Percutaneous ultrasound-guided cryoablation for early-stage primary breast cancer: a follow-up study in Japan.

BACKGROUND: Ultrasound-guided percutaneous cryoablation (PCA) for early-stage breast cancer (ESBC) can be performed under local anesthesia in an outpatient clinic. This study continues a pilot stage to examine local control, safety, patient quality of life (QoL), satisfaction and cosmetic outcomes of cryoablation for ESBC. METHODS: PCA was performed under local anesthesia for patients with primary ESBC, followed by radiation and endocrine therapies. Oncologic outcomes were examined by imaging (mammography, ultrasound, MRI) at baseline and 1, 6, 12, 24, 36, and 60 months post-cryoablation. EQ-VAS, EQ-5D-5L, subjective satisfaction and Moiré topography were used to measure health-related QoL outcomes. RESULTS: Eighteen patients, mean aged 59.0 ± 9.0 years, mean tumor size 9.8 ± 2.3 mm, ER + , PR + (17/18), HER2-, Ki67 < 20% (15/18), underwent PCA and were followed for a mean of 44.3 months. No serious adverse events were reported, and no patients had local recurrence or distant metastasis in the 5-year follow-up. Cosmetic outcomes, satisfaction level, and QoL all improved post-cryoablation. Five-year average reduction rates of the cryolesion long, short, and depth diameters, on US, were 61.3%, 42.3%, and 22.8%, respectively, compared to the 86.2% volume reduction rate on MRI. The correlation coefficient between MRI and US measurement criteria was highest for the long diameter. During follow-up, calcification of the treated area was observed in 13/18 cases. CONCLUSION: Cryoablation for ESBC is an effective and safe procedure with excellent cosmetic outcomes and improved QoL. This study contributes to the growing evidence supporting cryoablation as a potential standard treatment for ESBC, given compliance to pre-defined patient selection criteria.

Association between genetic variants and the risk of nivolumab-induced immune-related adverse events.

Aim: We sought to identify the variants that could predict the risk of nivolumab-induced immune-related adverse events (irAEs) in patients with cancer. Patients & methods: We enrolled 622 Japanese patients and carried out a genome-wide association study. The associations for 507 single nucleotide polymorphisms (SNPs) showing p < 0.001 were further investigated using an independent cohort. Results: In the combined analysis, possible associations were found for a total of 90 SNPs. Although no SNPs were identified to be significantly associated with nivolumab-induced irAEs, the SNP most strongly associated with nivolumab-induced irAEs was rs469490. Conclusion: This study is an important hypothesis-generating study to guide future studies in larger and/or other ethnic cohorts.

Replication Study for the Association of Five SNPs Identified by GWAS and Trastuzumab-Induced Cardiotoxicity in Japanese and Singaporean Cohorts.

Trastuzumab (herceptin) is an effective drug for human epidermal growth factor receptor type 2 (HER2)-positive cancer. However, cardiotoxicity remains a serious complication. In our previous genome-wide association study (GWAS), we identified potential associations for five single nucleotide polymorphisms (SNPs) with trastuzumab-induced cardiotoxicity in a Japanese population. To validate this association, here we performed replication studies using Japanese and Singaporean case-control cohorts (Japan: 6 cases and 206 controls; Singapore: 22 cases and 178 controls). Although none of the SNPs showed a statistically significant association with trastuzumab-induced cardiotoxicity, we show that three (rs8032978, rs7406710 and rs9316695) and four (rs8032978, rs7406710, rs28415722 and rs11932853) SNPs had an effect in the same direction in the Japanese and the Singaporean cohort, respectively, as that in our previous study. Combining the previous study with the current replication studies, we find a strong association for two SNPs, rs8032978 and rs7406710, with trastuzumab-induced cardiotoxicity (Pcombined = 4.92 × 10-5 and 5.50 × 10-5, respectively). These data suggest that rs8032978 and rs7406710 could be predictive markers of trastuzumab-induced cardiotoxicity in Japanese and Singaporean populations, and support their potential use in clinical risk assessment. These findings offer a first step toward the development of clinically available markers for the potential risk of trastuzumab-induced cardiotoxicity as well as an improved understanding of the pathogenesis of this complication.

Chemical Ecology and Olfaction in Short-Horned Grasshoppers (Orthoptera: Acrididae).

