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Introduction This study described, in routine clinical practice in Japan, the patient characteristics, treatment patterns, and outcomes of female patients with HR + /HER2- metastatic breast cancer (MBC) who started abemaciclib treatment. Methods Clinical charts were reviewed for patients starting abemaciclib in 12/2018–08/2021 with a minimum of 3 months follow-up data post-abemaciclib initiation regardless of abemaciclib discontinuation. Patient characteristics, treatment patterns, and tumor response were descriptively summarized. Kaplan–Meier curves estimated progression-free survival (PFS). Results 200 patients from 14 institutions were included. At abemaciclib initiation, median age was 59 years, and the Eastern Cooperative Oncology Group performance status score was 0/1/2 for 102/68/5 patients (58.3/38.9/2.9%), respectively. Most had an abemaciclib starting dose of 150 mg (92.5%). The percentage of patients receiving abemaciclib as 1st, 2nd, or 3rd line treatment was 31.5%, 25.8%, and 25.2%, respectively. The most frequent endocrine therapy drugs used with abemaciclib were fulvestrant (59%) and aromatase inhibitors (40%). Evaluation of tumor response was available for 171 patients, 30.4% of whom had complete/partial response. Median PFS was 13.0 months (95% CI 10.1–15.8 months). Conclusions In a routine clinical practice setting in Japan, patients with HR + , HER2- MBC appear to benefit from abemaciclib treatment in terms of treatment response and median PFS, with the results broadly reflecting the evidence demonstrated in clinical trials.

Background 5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients. Methods This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents. Results Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P < 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P < 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81). Conclusion Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.

Immediate breast reconstruction (IBR) is a standard option for breast cancer patients, although its utility in patients with advanced breast cancer requiring neoadjuvant chemotherapy (NAC) is debatable. We assessed the short-term complications and long-term prognosis of IBR after NAC. We retrospectively analyzed 1135 patients with IBR and/or NAC between 2010 and 2018, 43 of whom underwent IBR after NAC. Twenty-five patients underwent reconstruction with a tissue expander (TE) followed by silicon breast implantation, 5 with a latissimus dorsi muscle transfer flap, and 13 with a deep inferior epigastric perforator flap. Complete surgical resection with a free margin confirmed by a pathological assessment was achieved in all patients. The evaluation of the short-term complications indicated no cases of total flap necrosis, two cases of partial flap necrosis, and one case of wound infection. Only one case required postponement of subsequent therapy due to partial flap necrosis. A long-term evaluation indicated no local recurrence, although distant metastasis was observed in 4 cases, 3 patients died, and TE removal after post-mastectomy radiotherapy (PMRT) was performed in 2 of 11 TE cases. IBR may be a viable option in patients with advanced breast cancer who achieve complete surgical resection after NAC.

Purpose To compare monthly versus pro re nata (PRN) ranibizumab injections in the treatment of exudative macular degeneration (AMD) while assessing the utility of microperimetry (MP) and multifocal electroretinography (mfERG) testing when monitoring response to treatment. Methods A randomized exploratory trial comparing the efficacy of monthly versus PRN dosing of ranibizumab (0.5 mg or 2.0 mg) for patients with exudative AMD over 12 months. High-resolution optical coherence tomography (HR-OCT) studies were used to guide PRN treatment and any cystic spaces or subretinal fluid prompted retreatment. Macular function was assessed using mean sensitivity on MP and N1-P1 response density on mfERG. Best-corrected visual acuity (BCVA) was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) letters and anatomic response assessed with central foveal thickness (CFT) using HR-OCT studies. Results The 12-month study was completed by 43 patients in the PRN cohort and 33 patients in the monthly cohort. Mean BCVA improved by 6.0 ± 1.3 ETDRS letters in the PRN cohort compared to 7.3 ± 2.8 ETDRS letters in the monthly cohort (p=0.68). A reduction in mean CFT of 64.5 ± 13.3 and 96.3 ± 22.0 µm occurred in the PRN and monthly cohorts, respectively (p=0.22). Macular function assessed with mfERG decreased comparably in both the PRN and monthly cohorts (p=0.33). For all patients, average mean sensitivity significantly improved by 1.7 ± 0.5 dB (p

