Faculty Profiles - MIYATA Kazushi

TLK1 Inhibition Enhances the Anticancer Effect of Deep UV Irradiation Through CHK1 Activation.

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 Vol. 79 ( 8 ) page： 914 - 919 2024.8

Koike Y, 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 Vol. 44 ( 7 ) page： 2827 - 2836 2024.7

Language：English Publisher：Anticancer Research

Background/Aim: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells. Materials and Methods: Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks. Results: DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups. Conclusion: TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.

DOI： 10.21873/anticanres.17095

上部消化管高度進行胃癌に対するコンバージョン手術の個別化治癒切除不能胃癌におけるConversion Surgeryの至適タイミングと予後因子の検討

中西香企, 田中千恵, 神田光郎, 宮田一志, 清水大, 杉田静紀, 藤原道隆, 江畑智希, 小寺泰弘

日本消化器外科学会総会 Vol. 79回 page： 542 - 542 2024.7

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

Yao Liang, Osamu Maeda, Kazushi Miyata, Mitsuro Kanda, Shizuki Sugita, Dai Shimizu, Kazuki Nishida, Yasuhiro Kodera, Yuichi Ando

Cancer chemotherapy and pharmacology Vol. 93 ( 2 ) page： 121 - 127 2024.2

Language：English Publishing type：Research paper (scientific journal)

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

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 Vol. 86 ( 1 ) page： 43 - 51 2024.2

Language：English Publisher：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

Risk factors for venous thrombosis after esophagectomy.

術後合併症の予測と対策ドレーンアミラーゼ値を用いた腹腔内感染症の早期予測法

中西香企, 神田光郎, 田中千恵, 杉田静紀, 清水大, 宮田一志, 藤原道隆, 江畑智希, 小寺泰弘

日本胃癌学会総会記事 Vol. 96回 page： 179 - 179 2024.2

Torii N, Miyata K, Fukaya M, Ebata T

Esophagus : official journal of the Japan Esophageal Society 2024.1

Language：English Publisher：Esophagus

Background: Venous thrombosis (VT) after esophagectomy for esophageal cancer is an important complication, potentially leading to pulmonary embolism. However, there are few available information about the risk for the postsurgical VT. Methods: This study included 271 patients who underwent esophagectomy for esophageal cancer between 2006 and 2019. Contrast-enhanced computed tomography (CT) was performed for all patients on the seventh postoperative day to survey complications, including VT. Results: VT was radiologically visualized in 48 patients (17.7%), 8 of whom (16.7%) had pulmonary embolism. The thrombus disappeared in 42 patients, the thrombus size was unchanged in 5 patients, and 1 patient died. Multivariate analysis was performed on factors clinically considered to have a significant influence on thrombus formation. The analysis showed that CVC insertion via the femoral vein (odds ratio, 7.67; 95% CI, 2.64–22.27; P < 0.001), retrosternal reconstruction route (odds ratio, 3.94; 95% CI, 1.90–8.17; P < 0.001) and intraoperative fluid balance < 5 ml/kg/hr (odds ratio, 0.38; 95% CI, 0.17–0.85; P = 0.019) were independently related to VT. Conclusions: Intraoperative fluid balance < 5 ml/kg/hr, along with CVC insertion via the femoral vein and retrosternal reconstruction may be potential risk factors for VT after esophagectomy.

DOI： 10.1007/s10388-023-01038-4

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

Osamu Maeda, Satoshi Furune, Mitsuro Kanda, Kazushi Miyata, Dai Shimizu, Shizuki Sugita, Kazuki Nishida, Masahiko Ando, Yasuhiro Kodera, Yuichi Ando

Cancer medicine Vol. 13 ( 2 ) page： e6974 2024.1

Language：English Publishing type：Research paper (scientific journal)

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

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.

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, 田中千恵, 宮田一志, 中西香企, 稲田亘佑, 田根雄一郎, 神田光郎, 清水大, 小寺泰弘, 江畑智希

日本内視鏡外科学会雑誌 Vol. 28 ( 7 ) page： 1969 - 1969 2023.12

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 Vol. 15 ( 21 ) 2023.10

Language：English Publisher：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

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

Shizuki Sugita, Kazushi Miyata, Daisuke Shimizu, Tomoki Ebata, Yukihiro Yokoyama

Japanese journal of clinical oncology Vol. 53 ( 10 ) page： 936 - 941 2023.10

Language：English Publishing type：Research paper (scientific journal)

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

A cell wall-localized cytokinin/purine riboside nucleosidase is involved in apoplastic cytokinin metabolism in Oryza sativa.

Kojima M, Makita N, Miyata K, Yoshino M, Iwase A, Ohashi M, Surjana A, Kudo T, Takeda-Kamiya N, Toyooka K, Miyao A, Hirochika H, Ando T, Shomura A, Yano M, Yamamoto T, Hobo T, Sakakibara H

Proceedings of the National Academy of Sciences of the United States of America Vol. 120 ( 36 ) page： e2217708120 2023.9

Language：English Publisher：Proceedings of the National Academy of Sciences of the United States of America

In the final step of cytokinin biosynthesis, the main pathway is the elimination of a ribose-phosphate moiety from the cytokinin nucleotide precursor by phosphoribohydrolase, an enzyme encoded by a gene named LONELY GUY (LOG). This reaction accounts for most of the cytokinin supply needed for regulating plant growth and development. In contrast, the LOG-independent pathway, in which dephosphorylation and deribosylation sequentially occur, is also thought to play a role in cytokinin biosynthesis, but the gene entity and physiological contribution have been elusive. In this study, we profiled the phytohormone content of chromosome segment substitution lines of Oryza sativa and searched for genes affecting the endogenous levels of cytokinin ribosides by quantitative trait loci analysis. Our approach identified a gene encoding an enzyme that catalyzes the deribosylation of cytokinin nucleoside precursors and other purine nucleosides. The cytokinin/purine riboside nucleosidase 1 (CPN1) we identified is a cell wall-localized protein. Loss-of-function mutations (cpn1) were created by inserting a Tos17-retrotransposon that altered the cytokinin composition in seedling shoots and leaf apoplastic fluid. The cpn1 mutation also abolished cytokinin riboside nucleosidase activity in leaf extracts and attenuated the trans-zeatin riboside-responsive expression of cytokinin marker genes. Grain yield of the mutants declined due to altered panicle morphology under field-grown conditions. These results suggest that the cell wall-localized LOG-independent cytokinin activating pathway catalyzed by CPN1 plays a role in cytokinin control of rice growth. Our finding broadens our spatial perspective of the cytokinin metabolic system.

DOI： 10.1073/pnas.2217708120

TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.

Suzuki MM, Iijima K, Ogami K, Shinjo K, Murofushi Y, Xie J, Wang X, Kitano Y, Mamiya A, Kibe Y, Nishimura T, Ohka F, Saito R, Sato S, Kobayashi J, Yao R, Miyata K, Kataoka K, Suzuki HI, Kondo Y

Nature communications Vol. 14 ( 1 ) page： 4521 2023.8

Language：English Publisher：Nature Communications

Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.

