Yutaka Konishi

Abstract P1-13-07: Chemotherapy, but not body mass index has impact on joint symptoms in postmenopausal Japanese breast cancer patients treated with anastrozole: A prospective multicenter cohort study of patient-reported outcomes

Background: Endocrine treatment-related adverse events have a strong impact on patients’ quality of life and sometimes result in treatment discontinuation. Since joint symptoms are the most frequently recognized side-effect of aromatase inhibitors, evaluation of associated risk factors may well be important. Among high body mass index (BMI) and chemotherapy have been associated with the development of joint symptoms in patients enrolled in ATAC trials. To determine the impact of these factors on treatment-emergent joint symptoms in Japanese breast cancer treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs). Patients and Methods: Postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled in this prospective cohort study (SAVS-JP, UMIN000002455). A total of 416 patients were recruited from 30 centers for PRO assessment at their after-care appointments between August 2009 and April 2012. Patients completed the self-report questionnaire at baseline, 3, 6, 9 and 12 months. Symptoms were assessed as four categories (none, Grade 1: somewhat, Grade 2: quite a bit, Grade 3: very much). Pre-existing symptoms were only included if they worsened from baseline. The endpoint of this study was the frequencies of treatment-related joint symptoms, which included reports of arthralgia, decrease of joint motion, and joint stiffness. Results: We obtained PROs from 391 (94.0%) of the 416 patients at baseline and at one or more points during treatment, so that 391 patients were analysed. Joint symptoms at baseline were reported by 134 (34.3%) patients and new or worsening symptoms were experienced by 258 (66.0%) patients. The symptoms were graded as: grade 1, 53.1%; grade 2, 37.6%; grade 3, 9.3%. Mean time to onset of joint symptoms was 5.4 months, and nearly 80% had developed symptoms by 6 months. Twelve patents discontinued treatment during the first year and two patients withdrew due to joint symptoms. Patients with joint symptoms were significantly younger (age: 63.1; standard deviation: 7.9) than those without symptoms (age: 65.8: 8.4; p = 0.0045). We categorized BMI into three groups (low: Discussion: The incidence of anastrozole-associated joint symptoms was more than 60%, with most women having developed symptoms by 6 months. The PROs may disclose higher prevalence rates than physician ratings for symptoms published in pivotal clinical trials. We found that younger age and adjuvant chemotherapy, but not high BMI, were significantly associated with joint symptoms. These data should prove useful for counseling before initiating treatment with adjuvant aromatase inhibitors for postmenopausal Japanese women. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-07.

Abstract P1-12-04: Factors influencing on discontinuation of adjuvant anastrozole in postmenopausal Japanese breast cancer patients: Results from a prospective multicenter cohort study of patient-reported outcomes

Background: Adjuvant five-year treatment with aromatase inhibitors is standard for postmenopausal women with estrogen receptor positive breast cancer. However, aromatase inhibitor-related adverse events including joint symptoms and vasomotor symptoms have a strong impact on patients9 quality of life and sometimes result in treatment discontinuation. The aim of this study is to determine risk factors for discontinuation of endocrine therapy in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole in a prospective cohort study based on patient-reported outcomes (PROs). Patients and Methods: A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers in this prospective cohort study (SAVS-JP, UMIN000002455). PROs assessment was obtained at baseline, 3, 6, 9 and 12 months which included joint and vasomotor symptoms. Long-term adherence of anastrozole was obtained form 364 out of 391 patients (median follow-up: 44 months, range: 5-105months). We analyzed the relationship of discontinuation of anastrozole with joint and vasomotor symptoms induced by treatment, and patients’ characteristics. Results: Among 364 patients, 64 (17.6%) discontinued, 297 (81.6%) are ongoing and 3 (0.8%) have completed five-year anastrozole treatment. The reasons for discontinuation were recurrence: 20 (31.3%), secondary malignancies: 5 (7.8%), death from non-breast cancer: 1 (1.6%) and adverse events: 38 (59.4%). These 38 patients who stopped treatment caused by adverse events were compared with other 323 patients. Joint and vasomotor symptoms were categorized into grade 0 (no symptom or no change from baseline), grade 1+2 (mild+moderate) and grade 3 (severe). Grades of joint symptoms were significantly associated with discontinuation of anastrozole (Grade 0: 9.7%, grade 1+2: 7.8%, grade 3: 25.0%, p=0.02). Patients with longer time after menopause (16 years or longer) were significantly higher frequency of discontinuation as compared with shorter time after menopause (0-15years) (14.9% vs 8.0%, p=0.04). Univariate analysis revealed that grade 3 joint symptoms (odds ratio: 3.67, 95% confidence interval: 1.34-10.04, p=0.01) and longer time after menopause (OR: 2.01, 95%CI: 1.01-4.00, p=0.04) were significant risk factors for discontinuation. By multivariate analysis, both grade 3 joint symptoms and long time after menopause were independently associated with discontinuation. Conclusion: In the present study, we have identified that grade 3 joint symptoms and longer time after menopause were risk factors for discontinuation of adjuvant anastrozole. These data might give us useful information for counseling in patients with adjuvant aromatase inhibitors for postmenopausal Japanese women. Citation Format: Chiyomi Egawa, Shintaro Takao, Kazuhiko Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Yasuo Miyoshi. Factors influencing on discontinuation of adjuvant anastrozole in postmenopausal Japanese breast cancer patients: Results from a prospective multicenter cohort study of patient-reported outcomes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-04.