Background Intestinal Behçet's disease (BD) is a relapsing-remitting disease typically associated with punched-out ulcers in the ileocecal region. Optimal monitoring of disease activity is necessary; however, ileocolonoscopy cannot be performed on a regular basis as it is invasive, resource-intensive and causes considerable patient discomfort. Furthermore, there are risks of intestinal bleeding and perforation caused by pretreatment laxatives and air insufflation during the examination. Hence, other follow-up examinations are required. Intestinal ultrasonography (IUS) is a minimally invasive imaging method, but there are no previous reports of comparisons between IUS and endoscopy for intestinal BD. This study aimed to evaluate the usefulness of IUS in assessing the activity of ileocecal ulcers in intestinal BD. Methods This retrospective single-centre study included patients with intestinal BD who underwent colonoscopy and IUS within 2 weeks, from 2007 to 2020. Correlations between the corresponding endoscopic activity using the Sakita–Miwa classification and six IUS variables (bowel wall thickness [BWT], vascularity, bowel wall stratification, intramural and extramural abscesses, fistulas and mesenteric lymphadenopathy) were assessed and used to select the variables that should be included in the new simple score. IUS findings were also compared with biomarker (C-reactive protein [CRP]) concentrations and clinical severity indices (Crohn’s disease activity index and disease activity index for intestinal BD [DAIBD]). Results Seventy-nine IUS examinations from 53 patients were included. Univariate analysis revealed that CRP and DAIBD and the IUS findings BWT, vascularity and bowel wall stratification and intramural and extramural abscesses differed significantly according to endoscopic ulcer activity. Multivariate analysis using a logistic regression model revealed that only BWT and vascularity were statistically different; therefore, a new simple score ([2*BWT] + [5*vascularity]) was constructed. Receiver operating characteristic curve analysis revealed an area under the curve of 0.91 for detecting endoscopic activity, which was superior to those of CRP (0.80; P=0.069), Crohn’s disease activity index (0.69; P=0.002) and DAIBD (0.67; P Conclusion A new simple ultrasound activity index for intestinal BD comprising BWT and vascularity was constructed and correlated well with endoscopic disease activity. This is the first report describing the usefulness of IUS for intestinal BD, and we believe the findings will have many implications in clinical practice.

PURPOSE To illustrate a potentially concerning artifact on Optos wide-angle imaging. METHODS Case report. RESULTS A healthy 11-year-old girl, with no medical history, was found to have a lightly pigmented superotemporal choroidal tumor, suspicious for melanoma, which was detected on Optos wide-angle imaging by her optometrist. On referral to the retinal specialist, the mass was not visible on funduscopy. B-scan ultrasonography depicted flat retina and no visible mass. Review of the Optos image revealed that the pseudomelanoma represented the patient's nose. CONCLUSION Optos wide-angle imaging provides broad retinal imaging; however, artifacts from patient positioning can lead to the nose artifact.