DOI： 10.1038/s41467-023-40243-8

A feasibility study of modified docetaxel, cisplatin, and capecitabine for advanced gastric cancer followed by gastrectomy. International journal

Yao Liang, Osamu Maeda, Kazushi Miyata, Chie Tanaka, Mitsuro Kanda, Dai Shimizu, Masahide Fukaya, Masahiko Koike, Yasuhiro Kodera, Yuichi Ando

Asia-Pacific journal of clinical oncology 2023.7

Language：English Publishing type：Research paper (scientific journal)

AIMS: To explore the feasibility of modified docetaxel, cisplatin, and capecitabine (mDCX) chemotherapy with a lower dose of docetaxel than previously reported for stage III resectable gastric cancer patients with a high risk of recurrence or for stage IV gastric cancer patients aiming for conversion surgery. METHODS: Patients with stage III resectable HER2-negative gastric cancer with large type 3 or type 4 tumors or extensive lymph node metastasis (bulky N or cN3) and those who had stage IV HER2-negative gastric cancer with distant metastasis were enrolled to receive 30 mg/m2 docetaxel and 60 mg/m2 cisplatin on day 1, followed by 2000 mg/m2 capecitabine per day for 2 weeks every 3 weeks. RESULTS: Five patients with stage III gastric cancer with a high risk of recurrence received three courses of mDCX, and four patients with stage IV gastric cancer received three or four courses of mDCX. In terms of grade 3 or worse adverse events, leukopenia was observed in one (11%) patient, neutropenia in two (22%) patients, anemia in one (11%) patient, anorexia in two (22%) patients and nausea in two (22%) patients. All six patients with measurable lesions achieved a partial response. All nine patients underwent subsequent surgeries. The histological responses of the nine patients revealed grade 3 in one (11%) patient, grade 2 in five (56%) patients, and grade 1a in three (33%) patients. Three of the nine patients survived without recurrence, and two of them survived for more than four years. CONCLUSIONS: mDCX seems to be feasible and may be helpful as neoadjuvant chemotherapy for patients at high risk of recurrence or as chemotherapy for patients who are likely to undergo conversion surgery.

DOI： 10.1111/ajco.13995

A Case Report of Localized Peritoneal Disseminated Recurrence of Microsatellite Instability-High Colorectal Cancer with Pathologic Complete Response after Immune Checkpoint Inhibitor Therapy

【上部】【Challenges beyond borders】高度進行胃癌に対するconversion surgeryの現状と新たな治療戦略高齢者における治癒切除不能胃癌に対するconversion surgeryの治療成績

中西香企, 田中千恵, 神田光郎, 宮田一志, 清水大, 杉田静紀, 藤原道隆, 江畑智希, 小寺泰弘

日本消化器外科学会総会 Vol. 78回 page： PD3 - 9 2023.7

病理学的T3N0,T1N2,3を含むpStageII胃癌の治療成績の検討

杉田静紀, 宮田一志, 田中千恵, 中西香企, 清水大輔, 小倉淳司, 村田悠記, 水野隆史, 小寺泰弘, 江畑智希

日本消化器外科学会総会 Vol. 78回 page： P062 - 3 2023.7

Nishimura Motonobu, Uehara Kay, Ogura Atsushi, Murata Yuki, Kobayashi Ryutaro, Mizuno Takashi, Miyata Kazushi, Yokoyama Yukihiro, Ebata Tomoki

The Japanese Journal of Gastroenterological Surgery Vol. 56 ( 4 ) page： 221 - 228 2023.4

Language：Japanese Publisher：The Japanese Society of Gastroenterological Surgery

Use of immune checkpoint inhibitors (ICIs) has recently been recommended for treatment of unresectable or recurrent colorectal cancer with a microsatellite instability-high (MSI-H) status. We report a case of recurrent sigmoid colon cancer that was treated with ICIs followed by radical resection. One year after primary resection, the patient was diagnosed with localized peritoneal metastasis invading the left lower abdominal wall. The tumor presented as RAS/BRAF wild-type and was treated with FOLFIRI+panitumumab as 1st line chemotherapy. After shrinkage was observed, the patient was referred to our department for possible resection. Treated with ipilimumab plus nivolumab was used for further disease control of the borderline resectable tumor. However, interim imaging showed a slight increase in tumor size, so radical surgery (abdominal wall tumor resection+lymph node dissection+fascia lata abdominal wall reconstruction) was performed after three courses of ICI treatment. The pathological results showed a complete response, and the patient is now under observation with neither adjuvant therapy nor recurrence.

DOI： 10.5833/jjgs.2022.0056

Feasibility assessment of global standard chemoradiotherapy followed by surgery in patients with esophageal cancer. International journal

Yao Liang, Osamu Maeda, Kazushi Miyata, Mitsuro Kanda, Dai Shimizu, Shizuki Sugita, Tohru Okada, Junji Ito, Mariko Kawamura, Shunichi Ishihara, Masahiro Nakatochi, Masahiko Ando, Yasuhiro Kodera, Yuichi Ando

Molecular and clinical oncology Vol. 18 ( 4 ) page： 34 - 34 2023.4

Language：English Publishing type：Research paper (scientific journal)

The present study aimed to assess the feasibility of global standard chemoradiotherapy (CRT) followed by surgery in patients with esophageal cancer. A prospective study was conducted at Nagoya University Hospital (Nagoya, Japan) to evaluate global standard CRT followed by surgery in patients with esophageal cancer. The CRT regimen consisted of 75 mg/m2 cisplatin on day 1 and 1,000 mg/m2 fluorouracil daily on days 1-4 given twice 4 weeks apart together with concurrent esophageal irradiation starting on day 1 (group A). For comparison, 17 patients with esophageal cancer who had received the same chemotherapy regimen but with lower drug doses were retrospectively reviewed: 70 mg/m2 cisplatin on day 1 and 700 mg/m2 fluorouracil daily on days 1-4 given twice 4 weeks apart together with concurrent esophageal irradiation starting on day 1 (group B). Grade 3 or worse adverse events were observed in 9 of the 12 patients (75%) in group A and in 5 of the 17 patients (29%) in group B. The patients in group A were more likely to experience grade 3 or worse neutropenia (50%) than those in group B (6%). No febrile neutropenia or treatment-related deaths occurred in either group. A total of 11 patients (92%) in group A and 16 patients (94%) in group B subsequently underwent an esophagectomy, and 9 (82%) and 14 (88%) of these patients, respectively, achieved microscopically margin-negative resection (R0 resection). In conclusion, global standard CRT was more likely to cause severe but manageable adverse events. There was no apparent difference in the R0 resection rate or postoperative complications between the two treatments. This clinical trial was registered at the Japan Registry of Clinical Trials (trial registration number: jRCT1041180004) on September 11, 2018.

DOI： 10.3892/mco.2023.2630

治癒切除不能胃癌におけるconversion surgery対象選択の客観的指標とはなにか?

