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Purpose: Radiotherapy (RT) and endocrine therapy (ET) are standard treatment options after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We investigated the national patterns of adjuvant therapy use after BCS for DCIS in Japan., Methods: We obtained relevant data of patients diagnosed with DCIS undergoing surgery and treated with BCS between 2014 and 2016 from the Japanese Breast Cancer Registry database. The relationship between the clinicopathologic, institutional, and regional factors, and adjuvant treatment was examined using multivariable analyses., Results: We identified 9516 patients who underwent BCS for DCIS. Overall, 23% received no adjuvant treatment, 71% received RT, 32% received ET, and 26% received combination therapy. The percentages of patients who received ET and combination therapy in 2016 were significantly lower [odds ratio (OR): 0.71, 0.77, respectively] than in 2014. The proportion of RT was low among young or elderly patients (OR: 0.75, 0.44, respectively) and in non-certified facilities (OR: 0.56). The proportion of ET was high in non-certified facilities (OR: 1.58) and among patients with positive margins (OR: 1.62). Combination therapy was higher among patients with positive margins (OR: 1.53)., Conclusions: Our study found a distinct adjuvant treatment pattern after BCS for DCIS depending on clinicopathologic factors, year, age, which indicate that physicians provide individualized treatment according to the background of the patients and the biology of DCIS. The facilities and regions remain significant factors of influencing adjuvant treatment pattern., (© 2021. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Objective: To investigate the frequency of laparoscopic liver resection (LLR) nationwide in Japan., Background: LLR was initially limited to basic liver resection, but is becoming more common in advanced liver resection., Methods: Retrospective observational study of 148,507 patients registered in the National Clinical Database 2011-2017. Excluded: liver resection with biliary and vascular reconstruction., Results: LLR or open liver resection (OLR) was performed in 1848 (9.9%) and 16,888 (90.1%) patients, respectively, in 2011, whereas in 2017, LLR had increased to 24.8% and OLR decreased to 75.2% of resections (5648 and 17,099 patients, respectively). There was an annual increasing trend of LLR, starting at 9.9%, then 13.8%, 17.3%, 21.2%, 18.1%, 21.0%, and finally 24.8% in 2017. Basic LLR became more common, up to 30.8% of LR in 2017. Advanced LLR increased from 3.3% of all resections in 2011 to 10.8% in 2017. Throughout the years observed, there were fewer complications in LLR than OLR. Operative mortality was 3.6% for both advanced LLR and OLR in 2011, and decreased to 1.0% and 2.0%, respectively, in 2017. Mortality for both basic LLR and basic OLR were low and did not change throughout the study, at 0.5% and 1.6%, respectively, in 2011 and 0.5% and 1.1%, in 2017., Conclusions: LLR has rapidly become widespread in Japan. Basic LLR is now a standard option, and advanced LLR, while not as common yet, has been increasing year by year. LLR has been safely developed with low mortality and complications rate relative to OLR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: This study aimed at investigating the real-world prognostic impact of systemic treatment in older patients with stage II/III breast cancer (BC)., Methods: This retrospective cohort study included patients with stage II/III primary BC, aged ≥55 years, and registered in the Japanese Breast Cancer Registry from 2004 to 2011. The clinicopathological characteristics, treatments, and prognosis of patients aged ≥75 years (older) were compared to those of younger patients., Results: In total, 56,093 patients (12,727, ≥75 years; 17,860, 65-74 years; 25,506, 55-64 years) were enrolled. In the older group, 9.2% with a luminal (hormone receptor [HR]+/human epidermal growth factor receptor 2 [HER2]-), 32.9% with a triple-negative (TN, HR-/HER2-), and 27.4% with a HER2-positive (any-HR/HER2+) receptor were administered chemotherapy. In those with luminal cancer, the 5-year breast cancer-specific survival (BCSS) was approximately 95% in all age groups. Meanwhile, among those with TN and HER2-positive BC, the older group had a poorer BCSS. The 5-year overall survival (OS) was also poorer in the older group across all subtypes. Among older patients matched using clinicopathological factors, chemotherapy use was associated with improved OS in the luminal and HER2-positive subtypes., Conclusions: Chemotherapy use was lower among older patients with stage II/III breast cancer. Those with TN and HER2-positive BC had a lower BCSS than their younger counterparts. Chemotherapy may be beneficial in improving the OS in older patients with luminal and HER2-positive BCs. Treatment for older patients should be individualized, based on tumor-related factors, quality of life, and the patient's health status., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships that may be considered as potential competing interests: HK has received a speaker’s fee from Pfizer Japan Inc. and a consultation fee from Mitsubishi Tanabe Pharma Corporation. HK and HM are affiliated with the Department of Health Quality Assessment at the University of Tokyo, and the Social Collaboration Department, supported by the National Clinical Database, Johnson & Johnson K.K., and Nipro Corporation. SS received consulting fees from Novartis, Chugai, and Kyowa Kirin and fees for non-CME services received directly from commercial interest or their agents from Pfizer, Novartis, AstraZeneca, Eli-lilly, Eisai, Kyowa Kirin, and Chugai.All remaining authors have declared no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We recently reported early postoperative results comparing the use of an anastomosis-assist device with a side-biting clamp for ascending aorta during coronary artery bypass grafting (CABG). Transient neurological complications occurred less often with the device. Here, we evaluated the perioperative safety of the device compared with the aorta no-touch technique (no-touch)., Methods: We evaluated patients listed in the Japan Adult Cardiovascular Surgery Database who received isolated off-pump CABG with either the device or the no-touch approach from 2014 to 2016. We performed a one-to-one matched analysis based on a propensity score modeled from patient demographics, comorbidities, cardiac conditions, and procedural characteristics. We compared early outcomes in both groups using Pearson's chi-square or Wilcoxon rank sum test as appropriate; P less than .05 was statistically significant., Results: Among 9546 device and 6890 no-touch patients, we found 5012 patient matches for each group. The device operation time was significantly longer (293 versus 281 minutes; P < .001) and homologous transfusion was significantly greater (56.9% versus 51.0%; P < .001) than with no-touch. Thirty-day operative mortality (1.5% versus 1.7%; P = .34), morbidity and mortality (6.8% versus 7.5%; P = .17), and stroke (0.9% versus 1.1%; P = .36) were similar in both groups. New-onset atrial fibrillation (11.9% versus 10.3%; P = .01) occurred significantly more often with the device. Newly initiated dialysis (1.4% versus 1.9%; P = .051) was more frequent with no-touch whereas reoperation for graft occlusion was more frequent with the device (1.0% versus 0.6%; P = .06) but was not significant for either outcome., Conclusions: The clinical safety of use of the device in CABG was comparable to no-touch for mortality and morbidity. Hemostasis may be a key issue for accomplishing higher-level quality control when devices are used in proximal anastomosis of CABG., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The incidence of type 1 diabetes mellitus (T1DM) and hypothyroidism as immune-related adverse events (irAEs) after programmed cell death-1 inhibitor (PD-1i) administration has not yet been sufficiently evaluated in a real clinical setting. To assess the incidence of T1DM and hypothyroidism among PD-1is and to identify the risk factors associated with hypothyroidism using a large claims database., Methods: This cohort study used the Shizuoka Kokuho database in Japan from 2012 to 2018, including approximately 2.2 million people. We enrolled 695 PD-1i-treated patients. T1DM and hypothyroidism as irAEs were identified using International Classification of Diseases 10th Revision and Anatomical Therapeutic Chemical classification codes. Risk factors for hypothyroidism were explored using the multivariable Fine and Gray regression model after adjusting for age group and sex, treating death as a competing risk., Results: The cumulative incidences of T1DM and hypothyroidism were 0.3% and 8.3%, respectively. We described the detailed onset timing of irAEs in patients with T1DM and hypothyroidism; hypothyroidism was observed evenly within 1 year of the PD-1i prescription. Sex and certain cancer types, such as lung and urothelial cancers, were significantly associated with subdistribution hazard ratio (sHR) (female: sHR, 2.04 [95% CI, 1.20-3.47]; lung cancer: sHR, 0.55 [95% CI, 0.32-0.95]; and urothelial carcinoma: sHR, 2.40 [95% CI, 1.05-5.49])., Conclusion: The incidence of T1DM and hypothyroidism as irAEs and associated risk factors identified in this analysis were comparable to those found in previous studies. The use of a large claims database to detect irAEs, such as T1DM and hypothyroidism, may lead to safer use of PD-1is., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Background: There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis., Methods and results: Among the 281 patients with R-PH included in this study, there was a treatment-naïve cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI., Conclusions: This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.