Background: The American Joint Committee for Cancer (AJCC) 8th edition cancer staging system for breast cancer incorporated biologic factors in addition to the 7th edition anatomic stage. We analyzed how the new AJCC 8th edition prognostic stage refined its stratification compared with the anatomic stage. Methods: We reviewed the data of 4,134 patients with stage I to III breast cancer who underwent surgery at Tokyo Metropolitan Komagome Hospital between 2000 and 2016. The anatomic stage and prognostic stage were re-staged according to the AJCC 8th edition staging manual. Patients who received neoadjuvant chemotherapy or had bilateral breast cancer and those with unknown clinicopathologic factors were excluded. The 21-gene Oncotype DX breast recurrence score was not used for staging in this study. Results: A total of 2,469 patients with a median follow-up of 4.7 years (range 0.1-15.5 years) were identified. According to the anatomic stage, there were 1,259 patients of stage IA, 132 of IB, 591 of IIA, 206 of IIB, 130 of IIIA, 14 of IIIB and 73 of IIIC. According to the prognostic stage, there were 1,610 patients of stage IA, 331 of IB, 236 of IIA, 73 of IIB, 85 of IIIA, 43 of IIIB and 27 of IIIC. Sixty-four patients (2.6%) could not be assigned using the new staging system for the presence of micrometastases in lymph nodes with tumors larger than 2 cm. The 5-year disease-free survival (DFS) rates according to the anatomic stage were 97.4% for stage IA, 97.1% for IB, 95.8% for IIA, 86.5% for IIB, 77.9% for IIIA, 49.2% for IIIB and 54.9% for IIIC. According to the prognostic stage, the 5-year DFS rates were 97.9% for stage IA, 92.9% for IB, 91.2% for IIA, 79.8% for IIB, 67.4% for IIIA, 53.3% for IIIB and 38.7% for IIIC. Compared with the AJCC anatomic stage, the prognostic stage was increased in 148 patients (6.2%) and decreased in 808 patients (32.8%). For those in whom the stage changed, the change was by one stage up or down in 463 (19.3%), by 2 stages up or down in 401 (16.7%) and by 3 stages up or down in 92 (3.8%). Of the 1,842 patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative (HR+/HER2-) disease, 40.5% (745/1842) of cases were downstaged, and 0.7% (1/1842) were upstaged. Discussion: The AJCC 8th edition prognostic staging system provided more refined stratification than the anatomic stage. In the Japanese cohort, the proportion of the downstaging rate was higher than the upstaging rate, and the prognostic evaluation of HR+ patients in particular was improved. Citation Format: Miyamoto H, Saita C, Onishi M, Goto R, Iwamoto N, Honda Y, Aruga T. Validation of the AJCC eighth edition prognostic stage compared with the anatomic stage for breast cancer with a Japanese single-institutional cohort [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 P4-08-16.

Background The objective of this study was to evaluate the accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes (LN) in breast cancer, to compare the results of FNAC and pathological examination, and to distinguish patients with 1 to 2 metastatic LNs from those with ≥3 metastatic LNs in patients with FNAC-positive patients. Patients and methods This study included 198 breasts of 196 patients with breast cancer who underwent FNAC and surgery for the primary and axilla without neoadjuvant chemotherapy from January 2010 to August 2016. Axillary nodal status was assessed by ultrasound (US), and whether FNAC-positive had three or more suspicious LNs on US imaging was examined. Results The results of FNAC were positive in 75 (38%), negative in 97 (49%), suspicious in 2 (1%), indeterminate in 5 (2.5%), and insufficient in 19 patients (9.5%). FNAC sensitivity, specificity, positive predictive value, and negative predictive value were 62.6%, 100%, 100%, and 62.0%, respectively. Whereas 53% (18/34) of patients with false-negative FNAC had one metastatic LN on final pathology, 61% (47/77) patients who were FNAC-positive had three or more metastatic LNs. In the FNAC-positive patients, all patients had ≥3 metastatic LNs if they had ≥3 suspicious LNs on US imaging. Conclusion Patients with positive cytology were more likely to have ≥3 positive LNs compared to false-negative cytology patients. Patients with ≥3 abnormal LNs on US and positive FNAC might require axillary dissection.

Central nervous system lomentosporiosis is a rare pathological condition in immunocompromised patients. We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To our knowledge, no cases of Lomentospora meningitis following allo-HSCT have been reported previously. Particularly in neutropenic patients, it is important to consider L. prolificans when a fungal infection is suspected and antifungal agents are ineffective.