Chemoreception plays a crucial role in the reproduction and survival of insects, which often rely on their sense of smell and taste to find partners, suitable habitats, and food sources, and to avoid predators and noxious substances. There is a substantial body of work investigating the chemoreception and chemical ecology of Diptera (flies) and Lepidoptera (moths and butterflies); but less is known about the Orthoptera (grasshoppers, locusts, crickets, and weta). Within the Orthoptera, the family Acrididae contains about 6700 species of short-horned grasshoppers. Grasshoppers are fascinating organisms to study due to their significant taxonomic and ecological divergence, however, most chemoreception and chemical ecology studies have focused on locusts because they are agricultural pests (e.g., Schistocerca gregaria and Locusta migratoria). Here we review studies of chemosensory systems and chemical ecology of all short-horned grasshoppers. Applications of genome editing tools and entomopathogenic microorganism to control locusts in association with their chemical ecology are also discussed. Finally, we identify gaps in the current knowledge and suggest topics of interest for future studies.

No correlation between mean platelet volume and carotid artery thickness in patients with diabetes at intermediate or high risk for cardiovascular diseases.

The number of patients with diabetes with a risk of cardiovascular diseases (CVDs) is increasing worldwide, leading to a higher demand for evaluating atherosclerosis. Recently, the mean platelet volume (MPV) available from complete blood count is gaining attention as a marker of underlying atherosclerotic lesions. In the current study, we examined whether MPV can predict carotid atherosclerosis in patients with diabetes at an intermediate or high risk for CVD. A total of 224 patients with diabetes aged 36-85 years who underwent carotid ultrasound examination were assessed. The risk of CVD was evaluated using the Suita score. The greatest carotid intima-media thickness (IMT) in each common carotid artery (CCA Max-IMT), carotid bulb, internal carotid artery, or external carotid artery (Total Max-IMT) was measured. Subsequently, the relationship between MPV and IMT was analyzed. Patients were divided into three groups according to their MPV values (<9.5 fl, tertile 1; 9.5-10.2 fl, tertile 2; and >10.2 fl, tertile 3). A correlation was observed between MPV and platelet count (P < 0.001), platelet distribution width (P < 0.001), and glycated hemoglobin (P = 0.04); however, multivariate logistic regression analyses demonstrated no relationship between MPV and CCA Max-IMT [odds ratio, 0.89 (0.60-1.29), P = 0.54] or Total Max-IMT [odds ratio, 0.87 (0.61-1.24), P = 0.45]. MPV did not correlate with carotid artery thickness. Therefore, it is difficult to determine the significance of MPV in atherosclerotic conditions from this study.

[Clinical Significance of the Curative Effect after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer-Correlation to Prognosis].

We investigated factors related to the recurrence and prognosis of patients with triple-negative breast cancer (TNBC)after neoadjuvant chemotherapy(NAC). Of the 545 patients who underwent surgery after NAC between January 2013 and December 2016, 131 patients had TNBC. An analysis of each TNBC case indicated that the presence or absence of clinical lymph node metastasis(cN)before treatment might be a predictive factor of prognosis. There were 57(43.5%)pathological complete response(pCR)(ypT0 or ypTis/N0)cases after NAC. Overall survival(OS)and disease free survival(DFS) were significantly better in pCR cases than in non-pCR cases. However, recurrence was observed in 8 of 57(14%)pCR cases and 29 of 74(39%)non-pCR cases. The factors defining DFS from the univariate analysis of the non-pCR group were cN, ypT, ypN, and vascular invasion. The multivariate analysis of these factors suggested that residual cN and vascular invasion might be independent factors predicting DFS. Residual vascular invasion was found to predict OS, and was considered to be a poor prognostic factor.

A Genome-Wide Association Study Identifies Five Novel Genetic Markers for Trastuzumab-Induced Cardiotoxicity in Japanese Population.

Trastuzumab has been administered to patients with human epidermal growth factor receptor 2 (HER2)-positive cancer, however, the cardiotoxicity is identified as one of the life-threatening toxicities. Clinically useful biomarker for trastuzumab-induced cardiotoxicity has been expected to be developed. To identify a novel genetic marker(s) determining the risk of trastuzumab-induced cardiotoxicity, we performed a first genome-wide association study (GWAS) in Japanese population. We enrolled 481 patients who had been treated with trastuzumab and carried out a GWAS using 11 cases (with cardiotoxicity) and 257 controls (without cardiotoxicity). Top 100 single nucleotide polymorphisms (SNPs) which revealed the smallest p values in GWAS (p = 7.60 × 10-7 - 2.01 × 10-4) were further examined using replication samples consisted of 14 cases and 199 controls. The combined analysis of the GWAS and replication study indicated possible association of five loci with trastuzumab-induced cardiotoxicity (rs9316695 on chromosome 13q14.3, rs28415722 on chromosome 15q26.3, rs7406710 on chromosome 17q25.3, rs11932853 on chromosome 4q25, and rs8032978 on chromosome 15q26.3, Pcombined = 6.00 × 10-6, 8.88 × 10-5, 1.07 × 10-4, 1.42 × 10-4, 1.60 × 10-4, respectively). Furthermore, we developed a risk prediction model for trastuzumab-induced cardiotoxicity using the five marker SNPs. The incidence of trastuzumab-induced cardiotoxicity in patients with risk score ≥5 was significantly higher (42.5%) compared to that in patients with score ≤ 4 (1.8%) (p = 7.82 × 10-15, odds ratio = 40.0). These findings suggest the potential to improve the ability of physicians to avoid the trastuzumab-induced cardiotoxicity for patients with HER2-positive cancer.

