140 results on '"Kikumori T"'
Search Results
2. A longitudinal tracking and quantitative assessment of paclitaxel-induced peripheral neurotoxicity
- Author
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Matsuoka, A., primary, Mitsuma, A., additional, Maeda, O., additional, Tsunoda, N., additional, Kikumori, T., additional, and Ando, Y., additional
- Published
- 2019
- Full Text
- View/download PDF
3. Parathyroid hormone suppression by 22-oxacalcitriol in the severe parathyroid hyperplasia
- Author
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Funahashi, H., Tanaka, Yuji, Imai, T., Wada, M., Tsukamura, K., Hayakawa, Y., Matsuura, N., Kikumori, T., Oiwa, M., Tominaga, Y., and Takagi, H.
- Published
- 1998
- Full Text
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4. Intratumoral injection of herpes simplex virus HF10 in recurrent breast cancer
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Nakao, A., Kimata, H., Imai, T., Kikumori, T., Teshigahara, O., Nagasaka, T., Goshima, F., and Nishiyama, Y.
- Published
- 2004
5. Laparoscopic partial adrenalectomy
- Author
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Imai, T., Tanaka, Y., Kikumori, T., Ohiwa, M., Matsuura, N., Mase, T., and Funahashi, H.
- Published
- 1999
- Full Text
- View/download PDF
6. Section 3. Adrenal: Laparoscopic bilateral adrenalectomy for Cushing’s syndrome due to ACTH-independent macronodular adrenocortical hyperplasia
- Author
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Imai, T., Kikumori, T., Shibata, A., Fujiwara, M., and Nakao, A.
- Published
- 2002
- Full Text
- View/download PDF
7. Surgical management of Cushing's syndrome
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Imai, T., Kikumori, T., Funahashi, H., and Nakao, A.
- Published
- 2000
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8. The efficacy of eribulin mesylate with trastuzumab for locally advanced or metastatic HER2-positive breast cancer treated with prior pertuzumab and/or T-DM1: Results from a phase II, single arm, multicenter study (N-SOG 10 study)
- Author
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Fujii, M., primary, Tsunoda, N., additional, Hattori, M., additional, Murata, T., additional, Akahane, K., additional, Kamei, K., additional, Goto, Y., additional, Amemiya, T., additional, Nishimae, K., additional, Kubota, T., additional, Ito, Y., additional, Kurumiya, Y., additional, Yoshihara, M., additional, Nakanishi, K., additional, Kikumori, T., additional, Ando, M., additional, and Nagino, M., additional
- Published
- 2017
- Full Text
- View/download PDF
9. 1801P - A longitudinal tracking and quantitative assessment of paclitaxel-induced peripheral neurotoxicity
- Author
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Matsuoka, A., Mitsuma, A., Maeda, O., Tsunoda, N., Kikumori, T., and Ando, Y.
- Published
- 2019
- Full Text
- View/download PDF
10. Survey on QOL and cosmesis after intraoperative radiotherapy (IORT) in a multicenter phase II study of patients with early breast cancer
- Author
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Sawaki, M., primary, Miyamoto, T., additional, Fujisawa, T., additional, Yanagita, Y., additional, Kodaira, T., additional, Kikumori, T., additional, and Iwata, H., additional
- Published
- 2017
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- View/download PDF
11. 375PD A validation study of a new point-of-care nerve conduction device for the quantitative assesment of chemotherapy-induced peripheral neurotoxicity
- Author
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Matsuoka, A., primary, Mitsuma, A., additional, Maeda, O., additional, Uehara, K., additional, Kikumori, T., additional, Kajiyama, H., additional, Kiyoi, H., additional, Kodera, Y., additional, and Ando, Y., additional
- Published
- 2015
- Full Text
- View/download PDF
12. 101P - The efficacy of eribulin mesylate with trastuzumab for locally advanced or metastatic HER2-positive breast cancer treated with prior pertuzumab and/or T-DM1: Results from a phase II, single arm, multicenter study (N-SOG 10 study)
- Author
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Fujii, M., Tsunoda, N., Hattori, M., Murata, T., Akahane, K., Kamei, K., Goto, Y., Amemiya, T., Nishimae, K., Kubota, T., Ito, Y., Kurumiya, Y., Yoshihara, M., Nakanishi, K., Kikumori, T., Ando, M., and Nagino, M.
- Published
- 2017
- Full Text
- View/download PDF
13. SU-E-T-412: Evaluation of Tungsten-Based Functional Paper for Attenuation Device in Intraoperative Radiotherapy for Breast Cancer
- Author
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Kamomae, T, primary, Monzen, H, additional, Okudaira, K, additional, Miyake, Y, additional, Oguchi, H, additional, Komori, M, additional, Kawamura, M, additional, Itoh, Y, additional, Kikumori, T, additional, and Naganawa, S, additional
- Published
- 2015
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- View/download PDF
14. P157 - Survey on QOL and cosmesis after intraoperative radiotherapy (IORT) in a multicenter phase II study of patients with early breast cancer
- Author
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Sawaki, M., Miyamoto, T., Fujisawa, T., Yanagita, Y., Kodaira, T., Kikumori, T., and Iwata, H.
- Published
- 2017
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15. Thyrotropin modifies activation of nuclear factor kappaB by tumour necrosis factor alpha in rat thyroid cell line
- Author
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Kikumori, T, Kambe, F, Nagaya, T, Funahashi, H, and Seo, H
- Subjects
Transcriptional Activation ,endocrine system ,endocrine system diseases ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Colforsin ,NF-kappa B ,Thyroid Gland ,Thyrotropin ,Cell Line ,Rats ,Genes, Reporter ,Animals ,Humans ,RNA, Messenger ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Immunoglobulins, Thyroid-Stimulating - Abstract
We have recently demonstrated that nuclear factor kappaB (NF-kappaB) mediates the tumour necrosis factor alpha (TNF-alpha)-dependent expression of the gene encoding interleukin 6 (IL-6) in rat thyroid FRTL-5 cells cultured in the presence of thyrotropin (TSH). In the present study we investigated how TSH is involved in the activation of NF-kappaB by TNF-alpha in the cells. Electrophoretic mobility-shift assay revealed that, in the absence of TSH, TNF-alpha activated a single protein-DNA complex containing the p50 subunit but not other NF-kappaB subunits such as p65. In contrast, two distinct protein-DNA complexes were activated in the presence of TSH: the faster-migrating complex contained only p50 subunit; the slower-migrating complex consisted of p65-p50 heterodimer. This TSH effect was mimicked by forskolin and thyroid-stimulating antibodies obtained from patients with Graves's disease, suggesting that an increase in intracellular cAMP is responsible for the induction of different NF-kappaBs by TNF-alpha. A transient transfection study with a luciferase reporter gene driven by multimerized NF-kappaB sites demonstrated that TNF-alpha increased the luciferase activities only in the presence of TSH, and that this increase was inhibited by the co-transfection of mutant p65, which prevented the function of wild-type p65 in a dominant-negative manner. Accordingly, TNF-alpha activated the expression of the IL-6 gene in the presence of TSH but not in its absence. Although the expression of the p105 gene, another known target for NF-kappaB, was increased by TNF-alpha in the absence of TSH, the presence of TSH further increased the mRNA level. Taken together, these observations indicate that the presence of TSH is crucial for the NF-kappaB-mediated actions of TNF-alpha on thyroid follicular cells.
