Safety, technical transferability, and oncological outcomes of multi-institutional robotic distal gastrectomy for gastric cancer: impact of surgeons qualified under the endoscopic surgical skill qualification system of the Japan Society for Endoscopic Surgery
Yuma Ebihara, Noriaki Kyogoku, Hironobu Takano, Hideyuki Wada, Takeo Nitta, Daisuke Saikawa, Yoshiyuki Yamamura, Minoru Takada, Toshiaki Shichinohe, Satoshi Hirano
Journal of Robotic Surgery, 2026年03月10日
研究論文（学術雑誌）

Surgical and Oncologic Outcomes of Robotic Versus Laparoscopic Distal Gastrectomy for Gastric Cancer: Real-World Data From a Multi-Institutional Propensity Score-Matched Study.
Noriaki Kyogoku, Yuma Ebihara, Takeo Nitta, Hideyuki Wada, Hironobu Takano, Minoru Takada, Yoshiyuki Yamamura, Daisuke Saikawa, Toshiaki Shichinohe, Satoshi Hirano
Asian journal of endoscopic surgery, 19, 1, e70274, 2026年, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Robotic gastrectomy (RG) has been increasingly adopted for gastric cancer (GC). Although high-volume centers report superior outcomes compared with laparoscopic gastrectomy (LG), real-world evidence remains limited. This study compared short- and long-term outcomes of robotic distal gastrectomy (RDG) and laparoscopic distal gastrectomy (LDG) using propensity score matching. METHODS: Patients who underwent curative RDG or LDG between April 2018 and December 2024 were retrospectively reviewed. Propensity score matching was performed based on demographics, clinical factors, surgical procedures, pathological stage (Japanese Classification of Gastric Carcinoma), and perioperative chemotherapy. Surgical, postoperative, and oncological outcomes were compared. RESULTS: Among 821 patients, 228 matched pairs were analyzed. Operative time was longer in the RDG group than in the LDG group (median 333 vs. 272.5 min, p < 0.0001). RDG was associated with lower rates of postoperative intra-abdominal infectious complications, both overall and Clavien-Dindo grade ≥ II. Postoperative hospital stay was shorter in the RDG group (median 9 vs. 10 days, p = 0.0126). In patients with pathological stage III disease, operative time did not differ significantly between groups. The maximum postoperative serum C-reactive protein level was lower in the RDG group, indicating a reduced inflammatory response. Overall and recurrence-free survival did not differ significantly between groups. CONCLUSION: RDG was associated with fewer intra-abdominal infections, shorter hospital stay, and reduced inflammatory response compared with LDG. For advanced GC (pStage III), RDG did not increase operative time and may provide clinical advantages. RG may be particularly beneficial for patients with advanced disease.

Male Sex as a Risk Factor for Perioperative Morbidity and Recurrence Following Minimally Invasive Distal Gastrectomy for Gastric Cancer: A Propensity Score Matching Analysis.
Yuma Ebihara, Noriaki Kyogoku, Hironobu Takano, Hideyuki Wada, Takeo Nitta, Daisuke Saikawa, Yoshiyuki Yamamura, Minoru Takada, Toshiaki Shichinohe, Satoshi Hirano
In vivo (Athens, Greece), 40, 2, 992, 1006, 2026年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/AIM: This study aimed to investigate the effect of sex-related differences on surgical outcomes, postoperative complications, and prognosis in patients undergoing minimally invasive distal gastrectomy (MIDG) for gastric cancer (GC). PATIENTS AND METHODS: We retrospectively analyzed 988 patients who underwent MIDG for GC at five institutions between January 2018 and December 2024. The patients were categorized according to sex (male or female). To minimize selection bias, propensity score matching (PSM) was performed using the following covariates: age, body mass index, the American Society of Anesthesiologists physical status classification, surgical approach (laparoscopic or robotic), reconstruction method, adjuvant chemotherapy, clinical stage, postoperative complications (Clavien-Dindo classification: CD), and prognoses, including overall survival (OS), relapse-free survival (RFS), and Cancer-Specific Survival (CSS). RESULTS: Even after the PSM, male patients demonstrated significantly worse outcomes in surgical and long-term settings. Compared with the females, males had a longer median operation time (293 min vs. 274 min, p<0.001) and greater blood loss (median 5 ml vs. 0 ml, p<0.001). Incidence of postoperative complications (CD II) was significantly higher in the male group (15.4% vs. 9.5%, p=0.037) than that in the female group. Multivariate logistic regression analysis identified male sex as an independent risk factor for postoperative complications (odds ratio: 1.727; 95% confidence interval=1.032-2.939; p=0.037). In a multivariate Cox regression analysis, male sex was as an independent risk factor for poorer RFS. CONCLUSION: Male patients undergoing MIDG face significantly higher risks of postoperative complications and cancer recurrence than female patients, independent of baseline clinical and pathological factors.

Minimally invasive abdominal and left thoracic approach (MALTA) for Siewert type II esophagogastric junction adenocarcinoma: A retrospective cohort study of perioperative and oncologic outcomes.
Takeo Nitta, Yuma Ebihara, Ryo Takagi, Hironobu Takano, Saseem Poudel, Hideyuki Wada, Toshiaki Shichinohe, Satoshi Hirano
Surgical endoscopy, 40, 1, 586, 597, 2026年01月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The optimal surgical approach for Siewert type II adenocarcinoma of the esophagogastric junction (AEG) remains controversial because of the complex lymphatic spread and anatomical constraints. We previously developed a novel minimally invasive abdominal and left thoracic approach (MALTA) to overcome the limitations of conventional techniques. This study aimed to provide an updated analysis of MALTA with extended follow-up period compared with our initial report. METHOD: A retrospective review was conducted on 16 consecutive patients who underwent MALTA for Siewert type II AEG between 2013 and 2023. The procedure combined laparoscopic gastrectomy and thoracoscopic lower mediastinal esophagectomy with intrathoracic reconstruction, both of which were performed without intraoperative repositioning. Perioperative outcomes, postoperative complications, and survival rates were analyzed. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). The primary outcome was feasibility and safety (R0 resection rate and postoperative complications). Secondary outcomes included OS and DFS. RESULTS: R0 resection was achieved in all patients. The median operative time was 438 min, and median blood loss was 28 mL. Postoperative complications occurred in 31.3% of the patients, including anastomotic leakage (12.5%) and empyema (18.8%). No in-hospital deaths or respiratory complications were reported. The median follow-up duration was 51 months. The 1-, 3-, and 5-year OS rates were 87.5% (95% confidence interval [CI], 61.4-96.9), 67.7% (95% CI, 41.8-85.9), and 60.2% (95% CI, 34.7-81.1), respectively. The DFS rates were 68.8% (95% CI, 43.3-86.4), 56.3% (95% CI, 32.4-77.5), and 42.9% (95% CI, 21.5-67.3), respectively. CONCLUSIONS: MALTA appears to be a feasible, safe, and minimally invasive option for Siewert type II AEG, enabling stable intrathoracic anastomosis without patient repositioning. These results suggest its potential utility in achieving favorable perioperative and survival outcomes.

