Japanese Real-world Clinical Practice Research Articles

Clinical impact of the intensity of follow-up cystoscopy in patients with high-risk non-muscle-invasive bladder cancer.

There is significant lack on evidence regarding the effect of non-adherence to a recommended protocol in follow-up of high-risk non-muscle-invasive bladder cancer (NMIBC), or the impact of delaying detection of recurrent lesion. Here, we aimed to investigate the optimal frequency of follow-up cystoscopy of high-risk NMIBC with respect to oncological safety in the Japanese real-world clinical practice. This retrospective single-center study included 206 patients with primary high-risk NMIBC. The intensity (%) of follow-up cystoscopy was calculated based on actual visits for cystoscopy and guideline-recommended frequency in the first 24-month follow-up period. Inverse probability of treatment weighting analyses was used to reduce the risk of bias between groups. We performed a restricted cubic spline analysis with knots at intensity of follow-up cystoscopy ≤ 100% group to examine the possible association of progression risk with the intensity of follow-up as a continuous exposure. The median intensity was 87.5% (interquartile range, 75-100). Adjusted multivariate analysis for MIBC-free and progression-free survival demonstrated no significant difference between adjusted ≤ 75% and > 75% intensity groups. A restricted cubic spline analysis suggested no significant effect of the intensity of follow-up on progression risk, and hazard ratios of patients of < 100% intensity were equivalent to those of patients of 100% intensity. Our finding suggested decreased intensity of follow-up cystoscopy did not affect oncological outcomes in patients with high-risk NMIBC. Further prospective trials directly aimed at investigating optimized follow-up schedules for NMIBC are mandatory before substantial changes to existing clinical guidelines.

Kidney Outcomes Associated with Adherence to Recommendation from Evidence-Based Clinical Practice Guidelines for CKD 2018 in Japanese Real-World Clinical Practice

Kidney Outcomes Associated with Adherence to Recommendation from Evidence-Based Clinical Practice Guidelines for CKD 2018 in Japanese Real-World Clinical Practice

166P Comparative assessment of prognostic outcomes between vintage hormonal therapy and androgen deprivation therapy combined with novel androgen pathway inhibitor in Japanese patients with metastatic castration-sensitive prostate cancer

In recent years, therapeutic strategy for metastatic castration-sensitive prostate cancer (mCSPC) have been drastically changed since the introduction of combined treatment with conventional androgen-deprivation therapy (ADT) and novel androgen pathway inhibitor (ARPI). In Japanese real-world clinical practice, however, it remains common to perform vintage hormonal therapy (VHT) either by ADT alone or combined androgen blockade (CAB). The objective of this study was to analyze the impacts of upfront hormonal therapies on the prognostic outcomes in Japanese mCSPC patients. This study included 581 consecutive mCSPC patients consisting of 305 and 276 who received VHT (VHT group) and ADT plus ARPI (ARPI group), respectively, as first-line therapy. Potential parameters associated with PSA-progression free survival (PFS) and overall survival (OS) in these patients were investigated. Median PFS and OS of the 581 patients was 27 months and not reached, respectively. Multivariate analyses of several factors identified independent predictors associated with unfavorable PFS as follows: high alkaline phosphatase, high lactate dehydrogenase (LDH), number of bone metastasis ≥3, existence of symptoms, treatment with VHT, and those associated with unfavorable OS as follows: older age, poor performance status, high LDH, existence of symptoms. In LATITUDE low risk patients, the median PFSs were 36.6 months and not reached in the VHT and ARPI groups (P = 0.071), respectively, and the median OSs were not reached in both groups (P = 0.60). In LATITUDE high risk patients, the median PFSs were 12.4 months and not reached in the VHT and ARPI groups (P <0.001), respectively, and the median OSs were 40.2 months and not reached in the VHT and ARPI groups (P = 0.023), respectively. These findings suggest that it could be expected to achieve favorable prognostic outcomes in mCSPC patients, particularly those classified into LATITUDE high risk, by introducing ADT plus ARPI, rather than VHT, as first-line therapy.

