Saizu: A Very Big Loanword in Japanese

The tradition of student-centered active learning for development of critical thinking at Miyazaki International College provides valuable opportunities for discovery in the classroom. This brief paper outlines the results of one such student project in LL3141, Topics in Linguistics, taught by Debra J Occhi in fall semester of 2013. Students were inspired to undertake this research while reading and discussing Language Contact Meets Cognitive Linguistics: A Case of Getto-suru in Japanese (Horie & Occhi 2001). This paper reviews those findings, presents issues students found especially relevant about loanword behavior discussed in Olah (2007) and about English made in Japan (wasei eigo, discussed in Miller 1997), lists noun loanwords found in Japanese-English dictionaries, presents and analyzes instances of use of the loanword saizu (from English “size”)

ベバシズマブ併用化学療法中に消化管穿孔をきたした再発乳癌の１例

　ベバシズマブはパクリタキセルとの併用でHER2陰性の進行・再発乳癌に対する有効性が示されており，無増悪生存期間を有意に延長させる．しかし，ベバシズマブ特有の有害事象も報告されており，投与の際には注意を要する．今回，再発乳癌に対しベバシズマブを使用し，腸管穿孔を起こした１例を経験した．症例は72歳女性．右乳癌術後５年目に多発リンパ節，肺転移を認め，化学療法で治療中に８次治療としてベバシズマブとパクリタキセル（BP）療法を開始した．１年ほど奏効したが，突然，腹痛を訴え受診した．CT で腹腔内にfree air を認めたため緊急開腹術を施行した．小腸に１か所の穿孔部位を認めた．病理組織検査では，穿孔部に乳癌の転移巣が認められた．乳癌に対するベバシズマブ併用化学療法中の消化管穿孔は報告が少ない．腹膜播種を認める症例やベバシズマブ投与期間の長い患者では，腹部膨満感や腹痛を訴えた際は消化管穿孔を念頭におく必要がある．　Combination therapy with bevacizumab and paclitaxel (BP therapy) has been reported to be effective for the treatment of HER2-negative metastatic breast cancer and to significantly prolong progression-free survival. However, there are specific adverse effects induced by bevacizumab that physicians should pay attention to. We report a recent case of metastatic breast cancer with gastrointestinal perforation during bevacizumab therapy. A 72-year-old female patient had metastases into multiple lymph nodes and lungs five years after surgery for primary breast cancer, and was treated with several chemotherapies. The patient received BP therapy as the eighth treatment regimen. Although the therapy led to stable disease for approximately one year, the patient suddenly developed abdominal pain. Emergency laparotomy was performed because computed tomography revealed free air in the peritoneal cavity. A perforated lesion was found in her small intestine. On pathological examination, breast cancer metastasis was noted around the perforated site. There are few reports of gastrointestinal perforation during bevacizumab therapy for patients with metastatic breast cancer. When a patient has peritoneal dissemination, long-term BP therapy and abdominal pain, physicians should keep in mind the possibility of gastrointestinal perforation during BP therapy. (187 words

Characteristics and prognosis of adolescent and young adult (AYA) breast cancers at Kawasaki Medical School Hospital, Okayama