中西香企, 田中千恵, 神田光郎, 宮田一志, 清水大, 杉田静紀, 藤原道隆, 江畑智希, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 123回 page： SF - 5 2023.4

Risk Factors for Muscle Loss During Neoadjuvant Therapy for Esophageal Cancer. International journal

Daisuke Shimizu, Kazushi Miyata, Masahide Fukaya, Shizuki Sugita, Tomoki Ebata

Anticancer research Vol. 43 ( 3 ) page： 1309 - 1315 2023.3

Language：English Publishing type：Research paper (scientific journal)

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

Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer. International journal

Mikiko Takebayashi Kano, Toshio Kokuryo, Taisuke Baba, Kimitoshi Yamazaki, Junpei Yamaguchi, Masaki Sunagawa, Atsushi Ogura, Nobuyuki Watanabe, Shunsuke Onoe, Kazushi Miyata, Takashi Mizuno, Kay Uehara, Tsuyoshi Igami, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino

Anticancer research Vol. 43 ( 3 ) page： 1009 - 1016 2023.3

Language：English Publishing type：Research paper (scientific journal)

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 CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB 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

Antitumor Effects of Deep Ultraviolet Irradiation for Pancreatic Cancer. International journal

Kimitoshi Yamazaki, Toshio Kokuryo, Junpei Yamaguchi, Masaki Sunagawa, Atsushi Ogura, Nobuyuki Watanabe, Shunsuke Onoe, Kazushi Miyata, Takashi Mizuno, Kay Uehara, Tsuyoshi Igami, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino

Anticancer research Vol. 43 ( 2 ) page： 621 - 630 2023.2

Language：English Publishing type：Research paper (scientific journal)

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

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

Kazuhiro Ohtakara, Kuniaki Tanahashi, Takeshi Kamomae, Kazushi Miyata, Kojiro Suzuki

Cureus Vol. 15 ( 1 ) page： e33411 2023.1

Language：English

Stereotactic radiosurgery (SRS) with >5 fraction (fr) has been increasingly adopted for brain metastases (BMs), given the current awareness of limited brain tolerance for ≤5 fr. The target volume/configuration change and/or deviation within the cranium during fractionated SRS can be unpredictable and critical uncertainties affecting treatment accuracy, plus the effect of these events on the long-term outcome remains uncertain. Herein, we describe a case of two challenging BMs treated by 10 fr SRS with a unique dose-gradient optimization strategy, in which the large cystic tumor revealed an intriguing correlation of such inter-fractional change with late radiographic sequela, suggesting a dose threshold for attaining long-term local tumor control and being immune to symptomatic brain necrosis. A 63-year-old man presented with two cystic lesions located in the left parietal lobe (19.9 cm3) and pons (1.1 cm3) one month after surgery for esophageal squamous cell carcinoma. The principles for 10 fr SRS were as follows: (1) very inhomogeneous gross tumor volume (GTV) dose covered by 53 Gy, biologically effective dose with an alpha/beta ratio of 10 (BED10) of ≥80 Gy; (2) moderate dose spillage margin outside the GTV boundary: 2-2.5 mm outside the GTV margin was covered by 37 Gy, BED10 of ≈50 Gy; (3) concentrically-laminated, steep dose increase inside the GTV boundary: 2 mm inside the GTV margin was covered by ≥62 Gy, BED10 of ≥100 Gy. At the completion of SRS, the parietal lesion showed significant shrinking and dorsomedial shifting with slight evisceration of the GTV, followed by marked regression of the parietal lesion within four months. At 13.5 months, a cystic change was noted at the dorsal part of the remnant. At 16.7 months, ventral enhancement gradually expanded without enlargement of the dorsal cystic component. On the T2-weighted images, the dorsal low-intensity remnant and ventral iso-intensity blurry-demarcated component were contrasting. Pathological examinations during and after lesionectomy at 17.4 months revealed necrosis only. At 30.5 months, the patient had a left visual field defect without recurrence. In contrast, the pons lesion showed no notable change during 10 fr SRS and nearly complete remission over six months with its sustainment without radiation injury at 30.5 months. Taken together, 10 fr SRS with a sufficient BED10 can provide superior tumor response and safety for BM that is not amenable to ≤5 fr SRS. Although a very inhomogeneous GTV dose can contribute to early and adequate tumor shrinkage and subsequent local tumor eradication, significant tumor shrinkage during fractionated SRS (fSRS) inevitably results in unnecessary higher dose exposure to the surrounding brain, which could lead to late radiation injury requiring intervention. The optimum dose should be determined through further investigation, in consideration of the dynamic and unpredictable nature of the actual absorbed doses to both the tumor and the surrounding brain.

DOI： 10.7759/cureus.33411

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

Miyata K., Kawazoe Y., Hara S.

IEEJ Journal of Industry Applications Vol. 12 ( 2 ) page： 153 - 154 2023

Publisher：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

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

Osamu Maeda, Masahide Fukaya, Masahiko Koike, Kazushi Miyata, Mitsuro Kanda, Kazuki Nishida, Masahiko Ando, Yasuhiro Kodera, Yuichi Ando

Asia-Pacific journal of clinical oncology Vol. 18 ( 6 ) page： 578 - 585 2022.12

Language：English Publishing type：Research paper (scientific journal)

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

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

Koudai Nishimura, Kazushi Miyata, Masahide Fukaya, Yukihiro Yokoyama, Kay Uehara, Junpei Yamaguchi, Takashi Mizuno, Shunsuke Onoe, Atsushi Ogura, Tomoki Ebata

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus Vol. 35 ( 11 ) 2022.11

Language：English Publishing type：Research paper (scientific journal)

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

Trefoil factor 1 inhibits the development of esophageal adenocarcinoma from Barrett's epithelium. International journal

Keiji Hasebe, Kimitoshi Yamazaki, Junpei Yamaguchi, Toshio Kokuryo, Yukihiro Yokoyama, Kazushi Miyata, Masahide Fukaya, Masato Nagino, Tomoki Ebata

Laboratory investigation; a journal of technical methods and pathology Vol. 102 ( 8 ) page： 885 - 895 2022.8

Language：English Publishing type：Research paper (scientific journal)

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

Two Resected Cases of Cholangiocarcinoma with a Small Cell Carcinoma Component

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 Vol. 77 ( 5 ) page： 514 - 519 2022.5

【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 Vol. 123 ( 3 ) page： 255 - 261 2022.5

【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 Vol. 123 ( 3 ) page： 255 - 261 2022.5

Language：Japanese Publisher：(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)

Minami Takayuki, Mizuno Takashi, Yamaguchi Junpei, Onoe Shunsuke, Watanabe Nobuyuki, Igami Tsuyoshi, Uehara Kay, Miyata Kazushi, Yokoyama Yukihiro, Ebata Tomoki

The Japanese Journal of Gastroenterological Surgery Vol. 55 ( 4 ) page： 240 - 250 2022.4

