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Complementary metal-oxide-semiconductor (CMOS) image sensors have widely been used in internet of thinking (IoT) devices such as smartphones, smart watch and personal computer tablets [1] . The consumer market strongly requires higher sensitivity and higher speed image data processing to realize high functional CMOS image sensors such as three dimensionally stacked back-side-illuminated CMOS image sensors (3D-CIS) [2] . However, there are some serious technological issues in the fabrication of advanced CMOS image sensors as shown in Fig. 1 .

Microalbuminuria is thought to be a risk factor for progression to macroalbuminuria, an indicator of renal functional decline in patients with type 1 or 2 diabetes. However, it remains unknown which renal histological factors predict the onset of macroalbuminuria or eGFR Conclusions: Aggravated arteriolar hyalinosis is a histological risk factor for renal functional decline and predicts the onset of macroalbuminuria and CKD in patients with type 2 diabetes, normo-microalbuminuria, and normal renal function regardless of microalbuminuria grade. This finding might reflect initial changes in early diabetic nephropathy. Disclosure T. Moriya: None. A. Hayashi: None. A. Suzuki: None. M. Matsubara: None. M. Ouchi: None.

A high urinary albumin excretion (UAE) and low glomerular filtration rate (GFR) are risk factors for progressive renal function loss in type 2 diabetic patients. In addition, diabetic retinopathy (DR) is also a risk factor for progressive renal function decline in microalbuminuric type 2 diabetic patients. We aimed to elucidate the factors, including DR, associated with a more severe situation of diabetic nephropathy, i.e., hemodialysis (HD) induction in normo- and microalbuminuric type 2 diabetic patients without renal dysfunction.Normo- and microalbuminuric type 2 diabetic patients with normal renal function whose GFRs had been measured by iohexol injection in 1995-1997 and had been followed for over 5 years were analyzed (n = 199). HbA1c levels was divided into HbA1c ≥ 7.0 (n = 146) and7.0 (n = 53) groups. The UAE levels were classified as normoalbuminuria (NA, n = 114) and microalbuminuria (MA, n = 85). Seventy-two patients had DR, and 96 had hypertension. Patients were followed up for 15.7 ± 6.0 years and frequency of and duration to the HD induction were evaluated.During the study period, 8 patients received HD induction. There were no remarkable differences in the rates of HD induction between patients with and without HbA1c ≥7.0, microalbuminuria, DR or hypertension. A Kaplan-Meier analysis revealed that HbA1c ≥7.0 (p = 0.037) and DR (p = 0.037) were associated with a significantly higher risk of HD induction than HbA1c7.0 and no DR, respectively while albuminuria grade and hypertension were not associated with the risk of HD induction. There was significant negative correlation between HbA1c and annual decline rate of eGFR and annual decline rate of eGFR in the patients with prepro-proliferative DR (PDR) was significantly higher than that in the patients without DR. In the multivariate analysis, HbA1c and PDR showed significant relationships with the annual decline rate of eGFR.It was reasonable that poorer glycemic control affected HD induction for 16 years follow-up. However, DR, especially PDR, should also be considered a substantial risk factor for HD induction although microalbuminuria and hypertension did not predict it at the early stage of diabetic nephropathy in type 2 diabetic patients with normal renal function.

Background: HER2 (human epidermal growth factor receptor 2) testing performed by IHC (immunohistochemical) methods and FISH (fluorescence in situ hybridization) is semi-quantitative. Exact quantification of HER2 is needed to predict which patients are more or less likely to response to anti HER2 therapy. To improve the method for cancer patients' HER2 status, we developed a novel fluorescence IHC method using new fluorescence nanoparticle. The fluorescent intensity of this new nanoparticles, termed phosphor-integrated dot (PID), was approximately 100-fold brighter than that of Quantum dots. Because of its increased brightness and analyzing technology, this PID-based fluorescent IHC(IHC-PIC) has an ability of quantifying the biomarker protein in the cancer tissue sample at single particle level. In this study, the primary objective was to investigate if pathological complete response (pCR) rate in HER2- positive breast cancer treated by trastuzumab and lapatinib containing neoadjuvant systemic therapy would depend on the level of HER2, EGFR, HER3, Ki67, ER and PgR protein quantified by this new method. Methods: The Neo-LaTH study is a randomized phase II multicenter trial evaluating the efficacy and safety of lapatinib and trastuzumab followed by lapatinib and trastuzumab plus weekly paclitaxel with or without prolongation of anti-HER2 therapy prior to chemotherapy (18 weeks vs. 6 weeks). The primary endpoint was the comprehensive pCR rate. We evaluated the HER2, EGFR, HER3, Ki67, ER and PgR amount by nano-patho method using PID in formalin-fixed paraffin-embedded core biopsy samples taken at diagnosis retrospective analysis. Univariate and multivariate analyses were performed to determine the association between pCR and variables, including HER2, EGFR, HER3, Ki67, ER and PgR nano-patho score and clinicopathological factors including histological grade, tumor status, nodal status and HER2 FISH ratio. Results: A total of 96 tumor samples from patients were used for the present analysis.The pCR rate was 60.4%. We obtained the images of only PID signal by the image analyses, and calculated the number of PID particles in a cell and defined it as IHC-PID score that reflects the level of HER2, EGFR, HER3, Ki67, ER and PgR protein expression in cancer cells. Univariate analysis showed that HER2 IHC-PID score(p Conclusion: We successfully performed the quantitative IHC-PID for HER2, EGFR, HER3, Ki67, ER and PgR. And we propose using HER2 IHC-PID score as a predictive factor for trastuzumab and lapatinib containing neoadjuvant systemic therapy. This quantitative diagnostic method would be expected to contribute to the development of a molecular therapeutic strategy. Citation Format: Tada H, Miyashita M, Gonda K, Watanabe M, Suzuki A, Watanabe G, Harada N, Sato A, Hamanaka Y, Masuda N, Toi M, Ohno S, Bando H, Ishiguro H, Inoue K, Yamamoto N, Kuroi K, Ohuchi N, Ishida T. New quantitative diagnostic method by fluorescence nanoparticle for HER2 positive breast cancer treated with neoadjuvant lapatinib and trastuzumab: The Neo LaTH study (JBCRG-16TR) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-28.