Comparison of Clinical Outcomes Between Billroth-I and Roux-en-Y Reconstruction Following Minimally Invasive Distal Gastrectomy for Gastric Cancer: A Multicenter Retrospective Propensity Score-Matched Analysis.
Yuma Ebihara, Noriaki Kyogoku, Hironobu Takano, Hideyuki Wada, Takeo Nitta, Daisuke Saikawa, Yoshiyuki Yamamura, Minoru Takada, Toshiaki Shichinohe, Satoshi Hirano
Surgical laparoscopy, endoscopy & percutaneous techniques, 35, 6, 2025年12月01日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Gastric cancer (GC) is the third leading cause of cancer deaths, with surgery as the primary treatment; however, the outcomes of different types of surgeries still need to be understood further. This study evaluated the surgical outcomes and prognosis after minimally invasive distal gastrectomy (MIDG) for GC in a multicenter retrospective cohort using propensity score matching. METHODS: This study retrospectively enrolled 688 patients who underwent curative MIDG for GC at five institutions between January 2018 and December 2024. Patients were categorized into Billroth-I reconstruction (B-I) and Roux-en-Y (R-Y) reconstruction groups. Propensity score matching was performed using the following covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, Japanese Classification of Gastric Carcinoma stage, neoadjuvant chemotherapy, and adjuvant chemotherapy. Surgical outcomes and prognoses were compared. RESULTS: Three hundred propensity score-matched pairs were identified. The R-Y group had longer median operation time [309 (131 to 531) min vs. 265 (126 to 532) min; P <0.001], longer postoperative hospital stay [10 (5 to 110) d vs. 10 (5 to 43) d; P =0.042], and greater median blood loss ( P =0.047) than the B-I group. Complications of Clavien-Dindo (CD) grade II ( P <0.001) and grade III ( P =0.027) were more frequent in the R-Y group than in the B-I group. Five-year overall survival (OS) was significantly higher in the B-I group than in the R-Y group (91.1% vs. 83.4%; P =0.019), whereas 5-year relapse-free survival (RFS) showed no significant difference between these 2 groups ( P =0.056). Independent prognostic factors included reconstruction method, postoperative complications (≥CD III), and lymph node metastasis (pN) for OS and age (≥80), pT, and pN for RFS. CONCLUSIONS: Patients who underwent R-Y reconstruction had more frequent postoperative complications than those who underwent B-I reconstruction after MIDG. Although not significantly associated with RFS, these complications may affect OS. The findings of this study could help develop strategies for improving GC treatment.

Postoperative Complications, Including Minor Complications, Worsen Prognosis After Laparoscopic Distal Gastrectomy for Gastric Cancer.
Yuma Ebihara, Noriaki Kyogoku, Hironobu Takano, Hideyuki Wada, Takeo Nitta, Daisuke Saikawa, Yoshiyuki Yamamura, Minoru Takada, Toshiaki Shichinohe, Satoshi Hirano
Anticancer research, 45, 12, 5619, 5631, 2025年12月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND/AIM: The relationship between postoperative complications and prognosis after laparoscopic distal gastrectomy (LDG) for gastric cancer (GC) remains controversial. This study evaluated this association using propensity score-matched analysis. PATIENTS AND METHODS: We analyzed data of 590 patients who underwent curative LDG for GC at five institutions between January 2018 and December 2024. Patients were categorized into non-complication and complication groups (non-CG and CG, respectively), with complications defined as Clavien-Dindo grade ≥II (CD ≥II). Minor complications were defined as CD grades I or II, and major complications were defined as CD grades ≥III. Propensity score matching (PSM) was performed using the following covariates: age, sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, reconstruction method, Japanese Classification of Gastric Carcinoma stage, neoadjuvant chemotherapy, and adjuvant chemotherapy. Survival curves were compared using the log-rank test, and multivariate analysis was performed using the Cox proportional hazard models. RESULTS: Overall incidence of postoperative complications (CD ≥II) was 14.9% (88/590 patients). After the PSM (85 pairs), the CG group had a significantly longer postoperative hospital stay than the non-CG group [median (range), 18 (7-110) days vs. 9 (5-18) days; p<0.001]. Five-year overall survival (OS) rate was 90.7% in the non-CG group and 70.4% in the CG group (p=0.009), and 5-year relapse-free survival rate was 87.7% in the non-CG group and 70.9% in the CG group (p=0.027). Multivariable analysis identified age ≥80 years, postoperative complications (CD ≥II), and lymph node metastasis (pN) as independent prognostic factors for OS. CONCLUSION: Reducing the incidence of postoperative complications (CD ≥II) may improve prognosis in patients with GC undergoing LDG, contributing to better treatment strategies for GC.