　Adolescent and young adults（AYA）世代の癌は一般成人の癌に比べ，頻度は低いものの妊孕性の維持など複雑な問題を抱えている．AYA 世代の後半30から39歳では，乳癌の発生頻度が最も高い．今回我々は，AYA 世代の乳癌患者を後方視的に調査し，予後因子を解析した．　対象は2010年１月～2018年12月に川崎医科大学附属病院乳腺甲状腺外科で治療を行った40歳未満の AYA 世代乳癌患者123名（AYA 群）．また同期間に治療を受けた40歳以上の非若年乳癌患者1,541名（非若年群）と予後の比較を行った．無病生存率（DFS），全生存率（OS）の予後因子は，単変量解析及び多変量解析で分析した．　両側性乳癌，非浸潤癌，データ不足例を除外した1,322名（AYA 群が99名，非若年群が1,223名）の乳癌患者が予後解析の対象となった．５年 DFS は AYA 群で81.5％，非若年群は91.3％であり，AYA 群で有意に不良であった（P = 0.0007）．臨床病期を揃えると，病期Ⅱのみで両群間に有意差が認められた（P = 0.0319）．５年 OS は AYA 群，非若年群ともに96.7% であり，差は認められなかった．AYA 群の DFS 予測因子は，単変量解析では，臨床病期Ⅱ期以上，腫瘍浸潤径２cm 超，血管侵襲陽性が有意の予後不良因子であった．多変量解析では，臨床病期Ⅱ期以上，血管侵襲陽性が独立した予後不良因子であった．OS では，単変量解析では血管侵襲因子のみが OS の有意の予測因子として抽出された．多変量解析では，血管侵襲因子とトリプルネガティブサブタイプが，独立した予後不良因子であった．妊娠関連乳癌は，DFS, OS ともに有意の予後因子とならなかった．　AYA 群は非若年群に比べて５年 DFS が有意に悪かった．AYA 群の予後因子として，血管侵襲因子が重要なことが示唆された．　Adolescent and young adult (AYA) cancers are infrequent compared with common cancers but have complicated problems such as fertility preservation. Breast cancer is the most common cancer in women aged between 30 and 39. In the present study, we conducted a retrospective cohort study to characterize AYA breast cancers and to analyze predictive factors for prognosis.　A total of 123 AYA breast cancer patients under 40 years-old treated in our department in Kawasaki Medical School Hospital, Okayama, between January 2010 and December 2018 (AYA group) were the study subject group. Prognostic data of 1,541 breast cancer patients older than 39 years of age treated in the same department and period (elder group) was obtained to compare with that of the AYA group. Possible prognostic factors for disease-free survival (DFS) and overall survival (OS) were investigated using either univariate or multivariate analyses.　After excluding patients with bilateral breast cancers, non-invasive breast cancers and/or insufficient clinicopathological data, a total of 1,332 patients (99 for the AYA group and 1,223 for the elder group) were the subjects for analysis of prognosis. Five-year DFS for the AYA group was significantly worse than that for the elder group (81.5% for the former, 91.3% for the latter, P = 0.0007). This was significantly worse in the AYA group at stageⅡ(P = 0.0319) but not at the other stages. Five-year OS was almost identical between the two groups (P = 0.5532). Univariate analysis for DFS in the AYA group showed that later stage (stageⅡor Ⅲ), invasive tumor size of over 2 cm and positive vascular invasion were significantly worse prognostic factors. Multivariate analysis showed that later stage and positive vascular invasion were independent prognostic factors. With regard to OS, univariate analysis revealed that only positive vascular invasion was a worse prognostic factor. Multivariate analysis revealed that positive vascular invasion and triple negative subtype were independent worse prognostic factors. Pregnancy-associated breast cancer was not a significant prognostic factor for either DFS or OS.　In conclusion, five-year DFS was significantly worse in the AYA group than in the elder group. Presence of vascular invasion was suggested to be an important worse prognostic factor for either DFS or OS