- Published
- 2001
16. Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer
- Author
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Sahin, T T, primary, Kasuya, H, additional, Nomura, N, additional, Shikano, T, additional, Yamamura, K, additional, Gewen, T, additional, Kanzaki, A, additional, Fujii, T, additional, Sugae, T, additional, Imai, T, additional, Nomoto, S, additional, Takeda, S, additional, Sugimoto, H, additional, Kikumori, T, additional, Kodera, Y, additional, Nishiyama, Y, additional, and Nakao, A, additional
- Published
- 2011
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17. The Feasibility Study of Docetaxel in Patients with Anaplastic Thyroid Cancer
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Kawada, K., primary, Kitagawa, K., additional, Kamei, S., additional, Inada, M., additional, Mitsuma, A., additional, Sawaki, M., additional, Kikumori, T., additional, Fujimoto, Y., additional, Arima, H., additional, Imai, T., additional, and Ando, Y., additional
- Published
- 2010
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18. 0118 A preliminary report of a phase I study of intraoperative radiotherapy (IORT) for early breast cancer in Japan
- Author
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Sawaki, M., primary, Sato, S., additional, Kagawa, C., additional, Yamada, T., additional, Takada, H., additional, Kikumori, T., additional, Oda, K., additional, Ishihara, S., additional, Ito, Y., additional, and Imai, T., additional
- Published
- 2009
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19. The effect of toremifene on lipid metabolism compared with that of tamoxifen in vitro
- Author
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Sawaki, M., primary, Watanabe, R., additional, Kagawa, C., additional, Sasa, M., additional, Takada, H., additional, Sato, S., additional, Yamada, T., additional, Kikumori, T., additional, and Imai, T., additional
- Published
- 2008
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20. Clinical Experiment of Mutant Herpes Simplex Virus HF10 Therapy for Cancer
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Nakao, A., primary, Takeda, S., additional, Shimoyama, S., additional, Kasuya, H., additional, Kimata, H., additional, Teshigahara, O., additional, Sawaki, M., additional, Kikumori, T., additional, Kodera, Y., additional, Nagasaka, T., additional, Goshima, F., additional, Nishiyama, Y., additional, and Imai, T., additional
- Published
- 2007
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- View/download PDF
21. Section 3. Adrenal
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Imai, T., primary, Kikumori, T., additional, Shibata, A., additional, Fujiwara, M., additional, and Nakao, A., additional
- Published
- 2002
- Full Text
- View/download PDF
22. Nighttime Bandaging to Reduce Lymphedema Swelling
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Nakanishi Keisuke, Mawaki Ayana, Oshima Chika, Takeno Yukari, Kurono Fumiya, Taniho Yuiko, Murotani Kenta, Kikumori Toyone, and Fujimoto Etsuko
- Subjects
Nursing ,RT1-120 - Abstract
Multilayer compression bandaging (MLB) for breast cancer-related lymphedema (BCRL) patients may be easier to apply during nighttime sleep. Little is known about the specific effects of nighttime multilayer bandaging (NMLB) alone. In the present study, we examined whether NMLB alone significantly improved the negative symptoms of BCRL such as excessive swelling and an unpleasant feeling. A pre–post study was conducted as a basis for the development of efficient self-care treatment. Eight middle-aged female patients with unilateral upper extremity BCRL voluntarily participated in this study. During the first 2 weeks, the participants were educated and trained in the self-bandaging technique. The participants then wore MLB on the affected extremity for the following seven nights at home from bedtime to the next morning (hereafter referred to as the intervention ). We measured the segmental total body water (STBW) volume on the affected upper extremity using bioimpedance spectroscopy and subjective symptoms using a visual analog scale. Each parameter was measured at the beginning and end of the intervention periods. It was found that the STBW volume on the affected upper extremity decreased significantly during intervention. The mean STBW volume reduction was 0.088 L ( p = .047, 95% CI [0.001, 0.175] L]). Subjective symptoms related to swelling (i.e., tightness, heaviness, and fullness) decreased significantly during intervention ( p
- Published
- 2017
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23. Virilizing adrenocortical adenoma: In vitro steroidogenesis, immunohistochemical studies of steroidogenic enzymes, and gene expression of corticotropin receptor
- Author
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Imai, T., Tobinaga, J.i., Morita-Matsuyama, T., Kikumori, T., Sasano, H., Seo, H., and Funahashi, H.
- Abstract
Background: No reports have yet precisely determined corticotropin (ACTH) responsiveness in virilizing adrenocortical adenoma. Methods: Five women with an androgen-secreting adrenal adenoma were reviewed. Three of them were examined by in vitro steroidogenesis. Two of these 3 patients were studied by immunohistochemistry of steroidogenic enzymes and for the gene expression of ACTH receptor by Northern blot analysis. Results: In preoperative hormonal determinations plasma and urine androgens had increased. Dexamethasone did not suppress plasma and urinary androgens, nor did ACTH increase them. In vitro steroidogenesis revealed that the adenoma cells produced mainly dehydroepiandrosterone and a small amount of testosterone. ACTH did not increase the in vitro production of androgens. In immunohistochemical staining 5 enzymes involved in adrenal steroidogenesis were all expressed, especially 17@a-hydroxylase, which was strongly expressed in tumor cells. ACTH receptor messenger RNA was not detected in virilizing tumor tissues, whereas it was expressed in attached adrenal tissues. Conclusions: The lack of response to ACTH is the result of a deficiency of ACTH receptor expression in the virilizing tumor cells. Androgens were autonomously produced in adrenal adenoma cells without ACTH regulation. (Surgery 1999;125:396-402.)
- Published
- 1999
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24. Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: Long-term follow-up of grafted parathyroid function
- Author
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Kikumori, T., Imai, T., Tanaka, Y., Oiwa, M., Mase, T., and Funahashi, H.
- Abstract
Background: Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. Methods: Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. Results: The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 @mg of 1@a-vitamin D"3. Four hypoparathyroid patients were normocalcemic with 2 @mg of 1@a-vitamin D"3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. Conclusions: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible. (Surgery 1999;125:504-8.)
- Published
- 1999
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25. A case-controlled study of laparoscopic compared with open lateral adrenalectomy - a case-control study of 100 patients
- Author
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Imai, T., Kikumori, T., Ohiwa, M., Mase, T., and Funahashi, H.
- Published
- 1999
- Full Text
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26. Phase I Dose-escalation Clinical Trial of HF10 Oncolytic Herpes Virus in 17 Japanese Patients with Advanced Cancer
- Author
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Kasuya, H., Yasuhiro Kodera, Nakao, A., Yamamura, K., Gewen, T., Zhiwen, W., Hotta, Y., Yamada, S., Fujii, T., Fukuda, S., Tsurumaru, N., Kuwahara, T., Kikumori, T., Koide, Y., Fujimoto, Y., Nakashima, T., Hirooka, Y., Shiku, H., Tanaka, M., Takesako, K., Kondo, T., Aleksic, B., Kawashima, H., Goto, H., and Nishiyama, Y.
- Subjects
Male ,Oncolytic Virotherapy ,Time Factors ,Herpesvirus 1, Human ,Middle Aged ,Virus Replication ,Oncolytic Viruses ,Treatment Outcome ,Japan ,Neoplasms ,Mutation ,Humans ,Female ,Neoplasm Staging - Abstract
Oncolytic virus therapy is a promising new therapeutic method, one of an eagerly anticipated class of biological therapies against cancer. There are many different classes of oncolytic virus. One of these, herpes oncolytic virus, is strongly oncolytic and has a large DNA genome as 150k bp. HF10 is a spontaneous mutant of herpes simplex virus -1 (HSV-1) that replicates within tumors and destroys cancers without damaging normal tissue and organs. Clinical trials of HF10 are underway in Japan and the United States. The first pilot study of HF10 was initiated in Japan in 2003. This study examined the safety and efficacy of HF10 in the treatment of breast cancer and head and neck cancers; the trial also included careful dose escalation studies. In 2005, a clinical trial using HF10 to treat pancreatic cancer was initiated. screened In this Japanese study, 17 patients received HF10 in their tumor sites. A clinical trial in the United States is also ongoing to evaluate safety, tolerability and evidence of antitumor activity in patients with refractory superficial solid tumors. Here, we report the evaluation of the 17 patients treated in Japan. Among the patients, 6 had recurrent breast cancer, 3 had recurrent head and neck cancer, and 8 had non-resectable pancreatic cancer. No severe adverse side effects have been observed, and some therapeutic potential has been reported based on pathological findings, tumor markers, and diagnostic radiography. Those results should encourage further clinical trials of HF10 around the world.