Effectiveness of Pembrolizumab in Patients with HNSCC in Japanese Real-World Clinical Practice

Effectiveness of Pembrolizumab in Patients with HNSCC in Japanese Real-World Clinical Practice

Deciphering the clinical features of heterogeneous stage III non-small cell lung cancer in Japanese real-world clinical practice: Expanded cohort of the SOLUTION study

ObjectivesTo evaluate the actual treatment patterns with respective outcomes and the patient characteristics of stage III non-small cell lung cancer (NSCLC) in Japan. Materials and methodsPatients (aged ≥20 years at diagnosis) who were diagnosed with stage III NSCLC between January 2013 and December 2014 and underwent surgery, chemoradiotherapy (CRT), chemotherapy (CT), or radiotherapy (RT) at 11 institutions in Japan were consecutively registered in this retrospective, observational study (SOLUTION; UMIN000031385). Study measures included patient characteristics, first-line treatments, overall survival (OS), progression-free survival, objective response rate, and incidence of radiation-related adverse events. ResultsThe study population comprised 744 patients. The tumors were classified as stage IIIA and IIIB in 58.9% and 41.1% of patients, respectively. The tumors were considered resectable at diagnosis in 25.0% of patients. First-line treatments were surgery (20.0%), CRT (46.1%), CT (22.2%), and RT (11.7%). The median OS (mOS) in the overall population was 25.4 months and the 3-year OS rate was 38.7%. Among the four first-line treatment cohorts, OS most favored the surgery cohort: mOS was 43.4 months and the 3-year OS rate was 53.8%. Prognostic factors for OS in each treatment modality were analyzed using multivariable analysis and included the following: age, performance status, and histological type for the surgery cohort; sex, histological type, and primary lesion location (lower lobe) for the CRT cohort; and performance status and clinical stage for the RT cohort. The timing of peak incidence of pneumonitis from the start of first-line treatment was 18–20 and 12–14 weeks in the CRT and RT cohorts, respectively. ConclusionPatients with clinical stage III NSCLC received a variety of treatments selected to the clinical background and tumor status, and we clarified the outcome and prognostic factors. These findings will be a useful reference for future studies evaluating newly introduced treatments for stage III NSCLC.

Incidence and Clinical Features of Venous Thromboembolism in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Japan.

Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE. Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.

The real-world benefit of novel androgen receptor-targeting agents (ARTA) before and after docetaxel in CRPC with bone metastases in Japan: A subanalysis of the PROSTAT-BSI, a prospective observational study before and after approval of novel ARTAs.

43 Background: ARTAs (enzalutamide and abiraterone) have been approved for relapse of prostate cancer in Japan since 2014. However, the efficacy of ARTAs for overall survival (OS) has not yet been proven in Japanese real-world clinical practice. Bone Scan Index (BSI), amount of bone metastasis in a unit of %, has become available for bone scintigraphy using software of BONENAVI (EXINIbone) in Japan. To confirm the benefit of BSI, we conducted a prospective observational study from 2012 to 2017 on mHSPC and mCRPC prior to docetaxel (presented at ASCO-GU 2020). Then we conducted this subanalysis to investigate the real-world benefit of ARTAs on OS before and after docetaxel. Methods: Patients enrolled as the mHSPC (N = 148) and mCRPC (N = 99) groups in the PROSTAT-BSI registry over a 3-year observation period were analyzed with or without ARTAs or flutamide. Patients were evaluated for PSA progression, BSI progression, and OS during hormonal therapy or chemotherapy. Results: In the mHSPC group, 123 patients were treated with combined androgen blockade (androgen deprivation + 80 mg bicalutamide) as an initial hormonal therapy. Thirty-seven patients were treated with flutamide after PSA progression. Thirty-seven patients were also treated with ARTAs as 2nd or later. Docetaxel was used in 25 patients. There was no significant difference in PSA (median: 265.5 and 248.0 ng/mL; P = 0.877) and BSI (median: 1.28% and 1.68%; P = 0.131) between the ARTA (-) and ARTA (+) groups at the start of hormonal therapy, respectively. Despite a median PSA-PFS disadvantage of 16 months in the ARTA (+) group compared to the ARTA (-) group (median: 8.9 and 25.2 months), OS of both groups were comparable (3-year survival rate: 84.0% and 75.7%; HR [95% CI]:0.556 [0.238-1.299], P = 0.232), respectively, indicating favorable effect of ARTA on OS. Furthermore, OS tended to be more extended in patients who received flutamide prior to ARTAs (N = 21) (HR [95% CI]:0.3175 [0.050-2.026], P = 0.225). In the mCRPC group, 8 patients who used ARTA prior to docetaxel were excluded from this analysis. ARTAs were used to treat relapse after docetaxel in 44 patients. Cabazitaxel was used in 14 patients. There was no significant difference in PSA (median: 16.8 and 26.8 ng/mL; P = 0.240) and BSI (median: 2.43% and 1.48%; P = 0.105) between the ARTA (-) and ARTA (+) groups at the start of docetaxel, respectively. There was no significant difference in PSA-PFS between the ARTA (-) and ARTA (+) groups (median PSA-PFS: 4.3 months and 7.0 months; P = 0.999), but OS was significantly better in the ARTA (+) group in the ARTA (-) group (median OS: 28.9 months vs 21.1 months; HR [95% CI]: 0.484 [0.264-0.888]; P = 0.019). Conclusions: This subanalysis demonstrates the benefit of ARTAs for OS before and after docetaxel in clinical practice.