Language：Japanese Publisher：The Japanese Society of Gastroenterological Surgery

We report two cases of cholangiocarcinoma with a small cell carcinoma (SCC) component that exhibited contrasting courses after resection, with early death versus long-term survival. Case 1 was a 70-year-old man who underwent left hepatectomy with caudate lobectomy for perihilar cholangiocarcinoma. Histopathological examination showed adeno-neuroendocrine carcinoma composed of papillary adenocarcinoma and SCC. The tumor was classified as pT2N0M0, Stage II, but with extensive venous invasion from SCC. Gemcitabine alone was administered postoperatively based on normal treatment of biliary tract cancer, but the patient died only five months after surgery due to early relapse with multiple liver metastases. Case 2 was a 65-year-old man who underwent subtotal stomach preserving pancreatoduodenectomy for distal cholangiocarcinoma. Histopathological examination showed neuroendocrine SCC with lymph node metastasis. The tumor was classified as pT2N1M0, Stage III. As standard chemotherapy for pulmonary SCC, cisplatin plus etoposide was given for 4 cycles postoperatively. The patient has been alive without recurrence for 8 years after surgery. An SCC component in cholangiocarcinoma often leads to early relapse with subsequent cancer-related death after resection. Therefore, multidisciplinary approach including chemotherapy similar to that for pulmonary SCC should be considered in this setting.

DOI： 10.5833/jjgs.2021.0083

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 Vol. 122回 page： SF - 7 2022.4

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 Vol. 122回 page： DP - 8 2022.4

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 Vol. 84 ( 2 ) page： 136 - 141 2022.2

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

Masahide Fukaya, Yukihiro Yokoyama, Hiroaki Usui, Hironori Fujieda, Yayoi Sakatoku, Takamasa Takahashi, Kazushi Miyata, Mai Niikura, Takuya Sugimoto, Takashi Asahara, Masato Nagino, Tomoki Ebata

Clinical nutrition (Edinburgh, Scotland) Vol. 40 ( 12 ) page： 5781 - 5791 2021.12

Language：English Publishing type：Research paper (scientific journal)

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

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. International journal

Mitsuro Kanda, Dai Shimizu, Kazushi Miyata, Osamu Maeda, Chie Tanaka, Yoshikuni Inokawa, Norofumi Hattori, Masamichi Hayashi, Masahiko Ando, Yachiyo Kuwatsuka, Kenta Murotani, Goro Nakayama, Masahiko Koike, Yuichi Ando, Tomoki Ebata, Yasuhiro Kodera

Contemporary clinical trials communications Vol. 24 page： 100853 - 100853 2021.12

Language：English Publishing type：Research paper (scientific journal)

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

II. Treatment for Recurrent Cholangiocarcinoma

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 Vol. 76 ( 11 ) page： 128 - 137 2021.10

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 Vol. 48 ( 10 ) page： 1223 - 1226 2021.10

[Ⅱ.Treatment for Recurrent Cholangiocarcinoma].

Nobuyuki Watanabe, Yukihiro Yokoyama, Tsuyoshi Igami, Kay Uehara, Takashi Mizuno, Junpei Yamaguchi, Kazushi Miyata, Shunsuke Onoe, Atsushi Ogura, Tomoki Ebata

Gan to kagaku ryoho. Cancer & chemotherapy Vol. 48 ( 10 ) page： 1223 - 1226 2021.10

Liver、Pancreas、Biliary Tract Cancer 肝・胆・膵癌再発肝胆膵がんへの新たな挑戦 II.胆管癌切除後再発への治療方針

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

癌と化学療法 Vol. 48 ( 10 ) page： 1223 - 1226 2021.10

特集側方リンパ節郭清のすべて-開腹からロボット手術まで手技の実際経肛門的アプローチによる側方リンパ節郭清

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

臨床外科 Vol. 76 ( 5 ) page： 596 - 602 2021.5

手術症例報告下咽頭癌術後の腹臥位胸腔鏡下食道癌手術─永久気管孔,両側DP(deltopectoral)皮弁の取り扱いに注意を要した1例

川上次郎, 深谷昌秀, 宮田一志, 富永健太, 丸尾貴志, 江畑智希

手術 Vol. 75 ( 5 ) page： 905 - 910 2021.4

Pathological Complete Response to Second Line Chemotherapy in a Patient with Cervical Lymph Node Metastasis from Transverse Colon Cancer with RAS and BRAF V600E Mutations: A Case Report

Murata Yuki, Uehara Kay, Aiba Toshisada, Ogura Atsushi, Fukaya Masahide, Miyata Kazushi, Tanaka Aya, Ohara Noriaki, Jinno Takanori, Ebata Tomoki

The Japanese Journal of Gastroenterological Surgery Vol. 54 ( 4 ) page： 278 - 284 2021.4

Language：Japanese Publisher：The Japanese Society of Gastroenterological Surgery

Patients with colorectal cancer with the BRAF V600E mutation, which rarely coexists with a RAS mutation, have an extremely poor prognosis. In contrast, the outcomes of patients with a BRAF mutation and high microsatellite instability (MSI-high) have been found to be favorable. Thus, the significance of having multiple mutations remains unclear. We experienced a rare case with cervical lymph node metastasis from right-sided transverse colon cancer with RAS mutation, BRAF mutation and MSI-high, which developed 9 months after primary resection, just after completion of oxaliplatin-based 6-month adjuvant chemotherapy. As second-line chemotherapy, the patient received FOLFIRI plus aflibercept for 12 months. The tumor shrank markedly from 37 mm to 12 mm in maximum diameter and no new lesion was found; therefore, she underwent conversion surgery. Pathological findings confirmed no residual cancer cells (pathological complete response). Although the postoperative follow-up period is still <9 months, the patient has had no additional treatment after conversion surgery and is alive without recurrence. This case suggests that even in patients with metastatic colorectal cancer with the BRAF V600E mutation, aggressive surgical treatment might be an option in a situation of well-controlled systemic disease similar to that without a BRAF mutation. Further investigation of the significance of coexisting MSI-high with a BRAF mutation is required.

