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Background: Lymphedema may develop when axillary lymph node dissection (ALND) injures and obstructs the lymph ducts in the upper limb. In patients with breast cancer, lymphedema is difficult to treat and can cause arm swelling, heaviness, and restricted movement. We aimed to identify the prevalence and risk factors for lymphedema after ALND in patients with breast cancer. Methods and Results: This retrospective study included 175 patients with breast cancer who underwent ALND in the Nagasaki University Hospital, Japan, between 2005 and 2018. Lymphedema was defined as symptomatic arm swelling with a >2-cm difference in the arm circumference between the affected and contralateral arms. Patients were divided into two groups according to the presence or absence of lymphedema. Surgical and pathological findings were compared between the two groups. Univariate and multivariate analyses were performed, including the chi-square test, Student’s t-test, and logistic regression analysis. Lymphedema was prevalent in 20% of the study participants, and the mean time interval from surgery to development of lymphedema was 479 days. In the univariate analysis, a body mass index of >26 kg/m2, smoking, radiotherapy (RT), and dissection of >18 axillary lymph nodes (ALNs) significantly increased the risk of lymphedema. In the multivariate analysis, smoking, RT, and dissection of >18 ALNs significantly increased the risk of lymphedema. Conclusions: The prevalence of lymphedema in our study was 20%. Our findings suggest that smoking, RT, and dissection of >18 ALNs are risk factors for lymphedema. Aggressive and empiric ALND might be associated with axillary lymph duct damage., Lymphatic research and biology, 20(6), pp.600-606; 2022

Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy.

Cell–cell interactions in the central nervous system play important roles in neurologic diseases. However, little is known about the specific molecular pathways involved, and methods for their systematic identification are limited. Here, we developed a forward genetic screening platform that combines CRISPR-Cas9 perturbations, cell coculture in picoliter droplets, and microfluidic-based fluorescence-activated droplet sorting to identify mechanisms of cell–cell communication. We used SPEAC-seq (systematic perturbation of encapsulated associated cells followed by sequencing), in combination with in vivo genetic perturbations, to identify microglia-produced amphiregulin as a suppressor of disease-promoting astrocyte responses in multiple sclerosis preclinical models and clinical samples. Thus, SPEAC-seq enables the high-throughput systematic identification of cell–cell communication mechanisms.

We present a rare tumor of adenoid cystic carcinoma, solid-basaloid subtype of the breast. Solid-basaloid adenoid cystic carcinoma may have a worse prognosis than classical adenoid cystic carcinoma. A 70-year-old woman presented with a mass in her left breast. Malignancy was suspected on imaging and confirmed via core needle biopsy. Left breast partial mastectomy and sentinel lymph node biopsy were performed. Histologically, the tumor was composed of basaloid cells with hyperchromatic nuclei and frequent mitotic figures, as are small-cell neuroendocrine carcinomas. Immunohistochemical analysis of the tumor cells showed high expression of KIT and CD10 and focal expression of keratin 7. Synaptophysin, chromogranin A, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were not expressed. This patient should be followed up carefully for distant metastases and recurrences.

The aim of this study was to evaluate the knowledge and educational needs with regard to hereditary breast and ovarian cancer among nurses working in breast cancer care in the Nagasaki Prefecture. In breast cancer care, the identification of patients at risk for hereditary breast and ovarian cancer is necessary for the implementation of genetic testing and counseling. Nurses should be involved in this process, since they play a crucial role in the care of patients with breast cancer. However, the knowledge regarding hereditary breast and ovarian cancer among nurses working in oncology care in Japan has not been assessed. The design of this study is cross-sectional design. We distributed 597 surveys to nurses working in breast cancer care. The surveys assessed the nurses’ demographic data, their current knowledge and practices regarding cancer genetics and hereditary breast and ovarian cancer, and their attitude and preferences regarding learning about the condition. We received 317 valid replies. Nurses had limited knowledge about hereditary breast and ovarian cancer characteristics: 41.6% reported that they do not know about the condition, whereas less than 10% knew its characteristics. However, nurses were aware of hereditary breast and ovarian cancer significance and were willing to learn about it: 91% wished to learn about the condition, and 88.6% wanted to participate in study group meetings. Further, nurses’ preferences regarding educational programs were clarified. Overall, our results show that educational programs should be implemented to advance nurses’ knowledge of hereditary breast and ovarian cancer characteristics.