Background: Minimal data are available to support the clinical management of older breast cancer patients. Consequently, the standard of care remains unclear. Our aim was to clarify the clinicopathological characteristics, practical treatments, and prognosis of older Japanese breast cancer patients and discuss clinical issues., Methods: We reviewed 132,240 cases, diagnosed between 2004 and 2011, from the Japanese Breast Cancer Registry. Focusing on older patients, we compared data among three age groups: 75 years and over (n = 27,385), 65-74 years (n = 43,839), and 55-64 years (n = 61,016)., Results: Data revealed the proportions of mucinous and apocrine carcinoma were higher in older patients, and they more frequently had clinical stage II and III cancer. Their ER-positive rates were higher, in contrast to the lower HER2-positive, breast-conserving surgery (BCS), post-BCS irradiation, and adjuvant chemotherapy rates. Almost half of the older patients who underwent chemotherapy received CMF or oral 5FU, during hormone therapy, Tamoxifen was administered more frequently. The overall survival rate decreased with age, but the breast cancer-specific survival (BCSS) at 5 years remained similar. The rate of other cause of death in the oldest group was about a half, and more than double that in those aged 55-64 years., Conclusions: We showed clinical data of older breast cancer patients in Japan. Their disease was more advanced at the time of diagnosis, post-BCS irradiation and primary systemic chemotherapy were omitted more frequently, and overall, BCSS was similar among age categories, although the rate of other causes of death was higher.