27. Long-term response to MEK inhibitor monotherapy in a patient with papillary thyroid carcinoma harboring BRAF V600E mutation.
- Author
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Takano Y, Shimokata T, Urakawa H, Kikumori T, and Ando Y
- Abstract
Solid tumors harboring mutations in the Braf gene ( BRAF ) are currently treated by combination Braf/MEK inhibitor therapy, and there is an extensive literature on patient response rates. Alternatively, few studies have documented the clinical response of BRAF mutation-positive solid tumors to MEK inhibitor monotherapy. We report the case of a 57-year-old female diagnosed with papillary thyroid carcinoma and progressive lung metastases initially treated by total thyroidectomy and subsequent thyroid-stimulating hormone suppression therapy. Next-generation sequencing revealed that the tumor harbored a BRAF
V600E mutation, and the patient was enrolled in a clinical study of the oral MEK1/2 inhibitor binimetinib. Shortly after starting treatment, the patient experienced pneumothorax due to rapid regression of lung metastases, and computed tomography after 6 months of binimetinib treatment revealed a partial sustained response. One year later, the dose was reduced because of an acneiform rash. After 5 years of binimetinib treatment, lung metastases had regrown, and treatment was switched to the oral multikinase inhibitor lenvatinib. This case demonstrates the potential of MEK inhibitor monotherapy as an alternative treatment for BRAF mutation-positive papillary thyroid carcinoma., Competing Interests: Conflict of interestYA received a speaker honorarium from Chugai Pharmaceutical Co., Ltd. and Bayer Holding Ltd. He received research funding from Chugai Pharmaceutical Co., Ltd. and Geo Holding Corporation. The other authors have no conflicts of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)- Published
- 2024
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28. Exploring Indicators of Subcutaneous Tissue Fluid Accumulation in Breast Cancer-Related Lymphedema Patients Using Fractal Analysis with Virtual Volume.
- Author
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Niwa S, Hisano F, Mawaki A, Nakanishi K, Watanabe S, Fukuyama A, Kikumori T, Shimamoto K, Imai K, Fujimoto E, and Oshima C
- Subjects
- Humans, Female, Subcutaneous Tissue diagnostic imaging, Fractals, Breast Neoplasms complications, Breast Neoplasms diagnostic imaging, Breast Neoplasms therapy, Breast Cancer Lymphedema diagnostic imaging, Breast Cancer Lymphedema etiology, Lymphedema diagnostic imaging, Lymphedema etiology
- Abstract
Background: Breast cancer treatment sometimes causes a chronic swelling of the arm called breast cancer-related lymphedema (BCRL). Its progression is believed to be irreversible and is accompanied by tissue fibrosis and lipidosis, so preventing lymphedema from progressing by appropriate intervention at the site of fluid accumulation at an early stage is crucial. The tissue structure can be evaluated in real time by ultrasonography, and this study aims at assessing the ability of fractal analysis using virtual volume in detecting fluid accumulation within BCRL subcutaneous tissue via ultrasound imaging. Methods and Results: We worked with 21 women who developed BCRL (International Society of Lymphology stage II) after unilateral breast cancer treatment. Their subcutaneous tissues were scanned with an ultrasound system (Sonosite Edge II; Sonosite, Inc., FUJIFILM) using a 6- to 15-MHz linear transducer. Then, a 3-Tesla MR system was used to confirm fluid accumulation in the corresponding area of the ultrasound system. Significant differences in both H + 2 and complexity were observed among the three groups (with hyperintense area, without hyperintense area, and unaffected side) ( p < 0.05). Post hoc analysis (Mann-Whitney U test; Bonferroni correction p < 0.0167) revealed a significant difference for "complexity." The evaluation of the distribution in Euclidean space showed that the variation of the distribution decreased in the order of unaffected, without hyperintense area, and with hyperintense area. Conclusion: The "complexity" of the fractal using virtual volume seems to be an effective indicator of the presence or absence of subcutaneous tissue fluid accumulation in BCRL.
- Published
- 2023
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29. Robotic resection of ectopic mediastinal parathyroid adenoma in multiple endocrine neoplasia 1.
- Author
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Ohara Y, Kadomatsu Y, Kikumori T, and Chen-Yoshikawa TF
- Abstract
Background: Hyperparathyroidism in patients with multiple endocrine neoplasia 1 is attributed to the excessive secretion of parathyroid hormone (PTH) from multiple parathyroid glands. This can be successfully treated through complete resection of the parathyroid glands; however, subsequent surgery is often required because of the presence of supernumerary or ectopic parathyroid glands. Therefore, identifying the locations of all functional glands is crucial for precise resection. Here, we report a case of ectopic mediastinal parathyroid adenoma that was successfully resected using robot-assisted thoracoscopic surgery., Case Presentation: A 53-year-old woman underwent a total parathyroidectomy with autotransplantation for multiple endocrine neoplasia 1-associated primary hyperparathyroidism. The patient previously underwent laparoscopic distal pancreatectomy for a pancreatic neuroendocrine tumor. She also presented with a mediastinal tumor and nonfunctional pituitary adenoma that could be followed up. Blood tests before total parathyroidectomy showed high levels of intact PTH (183 pg/mL) and calcium (Ca; 10.3 mg/dL); however, postoperative blood tests still revealed high levels of intact PTH (103 pg/mL) and Ca (11.4 mg/dL). Computed tomography and magnetic resonance imaging revealed a 45-mm-sized mass in the right upper mediastinum as a well-defined solid and cystic lesion, whereas
99m Tc-methoxyisobutylisonitrile scintigraphy indicated a strong accumulation of tracers, suggesting an ectopic lesion in the mediastinum. Persistent hyperparathyroidism after total parathyroidectomy via neck incision was attributed to an ectopic parathyroid tumor in the mediastinum. Thus, we decided to resect the tumor using robot-assisted thoracoscopic surgery to perform the procedure gently and carefully. During surgery, a mediastinal tumor was identified as it was detected radiographically. Because it did not invade the surrounding tissues, it could be completely resected without injuring the capsule. The patient was discharged without complications. Postoperatively, Ca and intact PTH levels decreased back to normal. The final pathological diagnosis confirmed that the mass was an ectopic mediastinal parathyroid adenoma., Conclusions: Minimally invasive surgical resection of a remnant ectopic lesion was successfully performed in a patient with multiple endocrine neoplasia 1 using robot-assisted thoracoscopic surgery., (© 2023. The Author(s).)- Published
- 2023
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30. Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade.
