研究者業績

脇屋 太一

ワキヤ タイイチ  (Wakiya Taiichi)

基本情報

所属
自治医科大学 医学部外科学講座 消化器一般移植外科学部門 講師
学位
博士(医学)(2012年 弘前大学)

連絡先
wakiya.taiichijichi.ac.jp
研究者番号
50571246
ORCID ID
 https://orcid.org/0000-0003-3681-7736
J-GLOBAL ID
202001018332988010
Researcher ID
F-4792-2015
researchmap会員ID
B000382357

論文

 152
  • Kentaro Ushijima, Yukihiro Sanada, Shinya Otomo, Keiko Ogaki, Taiichi Wakiya, Noriki Okada, Yuta Hirata, Toshio Horiuchi, Takahiko Omameuda, Kiichiro Takadra, Ryosuke Akimoto, Yasuharu Onishi, Yasunaru Sakuma, Koichi Mizuta
    BMC infectious diseases 25(1) 97-97 2025年1月21日  
    BACKGROUND: Cytomegalovirus (CMV) is a major infectious complication in solid-organ transplant recipients, particularly in the context of pediatric liver transplantation. CMV serostatus is a well-established risk factor for postoperative CMV infection, with CMV seronegative recipients who receive organs from seropositive donors (D+/R-) being at the highest risk. Our previous research indicated a higher incidence of CMV infection in recipients with inherited metabolic diseases (IMDs) compared with those with biliary atresia (BA). This study aimed to determine whether IMDs constitute an independent risk factor for postoperative CMV infection. METHODS: We retrospectively analyzed data from 45 IMD and 230 BA recipients. We collected information on the occurrence and timing of episodes of CMV infections, methylprednisolone (mPSL) pulse therapy, patient characteristics, and peri- and postoperative data. RESULTS: Multivariable analysis identified mPSL pulse therapy (Odds Ratio (OR): 4.43), CMV serostatus (D+/R-) (OR: 6.03), and underlying IMDs (OR: 3.28) as independent risk factors for CMV infection. Further stratified analysis, which considered the timing of CMV infection diagnosis relative to mPSL pulse therapy, confirmed that CMV serostatus with (D+/R-) (OR: 5.61) and underlying IMDs (OR: 2.83) remained independent predictors of CMV infection, even when excluding the influence of mPSL pulse therapy. CONCLUSIONS: This study demonstrates that IMDs are a potent independent risk factor for CMV infection following pediatric liver transplantation. CLINICAL TRIAL NUMBER: Not applicable.
  • Takahiko Omameuda, Yukihiro Sanada, Yasunaru Sakuma, Yasuharu Onishi, Taiichi Wakiya, Yuta Hirata, Toshio Horiuchi, Kiichiro Takadera, Ryosuke Akimoto, Naohiro Sata
    Clinical journal of gastroenterology 17(6) 1080-1086 2024年12月  
    Portal cavernoma cholangiopathy (PCC) is a complex condition associated with portal hypertension, particularly in patients with extrahepatic portal vein obstruction (EHPVO). Herein, we present a case of liver failure with PCC in a 55-year-old male successfully treated with living-donor liver transplantation (LDLT). The patient had a history of gastrointestinal bleeding and recurrence of cholangitis. Imaging studies confirmed cavernous transformation and pericholedochal varices. Preoperative angiography verified hepatopetal flow in the pericholedochal varix, which facilitated successful anastomosis with the donor's portal vein during LDLT. Histological examination of the explanted liver confirmed vanishing bile duct syndrome (VBDS) and secondary bile stasis was considered to have caused liver failure. No postoperative complications were observed within 13 months of LDLT. We report the first case of VBDS in the PCC resulting from EHPVO that was successfully managed with LDLT. Careful management of similar cases should involve angiography and long-term postoperative monitoring of portal vein complications.
  • Hiroaki Fujita, Taiichi Wakiya, Yota Tatara, Keinosuke Ishido, Yoshiyuki Sakamoto, Norihisa Kimura, Hajime Morohashi, Takuya Miura, Takahiro Muroya, Harue Akasaka, Hiroshi Yokoyama, Taishu Kanda, Shunsuke Kubota, Aika Ichisawa, Kenta Ogasawara, Daisuke Kuwata, Yoshiya Takahashi, Akie Nakamura, Keisuke Yamazaki, Takahiro Yamada, Ryo Matsuyama, Masanobu Kanou, Kei Yamana, Ken Itoh, Kenichi Hakamada
    Scientific reports 14(1) 16557-16557 2024年7月17日  
    Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066.
