Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS Trial): Study protocol for a randomized controlled trial

AbstractBackgroundAlthough the positive association between achieved low-density lipoprotein cholesterol (LDL-C) level and the risk of coronary artery disease (CAD) has been confirmed by randomized studies with statins, many patients remain at high residual risk of events suggesting the necessity of novel pharmacologic strategies. The combination of ezetimibe/statin produces greater reductions in LDL-C compared to statin monotherapy.PurposeThe Plaque REgression with Cholesterol absorption Inhibitor or Synthesis inhibitor Evaluated by IntraVascular UltraSound (PRECISE-IVUS) trial was aimed at evaluating the effects of ezetimibe addition to atorvastatin, compared with atorvastatin monotherapy, on coronary plaque regression and change in lipid profile in patients with CAD.MethodsThe study is a prospective, randomized, controlled, multicenter study. The eligible patients undergoing IVUS-guided percutaneous coronary intervention will be randomly assigned to receive either atorvastatin alone or atorvastatin plus ezetimibe (10mg) daily using a web-based randomization software. The dosage of atorvastatin will be increased by titration within the usual dose range with a treatment goal of lowering LDL-C below 70mg/dL based on consecutive measures of LDL-C at follow-up visits. IVUS will be performed at baseline and 9–12 months follow-up time point at participating cardiovascular centers. The primary endpoint will be the nominal change in percent coronary atheroma volume measured by volumetric IVUS analysis.ConclusionPRECISE-IVUS will assess whether the efficacy of combination of ezetimibe/atorvastatin is noninferior to atorvastatin monotherapy for coronary plaque reduction, and will translate into increased clinical benefit of dual lipid-lowering strategy in a Japanese population

Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention The Multicenter Randomized Controlled PRECISE-IVUS Trial

AbstractBackgroundDespite standard statin therapy, a majority of patients retain a high “residual risk” of cardiovascular events.ObjectivesThe aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI).MethodsThis trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients.ResultsThe combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the 2 groups (–1.538%; 95% confidence interval [CI]: –3.079% to 0.003%) did not exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (–1.4%; 95% CI: –3.4% to –0.1% vs. –0.3%; 95% CI: –1.9% to 0.9% with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events.ConclusionsCompared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition–induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex

Phase II study of combined chemotherapy with irinotecan and S-1 (IRIS) plus bevacizumab in patients with inoperable recurrent or advanced colorectal cancer

Background. In Japan, a study comparing the effectiveness and safety of irinotecan plus S-1 (IRIS) with those of a combination of 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line treatment in patients with advanced or recurrent colorectal cancer demonstrated that IRIS was non-inferior to FOLFIRI. We previously reported that IRIS is also effective as first-line treatment. Patients and Methods. Eligibility criteria included inoperable recurrent colorectal cancer with a confirmed diagnosis of adenocarcinoma, age ≥ 20 years, and no history of prior chemotherapy. S-1 (40-60 mg twice daily) was given orally on days 1 to 14, and irinotecan (100 mg/m2) and bevacizumab (5 mg/kg) were given intravenously on days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results. A total of 52 eligible patients were enrolled from October 2007 through March 2009. In safety analysis, the incidences of grade 3 or 4 adverse reactions were as follows: neutropenia, 27%; hypertension, 21%; and diarrhea, 17%. The overall response rate was 57.7%. Median progression-free survival was 16.7 months. Conclusion. IRIS plus bevacizumab is a well-tolerated, highly effective chemotherapeutic regimen that is easy to administer

Study protocol of HGCSG1404 SNOW study : a phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to patients with advanced gastric cancer

Background: In Japan, S-1 plus cisplatin (SP) regimen has become a standard therapy for patients with advanced gastric cancer. Moreover, the S-1 plus oxaliplatin regimen is now a standard treatment. Nab-paclitaxel was developed for chemotherapy of gastric cancer in Japanese clinical practice. Nab-paclitaxel, created with albumin-bound paclitaxel particles, has high transferability to tumour tissues and does not cause hypersensitivity reactions because of a different chemical composition compared with docetaxel and paclitaxel. A combination of S-1, nab-paclitaxel and oxaliplatin (which we named ‘SNOW regimen’) can be a promising triplet therapy for advanced gastric cancer. Although we have to pay attention to chemotherapy-induced neuropathy, we aim to investigate the recommended dose of this regimen in a phase I study. Furthermore, we will investigate its efficacy and toxicity in a phase II study. Methods: The phase I study is a dose-escalation study using a standard 3 plus 3 design, followed by expansion cohorts. The SNOW regimen involves 28-day cycles with escalated doses of nab-paclitaxel (100-175 mg/m2 on days 1 and 15) and fixed doses of oxaliplatin (65 mg/ m2 on days 1 and 15) and S-1 (80 mg/m2/day on day 1 to 14). The primary endpoints are assessment of dose limiting toxicities and determination of maximum tolerated dose to investigate the recommended dose in the subsequent phase II study. In the phase II study, the primary endpoint is objective response rate. Secondary endpoints are assessment of safety, progression-free survival, disease control rate, overall survival and time to treatment failure. Adverse events were monitored and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Discussion: Triplet therapies for advanced gastric cancer patients have been evaluated in clinical trials. The SNOW regimen can be a promising new triplet therapy. Trial registration: This study is performed at institutes that participate in Hokkaido Gastrointestinal Cancer Study Group (HGCSG) and registered as UMIN000016788. Registrated 16 March 2015

Adenocarcinoma arising from an ectopic pancreas in the duodenum : a case report

Background The malignant transformation of an ectopic pancreas in the duodenum is extremely rare. Herein, we report a case of an adenocarcinoma that arose from an ectopic pancreas. We also reviewed 14 cases of malignant transformations arising from an ectopic pancreas in the duodenum that were previously published. Case presentation An 81-year-old man with a 1-month history of vomiting was admitted to our institution. Esophagogastroduodenoscopy (EGD) and computed tomography (CT) scans revealed an obstruction at the first part of the duodenum. A distal gastrectomy was performed for diagnostic and therapeutic purposes. The histopathological examination of the resected specimen showed adenocarcinoma that arose from an ectopic pancreas (Heinrich type 1). The patient is alive without relapse at 18 months of follow-up. Conclusions Adenocarcinoma that arises from an ectopic pancreas should be considered when an obstruction is identified in the duodenum