Glucagon-Like Peptide-1 Receptor Agonist Utilization in Type 2 Diabetes in Japan: A Retrospective Database Analysis (JDDM 57).

IntroductionThere are limited real-world data on the prescribing of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for patients with type 2 diabetes mellitus (T2DM).MethodsThis was a retrospective analysis of the CoDiC® database of the Japan Diabetes Clinical Data Management Study Group (JDDM). Demographic and clinical characteristics, concomitant treatment patterns, and GLP-1 RA treatment persistence or modification in patients with T2DM initiating GLP-1 RA therapy were evaluated.ResultsThe analysis included 932 eligible patients with T2DM who had their first GLP-1 RA prescription (index date) between September 2016 and July 2018. Mean age was 63.8 years and 56.0% were male. Most patients had an index GLP-1 RA of dulaglutide (65.7%) or liraglutide (29.1%). Common comorbidities were obesity (58.7%), hypertension (54.7%), dyslipidemia (52.0%), retinopathy (11.3%), and nephropathy (10.2%). Mean hemoglobin A1c (HbA1c) levels decreased from 8.3 to 7.8% over 6 months after GLP-1 RA initiation, and the proportion of patients achieving HbA1c < 7.0% increased from 14.4% at index date to 22.9% at 6 months. Reductions occurred in mean body weight, body mass index, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and adjusted urinary albumin over 6 months. Antidiabetic medication use decreased after GLP-1 RA initiation, whereas non-antidiabetic medication prescribing showed little change. Index GLP-1 RA persistence rates were 80.5%, 66.2%, and 51.6% at 6, 12, and 18 months post-index, respectively, with a median persistence until discontinuation or switch of 600 days. Persistence rates at 6, 12, and 18 months post-index, respectively, were 81.9%, 70.7%, and 65.4% for dulaglutide and 79.7%, 60.0%, and 30.4% for liraglutide.ConclusionThe study shows real-world benefits of GLP-1 RA therapy for T2DM, including improvements in HbA1c, body weight, and blood lipid profile, and supports the high rates of long-term persistence previously reported with dulaglutide, the GLP-1 RA most commonly prescribed for T2DM in Japanese clinical practice.Supplementary InformationThe online version of this article (10.1007/s13300-020-00977-w) contains supplementary material, which is available to authorized users.

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

BackgroundTo fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.MethodsThis was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.ResultsOverall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.ConclusionsThe effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.Trial registration numberUMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

Fixed-ratio combination of basal insulin and glucagon-like peptide-1 receptor agonists in the treatment of Japanese people with type 2 diabetes: An innovative solution to a complex therapeutic challenge.