Background: Postoperative intra-abdominal infectious complication (PIIC) after gastrectomy for gastric cancer worsens in-hospital death or long-term survival. However, the methodology for PIIC preoperative risk assessment remains unestablished. We aimed to develop a preoperative risk model for postgastrectomy PIIC., Methods: We collected 183,936 patients' data on distal or total gastrectomy performed in 2013-2016 for gastric cancer from the Japanese National Clinical Database and divided into development (2013-2015; n = 140,558) and validation (2016; n = 43,378) cohort. The primary outcome was the incidence of PIIC. The risk model for PIIC was developed using 18 preoperative factors: age, sex, body mass index, activities of daily living, 12 comorbidity types, gastric cancer stage, and surgical procedure in the development cohort. Secondarily, we developed another model based on the new scoring system for clinical use using selected factors., Results: The overall incidence of PIIC was 4.7%, including 2.6%, 1.7%, and 1.3% in anastomotic leakage, pancreatic fistula, and intra-abdominal abscess, respectively. Among the 18 preoperative factors, male [odds ratio, (OR) 1.92], obesity (OR, 1.52-1.96), peripheral vascular disease (OR, 1.55), steroid use (OR, 1.83), and total gastrectomy (OR, 1.89) strongly correlated with PIIC incidence. The entire model using the 18 factors had good discrimination and calibration in the validation cohort. We selected eight relevant factors to create a simple scoring system, using which we categorized the patients into three risk groups, which showed good calibration., Conclusion: Using nationwide clinical practice data, we created a preoperative risk model for postgastrectomy PIIC for gastric cancer.

Background: Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US residents with Japanese origin (USJ), and US residents with other origins (USO)., Method: Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status., Results: We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval [CI] 0.45-0.47 for Japanese and 0.66 [95% CI 0.59-0.74] for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 [95% CI 0.51-0.55] for Japanese and 0.53 [95% CI 0.52-0.74] for USJ)., Conclusions: In stage I-III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.

Background: The Japanese Breast Cancer Society Registry started in 1975; it was transferred to the registry platform of the National Clinical Database in 2012. We provide the annual data and an analysis of the Breast Cancer Registry for 2017., Methods: Patients' characteristics and pathological data of the 95,203 registered Japanese breast cancer patients from 1,427 institutes in 2017 were obtained. Trends in age at diagnosis and pathological stage were determined during the most recent 6 years (2012-2017)., Results: The mean onset age was 60.2 years with bimodal peaks at 45-49 years and 65-69 years. A short-term trend of the most recent 6 years of data caused the second, older peak. At diagnosis, 32.4% of breast cancer patients were premenopausal. The distribution of stages revealed that the proportion of early stage breast cancer (stage 0-I) increased up to 60%. At the initial diagnosis, 2.2% of patients presented with metastatic disease. Sentinel node biopsy without axillary node dissection was performed without neoadjuvant chemotherapy (NAC) in 68.8%, and with NAC in 31.1%, of patients. For patients without NAC, lymph node metastasis was less than 3% if the tumor size was less than 1 cm. The proportion of node-negativity decreased to 79.5% when tumor size was 2.1-5 cm., Conclusions: This analysis of the registry provides new information for effective treatment in clinical practice, cancer prevention, and the conduct of clinical trials. Further development of the registry and progress in collecting prognostic data will greatly enhance its scientific value.

