Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings

傷害に対するスギ木部放射柔細胞の初期の反応 : 変色と細胞内容物の季節的変化

傷害に対する木部柔細胞の初期の反応を, 主として細胞学的な観点から検討した。このため実験的に機械的傷害を与え, 傷害を与えた時点で木部を構成していた組織の変化を, 各季節において, 時間的経過を追って観察した。なお, 機械的傷害として1組の剥皮を行い, 一方はそのまま放置 (open) し, 他方は傷害後ただちに表面をエポキシ樹脂系接着剤で被覆 (sealed) した。得られた結果は以下のとおりである。(1) 傷害後木部は一般に変色を示した。変色の広がりは季節により異なった。すなわち春・夏には変色は広範囲に広がり, 秋にはやや狭く, 冬には最小値を示した。(2) 放射柔細胞内容物の変化は, 春・夏と秋・冬で異なった。すなわち前者では, 核の変形, 細胞質基質の変色, 貯蔵物質の減少の順に生じたが, 後者では細胞質基質の変色の後に核の変形がおこった。(3) openとsealedの両者において, 材の変色や放射柔細胞内容物の変化が見られた。しかしopenの方が一般に変化範囲が広く, また変色は濃色を示した。(4) 変色と菌類との関係を検討したところ, 材の変色にとって, 菌類の存在は必須のものではないと判断された。(5) 以上の結果から, 樹幹は機械的傷害に伴い, 必ず変色することが明らかになった。また傷害に伴う組織の生理的条件の変化が, 変色に必須であると判断された

Carbon Ion Radiotherapy for Unresectable Sacral Chordoma

Purpose: The results of carbon ion radiotherapy for unresectable sacral chordoma were summarized to evaluate efficacy and safety. Patients and Methods: We performed a retrospective analysis on 175 patients with unresectable sacral chordomas treated with carbon ion radiotherapy between June 1996 and February 2012. All of the patients in this study presented without prior treatment. The applied carbon ion dose ranged from 64.0 GyE to 73.6 GyE (Gray equivalent, median 70.4 GyE) in a total of 16 fixed fractions over four weeks. Results: The median age of the patients was 67 ranging from 26 to 87. The study group consisted of 55 females and 120 males. The cranial extension of tumor was S2 or higher level in 70% of the patients. The median clinical target volume was 344 cm3. The median follow up period was 59 months. Five-year overall survival and 5-year local control rates were 82% and 79%, respectively. After carbon ion radiotherapy, the ambulatory in 97% of the patients remained with or without supportive devices. Two patients experienced severe skin/soft tissue complications requiring skin grafts.Conclusion: CIRT appears effective and safe in the management of patients with unresectable sacral chordoma and offers a promising alternative to surgery.Heavy Ion in Therapy and Space Radiation Symposium 2013(HITSRS2013

Relationship between the quantity of serum reactive oxygen metabolites and skin toxicity grade in the irradiated rat model

The 17th ECCO- 38th ESMO- 32nd ESTRO European Cancer Congres