DOI： 10.5833/jjgs.2020.0057

下咽頭癌術後の腹臥位胸腔鏡下食道癌手術永久気管孔,両側DP(deltopectoral)皮弁の取り扱いに注意を要した1例

川上次郎, 深谷昌秀, 宮田一志, 富永健太, 丸尾貴志, 江畑智希

手術 Vol. 75 ( 5 ) page： 905 - 910 2021.4

Language：Japanese Publisher：金原出版(株)

症例は60歳代男性で、下咽頭癌術後7年の上部消化管内視鏡検査で中咽頭癌と胸部上部表在食道癌が指摘された。中咽頭癌に対するELPS(endoscopic laryngopharyngeal surgery)を先行し、その後、食道癌に対するESD(endoscopic submucosal dissection)を予定した。下咽頭癌に対する手術時、術後に永久気管孔壊死と皮弁壊死を繰り返し、右DP(deltopectoral)皮弁再建、さらに左DP皮弁再建が追加された。気管血流を温存することに配慮して術式を立案した。気管支動脈、奇静脈弓のほか、伴走する右気管支動脈の上行枝と下行枝を温存し、大動脈弓から直接分岐する左気管枝動脈も温存し、気管分岐部の郭清を省略した。さらに、腹腔鏡用手補助下胃管を作製、後縦隔経路で胃管を挙上した。頸部は皮弁からの気管孔血流を温存するため、左DP皮弁外縁で切開、遊離空腸-食道吻合部で離断し、残食道を全摘した。その後、吻合部狭窄に対しバルーン拡張を、嚥下機能低下に対し嚥下訓練を行い、術後101日から食事を開始し術後138日に退院した。

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Repair of gastro-tracheobronchial fistula after esophagectomy for esophageal cancer using intercostal muscle and latissimus dorsi muscle flaps: a case report. International journal

Kazushi Miyata, Masahide Fukaya, Masato Nagino

Surgical case reports Vol. 6 ( 1 ) page： 172 - 172 2020.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Gastro-tracheobronchial fistula after esophagectomy is a rare but life-threatening complication associated with high mortality. Several authors reported postoperative management of tracheobronchial fistula. However, treatment is demanding and challenging, and the strategy is still controversial. CASE PRESENTATION: A 64-year-old man underwent thoracoscopic esophagectomy with two-field lymph node dissection and gastric conduit reconstruction by an intrathoracic anastomosis for esophageal cancer at a local hospital in June 2013. After surgery, a gastro-tracheal fistula and a gastro-bronchial fistula of the left main bronchus were diagnosed, and the patient was referred to our hospital for the management of the gastro-tracheobronchial fistula. CT and bronchoscopy and esophagogastroduodenoscopy performed at our hospital revealed that the gastro-bronchial fistula of the left main bronchus was cured by packing with the omentum from the gastric conduit and the gastro-tracheal fistula located 3 cm above the carina remained open. We concluded that the fistula would not resolve without further surgical procedure. However, such an operation was expected to be difficult and to need much time due to severe adhesion among the gastric conduit and/or trachea, bronchus, lung, and chest wall. Therefore, a two-stage operation was planned for safety and outcome certainty. The first operation was performed to close the fistula in October 2013. The gastric conduit was separated from the trachea and resected; then, the fistula was sutured and covered by intercostal muscle and latissimus dorsi muscle flaps. A month after the first operation, reconstruction with pedunculated jejunum was performed via the percutaneous route. The patient's postoperative course was uneventful. CONCLUSION: If the omentum is not observed between the gastric conduit and the tracheobronchus when a gastro-tracheobronchial fistula occurs after esophagectomy, surgeons should perform surgical treatment because conservative treatment is unlikely to cure. During surgery, the use of two types of muscle flaps, such as the intercostal muscle and the latissimus dorsi muscle flaps, is helpful for the closure of gastro-tracheobronchial fistulas.

DOI： 10.1186/s40792-020-00936-4

Successful two-stage operation for esophageal necrosis due to proton beam therapy followed by sorafenib in a case of large hepatocellular carcinoma. International journal

Eiji Higaki, Masahide Fukaya, Kazushi Miyata, Ryosuke Kawai, Tetsuya Abe

Surgical case reports Vol. 6 ( 1 ) page： 138 - 138 2020.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Locally advanced hepatocellular carcinoma (HCC), which is unsuitable for standard locoregional therapies, remains a challenge to manage. Among the recently developed treatments, proton beam therapy (PBT) has been reported to achieve good local control. However, in patients with large HCC adjacent to the esophagus, high-dose PBT may rarely lead to radiation-induced esophageal necrosis or perforation. Furthermore, the optimal strategy to safely treat these fatal complications remains unclear. CASE PRESENTATION: A 49-year-old man who was diagnosed with a large (16 cm) HCC in the right lobe with tumor thrombosis in the main trunk of the portal vein (PVTT) received high-dose hypofractionated PBT in another hospital. A total dose of 66 GyE in 10 fractions was administered to the primary tumor and the PVTT. After 5 months, a 1-cm solitary nodule was noted in the upper lobe of the right lung. Therefore, sorafenib was started. About 6 months after the PBT, lower esophageal mucosal inflammation that progressed to an ulcer was noted. About 7 months after the PBT, the lower esophagus developed full-thickness necrosis. Therefore, emergency thoracoscopic esophagectomy was performed, followed by two-stage reconstruction 2 months later. The operation and postoperative clinical course were mostly uneventful, except for a minor anastomotic leakage. The outcome of the primary HCC, including the PVTT, was graded as a complete response, which has been maintained for 51 months after the PBT. CONCLUSION: PBT is a promising option for patients with locally advanced HCC; however, for large tumors adjacent to the esophagus, ischemic esophageal necrosis due to antiangiogenic effects may occur, particularly with the combined use of PBT and sorafenib. In such a life-threatening condition, the thoracoscopic esophagectomy and the two-stage reconstruction are a safe option that can prevent critical postoperative complications due to the poor general condition, effects of PBT on the remnant gastric conduit, and use of sorafenib.

DOI： 10.1186/s40792-020-00902-0

A prospective trial to evaluate treatment effects of a β-hydroxy-β-methylbutyrate containing nutrient for leakage at the anastomotic site after esophagectomy.

特集進行直腸癌のベストプラクティス II. 各論 5.局所再発直腸癌の再発部位を意識した治療戦略

小倉淳司, 上原圭介, 相場利貞, 江畑智希, 横山幸浩, 國料俊男, 伊神剛, 深谷昌秀, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 梛野正人

外科 Vol. 82 ( 7 ) page： 742 - 748 2020.6

Mitsuro Kanda, Masahiko Koike, Masahide Fukaya, Kazushi Miyata, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Kenta Murotani, Michitaka Fujiwara, Masato Nagino, Yasuhiro Kodera

Nagoya journal of medical science Vol. 82 ( 1 ) page： 33 - 37 2020.2

Language：English Publishing type：Research paper (scientific journal)

Anastomotic leakage after esophagectomy is associated with prolonged hospitalization and increased medical cost. Additionally, it sometimes leads to a fatal condition and impaired postoperative quality of life. During the process of wound healing, β-hydroxy-β-methylbutyrate (HMB) is important for collagen biosynthesis. An open-label prospective intervention trial has been designed to evaluate the treatment effect of an enteral nutrient containing HMB with arginine and glutamine (Abound, Abbott Japan Co., Ltd.) for leakage at the anastomotic site after esophagectomy. Patients in whom leakage at the anastomotic site developed within 14 days after esophagectomy are eligible and Abound (24 g) is administered for 14 days through an enteral feeding tube. The target sample size is 10. The primary endpoint is duration between diagnosis and cure of leakage. Surgical procedure, safety, length of fasting, drainage placement and hospital stay, and nutritional status are determined as secondary endpoints. A historical control consisting of 20 patients who had leakage at the anastomotic site after esophagectomy between 2005 and 2018 at Nagoya University Hospital is compared with enrolled patients.