A correction to this paper has been published: https://doi.org/10.1007/s12282-021-01251-y

Key Points Question Does the performance of adjunctive ultrasonography for breast cancer detection among women undergoing screening mammography change according to breast tissue density? Findings In this secondary analysis of a randomized clinical trial, screening mammography alone demonstrated low sensitivity, whereas adjunctive ultrasonography improved sensitivity both in dense and nondense breasts. Meaning These findings suggest that adjunctive ultrasonography has the potential to improve the detection of early-stage and invasive cancers across both dense and nondense breasts and to mitigate the flaws of mammographic screening., This secondary analysis of a randomized clinical trial evaluates the performance of adjunctive ultrasonography for breast cancer screening in asymptomatic women aged 40 to 49 years undergoing screening mammography according to differences in breast density., Importance Mammography has limited accuracy in breast cancer screening. Ultrasonography, when used in conjunction with mammography screening, is helpful to detect early-stage and invasive cancers for asymptomatic women with dense and nondense breasts. Objective To evaluate the performance of adjunctive ultrasonography with mammography for breast cancer screening, according to differences in breast density. Design, Setting, and Participants This study is a secondary analysis of the Japan Strategic Anti-cancer Randomized Trial. Between July 2007 and March 2011, asymptomatic women aged 40 to 49 years were enrolled in Japan. The present study used data from cases enrolled from the screening center in Miyagi prefecture during 2007 to 2020. Participants were randomly assigned in a 1:1 ratio to undergo either mammography with ultrasonography (intervention group) or mammography alone (control group). Data analysis was performed from February to March 2020. Exposures Ultrasonography adjunctive to mammography for breast cancer screening regardless of breast density. Main Outcomes and Measures Sensitivity, specificity, recall rates, biopsy rates, and characteristics of screen-detected cancers and interval breast cancers were evaluated between study groups and for each modality according to breast density. Results A total of 76 119 women were enrolled, and data for 19 213 women (mean [SD] age, 44.5 [2.8] years) from the Miyagi prefecture were analyzed; 9705 were randomized to the intervention group and 9508 were randomized to the control group. A total of 11 390 women (59.3%) had heterogeneously or extremely dense breasts. Among the overall group, 130 cancers were found. Sensitivity was significantly higher in the intervention group than the control group (93.2% [95% CI, 87.4%-99.0%] vs 66.7% [95% CI, 54.4%-78.9%]; P

We aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose (18F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff. Sixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining 18F-FDG accumulation were scanned by high-resolution PEM. At least 1 day after surgery, tumour extension was evaluated by three independent experienced readers and by binarized images from the specimen-PEM data. Intraoperative exposure of medical staff to 18F-FDG was measured. Specimen-PEM evaluations of binarized images and the three investigators detected all (100 %, 12/12) invasive lesions and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive value of the accumulated lesions was 74.4 % (29/39) for the binarized images and 82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen sections detected 100 % (2/2) of the margin-positive cases, also detected by both specimen-PEM evaluation methods with no false-positive margin cases. The mean exposure of the medical staff to 18F was 18 μSv. Specimen-PEM detected invasive and in situ lesions with high accuracy and allowable radiation exposure. • Specimen-PEM detected invasive and in situ lesions with high accuracy. • Specimen-PEM predicted complete resection with the same accuracy as frozen section analysis. • Breast-conserving surgery after fluorodeoxyglucose injection was performed with low medical staff exposure.

