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INTRODUCTION: The aim of this study is to characterize health related quality of life (HRQOL) in Japanese patients after bladder cancer surgery and to perform cross-cultural comparison between Japanese and American patients. METHODS: Firstly, we cross-sectionally assessed HRQOL of 371 patients in Japan using the Bladder Cancer Index (BCI-Japanese). HRQOL of the four groups of patients (native bladder without intravesical therapy, native bladder with intravesical therapy, cystectomy with ileal conduit, and cystectomy with neobladder) were assessed. Secondly, we compared the Japanese with the American cohort (n = 315) from the original BCI paper. After adjusting for age and gender, the differences in each BCI subdomain score was analyzed. RESULTS: Among Japanese patients, the urinary domain function score was significantly lower among the cystectomy with neobladder group, compared to the cystectomy with ileal conduit group (p

Oral fluoropyrimidines, such as S-1, have been shown to have a role in controlling disease progression in metastatic breast cancer. We examined adjuvant treatment with S-1 in patients with oestrogen receptor (ER)-positive and HER2-negative primary breast cancer.We did a multicentre, open-label, randomised, controlled, phase 3 trial in 139 sites (137 hospitals and two clinics). Eligible patients were women aged 20-75 years with histologically diagnosed stage I to IIIB invasive breast cancer (intermediate to high risk of recurrence). Patients were temporarily registered at participating institutions and biopsy or surgical samples were collected and sent for central pathological assessment. Patients received 5 years of standard adjuvant endocrine therapy (selective oestrogen receptor modulators with or without ovarian suppression and aromatase inhibitors) with or without 1 year of S-1. Oral S-1 80-120 mg/day was administered twice a day for 14 days with 7 days off. Randomisation (1:1) using the minimisation method was done with six stratification factors (age, axillary lymph node metastasis at surgery or sentinel lymph node biopsy, preoperative or postoperative (neoadjuvant or adjuvant) chemotherapy, preoperative endocrine therapy, proportion of ER-positive cells, and study site). The primary endpoint was invasive disease-free survival, in the full analysis set (all randomly assigned patients, excluding those with significant protocol deviations). The safety analysis set consisted of all patients who received at least one dose of study treatment. Here, we report the results from the interim analysis at the data cutoff date Jan 31, 2019. This trial is registered with Japan Registry of Clinical Trials, jRCTs051180057, and the University hospital Medical Information Network, UMIN000003969.Between Feb 1, 2012, and Feb 1, 2016, 1930 patients were enrolled in the full analysis set, 957 (50%) received endocrine therapy plus S-1 and 973 (50%) received endocrine therapy alone. Median follow-up was 52·2 months (IQR 42·1-58·9). 155 (16%) patients in the endocrine therapy alone group and in 101 (11%) patients in the endocrine therapy plus S-1 group had invasive disease-free survival events (hazard ratio 0·63, 95% CI 0·49-0·81, p=0·0003). As the primary endpoint was met at interim analysis, the trial was terminated early. The most common grade 3 or worse adverse events were decreased neutrophil count (72 [8%] of 954 patients in the endocrine therapy plus S-1 group vs seven [1%] of 970 patients in the endocrine therapy alone group), diarrhoea (18 [2%] vs none), decreased white blood cells (15 [2%] vs two [1%]), and fatigue (six [1%] vs none). Serious adverse events were reported in nine (1%) of 970 patients in the endocrine therapy alone group and 25 (3%) of 954 patients in the endocrine therapy plus S-1 group. There was one (1%) possible treatment-related death in the endocrine therapy plus S-1 group due to suspected pulmonary artery thrombosis.These data suggest that this combination of S-1 with endocrine therapy could be a potential treatment option for this intermediate and high-risk group of patients with ER-positive, HER2-negative primary breast cancer.Public Health Research Foundation (Japan), Taiho Pharmaceutical.

Introduction We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures. Methods The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed. Results This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12–66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach’s alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = − 0.19). A missing value percentage of > 15% was associated with old age (p Conclusions Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

Although acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever (ARF) are well-known complications of group A streptococcus infection, concomitant occurrence of both diseases is rare. We report an 11-year-old Japanese girl with primary Sjögren's syndrome complicated by acute renal failure about 2 weeks after the onset of pharyngitis. Although histopathological findings of the kidney were not confirmative, APSGN was suggested by the spontaneous recovery of her renal function, typical latent period with high levels of antistreptolysin O and low serum levels of C3 but not of C4. In addition, cardiac hypomotility and regurgitation of the 4 valves progressed in the convalescent phase of APSGN, which was accompanied by elevation of serum C-reactive protein and plasma brain natriuretic peptide (BNP) levels. Myocarditis was suggested by delayed gadolinium-enhancement of cardiac walls on cardiac magnetic resonance imaging. She was diagnosed with APSGN and ARF and was treated with a combination of short course prednisolone and prophylactic penicillin G. There is no relapse of renal or cardiac symptoms during 6 years follow-up. Unexpected elevation of plasma BNP in a convalescent stage of APSGN suggests the development of ARF. Underlying Sjögren's syndrome (SS) may modify the histopathological findings and make it difficult to differentiate APSGN from CTD-associated nephritis such as lupus nephritis (LN) even by renal biopsy.

