研究者詳細 - 宮田　一志

論文 - 宮田　一志

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Risk Factors for Muscle Loss During Neoadjuvant Therapy for Esophageal Cancer. 国際誌

Shimizu D, Miyata K, Fukaya M, Sugita S, Ebata T

Anticancer research 43 巻 ( 3 ) 頁： 1309 - 1315 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Anticancer Research

Background/Aim: In patients with esophageal cancer, muscle loss induced by neoadjuvant therapy before esophagectomy is correlated with poor prognosis. However, little is known about the causes of muscle loss. Thus, the purpose of this retrospective study was to clarify the risk factors for muscle loss during neoadjuvant therapy. Patients and Methods: Patients with esophageal cancer who underwent neoadjuvant therapy before esophagectomy between 2009 and 2020 were investigated (n=132). The patients received either cisplatin plus 5-fluorouracil (CF); docetaxel, cisplatin plus 5-fluorouracil (DCF); or CF with radiotherapy as neoadjuvant therapy. The cross-sectional areas of the bilateral psoas muscles were measured at the level of the third lumbar vertebra using CT, before and after neoadjuvant therapy, and psoas muscle loss was calculated. The patients were divided into the high muscle loss group with 5% or more muscle loss or the low muscle loss group with less than 5% loss. Correlations between muscle loss and clinical factors were evaluated. Results: The median value of psoas muscle loss was 5.30%. Psoas muscle loss was significantly correlated with a poor 3-year overall survival rate (p=0.034). Multivariate analysis showed that the independent factors associated with muscle loss were age ≥70 years [odds ratio (OR)=2.43, p=0.022], treatment with DCF (OR=3.47, p=0.034), and a poor response to neoadjuvant therapy (OR=2.68, p=0.028). Conclusion: A regimen of DCF was a major trigger of muscle loss during neoadjuvant therapy.

DOI： 10.21873/anticanres.16278

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PubMed

Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer. 国際誌

Kano MT, Kokuryo T, Baba T, Yamazaki K, Yamaguchi J, Sunagawa M, Ogura A, Watanabe N, Onoe S, Miyata K, Mizuno T, Uehara K, Igami T, Yokoyama Y, Ebata T, Nagino M

Anticancer research 43 巻 ( 3 ) 頁： 1009 - 1016 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Anticancer Research

Background/Aim: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α- bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. Materials and Methods: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). Results: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CDBSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEMtreated groups. Conclusion: We clarified the efficiency of CDBSB in xenograft tumor using intravenous administration. α- Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α- bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

DOI： 10.21873/anticanres.16245

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Antitumor Effects of Deep Ultraviolet Irradiation for Pancreatic Cancer. 国際誌

Yamazaki K, Kokuryo T, Yamaguchi J, Sunagawa M, Ogura A, Watanabe N, Onoe S, Miyata K, Mizuno T, Uehara K, Igami T, Yokoyama Y, Ebata T, Nagino M

Anticancer research 43 巻 ( 2 ) 頁： 621 - 630 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Anticancer Research

Background/Aim: Deep ultraviolet (DUV) light spans within the 250 nm to 350 nm invisible wavelength range. Although it strongly damages various cells, the efficacy of DUV irradiation on pancreatic cancer cells has never been clarified. The purpose of this study was to reveal the antitumor effects of DUV irradiation on pancreatic cancer cells. Materials and Methods: Human pancreatic cancer cell lines were eradicated with DUV or ultraviolet A (UVA) for 5 s. Several angiogenesis-related proteins were studied in cancer cells after DUV irradiation using a protein antibody array. A subcutaneous xenograft model was established by inoculation of pancreatic cancer cells into mice. Tumors in this model were irradiated with DUV or UVA once or twice for two weeks. Tumor volumes in these groups (DUV×1: one irradiation, DUV×2: two irradiations, and untreated) were analyzed one week after the second irradiation. Results: DUV irradiation significantly changed the cytomorphology of pancreatic cancer cells. In addition, DUV irradiation induced apoptosis on pancreatic cancer cells more strongly than UVA irradiation and no irradiation. Interestingly, lower expression of thrombospondin 1 (TSP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was identified after DUV treatment. The tumor volume in the DUV-treated groups (DUV×1 and DUV×2) was smaller than that in the untreated group. Conclusion: Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

DOI： 10.21873/anticanres.16198

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PubMed

Correlation of Brain Metastasis Shrinking and Deviation During 10-Fraction Stereotactic Radiosurgery With Late Sequela: Suggesting Dose Ramification Between Tumor Eradication and Symptomatic Radionecrosis. 国際誌

Ohtakara K, Tanahashi K, Kamomae T, Miyata K, Suzuki K

Cureus 15 巻 ( 1 ) 頁： e33411 2023年1月

Proposal for Shape Memory Alloy Positioning Actuator using Electric Parameter Based Controller

Miyata K., Kawazoe Y., Hara S.