Metabolomics has recently emerged as a tool for understanding comprehensive tumor-associated metabolic dysregulation. However, only limited application of this technology has been introduced into the clinical setting of breast cancer. The aim of this study was to determine the feasibility of metabolome analysis using routine CNB/VAB samples from breast cancer patients and to elucidate metabolic signatures using metabolic profiling. After breast cancer screenings, 20 consecutive patients underwent CNB/VAB, and diagnosed with benign, DCIS and IDC by histology. Metabolome analysis was performed using CE–MS. Differential metabolites were then analyzed and evaluated with MetaboAnalyst 4.0. We measured 116-targeted metabolites involved in energy metabolism. Principal component analysis and unsupervised hierarchical analysis revealed a distinct metabolic signature unique to namely “pure” IDC samples, whereas that of DCIS was similar to benign samples. Pathway analysis unveiled the most affected pathways of the “pure” IDC metabotype, including “pyrimidine,” “alanine, aspartate, and glutamate” and “arginine and proline” pathways. Our proof-of-concept study demonstrated that CE–MS-based CNB/VAB metabolome analysis is feasible for implementation in routine clinical settings. The most affected pathways in this study may contribute to improved breast cancer stratification and precision medicine.

This article updates readers as to what is new in the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis, 2018 Edition. Breast cancer screening issues are covered, including matters of breast density and possible supplemental modalities, along with appropriate pre-operative/follow-up diagnostic breast imaging tests. Up-to-date clinical practice guidelines for breast cancer screening and diagnosis should help to provide patients and clinicians with not only evidence-based breast imaging options, but also accurate and balanced information about the benefits and harms of intervention, which ultimately enables shared decision making about imaging test plans.

Breast cancer is a heterogeneous disease, and immunohistochemical evaluation is a surrogate marker that is widely used in clinical settings to identify the intrinsic subtypes. The definition of the Luminal B-like breast cancer was changed at the 2013 St. Gallen meeting; therefore, we investigated the clinicopathological features of the new Luminal B-like breast cancer categorized in the latest definition. We also compared the conventional PgR-high Luminal B-like breast cancer with the conventional PgR-low or -negative Luminal B-like breast cancer. We investigated 118 Luminal HER2-negative breast cancer patients who were operated in 2005–2008 at a single institution. Data on each patient’s medical history were retrieved. A subset of patients (14.4 %) was categorized as the new Luminal B-like due to low or negative PgR: 58.8 % were histological grade I, 65 % were T1 in tumor size, and half had node involvement. Chemotherapy was performed in half of the cases. Breast cancer-related events were more frequent for the new Luminal B-like breast cancer than for the Luminal A-like breast cancer and were less frequent than for the conventional Luminal B-like breast cancer. Based on multivariate analysis, low or negative expression of PgR and the absence of hormonal therapy were worse prognostic factors. When categorized into two groups by the PgR status, 48.1 % of the conventional Luminal B-like breast cancer was PgR-high; tumor size was smaller, and nodal involvement was less in this group. The rate of adjuvant chemotherapy of the conventional PgR-high Luminal B-like breast cancer was less than that of the conventional PgR-low or -negative Luminal B-like breast cancer. Breast cancer-related events were significantly lower in the conventional PgR-high Luminal B-like breast cancer. Our results show the possibility that PgR status has some influence on the prognosis for Luminal HER2-negative breast cancers. Therefore, attention should be paid to the PgR status as well as Ki-67.

Mammography is the only method of breast cancer screening that has established evidence of a mortality reduction. However, mammography does not achieve sufficient accuracy in the high-density breasts of patients

Introduction Given modern treatment strategies, controversy remains regarding whether postmastectomy radiation therapy (PMRT) is necessary for breast cancer patients with 1–3 positive axillary lymph nodes (ALN). Our aim was to assess the significance of PMRT in the modern treatment era for these patients. Material and methods We have conducted the retrospective multicenter study and identified 658 patients with 1–3 positive ALN who were treated with mastectomy and ALN dissection between 1999 and 2012. Propensity score weighting was used to minimize the influence of confounding factors between the PMRT and no-PMRT groups. The variables including tumor size, lymph nodes status, skin and/or muscle invasion, histological grade, lymphovascular invasion and ER positivity which were statistically unbalanced between the groups were used to define the propensity scores. Results The median follow-up time was 7.3 years. In the modern era (2006–2012), no significant difference in locoregional recurrence (LRR)-free survival was noted between the PMRT and no-PMRT groups ( P = 0.3625). The 8-year LRR-free survival rates of the PMRT and no-PMRT groups were 98.2% and 95.3%, respectively. After matching patients by propensity scores, the PMRT group, compared to the no-PMRT group, exhibited significantly better locoregional control ( P = 0.0366) in the entire cohort. The 10-year LRR-free survival rates were 97.8% and 88.4% in the PMRT and no-PMRT groups, respectively. In contrast, no significant difference in LRR-free survival was noted between the PMRT and no-PMRT groups in the modern era ( P = 0.5298). The 8-year LRR-free survival rates of patients treated in the modern era were approximately the same between the groups (98.0% and 95.7% in the PMRT and no-PMRT groups, respectively). Particularly, LRR-free survival of HER2 positive breast cancer significantly improved in the modern treatment era, compared with that of the old treatment era ( P = 0.0349). Conclusion PMRT had minimal impact on LRR for breast cancer patients with 1–3 positive ALN in the modern treatment era.