Background: Endoscopic ultrasonography (EUS) is one of the helpful tools to diagnose depth of early gastric cancer (EGC). In this study, we examined efficiencies of EUS for EGC such as overall accuracy, risk factors of over/under-staging, and accuracies of each invasive distance. Methods: A total of 403 EGC lesions that could be investigated by EUS during pre-operation and histological diagnosis after endoscopic submucosal dissection (ESD) or surgery were enrolled in this study. For the 403 cases, we analyzed the accuracies of depth by conventional endoscopy (CE) and EUS retrospectively. We evaluated the clinical survey items of CE and EUS which will be described later to compare the differences between “accuracy group” and “over-staging group”, and between “accuracy group” and “under-staging group”, retrospectively. Additionally, 78 EGC lesions which were confined to the submucosa and for which it was possible to measure accurate invasive distance from the muscularis mucosae were examined for the relationship between preoperative diagnosis of depth by CE and EUS and invasive distance retrospectively. Results: The overall accuracies of both CE and EUS in predicting EGC invasion depth were 87.3%. For CE staging, histological classification was the factor which influenced over-staging. Gastric regions and tumor area were the factors which influenced under-staging of CE. For EUS staging, tumor area was the factor which influenced over-staging, and gastric regions were the factors which influenced under-staging. Both CE and EUS were not sufficient for predicting the lesions confined to < 500 µm from the muscularis mucosae because the accuracies of both in predicting depth were less than 50%. However, EUS has a higher accuracy than CE for the lesions confined to 500 - 2,000 µm. Conclusions: The overall accuracies of both CE and EUS in predicting EGC invasion depth were equal, but the contributing factors for over/under-staging were different. Both CE and EUS are not sufficient at present to predict the lesions confined to < 500 µm from the muscularis mucosae. However, the accuracy of EUS in predicting them may increase if high-performance EUS systems are developed in the future. J Clin Med Res. 2021;13(4):222-229 doi: https://doi.org/10.14740/jocmr4465

Background: Adjuvant endocrine therapy for 5-10 years reduces breast cancer (BC) mortality in women with hormone receptor-positive BC. However, aromatase inhibitors (AIs) decrease bone mineral density (BMD), and increase fractures, joint stiffness, and joint pain. Although dual energy X-ray absorptiometry (DXA) is widely used to assess BMD, it is a two-dimensional method and thus cannot analyze trabecular and cortical bone microstructure. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows in vivo analysis of peripheral bone microarchitecture with high spatial resolution and low radiation exposure. We used HR-pQCT to evaluate changes in volumetric bone density and microstructure consisting of trabecular and cortical bone associated with AI treatment in patients with early BC. Methods: This was a prospective single-center observational study of nonosteoporotic, postmenopausal women with hormone receptor-positive BC, whose baseline DXA lumber spine and femoral neck T-scores were > −2.5. All patients were scheduled to receive DXA and HR-pQCT at baseline and at 6 and 12 months after starting AI therapy. The primary endpoint was to examine changes in total volumetric BMD (Tt. vBMD), trabecular volumetric BMD (Tb. vBMD), cortical volumetric BMD (Ct. vBMD) change at the distal radius and the distal radius between baseline and 6 and 12 months after starting endocrine therapy. Results: Of the 20 women in the study (median age: 57.5 years; range: 55-72 years), 8 had undergone chemotherapy before registration. Their mean change in Tt. vBMD between baseline and 1 year were distal radius: −5.7% (SD: 2.5%, P Citation Format: Sayaka Kuba, Konosuke Watanabe, Megumi Matsumoto, Ko Chiba, Kosho Yamanouchi, Ayako Fukushima, Michi Morita, Ryota Otsubo, Hiroshi Yano, Kengo Kanetaka, Makoto Osaki, Takeshi Nagayasu, Susumu Eguchi. Second-generation HR-pQCT analysis of bone mineral density and microstructure in women with breast cancer who underwent adjuvant endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-23.