進行・再発乳癌患者に対するフルベストラントの有用性

　ホルモン受容体陽性の閉経後進行・再発乳癌患者に対する内分泌療法として，フルベストラントが本邦で臨床導入されて６年余りが経過した．本剤の有用性を検討するため，2012年１月〜2016年10月に川崎医科大学附属病院乳腺甲状腺外科において，フルベストラントが単独使用され，治療評価が可能であった51症例の電子カルテを後方視的に調査した．対象患者の年齢の中央値は70歳．進行例が９例，再発例が42例．臓器転移ありが23例．観察期間の中央値は18か月．前内分泌療法数の中央値は２．前化学療法歴ありは21例．治療効果は，完全奏効が３例，部分奏効が６例，安定が25 例（うち長期安定は20例），進行が16例であった．客観的奏効は９例（17.6%），臨床的有用は29例（56.9%）であった．無増悪生存（PFS）期間の中央値は８か月，全生存（OS）期間の中央値は34か月であった．治療効果の予測因子を調べるため，サブグループに分けてPFS及びOS を解析した．肝転移の有無では，PFS 期間の中央値は，なしが9.5か月，ありが５か月（P= 0.0386），OS 期間の中央値は，なしが41か月，ありが15か月（P = 0.0036）であった．前化学療法の有無では，PFS 期間の中央値は，なしが12.5か月，ありが3.5か月（P < 0.0001），OS 期間の中央値は，なしが41か月，ありが24か月（P = 0.0208）．多変量解析では，前化学療法歴の有無が唯一のPFS の有意な予測因子であった．また，肝転移の有無が唯一のOS の有意な予測因子であった．有害事象は６例（11.7%）に認めたが，いずれも軽微であり治療が中断されることはなかった．要約すると，ホルモン受容体陽性の進行・再発乳癌の治療薬として，フルベストラントは17.6% の客観的奏効率，56.9% の臨床的有用性が認められ，既知の報告と同等の治療効果であった．フルベストラントは，化学療法歴のある症例，肝転移のある症例では，有用性が低いと考えられた．　Fulvestrant has been used for the treatment of postmenopausal patients with advanced or recurrent breast cancer in Japan for over six years. To investigate the utility of fulvestrant, we retrospectively reviewed electronic medical records and evaluated the responses of 51 patients with advanced or recurrent breast cancer treated with fulvestrant alone at the Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital between January 2001 and December 2016. The median age of the subjects was 70 years old. Nine had stage IV diseases and 42 had recurrent diseases. Twenty-three patients had visceral metastases. The median follow-up time after the start of fulvestrant treatment was 18 months. The median number of previous endocrine therapies was 2. Twenty-one patients received chemotherapy previously. Three patients had a complete response, six had a partial response, 25 had a stable disease including 20 patients with a long-term stable disease, and 16 had progressive disease. The objective response rate was 17.6% (9 out of 51), and the clinical benefit rate was 56.9% (29 out of 51). The median progression-free survival (PFS) time was 8 months. The median overall survival (OS) time was 34 months. To investigate predictive factors for response to fulvestrant, subgroup analyses were performed. For liver metastasis, the median PFS and OS time were 9.5 and 41.0 months, respectively, in patients without liver metastasis but 5.0 and 15.0 months, respectively, in those with liver metastasis (P = 0.0386 and P = 0.0036, respectively). For previous chemotherapy, the median PFS and OS time were 12.5 and 41.0 months, respectively, in patients without previous chemotherapy but 3.5 and 24.0 months, respectively, in those with previous chemotherapy (P < 0.0001 and P = 0.0208, respectively). In addition, the Cox’s proportional hazards model revealed that previous chemotherapy was only an independent predictive factor for PFS and that liver metastasis was only an independent predictive factor for worse OS. Although toxicities were recorded in 6 of 51 patients (11.7%), all instances were slight and no patient stopped fulvestrant therapy because of toxicities. In summary, fulvestrant therapy at our hospital provided a 17.6% objective response rate and 56.9% clinical benefit rate in patients with advanced or recurrent breast cancer. These results were similar to those reported previously. According to our subgroup analyses, fulvestrant was unlikely to be effective in patients who received previous chemotherapy or had liver metastasis