To confirm the constitutive model developed by the present authors, example calculations are conducted for the transformation behavior of shape memory alloys. The constitutive model describes the transformation behavior of the material by calculating the transformation stress and strain of transformation systems of micro structures in the material. In the calculating, the accommodation mechanism acting on microstructures of the material is also taken into consideration. Computational results by the constitutive model for these loading paths are revealed to be reasonable in comparing with experimental observations.

The effectiveness of screening mammography (SMG) on mortality has been established in randomized controlled trials in Western countries, but not in Japan. This study evaluated the effectiveness by comparing the survival based on detection methods. The survivals were estimated by the Kaplan-Meier method. Breast cancer patients diagnosed from 1 January 1989 to 31 December 2000 were determined using the Miyagi Prefectural Cancer Registry and follow-up was performed from the date of the diagnosis until the date of death or the end of follow-up, 31 December 2005. The hazard ratios (HR) and 95% confidence interval (CI) of breast cancer death based on the detection methods were estimated by the Cox proportional-hazard regression model. The mean age of the 7513 patients was 55.7 years (range, 15.0-99.3). The 5-year survival associated with the SMG group, the clinical breast examination (CBE) group, and the self-detection group was 98.3%, 94.3%, and 84.8%, respectively. The HR (95% CI) of deaths from breast cancer was 2.50 (1.10-5.69) for patients in the CBE group and 6.57 (2.94-14.64) for the self-detection group in comparison to the SMG group. In women aged 50-59, the HRs were 1.64 (0.58-4.62) among the CBE group and 3.74 (1.39-10.03) among the self-detection group, and the HRs for the CBE and self-detection groups in women aged 60-69 were 2.96 (0.68-12.83) and 9.51 (2.36-38.26), respectively. After adjusting for stage, the HRs dropped remarkably. Screening mammography may be more effective in the elderly group and be able to reduce the mortality of breast cancer in Japan.

The purpose of this paper is to report the integration studies of business modeling and roadmapping methods for the “Innovation Support Technology (IST)” and the IST's practical application to real-world cases. The IST is conducted for the purpose of offering a convenient tool for engineers and researchers in order to enhance corporate value from R&D outputs. “Japan's lost decade” has forced companies to change R&D management and R&D operation style, especially regional industries. We propose the framework for revitalization of regional industries by using the Strategic Technology Roadmap made by the Ministry of Economy, Trade and Industry (METI-TRM) with business modeling. We applied this IST method to several real-world cases to show its effectiveness. This study represents the result of over four years (fall 2002) of work with the value creation framework of the business modeling method for R&D outputs, done by a group of researchers from JATES (Japan Techno-Economics Society).

The age-specific sensitivity of a screening program was investigated using a population-based cancer registry as a source of false-negative cancer cases. A population-based screening program for breast cancer was run using either clinical breast examinations (CBE) alone or mammography combined with CBE in the Miyagi Prefecture from 1997 to 2002. Interval cancers were newly identified by linking the screening records to the population-based cancer registry to estimate the number of false-negative cases of screening program. Among 112 071 women screened by mammography combined with CBE, the number of detected cancers, false-negative cases and the sensitivity were 289, 22 and 92.9%, respectively, based on the reports from participating municipalities. The number of newly found false-negative cases and corrected sensitivity when using the registry were 34 and 83.8%, respectively. In detected cancers, the sensitivity of screening by mammography combined with CBE in women ranging from 40 to 49 years of age based on a population-based cancer registry was much lower than that in women 50-59 and 60-69 years of age (40-49: 18, 71.4%, 50-59: 19, 85.8%, 60-69: 19, 87.2%). These data suggest that the accurate outcome of an evaluation of breast cancer screening must include the use of a population-based cancer registry for detecting false-negative cases. Screening by mammography combined with CBE may therefore not be sufficiently sensitive for women ranging from 40 to 49 years of age.

This paper presents the results of a survey as well as an argument from the viewpoint of behavioral economics with the aim of clarifying how consumers make decisions about electrical appliance use in the home. A survey of consumers showed that most have little awareness of the energy efficiency of appliances, the price of the services produced by electrical appliances, or electricity rates. These findings indicate that price does not function as a signal in electricity consumption through electrical appliance use. Rather, we found that consumer decision-making in electricity consumption is dependent on the characteristics of the particular electrical appliances they use. Additionally, we argue that the payment system for home electricity consumption plays an important role in decision-making, causing biases due to aspects of human psychology discussed here in terms of satisficing and heuristics, payment decoupling, and budgeting. We conclude that decision-making about electrical appliance use and electricity consumption in the home is not always rational and is affected both by the particular characteristics of appliances and the payment system for electricity consumption along with human psychology.