Background: The semi-dry dot-blot (SDB) method, a diagnostic procedure for detecting lymph node (LN) metastases using anti-cytokeratin (CK) antibody, is based on the theory that epithelial components such as CK are not found in normal LNs. Thus, metastases are diagnosed on basis of the presence of CK in lavage fluid of sectioned LNs. We prospectively evaluated novel SDB kits that use a newly developed anti-CK19 antibody and an automatic reader for diagnosing LN metastases in patients with breast cancer. Methods: We obtained 117 LNs dissected from 58 patients with breast cancer between January 2020 and June 2020 at Nagasaki University Hospital. These were sliced at 2-mm intervals and washed with phosphate-buffered saline. Cells suspended in the lavage fluid of sliced LNs were centrifuged and lysed to extract protein. The extracted protein was applied to the SDB kit to diagnose LN metastasis using an automatic reader that evaluates absorbance. Hematoxylin and eosin (H&E) stained washed LNs were blindly examined by pathologists. Diagnoses based on SDB kit and automatic reader findings were compared with diagnoses made by histological examination of paraffin-embedded H&E stained sections of the LNs. Results: Six of the 117 LNs were assessed as positive and 111 as negative by histological examination. With a borderline CK19 absorbance of 50 milli-absorbance (mAbs) for detecting LN metastases excluding isolated tumor cells, the sensitivity, specificity, and overall agreement of the SDB kit were 66.7%, 99.1%, and 97.4%, respectively. Two patients with false-negatives had micrometastases of 0.6 and 0.5 mm in diameter. There was contamination by breast epithelial tissue in one false-positive case. With a borderline CK19 absorbance of 100 mAbs for distinguishing macrometastases from micrometastases, the sensitivity, specificity, and overall agreement of the SDB kit were 100%, 100%, and 100%, respectively. Furthermore, the kits and the automatic reader yielded diagnoses in approximately 20 min at a cost of less than 30 USD. Conclusions: The kits with an automatic reader used in our study were accurate, quick, and cost-effective in diagnosing LN metastases without loss of LN tissue, and were especially useful for detecting distinguish macrometastases. We plan to start a prospective multi-center study to evaluate clinical performance soon. Citation Format: Ryota Otsubo, Hiroshi Yano, Megumi Matsumoto, Aya Tanaka, Ayako Fukushima, Sayaka Kuba, Michi Morita, Naoki Uno, Han-Seung Yoon, Katsunori Yanagihara, Susumu Eguchi, Takeshi Nagayasu. Evaluation of novel diagnostic kits using the semi-dry dot-blot method combined with an automatic reader for detecting metastases in lymph nodes of patients with breast cancer : A single-center prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-39.

Highlights • Few studies have examined management of breast cancer patients on hemodialysis. • Dosage for anticancer drugs should be carefully adjusted based on adverse events. • Combined therapy improves survival and quality of life., Introduction Management of breast cancer patients undergoing hemodialysis (HD) is difficult because of a lack of evidence about drug selection, dose adjustment, and surgical procedures. We herein present a case of metastatic breast cancer in a patient undergoing HD. Presentation of case A 58-year-old Japanese woman with breast cancer undergoing HD underwent total mastectomy of the left breast and left axillary dissection. Histopathological examination revealed invasive ductal carcinoma, and the diagnosis was pT2N3cM0 Stage ⅢC. Immunostaining of the resected specimen indicated that the tumor was estrogen receptor-positive, progesterone receptor-negative, human epithelial growth factor receptor 2-positive, and the Ki-67 labeling index was 70%. A postoperative positron emission tomography/computed tomography (PET/CT) scan indicated fluorodeoxyglucose uptake in the supraclavicular nodes. She received adjuvant therapy of epirubicin and cyclophosphamide followed by docetaxel, trastuzumab (T-mab) and radiation therapy. However, she developed multiple liver metastases during adjuvant T-mab and hormone therapy. Therefore, her regimen was changed to trastuzumab emtansine (T-DM1) as first-line therapy, T-mab, pertuzumab (P-mab), and eribulin as second-line therapy, and T-mab, P-mab, and weekly paclitaxel as third-line therapy. Eventually, she was administered fourth-line treatment of T-mab, P-mab, and vinorelbine because of adverse events. She has survived more than 25 months after the initial detection of recurrence of breast cancer and maintained quality of life. Conclusion We report a case of breast cancer in a patient undergoing HD. It is very difficult to identify the appropriate drugs and dosages in patients undergoing HD to improve survival and quality of life.