Parthenogenetic Females of the Stick Insect Clitarchus hookeri Maintain Sexual Traits.

The New Zealand stick insect Clitarchus hookeri has both sexual and parthenogenetic (all-female) populations. Sexual populations exhibit a scramble competition mating system with distinctive sex roles, where females are signalers and males are searchers, which may lead to differences in the chemical and morphological traits between sexes. Evidence from a range of insect species has shown a decay of sexual traits is common in parthenogenetic lineages, especially those traits related to mate attraction and location, presumably due to their high cost. However, in some cases, sexual traits remain functional, either due to the recent evolution of the parthenogenetic lineage, low cost of maintenance, or because there might be an advantage in maintaining them. We measured morphological and chemical traits of C. hookeri to identify differences between males and females and between females from sexual and parthenogenetic populations. We also tested the ability of males to discriminate between sexual and parthenogenetic females in a laboratory bioassay. Our results show that male C. hookeri has morphological traits that facilitate mobility (smaller body with disproportionately longer legs) and mate detection (disproportionately longer antennae), and adult females release significantly higher amounts of volatile organic compounds than males when this species is sexually active, in accordance with their distinctive sex roles. Although some differences were detected between sexual and parthenogenetic females, the latter appear to maintain copulatory behaviors and chemical signaling. Males were unable to distinguish between sexual and parthenogenetic females, suggesting that there has been little decay in the sexual traits in the parthenogenetic lineage of C. hookeri.

Prolonged Activated Partial Thromboplastin Time and False-Positive Results for Fibrinogen and Fibrin Degradation Products in a B-Cell Lymphoma Patient.

We report a unique case of a B-cell lymphoma patient in whom IgM monoclonal gammopathy resulted in a prolonged activated partial thromboplastin time (APTT) and false-positive results for fibrinogen and fibrin degradation products (FDPs). An 86-year-old man was referred to our hospital for further examination of abnormal cells in his peripheral blood. Laboratory data upon admission revealed an elevation of monoclonal IgM, presence of FDPs and marked prolongation of APTT (>180 s). Bone marrow examination revealed a predominant involvement of B lymphoma cells. In vitro examination revealed that IgM isolated from the patient's plasma had resulted in false-positive results for FDPs and APTT. Neither hemorrhagic nor thrombotic tendency was observed in this patient, suggesting that the abnormal coagulation data were due to interference by elevated monoclonal IgM levels.

Victims of Fukushima Daiichi nuclear power plant accident in long-lasting disillusionment phase.

This study describes the existence of the long-lasting disillusionment phase for the victims after the accident at the Fukushima Daiichi Nuclear Power Plant following the Great East Japan Earthquake in March 2011. Through analyzing the mental situation of the victims, the situations were categorized into 2 groups for forced evacuees: "in the disillusionment phase" and "in the reconstruction phase," Other 2 groups are for host Iwaki residents: "with negative feelings against evacuees" and "leading their life constructively." The negative feeling enhances the vicious psychological cycle for the evacuees in the long-lasting disillusionment phase and repeating emotion of survivor's guilt in the reconstruction phase. We propose that people who were getting back to a normal life while leading their life constructively should raise their voices in favor of living together with evacuees.

Chemical constituents of aerial parts and roots of Pycnanthemum flexuosum.

An extract of whole plants of Pycnanthemum flexuosum showed an inhibitory effect on hyaluronidase activity. From an 80% acetone extract of aerial parts, 3-[(3E)-4-phenylbut-3-enoylamino]propionic acid, 3-O-ß-D-glucuronopyranosyl-echinocystic acid 28-O-ß-D-xylopyranosyl-(1→3)-[3,4-diacetyl-ß-D-xylopyranosyl-(1→4)]-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester, vanillic acid 1-O-[(5-O-syringoyl)-ß-D-apiofuranosyl]-(1→2)-ß-D-glucopyranoside, and (4S,5R)-4-hydroxy-5-phenyl-tetrahydrofuran-2-one were isolated together with 30 known compounds. Six known compounds were isolated from an 80% acetone extract of roots, and eritrichin was revealed as a hyaluronidase inhibitor in P. flexuosum.