近赤外線蛍光分光システムLumifinderTMとインドシアニングリーン(ICG)を用いた食道切除術における胃管血流の定量評価
新田 健雄, 海老原 裕磨, 高野 博信, 和田 秀之, 七戸 俊明, 平野 聡
北海道医学雑誌, 100, 2, 106, 106, 北海道医学会, 2025年11月
日本語

Intrathoracic anastomotic leak after esophagojejunostomy in a patient with preoperative coronavirus disease 2019: A case treated with T-tube drainage.
Takuma Kurotaki, Yuma Ebihara, Hirotake Abe, Hideyuki Wada, Toshiaki Shichinohe, Satoshi Hirano
International journal of surgery case reports, 135, 111844, 111844, 2025年08月19日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Intrathoracic anastomotic leakage can lead to severe complications, such as mediastinitis and empyema, with a high mortality rate. However, the optimal treatment strategy for anastomotic leakage remains controversial. PRESENTATION OF CASE: This case involves a 55-year-old male patient with esophagogastric junction cancer who experienced intrathoracic anastomotic leakage following esophagojejunostomy, exacerbated by coronavirus disease 2019 (COVID-19)-related immunodeficiency. Following conservative therapy, the patient had a right-sided empyema, necessitating thoracoscopic pleural decortication on postoperative day (POD) 35. A T-tube was inserted at the anastomotic site, and its short limb maintained stability within the lumen, facilitating fistula formation. Postoperatively, the patient's body temperature and inflammatory markers gradually returned to normal. Oral intake was resumed on POD68, and the T-tube was removed on POD79. Subsequently, the patient was transferred to another hospital for rehabilitation on POD96. DISCUSSION: In this patient with COVID-19 infection and systemic sepsis, T-tube drainage facilitated fistula formation and ensured continuous decompression at the anastomotic site, contributing to successful conservative management. CONCLUSION: T-tube drainage may be an effective and feasible treatment option for intrathoracic anastomotic leakage in patients with severe immunodeficiency.

新規内視鏡用蛍光スペクトル測定装置「Lumifinder」を用いた術中腫瘍同定法(Detecting fluorescent marking clip with a novel laparoscopic fluorescence detection system)　　　　　　　　　　　　　　　
海老原 裕磨, 上村 志臣, 高野 博信, 和田 秀之, 新田 健雄, 小西 和哉, 七戸 俊明, 平野 聡
日本消化器外科学会総会, 80回, 747, 747, (一社)日本消化器外科学会, 2025年07月
日本語

新規内視鏡用蛍光スペクトル測定装置「Lumifinder」を用いた術中腫瘍同定法(Detecting fluorescent marking clip with a novel laparoscopic fluorescence detection system)　　　　　　　　　　　　　　　
海老原 裕磨, 上村 志臣, 高野 博信, 和田 秀之, 新田 健雄, 小西 和哉, 七戸 俊明, 平野 聡
日本消化器外科学会総会, 80回, 747, 747, (一社)日本消化器外科学会, 2025年07月
日本語

Feasibility of Detecting Fluorescent Marking Clip with Novel Fluorescence Detection System in Minimally Invasive Stomach and Esophageal Surgery.
Hideyuki Wada, Yuma Ebihara, Hironobu Takano, Mariko Hayashi, Takeo Nitta, Toshiaki Shichinohe, Satoshi Hirano
Journal of clinical medicine, 14, 3, 2025年01月23日, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Determining the optimal resection line for an organ that cannot be palpated is crucial, but challenging, in minimally invasive gastrointestinal (GI) surgery. Therefore, there is an urgent need to establish the most effective method for tumor localization. We hypothesize that our novel near-infrared (NIR) fluorescence detection system will enable the highly accurate detection of fluorescent clips marking GI cancer. Methods: Twenty-five patients with gastric cancer, esophagogastric junctional cancer, or esophageal cancer will be enrolled. NIR fluorescent clips will be placed endoscopically around the tumor on the day before surgery. Patients in whom clip dislodgement is confirmed by preoperative abdominal radiography will be excluded. The clips will be placed before the transection of the organ, and those on the surgical specimen will be observed after transection using both the novel NIR fluorescence detection system and an existing NIR fluorescence imaging system. The detection rate and time, the fluorescence intensity, surgical margins, and adverse events will be evaluated. This study has been registered in the Japan Registry of Clinical Trials, with the code jRCTs012240043. (Expected) Results: As the novel fluorescence detection system allows for higher-sensitivity detection by analyzing the spectral characteristics of fluorescence and measuring the peak values, we anticipate that this new system will detect the fluorescent clips with high accuracy. Conclusions: This study aims to establish a novel tumor-marking method using fluorescent clips and a new detection system that can be easily applied in various medical facilities.

Simultaneous Resection of Esophageal Carcinosarcoma with Cancer of the Stomach and Transverse Colon: A Case Report.
Kenichi Mizunuma, Masato Suzuoki, Ryo Takahashi, Shinya Otsuka, Hiroki Niwa, Hideyuki Wada, Kei Hiraoka, Kazuteru Komuro, Noriko Kimura, Nozomu Iwashiro, Masanori Ohara, Satoshi Hirano
Surgical case reports, 11, 1, 2025年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Esophageal carcinosarcoma is a rare malignant neoplasm composed of both carcinoma and sarcoma components. Here, we report a case of esophageal carcinosarcoma in a patient with cancers of the transverse colon and stomach who underwent simultaneous resection of all 3 malignancies. CASE PRESENTATION: A 71-year-old man presented with dysphagia and was diagnosed with carcinoma in the mid-thoracic esophagus. Laboratory data showed normal tumor markers-carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and carbohydrate antigen 19-9 (CA19-9). Esophagoscopy confirmed the presence of a polypoid tumor in the middle thoracic esophagus. Endoscopic biopsy specimens were reported as spindle cell carcinoma. Colonoscopy revealed a semicircular tumor in the transverse colon. Simultaneous esophagectomy and regional lymphadenectomy and transverse colon resection using video-assisted thoracoscopic surgery (VATS) and hand-assisted laparoscopic surgery (HALS) were planned. Intraoperative findings revealed advanced cancer in the upper part of the stomach, which was also resected. Macroscopically, there was an 11-cm type 1 tumor in the middle thoracic esophagus and a 3.5-cm type 3 tumor in the gastric cardia. Microscopically, the esophageal tumor was composed of well-differentiated squamous cell carcinoma and spindle-shaped cells resembling leiomyosarcoma and was diagnosed as carcinosarcoma. Spindle-shaped sarcomatous cells were positive for vimentin and α-smooth muscle actin (αSMA) by immunohistochemistry. Most of the tumor showed highly atypical sarcomatous component that reached deep into the submucosa, and regional lymph node metastases were observed. Gastric cancer was a moderately differentiated tubular adenocarcinoma that penetrated the serosa and reached the peritoneal cavity. The transverse colon tumor was a well-differentiated adenocarcinoma invading the muscularis mucosa. CONCLUSIONS: We report a rare case of triple cancer, including esophageal carcinosarcoma. Simultaneous resection of esophageal carcinosarcoma with multiple cancers should be carefully considered based on the patient's condition and reconstruction method.

