2024/09/19 更新

写真a

スギタ シズキ
杉田 静紀
SUGITA Shizuki
所属
医学部附属病院 消化器・腫瘍外科(肝胆膵) 助教
大学院担当
大学院医学系研究科
職名
助教
連絡先
メールアドレス
外部リンク

学位 2

  1. 博士(医学) ( 2021年3月   名古屋大学 ) 

  2. 学士(医学) ( 2009年3月   名古屋市立大学 ) 

研究分野 1

  1. ライフサイエンス / 外科学一般、小児外科学

経歴 2

  1. 名古屋大学   医学部附属病院 消化器外科1   助教

    2023年10月 - 現在

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    国名:日本国

  2. 名古屋大学   医学部附属病院 消化器外科一   病院助教

    2021年10月 - 2023年9月

学歴 1

  1. 名古屋市立大学   医学部   医学科

    2003年4月 - 2009年3月

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    国名: 日本国

所属学協会 3

  1. 日本内視鏡外科学会   評議員

  2. 日本消化器外科学会   消化器外科専門医、指導医

  3. 日本外科学会   専門医

 

論文 13

  1. 特集 合併症を起こさない食道癌手術!-ハイボリュームセンターの技を学ぼう 各施設における合併症を起こさない技と工夫 名古屋大学腫瘍外科の技と工夫

    宮田 一志, 杉田 静紀, 江畑 智希

    臨床外科   79 巻 ( 8 ) 頁: 914 - 919   2024年8月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1407214615

    CiNii Research

  2. Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer

    Liang, Y; Maeda, O; Miyata, K; Kanda, M; Sugita, S; Shimizu, D; Nishida, K; Kodera, Y; Ando, Y

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   93 巻 ( 2 ) 頁: 121 - 127   2024年2月

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    記述言語:英語   出版者・発行元:Cancer Chemotherapy and Pharmacology  

    Purpose: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. Methods: Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1–5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. Results: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3′-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). Conclusions: ABCC2-24C > T (rs717620), TYMS 3′-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

    DOI: 10.1007/s00280-023-04607-7

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  3. Protocol of a phase II study investigating the efficacy and safety of trifluridine/tipiracil plus ramucirumab as a third-line or later treatment for advanced gastric cancer

    Nakanishi, K; Tanaka, C; Kanda, M; Miyata, K; Machida, N; Sakai, M; Kobayashi, D; Teramoto, H; Ishiyama, A; Sato, B; Oshima, T; Kajikawa, M; Matsushita, H; Ishigure, K; Yamashita, K; Fujitake, S; Sueoka, S; Asada, T; Shimizu, D; Sugita, S; Kuwatsuka, Y; Maeda, O; Furune, S; Murotani, K; Ando, Y; Ebata, T; Kodera, Y

    NAGOYA JOURNAL OF MEDICAL SCIENCE   86 巻 ( 1 ) 頁: 43 - 51   2024年2月

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    記述言語:英語   出版者・発行元:Nagoya Journal of Medical Science  

    In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

    DOI: 10.18999/nagjms.86.1.43

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  4. Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer

    Maeda, O; Furune, S; Kanda, M; Miyata, K; Shimizu, D; Sugita, S; Nishida, K; Ando, M; Kodera, Y; Ando, Y

    CANCER MEDICINE   13 巻 ( 2 ) 頁: e6974   2024年1月

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    記述言語:英語   出版者・発行元:Cancer Medicine  

    Purpose: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Methods: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1–5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Results: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Conclusion: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

    DOI: 10.1002/cam4.6974

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  5. 特集 ハイボリュームセンターのオペ記事《消化管癌編》 胃癌 噴門側胃切除術のオペ記事-当科におけるロボット支援下噴門側胃切除術

    田中 千恵, 杉田 静紀, 中西 香企, 栗本 景介, 小寺 泰弘

    臨床外科   78 巻 ( 13 ) 頁: 1464 - 1468   2023年12月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1407214373

    CiNii Research

  6. Low Expectancy of Conversion Surgery with R0 Resection in Patients with CEA > 5.0 ng/mL at the Initial RECIST Evaluation for Metastatic Gastric Cancer

