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

Technetium-99m Methoxyisobutyl Isonitrile Scintigraphy of Bone Metastasis in Three Patients with Differentiated Thyroid Cancer

We studied the usefulness of ^Tc-methoxyisobutyl isonitrile (MIBI) scintigraphy in the detection of bone metastases and in evaluation of therapeutical response to ^I-Na in three patients with differentiated thyroid cancer. On ^Tc-MIBI scintigraphy, increased accumulations were observed in all bone metastatic lesions (14 lesions), whereas on bone scintigraphy using ^Tc-hydroxymethylene diphosphonate (^Tc-HMDP) both increased (eight lesions, 57%) and decreased (six lesions, 43%) accumulations were observed. Within two months after ^I-Na treatment, all 14 lesions were unchanged on bone scintigraphy. However, on ^Tc-MIJBI scintigraphy, disappearance of uptake (six lesions, 43%) and decreased uptake (seven lesions, 50%) were observed in 13/14 lesions (93%). Therefore, ^Tc-MIBI scintigraphy was useful not only in the detection of bone metastatic lesions but also in evaluation of the therapeutical response to ^I-Na in differentiated thyroid cancer

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

A case of isolated thyroid metastasis that was diagnosed 24 years after renal cancer surgery

　転移性甲状腺癌において原発部位は腎癌が最も多いとされているが，今回腎癌術後24年と長期間経過後に孤立性甲状腺転移の症例を経験したので報告する．症例は68歳，女性．既往歴に右乳癌，両側肺癌，左腎癌あり．右乳癌温存術後の放射線治療目的に前医より当院放射線治療部に紹介．位置決め CT で甲状腺右葉腫瘤を指摘され当科紹介．頸部超音波で甲状腺右葉に約３㎝大の被膜を有する低エコー腫瘤を認めた．穿刺吸引細胞診で良性との結果で経過観察としていた．その後，腫瘤の増大を認めたため，手術を勧め，甲状腺右葉切除術を行った．術後病理検査で腎癌（淡明細胞癌）の転移との診断であった．その後当院泌尿器科に紹介し，全身精査するも明らかな遠隔転移なく経過観察となっている．腎癌術後に甲状腺腫瘤を認める場合は転移の可能性を考慮する必要性があると考える．　Renal cancer is the most common primary site of metastatic thyroid cancer. We report a case of solitary thyroid metastasis 24 years after renal cancer surgery. The patient was a 68-year-old woman. She had a history of right breast cancer, bilateral lung cancer, and left kidney cancer. She was referred to our radiotherapy department by her previous doctor for radiotherapy after right breast-conserving surgery as a positioning CT scan revealed a mass in the right lobe of the thyroid gland. Cervical ultrasound showed a hypoechoic mass with a capsule about 3 cm in size in the right lobe of the thyroid gland. Puncture aspiration cytology revealed that the mass was benign, and the patient was followed up for observation. Subsequently, the mass was found to be enlarged and surgery was recommended. Right lobe thyroidectomy was performed. Postoperative pathological examination revealed metastasis of renal cancer (clear cell carcinoma). The patient was referred to the Department of Urology at our hospital for a full-body examination, but there was no obvious distant metastasis, and the patient was under observation. When a thyroid mass is found after renal cancer surgery, the possibility of metastasis should be considered

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

Risk Factors for Bleeding After Endoscopic Submucosal Dissection for Gastric Cancer in Elderly Patients Older Than 80 Years in Japan.

Introduction:As the aging of people in a society advances, the number of elderly patients older than 80 years in Japan with gastric cancer continues to increase. Although delayed ulcer bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about characteristic risk factors for bleeding in elderly patients undergoing ESD. This study aimed to evaluate risk factors for delayed bleeding after ESD for gastric cancer in elderly patients older than 80 years.Methods:We retrospectively evaluated the incidence of delayed bleeding after ESD in 10,320 patients with early-stage gastric cancer resected by ESD between November 2013 and January 2016 at 33 Japanese institutions and investigated risk factors for delayed bleeding in elderly patients older than 80 years.Results:The incidence of delayed bleeding in elderly patients older than 80 years was 5.7% (95% confidence interval [CI]: 4.6%-6.9%, 95/1,675), which was significantly higher than that in nonelderly (older than 20 years and younger than 80 years) patients (4.5%, 4.1%-5.0%, 393/8,645). Predictive factors for ESD-associated bleeding differed between nonelderly and elderly patients. On multivariate analysis of predictive factors at the time of treatment, risk factors in elderly patients were hemodialysis (odds ratio: 4.591, 95% CI: 2.056-10.248, P < 0.001) and warfarin use (odds ratio: 4.783, 95% CI: 1.689-13.540, P = 0.003).Discussion:This multicenter study found that the incidence of delayed bleeding after ESD in Japanese patients older than 80 years was high, especially in patients receiving hemodialysis and taking warfarin. Management of ESD to prevent delayed bleeding requires particular care in patients older than 80 years