Background Rare phyllodes tumors (PT) comprise a mixture of stromal and epithelial cells, and they can acquire malignant potential, which results in rapid progression and metastasis. Therefore, PT should be resected with an adequate free margin for curative intent. Fibroadenoma (FA) is a benign type of tumor that rarely becomes malignant, and usually does not require resection. However, PT and FA are morphologically and pathologically similar, which makes them difficult to distinguish in clinical practice. Thus, we aimed to determine a means of distinguishing them using a proteomic approach called Isobaric Tag for Relative and Absolute Quantitation (iTRAQ). We added different isobaric tags to normal and phyllodes tumor tissues, detected proteins using a database search and selected those that were at least three-fold more abundant than in normal tissue. Among them, we found high expression levels of calretinin, a specific marker for mesothelioma, in PT. Methods Tissue specimens were collected from 36 patients with PT (benign, n = 16; borderline, n = 15; malignant, n = 5), from 37 with FA and from three local recurrence sites of PT. All patients were treated by surgical resection at the Department of Breast Surgery, Tokyo Medical and Dental University, Japan, between March 2003 and August 2012. The specimens were analyzed by immunohistochemistry (IHC) using a calretinin antibody, and malignant mesothelioma as a positive control. Immunostaining for calretinin was analyzed by light microscopy in three high-power fields (HPF) and calretinin expression was assessed using Allred scores calculated on a scale from 0 to 8 as proportion (PS) plus intensity (IS) scores. We defined Allred scores of 0 and 2 as low (CLG) and those > 3 as high (CHG) calretin as reported for malignant mesothelioma. Data were analyzed using chi-square tests. Results All samples were stained. Stromal, but not epithelial cells tended to be positively stained for calretin. We found 20 and 17 FA, and 9 and 27 PT in CLG and CHG, respectively. More calretinin was expressed in PT than in FA (p = 0.011). Six and 25 benign or borderline PT were found in CLG and CHG, respectively. More calretinin was expressed in benign and borderline PT than in FA (p = 0.006). Three patients had local recurrence and one had distant metastasis. Recurrence did not significantly correlate with calretinin expression in PT; calretinin expression was low in all instances of local recurrence. Conclusion We found that calretinin could distinguish between PT and FA and could therefore function as an important marker when planning surgery. Malignant PT and sites of local recurrence tended to express low levels of calretinin. Further investigation of calretinin with PT and FA is needed. Citation Format: Tohiyuki Ishiba, Tomoyuki Aruga, Miyako Nara, Sakiko Yabe, Chiaki Saita, Mai Onishi, Naoko Iwamoto, Rika Yonekura, Hiromi Miyamoto, Yayoi Honda, Goshi Oda, Tsuyoshi Nakagawa, Akira Nakanishi, Hiroyuki Uetake, Yoshio Miki. Calretinin can be the specific marker for phyllodes tumor [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5449.

A DEAE-dextran-MMA copolymer (DDMC)-paclitaxel (PTX) conjugate was prepared using PTX as the guest and DDMC as the host. The resistance of B16F10 melanoma cells to PTX was confirmed, while the DDMC-PTX conjugate showed excellent anticancer activity that followed the Hill equation. The robustness in the tumor microenvironment of the allosteric system was confirmed via BIBO stability. This feedback control system, explained via a transfer function, was very stable and showed the sustainability of the system via a loop, and it showed superior anti-cancer activity without drug resistance from cancer cells. The block diagram of this signal system in the tumor microenvironment used its loop transfer function G(s) and the dN(s) of the external force. This indicial response is an ideal one without a time lag for the outlet response. The cell death rate of DDMC-PTX is more dependent on the Hill coefficient n than on the Michaelis constant Km. This means that this supermolecular reaction with tubulin follows an "induced fit model".

Purpose:To test the efficacy of an intravitreal dexamethasone implant in patients with recalcitrant macular edema secondary to retinal vein occlusion.Methods:A retrospective chart review was performed for 18 patients with retinal vein occlusion who received multiple bevacizumab intravitreal injectio

We have confirmed and extended previous reports of a wide distribution of septin proteins in the eukaryotic phylogeny. It now appears that septins are present in at least some representatives of every eukaryotic supergroup, with the possible exception of the Excavata. Presently, almost nothing is known of the structure, assembly, and biological roles of septins outside of the opisthokonts (animals, fungi, and their close relatives). Thus, studies of the septins in the highly diverse and distantly related nonopisthokont groups present a major opportunity to gain a much deeper understanding of septin core function and evolution, and we discuss briefly the excellent prospects for capitalizing on this opportunity in the next few years.