BACKGROUND: Although long-term prognostic outcomes of primary breast cancer (PBC) patients have been improved remarkably in recent years, the disease recurrence remains a serious problem. We have previously investigated a role for oral fluoropyrimidines in postoperative adjuvant treatments.In this study, we aimed to verify the usefulness of S-1 in combination with adjuvant endocrine therapy for PBC patients having luminal disease. PATIENTS AND METHODS: This open-label, randomized, phase 3 trial was carried out in 139 centers in Japan. StageI-IIIPBC patients, who had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negativestatus and intermediate or higher risk of recurrence were randomly assigned (1:1) to receive standard endocrine therapy alone (control arm) or endocrine therapy plus S-1 (S-1 arm). Recurrence risk assessment was performed using anatomical stage, pathological findings such as histologic grade, and centrally confirmed proliferative marker status. S-1 was administered postoperatively in combination with standard endocrine therapy. For patients who underwent multi-drug postoperative adjuvant or preoperative neoadjuvant chemotherapy, S-1 was administered following the multi-drug chemotherapy. Cases having no residual cancer in the breast and axillary node after the preoperative chemotherapy were excluded from this study. The S-1 dosage was chosen among 80 mg/day, 100 mg/day, and 120 mg/day according to the body surface area of each patient, and S-1 was administered for one year with a 2 weeks on/1 week off administration schedule. The primary endpoint was invasive disease-free survival (iDFS), defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death, and was analyzed on an intent-to-treat basis. Secondary endpoints included DFS, distant DFS, overall survival, and safety profile. RESULTS: From Feb 2012 to Feb 2016, 1959 patients were enrolled and 1932 patients were included in the full analysis set (control arm, 973; S-1 arm, 959). The results of the prespecified interim analysis met the primary end point, and this trial was terminated early. Median follow-up was 51.4 months. S-1 significantly reduced invasive events; 153 iDFS events were reported in the control arm and 99 iDFS events were reported in the S-1 arm [hazard ratio, 0.63 (95%CI, 0.49-0.81); p-value, 0.0003]. The 5-year iDFS estimate was 81.5% in the control arm and 86.9% in the S-1 arm. Distant recurrence as the first disease event was observed in 6.8% of patients in the S-1 arm and in 9.5% of those in the control arm. The safety data in patients treated with S-1 was consistent with the known profile of S-1. The S-1 treatment was well tolerated and manageable. CONCLUSIONS: It was concluded that the postoperative adjuvant use of an oralfluoropyrimidine S-1 significantly reduced iDFS events and improved 5-year iDFS estimate in PBC patients having HR-positive and HER2-negative disease, in the combination with standard endocrine therapy, with a feasible safety profile. Funding: This study was funded by the Comprehensive Support Project (CSP) of the Public Health Research Foundation. The research fund was provided to CSP by Taiho Pharmaceutical Co., Ltd. This trial was conducted as a study of ‘Advanced Medical Care,’ the Ministry of Health, Labour and Welfare, Japan. JRCT ID: jRCTs051180057, UMIN000003969 Citation Format: Masakazu Toi, Shigeru Imoto, Takanori Ishida, Yoshinori Ito, Hiroji Iwata, Norikazu Masuda, Hirofumi Mukai, Shigehira Saji, Akira Shimizu, Takafumi Ikeda, Hironori Haga, Toshiaki Saeki, Kenjiro Aogi, Tomoharu Sugie, Takayuki Ueno, Takayuki Kinoshita, Yuichiro Kai, Masahiro Kitada, Yasuyuki Sato, Kenjiro Jimbo, Nobuaki Sato, Hiroshi Ishiguro, Masahiro Takada, Yasuo Ohashi, Shinji Ohno. Addition of S-1 to endocrine therapy in the post-operative adjuvant treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative primary breast cancer: A multicenter, open-label, phase 3 randomized trial (POTENT trial) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS1-09.

Background Patients with refractory nephrotic syndrome (NS) are at high risk of medication-induced glucose metabolism disorders, because of their long-term use of diabetogenic medications, particularly glucocorticoids and calcineurin inhibitors (CNIs). However, there have been no comprehensive evaluations of glucose metabolism disorders in pediatric patients with refractory NS. Moreover, glucocorticoids and CNIs could not be discontinued in these patients until the effectiveness of rituximab on refractory NS was shown, and therefore, there has been limited opportunity to evaluate glucose metabolism disorders after discontinuation of these medications. Methods Consecutive pediatric patients who started rituximab treatment for refractory NS were enrolled. Their glucose metabolism conditions were evaluated using the oral glucose tolerance tests (OGTT) and HbA1c levels at the initiation of rituximab treatment. Patients with glucose metabolism disorders at the first evaluation were reevaluated after approximately 2 years. Results Overall, 57% (20/35) of study patients had glucose metabolism disorders, and 40% (8/20) of these patients were detected only by their 2-h OGTT blood glucose levels and not by their fasting blood glucose or HbA1c levels. Non-obese/non-overweight patients had significantly more glucose metabolism disorders than obese/overweight patients (p = 0.019). In addition, glucose metabolism disorders in 71% (10/14) of patients persisted after the discontinuation of glucocorticoids and CNIs. Conclusions Whether the patient is obese/overweight or not, patients with refractory NS are at high risk of developing glucose metabolism disorders, even in childhood. Non-obese/non-overweight patients who are at high risk of diabetes need extra vigilance.

INTRODUCTION AND OBJECTIVE:Patients who are diagnosed with high grade Ta, T1, or any Tis are generally regarded as high-risk non-muscle invasive bladder cancer (HR-NMIBC) according to the several p...

Background: Recently, comprehensive genetic approaches for steroid-resistant nephrotic syndrome (SRNS) using next-generation sequencing (NGS) have been established, but causative gene mutations could not be detected in almost 70% of SRNS patients. Main reason for the low variant detection rate is that most of them are SRNS caused not by genetic but by immunological factors. But some of them are probably because of the difficulty of detecting copy number variations (CNVs) in causative genes by NGS. Methods: In this study, we performed two analytical methods of NGS data-dependent pair analysis and custom array comparative genomic hybridization (aCGH) in addition to NGS analysis in an infantile nephrotic syndrome case. Results: We detected only one known pathogenic heterozygous missense mutation in exon 7 of COQ6 c.782C > T, p.(Pro261Leu) by NGS. With pair analysis, heterozygous exon 1–2 deletion was suspected and was confirmed by custom aCGH. As a result, a small CNV was successfully detected in the COQ6 gene. Because we could detect variants in COQ6 and could start treatment by coenzyme Q10 (CoQ10) in his very early stage of SRNS, the patient achieved complete remission. Conclusions: These relatively novel methods should be adopted in cases with negative results in gene tests by NGS analysis. Especially, in cases with CoQ10 deficiency, it is possible to delay initiating dialysis by starting treatment at their early stages.

Background Radiation therapy (RT) for women with ductal carcinoma in situ (DCIS) undergoing breast‐conserving surgery (BCS) may be overtreatment for some, especially for those in which DCIS is eradicated, and ipsilateral breast tumor recurrence (IBTR) risk approaches the contralateral breast cancer (CBC) level. The aim of this study was to clarify whether the polygon method, a new systematic method of en face (tangential, shaved) margin assessment, can identify a subset of DCIS that can be safely treated by BCS alone. Methods A key tool of the polygon method is an adjustable mold that prevents the “pancake phenomenon” (flattening) of breast tissue after surgical removal so that the specimen is fixed in the shape of a polygonal prism. This preanalytical procedure enables us to command a panoramic view of entire en face margins 3‐5‐mm deep from the real peripheral cut surfaces. Competing risk analysis was used to quantify rates of IBTR and CBC and to evaluate risk factors. Results From 2000 to 2013, we identified 146 DCIS patients undergoing BCS with a contralateral breast at risk. In 100 DCIS patients whose margin was negative by the polygon method, 5 IBTR (3 DCIS and 2 invasive ductal carcinoma [IDC]) and 10 CBC (6 DCIS and 4 IDC) cases were identified during a median follow‐up of 7.6 years (range, 0.9‐17.4). Five‐ and 10‐year cumulative incidence rates were 3.0% and 5.3% for IBTR, and 7.1% and 13.3% for CBC, respectively. Thus, patients with a negative margin consistently showed at least twofold lower IBTR than CBC despite omission of RT. Conclusions Japanese women classified with a negative margin by the polygon method show a very low risk of IBTR and account for approximately half of CBC cases. In this subset of DCIS patients, additional RT is not beneficial.