- Author
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Kobayashi T, Iwama S, Yamagami A, Yasuda Y, Okuji T, Ito M, Zhou X, Ando M, Onoue T, Miyata T, Sugiyama M, Hagiwara D, Suga H, Banno R, Hase T, Morise M, Ito T, Kikumori T, Inoue M, Ando Y, Masuda N, Kawashima H, Hashimoto N, and Arima H
- Subjects
- Antibodies, Monoclonal, Humanized adverse effects, Autoantibodies, B7-H1 Antigen, Humans, Ligands, Protein Kinase Inhibitors adverse effects, Risk Factors, Thyrotropin, Ramucirumab, Antineoplastic Agents adverse effects, Thyroiditis chemically induced
- Abstract
Background: Thyroid dysfunction is frequently caused by treatment with antiprogrammed cell death-1 ligand 1 antibodies (PD-L1-Abs) and anticancer drugs, including ramucirumab (RAM) and multitargeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients., Methods: A total of 148 patients treated with PD-L1-Abs were evaluated for antithyroid antibodies at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then were observed until the visits stopped., Results: Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in 8 and hypothyroidism without preceding thyrotoxicosis in 7). The prevalence of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs 4/133 [3.0%], P < .05), positive antithyroglobulin antibodies (TgAbs) at baseline (4/15 [26.7%] vs 5/133 [3.8%], P < .05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs 5/133 [3.8%], P < .05) were significantly higher in patients with vs without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with ORs of 7.098 (95% CI 1.154-43.638), 11.927 (95% CI 2.526-56.316), and 8.476 (95% CI 1.592-45.115), respectively., Conclusion: The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline, and prior treatment with RAM or multi-TKIs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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31. Prediction of the Presence of Fluid Accumulation in the Subcutaneous Tissue in BCRL Using Texture Analysis of Ultrasound Images.
- Author
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Niwa S, Mawaki A, Hisano F, Nakanishi K, Watanabe S, Fukuyama A, Kikumori T, Shimamoto K, Fujimoto E, and Oshima C
- Subjects
- Female, Humans, Male, Reproducibility of Results, Subcutaneous Tissue diagnostic imaging, Ultrasonography, Breast Cancer Lymphedema diagnosis, Breast Neoplasms therapy, Lymphedema diagnostic imaging, Lymphedema etiology
- Abstract
Background: Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm due to breast cancer treatment. Lymphedema is diagnosed and staged on the basis of limb circumference measurements and the patient's subjective symptoms, which have poor reproducibility and objectivity: these cannot detect any fluid accumulation in the tissue. Ultrasonography is a feasible noninvasive technique that can be used to evaluate tissue structure in real time. This study aimed to assess the ability of texture features for discriminating the presence of accumulated fluid within the subcutaneous tissue of BCRL using ultrasound (US) imaging. Methods and Results: This study included 20 women who were treated for unilateral breast cancer and who subsequently developed BCRL (International Society of Lymphology stage II). Subcutaneous tissue was scanned through an US system (Sonosite Edge II; Sonosite, Inc., FUJIFILM) using a 6- to 15-MHz linear transducer to assess the ability of texture features for discriminating the presence of accumulated fluid within the subcutaneous tissue of BCRL. Fluid accumulation was observed using a 3-Tesla MR system under double-echo steady-state conditions. There was a significant difference among the three groups (with hyperintense area, without hyperintense area, and unaffected side) in 11 of 14 textural features ( p < 0.05). Post hoc analysis (Mann-Whitney U test; Bonferroni correction p < 0.0167) revealed significant differences in seven textural features within the hyperintense area. Conclusions: This study revealed that seven texture features quantified by US imaging data can provide information regarding fluid accumulation in the subcutaneous tissue of lymphedema.
- Published
- 2022
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32. Platelet isoform of phosphofructokinase accelerates malignant features in breast cancer.
- Author
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Inaishi T, Shibata M, Ichikawa T, Kanda M, Hayashi M, Soeda I, Takeuchi D, Takano Y, Tsunoda N, Kodera Y, and Kikumori T
- Subjects
- Adult, Aged, Breast Neoplasms pathology, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation genetics, Disease Progression, Female, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Breast Neoplasms enzymology, Breast Neoplasms genetics, Phosphofructokinase-1, Type C genetics, Phosphofructokinases genetics
- Abstract
The platelet isoform of phosphofructokinase (PFKP) is one of the key enzymes in the glycolytic pathway. PFKP is highly expressed in several cancers, and it has been reported to be involved in the progression of cancer cells. However, its oncological role in breast cancer (BC) remains unclear. The present study aimed to evaluate the function of PFKP in BC cells and its expression level in patients with BC. Firstly, the mRNA and protein expression of PFKP was evaluated in BC and non‑cancerous mammary cell lines. Polymerase chain reaction (PCR) array analysis was conducted to evaluate the correlation between PFKP and 84 cancer‑related genes. Then, PFKP knockdown was conducted using small interfering RNA, and cell proliferation, invasiveness and migration were analyzed. Furthermore, the association between PFKP mRNA expression and clinicopathological factors was investigated in 167 patients with BC. PFKP was highly expressed in estrogen receptor‑negative and human epidermal growth factor receptor 2‑negative BC cell lines. PCR array analysis demonstrated that the expression level of PFKP was significantly correlated with that of transforming growth factor‑β1 and MYC proto‑oncogene. PFKP knockdown significantly decreased the proliferation and invasiveness of MCF7, SK‑BR‑3, and MDA‑MB‑231 cells. Furthermore, cell migration was inhibited in SK‑BR‑3 and MDA‑MB‑231 cells. In the clinical specimens, patients with T2/T3/T4, lymph node metastasis, or stage II/III/IV exhibited higher expression of PFKP mRNA than patients with less severe disease. In conclusion, the present findings indicated that PFKP is involved in promoting tumor‑progressive oncological roles in BC cells across different subtypes and is considered a possible novel therapeutic target for BC.
- Published
- 2022
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33. S-1 facilitates canerpaturev (C-REV)-induced antitumor efficacy in a triple-negative breast cancer model.
- Author
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Miyajima N, Ragab Eissa I, Abdelmoneim M, Naoe Y, Ichinose T, Matsumura S, Bustos-Villalobos I, Mukoyama N, Morimoto D, Shibata M, Takeuchi D, Tsunoda N, Kikumori T, Tanaka M, Kodera Y, and Kasuya H
- Subjects
- Animals, CD8-Positive T-Lymphocytes, Drug Combinations, Fluorouracil therapeutic use, Humans, Mice, Neoplasm Recurrence, Local, Pyridines therapeutic use, Antimetabolites, Antineoplastic therapeutic use, Oncolytic Viruses, Oxonic Acid therapeutic use, Tegafur therapeutic use, Triple Negative Breast Neoplasms drug therapy
- Abstract
Canerpaturev (C-REV) is a highly attenuated, replication-competent, mutant strain of oncolytic herpes simplex virus type 1 that may be an effective new cancer treatment option. S-1, an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, is used as a key chemotherapeutic agent for metastatic recurrent breast cancer. Although the antitumor effects of oncolytic viruses combined with 5-FU in vivo have been reported, the detailed mechanisms are unknown. Here, we investigated the antitumor mechanism of the combination of C-REV and S-1 in triple-negative breast cancer (TNBC) in the context of tumor immunity. The combined effect of C-REV and S-1 was evaluated in a bilateral tumor model of murine TNBC 4T1 in vivo. S-1 enhanced the TNBC growth inhibitory effects of C-REV, and decreased the number of tumor-infiltrating, myeloid-derived suppressor cells (MDSCs), which suppress both innate and adaptive immune responses. Moreover, C-REV alone and in combination with S-1 significantly increased the number of CD8
+ T cells in the tumor and the production of interferon γ (IFNγ) from these cells. Our findings indicate that C-REV suppresses TNBC tumor growth by inducing the expansion of effector CD8+ T cell subsets in tumors in which S-1 can inhibit MDSC function. Our study suggests that MDSCs may be an important cellular target for breast cancer treatment. The combination of C-REV and S-1 is a new approach that might be directly translated into future clinical trials against TNBC., Competing Interests: M.T. is an employee of Takara Bio Inc. The other authors declare no competing interests. The funding sponsor (Takara Bio, Inc.) had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish this paper.- Published
- 2021
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34. Authors' Reply: Development of a Rapid Intraoperative Point-of-Care Method Using Tissue Suspension to Differentiate Parathyroid Tissue: A Possible Substitute for Frozen Sections.
