[Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

Safety and effectiveness of gemcitabine in 260 patients with biliary tract cancer in a Japanese clinical practice based on post-marketing surveillance in Japan.

OBJECTIVE: Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. METHODS: Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. RESULTS: Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). CONCLUSIONS: In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

Increased risk of acute pancreatitis in patients with type 2 diabetes: an observational study using a Japanese hospital database.

BACKGROUND: Increased risks of acute pancreatitis in patients with type 2 diabetes mellitus have been reported recently in several countries. We aimed to estimate the risks of acute pancreatitis in Japanese patients with diabetes mellitus. METHODS/FINDINGS: We examined a large-scale hospital administrative database consisting of one million patients in 16 secondary medical care hospitals, from 2003 to 2010. The incidence rates of acute pancreatitis were estimated with cohort design; the odds ratios associated with diabetes mellitus and other comorbid risk factors were estimated with separate case-control analyses. In cohort analysis, the incidence of acute pancreatitis was higher in 14,707 diabetic patients than in 186,032 non-diabetic patients (4.75 vs. 1.65 per 1,000 patient-years) and increased in male patients and as age advanced. The adjusted odds ratio of acute pancreatitis in patients with diabetes mellitus was 1.86 (P<0.001) compared with non-diabetic patients in case-control analysis from 1,372 cases and 5,469 matched controls, which is consistent with the ones reported in previous studies. Alcoholism and gallstones were associated with a large increase in the risk of acute pancreatitis (adjusted odds ratio 13.40 and 14.29, respectively, P<0.001), although dyslipidemia was associated with significant risk reduction (adjusted odds ratio 0.62, P<0.001). CONCLUSIONS: This observational study ascertained the elevated incidence rates and risk of acute pancreatitis in Japanese patients with diabetes. The risk estimates in Japanese patients with diabetes were in agreement with the ones reported in previous studies, and the elevated risk of acute pancreatitis in patients with diabetes would be generalized in different locations/populations.

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study.

BACKGROUND: Pemetrexed in combination with cisplatin (Pem/Cis) is the only approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At the time of launch, limited safety information was available. The purpose of this postmarketing all-case registry study was to investigate the safety and effectiveness of pemetrexed in patients with MPM. METHODS: From January 2007 to May 2008, MPM patients to be treated with pemetrexed in Japan were registered to this study to monitor its safety and effectiveness. Supply of pemetrexed was restricted to institutions with experienced medical oncologists based on predetermined criteria. RESULTS: Of 953 patients registered, data from 903 patients were eligible for analysis. Most patients were male, with median age of 65 years and 68.5% had a history of asbestos exposure. More than 90% of patients received the first cycle of Pem/Cis treatment; median number of treatment cycles was 4.0. Treatment-associated death was reported in 0.8% of patients. The incidence of Interstitial lung disease (ILD) associated with Pem/Cis during the observation period was 0.9%. The frequency of ILD in patients with pre-existing asbestosis was higher than that in patients without it. For tumor response, the overall response rate was 25.0% (95% confidence interval (CI): 22.2-28.0%). The six-month survival rate estimated by the Kaplan-Meier method was 75.9%. CONCLUSIONS: This large scale all case registry study appeared to have enrolled a major portion of Japanese MPM patients. Treatment with pemetrexed was generally well tolerated and showed safety and effectiveness comparable to prior clinical trials.

Diagnosis of acute cholecystitis in patients with liver cirrhosis: waveform analysis of the cystic artery by color Doppler imaging.