This paper presents a new technology for constructing cool roofs composed of fractal shapes. The roofs consist of many Sierpinski tetrahedron units and block 100% sunlight from a particular direction. The sunlight from other directions partly penetrates the roof, creating a leafy shaded area under the roof. Compared with ordinary flat roofs, these roofs greatly reduce surface temperature and consequently provide a cool environment without strong heat radiation. The fractal structure of the tetrahedron units is similar to that of natural trees. Three-dimensional measurements revealed that natural trees have a fractal dimension of approximately 2, which is similar to that of the Sierpinski tetrahedrons. In this study, fractal roofs made from different materials were tested at two sites. The results showed that they were very effective in reducing surface temperatures in sunlight.

Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates the therapeutic effect of radiotherapy and chemotherapy, but previous studies found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration. To overcome these problems, Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated. We treated primary glioblastoma with 50 mM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of real-time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. The results showed that the Rg3-NPs are slick and uniform, the average diameter of the nanoparticles is 75-90 nm, and their entrapment efficiency is 89.7+1.7%. MTT showed that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependent manner. FCM testing showed Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei, causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes BUB1, CDC20, TTK, and CENPE, as determined by microarray analysis and verified by real-time PCR. Furthermore, Rg3-NPs induced the expression of the apoptotic and antimigratory protein p53 in cell lines. The results of the present study, together with the results of earlier studies, show that Rg3-NPs target genes involved in theprogressionoftheM-phaseofthecellcycle.Itisassociatedwithseveralimportant pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.

High-grade glioma is the most common brain tumor in adults, and the prognosis for patients diagnosed with this type of cancer is still poor. The biological behavior of the tumors is correlated to t ...

In the Tokaido Shinkansen, the instantaneous feeding power of substations has increased because of the high-density train schedule and the improved acceleration performance of the rolling stock. If the load power of feeding substations increases any further, it will not be possible to maintain the feeder voltage when the power converter supplies only reactive power. In consideration of such a situation in the frequency conversion section, an electronic frequency converter that controls the ac voltage using a fixed power factor method was developed. The superiority of the proposed control method is confirmed with electromagnetic transient program calculations and field test results. The electronic frequency converter has been in operation since February 2009 with good performance, showing the success of the system development described in this paper.

IL-17, the hallmark cytokine of the Th17 population, mediates immunity to extracellular pathogens and promotes autoimmune immunopathology. The signaling mechanisms triggered by the IL-17 receptor (IL-17RA) and related receptors are strikingly different from other cytokine subclasses. Namely, IL-17Rs contain a conserved SEF/IL-17R (SEFIR) subdomain that engages Act1, leading to activation of TRAF6, NF-κB, and other events. Although the SEFIR is critical for signaling, the molecular details of the functional subdomains within IL-17RA remain poorly characterized. Here, we provide a detailed structure-function analysis delineating the C-terminal boundary of the SEFIR-containing region of IL-17RA. We show that functionality of this domain requires a large extension to the previously identified SEFIR motif. In contrast to the SEFIR, this extension is not conserved among IL-17R family members. Surprisingly, Act1 recruitment is not sufficient for downstream signaling activation, whereas ubiquitination of TRAF6 correlates tightly with functional receptors. We further demonstrate that IL-17RA exhibits signaling properties that are nonredundant with other IL-17R family members. Finally, we report that IL-17 signals synergistically with lymphotoxin-α3, using the same signaling motifs within IL-17RA. These studies provide new insight into the structure-function relationships of IL-17RA and reveal distinct signaling differences among IL-17R family members.