    Nakanishi, K; Tanaka, C; Kanda, M; Miyata, K; Furukawa, K; Maeda, O; Shimizu, D; Sugita, S; Kakushima, N; Furune, S; Kawashima, H; Ando, Y; Ebata, T; Kodera, Y

    CANCERS   15 巻 ( 21 )   2023年11月

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    記述言語:英語   出版者・発行元:Cancers  

    This retrospective study examined early the predictive factors for successful conversion surgery (CS) with R0 resection in patients with metastatic gastric cancer (MGC) who underwent systemic chemotherapy. This study included 204 patients diagnosed with metastatic gastric adenocarcinoma, who received chemotherapy between 2009 and 2019. Of these patients, 31 (15%) underwent CS with R0 resection. The incidence of CS with R0 resection was not affected by the volume of metastatic lesions or the presence of peritoneal metastasis. The overall survival time of the CS with R0 resection group was significantly longer than that of the non-CS group (hazard ratio, 0.12; 95% confidence interval, 0.07–0.23; p < 0.0001), with a 5 year overall survival rate of 50.2%. Multivariate analysis of 150 patients, excluding those with disease progression until the initial Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, showed that carcinoembryonic antigen > 5.0 ng/mL at the initial RECIST evaluation was an independent, significant, and unfavorable predictor of CS with R0 resection (odds ratio, 0.21; p = 0.0108), whereas systemic chemotherapy with trastuzumab for HER2-positive cancer was a favorable factor (odds ratio, 4.20; p = 0.0119). Monitoring serum carcinoembryonic antigen levels during chemotherapy may be a useful predictor of the CS implementation in patients with MGC.

    DOI: 10.3390/cancers15215197

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  7. A risk scoring system for early diagnosis of anastomotic leakage after subtotal esophagectomy for esophageal cancer

    Sugita, S; Miyata, K; Shimizu, D; Ebata, T; Yokoyama, Y

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   53 巻 ( 10 ) 頁: 936 - 941   2023年10月

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    記述言語:英語   出版者・発行元:Japanese Journal of Clinical Oncology  

    Background: Anastomotic leakage (AL) is one of the most critical postoperative complications after subtotal esophagectomy in patients with esophageal cancer. This study attempted to develop an optimal scoring system for stratifying the risk for AL. Methods: The study included 171 patients who underwent subtotal esophagectomy for esophageal cancer followed by esophagogastrostomy in the cervical region from January 2011 to April 2021 at Nagoya University Hospital. AL was defined by radiologic or endoscopic evidence of anastomotic breakdown using some modalities. A risk scoring system for an early diagnosis of AL was established using factors determined in the multivariate analysis. A score was calculated for each patient, and the patients were classified into three categories according to the risk for AL: low-, intermediate- and high-risk. The trend of the risk for AL among the categories was evaluated. Results: Twenty-nine patients (17%) developed AL. Multivariate analysis demonstrated that sinistrous gross features of drain fluid (P < 0.001; odds ratio (OR), 10.2), radiologic air bubble sign (P < 0.001; OR, 15.0) and the level of drain amylase ≥280 U/L on postoperative Day 7 (P < 0.001; OR, 9.0) were significantly associated with AL. According to the matching number of the above three risk factors and categorization into three risk groups, the incidence of AL was 6.1% (8/131) in the low-risk group, 45.5% (15/33) in the intermediate-risk group and 85.7% (6/7) in the high-risk group (area under curve, 0.81; 95% confidence interval, 0.72-0.90). Conclusions: The present AL-risk scoring system may be useful in postoperative patient care after subtotal esophagectomy.