A Case of Congenital Esophagobronchial Fistula with Esophageal Cancer

症例は63歳の男性. 幼少時より頻回の咳嗽を, 特に成人後はビール摂取時の咳嗽を自覚していた. また, 肺炎を繰り返していた. 約3年半前に食道気管支瘻と診断されていたが, 今回当科にて食道造影, 食道内視鏡, 気管支鏡の各検査を行い, 胸部中部食道前壁と左主気管支との間に瘻孔を確認した. また瘻孔対側となる食道後壁には径約2cmの隆起性病変 (扁平上皮癌) を認めた. 同病変を内視鏡的に切除したところ深達度sm2であったため, 右開胸開腹にて食道切除を行い, 瘻管は結紮・切離した. 病理組織学的には瘻管内腔は重層扁平上皮で覆われており, 粘膜筋板を伴っていた. 病歴, 術中所見, 病理組織学的所見よりBraimbridge II型先天性食道気管支瘻と診断した. 本疾患と食道癌との合併例は極めてまれである. 当症例では瘻孔と食道癌病変の位置関係から, 瘻孔の存在が癌発生の一因になった可能性も考えられた.

Proximal bifurcation of hepatic artery: Novel findings on hepatic arteries demonstrated by ultrasound Doppler imaging, B-flow, and US angiography.

PurposeIt has generally been held that each portal branch is always accompanied by a single arterial branch in the liver. During Doppler ultrasound examination, however, we sometimes encounter a portal branch that appears to be associated with two arterial branches, a phenomenon referred to below asthis finding orthis phenomenon. Here we attempt to confirm that this finding is based on a correct interpretation of the image and to disclose its basic mechanism.Material and MethodsFive cases of chronic liver disease in which this phenomenon appeared were analyzed with B-flow imaging. Videotapes obtained from 30 patients who had chronic liver disease and had undergone ultrasound angiography (USAG) with arterial infusion of CO2 micro bubbles were reviewed in order to look for similar findings. Sixty-nine healthy controls were also examined with Doppler sonography for this purpose. Histopathologic specimens from 7 patients who had undergone hepatectomy (3 with hepatocellular carcinoma, 3 with metastatic tumor, and 1 with focal nodular hyperplasia) were examined to study the basic structure of the hepatic vessels.Results and DiscussionThree parallel color signals (two pulsatile and one of a constant waveform) observed on Doppler examination were confirmed by the B-flow method to be three independent vessels in all five cases in which both Doppler sonography and B-flow imaging were used. In 13 (43%) of the 30 cases of USAG, two vessels along a portal branch were visualized by the inflow of micro bubbles, indicating that the two vessels were arteries. The trio of one portal and two arterial branches was also detected with Doppler sonography in 12 (17%) of the 69 healthy controls. In 10 (59%) of the 17 cases (5 of liver disease and 12 normal) that showed this finding on Doppler examination, bifurcations of the hepatic artery and portal vein were both visualized. Hepatic arterial branches were found to bifurcate slightly more proximal to the hepatic hilus than the accompanying portal branch. Histopathologic study revealed Glisson’s areas that contained one portal branch and two arterial vessels in nontumorous parts of specimens from all 7 patients with hepatectomy.ConclusionTwo arterial branches can be demonstrated along a portal branch as a result of a more-proximal bifurcation of the hepatic artery than of the portal vein.