Photoacoustic mammography: initial clinical results.

[Purpose]Photoacoustic tomography can image the hemoglobin distribution and oxygenation state inside tissue with high spatial resolution. The purpose of this study is to investigate its clinical usefulness for diagnosis of breast cancer and evaluation of therapeutic response in relation to other diagnostic modalities. [Materials and methods]Using a prototype machine for photoacoustic mammography (PAM), 27 breast tumor lesions, including 21 invasive breast cancer (IBC), five ductal carcinoma in situ (DCIS), and one phyllodes tumor, were measured. Nine out of twenty-one IBC patients had received primary systemic therapy (PST). [Results]Eight out of twelve IBC without PST were visible. Notably, detection was possible in all five cases with DCIS, whereas it was not in one case with phyllodes tumor. Seven out of nine IBC with PST were assigned as visible in spite of decreased size of tumor after PST. The mean value of hemoglobin saturation in the visible lesions was 78.6 %, and hemoglobin concentration was 207 μM. The tumor images of PAM were comparable to those of magnetic resonance imaging (MRI). [Conclusions]It is suggested that PAM can image tumor vascularity and oxygenation, which may be useful for diagnosis and characterization of breast cancer

Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer

Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4–29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23–58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1–6.1 months) and 2.0 months (95% CI 1.2–3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction

SPring-8放射光微小血管造影法を利用したマウス腫瘍微小血管形態および血流動態の検討

京都大学0048新制・課程博士博士(医学)甲第20980号医博第4326号新制||医||1026(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 原田 浩, 教授 松田 道行, 教授 横出 正之学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Investigation of appropriate needle length considering skin thickness with the real injection posture for insulin injections in diabetic patients

Abstract Background Insulin treatment is widely used not only for type 1 but also for type 2 diabetes patients. Insulin must be injected into the subcutaneous tissue to be effective. The needle length has been shortened for safety and efficiency. However, whether patients use an appropriate needle length is unclear. Methods Skin thickness was measured by ultrasound with patients in their usual posture during injection. Furthermore, the effect of the intervention in which the needle length was changed was investigated. Results Thirty-eight percent of the patients had fluid leakage and injected the needle intradermally. The average skin thickness was 3.3 mm while sitting, which was greater than that in a previous report including measurements taken while lying down. Consequently, the skin thickness was > 4 mm in 9.5% of the patients who used 4-mm needles. Cases of leakage and intradermal injection decreased when the needle length was changed. Conclusions This study identified that the needle length should be considered in patients with thick skin or a lower body mass index due to possibility of intradermal injection

Photoacoustic mammography capable of simultaneously acquiring photoacoustic and ultrasound images

We have constructed a prototype photoacoustic mammography system (PAM-02) capable of simultaneously acquiring photoacoustic (PA) and ultrasound (US) images. Each PA, US, and fused PA/US image can be acquired over a wide area of the breast using the scanning module of a US transducer, a PA detector, and optical prisms. The resolution of the PA images exhibits improvement from 2 to 1 mm compared to images acquired using our previous prototype. The maximum scan area of PAM-02 is 90 mm along the horizontal axis and 150 mm along the vertical axis. In a phantom experiment, the available depth was at least 45 mm. A representative example of the application of the PAM-02 prototype in clinical research at Kyoto University is presented and shows S-factor images, which are considered an approximation parameter related to hemoglobin saturation of tumor-related blood vessels. We confirmed the applicability of the system for anatomical and biological research