Interleukin-17 (IL-17) has emerged as a central player in the mammalian immune system. Although this cytokine exerts a host-defensive role in many infectious diseases, it promotes inflammatory pathology in autoimmunity and other settings. A myriad of studies have focused on how IL-17-producing cells are generated. However, the means by which IL-17 achieves its effects, either for the benefit or the detriment of the host, are due in large part to the induction of new gene expression. Whereas many IL-17 target genes are common to different disease states, in some cases the effects of IL-17 differ depending on the target cell, infectious site or pathogen. Gene products induced by IL-17 include cytokines (IL-6, granulocyte-colony-stimulating factor, tumour necrosis factor-alpha), chemokines (CXCL1, CXCL2, CCL20, among many others), inflammatory effectors (acute-phase protesins, complement) and antimicrobial proteins (defensins, mucins). Different cell types appear to respond differently to IL-17 in terms of target gene expression, with notable differences seen in mesenchymal and epithelial cells compared with cells of haematopoietic origin. Here, we summarize the major IL-17 target genes that mediate this cytokine's activities in both autoimmune and chronic diseases as well as during various types of infections.

Background: When multiple radioactive sentinel lymph nodes (SLNs) are present during sentinel lymph node biopsy (SLNB), excision of those SLNs with >10% radioactive count per minute (high-CPM) of the most radioactive node (“10% rule”) has been proposed. Although this “10% rule” may avoid excessive removal of SLNs,the risk of false negative and remnant positive SLNs in the patients who have SLNs with Method: We reviewed the records of successful SLNBs using the radioisotope (RI) method performed between January 2001 and December 2016 in our institution. The radioactive count from each excised SLN was measured. Non-radioactive lymph nodes were excluded from this analysis. All SLNs were pathologically assessed by 2mm serial section with hematoxylin and eosin staining. Results: In the 3,043 patients with successful SLNB,the median number of radioactive SLNs removed was 2 (mean, 1.8; range, 1-10) and 599 patients (19.7%) had SLNs with low-CPM. The total number of radioactive SLNs was 5,472, and 875 (16.0%) out of 5,472 SLNs were low-CPM. Sixty-one (7.0%) out of these 875 SLNs with low CPM in 56 patients (1.8%) had metastatic disease by pathological assessment. The number of metastatic SLN with low-CPM was one in 51 patients and two in 5 patients. Nineteen patients (0.6%) had no metastatic lesion in SLNs with high-CPM. Discussion and Conclusions: If SLNB was performed by RI method alone with “10% rule”, false negative rate increased by 0.6% and underestimation increased up to 1.8%. Furthermore, 19.7% of the patients have the benefit of avoiding excessive removal of SLNs.Considering the risk and benefit, “10% rule” is a high validitymethod to capture metastatic SLNs even in the setting that ALND will not be performed. Citation Format: Miyamoto H, Aruga T, Onishi M, Goto R, Iwamoto N, Idera N, Horiguchi K, Honda Y. Re-evaluating the “10% rule” for sentinel lymph node biopsy with radioactive method in breast cancer; a single institutional retrospective study [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 P3-01-09.

