option to select the injected area was based on the amount of pain in the deltoid and gluteal sites, leading to the widespread use of aripiprazole LAI.

Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient improves the branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia: a prospective study.

OBJECTIVE: The present study aimed to elucidate the effect of switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient in patients with cirrhosis with hypoalbuminemia. METHODS: Twenty-six patients with cirrhosis with hypoalbuminemia despite treatment with branched-chain amino acid granules containing 12 g of branched-chain amino acid were enrolled in the prospective study. The branched-chain amino acid-enriched nutrient and control groups were composed of 16 and 10 patients, respectively. The patients in branched-chain amino acid-enriched nutrient group switched to branched-chain amino acid-enriched nutrient mixture containing 12.2 g of branched-chain amino acid and 410 kcal with a half of it consumed as a late evening snack, and the patients in the control group continued branched-chain amino acid granules. Laboratory data related to nutrition parameter were assessed at baseline, 3 months after baseline, and at 6 months after baseline. RESULTS: Two patients were withdrawn; hence, nine and 15 patients in the branched-chain amino acid granules and branched-chain amino acid-enriched nutrient groups, respectively, were subjected to full analysis. Serum albumin levels and total lymphocyte counts in both groups did not change in the study period. The branched-chain amino acid-to-tyrosine ratio in the branched-chain amino acid-enriched nutrient group significantly increased from baseline to 6 months after baseline (P = 0.030), whereas that in the control group did not increase. CONCLUSION: Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrients improves branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia.

Skeletal muscle mass depletion in patients with hepatitis C virus infection.

OBJECTIVE: The aim was to assess the relationship between muscle mass depletion and chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: We retrospectively evaluated abdominal computed tomography data for 611 patients. The participants included 302 patients with HCV infection and 309 patients with gallstones (as a control). The skeletal muscle mass at the level of the third lumber vertebra (L3) was measured from the computed tomography images and normalized for height to calculate the L3 skeletal muscle index (L3-SMI, cm/m). Statistical analysis was carried out separately for each sex, given that L3-SMI differs significantly between men and women. RESULTS: L3-SMI showed no significant difference between chronic hepatitis patients and gallstone patients in either sex. L3-SMI was significantly lower in male cirrhotic patients than in those with chronic hepatitis (P<0.001). The Child-Pugh score was correlated negatively with L3-SMI in male patients with HCV-related cirrhosis (ρ=0.200, P=0.031). In addition, the BMI in both sexes was associated with L3-SMI in the gallstone and chronic hepatitis group, in the chronic hepatitis and liver cirrhosis group, and in the liver cirrhosis group. CONCLUSION: Skeletal muscle mass is not affected by chronic HCV infection in patients without cirrhosis and decreases in accordance with liver disease progression in male patients with chronic HCV infection.

Evaluation of a 12-mm diameter covered self-expandable end bare metal stent for malignant biliary obstruction.

Background and study aims Biliary metallic stents are used to drain unresectable malignant distal biliary obstructions. This study aimed to evaluate the efficacy of a novel 12-mm-diameter covered, self-expandable end bare metal stent (12-mm CSEEMS). Patients and methods We evaluated 99 patients with unresectable malignant distal biliary obstructions treated with covered biliary metallic stents. Of the 99 patients, 33 underwent 12-mm CSEEMS placement between June 2015 and April 2017 (12-mm-CSEEMS group) and 66 underwent 10-mm fully-covered self-expandable metal stent (FCSEMS) placement between January 2010 and July 2015 (10-mm-FCSEMS group). The overall survival (OS), the recurrent biliary obstruction (RBO), cause of RBO, time to RBO (TRBO) and adverse events in 12-mm-CSEEMS group and 10-mm-FCSEMS group were evaluated retrospectively. Results The OS tended to be longer in the 12-mm-CSEEMS group (log rank, P  = 0.081) and TRBO was significantly longer in the 12-mm-CSEEMS group (log rank, P  = 0.001) than in the 10-mm-FCSEMS group. Both univariate (HR, 0.449; 95 % CI, 0.27967 - 0.72215; P  = 0.001) and multivariate (HR, 0.458; 95 % CI, 0.28395 - 0.73744; P  = 0.001) Cox hazard analysis found that risk of RBO was significantly lower in 12-mm CSEEMS than in 10-mm FCSEMS. There were no significant differences between the 12-mm-CSEEMS group and 10-mm-FCSEMS group regarding the cause of RBO and adverse events. Conclusions The 12-mm CSEEMS showed a low risk of RBO compared with 10-mm FCSEMS and was considered to be effective and safe for draining unresectable malignant distal biliary obstruction.