Breast-conserving treatment (BCT) is a standard therapy for early breast cancer. Many reports have described the effectiveness of post-BCT radiation therapy. However, the post-BCT local recurrence rate of only 5% to 10% indicates that radiation therapy may be unnecessary in many cases. To accurately select those patients who do not require post-BCT radiation therapy, we investigated the significance of irradiation in BCT by comparing local recurrence rates in irradiated and nonirradiated patients, grouped according to clinicopathological criteria that we evaluated. The patients were divided into two groups: a previous-criteria group and a present-criteria group. The former group included 85 patients in whom only two factors were considered as the criteria for radiation therapy: margin-positivity and lymphatic metastasis-positivity. The latter group included 318 patients in whom three additional factors were also considered: lymphatic invasion, intraductal extension, and metachronous/synchronous bilateral breast cancer. The use of five clinicopathological factors rather than two as the criteria for irradiation led to an increase in the irradiation ratio from 47.1% to 63.2% and a decrease in local recurrence from 12.9% to 2.2%. Because of the short average follow-up period of this study, further careful, regular follow-up and randomized comparative studies are required. It may also be necessary to include the patient age and margin condition as mandatory criteria for irradiation.

Endoscopic tumor ablation is a valuable option for inoperable postoperative laryngotracheal intraluminal invasion of well-differentiated thyroid carcinoma (DTC).To investigate whether DTC invasion to the laryngotracheal mucosa can be controlled by 'simple' tumor ablation considering its relatively slow-growing nature.Twenty-two consecutive patients underwent endoscopic tumor ablation caused by DTC for local control of intraluminal lesions with no significant extrinsic laryngotracheal compression in symptomatic or asymptomatic patients in whom radical operations were contraindicated. Debulking by Nd:YAG laser was followed by electrocoagulation and microwave coagulation for the residual tumor base.The critical complication, post-treatment supraglottic stenosis, was managed by prophylactic minitracheotomy. During the follow-up period of up to 125 months, 6 of 22 patients died (median survival 50 months), mainly of lung metastases, but all had a patent airway at death. Post-surgical extraluminal lesion growth is indolent and since relapse of the intraluminal lesion is the main cause of symptoms, satisfactory local control could be obtained by re-ablation of the mucosal lesion every few years. Lesions requiring retreatment within 1 year after initial treatment usually have high-grade malignancy, causing extrinsic compression, and prognosis is unfavorable.

Objective: The aim of this study was to evaluate the reliability of information obtained by core needle biopsy (CNB). Methods: We studied 111 women (112 lesions) with breast cancer who underwent CNB and subsequent surgical excision. Six factors (histological type, nuclear grade, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor receptor-2 (HER2) status) were evaluated in a blinded fashion at CNB and at surgical excision. Results: The histological type at CNB correlated exactly with that of the excisional specimen in 83% (87/105) of the cases. Of the 45 in situ lesions at CNB, 16 (36%) were found to have invasive carcinoma at surgical excision. The difference between the specimens from CNB and those from surgery in terms of the absolute concordance rate and k statistic value were 61% with a fair k value (0.26) in the nuclear grade, 75% with a moderate k value (0.55) in the histological grade, 95% with an almost perfect k value (0.84) in ER, 88% with a substantial k value (0.70) in PR and 88% with a substantial k value (0.65) in HER2. Regarding the evaluation of nuclear and histological grades, a trend toward greater accuracy was observed when thicker specimens were used. Conclusions: CNB provided reliable information on the histological type of invasive carcinoma. It also evaluated ER, PR and HER2 (only in cases where the score was 3þ) accurately in spite of the limited quantity of the specimen obtained with the thin (16-gauge) needle.

Mammography is the only proven method for breast cancer screening that reduces mortality, although it is inaccurate in young women or women with dense breasts. We investigated the efficacy of adjunctive ultrasonography.Between July, 2007, and March, 2011, we enrolled asymptomatic women aged 40-49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer Randomized Trial (J-START). Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years. Randomisation was done centrally by the Japan Clinical Research Support Unit. Participants were randomly assigned in 1:1 ratio to undergo mammography and ultrasonography (intervention group) or mammography alone (control group) twice in 2 years. The primary outcome was sensitivity, specificity, cancer detection rate, and stage distribution at the first round of screening. Analysis was by intention to treat. This study is registered, number UMIN000000757.Of 72,998 women enrolled, 36,859 were assigned to the intervention group and 36,139 to the control group. Sensitivity was significantly higher in the intervention group than in the control group (91·1%, 95% CI 87·2-95·0 vs 77·0%, 70·3-83·7; p=0·0004), whereas specificity was significantly lower (87·7%, 87·3-88·0 vs 91·4%, 91·1-91·7; p0·0001). More cancers were detected in the intervention group than in the control group (184 [0·50%] vs 117 [0·32%], p=0·0003) and were more frequently stage 0 and I (144 [71·3%] vs 79 [52·0%], p=0·0194). 18 (0·05%) interval cancers were detected in the intervention group compared with 35 (0·10%) in the control group (p=0·034).Adjunctive ultrasonography increases sensitivity and detection rate of early cancers.Ministry of Health, Labour and Welfare of Japan.