低侵襲手術における術中合併症とトラブルシューティング 腹腔鏡下食道空腸吻合のトラブルシューティング 胸腔鏡併用手術(MALTA)について　　　　　　　　　　　　　　　
海老原 裕磨, 林 真理子, 阿部 紘丈, 和田 秀之, 新田 健雄, 七戸 俊明, 平野 聡
日本内視鏡外科学会雑誌, 29, 7, WS1, 4, (一社)日本内視鏡外科学会, 2024年12月
日本語

低侵襲手術における術中合併症とトラブルシューティング 腹腔鏡下食道空腸吻合のトラブルシューティング 胸腔鏡併用手術(MALTA)について　　　　　　　　　　　　　　　
海老原 裕磨, 林 真理子, 阿部 紘丈, 和田 秀之, 新田 健雄, 七戸 俊明, 平野 聡
日本内視鏡外科学会雑誌, 29, 7, WS1, 4, (一社)日本内視鏡外科学会, 2024年12月
日本語

Perioperative chemotherapy with nivolumab for HER2-negative locally advanced gastric cancer: a case series.
Yuta Toji, Shintaro Takeuchi, Yuma Ebihara, Yo Kurashima, Kazuaki Harada, Mariko Hayashi, Hirotake Abe, Hideyuki Wada, Satoko Yorinaga, Toshiaki Shichinohe, Utano Tomaru, Yoshito Komatsu, Satoshi Hirano
Surgical case reports, 10, 1, 200, 200, 2024年08月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Nivolumab with chemotherapy has been transformative for metastatic gastric cancer (GC). The potential of this regimen for local tumor control could be utilized for perioperative chemotherapy in locally advanced GC with bulky tumors or lymph node metastasis involving other organs. CASE PRESENTATION: Five patients with HER2-negative advanced GC were treated with nivolumab and oxaliplatin-based chemotherapy. All patients presented with clinical stage III or IVA GC with tumors in contact with either the pancreas or liver. Following chemotherapy, all tumors demonstrated shrinkage, allowing successful radical gastrectomies including four minimally invasive approach without postoperative complications. Four patients avoided combined resection of other organs. CONCLUSIONS: Perioperative chemotherapy with nivolumab was effective for local disease control in this case series. This regimen could be a promising treatment approach for locally advanced GC; however, its survival benefits should be evaluated in clinical trials.

Laparoscopic ultrasound guided wedge resection of the stomach: a novel procedure for gastric submucosal tumor.
Hideyuki Wada, Katsuhiko Murakawa, Koichi Ono, Satoshi Hirano
Updates in surgery, 74, 1, 367, 372, 2022年02月, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, It is essential for the surgery of gastric submucosal tumors to resect the tumor with a negative margin and minimize the incision of the normal stomach wall. We developed a novel procedure for patients with gastric submucosal tumors using a laparoscopic ultrasound probe as a guide to determine the resection line. Since 2014, we have performed the laparoscopic ultrasound-guided wedge resection of the stomach in seven patients. The tumor was localized, and the property of the tumor was clearly identified using a laparoscopic ultrasound probe. As a result, the ideal incision line was determined without intraoperative endoscopy. The stomach wall was perforated along the marking on the planned incision line and the whole layer is subsequently incised along with the tumor. The surgical margins were negative, and there were no obvious injuries of the pseudocapsule, microscopically, in any case. It is possible that the laparoscopic ultrasound-guided wedge resection of the stomach contributes to a simplification of the surgery of gastric submucosal tumors resulting in reduced medical cost while maintaining curability and functional preservation.

[Hyperammonemic encephalopathy after treatment with modified FOLFOX6 regimen for recurrent gastric cancer:a case report].
Shota Kuwabara, Katsuhiko Murakawa, Kentaro Kumagai, Yuta Takeuchi, Hideyuki Wada, Masaomi Ichinokawa, Joe Matsumoto, Koichi Ono, Satoshi Hirano
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 119, 1, 72, 78, 2022年, ［国内誌］
日本語, 研究論文（学術雑誌）, A 64-year-old female received modified FOLFOX6 therapy with continuous administration of a high concentration of 5-fluorouracil (5-FU) for recurrence of peritoneal dissemination after total gastrectomy. Twenty-nine hours after the administration, there was the sudden onset of altered consciousness and hepatic dysfunction accompanied by hyperammonemia. The consciousness and hepatic function improved the following day after treatment with branched-chain amino acid formulation, lactulose, fresh frozen plasma, and continuous hemodiafiltration. Thus, the diagnosis was 5-FU-induced hyperammonemia. Improvement of dehydration and renal dysfunction would be important for avoiding the risk of developing the side effects. Because recurrent gastric cancer is often a progressive condition, post-treatment might be promptly transferred to the other posterior regimen without 5-FU as required.