DOI： 10.18999/nagjms.82.1.33

The impact of cervical lymph node dissection on acid and duodenogastroesophageal reflux after intrathoracic esophagogastrostomy following transthoracic esophagectomy.

Soichiro Asai, Masahide Fukaya, Kazushi Miyata, Keita Itatsu, Ryoji Miyahara, Kazuhiro Furukawa, Tomoki Ebata, Masato Nagino

Surgery today Vol. 49 ( 12 ) page： 1029 - 1034 2019.12

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: The aim of this study was to evaluate the impact of cervical lymph node dissection on acid reflux and duodenogastroesophageal reflux (DGER) in patients undergoing transthoracic esophagectomy with gastric tube reconstruction and intrathoracic esophagogastrostomy. METHODS: Thirty-one patients receiving transthoracic esophagectomy with gastric tube reconstruction by intrathoracic esophagogastrostomy were divided into the following two groups: a two-field lymph node dissection group (2F group) and a three-field lymph node dissection group (3F group). All patients underwent 24-h pH and bilirubin monitoring and gastrointestinal endoscopy at 1 year after surgery. The 24-h pH and bilirubin monitoring results, endoscopic findings, and reflux symptoms were compared between the 2 groups. RESULTS: No acid reflux was observed in the 2F group, whereas it was observed in 6 (40%) patients in the 3F group (p = 0.007). DGER was found in 2 patients (13%) in the 2F group and in 8 (53%) in the 3F group (p = 0.023). Four patients (25%) in the 2F group and 9 (60%) in the 3F group (p = 0.048) had reflux esophagitis. CONCLUSION: Cervical lymph node dissection increases acid reflux and DGER and can lead to an increase in the incidence of reflux esophagitis in patients undergoing intrathoracic esophagogastrostomy.

DOI： 10.1007/s00595-019-01835-4

Thoracoscopically Resected Esophageal Duplication Cyst with High Value of Serum CA19-9 at the First Visit—Report of a Case—

Esophageal reconstruction using a pedicled jejunum following esophagectomy for metastatic esophageal stricture from breast cancer in a patient with previous pancreatoduodenectomy

Asai Soichiro, Fukaya Masahide, Fujieda Hironori, Igami Tsuyoshi, Tsunoda Nobuyuki, Salcatoku Yayoi, Kamei Yuzuru, Miyata Kazushi, Nagino Masato

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 81 ( 4 ) page： 679 - 685 2019.11

Repeated episodes of thoracic empyema after spontaneous esophageal rupture

Sakatoku Yayoi, Fukaya Masahide, Kawaguchi Koji, Fujieda Hironori, Miyata Kazushi, Nagino Masato

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 81 ( 4 ) page： 693 - 699 2019.11

画像診断と病理食道平滑筋腫

兵藤良太, 岩野信吾, 長縄慎二, 宮田一志, 島田聡子

画像診断 Vol. 39 ( 7 ) page： 662 - 663 2019.5

ASAI Soichiro, FUKAYA Masahide, HIGAKI Eiji, MIYATA Kazushi, MIURA Yasutomo, NAGINO Masato

Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) Vol. 80 ( 4 ) page： 700 - 706 2019

Language：Japanese Publisher：Japan Surgical Association

A 41-year-old man with chest pain visited a nearby hospital in February 2017. Chest CT scan detected a mediastinal cystic tumor, and he was referred to our hospital for further examination and treatment. In the blood test, the serum CA19-9 level was as high as 5,960 U/ml, and upper gastrointestinal endoscopy showed a submucosal bulging with bluish purple mucosa encircling the half of the lumen in the middle to lower esophagus.Ultrasound endoscopy visualized the lesion as a tumor with mosaic pattern contents, indicating the presence of hematoma. CT scan showed an 83 × 41 × 115 mm bilocular cystic lesion in the anterior surface of the esophagus which compressed and narrowed the esophagus. Although it was diagnosed as esophageal cyst, he had chest pain and dysphagia, and so cystectomy using thoracoscopy was performed in March. The postoperative course was uneventful and he was discharged on the 10th postoperative day. Histologically, pseudostratified epithelium was found on the inner surface of the cyst and the cystic wall had two muscular layers. Duplication cyst was thus diagnosed.

DOI： 10.3919/jjsa.80.700

The management for Clavien-Dindo grade Ⅲ・Ⅳ complications after hepatectomy with extrahepatic bile duct resection

Docetaxel, cisplatin and fluorouracil as neoadjuvant chemotherapy for esophageal cancer with prophylactic pegfilgrastim

Maeda Osamu, Koike Masahiko, Fukaya Masahide, Miyata Kazushi, Iwata Naoki, Nagino Masato, Kodera Yasuhiro, Ando Yuichi

ANNALS OF ONCOLOGY Vol. 29 2018.10

特集消化器癌に対する最新の集学的治療戦略 II. 各論 6.胆道癌の集学的治療戦略

江畑智希, 水野隆史, 横山幸浩, 伊神剛, 山口淳平, 尾上俊介, 深谷昌秀, 上原圭介, 宮田一志, 相場利貞, 梛野正人

外科 Vol. 80 ( 8 ) page： 851 - 858 2018.7

Sugawara Gen, Yokoyama Yukihiro, Ebata Tomoki, Igami Tsuyoshi, Yamaguchi Junpei, Onoe Shunsuke, Kokuryo Toshio, Tsunoda Nobuyuki, Fukaya Masahide, Uehara Keisuke, Miyata Kazushi, Aiba Toshisada, Nagino Masato

Journal of Japan Society for Surgical Infection Vol. 15 ( 3 ) page： 201 - 208 2018.6

Language：Japanese Publisher：Japan Society for Surgical Infection

【Aim】To report the course and management for Clavien-Dindo gradeⅢ・Ⅳ complications after hepatectomy with extrahepatic bile duct resection.【Patient】428 consecutive patients who underwent hepatobiliary resection with cholangiojejunostomy between January 2009 and December 2015 were analyzed retrospectively.【Results】There were 278 men and 150 women, with a median age of 68 years (range 29-89 years) . The cases of Grade Ⅲ complications were 229, and those of Ⅳ were 28. Compared with Grade Ⅲ, the rate of male patients, the incidence of preoperative bacteremia of patients with Grade Ⅳ was significantly higher. Compared with Grade Ⅲ, the incidence of combined vascular resection of patients with Grade Ⅳ was significantly higher, operative time was longer, and blood loss was much more. Compared with Grade Ⅲ, the incidence of incisional SSI, pneumoniae, and postoperative bacteremia of patients with Grade Ⅳ was significantly higher. The amount of blood loss more than 1,500mL, presence of pneumoniae, and bacteremia were recognized as a risk factor of postoperative hepatic failure. 【Conclusion】 The management and control for Clavien-Dindo grade Ⅲ complications leads to prevention of occurrence of Grade Ⅳ complications.