Nonadherence to antihypertensive drugs is a primary reason for suboptimal clinical outcomes among hypertensive patients. We assessed adherence to newly initiated antihypertensive medications in non-elderly Japanese patients and examined which patient and facility characteristics were associated with low adherence. We selected new oral antihypertensive drug users, aged 30-74 years, between 2014 and 2016 from a large administrative claims database. We measured adherence as the proportion of days covered (PDC) during a 1-year follow-up and divided patients into three groups of low (PDC < 40%), intermediate (PDC ≥ 40% to <80%), and high (PDC ≥ 80%) adherence. Factors associated with low adherence were assessed by logistic regression analysis with generalized estimating equations. Among 31,592 patients (mean age, 51.7 years; 41.2% female), the median 1-year PDC was 88.5% (IQR: 41.9-98.1%). In total, 59.2%, 16.6%, and 24.2% of patients were categorized as having high, intermediate, and low adherence, respectively. Female sex (odds ratio [OR] 1.15, 95% confidential interval [95% CI] 1.08-1.22), younger age, and the initiation of angiotensin-converting enzyme inhibitors (OR 1.37, 95% CI 1.12-1.66), beta-blockers and thiazide diuretics (OR 4.82, 95% CI 4.34-5.36 and OR 3.91, 95% CI 2.79-5.46, respectively; compared with angiotensin II receptor blockers) were associated with low adherence. Patients initiating antihypertensives at larger hospitals (≥200 beds) were more likely to be adherent. While adherence to antihypertensive drugs in non-elderly Japanese patients was relatively high compared with that reported in previous studies in Western countries, patients with intermediate-low adherence may benefit from targeted interventions.

The Japanese Breast Cancer Society (JBCS) registry began data collection in 1975, and it was integrated into National Clinical Database in 2012. As of 2016, the JBCS registry contains records of 656,896 breast cancer patients from more than 1400 hospitals throughout Japan. In the 2016 registration, the number of institutes involved was 1422, and the total number of patients was 95,870. We herein present the summary of the annual data of the JBCS registry collected in 2016. We analyzed the demographic and clinicopathologic characteristics of registered breast cancer patients from various angles. Especially, we examined the registrations on family history, menstruation, onset age, body mass index according to age, nodal status based on tumor size and subtype, and proportion based on ER, PgR, and HER2 status. This report based on the JBCS registry would support clinical management for breast cancer patients and clinical study in the near future.

Objective: To determine the pattern of antidiabetic drug use, with a particular focus on the metformin dose, among patients with type 2 diabetes mellitus (T2DM) in a Japanese working population. Methods: We used an administrative claims database linked to yearly health check-up data from large corporations. Data were collected for T2DM patients who began using an antidiabetic drug between 2014 and 2017 ( n  = 20,401). We evaluated the type of antidiabetic drug used and the characteristics of the patients using each type of drug. Among the metformin users, we assessed the titration in its dose or treatment during the 12 month period after initiation at 3 month intervals. Results: Among 20,401 new antidiabetic users, the most frequently used agents during the study period were dipeptidyl peptidase-4 inhibitors (DPP4is; 47.4%), followed by biguanides (18.5%) and sodium glucose cotransporter-2 inhibitors (SGLT2is; 6.7%). Most patients who initiated with metformin were prescribed 500 mg or less daily (72.9%); only 2.0% were prescribed a daily dose of >1000 mg. Moreover, 27% remained on the same daily dose during the 1 year follow-up, whereas another 29.9% discontinued their antidiabetic treatment altogether. Conclusions: A unique pattern of prescription was observed amongst Japanese patients with T2DM, and DPP4is, rather than metformin, were predominantly used as the first-line treatment. SGLT2is were infrequently prescribed. Metformin was prescribed at a daily dose of ≤500 mg in many patients. Greater efforts are needed to assess the comparative effectiveness of these treatment strategies.