- Author
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Kikumori T, Shibata M, and Takeuchi D
- Subjects
- Humans, Parathyroid Glands surgery, Parathyroidectomy, Frozen Sections, Point-of-Care Systems
- Published
- 2021
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35. Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer.
- Author
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Ichikawa T, Shibata M, Inaishi T, Soeda I, Kanda M, Hayashi M, Takano Y, Takeuchi D, Tsunoda N, Kodera Y, and Kikumori T
- Subjects
- Female, Humans, Signal Transduction, Synaptotagmins genetics, Breast Neoplasms genetics, Receptors, Estrogen genetics, Receptors, Estrogen metabolism
- Abstract
Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 ( SYT13 ) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC., Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients' clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database., Results: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1 , AKT serine/threonine kinase 1 , and cyclin-dependent kinases 4 . In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients., Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways.
- Published
- 2021
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36. Identifying the tumor-progressive gene expression profile in high-risk papillary thyroid cancer.
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Shibata M, Inaishi T, Ichikawa T, Shimizu D, Soeda I, Takano Y, Takeuchi D, Tsunoda N, and Kikumori T
- Subjects
- Adult, Aged, Disease Progression, Disease-Free Survival, Female, Gene Expression, Humans, Inhibin-beta Subunits genetics, Inhibin-beta Subunits metabolism, Male, Middle Aged, Prognosis, Risk, Thyroid Cancer, Papillary mortality, Thyroid Cancer, Papillary pathology, Thyroid Neoplasms mortality, Thyroid Neoplasms pathology, Young Adult, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Chemokine CCL11 genetics, Chemokine CCL11 metabolism, Collagen Type VI genetics, Collagen Type VI metabolism, Genetic Association Studies methods, Membrane Proteins genetics, Membrane Proteins metabolism, Neoplasm Metastasis genetics, Neoplasm Metastasis pathology, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Thyroid Cancer, Papillary genetics, Thyroid Neoplasms genetics, Transcriptome genetics
- Abstract
Purpose: Papillary thyroid cancer (PTC) is generally associated with a favorable prognosis. However, some patients have fatal disease, with locally infiltrating tumors or progressive distant metastases; yet few studies have investigated the characteristics of the tumor-progressive gene expression profile in advanced PTC. We conducted this study to clarify the gene expression status in advanced PTC and identify candidate molecules for prognostic biomarkers., Methods: We analyzed 740 tumor-progressive gene expression levels from formalin-fixed paraffin-embedded blocks of samples from six patients with low-risk PTC and six patients with high-risk PTC, using the nCounter PanCancer Progression panel. Then, we investigated the association between the expression levels of focused genes and pathological factors in PTC patients in The Cancer Genome Atlas (TCGA) database., Results: The expression levels of 14 genes in the high-risk PTC specimens were more than two-fold those in the low-risk PTC specimens. In the TCGA database, expression levels of four genes (CCL11, COL6A3, INHBA, and SRPX2) were significantly higher in patients with advanced PTC. Among the patients with advanced PTC, those with high SRPX2 expression levels had poor disease-free survival. Univariate and multivariate analyses revealed that high SRPX2 expression was an independent prognostic factor., Conclusion: Based on the findings of this study, CCL11, COL6A3, INHBA, and SRPX2 are potential biomarkers that indicate advanced PTC. SRPX2, in particular, is considered a prognostic biomarker., (© 2021. Springer Nature Singapore Pte Ltd.)
- Published
- 2021
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37. The CD44/COL17A1 pathway promotes the formation of multilayered, transformed epithelia.
- Author
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Kozawa K, Sekai M, Ohba K, Ito S, Sako H, Maruyama T, Kakeno M, Shirai T, Kuromiya K, Kamasaki T, Kohashi K, Tanaka S, Ishikawa S, Sato N, Asano S, Suzuki H, Tanimura N, Mukai Y, Gotoh N, Tanino M, Tanaka S, Natsuga K, Soga T, Nakamura T, Yabuta Y, Saitou M, Ito T, Matsuura K, Tsunoda M, Kikumori T, Iida T, Mizutani Y, Miyai Y, Kaibuchi K, Enomoto A, and Fujita Y
- Subjects
- Animals, Cell Line, Dogs, Ferroptosis, Humans, Madin Darby Canine Kidney Cells, Membrane Potential, Mitochondrial, Mice, Reactive Oxygen Species, Cell Transformation, Neoplastic genetics, Epithelium growth & development, Hyaluronan Receptors metabolism, Non-Fibrillar Collagens metabolism
- Abstract
At the early stage of cancer development, oncogenic mutations often cause multilayered epithelial structures. However, the underlying molecular mechanism still remains enigmatic. By performing a series of screenings targeting plasma membrane proteins, we have found that collagen XVII (COL17A1) and CD44 accumulate in RasV12-, Src-, or ErbB2-transformed epithelial cells. In addition, the expression of COL17A1 and CD44 is also regulated by cell density and upon apical cell extrusion. We further demonstrate that the expression of COL17A1 and CD44 is profoundly upregulated at the upper layers of multilayered, transformed epithelia in vitro and in vivo. The accumulated COL17A1 and CD44 suppress mitochondrial membrane potential and reactive oxygen species (ROS) production. The diminished intracellular ROS level then promotes resistance against ferroptosis-mediated cell death upon cell extrusion, thereby positively regulating the formation of multilayered structures. To further understand the functional role of COL17A1, we performed comprehensive metabolome analysis and compared intracellular metabolites between RasV12 and COL17A1-knockout RasV12 cells. The data imply that COL17A1 regulates the metabolic pathway from the GABA shunt to mitochondrial complex I through succinate, thereby suppressing the ROS production. Moreover, we demonstrate that CD44 regulates membrane accumulation of COL17A1 in multilayered structures. These results suggest that CD44 and COL17A1 are crucial regulators for the clonal expansion of transformed cells within multilayered epithelia, thus being potential targets for early diagnosis and preventive treatment for precancerous lesions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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38. Development of a Rapid Intraoperative Point-of-Care Method Using Tissue Suspension to Differentiate Parathyroid Tissue: A Possible Substitute for Frozen Sections.
- Author
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Kikumori T, Shibata M, and Takeuchi D
- Subjects
- Humans, Japan, Parathyroidectomy, Suspensions, Frozen Sections, Point-of-Care Systems
- Abstract
Background: We reported that aspartate aminotransferase (AST)/lactate dehydrogenase (LDH) ratio of a tissue suspension can precisely differentiate normal and hyperfunctioning parathyroid tissue (PT) from other tissues. However, in these studies, LDH and AST were measured using the standard method for blood samples, with a turnaround time of approximately 1 h, hampering clinical application. Here, we developed a rapid and robust method to differentiate PT instead of using frozen sections., Methods: Excised specimens from 28 patients (n = 69) who underwent thyroid or parathyroid surgery between October 2019 and April 2020 were analyzed. AST and LDH were measured in suspensions of PT or other tissues, using both the standard method in the in-facility laboratory and a point-of-care testing device (NX500, Fujifilm, Japan)., Results and Conclusions: A good correlation was found between the standard method and NX500 for AST and LDH levels >10 IU/L. In the analyses using 52 specimens with ≥ 10 IU/L of both AST and LDH measured using the NX500, PT was distinguished with 100% sensitivity and specificity using an optimal cutoff AST/LDH ratio of 0.48. The turnaround time was estimated to be less than 10 min. This method could be a cost- and labor-effective alternative to frozen sections to reduce the incidence of postoperative hypoparathyroidism and improve the outcome of primary hyperparathyroidism in low-resource areas.