Over 10 million people in Japan have known or suspected type 2 diabetes (T2D), and this number is expected to rise. Although many people require therapy escalation because of the progressive nature of T2D, this appears to be suboptimal in Japanese real-world clinical practice. Insulin therapy tends to be introduced only when glycaemic control is very poor (mean glycated haemoglobin >9%). Although basal insulin therapy is effective in reducing fasting plasma glucose (FPG), postprandial plasma glucose often remains uncontrolled. Basal-bolus insulin regimens are complex and carry the risk of weight gain and hypoglycaemia. Recently, fixed-ratio combinations (FRCs) of BI and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown efficacy in reducing both FPG and postprandial plasma glucose with a single injection and without increased risk of hypoglycaemia or weight gain. IDegLira, a titratable FRC of insulin degludec (100 U/mL) and liraglutide, is currently available in Japan and the United States/European Union at a ratio of 1 U (unit):0.036 mg. iGlarLixi (insulin glargine 100 U/mL and lixisenatide at a ratio of 1:1 (20 U/20 μg) has recently been approved in Japan. Phase 3 trials in Japan for IDegLira (DUAL Japan) and iGlarLixi (LixiLan JP) have shown that both FRCs are efficacious. This review provides an overview of IDegLira and iGlarLixi (Japanese formulation) and considers their potential use as new therapeutic options to address the clinical need for early glycaemic control in Japanese people with T2D.

Clinical Risk Factors of Thromboembolic and Major Bleeding Events for Patients with Atrial Fibrillation Treated with Rivaroxaban in Japan

Background: It is important to understand the risk of thromboembolism and bleeding in patients with nonvalvular atrial fibrillation (NVAF) receiving direct oral anticoagulants; however, data on risk factors in Japanese patients are limited. Methods: XAPASS (Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation) is a prospective observational study examining the safety and effectiveness of rivaroxaban in Japanese real-world clinical practice. We investigated risk factors for stroke/noncentral nervous system systemic embolism (non-CNS SE)/myocardial infarction (MI) and major bleeding using 1-year follow-up data. Associations between baseline characteristics and outcomes were examined by Cox regression analysis. Results: During April 2012-June 2014, 11,308 patients newly started with rivaroxaban treatment were enrolled. Of 9578 patients with 1-year data fixed as of September 2017, 6220 patients who received appropriate dosages of rivaroxaban for their creatinine clearance were included in the present safety outcomes subanalysis, and 6198 were included in the effectiveness outcomes analysis. Stroke/non-CNS SE/MI was observed in 97 of 6198 patients (1.6%, 1.8 events/100 patient-years), and major bleeding occurred in 102 of 6220 patients (1.6%, 1.9 events/100 patient-years). Age greater than or equal to 75 years (hazard ratio [HR]: 2.27; [95% confidence interval (CI): 1.49, 3.47]), prior ischemic stroke/transient ischemic attack (2.08; [1.38, 3.13]), and antiplatelet use (3.23; [1.83, 5.70]) were associated with stroke/non-CNS SE/MI. Creatinine clearance less than 50 mL/min (HR: 1.86; [95% CI: 1.26, 2.75]), diabetes (1.55; [1.02, 2.35]), and antiplatelet use (3.04; [1.70, 5.45]) were associated with major bleeding. Conclusions: These results would help physicians to assess risks in Japanese patients with NVAF receiving rivaroxaban.

2350-PUB: Renoprotective Effects of SGLT2 Inhibitors in Japanese Real-World Clinical Practice