Background/Aims: Calcineurin inhibitors (CNIs) such as cyclosporine A (CsA) and tacrolimus are immunosuppressants that are frequently used as “key drugs” in the fields of transplantation, steroid resistance, refractory nephrotic syndrome, and autoimmune disease. However, long-term CNI use causes nephrotoxicity, the features of which are arteriolar hyalinosis, tubular atrophy, striped interstitial fibrosis, and focal segmental glomerulosclerosis (FSGS). We investigated whether FSGS in CNI-induced nephrotoxicity is associated with CD44-positive glomerular parietal epithelial cells (PECs), which play a significant role in experimental and human FSGS pathogenesis. Methods: We utilized the mouse model of CsA-induced nephrotoxicity, as well as controls. Histopathological and functional data were sequentially collected from 1 to 25 weeks after CsA injection. Glomerular expression of CD44 was immunohistochemically evaluated, as were markers for glomerular podocytes and PECs. Results: Glomerular CD44 expression occurred from 2 weeks after CsA injection and gradually increased in the CsA group. CD44-positive glomerular cells showed coexpression of claudin-1 (PEC marker) but not of synaptopodin (podocyte marker). From 20 weeks after CsA injection, the cells formed a bridge between Bowman’s capsule and the capillary tuft. These features are compatible with those of activated PECs, in which increased foot process effacement leads to bridge formation, and subsequently to an increase in glomerulosclerosis and a decrease in the expression of podocyte markers from 20 weeks. Conclusion: CD44-positive (activated) PECs reflect extremely early podocyte injury in the progression of FSGS formation and may be a good marker for early detection of CNI-induced nephrotoxicity.

BACKGROUND Rituximab (RTX) is an effective treatment for maintaining remission in patients with nephrotic syndrome (NS), but there are few reports on the effect of RTX treatment on quality of life (QOL). The purpose of this study was to examine the effect of periodically repeated RTX treatment from the perspective of QOL. METHODS We systematically assessed the QOL of pediatric patients with refractory NS and parents' perceptions of their children's QOL through a 2 year RTX treatment protocol. Pediatric patients from Hokkaido University Hospital with refractory NS who met our specific criteria were enrolled between January 2015 and December 2015. The RTX infusion was performed 4 times at 6-month intervals, followed by mizoribine administration with early discontinuation of calcineurin inhibitors. Quality of life scores were measured by the Pediatric Quality of Life Inventory version 4.0 (PedsQL) at each RTX administration and evaluated 2 years later. RESULTS Twenty-two patients were analyzed. The patients' QOL and their parents' perceptions of their QOL improved over our 2 year treatment protocol. Nevertheless, the parents' scores were lower than the patients' scores on all scales, with slower improvement. CONCLUSIONS Our treatment protocol showed a significant improvement of QOL in patients with refractory NS. Although the risk of the RTX treatment should be considered, the treatment is useful for patients with refractory NS.

Background: Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on the risk of breast cancer recurrence. Methods: This prospective, randomised, multicentre open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients with stage I–IIIA hormone receptor-positive breast cancer who were disease-free after treatment with either 5 years of anastrozole alone or 2–3 years of tamoxifen followed by 2–3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole (1 mg/day orally) for an additional 5 years or stop anastrozole, using the central computer at the Comprehensive Support Project for Oncology Research Data Centre. Randomisation was stratified by type of postoperative endocrine therapy, nodal status, prior adjuvant chemotherapy, and facility. The primary endpoint was disease-free survival, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with UMIN clinical trials registry, number UMIN000000818. Findings: We enrolled 1697 patients from 117 facilities between November 2007 and November 2012. Patients were assigned randomly to the continue group (n=849) or the stop group (n=848). Follow-up information was available for 1593 patients (n=787 in the continue group, n=806 in the stop group) as the full analysis set. After a median follow-up of 5·1 years, there were 172 events involving disease recurrence or the occurrence of contralateral breast cancer (75 in the continue group and 97 in the stop group) and 40 deaths (21 in the continue group and 19 in the stop group). The 5-year disease-free survival rates were 91% (95% confidence interval [CI] 89–93) in the continue group and 86% (95% CI 83–88) in the stop group (hazard ratio [HR] for disease-free survival 0·61, 95% CI 0·46–0·82; p

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, especially in children. Owing to the short-term observational period and the small number of patients analyzed in previous reports, the long-term clinical and laboratory characteristics and renal prognosis of children with TINU syndrome remain unclear. In this retrospective observational study, we enrolled 29 children with TINU syndrome from February 1990 to February 2019. During the median follow-up duration of 38 months, the kidney function, urinary β2 microglobulin-creatinine ratio (U-β2MG/Cr), and uveitis in the patients had significantly improved at 24, 6, and 36 months after diagnosis. Higher U-β2MG/Cr was associated with longer duration of kidney function normalization. Half of the patients required uveitis treatment for 5 years after the diagnosis. Patients with severe low-molecular weight proteinuria at diagnosis needed a longer duration to achieve improvements in kidney function. Uveitis has a much longer treatment period than tubulointerstitial nephritis. This study demonstrates the good prognosis of children with TINU syndrome in terms of their long-term clinical and laboratory characteristics.

Herein, we propose a quantitative method to evaluate swallowing ability. In Japan, where the population is aging, the number of patients with aspiration pneumonia will increase in the future. Methods to quantitatively assess swallowing ability are currently not being developed, and some doctors make decisions based on x-rays, endoscopes, and water drinking tests. These methods are invasive to the patient and the amount of information obtained is insufficient. The purpose of this study is to quantitatively evaluate the swallowing ability by photographing the state of swallowing food with an ultrasonic diagnostic device and processing the images. Muscle and food in the images were separated using filters, labeling, and single regression analysis. Swallowing ability was assessed quantitatively using optical flow.

Dialysis is a type of long-term treatment that lasts four hours per session, creating a burden on the patient. Blood pressure fluctuations are likely to occur because a large amount of blood is extracted from the body, and these fluctuations have dangerous effects on the patient's physical condition. In this study, we develop a system to alleviate these dangers by detecting the signs of blood pressure fluctuations in dialysis, and notifying doctors accordingly. Specifically, we investigate and analyze blood flow sound data during dialysis to explore the relationship between blood flow and blood pressure fluctuations. We removed the Noise from blood flow sounds collected from actual dialysis patients, and calculated the sound pressure and RRI from these. We tried to detect abnormalities during dialysis by analyzing the results of these calculations and examining various viewpoints. In this research, we have discovered the possibility of unexpected pulsation and the possibility of a signal.