    DOI: 10.1093/jjco/hyad072

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  8. Risk Factors for Muscle Loss During Neoadjuvant Therapy for Esophageal Cancer

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

    ANTICANCER RESEARCH   43 巻 ( 3 ) 頁: 1309 - 1315   2023年3月

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    記述言語:英語   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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  9. 特集 直腸癌局所再発に挑む-最新の治療戦略と手術手技 総論 局所再発直腸癌の治療方針-臓器温存手術や遠隔転移併存症例の手術適応も含めて

    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

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1407213704

    CiNii Research

  10. Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry

    Watanabe, M; Kuwata, T; Setsuda, A; Tokunaga, M; Kaito, A; Sugita, S; Tonouchi, A; Kinoshita, T; Nagino, M

    SCIENTIFIC REPORTS   11 巻 ( 1 ) 頁: 4165   2021年2月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Gastric stump cancer (GSC) has distinct clinicopathological characteristics from primary gastric cancer. However, the detailed molecular and pathological characteristics of GSC remain to be clarified because of its rarity. In this study, a set of tissue microarrays from 89 GSC patients was analysed by immunohistochemistry and in situ hybridisation. Programmed death ligand 1 (PD-L1) was expressed in 98.9% of tumour-infiltrating immune cells (TIICs) and 6.7% of tumour cells (TCs). Epstein–Barr virus (EBV) was detected in 18 patients (20.2%). Overexpression of human epidermal growth factor receptor 2 and deficiency of mismatch repair (MMR) protein expression were observed in 5.6% and 1.1% of cases, respectively. Moreover, we used next-generation sequencing to determine the gene mutation profiles of a subset of the 50 most recent patients. The most frequently mutated genes were TP53 (42.0%) followed by SMAD4 (18.0%) and PTEN (16.0%), all of which are tumour suppressor genes. A high frequency of PD-L1 expression in TIICs and a high EBV infection rate suggest immune checkpoint inhibitors for treatment of GSC despite a relatively low frequency of deficient MMR gene expression. Other molecular characteristics such as PTEN and SMAD4 mutations might be considered to develop new treatment strategies.

    DOI: 10.1038/s41598-021-83711-1

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  11. Long-term oncological outcomes of laparoscopic versus open transhiatal resection for patients with Siewert type II adenocarcinoma of the esophagogastric junction

    Sugita, S; Kinoshita, T; Kuwata, T; Tokunaga, M; Kaito, A; Watanabe, M; Tonouchi, A; Sato, R; Nagino, M

    SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES   35 巻 ( 1 ) 頁: 340 - 348   2021年1月

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    記述言語:英語   出版者・発行元:Surgical Endoscopy  

    Background: Insufficient information is available about the long-term outcomes of patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) who undergo laparoscopic transhiatal approach (LTH). Here we evaluated the oncological safety of LTH for patients with Siewert type II AEG compared with the open transhiatal approach (OTH). Methods: Subjects included 79 patients with Siewert type II AEG who underwent gastrectomy combined with lower esophagectomy from 2008 to 2018 at our institution. Overall survival (OS), recurrence-free survival (RFS), status of adjuvant chemotherapy, late-phase complications, and recurrence patterns were compared between the OTH (n = 29) and LTH groups (n = 43). Results: The median observation periods were 60 months (6–120 months) and 36 months (1–88) for the OTH and LTH groups, respectively. The 5-year OS rates were significantly different: 74% (95% CI 71–77%) and 98% (95% CI 97–99) in the OTH and LTH groups (HR 0.10, 95% CI 0.01–0.83), respectively, though the OTH group included more patients with advanced disease. After stratification, according to pathological stage to adjust for selection bias, the 5-year OS and RFS rates were longer, but not significantly different among patients in the LTH group with pStage III (HR 0.42, 95% CI 0.05–3.47; HR 0.47, 95% CI 0.10–2.12, respectively). Recurrence patterns were similar in the both groups. Conclusions: Long-term outcomes of the LTH group were not inferior to those of the OTH group, suggesting the possibility of LTH as a treatment option for selected patients with Siewert type II AEG.

    DOI: 10.1007/s00464-020-07406-w

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  12. Clinical significance of lymphatic invasion in the esophageal region in patients with adenocarcinoma of the esophagogastric junction

    Sugita, S; Kuwata, T; Tokunaga, M; Kaito, A; Watanabe, M; Tonouchi, A; Kinoshita, T; Nagino, M

    JOURNAL OF SURGICAL ONCOLOGY   122 巻 ( 3 ) 頁: 433 - 441   2020年9月

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    記述言語:英語   出版者・発行元:Journal of Surgical Oncology  

