No abstract

No abstract

The effectiveness and safety of yokukansan (TJ-54), a traditional Japanese medicine (kampo) for the treatment of the behavioural and psychological symptoms of dementia (BPSD), were evaluated in 106 patients diagnosed as having Alzheimer's disease (AD) (including mixed-type dementia) or dementia with Lewy bodies. Patients were randomly assigned to group A (TJ-54 treatment in period I and no treatment in period II; each period lasting 4 wk) or group B (no treatment in period I and TJ-54 treatment in period II). BPSD and cognitive functions were evaluated using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE), respectively. Activities of daily living (ADL) were evaluated using Instrumental Activities of Daily Living (IADL) in outpatients and the Barthel Index in in-patients. For the safety evaluation, adverse events were investigated. Significant improvements in mean total NPI score associated with TJ-54 treatment were observed in both periods (Wilcoxon test, p=0.040 in period I and p=0.048 in period II). The mean NPI scores significantly improved during TJ-54 treatment in groups A and B (p=0.002 and p=0.007, respectively) but not during periods of no treatment. Among the NPI subscales, significant improvements were observed in delusions, hallucinations, agitation/aggression, depression, anxiety, and irritability/lability. The effects of TJ-54 persisted for 1 month without any psychological withdrawal symptoms in group A. TJ-54 did not show any effect on either cognitive function or ADL. No serious adverse reactions were observed. The present study suggests that TJ-54 is an effective and well-tolerated treatment for patients with BPSD.

Potentially curative treatments for early‐stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early‐stage HCC. Consecutive patients with ≤3 early‐stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3‐year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7‐9.2; versus 12.9%, 95% CI, 9.9‐16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3‐year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2‐77.7; and 70.4%; 95% CI, 58.5‐79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well‐compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.

No abstract

No abstract

The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) is not well known. The aims of this study are to determine HCC incidence and survival, and to identify risk factors associated with these outcomes in patients with PBC. We collected information on 396 patients with PBC at enrollment and followed-up from 6 to 271 months. They were all negative for hepatitis B and C virus markers. HCC was detected by scanning with ultrasonography, computed tomography, or both every 4 to 6 months. Life expectancy (LE) was approximated with the declining exponential approximation of LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by the tenth year, respectively. P ‫؍‬ .021). Proportional hazards analysis showed 3 factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, and history of blood transfusion. Age, male gender, and advanced-stage PBC were associated with survival, but HCC development was not. The disease-specific annual mortality rate was estimated to be 0.008 for women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in old patients with advanced-stage PBC, but HCC does not affect the patients' survival. P rimary biliary cirrhosis (PBC) is a chronic liver disease of unknown etiology presenting a variety of disease spectrum from asymptomatic disease state to full-blown cirrhosis. Patients with liver cirrhosis caused by chronic infection of hepatitis C virus (HCV) or hepatitis B virus (HBV) are at high risk of hepatocellular carcinoma (HCC); however, it is not known whether the HCC incidence is high in patients with PBC. Although there are 9 studies about HCC incidence in PBC, the results are not consistent. 1-9 Some studies 3,4 show that patients with PBC have no excess risk of developing HCC and others [5][6][7][8][9] show that the incidence of HCC is high in those patients. An Italian study indicated that HCC has a relatively high prevalence in PBC and HCV superinfection may play an important part in favoring HCC. 7 Even though without HBV or HCV infection, a study conducted in UK showed 5.9% of patients with PBC in precirrhotic or cirrhotic stage had developed HCC. 6 The authors of this large-scale cohort study concluded that men with advanced-stage PBC have a higher risk of developing HCC. A recent retrospective study in the Mayo Clinic also reported that patients with PBC 8 are at high risk of hepatobiliary malignancies but the authors did not mention risk factors for HCC development.The aims of the present study are to analyze the survival of patients with PBC, to quantify the incidence at which they develop HCC, and to identify HCC risk factors. In addition, we determined whether HCC affected the survival of patients with PBC. Therefore, we tested 2 hypotheses: (1) that the patients with advanced-stage PBC sur...

BackgroundThrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD.MethodsIn this multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD patients with platelet count < 50 × 103/µL at screening were randomized to placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28-day post-treatment assessment period. The primary efficacy endpoint was the proportion of patients who did not require platelet transfusion before RFA. The pre-specified key secondary efficacy endpoint was the proportion of responders. Adverse events (AEs) and thrombosis-related AEs were evaluated.ResultsThe proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (p < 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set.ConclusionsLusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count.Clinical trial registrationThe study is registered at JapicCTI-121944.Electronic supplementary materialThe online version of this article (10.1007/s00535-018-1499-2) contains supplementary material, which is available to authorized users.