Association of prediabetes with reduced brain volume in a general elderly Japanese population.

OBJECTIVES: Diabetes frequently results in cognitive impairment, but it is less clear if brain health is adversely affected during the prediabetic stage. Our aim is to identify possible changes in brain volume as measured by magnetic resonance imaging (MRI) in a large elderly population stratified according to level of "dysglycemia." METHODS: This is a cross-sectional study of 2144 participants (median age 69 years, 60.9% female) who underwent 3-T brain MRI. Participants were divided into 4 dysglycemia groups based on HbA1c levels (%): normal glucose metabolism (NGM) (< 5.7%), prediabetes (5.7 to < 6.5%), undiagnosed diabetes (6.5% or higher), and known diabetes (defined by self-report). RESULTS: Of the 2144 participants, 982 had NGM, 845 prediabetes, 61 undiagnosed diabetes, and 256 known diabetes. After adjustment for age, sex, education, body weight, cognitive status, smoking, drinking, and disease history, total gray matter volume was significantly lower among participants with prediabetes (0.41% lower, standardized ß = - 0.0021 [95% CI - 0.0039, - 0.00039], p = 0.016), undiagnosed diabetes (1.4% lower, standardized ß = - 0.0069 [95% CI - 0.012, - 0.002], p = 0.005), and known diabetes (1.1% lower, standardized ß = - 0.0055 [95% CI - 0.0081, - 0.0029], p < 0.001) compared to the NGM group. After adjustment, total white matter volume and hippocampal volume did not differ significantly between the NGM group and either the prediabetes group or the diabetes group. CONCLUSION: Sustained hyperglycemia may have deleterious effects on gray matter integrity even prior to the onset of clinical diabetes. KEY POINTS: • Sustained hyperglycemia has deleterious effects on gray matter integrity even prior to the onset of clinical diabetes.

Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial.

BACKGROUND: Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. METHODS: This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0-2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. FINDINGS: Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3-49·3), median overall survival periods were 2·93 years (95% CI 2·60-3·79) and 2·74 years (95%CI 2·26-3·21), respectively (hazard ratio 0·90 [95% CI 0·71-1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88-1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. INTERPRETATION: In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.

A retrospective comparative study of epirubicin-lipiodol emulsion and cisplatin-lipiodol suspension for use with transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is widely used to treat unresectable hepatocellular carcinoma (HCC). Recently, a fine-powder formulation of cisplatin (DDP-H) was developed in Japan. We aimed to compare clinical outcomes after TACE using epirubicin or DDP-H in patients with HCC. We evaluated 202 patients who were treated with TACE alone, using either epirubicin-lipiodol emulsion or DDP-H-lipiodol suspension. Of these, epirubicin and DDP-H treatment groups comprised 106 and 96 patients, respectively. The median follow-up time was 32 months (range: 1-45 months). The progression free survival rate in the DDP-H­lipiodol group was significantly higher than in the epirubicin-lipiodol group (log-rank test, P =0.0164). Moreover, the DDP-H­lipiodol group showed significantly better overall survival than the epirubicin-lipiodol group (log-rank test: P =0.0052). The overall survival rate at 1, 2, and 3 years was 88.5, 71.8 and 62.4%, respectively, for the DDP-H-lipiodol group and 83.0, 57.9 and 36.5%, respectively, in the epirubicin-lipiodol group. In a multivariate analysis, the independent factors affecting overall survival were drug (epirubicin vs. DDP-H; hazard ratio 0.44, P= 0.0001), clinical stage (I/II vs. III/IV; hazard ratio 1.93, P = 0.0026), and Child-Pugh score (A vs. B/C; hazard ratio 3.15, P < 0.0001). TACE using a gelatin sponge and lipiodol with DDP-H showed better progression-free survival and overall survival rates than TACE with the epirubicin-lipiodol emulsion in patients with HCC. The improvement of overall survival in patients with HCC receiving this treatment warrants further investigation as a randomized control trial.

Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma.

AIM: Intra-arterial cisplatin appears to have high therapeutic efficacy, but this has not been studied in detail. Accordingly, we developed a fine-powder cisplatin formulation and tested it in advanced hepatocellular carcinoma (HCC) patients in an open-label, uncontrolled study in which 27 institutions participated. METHODS: The patients in this study had inoperable advanced HCC without extrahepatic metastases. All received two infusions of high-concentration cisplatin (1.43 mg/mL) via the hepatic artery at a dose of 65 mg/m(2), with an intervening 4-6 week interval. RESULTS: Cisplatin efficacy and safety were assessed in 80 patients. We found partial responses in 27 cases, no change in 37, and progressive disease in 11 (five were not evaluated). The overall response rate was 33.8%. The 1-year survival rate was 67.5% and the 2-year survival rate was 50.8%. Severe adverse effects (>/=grade 3) included anorexia in 22.5%, vomiting in 6.3%, abdominal pain in 1.3%, thrombocytopenia in 25%, neutropenia in 13%, leukopenia in 1.3%, hypochromia in 1.3%, elevated serum aspartate aminotransferase in 32.5%, elevated serum alanine aminotransferase in 11.3%, elevated serum bilirubin in 3.8%, decreased serum albumin in 1.3%, elevated serum alkaline phosphatase in 1.3%, elevated gamma-glutamyltranspeptidase in 3.8%, and elevated serum creatinine in 2.5%. Death from myocardial infarction occurred as an incidental event in one case, and no other life-threatening, adverse events were observed. CONCLUSION: Although intra-arterial cisplatin has substantial local and systemic toxicity, high therapeutic efficacy suggests the potential usefulness of this agent in the treatment of advanced HCC.

Increased signal intensity in the normal glenoid labrum in MR imaging: diagnostic pitfalls caused by the magic-angle effect.

PURPOSE: To determine the effect of the magic-angle effect on the MR signal in the posterosuperior portion of the glenoid labrum. METHODS: MR imaging of 15 arthroscopically evaluated shoulders, five with posterosuperior labrum injury and ten intact, was retrospectively reviewed. In the first part of the study, the signal intensity of the posterosuperior labrum on gradient-recalled echo (GRE) T2*-weighted axial images was correlated with the arthroscopy findings. The second part of the study was designed to illustrate the orientation-dependent signal that occurs in the posterosuperior labrum of three asymptomatic volunteers when imaged in the conventional supine position and in a position similar to Trendelenburg's. Another three volunteers were examined with GRE T2*-weighted axial images to assess the echo-time (TE)-dependent signal in the labrum. RESULTS: The signal increase in the posterosuperior labrum was identified not only in the injured labra but also in nine of 10 intact labra. In the volunteers' studies, the signal in the posterosuperior labrum changed according to the examinees' positions (conventional supine or similar to Trendelenburg's) and according to TE. CONCLUSIONS: Increased signal intensity due to the magic-angle effect may be misdiagnosed as a labrum injury. Awareness of this pitfall is particularly important in MR imaging of throwing athletes whose posterosuperior labra are frequently injured by posterosuperior glenoid impingement.