    Background and Objectives: The lymphatic flow around the esophagogastric junction is complicated. Therefore, it is unclear whether lymphatic invasion in the esophageal region (eLI) and in the gastric region (gLI) in patients with adenocarcinoma of the esophagogastric junction (AEG) equally affect the incidence of lymph node metastases (LNM), and consequently, survival. Methods: We retrospectively reviewed clinicopathological data of 175 patients with AEG between January 2008 and July 2017. Risk factors for LNM and impacts of eLI or gLI on survival outcomes were investigated. Results: eLI was identified in 34% of the patients (59/175). By multivariate analysis, eLI was associated with an increased risk of both mediastinal LNM (odds ratio [OR] = 2.98, 95% confidence interval [CI]: 1.26-7.05) and abdominal LNM (OR = 5.44, 95% CI: 1.95-15.20). The 5-year overall survival for patients with eLI (53%) was significantly worse than for patients without eLI (76%) (hazard ratio = 2.45, 95% CI: 1.37-10.01). gLI was not selected in either of these analyses. Conclusions: Positive eLI was strongly associated with mediastinal and abdominal LNM and worse survival in patients with AEG compared with gLI. In the histopathological examination, it seems to make sense to assess eLI and gLI separately.

    DOI: 10.1002/jso.25964

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  13. Intramucosal-lymphatic invasion has a slight impact on lymph node metastasis in patients with early gastric cancer

    Sugita, S; Kinoshita, T; Kuwata, T; Tokunaga, M; Kaito, A; Watanabe, M; Tonouchi, A; Sato, R; Nagino, M

    SURGERY TODAY   50 巻 ( 5 ) 頁: 484 - 489   2020年5月

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    記述言語:英語   出版者・発行元:Surgery Today  

    Purpose: Lymphatic invasion (LI) is associated with lymph node metastasis (LNM) and a poor prognosis in patients with early gastric cancer (EGC). Although the impact of the LI volume on LNM has been described, no reports have assessed the impact of its depth on LNM. Methods: A total of 360 EGC patients with pathologically proven LI who underwent radical gastrectomy with lymphadenectomy between January 2005 and June 2018 at our institution were extracted from our database. Patients were divided into 2 groups: the mLI group, in which LI was limited to the muscularis mucosae (n = 34); and the smLI group, in which LI reached the submucosal region (n = 326). Clinicopathological features, including the LNM incidence, were compared between the groups. Results: LNM was recognized in 3 patients (9%) in the mLI group and 101 (31%) in the smLI group (P = 0.005). In the mLI group, LNM was not recorded in any patients who met the curative criteria of ESD other than mLI. Conclusions: LI limited to the mucosal region does not seem to be a strong indicator for LNM. When pathological findings of an endoscopic submucosal dissection specimen show only mLI as a non-curative criterion, the probability of LNM may be very low.

    DOI: 10.1007/s00595-019-01913-7

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▼全件表示

書籍等出版物 1

  1. 消化器ナーシング2023年秋季増刊 解剖生理も、最新の治療も、患者ケアも 決定版! まるごと知りたい消化管

    福井大学医学部 消化器・乳腺内分泌・小児外科外科学講座 教授 五井 孝憲 監修( 担当: 分担執筆 ,  範囲: 4章しっかり消化!胃・十二指腸のすべて 治療・ケア編 01 噴門側胃切除術)

    株式会社メディカ出版  2023年10月 

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    総ページ数:240   記述言語:日本語

講演・口頭発表等 8

  1. 胃癌手術におけるサルコペニアと高齢者総合的機能評価の関連性の検討

    杉田 静紀

    第124回日本外科学会定期学術集会  2024年4月18日 

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    開催年月日: 2024年4月

    記述言語:日本語   会議種別:口頭発表(一般)  

    国名:日本国  

  2. 胃癌手術におけるサルコペニアが短期成績とADLに与える影響の検討

    杉田静紀

    第96回日本胃癌学会総会  2024年3月1日 

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    開催年月日: 2024年2月 - 2024年3月

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:京都  

  3. 徐々に適応を拡大したロボット支援胃切除の短期成績

    杉田静紀

    第36回日本内視鏡外科学会総会  2023年12月9日 

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    開催年月日: 2023年12月

    記述言語:日本語   会議種別:口頭発表(一般)  