センチネルリンパ節生検を施行した腋窩リンパ節微小転移乳癌症例の検討

N0乳癌において症例を選べば，センチネルリンパ節転移陽性例であっても，腋窩リンパ節郭清（ALND）の省略が可能であると報告されている．微小転移（pN1mi）乳癌においても，同様の結果が得られている．当科でセンチネルリンパ節生検（SLNB）を施行し，pN1mi であった66例を研究対象とした．SLNB の方法は，99mTc-フチン酸を用いたRI 法とインドシアニングリーンを用いた色素法の併用法で行った．SLNB 群52例とSLNB → ALND 群14例に分け，予後を中心に検討し，ALND 省略の可能性について検討した．結果は，１）SLNB 群とSLNB → ALND 群で無病生存率および全生存率に有意差を認めなかった．２）乳房切除症例でも同様の結果であった．３）スキップ症例や術後にpN1mi と判明する症例が存在する．pN1mi 症例では乳房の術式にかかわらずALND の省略が可能である．It has been reported that axillary lymph node dissection (ALND) can be safely omitted if we carefully select breast cancer patients with sentinel lymph node metastases, including breast cancer patients with micrometastases (pN1mi). The subjects were 66 breast cancer patients with pN1mi who underwent sentinel lymph node biopsy (SLNB) in our department. SLNB was performed by the dual method using 99mTc-phytate and indocyanine green. We divided the subjects into the SLNB group (n=52) and SLNB → ALND group (n=14). Clinico-pathological factors, in particular prognosis of the patients were retrospectively studied. 1) No significant difference in disease-free survival and overall survival between the SLNB → ALND group and the SLNB group. 2) The similar findings were observed in patients who underwent mastectomy. 3) The pN1mi patients consisted of patients with so-called skip metastases and patients whose micrometastases were found in permanent sections after surgery. The omission of ALND is possible regardless of surgical methods, i.e., mastectomy or breast-conserving surgery, in pN1mi patients

Scaling study of natural vibration induced by laser ablation

レーザー照射時に生じる振動現象の時空間ダイナミクスを追究し、検証を行った。具体的な検証項目は、振り子などの物理的な加振とレーザーによる加振の違い、アブレーションを介さない光熱弾性波を用いた時の時空間ダイナミクス、そして、アブレーションを介したプラズマ発生を伴う際の時空間ダイナミクスの3点である。 物理的およびレーザーによる加振の違いとして、高次振動発生が最も異なることを明らかにした。光熱弾性波による時空間ダイナミクスは、熱拡散方程式で説明可能な線形現象であることを見出した。アブレーションを介した場合は、変位計測ではなく速度計測により評価可能であることを明らかにするに至った。We investigated the spatio-temporal dynamics of the vibrational phenomena that occur during laser irradiation. Three specific contents were considerated: the difference between physical excitation (e.g., pendulum) and laser excitation, the spatio-temporal dynamics of photo-thermal elastic waves without ablation, and the spatio-temporal dynamics in the case of plasma generation with ablation. The most distinct difference between physical and laser excitation was found to be the generation of higher-order vibrations. We found that the spatio-temporal dynamics due to photo-thermal elastic waves is a linear phenomenon that can be explained by the thermal diffusion equation. Additionally, it was found that the ablation case can be evaluated by velocity measurement instead of displacement measurement.研究分野：レーザー計

Short pulse soft x-ray laser ablation research

The short pulse laser ablation have been extensively studied for confirmation and discussion of damage formation including estimations of damage thresholds and probabilities of surface machining. Irradiation examines by the femtosecond soft x-ray laser reveals formations of smooth craters on silica glass surfaces, and the appropriate selection of the laser wavelength can make the nanometer size modification on silicon surface in the vicinity of the damage threshold. On the other hand, we also revealed that damage thresholds and modification structures obtained by the picosecond soft x-ray laser irradiation provide the same results as the femtosecond soft x-ray laser. This means that not only femtosecond but also picosecond soft x-ray laser irradiation experiments can be contribute to deep understandings of the ablation phenomena

Sweep Pulse Excitation Method for Enhancing Photoacoustic Elastic Waves at Different Laser Irradiation Parameters

Laser remote sensing using a sweep pulse excitation method, in which a laser beam is irradiated at the same repetition frequency as the natural frequency, for enhancing photoacoustic elastic waves through resonance effect has been studied. The sweep pulse excitation method, which is based on the principle of detecting natural frequency fluctuations, such as hammering tests, can detect natural frequencies in the audible sound region with low average laser power and contribute to the convenience and low cost of an installation strength diagnosis of fastening bolts. In this study, we investigated the dynamics of the swept excitation method for optimization by evaluating the dependence of the laser irradiation conditions (pulse width, spot size, and average power) on different metal disc samples. We discovered that the magnitude of the photoacoustic elastic wave is proportional to the absorption of laser power, and the spatiotemporal dynamics can be explained through thermal diffusion phenomena. These findings contribute to the development of laser-sensing technology based on photoacoustic elastic waves