Effects of SGLT2 inhibitors (SGLT2i) on renal functions were examined in patients with type 2 diabetes followed by our clinic. Subjects were 395 outpatients treated with SGLT2i (ipragliflozin 135; empagliflozin 101; canagliflozin 83; dapagliflozin 76; age 51.6 ± 11.3 years; duration of diabetes 7.21 ± 6.8 years; BMI 28.6 ± 4.5). Changes in eGFR at 1 year before and 2 years after the administration of SGLT2i versus at baseline were retrospectively analyzed in 2 groups divided by the baseline eGFR; eGFR&amp;lt;90 ml/min/1.73m2 group and eGFR≧90 group. The changes in urinary albumin excretion rate (UAER) and HbA1c levels were also examined. The average values of each four measures in a year were used as the levels for each period. In the eGFR&amp;lt;90 group (n = 179), the annual change in eGFR (ΔGFR) was -2.1 ± 5.5/year before administration of SGLT2i (p &amp;lt;0.001), -1.4 ± 7.5/year after 1 year (p = 0.020) and +0.2 ± 5.9/year between 1 and 2 years (p = 0.704). In the eGFR≧90 group (n = 164), ΔGFR was -1.2 ± 8.0/year before administration of SGLT2i (p = 0.180), -3.2 ± 11.6/year after 1 year (p = 0.001) and -1.2 ± 8.2/year between 1 and 2 years (p = 0.133). In the group with ΔGFR?-5/year before administration of SGLT2i (n = 56), ΔGFR was -9.1 ± 3.5/year before administration (p &amp;lt;0.001), -0.9 ± 8.9/year after 1 year (p = 0.473) and -2.4 ± 10.6/year between 1 and 2 years (p = 0.176). In the group with ΔGFR &amp;gt;-5/year before administration (n = 137), ΔGFR was +1.9 ± 5.3/year before administration (p &amp;lt;0.001), -4.1 ± 9.5/year after 1 year (p &amp;lt;0.001) and +0.6 ± 6.0/year between 1 and 2 years (p = 0.306). UAER changes in total subjects were +41.1 ± 267.5 mg/g creatinine/year before administration of SGLT2i (p = 0.039), -8.8 ± 220.1/year after 1 year (p = 0.474) and +8.0 ± 88.0/year between 1 and 2 years (p = 0.144). HbA1c levels were 7.27 ± 1.19% and 7.67 ± 1.31 at 1 year before and baseline, respectively, and decreased at 2 years (-0.49 ± 1.16%, p &amp;lt;0.001, n = 145). These observations suggest that SGLT2i may have protective effects on renal functions in the real-world clinical practice. Disclosure T. Tosaki: Research Support; Self; Daiichi Sankyo Company, Limited, Sanofi K.K. Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. S.T. Sato: None. M. Kondo: None. Y. Yamada: None. A. Inagaki: None. S. Tsunekawa: None. T. Himeno: None. Y. Kato: Speaker's Bureau; Self; Merck &amp; Co., Inc. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K.

Real-world outcomes of the Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS)

BackgroundAlthough the efficacy and safety of the factor Xa inhibitor rivaroxaban for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) were shown in global and Japanese phase III clinical trials, safety and effectiveness data from unselected patients in everyday clinical practice are limited. The objective of the XAPASS (Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation) is to investigate the safety and effectiveness of rivaroxaban in Japanese real-world clinical practice. MethodsThe XAPASS is a prospective, single-arm, real-world observational study mandated by the Japanese authority as post-marketing surveillance. In total, 11,308 patients with NVAF who began treatment with rivaroxaban were enrolled from April 2012 to June 2014, and 9578 patients were analyzed to examine the one-year outcomes. ResultsThe mean treatment duration was 300±119 days. The patients’ age was 73.2±9.8 years, and their CHADS2 score was 2.2±1.3. Any bleeding and major bleeding occurred in 602 patients (7.6 events per 100 patient-years) and 143 patients (1.8 events per 100 patient-years), respectively. Stroke/non-central nervous system systemic embolism/myocardial infarction was observed in 144 patients (1.8 events per 100 patient-years). ConclusionsReal-world outcomes of the XAPASS showed incidence rates of major bleeding and thromboembolic events, suggesting that rivaroxaban is safe and effective in Japanese daily clinical practice (Clinicaltrials.gov: NCT01582737).

MP58-18 OUTCOME OF METASTATIC UROTHELIAL CARCINOMA IN GC ERA: PROGNOSTIC FACTORS FROM REAL-WORLD CLINICAL PRACTICE IN JAPAN

