The Kago low-sulfidation gold and silver deposit: a peripheral mineralisation to the Nansatsu high-sulfidation system, southern Kyushu, Japan

The Kago deposit is a small deposit located at the southern tip of the Satsuma Peninsula of Southern Kyushu, Japan. It lies proximal to the well-known Nansatsu-type mineralisation province dominated by high-sulfidation type epithermal deposits. The deposit was heavily mined in the 18 th Century, largely for its relatively higher gold compared to that of surrounding and regional deposits. The Kago deposit is a typical low-sulfidation deposit, characterised by adularia-quartz veins, composed of electrum, Ag-tetrahedrite, polybasite, chalcopyrite and pyrite. Based on mine records, the grade ranged from 4.1 to 13.3 g/t Au and 2.6–6.6 g/t Ag. Alteration grades from low to high temperature argillic into a propylitic zone at the extremes of the vein exposures. Carbonate is absent. Fluid inclusion microthermometry reveals a typical temperature range of 220–240 °C with salinity of 0.7–2.6 NaCl eq. wt%. Electrum from high-grade ore ranges from 66 to 69 wt% Au. 40Ar/39Ar age dating of adularia bearing colloform/crustiform and brecciated veins, suggests a mineralisation event from 4.23 to 4.0 Ma. δ18O of veined and silicified quartz ranges from +4.0 to +18.4‰. δ18OH2O of fluids in equilibrium with quartz, in the dominant range of measured fluid inclusion temperatures, ranges from −6.5‰ to −0.2‰. δ34S of pyrite has a narrow range from −1.8 to 2.7‰. The deposit lies at the northern extent of the classic Nansatsu high-sulfidation epithermal area, in which a number of silicified bodies punctuate the region in a roughly semi-circular shape. The Kago deposit lies within the principle mineralisation age range of the high-sulfidation deposits, which range from 5.5 to 3.7 Ma. The structural displacement of the Kago deposit from the Nansatsu mineralisation and the differing host rocks has greatly influenced alteration, ore and rock-water interaction of the ore depositing fluids. Here we seek to establish the relationship that this extended mineral province has between the differing styles of mineralisation

Predictors for the outcomes of patients with estrogen receptor-positive, HER2-negative advanced breast cancer treated using palbociclib plus endocrine therapy

　A cyclin-dependent kinase (CDK) 4/6 inhibitor, palbociclib (PAL), combined with endocrine therapy is frequently used for the treatment of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer. However, as predictors for the outcomes remain unclear, we retrospectively investigated them.　A total of 36 patients with ER-positive, HER2-negative advanced breast cancer were treated using PAL plus endocrine therapy at our hospital. Treatment outcomes, objective response rates (ORR), progression-free survival (PFS) and post-treatment overall survival (OS) were analyzed. As possible predictive biomarkers, retinoblastoma protein (Rb), phosphorylated Rb (pRb) and different CDKs were immunohistochemically investigated using primary tumor tissues. Non-visceral metastasis, use of fulvestrant (FUL) and the 1st- or 2nd-line treatment were significant predictors for a better ORR (P = 0.0080, P = 0.0080 and P = 0.0080, respectively). No objective response (OR) was observed in patients with progesterone receptor (PR)-negative, CDK6-positive or cytosolic cyclin E1-positive tumors. Non-visceral metastasis and use of FUL were significant predictors for a better PFS (P = 0.0030 and P = 0.0443, respectively). The Cox proportional hazards model revealed that visceral metastasis (hazard ratio [HR], 4.9; P = 0.0019) and PR-negativity (HR, 3.2; P = 0.0411) were independent predictors for a poorer PFS. Nonvisceral metastasis, pRb-negativity and CDK6-negativity were significant predictors for a better OS (P = 0.0281, P = 0.0014 and P = 0.0396, respectively). The Cox proportional hazards model revealed that visceral metastasis (HR, 7.2; P = 0.0131) and pRb-positivity (HR, 18.5; P = 0.0060) were independent predictors for a poorer OS.　In conclusion, PR-negativity and pRb-positivity in primary tumors may be independent predictors for PFS and OS, respectively. CDK6-positivity and cytosolic cyclin E1-positivity may be predictors for a poorer OS and ORR, respectively. Further investigation is needed to confirm these factors

Longitudinal change of postoperative serum anti-thyroglobulin antibody levels in patients without total thyroidectomy and remnant ablation