Colonic varices treated with embolization after pancreatoduodenectomy with portal vein resection: a case report.
Shota Kuwabara, Joe Matsumoto, Hiroyasu Tojima, Hideyuki Wada, Kohei Kato, Yukiko Tabata, Masaomi Ichinokawa, Tatsuya Yoshioka, Katsuhiko Murakawa, Atsushi Ikeda, Setsuyuki Ohtake, Koichi Ono
Surgical case reports, 6, 1, 126, 126, 2020年06月03日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Pancreatoduodenectomy with resection of the portal vein or superior mesenteric vein confluence has been safely performed in patients with pancreatic head cancer associated with infiltration of the portal vein or superior mesenteric vein. In recent years, left-sided portal hypertension, a late postoperative complication, has received focus owing to increased long-term survival with advances in chemotherapy. Left-sided hypertension may sometimes cause fatal gastrointestinal bleeding because of the rupture of gastrointestinal varices. Here, we present a case of colonic varices caused by left-sided portal hypertension after pancreatoduodenectomy with portal vein resection. CASE PRESENTATION: A 69-year-old man diagnosed with pancreatic head cancer was referred to our department for surgery after undergoing chemotherapy with nine courses of gemcitabine and nab-paclitaxel. Computed tomography showed a mass 25 mm in diameter and in contact with the portal vein. He had undergone subtotal stomach-preserving pancreatoduodenectomy with portal vein resection. Four centimeters of the portal vein had been resected, and end-to-end anastomosis was performed without splenic vein reconstruction. We had to completely resect the right colic vein, accessary right colic vein, and middle colic vein due to tumor invasion. The pathological diagnosis was ypT3, ypN1a, ypM0, and ypStageIIB, and he was administered TS-1 as postoperative adjuvant chemotherapy. Seven months after therapeutic radical surgery, he presented with melena with progressive anemia. Computed tomography revealed transverse colonic varices. He was offered interventional radiology. Trans-splenic arterial splenic venography showed that transverse colonic varices had developed as collateral circulation of the splenic vein and inferior mesenteric vein system. An embolic substance was injected into the transverse colonic varices, which halted the progression of the anemia caused by melena. Fifteen months after therapeutic radical surgery, local recurrence of the tumor occurred; he died 28 months after the surgery. CONCLUSIONS: When subtotal stomach-preserving pancreatoduodenectomy with portal vein resection is performed without splenic vein reconstruction, colonic varices may result from left-sided portal hypertension. Interventional radiology is an effective treatment for gastrointestinal bleeding due to colonic varices, but it is important to be observant for colonic necrosis and new varices.

A rare case of localized IgG4-related sclerosing cholecystitis mimicking gallbladder cancer.
Masaomi Ichinokawa, Joe Matsumoto, Tomotaka Kuraya, Shota Kuwabara, Hideyuki Wada, Kohei Kato, Atsushi Ikeda, Katsuhiko Murakawa, Koichi Ono
Journal of rural medicine : JRM, 14, 1, 138, 142, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: IgG4-related sclerosing cholecystitis is generally associated with IgG4-related sclerosing cholangitis and presents with diffuse, circumferential thickening of the gallbladder wall. We report a rare case of localized IgG4-related sclerosing cholecystitis without IgG4-related sclerosing cholangitis, which was difficult to differentiate from gallbladder cancer preoperatively. Patient: A 56-year-old man with suspected IgG4-related disease or gallbladder cancer was admitted to our ward. The serum IgG4 level was elevated at 721 mg/dL. Computed tomography (CT) demonstrated focal wall thickening of the gallbladder fundus. Drip infusion cholecystocholangiography with CT revealed no dilation, stenosis, or border irregularity of the bile duct. Results: For diagnostic and treatment purposes, cholecystectomy with wedge resection of the gallbladder bed was performed. The pathological diagnosis was IgG4-related sclerosing cholecystitis. Conclusion: It is difficult to differentiate IgG4-related sclerosing cholecystitis from gallbladder cancer in cases involving localized thickening of the gallbladder wall. In similar cases, surgical resection with cancer in mind might be performed based on present clinical knowledge.

Multivalent Mannose-Decorated NIR Nanoprobes for Targeting Pan Lymph Nodes.
Hideyuki Wada, Hoon Hyun, Kai Bao, Jeong Heon Lee, Georges El Fakhri, Yongdoo Choi, Hak Soo Choi
Chemical engineering journal (Lausanne, Switzerland : 1996), 340, 51, 57, 2018年05月15日, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Lymphadenectomy is a prerequisite for most malignancies to define the precise staging of cancer, as well as resect the possible metastases completely. While it improves prognosis, lymphadenectomy often causes postoperative edema or bleeding because of unclear surgical margins. In this study, we synthesized near-infrared (NIR) fluorescent nanoprobes with conjugating various mannose moieties on the surface to target macrophages in the lymph node. Armed with these NIR nanoprobes, we demonstrated the feasibility of intraoperative pan lymph nodes (PLN) mapping and real-time optical imaging under the NIR fluorescence imaging system. We found that even single mannose-conjugated ZW800-1 showed specific uptake in lymph nodes within 4 h, and multiple mannose-employed polyrotaxanes highlighted PLN efficiently with low background signals in major organs. This technology can help surgeons perform lymphadenectomy with ease and safety by identifying all regional lymph nodes proficiently after a single intravenous injection of NIR nanoprobes.

Intraoperative Near-Infrared Fluorescence Imaging of Thymus in Preclinical Models.
Hideyuki Wada, Hoon Hyun, Homan Kang, Julien Gravier, Maged Henary, Mark W Bordo, Hak Soo Choi, John V Frangioni
The Annals of thoracic surgery, 103, 4, 1132, 1141, 2017年04月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There are currently no thymus-specific contrast agents for biomedical imaging. Thus, finding ectopic thymic tissue during certain operations is extremely difficult. The purpose of the present study was to determine if near-infrared (NIR) fluorescence imaging could provide high sensitivity, real-time identification of thymic tissue during the operation. METHODS: After initial in vivo screening of a 315-compound NIR fluorophore library for thymic uptake, methylene blue and five different 700-nm emitting candidate molecules were injected into CD-1 mice for quantitation of the signal-to-background ratio as a function of kinetics and dosing. Results were confirmed in 35-kg Yorkshire pigs. Dual-channel NIR imaging was also performed using a variety of 800-nm emitting NIR fluorophores targeted to various tissues in the mediastinum and neck. RESULTS: The compound Oxazine 170 demonstrated the highest signal-to-background ratio (≥3) for thymic tissue relative to mediastinal fat, heart, lung, muscle, thyroid gland, and parathyroid gland, with peak signal-to-background ratio occurring 4 h after 1 intravenous injection of a human equivalent dose of approximately 7 mg. Simultaneous dual-channel NIR imaging permitted unambiguous identification of the thymus from surrounding tissues, such as endocrine glands and lymph nodes. CONCLUSIONS: In mouse and pig, NIR fluorescence imaging using Oxazine 170 permits high sensitivity, real-time identification of thymic tissue for surgical procedures requiring its resection or avoidance. The performance of Oxazine 170 for imaging human thymic tissue is currently not known.