IEEJ Journal of Industry Applications 12 巻 ( 2 ) 頁： 153 - 154 2023年

出版者・発行元：IEEJ Journal of Industry Applications

This paper proposes the controller design for a shape memory alloy (SMA) positioning actuator system. The system utilizes spiral-formed SMA wire as the driving power source. SMA generates force via temperature-based crystalline phase transitions. The wire is deformed in the spiral form under low temperature and heated by applying direct current, it recovers to the original form and generates the recovering force, which rotates the attached load. This paper proposes using the electric resistance of the SMA, which is related to its crystalline phase status, for designing the controller of the actuator system. The feasibility of the proposed system and controller design are evaluated experimentally with a sample test device, manufactured using a 3D printer, and the device achieves the designed rotation.

DOI： 10.1541/ieejjia.L22000583

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Preoperative docetaxel, cisplatin, and fluorouracil treatment with pegfilgrastim on day 7 for patients with esophageal cancer: A phase II study. 国際誌

Maeda O, Fukaya M, Koike M, Miyata K, Kanda M, Nishida K, Ando M, Kodera Y, Ando Y

Asia-Pacific journal of clinical oncology 18 巻 ( 6 ) 頁： 578 - 585 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Asia-Pacific Journal of Clinical Oncology

Aims: The docetaxel and cisplatin plus 5-fluorouracil (5-FU) (DCF) regimen is expected to be superior to cisplatin plus 5-FU for the preoperative treatment of esophageal cancer. However, a high risk of adverse effects, including febrile neutropenia (FN), has been reported. To evaluate the effectiveness and safety of DCF with prophylactic pegfilgrastim, we conducted a phase II study. Methods: The regimen consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and a continuous infusion of 5-FU (750 mg/m2 per day) on days 1–5. A single 3.6-mg dose of pegfilgrastim was given as a subcutaneous injection on day 7 of each cycle. This regimen was repeated every 3 weeks for a maximum of three cycles. The primary endpoint was the grade-2/3 histopathological response rate. Results: Thirty-seven eligible patients were enrolled and received DCF. Thirty-four patients underwent esophagectomy. Two patients received chemoradiotherapy or radiotherapy without surgery. One patient withdrew consent and ended his hospital visit. One patient received additional radiotherapy before surgery. Histopathological responses of grade 3, grade 2, grade 1b, and grade 1a were observed in two (5.4%), 14 (37.8%), 10 (27.0%), and seven (18.9%) patients, respectively, and the primary endpoint was met. Of the 37 eligible patients, 11 (29.7%) developed FN in the first cycle. Conclusions: Since the histopathological responses were as expected, DCF with prophylactic pegfilgrastim is considered to be effective as preoperative chemotherapy. However, the prophylactic use of pegfilgrastim on day 7 was insufficient to prevent FN.

DOI： 10.1111/ajco.13755

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PubMed

Early volume loss of skeletal muscle after esophagectomy: a risk for late-onset postoperative pneumonia. 国際誌

Nishimura K, Miyata K, Fukaya M, Yokoyama Y, Uehara K, Yamaguchi J, Mizuno T, Onoe S, Ogura A, Ebata T

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 35 巻 ( 11 ) 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Diseases of the Esophagus