Background: International collaboration has an interest in health care quality evaluation. We compared characteristics and surgical outcomes between Asian patients in the United States and Japanese patients who undergo adult cardiac surgery., Methods: Using the Japan Adult Cardiovascular Surgery Database (JCVSD) and The Society of Thoracic Surgeons (STS) National Database, we compared Asian patients undergoing isolated coronary artery bypass graft surgery between 2013 and 2016 in Japan and the United States. The STS had 16,903 Asian patients among 573,823 patients of all races undergoing isolated coronary artery bypass graft surgery (2.95%); the JCVSD had 55,570 patients, almost all of whom are Japanese. Descriptive statistics were analyzed independently, then the data were aggregated for comparison., Results: The JCVSD patients were older (69 vs 65 years) with a smaller body surface area (1.65 m 2 vs 1.81 m 2 ) and body mass index (24 kg/m 2 vs 26 kg/m 2 ). The proportion of males (79% vs 78%), prevalence of chronic lung disease (82% vs 86%), and diabetes mellitus (54% vs 60%) were similar. The JCVSD had higher prevalence of renal disease requiring dialysis (11% vs 6%). The numbers of anastomoses were similar (3.1 vs 3.3); off-pump procedures and the usage of right internal mammary artery were more prevalent (60% vs 15% and 38% vs 7%, respectively) in the JCVSD. The unadjusted operative mortality was 2.7% in the JCVSD and 2.1% in the STS database., Conclusions: Comparisons of coronary artery bypass graft surgery characteristics and outcomes were conducted between the STS National Database and the JCVSD to illustrate the value of international collaboration on adult cardiac surgery databases., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The introduction of transcatheter aortic valve implantation (TAVI) into Japan was strictly controlled to optimize patient outcomes. The goal of this study was to assess if increasing experience during the introduction of this procedure was associated with outcomes., Methods and results: The initial 1,752 patients registered in the Japanese national TAVI registry were included in the study. The association between operator procedure number and incidence of the early safety endpoint at 30 days (ESE30) as defined in the Valve Academic Research Consortium-2 consensus document was evaluated. Patients were divided into 4 groups by quartiles of procedure count (Groups I-IV in order of increasing number of procedures). Median patient age was 85 years, and 30.5% were male. The 30-day mortality rate was 1.4% (n=24), and 78 patients (7.9%) experienced 95 ESE30. Among the variables included in the model, ESE30 was associated with non-transfemoral approach (P=0.004), renal dysfunction (Cr >2.0 mg/dL) (P=0.01) and NYHA class III/IV (P=0.04). ESE30 incidence was not significantly different between Groups I-III and Group IV. Spline plots demonstrated that experience of 15-20 cases in total was needed to achieve a consistent low risk of ESE30., Conclusions: Increasing experience was associated with better outcomes, but to a lesser degree than in previous reports. Our findings suggested that the risks associated with the learning curve process were appropriately mitigated.

Background: The trend of the initial treatment strategy for pulmonary arterial hypertension (PAH) has changed from monotherapies to upfront combination therapies. This study analyzed treatments and outcomes in Japanese patients with PAH, using data from the Japan PH Registry (JAPHR), which is the first organized multicenter registry for PAH in Japan., Methods and results: We studied 189 consecutive patients (108 treatment-naïve and 81 background therapy patients) with PAH in 8 pulmonary hypertension (PH) centers enrolled from April 2008 to March 2013. We performed retrospective survival analyses and analyzed the association between upfront combination and hemodynamic improvement, adjusting for baseline NYHA classification status. Among the 189 patients, 1-, 2-, and 3-year survival rates were 97.0% (95% CI: 92.1-98.4), 92.6% (95% CI: 87.0-95.9), and 88.2% (95% CI: 81.3-92.7), respectively. In the treatment-naïve cohort, 33% of the patients received upfront combination therapy. In this cohort, 1-, 2-, and 3-year survival rates were 97.6% (95% CI: 90.6-99.4), 97.6% (95% CI: 90.6-99.4), and 95.7% (95% CI: 86.9-98.6), respectively. Patients on upfront combination therapy were 5.27-fold more likely to show hemodynamic improvement at the first follow-up compared with monotherapy (95% CI: 2.68-10.36)., Conclusions: According to JAPHR data, initial upfront combination therapy is associated with improvement in hemodynamic status.