HLA-DQ gene polymorphisms are associated with hepatocellular carcinoma and hepatitis B surface antigen in chronic hepatitis B virus infection.

AIM: Genome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection. METHODS: The SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection. RESULTS: In 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG + GG had significantly lower hepatitis B core-related antigen levels (P = 0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P = 0.0433), and less frequent HCC development (P = 0.0256) than those with genotype AA. Multivariate analysis selected age (P = 0.0460), platelet count (P = 0.0481), γ-glutamyl transpeptidase (P = 0.0030), and nucleotide/nucleoside analog treatment (P = 0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P < 0.0001), a higher prevalence of HBV genotype C (P = 0.0063), and a lower prevalence of the wild-type basal core promoter region (P = 0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P < 0.0001), platelet count (P = 0.0021), HBV DNA levels (P = 0.0314), wild type of precore region (P = 0.0015), and rs7453920 (P < 0.0001) as factors independently associated with HBsAg levels. CONCLUSION: This study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.

Vitamin E reduces liver stiffness in nonalcoholic fatty liver disease.

AIM: To evaluate the efficacy of vitamin E treatment on liver stiffness in nonalcoholic fatty liver disease (NAFLD). METHODS: Thirty-eight NAFLD patients were administered vitamin E for > 1 year. The doses of vitamin E were 150, 300, or 600 mg; three times per day after each meal. Responses were assessed by liver enzyme levels [aspartate aminotransferase (AST), alanine aminotranferease (ALT), and γ-glutamyl transpeptidase (γ-GTP)], noninvasive scoring systems of hepatic fibrosis-4 [FIB-4 index and aspartate aminotransferase-to-platelet index (APRI)], and liver stiffness [velocity of shear wave (Vs)] measured by acoustic radiation force impulse elastography. Vs measurements were performed at baseline and 12 mo after baseline. The patients were genotyped for the patatin-like phospholipase domain containing 3 (PNPLA3) polymorphisms and then divided into either the CC/CG or GG group to examine each group's responses to vitamin E treatment. RESULTS: We found marked differences in the platelet count, serum albumin levels, alkaline phosphatase levels, FIB-4 index, APRI, and Vs at baseline depending on the PNPLA3 polymorphism. AST, ALT, and γ-GTP levels (all P < 0.001); FIB-4 index (P = 0.035); APRI (P < 0.001); and Vs (P < 0.001) significantly decreased from baseline to 12 mo in the analysis of all patients. In the subset analyses of PNPLA3 genotypes, AST levels (P = 0.011), ALT levels (P < 0.001), γ-GTP levels (P = 0.005), APRI (P = 0.036), and Vs (P = 0.029) in genotype GG patients significantly improved, and AST and ALT levels (both P < 0.001), γ-GTP levels (P = 0.003), FIB-4 index (P = 0.017), and APRI (P < 0.001) in genotype CC/CG patients. CONCLUSION: One year of vitamin E treatment improved noninvasive fibrosis scores and liver stiffness in NAFLD patients. The responses were similar between different PNPLA3 genotypes.

Additional BCAA-enriched nutrient mixture improves the nutritional condition in cirrhotic patients with hypoalbuminemia despite treatment with regular BCAA granules: A pilot study.

BACKGROUND/AIMS: To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. MATERIALS AND METHODS: A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. RESULTS: Serum albumin levels significantly decreased from 6 months before baseline (3.14±0.47 g/dL) to baseline (2.83±0.46 g/dL), despite the treatment with BCAA granules (p<0.001), and tended to increase from baseline to 6 months after baseline (2.95±0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93±0.38 g/dL) to 6 months after baseline (3.15±0.34 g/dL) (p=0.014). CONCLUSION: Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.

[Medical economics evaluation of 5-HT3 receptor antagonist drugs].

At Komaki City Hospital, the drug cost in connection with cancer chemotherapy was re-examined as part of improved management along with the introduction of DPC in July 2008. With due attention to the 5-HT3 receptor antagonists, both the change from injections to oral drugs and the change from brand-name drugs to generic drugs were tried between July 2008 and June 2009. After that, in order to examine the economic impact of these changes, we investigated and analyzed the number of medications, the cost of medicine purchased, and the average drug cost per medication of the 5-HT3 receptor antagonists between April 2008 and September 2009. As a result, the cost of 5-HT3 receptor antagonists purchased decreased greatly, and the impact of the improvement was mainly due to the change to oral drugs, and partially to the change to generic drugs. Therefore, from the viewpoint of hospital economic improvement in DPC, it was thought that the change to oral drugs(5-HT3 receptor antagonists)is given top priority.