- Published
- 2021
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39. Correlation Between the Metabolic Conversion of a Capecitabine Metabolite, 5'-Deoxy-5-fluorocytidine, and Creatinine Clearance.
- Author
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Inaishi T, Fujita KI, Matsumoto N, Shimokata T, Maeda O, Kikumori T, Hattori N, Nakayama G, and Ando Y
- Subjects
- Capecitabine, Creatinine, Humans, Prospective Studies, Deoxycytidine analogs & derivatives, Fluorouracil
- Abstract
Aim: Capecitabine is a prodrug that is metabolized to its active form, 5-fluorouracil (5-FU), in three enzymatic steps. This prospective pharmacokinetic study evaluated cytidine deaminase (CDA) activity, the second drug-metabolizing enzyme that generates 5'-deoxy-5-fluorouridine (5'-DFUR) from 5'-deoxy-5-fluorocytidine (5'-DFCR), as well as creatinine clearance (CLcr)., Patients and Methods: Patients with colorectal cancer who received capecitabine plus oxaliplatin were selected. Pharmacokinetics of capecitabine and its metabolites, and CDA activity in plasma were analyzed., Results: Eighteen patients were examined. The area under the plasma concentration-time curve (AUC) of 5'-DFUR showed a significant inverse correlation with CLcr (p=0.003). The metabolic ratio, i.e. the ratios of the AUC of 5'-DFUR plus that of 5-FU to the AUC of 5'-DFCR, significantly increased when CLcr decreased (p=0.001) but did not depend on plasma CDA activity., Conclusion: Metabolism of 5'-DFCR to form 5'-DFUR increased as CLcr decreased but the mechanism remains unknown., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2020
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40. Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases.
- Author
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Shizuku M, Shibata M, Okumura M, Takeuchi D, Kikumori T, and Mizuno Y
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bone Density Conservation Agents administration & dosage, Bone Neoplasms drug therapy, Bone Neoplasms secondary, Bone Neoplasms urine, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Breast Neoplasms urine, Denosumab administration & dosage, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Middle Aged, Radionuclide Imaging, Retrospective Studies, Risk Assessment methods, Biomarkers, Tumor urine, Bone Neoplasms mortality, Breast Neoplasms mortality, Collagen Type I urine, Peptides urine
- Abstract
Background: Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab., Methods: Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1 month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis., Results: Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0 months; high group 54.0 months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028)., Conclusion: We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.
- Published
- 2020
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41. MZB1 expression indicates poor prognosis in estrogen receptor-positive breast cancer.
- Author
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Watanabe M, Shibata M, Inaishi T, Ichikawa T, Soeda I, Miyajima N, Takano Y, Takeuchi D, Tsunoda N, Kanda M, Kikumori T, Kodera Y, and Nagino M
- Abstract
Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, MZB1 mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. MZB1 mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of MZB1 mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker., (Copyright: © Watanabe et al.)
- Published
- 2020
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42. Measurement of the AST to LD Ratio in Parathyroid Tissue Suspension Can Precisely Differentiate a Hyperfunctioning Parathyroid.
- Author
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Kikumori T, Ichikawa T, Inaishi T, Miyajima N, Shibata M, and Takeuchi D
- Subjects
- Adipose Tissue pathology, Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Feasibility Studies, Female, Humans, Hyperparathyroidism, Primary etiology, Hyperparathyroidism, Primary physiopathology, Hyperparathyroidism, Primary surgery, Male, Middle Aged, Parathyroid Glands physiopathology, Parathyroid Neoplasms complications, Parathyroid Neoplasms pathology, Parathyroid Neoplasms physiopathology, Parathyroidectomy, Prospective Studies, ROC Curve, Reference Values, Suspensions, Thyroid Gland pathology, Aspartate Aminotransferases analysis, Diagnostic Techniques, Endocrine, Hyperparathyroidism, Primary diagnosis, L-Lactate Dehydrogenase analysis, Parathyroid Glands pathology, Parathyroid Neoplasms diagnosis
- Abstract
Background: Frozen section of excised tissue is used to confirm removal of the etiology of primary hyperparathyroidism in the current era of intraoperative parathyroid hormone measurement and provides safeguards for surgeons. We recently reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LD) ratio in tissue suspension can accurately distinguish normal parathyroid tissue from other tissues. Therefore, we hypothesized that this ratio may also be applied to distinguish hyperfunctioning parathyroid tissue (HPT) from other tissues., Methods: We prospectively analyzed 22 patients who underwent parathyroidectomy for primary hyperparathyroidism (benign, 21; malignant, 1) from July 2018 to October 2019. In total, 27 specimens were examined. Approximately 1 mm3 of minced HPT as confirmed by frozen sections was suspended in 1 mL of normal saline and AST and LD levels were measured. The AST/LD ratios of other tissues (normal parathyroid tissue, thyroid gland, adipose tissue, and others; n = 94) were obtained from our previous report., Results: The AST/LD ratio of benign HPT was consistently higher than that of other tissues (P < 0.001). The optimal cut-off value was 0.36 according to the receiver operating characteristic curve, with 100% sensitivity and specificity. The AST/LD ratio in malignant HPT was also markedly lower than that in benign HPT., Conclusion: This method might be a new adjunct for intraoperative differentiation of HPT with an accuracy and turnaround time comparable with those of frozen sections, minimal cost, and no need for dedicated pathological staff. Additionally, this method might increase the treatment success rate in settings with limited medical resources., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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43. A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 10-year results with critical evaluation.
- Author
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Kawamura M, Itoh Y, Kamomae T, Sawaki M, Kikumori T, Tsunoda N, Ito J, Shimoyama Y, Satake H, and Naganawa S
- Subjects
- Aged, Asian People, Combined Modality Therapy, Contrast Media, Female, Follow-Up Studies, Humans, Intraoperative Care methods, Intraoperative Period, Magnetic Resonance Imaging, Mammography, Mastectomy, Segmental adverse effects, Mastectomy, Segmental methods, Middle Aged, Neoplasm Recurrence, Local, Prospective Studies, Radiotherapy Dosage, Ultrasonography, Mammary, Breast Neoplasms radiotherapy, Radiotherapy methods
- Abstract
Although phase III trials have been published comparing whole breast irradiation (WBI) with accelerated partial breast irradiation (APBI) using intraoperative radiotherapy (IORT), long-term follow-up results are lacking. We report the 10-year follow-up results of a prospective phase I/II clinical trial of IORT. The inclusion criteria were as follows: (i) tumor size <2.5 cm, (ii) desire for breast-conserving surgery, (iii) age >50 years, (iv) negative margins after resection and (v) sentinel lymph node-negative disease. A single dose of IORT (19-21 Gy) was delivered to the tumor bed in the operation room just after wide local excision of the primary breast cancer using a 6-12 MeV electron beam. Local recurrence was defined as recurrence or new disease within the treated breast and was evaluated annually using mammography and ultrasonography. A total of 32 patients were eligible for evaluation. The median patient age was 65 years and the median follow-up time was 10 years. Two patients experienced local recurrence just under the nipple, out of the irradiated field, after 8 years of follow-up. Three patients had contralateral breast cancer and one patient experienced bone metastasis after 10 years of follow-up. No patient experienced in-field recurrence nor breast cancer death. Eight patients had hypertrophic scarring at the last follow-up. There were no lung or heart adverse effects. This is the first report of 10-year follow-up results of IORT as APBI. The findings suggest that breast cancer with extended intraductal components should be treated with great caution., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)
- Published
- 2020
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44. Clinical value of serum bone resorption markers for predicting clinical outcomes after use of bone modifying agents in metastatic bone tumors: A prospective cohort study.