Background Approximately 15% of patients with Dent disease have pathogenic variants in theOCRLgene on Xq25-26, a condition that is referred to as Dent disease 2 (Dent-2). Dent-2 patients sometimes show mild extrarenal features of Lowe syndrome, such as mild mental retardation, suggesting that Dent-2 represents a mild form of Lowe syndrome. To date, eight female patients with Lowe syndrome have been reported, but no female Dent-2 patients have been reported. Methods In this study, we performed genetic testing of the first female Dent-2 patient to detect the presence of anOCRLvariant. Aberrant splicing was demonstrated by in vivo, in vitro, and in silico assays, and skewed X-chromosome inactivation (XCI) in our patient and asymptomatic mothers of three Lowe patients with the heterozygousOCRLvariant was evaluated by HUMARA assays using genomic DNA and RNA expression analysis. Results Our patient had anOCRLheterozygous intronic variant of c.1603-3G > C in intron 15 that led to a 169-bp insertion in exon 16, yielding the truncating mutation r.1602_1603ins (169) (p.Val535Glyfs*6) in exon 16. HUMARA assays of leukocytes obtained from this patient demonstrated incompletely skewed XCI (not extremely skewed). On the other hand, the asymptomatic mothers of 3 Lowe patients demonstrated random XCI. These results may lead to our patient's Dent-2 phenotype. Conclusions This is the first report of a female patient clinically and genetically diagnosed with Dent-2 caused by anOCRLheterozygous splicing site variant and skewed XCI. Skewed XCI may be one of the factors associated with phenotypic diversity in female patients with Lowe syndrome and Dent-2.

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end-stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver-kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver-kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4-11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9-14.7) years in all patients. Overwhelming post-splenectomy infections and cholangitis did not occur during the median follow-up period of 6.3 (range, 1.0-13.2) years. The estimated glomerular filtration rate at the last follow-up was 53 (range, 35-107) mL/min/1.73 m2 . No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation.

Sensitivity to detect breast cancer (BC) is not high in a dense breast due to masking in mammography. To evaluate the breast density, a volumetric measurement system has been recently developed that measures the percent fibroglandular tissue volume (percent FGV, hereafter termed as “FG%”) to the breast volume (BV). This study was designed to investigate whether evaluation using FG% can accurately predict the masking risk by comparing with the current standard method of subjective visual estimation (SVE). Using pre-biopsy mammograms of 114 cases histopathologically diagnosed with BC in our facility, SVE based on BI-RADS (5th edition) and volumetric measurements of FG% were conducted. Performance to predict the masking risk was evaluated using the area under the receiver operating characteristic curve (AUC). Relationship between these parameters and the masking risk was evaluated by the adjusted multivariate linear regression analysis. The AUC of SVE values was 0.742 (95% CI 0.641–0.822), while that of FG% was as significantly low as 0.560 (95% CI 0.427–0.685) (P = 0.0014). The SVE values correlated with the detection of BC in mammography (P = 0.0035), but there was no significant relationship with FG% (P = 0.74). The median BV and FGV were 313 cm3 (IQR 191–440) and 63 cm3 (IQR 44–102), respectively. The FGV was comparable to the data for Caucasian women reported in previous studies, but the BV was one-half of the previous data. The current volumetric measurement system to evaluate FG% to BV was found to be insufficient in the performance to predict the masking risk in Japanese women with relatively small-sized breasts.

The main barrier to adoption of digital breast tomosynthesis (DBT) plus full-field digital mammography (FFDM) is radiation exposure dose. The purpose of this study was to evaluate the diagnostic performance of DBT plus FFDM, both with newly developed technology (nd), at a dose comparable to that of the conventional FFDM alone. Nine hundred and thirteen participants were recruited from May 2014 to January 2016 consecutively. For each subject, the exposure setting for DBT(nd) + FFDM(nd) was also used for the conventional FFDM alone. Retrospective reader studies were performed: DBT(nd) + FFDM(nd) (142 cases, including 42 cancer cases) and conventional FFDM (258 cases, including 87 cancer cases). Eight radiologists provided Japanese categorizations and probability of malignancy independently. Diagnostic performance was assessed by comparing sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Two-sided P values were calculated. DBT(nd) + FFDM(nd) showed sensitivity and AUC significantly increased over the conventional FFDM (85.4 vs. 80.3%, P = 0.015 and 90.9 vs. 88.3%, P = 0.049) and specificity did not significantly increase (89.6 vs. 88.4%, P = 0.52). The mean glandular dose (MGD) difference of DBT(nd) + FFDM(nd) and conventional FFDM was not significant (difference − 0.11 mGy, P = 0.08). In this study population, DBT plus FFDM, both with newly developed technology, provided diagnostic performance improved over the conventional FFDM alone, even at comparable MGD.

The reasons for improved outcomes associated with preemptive kidney transplantation (PKT) are incompletely understood, and post-transplant complications have been scarcely investigated. We evaluated the outcomes of PKT in both unmatched (n = 1060) and propensity score matched cohorts (n = 186) of adults who underwent living kidney transplant between 2000 and 2014. Outcomes were estimated glomerular filtration rate (eGFR), biopsy-proven rejection, cytomegalovirus (CMV) infection, post-transplant diabetes mellitus (PTDM), cardiovascular disease (CVD), graft failure (non-censored for death), and malignancy. Primary endpoint was post-transplant renal function assessed with eGFR. A total of 95 patients (9.0 %) underwent PKT. The 2-week mean eGFR after transplant was comparable between the matched PKT and non-PKT groups (45.2 vs. 46.5 mL/min/1.73 m2, respectively, P = 0.56). Sensitivity analysis using various formulas did not change the results. PKT was not superior to non-PKT in reducing the risk of biopsy-proven rejection, CMV, PTDM, and malignancy, regardless of matching. The risk of graft failure and CVD was significantly reduced in the unmatched PKT group (ARR, −6.2 %; 95 % CI, −8.6 to −0.7; P = 0.03, and ARR, −6.7 %; 95 % CI, −9.6 to −0.7, P = 0.03, respectively); nevertheless, the corresponding ARRs were −3.2 % (95 % CI, −10.0 to 2.9; P = 0.44) and −2.2 % (95 % CI, −9.1 to 4.4; P = 0.72) after matching. PKT was associated with neither improvement of post-transplant renal function nor a lower rate of common post-transplant complications than non-PKT among patients with end-stage renal disease who underwent living KT.