Introduction The status of tumor-infiltrating lymphocytes (TILs) has been recently proposed to predict clinical outcome of patients with breast cancer. We therefore studied the prognostic significance of CD8+ TILs and FOXP3+ TILs in residual tumors after neoadjuvant chemotherapy (NAC) and the alterations in these parameters before and after NAC in patients with triple-negative breast cancer (TNBC). Methods One hundred thirty-one TNBC patients who received NAC at three institutions were examined. CD8+ TIL and FOXP3+ TIL in residual tumors and biopsy specimens were evaluated by double-staining immunohistochemistry. The CD8+ TIL and FOXP3+ TIL status of the residual tumors was assessed, and the rates of their changes before and after NAC were calculated. Results TNBC patients with high CD8+ TIL levels or a high CD8/FOXP3 ratio in residual tumors had significantly better recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) than patients with low values of these parameters. In multivariate analyses, CD8+ TIL exhibited strong prognostic significance for RFS, with a hazard ratio (HR) of 3.09 (95 % confidence interval (CI) 1.537–6.614, P=0.0013). The CD8/FOXP3 ratio was also significantly correlated with RFS (HR=2.07, 95 % CI 1.029–4.436, P=0.0412). TNBC with larger residual tumor size and positive lymph node status, which are known prognostic factors, was independently associated with worse RFS (P=0.0064 and P=0.0015, respectively). High CD8+ TIL levels were a markedly powerful indicator of improved BCSS, with an HR of 3.59 (95 % CI 1.499–9.581, P=0.0036). Nodal status was also associated with BCSS (P=0.0024). TNBC with a high rate of CD8+ TIL changes was associated with significantly better RFS compared with the low group (P=0.011). Higher rates of changes in the CD8/FOXP3 ratio were significantly correlated with both better RFS and BCSS compared with lower rates (P=0.011 and P=0.023, respectively). Conclusions This is the first study to demonstrate that high CD8+ TIL and a high CD8/FOXP3 ratio in residual tumors and increment of these parameters following NAC and accurately predict improved prognosis in TNBC patients with non-pathological complete response following NAC. These parameters could serve as a surrogate one for adjuvant treatment in patients with residual disease in the neoadjuvant setting. Electronic supplementary material The online version of this article (doi:10.1186/s13058-015-0632-x) contains supplementary material, which is available to authorized users.

An archive autopsy case of a 50-year-old man who died of Hodgkin's lymphoma had a 4-year, 4-month history of dementia. After radiochemotherapy, the lymphoma subsided except for involvement of the spleen, but the dementia remained. Neuropathological examination revealed that the pathology was confined to the hippocampus, both hippocampi showing sclerosis without inflammation. Neurons of sector cornu ammonis (CA) 1 were completely lost whereas moderate neuron loss was also observed in sectors CA3 and 4, and the dentate gyrus. Neurons of sector CA2 were relatively well preserved and the subiculum was intact. There was no evidence of global hypoxia, or of neurodegenerative disorders with pathological changes affecting the hippocampus. Although there was a long preneoplastic history, and no inflammatory changes were found at autopsy, the present case of hippocampal sclerosis could be included in the category of paraneoplastic limbic encephalitis associated with Hodgkin's lymphoma or the Ophelia syndrome.

症例は63歳の女性で2002年3月, 前医で直腸癌に対し低位前方切除術を施行されたが, 術後早期より膣からの便汁の排泄があり直腸膣瘻と診断された. 2回の瘻孔切除縫合術, 4回の内視鏡的クリッピング術, 人工肛門造設を行うも治癒しえず, 2002年11月, 当科に紹介となった. 2003年月, 手術を施行した. 瘻孔部の切除を行い, 右薄筋の筋皮弁を用い膣後壁, 直腸瘻孔部を充填形成した. 術後経過は良好で問題となるような機能障害も出現しなかった. 2003年6月人工肛門を閉鎖. 現在, 術後約1年を経過したが瘻孔再発の徴候はない. 直腸術後の難治性直腸膣瘻に対する, 薄筋筋皮弁による外陰部形成術は機能障害の出現もなく患者のQOL向上に非常に貢献しうる術式と考えられた.

Objective The natural history of the development of ovarian carcinoma is not known. It also remains undetermined whether ovarian carcinomas develop from benign and/or borderline malignant tumors or arise de novo from the ovarian surface epithelium. Methods To address these issues clinicopathologically, we reviewed the clinical charts of 543 patients with epithelial ovarian carcinoma and 252 patients with borderline tumors who underwent laparotomy at seven hospitals and collected patients whose clinical and transvaginal ultrasonography (USG) findings for adnexal regions 12 months or fewer prior to the surgery were available. Histological slides of the resected specimens were reexamined concerning the diagnosis and histological grade, as well as the presence or absence of benign- or borderline-like lesions adjacent to the carcinoma. Results Forty-nine patients had had gynecological examination with transvaginal USG 12 months or fewer prior to laparotomy. Among them, 35 had carcinomas (11 serous, 6 mucinous, 8 clear cell, 10 endometrioid) and 14 had borderline tumors (8 serous, 6 mucinous). Of the 35 patients with carcinoma, 19 (54%) had been followed up for benign-appearing cysts or endometriotic cysts. In these cases, serial USG examinations revealed an increase in size and/or appearance of the solid part of the cyst. In the remaining 16 (46%), however, there had been no apparent abnormalities in USG, and such cases occurred most frequently for serous carcinomas. Conclusion Our findings suggest that approximately half of ovarian carcinomas develop secondarily from preexisting, benign-appearing cysts or endometriotic cysts, whereas the remaining half seem to develop suddenly from a normal-appearing ovary. This appears to be consistent with two possible pathways of ovarian carcinoma development; adenoma–carcinoma sequence and de novo carcinogenesis.