Recent days have witnessed significant interests in applying quantum-enhanced techniques for solving a variety of machine learning tasks. Variational methods that use quantum resources of imperfect quantum devices with the help of classical computing techniques are popular for supervised learning. Variational quantum classification (VQC) is one of such methods with possible quantum advantage in using quantum-enhanced features that are hard to compute by classical methods. Its performance depends on the mapping of classical features into a quantum-enhanced feature space. Although there have been many quantum-mapping functions proposed so far, there is little discussion on efficient mapping of discrete features, such as age group, zip code, and others, which are often significant for classifying datasets of interest. We first introduce the use of quantum random-access coding (QRAC) to map such discrete features efficiently into limited number of qubits for VQC. In numerical simulations, we present a range of encoding strategies and demonstrate their limitations and capabilities. We experimentally show that QRAC can help speeding up the training of VQC by reducing its parameters via saving on the number of qubits for the mapping. We confirm the effectiveness of the QRAC in VQC by experimenting on classification of real-world datasets with both simulators and real quantum devices.

In this letter, the authors demonstrated superior electrical characteristics of a 1.2 kV SiC Schottky barrier diode-wall integrated trench MOSFET (SWITCH-MOS) with the higher Schottky barrier height of nickel. It was confirmed that a significant improvement in short-circuit capability was achieved with no sacrifice of on resistance, because the electron leakage current through the integrated Schottky barrier diode (SBD), caused by thermionic-field emission, could be successfully suppressed. Further, although the integrated SBD with nickel showed 0.25 V greater forward voltage drop than that with titanium, the on resistance and switching characteristics were similar in the two devices. The results of the study showed that the SWITCH-MOS with nickel can achieve 21.0% less power dissipation in high frequency pulse width modulation inverters, compared to standard SiC trench MOSFETs.

Background In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using any tumor marker or imaging tests. We aimed to determine whether differences in clinicopathological features, subtypes, prognosis, and treatment exist between asymptomatic and symptomatic MBCs. Methods We performed a multicenter, retrospective analysis of patients with MBC who visited our hospitals from 2008 to 2018. Patients were divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtypes: luminal (hormone receptor positive/hormone receptor negative/human epidermal growth factor receptor 2 (HER2) negative), HER2 (any hormone receptor/HER2 positive), and TN (hormone receptor negative/HER2 negative). Results Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts and TN patients in the asymptomatic group had longer post-recurrence survival (all cohorts: p p = 0.08, HER2: p = 0.09) but without significant difference in overall survival. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of post-recurrence survival. Regarding the luminal subtype, the asymptomatic group had longer durations of chemotherapy than the symptomatic group, with no significant difference observed in overall survival between the groups. Conclusion Asymptomatic and symptomatic MBCs require unique treatments due to prognostic differences.

The immune system and the peripheral nervous system are distributed throughout the body and surveil vital organs utilizing various sensory mechanisms. Previous studies have demonstrated that tissue-resident innate lymphoid cells (ILCs) and neurons are heavily enriched in the body's barrier surfaces, where it is critical to detect and rapidly adapt to the changes in dietary, microbial and other environmental stimuli. However, our understanding of how these two sensory systems cooperatively integrate these diverse signals to orchestrate host responses remains incomplete. Recent research has provided insights into how neurotrophic and neuronally derived factors regulate the functions of ILCs, establishing the neuro-ILC axis as a crucial component of broader neuro-immune interactions. Further, neurons express receptors for many cytokines produced by ILCs, opening the possibility for bidirectional neuro-immune interactions in regulating tissue homeostasis and inflammation. This review highlights recent advances in the cellular and molecular mechanisms of neuro-ILC interactions and their potential therapeutic implications.