The objectives of this study were: (1) to evaluate the detectability of full-field digital mammography (FFDM) plus dual-mode digital breast tomosynthesis (DBT) and compare it with that of FFDM alone and (2) to compare the detectability of high-resolution-mode (HR mode used with 40°-angle imaging, 100-µm pixel size, and higher dose) DBT with that of standard-mode (ST mode used with 15°-angle imaging, 150-µm pixel size, and lower dose) DBT for diagnostic evaluation. The local Institutional Review Board approved this retrospective study of two different sets of cases. All participants gave written informed consent. FFDM and DBT images of 471 women who were recalled were acquired between August 2013 and October 2014. HR mode and ST mode were applied to 155 breasts and 157 breasts, respectively. The cases of both modes were selected randomly. Eight radiologists interpreted the images. The detectability for recall cases and for follow cases, and area under the receiver operating characteristic curve (AUC) were calculated. Adding DBT to FFDM significantly increased the detectability for recall cases and AUC relative to those of FFDM alone (HR mode 8.9 %; 95 % confidence interval (CI) 5.7, 15.0 %; P = 0.013 and 4.9 %; 95 % CI 2.1, 7.7 %; P = 0.001; ST mode 8.3 %; 95 % CI 4.1, 12.1 %; P = 0.007 and 2.9 %; 95 % CI 0.5, 5.3 %; P = 0.02), whereas the detectability for follow cases did not significantly differ. The AUC increase was significantly higher in HR mode than in ST mode (1.5 %; 95 % CI 0.5, 3.7 %; P = 0.023). Adding HR-mode or ST-mode DBT to FFDM significantly improved the detectability for diagnostic evaluation case.

Background/Aims: De novo expression of CD44 is considered as a marker of parietal epithelial cell (PEC) activation. The aim of our study was to explore CD74 expression, which can form a complex with CD44, in PECs during the progression of focal segmental glomerulosclerosis (FSGS). To clarify the role of CD74 expression and of its interaction with CD44, we generated a new mouse model with enhanced PEC activation through lipopolysaccharide (LPS) application to adriamycin (ADR)-induced nephropathy mice (LPS-treated ADR mice). Methods: As a new model, LPS was intraperitoneally injected into the mice 3 weeks after ADR injection. The mice were divided into 3 categories: control mice, ADR mice and LPS-treated ADR mice. Renal function parameters, histologic changes and immunohistochemical expression of CD74 and other PEC activation markers were analyzed after LPS application. Results: After LPS stimulation, the glomeruli were characterized by enlarged epithelial cells with strong CD74 expression, followed by pseudo-crescent formation. By double staining, CD74-positive enlarged cells showed co-expression of classical PEC markers, but not of Lotus tetragonolobus lectin (marker of proximal tubular cells), suggesting amplification of PEC activation. Time-course analysis displayed marked upregulation of CD74 expression during rapid PEC activation compared with CD44. Additionally, the time-dependent change in ERK phosphorylation showed a similar pattern to CD74. Conclusion: Our results indicate that CD74 can be a marker for PEC activation in FSGS. By modifying the ADR mouse model through LPS treatment, we found that CD74 upregulation better reflects a rapid amplification of PEC activation than CD44 expression.

Idiopathic Fanconi syndrome (FS) is characterized by a generalized dysfunction of the renal proximal tubules. Patients with FS often exhibit growth retardation due to complex factors, such as hypophosphatemia, metabolic acidosis, disturbed vitamin D metabolism and hypokalemia. To date, one FS patient has been reported to exhibit growth failure due to growth hormone deficiency (GHD), but the long-term clinical course of recombinant human GH (rhGH) therapy has not been reported. At 10 months of age, the patient was admitted to our hospital due to growth failure. Blood and urinary biochemical abnormalities, such as hypophosphatemia, metabolic acidosis, glycosuria and low-molecular-weight proteinuria, indicated a generalized dysfunction of the renal proximal tubules. The presence of cystinosis, collagen diseases, toxic agents and metabolic diseases were excluded. These features are compatible with idiopathic FS. Treatment with high-dose alkali, potassium citrate, phosphate buffer, hydrochlorothiazide and vitamin D supplement was initiated. The biochemical abnormalities achieved nearly normal values, and the patient's height was within -2.5 SD at the age of 2 years. However, his height did not continue to increase at the same rate and gradually declined to -2.9 SD at 4 years of age. GH stimulation test demonstrated GHD. After initiation of rhGH therapy, his height improved to -2.0 SD at the age of 9 years with no adverse effects. In conclusion, we report the case of a patient with FS and GHD who continued rhGH therapy for 5 years. The differential diagnosis of GHD should also be considered for FS patients with short stature.

e14147 Background: In Japan, much labor has been devoted to handle occupational exposure to hazardous drugs (HDs) after the publication of a guideline for preventing HD exposure on cancer treatments in 2015. However, the safe HD handling systems have not yet constructed in Japanese hospitals. To find out the current HD exposure and construct the safe HD handling system, a multi-institutional surveillance of HD exposure in the National Hospital Organization (NHO) cancer hospitals was commenced from Feb 2016 to Mar 2018. Methods: Thirty-two NHO institutes joined in this survey. HD surveys were performed 3 times in each institute, evaluating cyclophosphamide and fluorouracil exposures using wipe and sampling sheet methods at 18 places in outpatient chemotherapy and pharmacology units. To share information and discuss about HD exposure handling procedures, the study group meeting was held several times. Furthermore, HD handling system in each hospital was evaluated using handling system scoring established by Yoshida in Osaka Institute of Public Health. As an additional study, factors affecting commitment wills of staffs were also evaluated during the safe HD handling system construction using a multiple regression model. Results: As HD control systems constructed, HD exposure in each hospital was improved gradually with construction of the handling system. Staffs’ commitment to their institutes was shown as the result of safety awareness improvement induced by the HD safe handling system construction (standardization coefficient β: 0.346). Conclusions: HD exposures were improved in NHO cancer hospitals through the HD exposure evaluation with constructions of the safe HD handling system.