Background Whole breast radiation therapy (WBRT) following lumpectomy for ductal carcinoma in situ (DCIS) is standard of care, however, the risk of local recurrence with and without radiation ranges as low as 0.9% vs. 6.7% over 7 years. Intraoperative radiotherapy (IORT) is a potential alternative with advantages of decreased toxicity to adjacent organs, convenience, and improved quality of life. While prospective trials of IORT for DCIS are ongoing, the objective of this study was to estimate the cost-effectiveness of IORT vs. WBRT vs. no radiation for DCIS. Methods We developed a Markov model using TreeAge Pro 2016 to evaluate the cost-effectiveness of WBRT, IORT, and no radiation in patients with DCIS following lumpectomy. Health states included disease free, local recurrence (ipsilateral DCIS or invasive cancer), distant recurrence or death due to breast cancer, and death due to non-breast cancer causes. A 10-year time horizon and societal perspective were used. Model input parameters were derived from the literature. Costs reflected 2016 Medicare rates. The primary endpoint was incremental cost-effectiveness ratio (ICER), defined as the difference in cost, divided by the difference in quality-adjusted life years (QALYs) of two interventions. We performed analyses of subgroups defined according to DCIS risk (histologic grade, Oncotype Dx® DCIS recurrence score, low risk per RTOG 9804 criteria) and endocrine therapy use (none, tamoxifen, aromatase inhibitor). Sensitivity analyses explored uncertainty in the model. Results IORT was the most cost-effective strategy, with an increase of 0.18 QALYs at an incremental cost of $4,728, corresponding to an ICER of $26,943/QALY when compared with no radiation therapy. WBRT resulted in an increase in 0.18 QALYs at an incremental cost of $6859, corresponding to an ICER of $39,085/QALY. For both strategies, the ICERs did not exceed the willingness to pay (WTP) threshold of $100,000. IORT remained the most cost-effective strategy across DCIS risk groups, but was more cost-effective in higher risk patients, as demonstrated by lower ICERs. In low risk DCIS defined by RTOG 9804 criteria, no radiation was most cost-effective. The ICERs for IORT and WBRT, $152,753 and $208,204/QALY, respectively, exceeded the WTP threshold. IORT remained cost-effective in the setting of endocrine therapy use. Incremental Cost-Effectiveness Ratios (ICER) for each radiation strategy for the base case and scenario analyses ICER ($/QALY) No RTIORTWBRTBase Case Analysis 26,94339,085 Scenario Analysis by DCIS Risk GroupHistologic Grade - Low 36,81152,219- High 25,64337,137 Oncotype Dx DCIS Score - Low 92,892126,398- High 32,00345,690 Low Risk DCIS 152,753208,204 Scenario Analysis by Endocrine TherapyNo Tamoxifen 23,38734,373Tamoxifen 47,81166,616 Tamoxifen 31,96146,272Aromatase Inhibitor 41,31658,674 Conclusion IORT was the most cost-effective radiation strategy for DCIS compared to WBRT and no radiation. This applied to all subgroups with the exception of low-risk DCIS defined by RTOG 9804 criteria for whom no radiation was the most cost-effective strategy. These findings provide support for ongoing studies examining the role of IORT for DCIS with high-risk features, as well as alternative treatment strategies for low-risk DCIS. Citation Format: Onishi M, Connolly EP, Wright JD, Vasan S, Gross T, Tsai W-Y, Chen L, Neugut AI, Accordino MK, Kalinsky K, Crew KD, Hershman DL. Cost-effectiveness analysis of intraoperative radiotherapy for ductal carcinoma in situ [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 PD7-03.

We developed CdTe double-sided strip detectors (DSDs or cross strip detectors) and evaluated their spectral and imaging performance for hard X-rays and gamma-rays. Though the double-sided strip configuration is suitable for imagers with a fine position resolution and a large detection area, CdTe diode DSDs with indium (In) anodes have yet to be realized due to the difficulty posed by the segmented In anodes. CdTe diode devices with aluminum (Al) anodes were recently established, followed by a CdTe device in which the Al anodes could be segmented into strips. We developed CdTe double-sided strip devices having Pt cathode strips and Al anode strips, and assembled prototype CdTe DSDs. These prototypes have a strip pitch of 400 micrometer. Signals from the strips are processed with analog ASICs (application specific integrated circuits). We have successfully performed gamma-ray imaging spectroscopy with a position resolution of 400 micrometer. Energy resolution of 1.8 keV (FWHM: full width at half maximum) was obtained at 59.54 keV. Moreover, the possibility of improved spectral performance by utilizing the energy information of both side strips was demonstrated. We designed and fabricated a new analog ASIC, VA32TA6, for the readout of semiconductor detectors, which is also suitable for DSDs. A new feature of the ASIC is its internal ADC function. We confirmed this function and good noise performance that reaches an equivalent noise charge of 110 e- under the condition of 3-4 pF input capacitance., 6 pages, 10 figures, accepted for publication in IEEE Transactions on Nuclear Science