　Backgroud: There is little information regarding postoperative anti-thyroglobulin antibody (TgAb) changes in patients without a total thyroidectomy and ablation. This study aimed to analyze the longitudinal change of TgAb levels in patients with remnant thyroid.　Methods: The study group were patients who had undergone a non-total thyroidectomy for papillary thyroid carcinoma from 1996 to 2018. The median follow-up period of measurement serum Tg and Tg Ab was 3.5 years (1-7.5 years). Eligible patients had a combined serum Tg and TgAb measurement at least three times biannually. We excluded patients with thyroid dysfunction at the initial diagnosis or with papillary carcinoma who had persistent or any recurrence of disease.　Results: A total of 209 patients were enrolled. In the preoperative analysis, 41 (31%) patients had positive TgAb values, and 91 were negative (69%). Seventeen years after the operation, a TgAb value over 800 IU/ml was not seen. The positive TgAb ratio was stable for 12 years (20%-30%); however, its positivity gradually increased from 13 years onward to 45.5%. The number of patients with consistently negative and positive TgAb values was 140 (67.0%) and 47 (22.5%), respectively. The number of patients with a mixture of positive and negative TgAb values was 10 (4.8%). The number of patients who changed from positive to negative values was six (2.9%) and, inversely, six (3.9%).　Conclusions: We found positivity of TgAb after surgery gradually increases up to 45.5% over about 10 years in patients with normal remnant thyroid. We might continue to measure both serum Tg and TgAb values concurrently for the patients with remnant thyroid tissue throughout

A Case of Adenomatous Goiter Involving Diffuse, Acute, and Painful Thyroid Enlargement after Fine-Needle Aspiration Cytology

The patient was a 44-year-old woman who exhibited a diffuse goiter during health screening. Her medical history did not include any significant medication-based treatment. An echographic examination detected a solid cystic tumor, which measured 21 × 14 × 10 mm, in her right thyroid lobe; however, she displayed normal thyroid function. After fine-needle aspiration cytology had been performed with a 22 G injection needle, the patient immediately complained of compression and pain extending from the front of her neck to her lower chin, which was not accompanied by dyspnea. A second echographic examination revealed diffuse and edematous enlargement and increased internal blood flow in the bilateral thyroid lobes as well as a thyroid nodule. We immediately iced the patient’s neck and administered 125 mg methylprednisolone via an intravenous infusion. Within one hour, her symptoms had markedly improved, but acute pain remained. Thus, we continued the steroid (prednisone) treatment, but the dose was gradually reduced from 10 mg/day to 5 mg/day at 1 week after the patient’s symptoms disappeared. The mechanism responsible for the patient’s condition remains unclear

Photo-induced orientation behaviors of azobenzene liquid crystal copolymers for photonic crystals

A certain wavelength of incident light is forbidden based on the optical periodicity related to the intervals and refractive indices of the comprising materials. For multi-bilayered films with periodicity, on–off switching of reflection is possible due to the presence or absence of a refractive index difference between two consisting films. Changes in the refractive index can be induced by stimuli-responsive orientation behaviors of liquid crystal (LC) molecules with birefringence. Azobenzene (Az) groups are employed for photo response and copolymerized with non-photo-responsive LC mesogen groups for cooperative orientation to improve light penetration by the dilution of Az concentration. LC mesogen groups are designed to have a high refractive index to improve the reflection contrast. The refractive indices and the orientation behaviors of the copolymer films are investigated. On–off switching of reflection for multi-bilayered films consisting of alternate Az-containing LC copolymers and poly vinyl alcohol is conducted using ultraviolet and visible light irradiation, and their reflection intensity and response speed are compared between the different LC mesogen types and molar ratios

On-off switching properties of one-dimensional photonic crystals consisting of azo-functionalized polymer liquid crystals having different methylene spacers and polyvinyl alcohol

In this paper, photoresponsive behavior of multi-bilayered films having precisely controlled layer thickness prepared by stacking an azo-functionalized polymer liquid crystal, PMAzXAc, and polyvinyl alcohol alternatively, PVA, is described. The multi-bilayered films were found to reflect a light of specific wavelength depending on the layer thickness and refractive index, and showed the reversible change in the reflection intensity by irradiation with visible and UV lights. The change in the reflection intensity was brought about by change in the molecular orientation of PMAzXAc between an out-of-plane orientation and a photo-induced isotropic state, and was strongly dependent on the number of methylene spacer of PMAzXAc linking the azobenzene side group with the acrylate polymer main chain. PMAz6Ac with hexa-methylene spacer showed the largest change in the reflection intensity, while smaller change in the reflection intensity was observed for PMAzXAc having shorter or longer methylene spacer than 6. The effect of the methylene spacers on the photochemical change in the molecular orientation of azobenzene chromophores in the multi-bilayered films will be discussed