PURPOSE: The aim of this study was to investigate the possibility of diagnosing acute cholecystitis in patients with liver cirrhosis using color Doppler imaging to demonstrate the hemodynamics. METHODS: Color Doppler imaging was used to analyze the waveform of the cystic artery in 28 cirrhotic subjects with thickened gallbladder walls and 56 normal controls. The cirrhotic group was further divided into the cholecystitis group, containing 6 cirrhotic patients with acute cholecystitis, and the liver cirrhosis group, containing 22 cirrhotic patients without acute cholecystitis. RESULTS: Maximum velocity (Vmax) was significantly higher in the cholecystitis group (31.6 ± 23.0 cm/s) than in the normal controls (16.1 ± 5.9 cm/s) (P < 0.01). The resistance index (RI) was higher in the liver cirrhosis group (0.84 ± 0.04) than in either the normal controls (0.70 ± 0.06) (P < 0.01) or the cholecystitis group (0.72 ± 0.09) (P < 0.01). Sensitivity and specificity were 100% when the diagnostic criteria of acute cholecystitis were a maximum velocity of more than 40 cm/s, a resistance index of more than 0.75, or both. CONCLUSION: A pulsatile signal with a maximum velocity of more than 40 cm/s, a resistance index lower than 0.75, or both indicated the presence of acute cholecystitis in patients with liver cirrhosis and a thickened gallbladder wall.

Risk of HCV transmission after needlestick injury, and the efficacy of short-duration interferon administration to prevent HCV transmission to medical personnel.

BACKGROUND: We carried out this study to assess the risk of hepatitis C virus (HCV) transmission after needlestick injuries in medical personnel, and to evaluate the efficacy of short-duration interferon administration to prevent HCV transmission. METHODS: A total of 684 personnel who had been occupationally exposed to an anti-HCV-positive source and followed for more than 3 months were retrospectively examined. RESULTS: Of the 684 subjects, 279 (41%) were treated with 1 to 3 days of interferon either just after or 1 to 12 days after the injury. One case of HCV infection was found in each of the treated (1/279; 0.4%) and nontreated (1/405; 0.2%) groups. There was no significant difference in the transmission of HCV between the two groups. Both infected patients were treated with interferon after developing acute hepatitis, and HCV was subsequently cleared. CONCLUSIONS: There is a lower risk of HCV transmission after needlestick accident than previously reported, and short-duration interferon administration at an early stage after the needlestick injury, to prevent HCV transmission, is unnecessary.

Proximal bifurcation of hepatic artery: Novel findings on hepatic arteries demonstrated by ultrasound Doppler imaging, B-flow, and US angiography.

PURPOSE: It has generally been held that each portal branch is always accompanied by a single arterial branch in the liver. During Doppler ultrasound examination, however, we sometimes encounter a portal branch that appears to be associated with two arterial branches, a phenomenon referred to below asthis finding orthis phenomenon. Here we attempt to confirm that this finding is based on a correct interpretation of the image and to disclose its basic mechanism. MATERIAL AND METHODS: Five cases of chronic liver disease in which this phenomenon appeared were analyzed with B-flow imaging. Videotapes obtained from 30 patients who had chronic liver disease and had undergone ultrasound angiography (USAG) with arterial infusion of CO2 micro bubbles were reviewed in order to look for similar findings. Sixty-nine healthy controls were also examined with Doppler sonography for this purpose. Histopathologic specimens from 7 patients who had undergone hepatectomy (3 with hepatocellular carcinoma, 3 with metastatic tumor, and 1 with focal nodular hyperplasia) were examined to study the basic structure of the hepatic vessels. RESULTS AND DISCUSSION: Three parallel color signals (two pulsatile and one of a constant waveform) observed on Doppler examination were confirmed by the B-flow method to be three independent vessels in all five cases in which both Doppler sonography and B-flow imaging were used. In 13 (43%) of the 30 cases of USAG, two vessels along a portal branch were visualized by the inflow of micro bubbles, indicating that the two vessels were arteries. The trio of one portal and two arterial branches was also detected with Doppler sonography in 12 (17%) of the 69 healthy controls. In 10 (59%) of the 17 cases (5 of liver disease and 12 normal) that showed this finding on Doppler examination, bifurcations of the hepatic artery and portal vein were both visualized. Hepatic arterial branches were found to bifurcate slightly more proximal to the hepatic hilus than the accompanying portal branch. Histopathologic study revealed Glisson's areas that contained one portal branch and two arterial vessels in nontumorous parts of specimens from all 7 patients with hepatectomy. CONCLUSION: Two arterial branches can be demonstrated along a portal branch as a result of a more-proximal bifurcation of the hepatic artery than of the portal vein.