427 Background: We developed a Japanese version of the Bladder Cancer Index (BCI) to measure HRQOL in Japanese patients treated with various surgical methods. In addition, we performed a cross-cultural comparison of sexual function and bother in bladder cancer patients between the United States and Japan. Methods: The Japanese version of the BCI was developed through a multistage process after a pilot study. Its reliability and validity were examined in Japanese bladder cancer patients via a cross-sectional analysis. The patients were enrolled from August 2016 to March 2018. They also completed the Japanese version of Short Form (SF)-12, the EuroQol five-dimension scale (EQ-5D), and the Functional Assessment of Cancer Therapy-Bladder (FACT-BL). We also compared the Japanese cohort with an American cohort; i.e., the validation cohort used to develop the original version of the English BCI. Results: In total, 371 patients with a median age of 72 years and a median disease duration of 29 months were enrolled. Of these patients, 221 underwent transurethral resection of the bladder tumor, and 150 underwent radical cystectomy. The internal consistency value was ≥0.7 for all subscales, except the bowel function subscale. Each BCI domain was poorly correlated with the SF-12 and EQ-5D, but moderately well correlated with the FACT-BL. The urinary function and bowel function scales exhibited minimal (2.1–9.7%) amounts of missing data, whereas relatively high (≥15%) levels of missing data were seen in items relating to urinary bother, bowel bother, sexual function, or sexual bother. A missing data value of ≥15% was correlated with higher age (p

Background Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage renal disease. Complement activation via the lectin pathway influences outcomes in IgAN. We examined the association of glomerular C4d deposition with clinicopathological severity at diagnosis and the disappearance of proteinuria in Japanese pediatric IgAN patients. Methods We retrospectively analyzed 25 children newly diagnosed with IgAN at Hokkaido University Hospital. We evaluated glomerular C4d immunofluorescent staining at diagnosis. We compared clinical findings, pathological findings (based on Oxford classification), and the disappearance of proteinuria within 24 months after renal biopsy between C4d-positive and C4d-negative patients. Results Glomerular C4d staining was observed in 14 patients (56.0%). C4d-positive patients had significantly higher proteinuria at diagnosis than C4d-negative patients (2.03 g/gCr vs 0.78 g/gCr; P = 0.005). The number of glomeruli with segmental glomerulosclerosis or adhesion (8.0% vs 0.0%; P = 0.046) and the extent of tubular atrophy/interstitial fibrosis (9.46% vs 2.86%; P = 0.031) were significantly increased in C4d-positive patients compared with C4d-negative patients. Further, the proportion of patients with modified T1 (>10%) was significantly higher in the C4d-positive group than the C4d-negative group. There was no significant difference, however, in the disappearance rate of proteinuria at 24 months after renal biopsy between groups (64% vs 82%; P = 0.149). Conclusions Glomerular C4d deposition was associated with clinicopathological severity at diagnosis in Japanese pediatric patients with IgAN. Glomerular C4d deposition, however, was not a predictor of the disappearance of proteinuria within 24 months after diagnosis in Japanese pediatric patients with IgAN.

Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy for 2-3 years is the treatment of choice for hormone-receptor-positive breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may reduce the risk of breast cancer recurrence. Methods: We conducted a prospective randomized multi-center open-label phase III trial to assess the effect of the extended use of anastrozole for an additional 5 years. Postmenopausal patients with stageI-III, hormone-receptor-positive breast cancer, disease-free after 5 years of either anastrozole alone or tamoxifen 2-3 years followed by anastrozole 3-2 years were randomized to continual group with anastrozole for an additional 5 years or stop group without an additional anastrozole. Our primary end point was disease-free survival. Results: We enrolled 1697 women. After a median follow up of 4.9 years, there were 149 events involving disease recurrence or the occurrence of contralateral breast cancer (51 in continual group and 98 in stop group) and 7 deaths (3 in continual group and 4 in stop group). The 5-year disease-free survival rate was 91.9% (95% confidence interval [CI], 89.4 to 93.8) in continual group and 84.4% (95% CI: 80.0 to 88.0) in stop group (hazard ratio for disease-free survival,0.548 ;P=0.0004. by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, institution, and choice of anastrozole or tamoxifen). The rate of 5-year overall survival was 99.5% in continual group and 99.6% in stop group. (hazard ratio,1.389 ;P=0.665). The rate of 5-year distant disease-free survival was 97.2% in continual group and 94.3% in stop group (hazard ratio,0.514 ;P=0.0077). Bone-related adverse events were observed more frequently among patients in continual group than among patients in stop group, including a higher incidence of bone pain, stiff joints, bone fractures, and new-onset osteoporosis. Conclusion: The extension of treatment with an adjuvant aromatase inhibitor (anastrozole) to 10 years resulted in significantly higher rates of disease-free survival and distant disease-free survival than those with no additional anastrozole, but the rate of overall survival was not different between two groups. Our study shows that it is safe and beneficial for postmenopausal patients with hormone-receptor-positive breast cancer to take an anastrozole as adjuvant therapy for an additional 5 years after initial treatment. (UMIN:000000818) Citation Format: Ohtani S, Iijima K, Higaki K, Sato Y, Hozumi Y, Hasegawa Y, Takei H, Tanaka M, Yagata H, Masuoka H, Tanabe M, Egawa C, Komoike Y, Saji S, Nakamura T, Yanagita Y, Ohtsu H, Mukai H, Iwase T. A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-04.

Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. Conclusion: In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.

The aromatase inhibitors exemestane and anastrozole are approved in Japan for first-line treatment of postmenopausal patients with advanced, hormone-receptor-positive breast cancer. This phase 3, randomized, double-blind study directly compared time to progression (TTP) for exemestane and anastrozole therapy in this patient population. Eligible patients were randomized to receive exemestane 25 mg or anastrozole 1 mg, each once daily. The primary endpoint was TTP based on assessment by an expert radiologic images review committee (ERIRC). Secondary endpoints included investigator-assessed TTP, time to treatment failure, overall survival, objective response rate, clinical benefit rate, and safety. A total 298 patients were randomized to receive exemestane (n = 149; mean age 63.4 years) or anastrozole (n = 149; mean age 64.0 years). Median ERIRC-assessed TTP was 13.8 and 11.1 months (hazard ratio = 1.007; 95 % confidence interval [CI]: 0.771, 1.317) and median investigator-assessed TTP was 13.8 and 13.7 months (hazard ratio = 1.059; 95 % CI: 0.816, 1.374) in the exemestane and anastrozole arms, respectively. Median overall survival was 60.1 months in the anastrozole arm and was not reached in the exemestane arm at data cutoff. The objective response rate was 43.9 % (95 % CI: 35.3, 52.8) and 39.1 % (95 % CI: 30.6, 48.1) in the exemestane and anastrozole arms, respectively. Treatment-related adverse events grade ≥3 occurred in 9.4 and 6.0 % of patients, and treatment-related serious adverse events occurred in 4.0 and 3.4 % of patients in the exemestane and anastrozole arms, respectively. In this study, the efficacy and safety profiles of exemestane were similar to those of anastrozole in Japanese patients with advanced, hormone-receptor-positive breast cancer; however, TTP non-inferiority of exemestane versus anastrozole was not confirmed.