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

初回治療から10年以上の無病期間を経て発症した副甲状腺腺腫の１例

症例報告Case Reportjournal articl

術前から副甲状腺癌を疑い手術を施行した原発性副甲状腺機能亢進症の１例

症例報告Case Reportjournal articl

当院における進行・再発乳癌に対するベバシズマブ・パクリタキセル併用療法の有用性の検討

　抗血管内皮増殖因子（vascular endothelial growth factor, VEGF）モノクローナル抗体ベバシズマブが進行・再発乳癌の治療薬として日本においても2011年から使用されている．日本乳癌学会乳癌診療ガイドライン2018年においてHER2陰性転移・再発乳癌に対する１次・２次の化学療法にベバシズマブを併用することが推奨されている．今回，当院における進行・転移再発乳癌に対するベバシズマブとパクリタキセル同時併用療法（BP 療法）の有用性の検討を行った．対象患者は2011年９月～2018年10月に当科でBP 療法を導入した79症例で，電子カルテを参照して後方視的検討を行った．年齢の中央値は58歳．ホルモン受容体（hormone receptor, HR）陽性humanepidermal growth factor receptor（HER）２陰性サブタイプが45例，HR 陽性HER2陽性サブタイプが２例，HR 陰性HER2陽性サブタイプが５例，HR 陰性HER2陰性（triple negative）サブタイプが27例であった．Stage Ⅳが24例，再発が55例であり，主な転移部位（重複あり）は骨が45例，肝が34例，肺が29例，胸膜が21例であった．前化学療法レジメン数の中央値は２レジメン（範囲：0-8）であった．奏効率は63.3%，無増悪生存期間（PFS）の中央値は5.4か月であり，全生存期間（OS）の中央値は9.4か月であった．HER2陰性症例における多変量解析の結果，performance status 2以上がOS を悪化させる因子であり（ハザード比 [HR] が2.85， p=0.002），triple negative サブタイプ（HR が2.44，p=0.025）と中枢神経転移あり（HR が3.24，p=0.045）がPFS を悪化させる因子であった．重篤な有害事象としては，消化管穿孔と皮膚・軟部組織潰瘍形成，縦隔気管瘻，肺膿瘍，脳出血，上部消化管出血，血尿，鼻出血が認められた．本研究対象は２次治療以降で使用された症例が多いため，既報の臨床試験の結果と比較するとPFS は短かったが，奏効率は同等であった．一方，重篤な有害事象も10% 以上の頻度で認められ，BP 療法施行時には慎重な観察が必要である．　The humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab has been used to treat advanced or metastatic breast cancer since 2011 in Japan. According to the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer 2018, the addition of bevacizumab to first- or second-line chemotherapy is recommended for patients with human epidermal growth factor receptor (HER) 2-negative advanced or metastatic breast cancer. We investigated the clinical utility of combined bevacizumab and paclitaxel therapy (BP therapy) for patients with advanced or metastatic breast cancer at our hospital. The study subjects were 79 breast cancer patients who received BP therapy at our hospital between September 2011 and October 2018, and their medical records were retrospectively reviewed. The median age of the subjects was 58 years old. Their primary tumors were categorized as follows: the hormone receptor (HR)-positive, HER2- negative subtype in 45 patients, the HR-positive, HER2-positive subtype in 2 patients, the HR-negative, HER2-positive subtype in 5 patients, and the HR-negative, HER2-negative (socalled triple-negative) subtype in 27 patients. Twenty-four patients had stage IV disease and 55 had recurrent disease. The main metastatic lesions were in bone in 45 patients, in the liver in 34 patients, in the lungs in 29 patients, and in pleura in 21 patients. The median number of previous chemotherapeutic regimens was 2 (range: 0-8). The objective response rate was 63.3%, the median progression-free survival (PFS) time was 5.4 months, and the median overall survival (OS) time was 9.4 months. Multivariate analyses of predictive factors for PFS or OS in HER2-negative subjects revealed a performance status of 2 or higher to be a significant predictor of poor OS (hazard ratio [HR]=2.85, p=0.002), and the triple-negative subtype and metastasis to the central nervous system to be predictors of poor PFS (HR=2.44，p=0.025 for the former and HR=3.24，p=0.045 for the latter). Serious adverse events, such as perforation of the gastrointestinal tract, ulcer formation in the skin and soft tissue, fistula formation between the trachea and mediastinum, pulmonary abscess, intracranial hemorrhage, gastrointestinal bleeding, macro-hematuria, and nasal bleeding, were observed during BP therapy. Most patients in this study received BP therapy as greater than second-line therapy; therefore, the PFS was slightly shorter, but the ORR was similar to that previously reported. As serious adverse events were observed in more than 10% of the study subjects, physicians should pay close attention during BP therapy