The risk of fracture does exist even in the carefully designed ceramic components under excess stress unexpected in design procedure such as high stresses caused by restraining the deformation at the contact region of the component. To assess the safety and the reliability of ceramics components under such circumstances, it is indispensable to take the damage tolerance of the material into consideration. Ceramics is thought to be perfectly brittle and have no damage tolerance. But, though very little, it has the damage tolerance. The important problems open to us now are to estimate the extent of the damage tolerance of ceramics quantitatively and to clear the relation between the damage tolerance of the material and the reliability of the component. In this paper, we demonstrate the existence of the damage tolerance in the ceramics by tests using specimens of a porous cordierite. The nonlinear stress-strain curve of the brittle material is thought to be a reflection of the damage tolerance of the material and it is shown that the nonlinear stress-strain curve obtained can be simulated by the distributed micro cracks model developed here. The relation between the damage tolerance and the reliability is also discussed through several simulation works. These simulations show that when the damage tolerance of the material is getting larger, the reliability of the component becomes higher. This conclusion is supported by the fracture test results using notched specimens of a porous cordierite where the notch sensitivity is shown to be very small in this material. This means that this material has the high reliability under the stress concentration.

Objective: The objective of the Japan Strategic Anti-cancer Randomized Trial was to verify the efficacy of the use of ultrasonography in breast cancer screening among women aged 40 –49 years. The purpose of this paper was to report the design and recruitment result of this study. Methods: In this study of women in their 40s, the participants were divided into two groups, one of which (the intervention group) was subjected to mammography and ultrasonography (using a standardized ultrasonography examination), while the other (the control group) was examined with mammography, in a randomized controlled trial, with the objective of verifying the accuracy and efficacy of examinations by comparing the two groups. Results: The cumulative total number of participants registered in the study was 76 196 (38 313 in the intervention group and 37 883 in the control group). 71.0% of participants registered to the study were under individual randomized controlled trial, 25.0% were under cluster randomized controlled trial and 3.9% were under non-randomized controlled group. The study was designed so that participants registered at their first examination underwent examinations by the same method for the subsequent two years. 74.1% of participants scheduled for a second examination had undertaken it, while information regarding the presence of interval cancer had been obtained from a further 20.6% using a questionnaire. At July 2013, the status of 5.3% of all participants was unclear. Conclusions: It was the first large-scale randomized controlled trial carried out in Japan. The scheduled second examinations were completed at the end of fiscal 2012. Once the proportion of participants whose status is unclear has fallen to � 5%, the authors plan to collate the data relating to the primary end points, and publish the results.

The floating behavior of a flexible belt on a steel trough by an air flow is analyzed to investigate the stable operation for a belt conveyer of air suspended type. The deformation behavior of a belt element is described by the curved beam theory and air flow is described by the Bernoulli equation including flow loss effect. These equations form a coupled system of equations of the structure (flexible belt) and the fluid (air flow). These equations are numerically solved by an iteration method based on the Newton-Raphson method. Experimental investigations are simultaneously conducted using the test equipment specially prepared. A good agreement between analytical and experimental results is obtained.

A feasibility study of a remote radiation monitoring system using an autonomous unmanned helicopter, mounted with a radiation detector and three CCD cameras, was carried out for surveying the dose-rate distribution of environmental radiation. This system can fly to destinations and return under automatic operation, measure radiation data during flight, and immediately transmit the data, including images, to a monitoring station on the ground. It is also possible to monitor the data on a map on a computer display in real time. Flight tests confirmed that the system can measure fluctuations of dose-rate distribution on the ground, and could be used for radiation monitoring in case of a nuclear emergency.