Renal anemia is an important complication of chronic kidney disease (CKD). One of the most important complications of renal anemia is reduced red blood cell (RBC) lifespan, but there has been little research conducted into the causes of and treatments for this anemia. We measured alveolar carbon monoxide (CO) and then estimated RBC lifespan in patients on hemodialysis (HD). We also examined their requirement for erythropoiesis-stimulating agents (ESA), HD dose, nutrition factors, iron metabolism factor, reticulocyte counts and % reticulocytes. We enrolled 140 patients undergoing intermittent HD; among this group, 31 were not administered ESA and the others were on ESA therapy. Twelve healthy volunteers served as controls. The RBC lifespans in the healthy volunteers and in the HD patients were 128 ± 28 and 89 ± 28 days (mean ± SD), respectively. The RBC lifespan significantly and negatively correlated with ESA requirement (r = -0.489, P < 0.0001) in the HD patients. Other factors suspected to influence the RBC lifespan did not significantly correlate with the RBC lifespan in HD patients, in contrast to the correlation observed for S-Cr, BUN, S-ALB and total cholesterol vs. RBC lifespan. A shortened RBC lifespan seems to rather significantly affect the ESA requirement. Better nutritional status or active HD patients also seem to have longer RBC lifespans and lower ESA requirement.

Background The steroidal irreversible aromatase inhibitor (AI) exemestane (E), the non-steroidal reversible AI anastrozole (A) and tamoxifen (T) are approved for the first-line treatment of the postmenopausal women with hormone receptor (HR) positive advanced breast cancer (ABC) in Japan. Although there are some studies which compare the efficacy and safety of AIs and T in the first-line disease setting, the number of studies that compare efficacy and safety of AIs is limited. We conducted this multicenter, randomized, double-blinded non-inferiority study, to evaluate the time to progression (TTP) in HR positive ABC randomized to therapy with E or A. Methods Patients (pts) who were ≥20 years [yrs], postmenopausal, ECOG PS ≤1 and had HR positive ABC that recurred after the adjuvant therapy or metastatic disease settings were eligible and randomized (1:1) to 25 mg/day of E or to 1 mg/day of A. Data were evaluated for non-inferiority of E compared to A defined as the upper limit of a two-sided 95% confidence interval (CI) of the hazard ratio (HR) of TTP being less than or equal to 1.25. The primary endpoint was TTP assessed by the independent radiological images review committee (RIRC). Secondary endpoints included TTP by investigator, time to treatment failure, overall survival (OS), objective response rate (ORR), clinical benefit rate, and safety. Results A total of 298 pts from 58 sites were randomized to E (n=149; mean age: 63.4 yrs) or A (n=149; mean age: 64.0 yrs). The mean BMI for the E and A arms were 23.0 kg/m2 and 23.6 kg/m2, respectively. Six pts (2 pts in E arm, 4 pts in A arm) were excluded from the full analysis set due to lack of evaluation for anti-tumor response after study medication started. Median TTP (as per RIRC) was 13.8 months (M) vs. 11.1 M for E vs. A, respectively (HR 1.007; 95% CI: 0.771−1.317). Median TTP (Investigator) was 13.8 M vs. 13.7 M for E vs. A, respectively (HR 1.059; 95% CI: 0.816−1.374). The median OS for A treated pts was 60.1 M, OS for E was not reached (as of data cut-off: December 8, 2010). ORR for E was 43.9% (95% CI: 35.3−52.8) and 39.1% (95% CI: 30.6−18.1) for A. Other analyses, including sub-population analyses are ongoing. The incidence of treatment related adverse events (AEs) in E arm was 71.1% (n=106) and in A arm 59.7% (n=89); the AEs were mostly grade 1 and 2 in 61.7% (n=92) and 53.7% (n=80) of pts respectively. They were expected and manageable. Treatment related SAEs were similar in both groups: 6 (4.0%) in E arm and 5 (3.4%) in A arm. The most common AEs for E were hot flushes (22.1%), arthralgias (16.8%), musculoskeletal stiffness (11.4%) and γ-GTP increased (10.1%); in A arm, hot flushes (14.8%) and arthralgia (16.8%) were observed in >10% pts. Conclusions Although median TTP (RIRC) of E is slightly improved compared with that of A, the result of TTP did not meet the non-inferiority criteria. There were no significant differences found between E and A in ORR. Although AEs in E were numerically higher, the observed AE profiles were similar to those previously reported for E and A. This study shows that E is comparable to A in efficacy and safety. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-16-01.

There is currently no standardized therapy available for metastatic breast cancer in patients with aromatase inhibitor (AI)-resistant breast cancer. We conducted a prospective study to examine the efficacy and safety of high-dose toremifene (TOR) treatment for the first-line treatment of metastatic breast cancer following AI adjuvant therapy. A multicenter phase II study was designed (Registry no.: UMIN000000489). Inclusion criteria comprised hormone-responsive postmenopausal women who had received adjuvant AI postoperatively for >1 year and had relapsed during the treatment or within 12 months of completion of adjuvant therapy. Treatment comprised oral intake of 120 mg TOR once a day. The primary endpoint was objective response rate (ORR). The secondary endpoints were evaluations of clinical benefit (CB), progression-free survival (PFS) and toxicity. A total of 13 patients were enrolled. ORR was 7.7% (1/13) [95% CI, 0.2–36.0%]. In total, 7 patients (53.8%) had stable disease (SD), 5 of whom were long SD, and 5 patients (38.5%) experienced progressive disease (PD). The CB rate was 46.2% (6/13) [95% CI, 19.2–74.9%]. The median time to PFS was 5.9 months. No serious adverse events were observed. Patients with HER2-positive disease exhibited marginally poorer PFS (p=0.08). Patients with PD had a relatively short duration of AI treatment in contrast to responders, who had a longer period of AI treatment (p=0.02). High-dose TOR as a first-line treatment following AI adjuvant therapy was effective and well tolerated. A longer duration of adjuvant AI therapy and negative HER2 overexpression may, with further studies, be beneficial as positive predictive factors for the effectiveness of TOR treatment.

Moritani S, Ichihara S, Hasegawa M, Endo T, Oiwa M, Shiraiwa M, Nishida C, Morita T, Sato Y, Hayashi T, Kato A, Aoyama H & Yoshikawa K (2011) Histopathology 58, 835–846 Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ Aim: To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA. Methods and results: In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non-high-grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(−) immunophenotype predominated. Most type B CIS were high-grade and six (54%) were ER(−)/PgR(−). Most type A were bcl-2(+)/p53(−) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl-2(−)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer. Conclusions: Most CIS involving SA arises within SA and high-grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.

e12573Background: The role of adjuvant or post-mastectomy radiation therapy (RT) for human epidermal growth factor receptor type 2 (HER2)-positive (HER2+) breast cancer patients treated with Trastu...