Late-onset postoperative pneumonia (LOPP) after esophagectomy is poorly understood. This study was designed to clarify the features and risk factors for this event. Patients who underwent esophagectomy for esophageal cancer between 2006 and 2016 were included. LOPP was defined as radiologically proven pneumonia that occurred over 3 months after surgery, and clinically relevant late-onset postoperative pneumonia (CR-LOPP) was defined as LOPP that required administration of oxygen and antibiotics in the hospital and/or more intensive treatment. The total psoas muscle area (TPA) was measured using preoperative and postoperative (at 3 months after surgery) computed tomography scan images. Potential risk factors for CR-LOPP were investigated. Among 175 study patients, 46 (26.3%) had LOPP, 29 (16.6%) of whom exhibited CR-LOPP with a cumulative incidence of 15.6% at 3 years and 22.4% at 5 years. Four (13.8%) of these patients died of LOPP. Univariable analysis showed that clinical stage ≥III (P = 0.005), preoperative prognostic nutritional index (PNI) <45 (P = 0.035), arrhythmia (P = 0.014), postoperative hospital stay ≥40 days (P = 0.003), and percent decrease of TPA more than 5% (P < 0.001) were associated with CR-LOPP but not early onset postoperative pneumonia. Multivariable analysis revealed that clinical stage ≥III (hazard ratio [HR] 3.01, P = 0.004), postoperative hospital stay ≥40 days (HR 2.51, P = 0.015), and percent decrease of TPA >5% (HR 9.93, P < 0.001) were independent risk factors for CR-LOPP. CR-LOPP occurred in over 20% of patients at 5 years, and early postoperative loss of TPA was a potential trigger for this delayed complication.

DOI： 10.1093/dote/doac019

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PubMed

Trefoil factor 1 inhibits the development of esophageal adenocarcinoma from Barrett's epithelium. 国際誌

Hasebe K, Yamazaki K, Yamaguchi J, Kokuryo T, Yokoyama Y, Miyata K, Fukaya M, Nagino M, Ebata T

Laboratory investigation; a journal of technical methods and pathology 102 巻 ( 8 ) 頁： 885 - 895 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Laboratory Investigation

Trefoil factor family 1 (TFF1) is one of three members of the trefoil factor family that are abundantly expressed in the gastrointestinal mucosal epithelium. Recent studies have shown that TFF1 acts as a tumor suppressor in gastric, pancreatic and hepatocellular carcinogenesis; however, little is known about its function in esophageal carcinogenesis, especially in esophageal adenocarcinoma (EAC). Barrett’s epithelium is the metaplastic columnar epithelium of the esophagus and a known premalignant lesion of EAC. To investigate the role of TFF1 in EAC development, a mouse model of Barrett’s epithelium was employed, and human specimens of EAC were assessed by immunohistochemistry (IHC) and methylation-specific PCR. Wild-type (WT) mice underwent gastrojejunostomy on the forestomach, resulting in the development of Barrett’s epithelium-like (BE-like) epithelium adjacent to the anastomotic site. BE-like epithelium in these mice expressed TFF1, indicating the association of TFF1 with esophageal adenocarcinoma. TFF1-knockout (TFF1KO) mice underwent the same procedure as well, revealing that a deficiency in TFF1 resulted in the development of adenocarcinoma in the anastomotic site, presumably from BE-like epithelium. IHC of human samples revealed strong TFF1 expression in Barrett’s epithelium, which was lost in some EACs, confirming the association between TFF1 and EAC development. Aberrant DNA hypermethylation in TFF1 promoter lesions was detected in TFF1-negative human EAC samples, further confirming not only the role of TFF1 in EAC but also the underlying mechanisms of TFF1 regulation. In addition, IHC revealed the nuclear translocation of β-catenin in human and mouse EAC, suggesting that activation of the Wnt/β-catenin pathway was induced by the loss of TFF1. In conclusion, these results indicate that TFF1 functions as a tumor suppressor to inhibit the development of esophageal carcinogenesis from Barrett’s epithelium.