De Novo Design of a Nanopore for DNA Detection Incorporating a β-hairpin Peptide

The amino acid sequence of a protein encodes information on its three-dimensional structure and specific functionality. De novo protein design has emerged as a method to manipulate the primary structure for the development of artificial proteins and peptides with desired functionality. This paper describes the de novo design of a pore-forming peptide that has a β-hairpin structure and assembles to form a stable nanopore in a bilayer lipid membrane. This large synthetic nanopore is an entirely artificial device with practical applications. This peptide, named SV28, forms nanopore structures ranging from 1.6 to 6.2 nm in diameter assembled from 7 to 18 monomers. The nanopore formed with a diameter of 5 nm is able to detect long double-stranded DNA (dsDNA) with 1 kbp length, and measurement of current signals allowed us to investigate the translocation behavior of dsDNA at the single molecule level. Such de novo design of peptide sequences has the potential to create assembled structure in lipid membrane such as novel nanopores, which would also be applicable in molecular transporter between inside and outside of lipid membrane

A giant axillary mass treated as breast cancer metastasis

　A 69-year-old woman with a giant fist-sized left axillary mass was admitted to the Dermatology Department of Kawasaki Medical School. No primary tumor was identified, and she was referred to the Department of Breast and Thyroid Surgery of Kawasaki Medical School Hospital. A 90-mm tumor was found in the left axilla, which exhibited ulceration and infection. Imaging analysis revealed no abnormalities in the breast or other organs such as the lungs. Needle biopsy revealed a poorly differentiated carcinoma exhibiting a mixture of glandular structures and keratinization, and it was difficult to determine the original tumor. The differential diagnoses were primary skin cancer, including adnexal organs, occult breast cancer, accessory breast cancer and metastatic tumor from unknown malignancy. Immunohistochemical analysis revealed that this tumor had no estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2 expression. Primary chemotherapy was initiated because the National Cancer Comprehensive Network guidelines recommend that unclassified axillary epithelial malignancies in women be treated as occult breast cancer. After 4 cycles of epirubicin plus cyclophosphamide followed by 4 cycles of docetaxel plus doxifluridine, the axillary tumor shrunk to 15 mm in size. Axillary lymph node dissection, including skin resection of the axilla, was performed, and radiotherapy to the left breast and left axilla/supraclavicular lymph node area was administered. There has been no recurrence for over 4 years

A Case of Takotsubo syndrome after Surgery for Papillary Thyroid Cancer

　The patient was an 82-year-old woman undergoing treatment for bronchial asthma. In December 200X, she visited her former doctor because of a left cervical mass and pain, and was referred to our hospital for detailed examination. A 19-mm mass was found in the left lobe of the thyroid gland and there were many swollen lymph nodes on both sides of her neck. Fine-needle aspiration cytology revealed malignant and papillary cancer in both the left lobe and left cervical lymph node, but no lung metastasis was found in chest CT, and it was judged to be T1bN1bM0 Stage IVa. Total thyroidectomy + bilateral cervival lymphnode dissection was performed. The left lobe mass of the thyroid gland invaded the sterno-thyroid muscle, but no infiltration to other organs, including the lymph nodes on both sides, was observed. On the night of the operation, wheezing, dyspnea, lower mandibular breathing, and impaired consciousness suddenly developed, and the oxygen saturation of peripheral artery (SpO2) decreased to 60%. No postoperative bleeding was observed. Chest CT demonstrated no signs of heart failure, but based on thickening of the bronchial wall, the cause of hypoxemia was considered to be bronchial asthma. Steroids and oxygen (high-dose, 15 L/ min) were administered, but respiratory acidosis developed and non-invasive positive pressure ventilation (NIPPV) was started. The respiratory condition gradually improved thereafter. Acute coronary syndrome (ACS) was suspected based on symptoms, increased troponin T, and ST elevation on ECG. Echocardiography revealed akinesis and left ventricular apical and basal hypercontractility. No coronary arterial stenosis was noted on coronary angiography and left ventriculography demonstrated Takotsubo-like wall movement (hypercontraction of the base and contraction failure of the apex), leading to a diagnosis of Takotsubo syndrome (TS). The subsequent course was good and she was discharged on the 10th postoperative day