Accurate Prediction of Tissue Viability at Postoperative Day 7 Using Only Two Intraoperative Subsecond Near-Infrared Fluorescence Images.
Hideyuki Wada, Christina R Vargas, Joseph Angelo, Beverly Faulkner-Jones, Marek A Paul, Olivia A Ho, Bernard T Lee, John V Frangioni
Plastic and reconstructive surgery, 139, 2, 354, 363, 2017年02月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The ability to predict the future viability of tissue while still in the operating room and able to intervene would have a major impact on patient outcome. Although several objective methods to evaluate tissue perfusion have been reported, none to date has sufficient accuracy. METHODS: In eight Sprague-Dawley rats, reverse McFarlane dorsal skin flaps were created. Continuous near-infrared fluorescence angiography using indocyanine green was performed immediately after surgery, for a total of 30 minutes. These dynamic measurements were used to quantify indocyanine green biodistribution and clearance, and to develop a simple metric that accurately predicted tissue viability at postoperative day 7. The new metric was compared to previously described metrics. RESULTS: Reproducible patterns of indocyanine green biodistribution and clearance from the flap permitted quantitative metrics to be developed for predicting flap viability at postoperative day 7. Previously described metrics, which set the boundary between healthy and necrotic tissue as either 17 or 25 percent of peak near-infrared fluorescence at 2 minutes after indocyanine green injection, underestimated the area of necrosis by 75 and 48 percent, respectively. Our data suggest that both the shape and area of clinical necrosis occurring at postoperative day 7 can be predicted intraoperatively, with the boundary defined as near-infrared fluorescence intensities of 40 to 55 percent of peak fluorescence measured at 5 minutes. CONCLUSION: Two 750-msec intraoperative near-infrared fluorescence images obtained at time 0 and at 5 minutes after injection of indocyanine green accurately predicted skin flap viability 7 days after surgery.

Intraoperative Real-Time Assessment of Liver Function with Near-Infrared Fluorescence Imaging.
Hajime Narasaki, Takehiro Noji, Hideyuki Wada, Yuma Ebihara, Takahiro Tsuchikawa, Keisuke Okamura, Eiichi Tanaka, Toshiaki Shichinohe, Satoshi Hirano
European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes, 58, 5-6, 235, 245, 2017年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Postoperative liver failure is a serious complication after major hepatectomy, and perioperative prediction of its incidence using current technology is still very difficult. Near-infrared (NIR) fluorescence imaging allows quantitative assessment of the fluorescent signal from indocyanine green (ICG) in regions of interest on the liver surface. This method might offer a new promising modality for evaluating regional liver reserve. However, data are lacking regarding the relationship between liver function and fluorescent signals on the liver surface after intravenous ICG injection. This study was conducted to obtain the data necessary to apply NIR fluorescence imaging as a modality for measuring liver function. MATERIALS AND METHODS: This study included 16 patients who underwent open hepatopancreatobiliary surgery between March 2011 and March 2012. After laparotomy, ICG was injected intravenously at 2.5 mg/L of liver volume, then the fluorescence intensity (FI) and signal-to-background ratio (SBR) in the lateral segment of the liver were assessed for 15 min. Intraoperative blood samples were also obtained to measure the plasma clearance rate of ICG (ICGK). Correlations between ICGK, liver volume, and SBR, as well as between ICGK, liver volume, and rate of change of FI were analyzed. RESULTS: The experimental procedure was performed in all 16 patients. The FI of the liver increased rapidly after ICG injection, then became more gradual, reaching a near-plateau after 15 min. A significant correlation was seen between ICGK and the rate of change of FI up to 15 min (|rS| = 0.5725, p < 0.05). CONCLUSION: This is the first report to show a relationship between liver function and fluorescent signals on the liver surface after intravenous ICG injection. Intraoperative NIR fluorescence imaging with ICG may be useful as a new method for assessing liver function.

Bioimaging of botulinum toxin and hyaluronate hydrogels using zwitterionic near-infrared fluorophores.
Ki Su Kim, Yun Seop Kim, Kai Bao, Hideyuki Wada, Hak Soo Choi, Sei Kwang Hahn
Biomaterials research, 21, 15, 15, 2017年, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The injection of botulinum toxin (BTX) to reduce facial wrinkles is one of the most frequently performed plastic surgery procedures. The biocompatible hydrogels are injected with BTX for effective tissue augmentation. However, it is difficult to determine the interval of injection for effective tissue augmentation. METHOD: BTX and hyaluronate (HA) hydrogels were labeled with zwitterionic (ZW) near-infrared (NIR) fluorophores and visualized for 3 weeks after injection to BALB/c nude mice. RESULTS: BTX-ZW conjugates and diaminohexane (DAH)-HA-ZW hydrogels were successfully prepared by the conventional EDC/NHS chemistry. Using the NIR fluorescence imaging, we confirmed that approximately 10% of BTX-ZW conjugates and 50% of DAH-HA-ZW hydrogels remained 3 weeks post-injection. CONCLUSION: This bioimaging technique using invisible NIR fluorescence light can be exploited for various biomedical applications.

Renal Clearable Organic Nanocarriers for Bioimaging and Drug Delivery.
Homan Kang, Julien Gravier, Kai Bao, Hideyuki Wada, Jeong Heon Lee, Yoonji Baek, Georges El Fakhri, Sylvain Gioux, Brian P Rubin, Jean-Luc Coll, Hak Soo Choi
Advanced materials (Deerfield Beach, Fla.), 28, 37, 8162, 8168, 2016年10月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Renally cleared zwitterionic nanocarriers (H-Dots) are composed of ε-polylysine backbone for charge variations, near-infrared fluorophores for bioimaging, and β-cyclodextrins for potential drug delivery. H-Dots show ideal systemic circulation and rapid distribution and excrete from normal tissue/organ via renal excretion after complete targeting to the tumor site without nonspecific uptake by the immune system.

