Macroscopic findings for breast VAB specimens

Purpose : Ultrasound-guided breast tissue biopsy is an essential technique for diagnosing breast disease, but sample errors reduce its accuracy. This study investigated whether the histopathological results can be inferred from the macroscopic findings for Ultrasound-guided breast Vacuum Assisted Biopsy (VAB) specimens. Methods: Biopsy specimens from 101 patients who underwent mammary gland VAB were photographed with a smartphone, and the relationships between the macroscopic findings and the pathological results were examined. Results : A significant difference was observed with regard to the presence / absence of turbidity: malignancy was detected in 33 / 37 (89%) specimens with turbidity and in 2 / 47 (4%) cases without turbidity (p < 0.001). A significant difference was also observed regarding the surface properties : malignancy was detected in 14 / 70 (19%) smooth specimens and in 24 / 29 (83%) rough specimens (p < 0.001). Also, malignancy was detected in 11 / 13 (85%) specimens with white spots, and the difference was significant (p < 0.001). In addition, the characteristics of intraductal papilloma, fibroadenoma, and mastopathy could be confirmed by macroscopic findings. Conclusions : When needle–biopsy of a lesion that is targeted for resection yields macroscopic findings that match the predicted histopathological findings, it can be thought that the biopsy had been properly performed. This means that false–negatives due to poor specimens can be prevented

DIP during perioperative chemotherapy

Purpose : Drug-induced interstitial pneumonia (DIP) that occurs during chemotherapy for breast cancer is a rare but a serious adverse event. Treatments of DIP requires interruption of breast cancer treatment, which may affect the patient’s prognosis. However, there are few reports which discuss DIP during breast cancer treatments. Purpose of this report is to make clear how DIP occurred and influenced breast cancer treatment in our hospital. Patients and Methods : A total of 74 patients who started perioperative chemotherapy in Tokushima Municipal Hospital for breast cancer from January 2019 to December 2020 were evaluated for DIP. Patients’ and tumors’ characteristics, and regimens which caused DIP were investigated. The clinical courses of the DIP patients were also followed up. Results : Twelve of the 74 patients developed DIP. All 12 patients had histories of cyclophosphamide administration ; however, the causative drug could not be determined. Ten of the 12 patients were treated with steroids, and all the patients recovered ultimately from the interstitial pneumonia. While chemotherapy was administered in six patients after mild DIP, no relapse of pneumonia was observed. Conclusion : DIP during perioperative chemotherapy for breast cancer was resolved with appropriate treatment. Patients were able to resume breast cancer treatment with minimal interruption

フィリピンにおける公衆衛生に関する留学記

As a second-year resident at the University of Tokushima Hospital, I report on my experience of overseas training in the Philippines under the training program of the National Institute of Health Sciences. The National Institute of Health Sciences is an institution that conducts education, investigation, and research related to health, medical care, and welfare, and I trained for two months in the Department of Clinical Training in Community Health, Specialty Course III. In addition to the out-of-hospital training at the Ministry of Health, Labour and Welfare, Chiba Prefectural Government, and National Institute of Infectious Diseases, the one week overseas training in the Philippines（Manila） consisted mainly of lectures and training on mosquito-borne infectious diseases, zoonosis, and parasites at the University of the Philippines, Philippine General Hospital, Suburban Health Center, and WHO Western Pacific Office. Infectious diseases are very different from those in Japan. The actual observation made us understand that rabies and parasitic infections are raging in the Philippines due to the sanitary conditions of the living environment, which is very different from that of Japan. By learning about the medical system at overseas medical facilities, we were able to rethink deeply about the merits of the Japanese medical system and the direction it should take in the future from various perspectives

遺伝性乳癌卵巣癌症候群

Hereditary breast and ovarian cancer（HBOC）syndrome is an autosomal dominant genetic disease, which represents about ５% of all breast cancers. The pathogenic mutations in the BRCA １／２genes involved in DNA repair pathway are known to be associated with an increased risk of not only breast cancer and ovarian cancer but also prostate cancer, pancreatic cancer and male breast cancer. The risk reduction management is required for BRCA mutation-positive patients. The surveillance using breast magnetic resonance imaging（MRI）is recommended for early detection of breast cancer in HBOC patients. Furthermore, it has been reported that risk reducing salpingooophorectomy（RRSO）reduces mortality caused by breast cancer and ovarian cancer, and contralateral risk-reducing mastectomy（CRRM）improves the overall survival in postoperative breast cancer patients

A case of juvenile fibroadenoma arising from axillary accessory mammary gland

A case is２０years old woman. She had previously noticed a mass in the left axilla. The mass grew, so she went to the hospital. Ultrasonography revealed a ７１ × ５１ mm well-defined tumor in the left axilla. We suspected a benign tumor but could not rule out axillary lymph node metastasis or accessory breast cancer. The findings of fine needle aspiration cytology suggested fibroadenoma or phyllodes tumor. Although we diagnosed fibroadenoma by needle biopsy, a definitive diagnosis was made by tumor resection because it is located in the axilla and large in size, and other diseases such as phyllodes tumors can be distinguished. The histopathological diagnosis of the excised specimen was juvenile fibroadenoma. We report a case of juvenile fibroadenoma arising from the axillary accessory mammary gland

HER2陽性乳癌の総リンパ球数の検討

Purpose : Several studies have shown that peripheral hematologic parameters, such as the absolute lymphocyte count（ALC）and neutrophil to lymphocyte ratio（NLR）can predict the prognosis for malignant tumor. We investigated the relation of these parameter and prognosis before neoadjuvant chemotherapy for human epidermal growth factor receptor-２（HER２）-positive breast cancer patients. Methods : From April ２００９ to March ２０１９, ８５ patients diagnosed with HER２‐positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy were included in this retrospective cohort study. The optimal cut-off for the NLR and ALC was identified using the receiver operating characteristic（ROC）curve analysis and Youden’s index. Results : The median age of patients at the start of treatment was ５８．９（range ３２‐８１）years. The median follow-up time for HER２-positive breast cancer patients was ５２．０（range：９．８‐１１４．３）months. In this period, １１ patients developed recurrence. The low-ALC group showed better disease free survival than the high-ALC group（p=０．０４８２）. There was no significant difference in disease free survival between the low- and high-NLR groups. Conclusion : ALC before neoadjuvant chemotherapy may be a predictor of prolonged disease free survival in HER２‐positive breast cancer patients

高齢者乳癌に対するAnthracycline回避レジメン

Tolerability and efficacy of chemotherapy avoiding anthracycline regimen were examined histologically in ER negative and HER２positive elderly and poor risked breast cancer patients because of serious toxicity of Anthracycline regimen. Neo-adjuvant chemotherapy with ４ to ６ courses of Paclitaxel with Trastuzumab was given to ６ patients, Pertuzumab was added in 2 cases to obtain complete response. Adverse events were controllable, the primary treatment was completed without reducing the dose of drugs（RDI was １００％）. Clinical CR rate was recognized in all ６ patients and pathological CR was proved in all of the operated５cases

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target