Mental health, mental fatigue and breast cancer screening examination behavior in adult women

　Breast cancer has attracted increasing attention recently, because the number of breast cancer patients has increased, and breast cancer has affected some famous people. In Japan, however, the rate of screening examinations for breast cancer remains low and has shown little increase. Various innovations have been introduced to raise the examination rate, but the existence of some kinds of psychosocial problems in examinees may be one reason for the limited effect of these efforts. Here we report a study on the mental health and mental fatigue level of adult women that could affect their behavior of undergoing examinations. 　Questionnaires on breast cancer screening examination behavior were distributed to 5,321 adult women from March to September 2014, and responses were obtained from 1,752 (32.9%). After excluding women under 40 years old and questionnaires with clearly inadequate responses, the subjects of the investigation were 1,047 women. 　Past experience of undergoing breast cancer screening and levels of mental health and mental fatigue using the WHO subjective well-being inventory (SUBI) were investigated. The SUBI consists of two scales for positive affect and negative affect that make up subjective well-being, with 11 subscales (General Well-Being Positive Affect, Expectation-Achievement Congruence, Confidence in Coping, Transcendence, Family Group Support, Social Support, Primary Group Concern, Inadequate Mental Mastery, Perceived Ill-Health, Deficiency in Social Contacts, and General Well-Being Negative Affect). It is used to assess levels of mental health and mental fatigue. 　802 people (51.6 ± 7.97) had undergone examinations in the past, and 245 (49.3 ± 7.29 years old) had not. The group that had never undergone examinations tended to be significantly younger (P < 0.0001). The score for mental health level was significantly higher in the group that had undergone examinations (P = 0.013), but no significant difference was seen in mental fatigue level (P = 0.847). Subjects with poor mental health (score < 31) were significantly less likely to undergo screening examinations (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.112-2.331, P = 0.012). The results of a multivariate analysis of the 11 subscales showed trends of women being less likely to undergo screening examinations with higher scores for Confidence in Coping (OR 1.175, 95% CI 1.026-1.346, P = 0.019), and more likely to undergo screening examinations with higher scores for Family Group Support (OR 0.872, 95% CI 0.777-0.979, P = 0.020). 　Low mental health level was found to be an impediment to the behavior of undergoing breast cancer screening examinations. Among the mental health items, family support and excessive confidence affected the behavior of undergoing examinations. Thus, approaches that raise mental health with that in mind are thought to be necessary

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

パルボシクリブ併用内分泌治療が著効した閉経前再発乳癌の１例

　パルボシクリブ併用内分泌療法が著効した閉経前再発乳癌の１例を報告する．８年前に乳房温存手術を受け，残存乳房への放射線治療後に化学内分泌補助療法（シクロフォスファミド＋エピルビシン（CE 90）を４サイクル後に毎週パクリタキセルを４サイクル施行．化学療法終了後からLH-RH アゴニスト２年間とタモキシフェン５年間）を行った．治療継続中も含め定期で外来受診を継続しており，年１回の画像検査（肺，肝，骨を標的）と３か月ごとの腫瘍マーカー測定では再発の兆候はなく経過していた．しかし，補助治療終了後約３年で発熱と肝機能障害をきっかけに多発遠隔再発（肺・骨・肝・子宮体部）を発見した．ホルモン感受性は残存している可能性はあったが，急速な再発であるために，再発後初回治療としてドセタキセルおよびデノスマブの投与を開始した．有効ではあったが投与後約半年でマーカーの再上昇と体動時呼吸困難（在宅酸素療法導入）および疲労・倦怠感の増強が出現した．有害事象と病勢進行のため再発後の二次治療としてパルボシクリブ，フルベストラント，LH-RH アゴニストを導入した．導入後１か月で体動時呼吸困難が消失し，３か月で在宅酸素療法が中止できた．半年後のPET/CT で集積が消失しており画像上は著効と判断できた．有害事象は白血球・好中球減少が出現した以外に認めなかった．再発治療としてパルボシクリブ併用内分泌治療が有用であった．　We have a case of pre-menopausal patient with recurrent breast cancer showing an excellent response to endocrine therapy with palbociclib. Eight years ago, she underwent breast conserving operation followed by adjuvant chemo-endocrine therapy (4 cycles of cyclophosphamide and doxorubicin, 4 cycles of paclitaxel and tamoxifen adding LHRH agonist). The administration of tamoxifen continued for 5 years as an adjuvant therapy. After 3 years of discontinuation of adjuvant medication, fever and liver dysfunction led to find the recurrence of breast cancer in lung, bone, liver and uterus. We chose to treat with chemotherapy as the first line, because the recurrence was rash and multiple. After 6 months of treatment of docetaxel and denosumab, serum decreased tumor markers elevated gradually and dyspnea and general fatigue worsened. She recieved palbociclib, fluvestrant and LH-RH agonist as a second endocrine therapy. Six months after the treatment, PET/CT revealed an excellent effect on each metastatic lesion. Adverse event was only seen in neutropenia to make one-level reduction of dose. Palbociclib and endocrine therapy appeared to be useful as a second-line treatment for recurrent breast patient

A case of superior mesenteric artery syndrome after left hemicolectomy for descending colon cancer

A 58-year-old man was diagnosed as having descending colon cancer and underwent a left colectomy with D3 node dissection and end-to-end anastomosis reconstruction. The accessory middle colic artery was secured as a feeding artery, and the middle colic artery was preserved. Diet was started on postoperative day 5 (POD5), and nausea and vomiting appeared on POD10. An upper gastrointestinal series revealed to-and-fro peristalsis in the third portion of the duodenum and dilatation of the proximal duodenum. Abdominal CT showed that the second portion of the duodenum was markedly dilated and the third portion was compressed by the superior mesenteric artery (SMA). As a result, he was diagnosed with post-operative superior mesenteric artery syndrome (SMAS) and treated with conservative therapy. The symptoms improved with a nasogastric tube, and he started to eat after POD26, followed by a successful outcome

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

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