- Author
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Urakawa H, Ando Y, Hase T, Kikumori T, Arai E, Maeda O, Mitsuma A, Sugishita M, Shimokata T, Ikuta K, Ishiguro N, and Nishida Y
- Subjects
- Adult, Aged, Aged, 80 and over, Bone Neoplasms blood, Bone Neoplasms prevention & control, Bone Neoplasms secondary, Bone Resorption blood, Bone Resorption prevention & control, Collagen Type I blood, Denosumab administration & dosage, Disease Progression, Female, Follow-Up Studies, Humans, Japan epidemiology, Kaplan-Meier Estimate, Lung Neoplasms blood, Lung Neoplasms mortality, Lung Neoplasms therapy, Male, Middle Aged, Peptides blood, Prognosis, Prospective Studies, Tartrate-Resistant Acid Phosphatase blood, Zoledronic Acid administration & dosage, Biomarkers, Tumor blood, Bone Density Conservation Agents administration & dosage, Bone Neoplasms epidemiology, Bone Resorption diagnosis, Lung Neoplasms pathology
- Abstract
Bone modifying agents (BMAs) have become a standard treatment to prevent skeletal-related events (SREs) in bone metastases (BMs). The aim of our study is to determine the clinical value of serum bone resorption markers for predicting clinical outcomes after using BMAs in patients with BM. Patients were enrolled between May 2013 and October 2017 at the Nagoya University Hospital, Japan. We prospectively observed changes in pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) during treatment with BMAs. The relationship between serum markers before and after treatment and clinical outcomes such as progression of bone disease (BD), SREs and overall survival (OS) were evaluated. Pearson chi-square test and Kaplan-Meier product limit methods were used for analysis. Sixty-seven patients were analyzed. The primary tumor sites were 21 lung, 16 breast and 30 others. Forty and 27 patients were treated with Denosumab and Zoledronic acid, respectively. Progression of BDs, SREs and death were observed in 10, 16 and 31 cases, respectively. The median follow-up period after using BMAs was 12.3 (range 0.3-66.3) months. ICTP at 3-4 weeks was significantly correlated with increasing BD progression, SREs and death after treatment in both the whole and lung cancer cohorts. Base line ICTP and TRACP-5b were also associated with increasing BD progression in the whole cohort. Our study showed that early posttreatment ICTP is useful for predicting BD progression, SREs and OS after use of BMAs in patients with BM and even in patients with lung cancer BM., (© 2019 UICC.)
- Published
- 2020
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45. Frequent FOXA1 -Activating Mutations in Extramammary Paget's Disease.
- Author
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Takeichi T, Okuno Y, Matsumoto T, Tsunoda N, Suzuki K, Tanahashi K, Kono M, Kikumori T, Muro Y, and Akiyama M
- Abstract
Extramammary Paget's disease (EMPD) is a neoplastic skin disease of indeterminate origin with an unknown genetic cause. We performed a comprehensive genetic analysis or targeted gene sequencing in 48 patients with EMPD. We identified FOXA1 mutations, a GAS6-FOXA1 fusion gene, and somatic hotspot mutations in the FOXA1 promoter region in 11 of the 48 EMPD patients (11/48, 23%). Additional mutations were identified in PIK3CA (six patients) and in HIST1H2BB , HIST1H2BC , and SMARCB1 (one patient each), but none were found in other frequently mutated genes in cancer. A global gene expression analysis using EMPD clinical samples found the upregulation of PI3 kinase-AKT-mTOR signaling. ABCC11 , which is specifically expressed in the apocrine secretory cells and is necessary for their sweat secretion, was upregulated in the EMPD samples. This upregulation suggests that Paget cells originate from apocrine secretory cells. Immunohistochemical staining revealed that FOXA1 expression was prevalent in all of the EMPD samples analyzed and was associated with estrogen receptor expression. Our genetic analysis indicates that EMPD frequently involves FOXA1 mutations. FOXA1 is a transcriptional pioneer factor for the estrogen receptor, and the present results suggest that certain treatments for hormone-dependent cancers could be effective for EMPD.
- Published
- 2020
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46. Robust, quick, and convenient intraoperative method to differentiate parathyroid tissue.
- Author
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Kikumori T, Inaishi T, Miyajima N, Shibata M, and Takeuchi D
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Aspartate Aminotransferases analysis, L-Lactate Dehydrogenase analysis, Parathyroid Glands enzymology, Parathyroidectomy methods
- Abstract
Background: Identification of parathyroid tissue during surgery is necessary for its preservation in situ or for autotransplantation to avoid postoperative hypoparathyroidism. Frozen sections are the gold standard for distinguishing parathyroid tissue from other tissues during thyroidectomy. Although frozen sections are very accurate, they are costly and require pathologists and technical staff. Parathyroid tissue is rich in mitochondria, which harbor Krebs-cycle enzymes such as aspartate aminotransferase. In contrast, lactate dehydrogenase is expressed ubiquitously. These 2 enzymes are measured routinely as "leaked" enzymes. We hypothesized that the aspartate aminotransferase-to-lactate dehydrogenase ratio in suspended tissue could distinguish parathyroid tissue from other tissues., Methods: We analyzed 94 specimens (43 parathyroid, 19 thyroid cancers, 13 normal lymph nodes, 10 adipose, 6 thyroid, and 3 miscellaneous tissues) from 55 patients who underwent thyroid or parathyroid surgery between March 2018 and June 2019 in our institution. Trace amounts of remnant parathyroid tissue from autotransplantation specimens were suspended in 1 mL of normal saline and measured for aspartate aminotransferase and lactate dehydrogenase. Approximately 1 mm
3 of apparently distinct tissue minced by scissors (eg, thyroid gland, metastatic lymph node, etc) or washouts of needles used for preoperative aspiration biopsy were also measured for comparison., Results: The aspartate aminotransferase-to-lactate dehydrogenase ratios in suspended parathyroid tissue specimens were consistently greater than those of other tissues (P < .001, Mann-Whitney test); 0.27 was the optimal cutoff value with 100% sensitivity and specificity., Conclusion: This method distinguished parathyroid tissue quickly and conveniently from other tissues intraoperatively with minimum cost and without dedicated pathologic staff. This methodology may serve useful in decreasing the incidence of postoperative hypoparathyroidism, especially in settings with limited access to pathologists., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2020
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47. Multicenter Phase II Study of Intraoperative Radiotherapy of Early Breast Cancer: Ipsilateral Tumor Recurrence.
- Author
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Sawaki M, Miyamoto T, Fujisawa T, Itoh Y, Ebara T, Tachibana H, Kodaira T, Kikumori T, Yanagita Y, and Iwata H
- Subjects
- Adenocarcinoma, Mucinous pathology, Adenocarcinoma, Mucinous radiotherapy, Adenocarcinoma, Mucinous surgery, Aged, Breast Neoplasms pathology, Breast Neoplasms surgery, Carcinoma, Ductal, Breast pathology, Carcinoma, Ductal, Breast surgery, Carcinoma, Lobular pathology, Carcinoma, Lobular radiotherapy, Carcinoma, Lobular surgery, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Incidence, Japan epidemiology, Middle Aged, Neoplasm Invasiveness, Neoplasm Recurrence, Local pathology, Prognosis, Breast Neoplasms radiotherapy, Carcinoma, Ductal, Breast radiotherapy, Intraoperative Care, Mastectomy, Segmental methods, Neoplasm Recurrence, Local epidemiology, Radiotherapy, Adjuvant methods
- Abstract
Background: We performed a multicenter phase II study on the efficacy and safety of intraoperative radiotherapy (IORT) as partial breast irradiation using multiple devices., Methods: The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Key inclusion criteria were T < 2.5 cm, age > 50 years, surgical margin > 1 cm, intraoperative pathologically free margins, and sentinel node negative. After resection of the tumor, radiation at 21 Gy was delivered directly to the mammary gland employing an electron linear accelerator in the operating room, otherwise the patient was transported from the surgical suite to the radiation room., Results: Overall, 142 patients were enrolled in this study and 129 underwent IORT. Stage 0: n = 4 (3.1%); stage I: n = 98 (76.0%); and stage IIA: n = 27 (20.9%). Luminal type: n = 116 (89.9%); triple-negative: n = 9 (7.0%); and human epidermal growth factor receptor 2: n = 4 (3.1%). Median follow-up time was 59.5 months (range 27.5-99.0), and the rate of IBTR was 3.1% (95% confidence interval 0.9-7.8). The toxicities included fibrosis in deep-connective tissue: grade 1, 78.1%; wound infection: grade 3, 1.6% and grade 2, 1.6%; and soft tissue necrosis: grade 3, 0.8% and grade 2, 0.8%. Recurrence in the breast occurred in four cases; the site of recurrence was just under the skin near the primary tumor site, with similar histology and subtype., Conclusions: In this multicenter phase II study, the rate of IBTR was low and IORT at 21 Gy was feasible in properly selected patients. It is important to use a careful surgical technique to reduce local recurrence because the skin is not included in the radiation field of IORT.