DOI： 10.1038/s41374-022-00771-1

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PubMed

村田悠記, 上原圭, 小倉淳司, 杉田静紀, 渡辺伸元, 砂川真輝, 尾上俊介, 宮田一志, 山口淳平, 水野隆史, 伊神剛, 國料俊男, 横山幸浩, 江畑智希

臨床外科 77 巻 ( 5 ) 頁： 514 - 519 2022年5月

【本邦の大腸癌治療の現状と展望-海外における標準治療と比較して】局所再発に対する治療選択と実践

上原圭, 小倉淳司, 村田悠記, 渡辺伸元, 砂川真輝, 尾上俊介, 宮田一志, 山口淳平, 水野隆史, 伊神剛, 國料俊男, 横山幸浩, 江畑智希

日本外科学会雑誌 123 巻 ( 3 ) 頁： 255 - 261 2022年5月

【本邦の大腸癌治療の現状と展望-海外における標準治療と比較して】局所再発に対する治療選択と実践

上原圭, 小倉淳司, 村田悠記, 渡辺伸元, 砂川真輝, 尾上俊介, 宮田一志, 山口淳平, 水野隆史, 伊神剛, 國料俊男, 横山幸浩, 江畑智希

日本外科学会雑誌 123 巻 ( 3 ) 頁： 255 - 261 2022年5月

記述言語：日本語出版者・発行元：(一社)日本外科学会

局所再発直腸癌に対する治療戦略はその病態の不均一性から治療は個々の症例に応じて選択すべきである.そのためには,手術技術を磨くことは当然のことであるが,近年発達著しい集学的治療の知識を身に着け,経験を積むことが必要不可欠である.性質上,無作為化比較試験からの情報を得ることが難しく,多くがセンター施設での経験に基づく指針ではあるが,本稿では,本邦および海外での局所再発直腸癌治療の現状と展望を述べる.(著者抄録)

小細胞癌成分を含む胆管癌の2切除例

南貴之, 水野隆史, 山口淳平, 尾上俊介, 渡辺伸元, 伊神剛, 上原圭, 宮田一志, 横山幸浩, 江畑智希

日本消化器外科学会雑誌 55 巻 ( 4 ) 頁： 240 - 250 2022年4月

記述言語：日本語出版者・発行元：一般社団法人日本消化器外科学会

<p>外科的切除後に対照的な経過を呈した胆管小細胞癌の2例を経験した．症例1は70歳の男性で，肝門部領域胆管癌に対して肝左葉尾状葉切除，肝外胆管切除を施行した．病理組織学的に乳頭腺癌と小細胞癌が混在する腺神経内分泌癌を認め，小細胞癌成分の静脈侵襲を認めた．進行度はpT2N0M0，fStage IIであった．術後にゲムシタビン単独療法を行ったが，術後4か月目に多発肝再発を認め，5か月目に原病死した．症例2は65歳の男性で，遠位胆管癌に対して亜全胃温存膵頭十二指腸切除を施行した．病理組織学的に神経内分泌癌（小細胞癌）を認め，進行度はpT2N1M0，fStage IIIと診断された．術後に，肺小細胞癌に準じてシスプラチン+エトポシド併用療法を4コース投与した．現在，術後8年無再発生存中である．胆管小細胞癌は根治切除後も早期再発する例が多く，肺小細胞癌に準じた薬物治療を含む集学的治療が必要である．</p>

DOI： 10.5833/jjgs.2021.0083

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CiNii Research

切除可能同時性肝転移症例の治療戦略肝実質温存術式の有用性

三品拓也, 水野隆史, 上原圭, 小倉淳司, 村田悠記, 小池佳勇, 神原祐一, 西村元伸, 小林龍太朗, 服部憲史, 中山吾郎, 國料俊男, 伊神剛, 山口淳平, 宮田一志, 尾上俊介, 砂川真輝, 渡辺伸元, 横山幸浩, 江畑智希

日本外科学会定期学術集会抄録集 122回巻頁： SF - 7 2022年4月

悪性転化した仙尾部奇形腫の2例

西村元伸, 上原圭, 小倉淳司, 村田悠記, 三品拓也, 小池佳勇, 神原祐一, 小林龍太朗, 神野孝徳, 國料俊男, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 砂川真輝, 渡辺伸元, 杉田静紀, 横山幸浩, 江畑智希

日本外科学会定期学術集会抄録集 122回巻頁： DP - 8 2022年4月

特集胆道癌治療の最前線 II. 各論 4.肝外胆管癌に対する手術術式と適応

尾上俊介, 水野隆史, 渡辺伸元, 横山幸浩, 國料俊男, 伊神剛, 上原圭, 山口淳平, 宮田一志, 砂川真輝, 小倉淳司, 江畑智希

外科 84 巻 ( 2 ) 頁： 136 - 141 2022年2月

Neoadjuvant docetaxel, oxaliplatin plus S-1 for treating clinical stage III squamous cell carcinoma of the esophagus: Study protocol of an open-label phase II trial. 国際誌

Kanda M, Shimizu D, Miyata K, Maeda O, Tanaka C, Inokawa Y, Hattori N, Hayashi M, Ando M, Kuwatsuka Y, Murotani K, Nakayama G, Koike M, Ando Y, Ebata T, Kodera Y

Contemporary clinical trials communications 24 巻頁： 100853 - 100853 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Contemporary Clinical Trials Communications