700-nm Zwitterionic Near-Infrared Fluorophores for Dual-Channel Image-Guided Surgery.
Hoon Hyun, Maged Henary, Tielong Gao, Lakshminarayana Narayana, Eric A Owens, Jeong Heon Lee, GwangLi Park, Hideyuki Wada, Yoshitomo Ashitate, John V Frangioni, Hak Soo Choi
Molecular imaging and biology, 18, 1, 52, 61, 2016年02月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The purpose of this study was to develop a family of 700-nm zwitterionic pentamethine indocyanine near-infrared fluorophores that would permit dual-channel image-guided surgery. PROCEDURES: Three complementary synthetic schemes were used to produce novel zwitterionic chemical structures. Physicochemical, optical, biodistribution, and clearance properties were compared to Cy5.5, a conventional pentamethine indocyanine now used for biomedical imaging. RESULTS: ZW700-1a, ZW700-1b, and ZW700-1c were synthesized, purified, and analyzed extensively in vitro and in vivo. All molecules had extinction coefficients ≥199,000 M(-1) cm(-1), emission ≥660 nm, and stability ≥99 % after 24 h in warm serum. In mice, rats, and pigs, ≥80 % of the injected dose was completely eliminated from the body via renal clearance within 4 h. Either alone or conjugated to a tumor targeting ligand, ZW700-1a permitted dual-channel, high SBR, and simultaneous imaging with 800-nm NIR fluorophores using the FLARE® imaging system. CONCLUSIONS: Novel 700-nm zwitterionic NIR fluorophores enable dual-NIR image-guided surgery.

Sentinel Lymph Node Mapping of Liver.
Hideyuki Wada, Hoon Hyun, Christina Vargas, Elizabeth M Genega, Julien Gravier, Sylvain Gioux, John V Frangioni, Hak Soo Choi
Annals of surgical oncology, 22 Suppl 3, 0 3, S1147-55, 2015年12月, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although the sentinel lymph node (SLN) hypothesis has been applied to many tissues and organs, liver has remained unstudied. Currently, it is unclear whether hepatic SLNs even exist. If so, they could alter the management of intrahepatic cholangiocarcinoma and other hepatic malignancies by minimizing the extent of surgery while still providing precise nodal staging. This study investigated whether invisible yet tissue-penetrating near-infrared (NIR) fluorescent light can provide simultaneous identification of both the SLN and all other regional lymph nodes (RLNs) in the liver. METHODS: In 25 Yorkshire pigs, this study determined whether SLNs exist in liver and compared the effectiveness of two clinically available NIR fluorophores [methylene blue and indocyanine green (ICG)], and two novel NIR fluorophores previously described by our group (ESNF14 and ZW800-3C) for SLN and RLN mapping. RESULTS: In this study, ESNF14 showed the highest signal-to-background ratio and the longest retention time in SLNs without leakage to second-tier lymph nodes. The findings showed that ICG had apparent leakage to second-tier nodes, and ZW800-3C had poor migration after intraparenchymal injection. However, when injected intravenously, ZW800-3C was able to highlight all RLNs in liver during a 4- to 6-h period. Simultaneous dual-channel imaging of SLN (ESNF14) and RLN (ZW800-3C) permitted unambiguous identification and image-guided resection of SLNs and RLNs in liver. CONCLUSION: The NIR imaging technology enables real-time intraoperative identification of SLNs and RLNs in the liver of swine. If these results are confirmed in patients, new strategies for the surgical management of intrahepatic malignancies should be possible.

Cartilage-Specific Near-Infrared Fluorophores for Biomedical Imaging.
Hoon Hyun, Eric A Owens, Hideyuki Wada, Andrew Levitz, GwangLi Park, Min Ho Park, John V Frangioni, Maged Henary, Hak Soo Choi
Angewandte Chemie (International ed. in English), 54, 30, 8648, 52, 2015年07月20日, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, A novel class of near-infrared fluorescent contrast agents was developed. These agents target cartilage with high specificity and this property is inherent to the chemical structure of the fluorophore. After a single low-dose intravenous injection and a clearance time of approximately 4 h, these agents bind to all three major types of cartilage (hyaline, elastic, and fibrocartilage) and perform equally well across species. Analysis of the chemical structure similarities revealed a potential pharmacophore for cartilage targeting. Our results lay the foundation for future improvements in tissue engineering, joint surgery, and cartilage-specific drug development.

Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging.
Hoon Hyun, Min Ho Park, Eric A Owens, Hideyuki Wada, Maged Henary, Henricus J M Handgraaf, Alexander L Vahrmeijer, John V Frangioni, Hak Soo Choi
Nature medicine, 21, 2, 192, 7, 2015年02月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, The typical method for creating targeted contrast agents requires covalent conjugation of separate targeting and fluorophore domains. In this study, we demonstrate that it is possible to create near-infrared (NIR) fluorophores with different tissue specificities driven by their inherent chemical structures. Thus, a single compact molecule performs both targeting and imaging. We use this strategy to solve a major problem in head and neck surgery: the identification and preservation of parathyroid and thyroid glands. We synthesized 700-nm and 800-nm halogenated fluorophores that show high uptake into these glands after a single intravenous (IV) injection of 0.06 mg kg(-1) in a pig. By using a dual-channel NIR imaging system, we observed-in real time and with high sensitivity-the unambiguous distinction of parathyroid and thyroid glands simultaneously in the context of blood and surrounding soft tissue. This novel technology lays a foundation for performing head and neck surgery with increased precision and efficiency along with potentially lower morbidity, and it provides a general strategy for developing targeted NIR fluorophores.

Pancreas-targeted NIR fluorophores for dual-channel image-guided abdominal surgery.
Hideyuki Wada, Hoon Hyun, Christina Vargas, Julien Gravier, GwangLi Park, Sylvain Gioux, John V Frangioni, Maged Henary, Hak Soo Choi
Theranostics, 5, 1, 1, 11, 2015年, ［査読有り］, ［筆頭著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury. DESIGN: After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands. RESULTS: T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice. In pigs, T700-F produced an SBR≥2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection. The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time. CONCLUSION: Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.