- Published
- 2019
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48. RASEF expression correlates with hormone receptor status in breast cancer.
- Author
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Shibata M, Kanda M, Shimizu D, Tanaka H, Umeda S, Miwa T, Hayashi M, Inaishi T, Miyajima N, Adachi Y, Takano Y, Nakanishi K, Takeuchi D, Noda S, Kodera Y, and Kikumori T
- Abstract
Breast cancer (BC) is the most frequently diagnosed malignant tumor in women worldwide, and the development of new molecules associated with BC is essential for the management of this disease. RAS and EF-hand domain-containing ( RASEF ) encodes the GTPase enzyme that belongs to the Rab family. Although the effects of this gene have been reported in several malignant tumor types, the role of RASEF in BC has not been completely elucidated. The aim of the present study was to investigate the importance of RASEF expression in BC. RASEF mRNA expression levels were evaluated in BC and non-cancerous mammary cell lines. The association between RASEF mRNA expression levels and clinicopathological factors in 167 patients with BC were then determined. Among the 13 examined BC cell lines, ER-negative/HER2-negative cell lines expressed lower RASEF mRNA levels, when compared with the other examined cell lines (P=0.014). Of the 167 patients examined, patients with negative hormone receptor status exhibited significantly lower RASEF mRNA expression levels (P<0.001). In addition low RASEF expression in BC tissues was associated with negative estrogen receptor status (P<0.001), negative progesterone receptor status (P<0.001), and triple-negative status (P<0.001). Additionally, although the differences were not statistically significant, patients with low RASEF expression levels exhibited poorer disease-free survival (P=0.123) and overall survival (P=0.086) than other patients. The results of the present study indicate that RASEF mRNA expression levels are associated with hormone receptor status in BC.
- Published
- 2018
- Full Text
- View/download PDF
49. Impact of Patient Age and Histological Type on Radioactive Iodine Avidity of Recurrent Lesions of Differentiated Thyroid Carcinoma.
- Author
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Nakanishi K, Kikumori T, Miyajima N, Takano Y, Noda S, Takeuchi D, Iwano S, and Kodera Y
- Subjects
- Adenocarcinoma, Follicular diagnostic imaging, Adenocarcinoma, Follicular epidemiology, Adenocarcinoma, Follicular pathology, Adult, Age Factors, Aged, Carcinoma, Papillary diagnostic imaging, Carcinoma, Papillary epidemiology, Carcinoma, Papillary pathology, Female, Humans, Lung Neoplasms secondary, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Recurrence, Local diagnostic imaging, Thyroid Cancer, Papillary, Thyroid Neoplasms diagnostic imaging, Thyroid Neoplasms epidemiology, Thyroid Neoplasms pathology, Adenocarcinoma, Follicular radiotherapy, Carcinoma, Papillary radiotherapy, Iodine Radioisotopes therapeutic use, Lung Neoplasms epidemiology, Neoplasm Recurrence, Local epidemiology, Radiopharmaceuticals therapeutic use, Thyroid Neoplasms radiotherapy
- Abstract
Background: Age is a prognostic factor for recurrent differentiated thyroid carcinoma (DTC) and may be related to radioactive iodine (RAI) nonavidity. Indications for molecular-targeted drugs (MTDs) are currently limited to RAI-refractory DTC. Demonstrating refractoriness to RAI, mainly indicated by RAI nonavidity, may be a barrier to the introduction of MTDs for elderly patients. The present study was conducted to evaluate the impact of age and histological type on the RAI avidity of recurrent lesions of DTC., Methods: Two hundred fifty-eight patients (189 patients with classic papillary thyroid carcinoma [cPTC], 8 patients with follicular variant of papillary thyroid carcinoma, and 61 patients with follicular thyroid carcinoma), who underwent their first RAI whole-body scanning for recurrent DTC at our institution between 2004 and 2013, were retrospectively studied. Radioactive iodine uptake was determined by visible uptake by metastatic lesion(s) in a diagnostic RAI-whole-body scan., Results: The prevalence of RAI-avid lung metastases in cPTC indicated a significant, inverse correlation with age (<55 years, 36.2%; ≥55 years, 3%; P < 0.001). By contrast, for follicular thyroid carcinoma, the prevalence of RAI avidity was not influenced by age. Similar tendencies were observed for lymph node metastases., Conclusions: Radioactive iodine avidity by metastatic lesions of cPTC in elderly patients, especially those older than 55 years, was seldom demonstrated. Adherence to a strategy of restricting MTD administration after confirmation of RAI refractoriness should be revisited for elderly patients. A strategy of omitting RAI treatment should be taken into account when considering age and histological type.
- Published
- 2018
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50. Obesity does not affect peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy.
- Author
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Inaishi T, Kikumori T, Takeuchi D, Ishihara H, Miyajima N, Shibata M, Takano Y, Nakanishi K, Noda S, and Kodera Y
- Subjects
- Adolescent, Adult, Aged, Body Mass Index, Female, Humans, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Treatment Outcome, Young Adult, Adrenal Glands surgery, Adrenalectomy methods, Laparoscopy methods, Obesity complications, Obesity surgery
- Abstract
Laparoscopic adrenalectomy is the gold standard procedure for most adrenal tumors. Obesity is considered as a risk factor for surgical complications. This study aimed to evaluate whether obesity affects peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy using body mass index (BMI). This retrospective study included 98 patients who underwent transabdominal laparoscopic adrenalectomy between January 2011 and December 2016. We divided the patients into 2 groups: non-obese group (BMI < 25 kg/m2) and obese group (BMI ≥ 25 kg/m2). We assessed perioperative outcomes and postoperative complications between the groups. A total of 98 patients were analyzed (70 without obesity and 28 with obesity). There were no significant differences between the non-obese and obese groups regarding operative time (111 vs 107 min; p = 0.795), blood loss (3.5 vs 3.5 ml; p = 0.740), rate of placement of additional trocars (14.3% vs 17.9%; p = 0.657), rate of open conversion (2.6% vs 3.6%; p = 0.853), and postoperative length of hospital stay (6 vs 5 days; p = 0.237). Furthermore, obesity was not a significant risk factor for postoperative complications (postoperative bleeding, wound infection, and pneumonia). There are no significant differences in peri- and postoperative outcomes of transabdominal laparoscopic adrenalectomy in patients with obesity compared with those without obesity. Transabdominal laparoscopic adrenalectomy is feasible and safe for patients with obesity.
- Published
- 2018
- Full Text
- View/download PDF
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