DOI： 10.24679/gekakansen.15.3_201

胆道再建を伴う肝切除後のClavien-Dindo Grade III・IV症例に対する感染管理

菅原元, 横山幸浩, 江畑智希, 伊神剛, 山口淳平, 尾上俊介, 國料俊男, 角田伸行, 深谷昌秀, 上原圭介, 宮田一志, 相場利貞, 梛野正人

日本外科感染症学会雑誌 Vol. 15 ( 3 ) page： 201 - 208 2018.6

Language：Japanese Publisher：(一社)日本外科感染症学会

【目的】胆道再建を伴う肝切除術後のClavien-Dindo Grade III・IV症例の経過について検討すること。【対象と方法】2009年から2015年の7年間における胆道再建を伴う肝切除施行例428例を対象として、Grade III・IV症例の患者背景・術式・術後合併症および治療経過について比較検討した。肝不全発症の危険因子についても検討した。【結果】Grade IV症例はIII症例に比較して、右肝切除施行および血管合併切除併施症例が多く、出血量が多かった。術後合併症では肺炎・敗血症の発症が多く、平均在院期間は長かった。肝不全発症の危険因子は出血量1,500mL以上、肺炎・敗血症の発症であった。Grade III・IV症例ともに治療法は、腹腔内のドレナージ状況を良好に保つこと、全身性の感染症が疑われる際は抗菌薬を追加投与することが基本となる。【結論】Clavien-Dindo Grade III症例に対する感染管理を徹底することが、Clavien-Dindo Grade IV症例の発症予防につながる。(著者抄録)

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Peritonitis after percutaneous endoscopic gastrojejunostomy for levodopa–carbidopa intestinal gel treatment despite concomitant use of gastropexy

Tsuboi T., Watanabe H., Funasaka K., Takebayashi M., Miyata K., Katsuno M.

Neurology and Clinical Neuroscience Vol. 6 ( 2 ) page： 64 - 66 2018.3

Publisher：Neurology and Clinical Neuroscience

A 58-year-old man with Parkinson's disease experienced peritonitis after percutaneous endoscopic gastrojejunostomy (PEG-J) for levodopa–carbidopa intestinal gel treatment despite concomitant use of gastropexy. Although gastropexy reduces complications including peritonitis, clinicians should consider structural characteristics of PEG-J devices and patients’ anatomical differences. We recommend that suture threads are removed 2–4 weeks after PEG-J and that the PEG-J tube length outside the body is routinely recorded to assess tube dislocation.

DOI： 10.1111/ncn3.12183

The Impact of the Location of Esophagogastrostomy on Acid and Duodenogastroesophageal Reflux After Transthoracic Esophagectomy with Gastric Tube Reconstruction and Intrathoracic Esophagogastrostomy. International journal

Hiroaki Usui, Masahide Fukaya, Keita Itatsu, Kazushi Miyata, Ryoji Miyahara, Kohei Funasaka, Masato Nagino

World journal of surgery Vol. 42 ( 2 ) page： 599 - 605 2018.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The aim of this study was to evaluate the impact of the location of esophagogastrostomy on acid and duodenogastroesophageal reflux (DGER) in patients undergoing gastric tube reconstruction and intrathoracic esophagogastrostomy. METHODS: Thirty patients receiving transthoracic esophagectomy without cervical lymph node dissection and gastric tube reconstruction by intrathoracic anastomosis were enrolled. All patients underwent 24-h pH and bilirubin monitoring and gastrointestinal endoscopy one year after surgery. Patients were divided into three groups according to esophagogastrostomy location: group A (n = 9), above the top of the aortic arch; group B (n = 15), between the top and bottom of the aortic arch; and group C (n = 6), below the bottom of the aortic arch. The relations among the esophagogastrostomy location, 24-h pH and bilirubin monitoring results, endoscopic findings, and reflux symptoms were investigated. RESULTS: No acid reflux into the remnant esophagus was observed in group A, whereas it was observed in three of 15 patients (20%) in group B and in two of six patients (33%) in group C (P = 0.139). No DGER was found in group A, whereas DGER was observed in eight (53%) patients in group B and all patients in group C (P < 0.001). Reflux esophagitis was observed in one patient (11%) in group A, five patients (33%) in group B, and all patients in group C (P = 0.002). CONCLUSION: In gastric tube reconstruction via intrathoracic anastomosis, esophagogastrostomy should be performed above the top of the aortic arch to prevent postoperative DGER and reduce the incidence of reflux esophagitis.

DOI： 10.1007/s00268-017-4186-1

A Case of Esophageal Cancer with Lymph Node Recurrence Three Times and Secondary Cancer after Definitive Chemoradiotherapy

SAKATOKU Yayoi, FUKAYA Masahide, MIYATA Kazushi, TAKAHASHI Takamasa, NAGINO Masato

Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) Vol. 79 ( 1 ) page： 84 - 89 2018

Language：Japanese Publisher：Japan Surgical Association

A 50-year-old woman was diagnosed with unresectable advanced middle thoracic esophageal cancer with lymph node metastases involving the trachea in July 2008. After definitive chemoradiotherapy (dCRT) with cisplatin (CDDP) / 5-fluorouracil (5-FU) and 60 Gy irradiation and additional 2 courses of CDDP / 5-FU were performed, complete response (CR) was obtained. Around half year after the treatment, positron emission tomography-computed tomography showed para-aortic lymph node (PAN) and supraclavicular lymph node (SCN) metastases. Five courses of CDDP / 5-FU and 3 courses of 5-FU / nedaplatin (CDGP) were performed. CR was achieved for PAN but not for SCN, which was judged as stable disease (SD). Since no other lesions were identified, she underwent salvage lymphadenectomy in July 2010. Seven months after the operation, paraesophageal and peri-gastric lymph nodes metastases were detected. After 5 courses of 5-FU / CDGP, the metastatic lymph nodes disappeared. However, relapse of paraesophageal lymph node metastasis and secondary primary esophageal cancer at 23 cm from the incisor teeth developed in February 2012. As R0 resection could be expected, salvage esophagectomy by laparotomy-right thoracotomy approach was performed in March 2012. The patient is now alive without recurrence for 3 years and 7 months after the salvage esophagectomy (or 7 years and 3 months after dCRT).