  4. Evaluation of the treatment outcomes in patients with pT3N0 or pT1N2,3 stage II gastric cancer.

    Shizuki Sugita

    2023年7月12日 

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    開催年月日: 2023年7月

    記述言語:英語   会議種別:口頭発表(一般)  

  5. 食道癌術後の縫合不全リスク評価システム

    杉田静紀

    第123回日本外科学会定期学術集会  2023年4月28日 

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    開催年月日: 2023年4月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:東京  

  6. 進行胃癌に対しての腹腔鏡下胃切除術の注意点と短期成績

    杉田 静紀

    第95回日本胃癌学会総会  2023年2月24日 

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    開催年月日: 2023年2月

    記述言語:日本語   会議種別:ポスター発表  

  7. 若手外科医が安全にロボット支援胃切除を導入するための工夫とスキル評価システム

    杉田 静紀

    第35回日本内視鏡外科学会総会  2022年12月9日 

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    開催年月日: 2022年12月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:名古屋   国名:日本国  

  8. 食道癌術後の縫合不全リスク評価システム 国際共著

    杉田 静紀

    第77回日本消化器外科学会総会  2022年7月21日 

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    開催年月日: 2022年7月

    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:横浜   国名:日本国  

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科研費 1

  1. 全ゲノム解析による食道癌の周術期補助療法と早期再発に関する研究

    研究課題/研究課題番号:22K16508  2022年4月 - 2025年3月

    科学研究費助成事業  若手研究

    杉田 静紀

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    担当区分:研究代表者 

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    食道癌の周術期補助療法として海外では術前補助化学放射線療法が、本邦では術前補助化学療法が主流であるが、それぞれが免疫微小環境に与える影響や遺伝子変異に関しての報告はほとんどない。また、根治切除後の早期に再発をきたす例も存在し、このメカニズムやリスク因子も明らかになっていない。
    本研究は食道癌において周術期補助療法が免疫微小環境に与える影響と術後早期再発の原因遺伝子を解明することを目的とする。今後の食道癌の個別化医療を目指し、遺伝子変異および早期再発原因遺伝子をターゲットとした新規診断治療法の開発を目指す。
    食道癌手術症例の中で比較的最近手術を行なった症例の中から、原発巣のブロック標本を用いてRNAシークエンスを行う前準備として、Agilent社のバイオアナライザーでRNAの状態の評価を行った。全体的に切除、固定してから時間が経過しており、残存しているRNAの質は不良の可能性も示唆されたが比較的質の良さそうなものを数例実験的にRNAシークエンスへ提出した。現在解析結果待ちである。
    また、原発巣は化学療法の影響で腫瘍自体が消失したりして微小環境の評価が難しい可能性が示唆されたため、腫瘍近傍のリンパ節(食道癌取扱規約の106recR)のリンパ節標本において、腫瘍微小環境の評価を行うために、PD-1、PD-L1、FoxP3、CD4、CD8等の免疫組織染色をおこなった。免疫組織染色の結果と患者の予後等を比較したところ、106recRリンパ節のPD-L1、FoxP3陽性と予後に相関を認めた。
    食道癌の早期再発に関わる遺伝子の候補をリストアップするため、本邦における公開データベース(NBDC)からデータを取り寄せたが、予後や再発に関する情報が含まれておらず、遺伝子変異と予後や再発との相関を検討することができなかった。
    RNAシークエンスを既存のブロック標本から行う予定であり、そもそも検査自体が可能かどうかを検証するために時間を要しているため。
    食道癌のリンパ節標本における免疫組織染色の症例数を増やす。現在は腫瘍近傍での微小環境の評価をおこなっているが、今後は腫瘍近傍と、腫瘍から離れた部分でのリンパ節標本における免疫微小環境の違いと予後に関する検討も行う予定であり、腫瘍から離れた部分でのリンパ節(取扱規約でいう3群に当たるリンパ節)の免疫組織染色も進めていく予定である。
    さらに、RNAシークエンスの結果を待って、評価可能であった場合は症例数を増やして早期再発と遺伝子変異の関連性を検証してく予定である。