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2015MP58-18 OUTCOME OF METASTATIC UROTHELIAL CARCINOMA IN GC ERA: PROGNOSTIC FACTORS FROM REAL-WORLD CLINICAL PRACTICE IN JAPAN Junji Ishizaki, Takashige Abe, Keita Minami, Ryuji Matsumoto, Toru Harabayashi, Ataru Sazawa, Tango Mochizuki, Satoshi Chiba, Tomoshige Akino, Masahi Murakumo, Naoto Miyajima, kunihiko Tsuchiya, Satoru Maruyama, and Nobuo Shinohara Junji IshizakiJunji Ishizaki More articles by this author , Takashige AbeTakashige Abe More articles by this author , Keita MinamiKeita Minami More articles by this author , Ryuji MatsumotoRyuji Matsumoto More articles by this author , Toru HarabayashiToru Harabayashi More articles by this author , Ataru SazawaAtaru Sazawa More articles by this author , Tango MochizukiTango Mochizuki More articles by this author , Satoshi ChibaSatoshi Chiba More articles by this author , Tomoshige AkinoTomoshige Akino More articles by this author , Masahi MurakumoMasahi Murakumo More articles by this author , Naoto MiyajimaNaoto Miyajima More articles by this author , kunihiko Tsuchiyakunihiko Tsuchiya More articles by this author , Satoru MaruyamaSatoru Maruyama More articles by this author , and Nobuo ShinoharaNobuo Shinohara More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2157AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Combinations of gemcitabine plus cisplatin (GC) or methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) are established as the standard induction regimens for metastatic urothelial carcinoma. However, most patients become refractory to treatment and, at present, optimal treatment in the second-line setting has not been determined. Clinicians treat this difficult disease with the use of salvage chemotherapy, bone-modifying agents in patients with bone metastasis, or the resection of metastasis. The present study investigated prognostic factors of metatstatic urothelial carcinoma in Japanese real-world clinical practice in the GC era. METHODS A total of 225 patients with metastatic urothelial carcinoma undergoing systemic chemotherapy between 2000 and 2013 at seven hospitals were included in the present study. The GC regimen was administered as induction chemotherapy to 128 patients, while MVAC or its modified regimen was given to 71 patients. Of the 225 patients, 117 underwent at least two different regimens during treatment and 25 patients underwent resection of metastases, aiming to improve the outcome. The relationship between clinical characteristics and survival was analyzed using the Cox proportional hazards model. The characteristics analyzed were age, sex, ECOG performance status, primary site, pathology of primary site, hemoglobin levels, LDH levels, CRP levels, corrected calcium levels, eGFR levels, history of prior chemotherapy, resection of primary site, metastatic sites, number of metastatic organs, and resection of metastasis. RESULTS The median survival time was 17 months (95% confidence interval: 14-20 months) for 225 patients. Using a multivariate model, female sex (HR=0.509, p=0.0007), ECOG-PS0 at presentation (HR=0.463, p=0.0002), Hb level of more than 10 g/dL (HR=0.458, p=0.0034), single organ metastasis (HR=0.565, p=0.0012), and resection of metastatsis (HR=0.447, p=0.0043) were significant independent predictors of prolonged survival. CONCLUSIONS A more favorable PS at presentation, normal Hb level, single organ metastasis, and resection of metatstasis were favorable prognostic factors. In addition, a female sex was associated with long-term disease control. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e728 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Junji Ishizaki More articles by this author Takashige Abe More articles by this author Keita Minami More articles by this author Ryuji Matsumoto More articles by this author Toru Harabayashi More articles by this author Ataru Sazawa More articles by this author Tango Mochizuki More articles by this author Satoshi Chiba More articles by this author Tomoshige Akino More articles by this author Masahi Murakumo More articles by this author Naoto Miyajima More articles by this author kunihiko Tsuchiya More articles by this author Satoru Maruyama More articles by this author Nobuo Shinohara More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prevalence and the long-term prognosis of functional mitral regurgitation in Japanese patients with symptomatic heart failure

Functional mitral regurgitation (FMR) is a common and critical condition in patients with heart failure (HF); however, the prevalence and clinical outcome of FMR in Japanese real-world clinical practice remain unclear. Within a single hospital-based cohort in the Shinken Database 2004-2011, which comprised all new patients (n = 17,517) who visited the Cardiovascular Institute, we followed symptomatic HF patients. A total of 1,701 patients were included: 104 FMR patients (who had moderate to severe FMR) and 1,597 non-FMR patients (who had none or mild FMR). FMR patients had lower rates of hypertension and dyslipidemia, but higher rates of dilated cardiomyopathy, atrial fibrillation, and New York Heart Association functional class III/IV. FMR patients had higher levels of brain natriuretic peptide and lower left ventricular function. Use of cardiovascular drugs was more common among FMR patients. Kaplan-Meier curves revealed that the incidences of all-cause death, cardiovascular death, and admission for HF were significantly higher in FMR patients. The adjusted Cox regression analysis showed that significant FMR was associated with higher incidences of all-cause death [hazard ratio (HR) 2.179, 95 % confidence interval (CI) 1.266-3.751; P = 0.005], cardiovascular death (HR 2.371, 95 % CI 1.157-4.858; P = 0.018), and admission for HF (HR 1.819, 95 % CI 1.133-2.920; P = 0.013). FMR was common in Japanese symptomatic HF patients and was associated with adverse long-term outcomes. Establishing optimal therapeutic strategies for FMR is warranted.