Background: Breast cancer surgery, including breast-conserving surgery or sentinel lymphnode biopsy, has become minimally invasive. Recent consensus guidelines on the margins for breast-conserving surgery have defined a negative margin as one with no ink on tumor, regardless of the distance from the tumor, whereas a positive margin has ink on the tumor. Therefore, the extent of required tumor resection will decrease for cosmoses and expand the indications for breast-conserving surgery. Therefore, there is a real need for a more accurate imaging of tumor spread. In particular, a functional imaging of breast cancer specimens will help determine negative margins in breast-conserving surgery. We collaborated with Sendai Medical Imaging Center (SMIC) who have high-resolution positron emission mammography (PEM) with the novel scintillator Pr3+-doped transparent ceramic Lu3Al5O12 (Pr:LuAG) for the imaging of breast cancer specimen with 18F-fluodeoxyglucose (FDG). Methods: With the approval of the hospital ethics committee, positron emission tomography (PET) was conducted preoperatively on the day of surgery with 18F-FDG. After the PET results were explained to the patients, breast-conserving surgery was performed in 11 patients from February to July 2014. In the operating room, medical staff exposures were calculated with a portable dosimeter. All of the cases were carried out intraoperative frozen sections that were taken from all sides of the outside of the specimens. The specimens were serially sectioned in 5-mm slices for permanent histology. After the specimens were removed, they were sent to the SMIC and high-resolution specimen-PEM (s-PEM) was conducted. We evaluated the detection rate of s-PEM in in situ or invasive lesions (extent of locations were tolerated up to a 10% error), the predictive value of margin status between s-PEM and frozen section analysis and medical stuff exposure. Results: In 11 breast specimens, eight invasive lesions and 15 in situ lesions (excluding the foci that exist in less than three carcinoma ducts) were confirmed by permanent histology. s-PEM detected all of the invasive lesions and 14 out of 15 in situ lesions. Three breast specimens had positive margins in permanent histology. Two out of three cases with positive margin accumulated 18F-FDG at the edge of the specimens, which were considered positive margins with s-PEM, whereas positive margins were only one out of three of the frozen section analysis. In contrast, a false positive margin was found in only one case with s-PEM, which confirmed the preoperative core-needle biopsy that was diagnosed as an intraductal proliferative lesion. Medical staff exposure was determined for the operator, first assistant, second assistant, anesthesiologist, scrab nurse and circulating nurse as 31, 34, 25, 11, 21 and 6 µSV, respectively. Conclusion: s-PEM detected not only invasive lesions but also in situ lesions with great accuracy. It might accelerate the decrease in the extent of resection required in breast-conserving surgery. However, further studies are needed to elucidate the characteristics of the false positive cases in s-PEM. Citation Format: Gou Watanabe, Masatoshi Itoh, Dan Kyokutou, Mika Watanabe, Takanori Ishida, Akihiko Suzuki, Minoru Miyashita, Hiroshi Tada, Naoko Mori, Noriaki Ohuchi. High-resolution specimen-positron emission mammography (s-PEM) indicates the spread of cancer in breast-conserving surgery [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-02-12.

Background We performed a multivariate analysis of clinical variables in 320 patients with renal cell carcinoma to identify important prognostic factors for long-term survival. Methods We retrospectively reviewed the medical records of 320 patients who presented with renal cell carcinoma. Survival curves were calculated by the Kaplan-Meier method and statistical differences were determined by the log-rank test. Significant prognostic factors were evaluated by Cox's multivariate proportional hazard model. Results The median follow-up period was 29 months. The overall survival rates at 1, 5, and 10 years were 90.0%, 77.6%, and 69.9%, respectively. Seventeen of the 19 prognostic factors evaluated were shown to be significant by the log-rank test: patient age, sex, performance status, body temperature, erythrocyte sedimentation rate (ESR), levels of hemoglobin, a2-globulin, C-reactive protein, fibrinogen, immunosuppressive acidic protein (IAP), size or involvement of tumor (T classification), regional lymph node involvement (N classification), extent of metastasis (M classification), pathologic grade, tumor cell type, mode of tumor infiltration, and the modality of treatment (curative surgery). Among them, the body temperature, ESR, a2-globulin, fibrinogen, IAP, and mode of tumor infiltration were excluded from multivariate analysis because of missing data. Curative surgery was also excluded because it is a treatment modality and different from the other variables which are clinical or pathologic characteristics. From the remaining 10 variables, multivariate analysis showed that age (P = 0.0389), N classification (P = 0.0289), and M classification (P

BRCA1 and BRCA2 mutations cause high breast cancer incidence rates as high as 80% Although prophylactic therapy is still controversial, several prophylactic therapies have been proposed and tried for BRCA1 and BRCA2 mutation carriers. Prophylactic surgery, chemo-prevention and precise screening have been proposed as prophylactic therapy. All BRCA1 and BRCA2 mutation carriers need knowledge about their disease and the countermeasures that are used to protect against onset of disease. Counseling plays an important role in this regard for people with genetic diseases. Therefore, collaboration between breast cancer clinics and genetic counseling services is the most important issue in clinical practice. Our group consists of three national universities and a general hospital. In this article we describe our trial to construct a clinical system against hereditary breast cancer as an interim report for the Japanese Ministry of Health, Labour and Welfare.Twenty familial breast cancer patients were registered in this study. The whole sequence of BRCA1 and BRCA2 were analyzed. If pathological mutations were detected, their first degree families were introduced to the counseling division at each institute when candidates visited counseling divisions.Four cases of a deleterious mutation in BRCA1 or BRCA2 were detected among 20 cases. Their first degree relatives are now under consideration for visiting counseling divisions. The clinical system described in this study should play a role to protect BRCA1 or BRCA2 mutation carriers in Japan.