In Japan, esophagectomy after two courses of 5-fluorouracil plus cisplatin is regarded a standard strategy for treating resectable stage II or III esophageal squamous cell carcinoma (ESCC). However, 5-fluorouracil plus cisplatin does not benefit cohorts with clinical stage III ESCC, suggesting the requirement for a more effective regimen. We are conducting a single-arm phase II study to assess the safety and efficacy of neoadjuvant docetaxel, oxaliplatin plus S-1 (DOS) for treating patients with clinical stage III ESCC. The primary endpoint is the pathological response rate, and the target number is 45 patients. Safety, response rate, R0 resection rate, and survival are secondary endpoints. This trial is registered in the Japan Registry of Clinical Trials as jRCTs041210023. We are conducting a prospective phase II trial to evaluate the safety and efficacy of three courses of neoadjuvant DOS treatment followed by radical esophagectomy for clinical stage III ESCC.

DOI： 10.1016/j.conctc.2021.100853

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Impact of synbiotics treatment on bacteremia induced during neoadjuvant chemotherapy for esophageal cancer: A randomised controlled trial. 国際誌

Fukaya M, Yokoyama Y, Usui H, Fujieda H, Sakatoku Y, Takahashi T, Miyata K, Niikura M, Sugimoto T, Asahara T, Nagino M, Ebata T

Clinical nutrition (Edinburgh, Scotland) 40 巻 ( 12 ) 頁： 5781 - 5791 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Clinical Nutrition

Background & aims: To elucidate the impact of synbiotics on bacterial translocation and subsequent bacteremia during neoadjuvant chemotherapy for esophageal cancer. Methods: Patients requiring neoadjuvant chemotherapy for esophageal cancer were randomized to receive synbiotics (synbiotics group) or no synbiotics (control group) during chemotherapy. Blood and fecal samples were taken before and after every chemotherapy cycle, and 1 day before surgery. Mesenteric lymph nodes (MLNs) were harvested at laparotomy (MLN-1) and after resection of the tumor (MLN-2). Bacteria in each sample were detected. Fecal microbiota and organic acid concentrations were also determined. The primary endpoint was the detection of bacteria in the blood samples, as well as the incidence of side effects during chemotherapy. The secondary endpoint was the detection rate of bacteria in the MLN samples collected during surgery. Results: The study recruited a total of 42 patients (22 in the control group, 20 in the synbiotics group). Bacteria were detected in 16 of 101 blood samples in the control group, whereas those were detected only 2 of 100 blood samples in the synbiotics group (p < 0.001) during neoadjuvant chemotherapy. Additionally, bacteria were detected in 12 of 34 MLN samples in the control group, whereas no bacteria were detected in 38 MLN samples in the synbiotics group (p < 0.001). Suppression of bacterial translocation was at least partly associated with an increased fecal acetic acid concentration as well as a lowered fecal pH by synbiotics. The incidence rate of grade 3 gastrointestinal toxicity during chemotherapy was lower in the synbiotics group compared to the control group (8/22 vs. 1/20, p = 0.022). Conclusions: Neoadjuvant chemotherapy for esophageal cancer may induce bacterial translocation and subsequent bacteremia, which can be prevented by synbiotics administration. Trial registration: The University Hospital Medical Information Network (http://www.umin.ac.jp; registration number ID 000007651).

DOI： 10.1016/j.clnu.2021.10.004

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PubMed

増刊号 Stepごとに要点解説標準術式アトラス最新版-特別付録Web動画 4.大腸直腸癌-骨盤内臓全摘術

小倉淳司, 上原圭, 村田悠記, 三品拓也, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 横山幸浩, 江畑智希

臨床外科 76 巻 ( 11 ) 頁： 128 - 137 2021年10月

II. Treatment for Recurrent Cholangiocarcinoma

Watanabe N., Yokoyama Y., Igami T., Uehara K., Mizuno T., Yamaguchi J., Miyata K., Onoe S., Ogura A., Ebata T.

Japanese Journal of Cancer and Chemotherapy 48 巻 ( 10 ) 頁： 1223 - 1226 2021年10月

[Ⅱ.Treatment for Recurrent Cholangiocarcinoma].

Watanabe N, Yokoyama Y, Igami T, Uehara K, Mizuno T, Yamaguchi J, Miyata K, Onoe S, Ogura A, Ebata T

Gan to kagaku ryoho. Cancer & chemotherapy 48 巻 ( 10 ) 頁： 1223 - 1226 2021年10月

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