DOI： 10.3919/jjsa.79.84

尾上俊介, 江畑智希, 横山幸浩, 國料俊男, 角田伸行, 伊神剛, 菅原元, 深谷昌秀, 上原圭介, 水野隆史, 山口淳平, 宮田一志, 相場利貞, 梛野正人

臨床外科 Vol. 72 ( 13 ) page： 1419 - 1422 2017.12

Clinical value of a prophylactic minitracheostomy after esophagectomy: analysis in patients at high risk for postoperative pulmonary complications. International journal

Yayoi Sakatoku, Masahide Fukaya, Kazushi Miyata, Keita Itatsu, Masato Nagino

BMC surgery Vol. 17 ( 1 ) page： 120 - 120 2017.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The aim of this study is to evaluate the clinical value of a prophylactic minitracheostomy (PMT) in patients undergoing an esophagectomy for esophageal cancer and to clarify the indications for a PMT. METHODS: Ninety-four patients who underwent right transthoracic esophagectomy for esophageal cancer between January 2009 and December 2013 were studied. Short surgical outcomes were retrospectively compared between 30 patients at high risk for postoperative pulmonary complications who underwent a PMT (PMT group) and 64 patients at standard risk without a PMT (non-PMT group). Furthermore, 12 patients who required a delayed minitracheostomy (DMT) due to postoperative sputum retention were reviewed in detail, and risk factors related to a DMT were also analyzed to assess the indications for a PMT. RESULTS: Preoperative pulmonary function was lower in the PMT group than in the non-PMT group: FEV1.0 (2.41 vs. 2.68 L, p = 0.035), and the proportion of patients with FEV1.0% <60 (13.3% vs. 0%, p = 0.009). No between-group differences were observed in the proportion of patients who suffered from postoperative pneumonia, atelectasis, or re-intubation due to respiratory failure. Of the 12 patients with a DMT, 11 developed postoperative pneumonia, and three required re-intubation due to severe pneumonia. Multivariate analysis revealed FEV1.0% <70% and vocal cord palsy were independent risk factors related to a DMT. CONCLUSION: A PMT for high-risk patients may prevent an increase in the incidence of postoperative pneumonia and re-intubation. The PMT indications should be expanded for patients with vocal cord palsy or mild obstructive respiratory disturbances.

DOI： 10.1186/s12893-017-0321-z

Successful bypass operation for esophageal obstruction after acute esophageal necrosis: a case report. International journal

Yayoi Sakatoku, Masahide Fukaya, Kazushi Miyata, Masato Nagino

Surgical case reports Vol. 3 ( 1 ) page： 4 - 4 2017.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Acute esophageal necrosis (AEN) is a rare clinical disorder. Esophageal stenosis or obstruction is one of severe complications, but there are a few reports about surgical treatments. In such a situation, it still remains controversial which to choose, esophagectomy or bypass operation. CASE PRESENTATION: A 61-year-old woman was admitted to the local hospital for septic shock with diabetic ketoacidosis due to necrotizing fasciitis of the right thigh. Three days later, she had hematemesis, and gastrointestinal endoscopy revealed black mucosal coloration throughout the entire esophagus. She was diagnosed as having AEN. Her general condition improved after intensive care, debridement, and treatment with antibiotics and a proton pump inhibitor; the esophageal mucosal color recovered. However, an esophageal stricture developed after 1 month, and the patient underwent gastrostomy to remove an esophageal obstruction after 3 months. She was referred to our hospital for surgical treatment 1 year and 4 months after the occurrence of AEN because of her strong desire for oral intake. Her medical condition was poor, and she could not walk due to generalized muscle weakness. After rehabilitation for 8 months, we performed an esophageal bypass using a gastric conduit via the percutaneous route rather than esophagectomy because of her multiple severe comorbidities including walking difficulty, chronic hepatitis C, cerebrovascular disease, and chronic renal failure. Minor leakage of the esophagogastrostomy occurred and was resolved with conservative treatment. The patient began oral intake on postoperative day 34 and was discharged on day 52. CONCLUSION: Esophageal obstruction after AEN was successfully treated by esophageal bypass using a gastric conduit in a high-risk patient. Because the majority of patients with AEN have multiple severe comorbidities, assessing the medical condition of the patient adequately is important prior to choosing either an esophagectomy or bypass surgery.

DOI： 10.1186/s40792-016-0277-8

Retrosternal Reconstruction Can be a Risk Factor for Upper Extremity Deep Vein Thrombosis After Esophagectomy. International journal

Takamasa Takahashi, Masahide Fukaya, Kazushi Miyata, Yayoi Sakatoku, Masato Nagino

World journal of surgery Vol. 41 ( 12 ) page： 3154 - 3163 2017.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is a rare but important complication because it can cause pulmonary embolism. The aim of this study was to investigate the incidence of UEDVT after esophagectomy and the risk factors related to UEDVT. METHODS: This study included 88 patients who underwent esophagectomy with retrosternal or posterior mediastinal reconstruction using gastric tube. The incidence of UEDVT and the diameter of left brachiocephalic vein were measured using postoperative contrast-enhanced computed tomography (CT). (a) The distance from sternum to brachiocephalic artery and (b) the distance from sternum to vertebra were measured by preoperative CT, and the ratio of (a) to (b) was defined as the width of the retrosternal space. RESULTS: Among the patients, 14 (15.9%) suffered from UEDVT. All UEDVTs were found in left-side upper extremity deep veins. Twelve of the 14 patients (85.7%) underwent retrosternal reconstruction. In a multivariate analysis, retrosternal reconstruction was an independent risk factor for UEDVT (odds ratio 5.48). The diameter of the left brachiocephalic vein in patients with retrosternal reconstruction was significantly smaller than that in patients with posterior mediastinal reconstruction (4.3 vs 6.9 mm; P < 0.001) due to compression of left brachiocephalic vein by the gastric tube. Among patients with retrosternal reconstruction, the width of the retrosternal space in patients with UEDVT was significantly smaller than that in patients without UEDVT (0.21 vs 0.27; P = 0.001). CONCLUSION: Retrosternal reconstruction can be a risk factor for UEDVT. In patients with small width of the retrosternal space, retrosternal reconstruction might be inappropriate.

DOI： 10.1007/s00268-017-4120-6

Gradually shrinking intra-abdominal desmoid tumor derived from the stomach in a young boy: a case report. International journal

Kazushi Miyata, Masahide Fukaya, Masato Nagino

Surgical case reports Vol. 3 ( 1 ) page： 54 - 54 2017.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Intra-abdominal desmoid tumors, particularly those derived from the stomach, are rare. Such tumors are associated with a history of familial adenomatous polyposis (FAP), trauma, or surgical procedures in general. In addition, spontaneous shrinking of an intra-abdominal desmoid tumor is rarer. And desmoid tumors most commonly arise during the fourth decade of life. CASE PRESENTATION: A 17-year-old boy with lower abdominal pain was diagnosed with a gastrointestinal stromal tumor (GIST) or a hematoma at a local hospital. He had no history of FAP, trauma, or previous surgery. Abdominal computed tomography (CT) was performed for observational purposes three times over a 9-month period. The tumor gradually decreased in size over time; however, the tumor did not shrink sufficiently to be diagnosed as a hematoma. Because there was a high possibility of a GIST from the stomach, he underwent laparotomy. Operative findings revealed that the tumor was a hard mass firmly attached to both the greater curvature of the stomach and the inferior pole of the spleen. Pathologically, the tumor was diagnosed as a desmoid tumor derived from the stomach. CONCLUSION: For a young boy without a history of FAP, trauma, or surgical procedures, it is difficult to define an intra-abdominal tumor near the stomach as a desmoid tumor. In such cases, surgical resection is recommended for a definitive diagnosis.

DOI： 10.1186/s40792-017-0330-2