The patient was a 30-year-old man who had undergone living-donor kidney transplantation for renal failure caused by IgA nephropathy at age 29. On post-transplantation day 83, he visited our department with a chief complaint of asymptomatic hematuria. CT performed on post-transplantation day 95 revealed a tumor (size, 4 cm) in the right native kidney that had not been observed at the time of transplantation. CT performed on post-transplantation day 153 showed that the tumor had enlarged to 6 cm, while retrograde pyelogram performed on post-transplantation day 171 was negative for renal pelvic tumor. On post-transplantation day 193, radical right nephrectomy was performed. The tumor had directly invaded the diaphragm and the lower surface of the liver, and was histopathologically diagnosed as rhabdoid tumor of the kidney. As the pathological tissue was extremely malignant, hepatic posterior segmentectomy, right adrenalectomy, and lymph node dissection were further performed for metastases on post-transplantation day 200. On the 23rd day after radical right nephrectomy (post-transplantation day 216), the patient developed dyspnea. Chest CT showed pleural effusion, hemothorax in right lung and metastases in both lungs. The patient's general status gradually worsened thereafter, and he died on the 53rd day after radical right nephrectomy (post-transplantation day 246). Rhabdoid tumor of the kidney is a rare renal tumor that affects children, and only four adult cases have been reported to date. We report our experience with this rare case.

This paper presents an identification technique of parameters of a high-frequency equivalent circuit of permanent magnet synchronous motors (PMSM) driven by a PWM inverter. The high-frequency oscillatory currents such as leakage current to the motor frame (common-mode current) and high-frequency oscillatory line current (normal-mode current) are generated by switching instants of inverter transistors. The parameters of the high-frequency equivalent circuit of PMSM which can simulate the oscillating current are identified by means of genetic algorithm. It is shown that the high-frequency equivalent circuit with identified parameters can generate the oscillating current by some simulation results. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(4): 57–66, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20717

副腎皮質癌の予後は悪く，進行および再発時の治療法としては確立されたものがないのが現状である．今回われわれは副腎皮質癌に対して化学療法を行い治療効果のみられた症例を経験したので報告する．症例は29歳，女性．17歳時悪性リンパ腫にて化学療法施行し寛解．27歳時発熱が続き検査施行したところ，CTにて後腹膜腫瘍を認め当院紹介となった．術前には確定診断がつかず，開腹手術施行．手術時生検結果で未分化癌と診断され切除せず術後EP療法を行っていたが，化学療法中に副腎皮質癌の診断となったため3クール施行しその後副腎腫瘍摘出術施行．経過観察中の術後1年4カ月後のCTにて腹膜腫瘤を認め，副腎皮質癌の腹膜再発と診断し再度EP療法を施行．8クール終了時のCTでは腹膜の腫瘤は画像上縮小しており，化学療法の効果が認められた．

To clarify the background, clinical symptoms, pathological characteristics, and duration of survival in patients with bladder cancer on hemodialysis and to examine the appropriate treatment strategies. Between April 1988 and May 2012, 28 patients in whom bladder cancer was diagnosed and treated after dialysis was initiated were included in this retrospective study. We examined the clinicopathological characteristics and survival. Twenty men and 8 women were included (mean age 64.1 ± 11.9 years). The mean duration of dialysis was 80.2 ± 79.1 months. The duration of follow-up after treatment was 43.9 ± 41.2 months. Fourteen patients underwent immediate total cystectomy after the diagnosis of muscle-invasive bladder cancer or high-grade pT1 tumors. Of these, four died of cancer and two had surgery-related deaths. Fourteen patients underwent transurethral resection, and the initial diagnosis was non-muscle-invasive bladder cancer. Of these, three underwent delayed total cystectomy because the time to recurrence was short or there were multiple intravesical recurrences; none died of cancer. The duration of hemodialysis tended to be longer in patients who underwent immediate total cystectomy than in those who underwent only transurethral resection or delayed total cystectomy (107.1 ± 92.0 vs. 53.3 ± 63.9 months, p = 0.10). Bladder cancer in hemodialysis patients can be treated using the same strategy as for the general population. Bladder cancer in longer-term hemodialysis patients tends to be pathologically more advanced; thus, total cystectomy, although highly invasive, is often needed. Establishing bladder cancer screening for patients on dialysis is desirable.

Dear Editor, Columnar cell lesions (CCLs) of the breast including flat epithelial atypia (FEA) are believed to be nonobligatory precursors of a low-nuclear-grade breast neoplasia family [1]. They are detected increasingly in needle core biopsies because of the presence of microcalcifications observed on screening mammography. Here, we report a hitherto undescribed artifact associated with CCLs of the breast, which superficially resembles micropapillary atypical ductal hyperplasia (ADH) or low-grade ductal carcinoma in situ (DCIS). The complexity of this artifact varies widely from a simple fold to a complex labyrinthine-like structure. If the latter is confused with genuine micropapillary structures or Roman bridges, overtreatment can occur because management of patients differs between pure CCLs and those associated with ADH/low-grade DCIS, especially when found in needle core biopsies. We have recently observed two cases of CCL of the breast that showed complex pseudo-micropapillary structures protruding into the duct lumen. Based on histopathological and immunohistochemical findings, we infer that these structures are not a true micropapillary overgrowth but an artifact, which originates from folding and adhesion of epithelial sheets detached from CCLs. The first case concerns a 49-year-old Japanese woman whose screening mammography revealed microcalcifications in the left breast. Vacuum-assisted needle core biopsy (VAB) was performed because the microcalcifications varied in size and shape and were localized to the upper half of the breast in a segmental fashion. The VAB was composed of 12 fragments of breast tissue. Four fragments contained CCLs; variably distended ductules were lined by columnar epithelial cells with apical cytoplasmic snouts (Fig. 1a–c). In the lumina of some dilated ductules, racetracks were seen or ribbon-like bridges continuous with the epithelial lining of CCL. These pseudo-micropapillary structures lacked fibrovascular cores and contained two epithelial layers. The cells were similar to luminal cells of CCL (Fig. 1c). Immunohistochemical staining with cytokeratin 5/6 demonstrated a few myoepithelial cells attached to the basal S. Ichihara (*) : S. Moritani :M. Hasegawa Department of Pathology, Nagoya Medical Center, 4-1-1 Sannomaru Naka-ku Nagoya, 460-0001 Aichi, Japan e-mail: shu-kkr@umin.ac.jp