In our previous work, we demonstrated the world’s first inversion-type p-channel diamond metal–oxide–semiconductor field-effect transistor (MOSFET). However, it exhibited low channel mobility due to high interface state density (Dit). In this study, the electronic states of Al2O3/diamond interfaces above the valence band edge (Ev) were carefully examined by capacitance–voltage (C–V) measurements in a wide frequency range of 1 Hz–10 MHz at 300, 350, and 400 K, providing an accurate characterization of deeper interface state density compared with our previous work (from 10 Hz to 10 kHz at room temperature) within the limitations of the high-low method. We observed humps in C–V curves, which became wider as the temperature increased and the frequency decreased, indicating the presence of interface states at deep energy levels. They can act as Coulomb scattering centers in diamond MOSFETs; thus, their characterization at low frequencies and high temperatures is necessary. The energy distribution of Dit was estimated using the high-low method at 400 K, indicating that Dit was in the range of (0.4–1.5) × 1012 cm−2eV−1 within 0.23–0.76 eV from Ev of diamond. More effective passivation techniques are required to reduce interface states at deep energy levels.

In this study, unique short-circuit failure mechanisms in 1.2-kV SiC metal–oxide–semiconductor field-effect transistors (MOSFETs) at 400 and 800-V dc bias were investigated using experiments and numerical TCAD simulations, taking electrical, thermal, and mechanical stress into account. It was found that the fracture of the interlayer dielectric, caused by high mechanical stress due to different thermal expansion rates, is the source of failure in the 400-V short-circuit transient. The activation of the parasitic bipolar junction transistor under extreme high temperature was confirmed to be the failure mechanism in the 800-V short-circuit transient.

SummaryPurpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013–April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0–11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.

Temperature-dependent Hall effect measurements were conducted to investigate the channel conduction mechanisms of 4H-SiC metal-oxide-semiconductor field-effect transistors (MOSFETs). This method allows us to discriminate the impact of the density of mobile (free) carriers in the inversion channels and their net mobility on the performance of SiC MOSFETs. It was found that, while the free carrier ratio of SiC MOSFETs with conventional gate oxides formed by dry oxidation is below 4% at 300 K, increasing the free carrier ratio due to thermal excitation of trapped electrons from SiO2/SiC interfaces leads to an unusual improvement in the field-effect mobility of SiC MOSFETs at elevated temperatures. Specifically, a significant increase in free carrier density surpasses the mobility degradation caused by phonon scattering for thermally grown SiO2/SiC interfaces. It was also found that, although nitrogen incorporation in SiO2/SiC interfaces increases the free carrier ratio typically up to around 30%, introduction of an additional scattering factor associated with interface nitridation compensates for the moderate amount of thermally generated mobile carriers at high temperatures, indicating a fundamental drawback of nitridation of SiO2/SiC interfaces. On the basis of these findings, we discuss the channel conduction mechanisms of SiC MOSFETs.

Background/aim To predict pCR during neoadjuvant chemotherapy is still difficult. The aim of this study was to evaluate the optimal tumor reduction rate and modalities for predicting pCR after two cycles of docetaxel. Patients and methods We analyzed 52 patients with HER2-positive or triple-negative breast cancer. The tumor reduction rate was evaluated after two 3-week cycles of docetaxel (plus trastuzumab for HER2-positive cancer patients). Patients without progression completed two additional cycles of docetaxel and four cycles of an anthracycline-containing regimen. Results Twenty-eight patients achieved pCR. The optimal tumor reduction rates for predicting pCR were 23, 39, 32, and 40% for US, caliper, MMG, and MRI measurements, respectively. The AUC was highest for caliper measurements. The optimal modality for predicting pCR differed among subtypes. Conclusion Although tumor reduction rate after two cycles of chemotherapy is highly predictive of pCR, the optimal cutoff value differed among the modalities and breast cancer subtype.

Hydroxyl radicals (˙OH) are responsible for much of the degradation of the proton exchange membrane (PEM) used in fuel cells. The conventional approach has been to use radical scavengers incorporated into the PEM, but performance is decreased. Here, we propose a counter-intuitive strategy in which the production of hydrogen peroxide, the precursor of ˙OH, is suppressed at the hydrogen anode, where oxygen diffusing from the cathode is reduced by adsorbed hydrogen atoms. This is accomplished via the use of a Pt skin-covered PtCo alloy anode catalyst, on which H is weakly adsorbed, as indicated by theoretical calculations. In particular, the H2O2 production on the hydrogen anode at a practical temperature of 80 °C was, for the first time, evaluated by the application of the channel flow double electrode (CFDE) technique. A remarkably longer lifetime of a PEM with the PtCo/C anode, in comparison with that for a commercial Pt/C anode, has been demonstrated in an accelerated stress test of a single cell (open circuit under pressurized gases).