Phosphonated near-infrared fluorophores for biomedical imaging of bone.
Hoon Hyun, Hideyuki Wada, Kai Bao, Julien Gravier, Yogesh Yadav, Matt Laramie, Maged Henary, John V Frangioni, Hak Soo Choi
Angewandte Chemie (International ed. in English), 53, 40, 10668, 72, 2014年09月26日, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. A new strategy is based on the incorporation of targeting moieties into the non-delocalized structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals in a model system, two families of bifunctional molecules that target bone without requiring a traditional bisphosphonate are synthesized. With peak fluorescence emissions at approximately 700 or 800 nm, these molecules can be used for fluorescence-assisted resection and exploration (FLARE) dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over five weeks, and histological analysis confirms their incorporation into the bone matrix. Taken together, a new strategy for creating ultra-compact, targeted near-infrared fluorophores for various bioimaging applications is described.

Prototype nerve-specific near-infrared fluorophores.
Min Ho Park, Hoon Hyun, Yoshitomo Ashitate, Hideyuki Wada, GwangLi Park, Jeong Heon Lee, Costyl Njiojob, Maged Henary, John V Frangioni, Hak Soo Choi
Theranostics, 4, 8, 823, 33, 2014年, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis. Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance. Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed. In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals. Among the targeted fluorophores, Oxazine 4 has peak emission near into the NIR, which provided nerve-targeted signal in the brachial plexus and sciatic nerve for up to 12 h after a single intravenous injection. In addition, recurrent laryngeal nerves were successfully identified and highlighted in real time in swine, which could be preserved during the course of thyroid resection. Although optical properties of these agents are not yet optimal, chemical structure analysis provides a basis for improving these prototype nerve-specific NIR fluorophores even further.

Central C-C Bonding Increases Optical and Chemical Stability of NIR Fluorophores.
Hoon Hyun, Eric A Owens, Lakshminarayana Narayana, Hideyuki Wada, Julien Gravier, Kai Bao, John V Frangioni, Hak Soo Choi, Maged Henary
RSC advances, 4, 102, 58762, 58768, 2014年01月01日, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Functional near-infrared (NIR) fluorophores have played a major role in the recent advances in bioimaging. However, the optical and physicochemical stabilities of NIR fluorophores in the biological and physiological environment are still a challenge. Especially, the ether linkage on the meso carbon of heptamethine core is fragile when exposed to serum proteins or other amine-rich biomolecules. To solve such a structural limitation, a rigid carbon-carbon bond was installed onto the framework of ether-linked NIR fluorophores through the Suzuki coupling. The robust fluorophores replaced as ZW800-1C and ZW800-3C displayed enhanced optical and chemical stability in various solvents and a 100% warm serum environment (> 99%, 24 h). The biodistribution and clearance of C-C coupled ZW800 compounds were almost identical to the previously developed oxygen-substituted ZW800 compounds. When conjugated with a small molecule ligand, ZW800-1C maintained the identical stable form in warm serum (>98%, 24 h), while ZW800-1A hydrolyzed quickly after 4 h incubation (34%, 24 h).

当科における腹腔鏡下膵体尾部切除術　　　　　　　　　　　　　　　
和田 秀之, 海老原 裕磨, 岡村 国茂, 中西 喜嗣, 吉岡 達也, 佐々木 剛志, 浅野 賢道, 福島 正之, 倉島 庸, 中村 透, 加藤 健太郎, 松本 譲, 土川 貴裕, 七戸 俊明, 田中 栄一, 平野 聡
日本内視鏡外科学会雑誌, 17, 7, 558, 558, (一社)日本内視鏡外科学会, 2012年12月
日本語

Video-assisted thoracoscopic left lower lobectomy in a patient with lung cancer and a right aortic arch.
Hideyuki Wada, Yasuhiro Hida, Kichizo Kaga, Ryunosuke Hase, Kazuto Ohtaka, Jun Muto, Nakada-Kubota Reiko, Satoshi Hirano, Yoshiro Matsui
Journal of cardiothoracic surgery, 7, 120, 120, 2012年11月13日, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, A right aortic arch is a rare congenital anomaly, with a reported incidence of around 0.1%. A patient with a right aortic arch underwent video-assisted thoracic surgery left lower lobectomy and mediastinal lymph node dissection for squamous cell carcinoma. There was no aortic arch or descending aorta in the left thoracic cavity, but the esophagus. There was no anomaly in the location or branching of the pulmonary vessels, the bronchi, and the lobulation of the lungs. The vagus nerve was found at the level of the left pulmonary artery. The arterial ligament was found between the left subclavian artery and the left pulmonary artery. The recurrent laryngeal nerve was recurrent around the left subclavian artery. A Kommerell diverticulum was found at the origin of the left subclavian artery. The patient experienced no complications. We conclude that video-assisted thoracoscopic lobectomy with mediastinal dissection is feasible for treating lung cancer with a right aortic arch.

原発性肺癌に対する胸腔鏡下手術開胸移行例の検討
長谷 龍之介, 和田 秀之, 高坂 琢磨, 中田 玲子, 大高 和人, 武藤 潤, 樋田 泰浩, 加賀 基知三, 平野 聡, 北海道外科雑誌, 56, 2, 162, 162, 2011年12月
北海道外科学会, 日本語

胸水細胞診、胸腔内洗浄細胞診(PLC)陽性肺癌の術前予測因子の検討
和田 秀之, 加賀 基知三, 樋田 泰浩, 長谷 龍之介, 大高 和人, 武藤 潤, 中田 玲子, 高坂 琢磨, 平野 聡, 肺癌, 51, 5, 413, 413, 2011年10月
(NPO)日本肺癌学会, 日本語

術後気管支断端瘻症例の検討
長谷 龍之介, 和田 秀之, 高坂 琢磨, 中田 玲子, 大高 和人, 武藤 潤, 樋田 泰浩, 加賀 基知三, 日本臨床外科学会雑誌, 72, 増刊, 746, 746, 2011年10月
日本臨床外科学会, 日本語

経験から学ぶ内視鏡下手術のトラブルシューティング(肺) 完全胸腔鏡下手術の出血に対する段階的対処法
長谷 龍之介, 和田 秀之, 高坂 琢磨, 中田 玲子, 大高 和人, 武藤 潤, 樋田 泰浩, 加賀 基知三, 平野 聡, 日本臨床外科学会雑誌, 72, 増刊, 344, 344, 2011年10月
日本臨床外科学会, 日本語