The long-term efficacy of cilostazol in addition to dual antiplatelet therapy after sirolimus-eluting stent implantation for Japanese patients: an analysis of the 3-year follow-up outcomes from the j-Cypher registry

Several clinical studies have reported the use of cilostazol in addition to aspirin and thienopyridine (triple antiplatelet therapy, TAPT) after percutaneous coronary intervention (PCI) decreases clinical events. However, the efficacy and safety of TAPT have not been fully evaluated in Japan. The prospectively collected data from 12824 Japanese patients received PCI as part of the j-Cypher Registry were analyzed. We selected 10356 patients who exclusively received implantation of sirolimus-eluting stents (SES), and compared the data from 10128 patients who received dual antiplatelet therapy (aspirin + thienopyridine, DAPT) with 228 patients who received TAPT at the time of discharge. Patients who received TAPT had more comorbidities, such as peripheral vascular disease, renal failure with hemodialysis or insulin dependent diabetes mellitus, and more patients received stenting for the left main trunk. The cardiovascular event rates at 3 years after PCI in the TAPT group were not significantly different from DAPT group, even after adjusted risks for cardiovascular events; all-cause death (7.8 vs. 6.7 %, log-rank p = 0.44, adjusted Hazard Ratio [HR] 0.88: 95 % confidence interval [CI] 0.52-1.38, p = 0.61), myocardial infarction (1.7 vs. 2.4 %, log-rank p = 0.49 and HR 0.71: 95 % CI 0.20-1.57, p = 0.40), target legion revascularization (12.7 vs. 9.9 %, log-rank p = 0.11 and HR 1.05: 95 % CI 0.71-1.50, p = 0.91) and stroke (3.9 vs. 3.2 %, log-rank p = 0.52 and HR 1.09: 95 % CI 0.52-2.00, p = 0.80). In conclusion, TAPT after SES implantation was associated with similar long-term clinical outcomes as DAPT in Japanese real-world clinical practice, although we did not evaluate the bleeding outcome.

Association of the use of proton pump inhibitors with adverse cardiovascular and bleeding outcomes after percutaneous coronary intervention in the Japanese real world clinical practice

Previous studies have shown inconsistent results regarding the effects of concomitant use of clopidogrel and proton pump inhibitors (PPI) on cardiovascular outcomes. We sought to evaluate the clinical impact of PPI-use in patients treated with thienopyridines after percutaneous coronary intervention (PCI) in a large Japanese observational database. Among 12446 patients discharged alive on thienopyridines (ticlopidine 90.4% and clopidogrel 9.6%), 3223 patients were treated with PPIs and 9223 patients without PPI at the time of hospital discharge. The PPI group included more patients with co-morbidities than the non-PPI group. The adjusted hazard ratio (HR) of PPI-use for a composite of cardiovascular death, myocardial infarction, and stroke was 1.26 (95% confidence interval (CI) 1.09-1.47, p=0.002). The adjusted HR of PPI-use for bleeding was 1.26 (95% CI 1.05-1.52, p=0.013). Cardiovascular and bleeding outcomes were not different among the three groups receiving three different types of PPI. The negative effect of PPI on cardiovascular outcome was consistently seen in both drug-eluting stent (DES) [HR 1.31 (95% CI 1.07-1.6, p=0.0097)] and non-DES strata [HR 1.25 (95% CI: 0.99-1.57, p=0.057)] (Interaction p=0.79) despite the fact that the duration of thienopyridine administration was significantly longer in patients receiving DES. In conclusion, cardiovascular outcomes after PCI were significantly worse in patients with PPI than in patients without PPI in the Japanese real clinical practice. However, the observed poorer cardiovascular outcome in patients receiving PPI was most likely to be related to residual confounding and seemed not causally related to attenuation of antiplatelet effect of thienopyridine through interaction with PPI.