Silica-based highly nonlinear fibers (HNLFs) have been utilized as platforms for various applications, including fiber lasers, optical amplifiers, and optical signal processings. For the practical applications, nonlinearity enhancement without degrading the attenuation and tailoring the chromatic dispersions remain the key issues. Herein, we initially discuss the design of chromatic dispersions of HNLFs for desired applications. Then the fabrication results, including HNLFs with a longitudinally uniform zero-dispersion wavelength or with optimized higher order dispersion, are presented. Furthermore, using evolved HNLFs, we demonstrate a unique four-wave-mixing-based wavelength conversion. In addition, suppression of the stimulated Brillouin scattering, a critical issue for high-power applications, is discussed. We fabricate Al2O3-doped HNLF that has lower Brillouin gain by 6.1 dB as compared with that of conventional GeO 2-doped HNLF.

著者人数: 11名, 資料番号: SA1000651000

著者人数: 12名, 資料番号: SA1000652000

Water-Nafion phase equilibria and proton conductivities were measured in two ways. First, Nafion was in contact with saturated water vapor. Second, Nafion was in contact with liquid water at the same temperature. At 29 degrees C, for preboiled, vapor-equilibrated Nafion exposed to water with an activity = 1 and air pressures ranging from 0 to 0.96 bar, the water content was lambda = 23 +/- 1 mol H(2)O/mol SO3-. For the preboiled, liquid-equilibrated membrane, lambda = 24 +/- 2. At 100% relative humidity (RH), the water content of preboiled Nafion decreased as the temperature rose from 30 to 80 degrees C but did not recover its initial water content when the temperature returned to 30 degrees C. The water content of predried Nafion at 1 atm and 30 degrees C was lambda = 13.7 +/- 0.2 when vapor-equilibrated and lambda = 13.1 +/- 0.5 when liquid-equilibrated. A Nafion membrane originally boiled in water had much higher liquid- and 100% RH vapor-equilibrated proton conductivities than the same membrane originally dried at 110 degrees C with a RH less than 2%. The liquid-equilibrated and 100% RH vapor-equilibrated membrane conductivities were the same when the membrane had the same thermal history. The conductivity data was fit to a model, and the water content was determined at different temperatures. The predried membrane water content increased with temperature, and the preboiled membrane's water content changed slightly with temperature. Both water sorption and proton-conductivity data do not exhibit Schroeder's paradox. These studies and previous results suggest that Schroeder's paradox is resolved when attention is given to the thermal history of the absorbing polymer.

We report our development of CdTe pixel detectors for Si/CdTe semiconductor Compton cameras. We have constructed a prototype of a Si/CdTe Compton camera, consisting of six layered double-sided silicon strip detectors and three CdTe pixel detectors. By using this prototype, we have demonstrated the concept of the Si/CdTe Compton cameras. We have successfully obtained Compton reconstructed images for 80–662 keV gamma-rays. The achieved angular resolution is about 4 degrees for 511 keV gamma-rays. The energy resolution is 14 keV (FWHM) at 511 keV. In order to improve the performance of the Compton camera, we have evaluated all CdTe pixel detectors we have constructed. We found that the I – V curve is helpful to select good detectors.

This study evaluated a novel non-verbal communication method for people with severe motor and intellectual disabilities (SMID) based on a biochemical marker, salivary amylase. The physical and psychological status of 10 people with SMID was quantitatively evaluated using a hand-held salivary amylase activity monitor. Each patient needed daily gastric and/or bronchial tube exchanges and these medical procedures were thought to cause severe distress and pain. Salivary amylase activity and heart rate were simultaneously measured during 32 medical procedures. The medical procedures resulted in a significant mean increase for individuals of 70% in salivary amylase activity. The increase in salivary amylase activity was more than four-fold that observed for heart rate. The structural equation modelling analysis also demonstrated a significant correlation between pain and salivary amylase activity. Our data indicate that salivary amylase activity might be used as a non-verbal method of assessing pain in people with SMID.