  • Ohira M, Aoki G, Orihashi Y, Yoshimura K, Toshima T, Hatano E, Eguchi S, Taizo Hibi, Hasegawa K, Umeda Y, Hashimoto T, Yasushi Hasegawa, Nobori S, Ogura Y, Nitta H, Egawa H, Hidetoshi Eguchi, Takada Y, Ueda Y, Kasahara M, Kawachi S, Soejima Y, Tokushige K, Nagano H, Haga H, Fukumoto T, Mochida S, Umeshita K, Hideki Ohdan, Japanese Liver Transplantation Society
    BJS open 2024年7月1日  
    <h4>Background</h4>Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set.<h4>Methods</h4>The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model.<h4>Results</h4>Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors.<h4>Conclusion</h4>This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.
  • Norihisa Kimura, Keinosuke Ishido, Taiichi Wakiya, Hayato Nagase, Tadashi Odagiri, Yusuke Wakasa, Kenichi Hakamada
    Pancreatology : Official journal of the international association of pancreatology (IAP) ... [et al.] 24(4) 630-642 2024年6月  
    BACKGROUND: Peripancreatic bacterial contamination (PBC) is a critical factor contributing to the development of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). Controlling pathogenic bacteria is essential in preventing CR-POPF; however, the precise relationship between specific bacteria and CR-POPF remains unclear. This study aimed to investigate the relationship between PBC and CR-POPF after PD, with a focus on identifying potentially causative bacteria. METHODS: This prospective observational study enrolled 370 patients who underwent PD. Microbial cultures were routinely collected from peripancreatic drain fluid on postoperative days (PODs) 1, 3, and 6. Predictive factors for CR-POPF and the bacteria involved in PBC were investigated. RESULTS: CR-POPF occurred in 86 (23.2%) patients. In multivariate analysis, PBC on POD1 (Odds ratio [OR] = 3.59; P = 0.005) was one of the main independent predictive factors for CR-POPF, while prophylactic use of antibiotics other than piperacillin/tazobactam independently influenced PBC on POD1 (OR = 2.95; P = 0.010). Notably, Enterococcus spp., particularly Enterococcus faecalis, were significantly isolated from PBC in patients with CR-POPF compared to those without CR-POPF on PODs 1 and 3 (P < 0.001), and they displayed high resistance to all cephalosporins. CONCLUSIONS: Early PBC plays a pivotal role in the development of CR-POPF following PD. Prophylactic antibiotic administration, specifically targeting Enterococcus faecalis, may effectively mitigate early PBC and subsequently reduce the risk of CR-POPF. This research sheds light on the importance of bacterial control strategies in preventing CR-POPF after PD.
  • Takahiko Omameuda, Taiichi Wakiya, Yasunaru Sakuma, Yasuharu Onishi, Toshiyuki Yamada, Katsutoshi Takanami, Yukihiro Sanada, Yuta Hirata, Toshio Horiuchi, Naohiro Sata
    Transplantation proceedings 56(5) 1148-1152 2024年6月  
    Alanine aminotransferase (ALT) is an enzyme that catalyzes the transfer of amino groups from alanine to ketoglutaric acid. ALT is an established marker of liver diseases. Occasionally, ALT levels may be abnormally low due to various factors, making accurate assessment difficult. To date, no studies have documented ALT alterations following Living donor liver transplantation (LDLT) in patients with low ALT levels. Here, we present a case of abnormally low ALT levels that were ameliorated by LDLT. A 27-year-old woman underwent LDLT for refractory cholangitis with biliary atresia. The patient's preoperative ALT level was 1 IU/L. Following graft reperfusion, ALT levels increased (peak value, 456 IU/L), primarily attributed to the donor liver. After LDLT, ALT levels consistently surpassed the lower limit. The differential diagnosis of abnormally low ALT levels suggested a genetic mutation as the most probable underlying cause. Even after LDLT, ALT levels in organs other than the transplanted liver would remain abnormally low. Therefore, to prevent underestimating liver damage, the standard ALT range for such cases should be set lower than the typical range.
  • Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Taishu Kanda, Shunsuke Kubota, Hiroaki Fujita, Yoshiya Takahashi, Takeshi Yamamoto, Kohei Chida, Junichi Saito, Kazuyoshi Hirota, Kenichi Hakamada
    Oncology letters 27(5) 236-236 2024年5月  
    Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, the impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the impact of ANH on long-term outcomes in patients with PDAC undergoing radical surgery. Data from 155 resectable PDAC cases were collected. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH. A total of 44 patients (28.4%) were included in the ANH group and 30 patients (19.4%) were included in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group had the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P=0.043) and DSS (P=0.029) compared with the STD group before applying Bonferroni correction; however, no significant difference was observed after applying Bonferroni correction. Cox regression analysis identified ANH as an independent prognostic factor for RFS [relative risk (RR), 1.696; P=0.019] and DSS (RR, 1.876; P=0.009). After PSM, the ANH group exhibited less favorable RFS [median survival time (MST), 12.1 vs. 18.1 months; P=0.097] and DSS (MST, 32.1 vs. 50.5 months; P=0.097) compared with the STD group; however, these differences were not statistically significant. In conclusion, while ANH was not as harmful as ABT, it exhibited potentially more negative effects on long-term postoperative outcomes in PDAC than STD.
  • Takahiro Yamada, Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Hayato Nagase, Shintaro Goto, Tadashi Yoshizawa, Hiroshi Kijima, Seiichi Kato, Kenichi Hakamada
    Clinical journal of gastroenterology 17(4) 788-794 2024年3月26日  
    A 72-year-old man was referred to our hospital for the examination of a pancreatic head mass. Abdominal computed tomography revealed a contrasted 8-cm-diameter tumor extending from the dorsal pancreatic head to the porta hepatis. The preoperative diagnosis was challenging due to the absence of specific imaging findings and the inability to perform a biopsy. Positron emission tomography/computed tomography and diffusion-weighted imaging suggested a malignant tumor originating from the organs surrounding the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed, as dissection from the pancreatic head proved unfeasible. Pathological examination identified the tumor as an enlarged lymph node consisting of pleomorphic large cells forming clusters, positive for follicular dendritic cell markers cluster of differentiation (CD) 21 and CD23. No evidence of tumor capsule infiltration, other organ infiltration, or metastasis to other lymph nodes was observed. The final diagnosis was nodal follicular dendritic cell sarcoma (FDCS) originating from the pancreatic head lymph nodes. No recurrence occurred at 3 years postoperatively with no postoperative treatment. Intraperitoneal nodal FDCS is extremely rare, and occasionally, it can lead to postoperative recurrence and progression. It is crucial to differentiate neoplastic lymph node enlargement around the pancreatic head from nodal FDCS.
  • Taiichi Wakiya, Yasunaru Sakuma, Yasuharu Onishi, Yukihiro Sanada, Noriki Okada, Yuta Hirata, Toshio Horiuchi, Takahiko Omameuda, Kiichiro Takadera, Naohiro Sata
    Scientific reports 14(1) 6753-6753 2024年3月21日  
    The liver and pancreas work together to recover homeostasis after hepatectomy. This study aimed to investigate the effect of liver resection volume on the pancreas. We collected clinical data from 336 living liver donors. They were categorized into left lateral sectionectomy (LLS), left lobectomy, and right lobectomy (RL) groups. Serum pancreatic enzymes were compared among the groups. Serum amylase values peaked on postoperative day (POD) 1. Though they quickly returned to preoperative levels on POD 3, 46% of cases showed abnormal values on POD 7 in the RL group. Serum lipase levels were highest at POD 7. Lipase values increased 5.7-fold on POD 7 in the RL group and 82% of cases showed abnormal values. The RL group's lipase was twice that of the LLS group. A negative correlation existed between the remnant liver volume and amylase (r = - 0.326)/lipase (r = - 0.367) on POD 7. Furthermore, a significant correlation was observed between POD 7 serum bilirubin and amylase (r = 0.379)/lipase (r = 0.381) levels, indicating cooccurrence with liver and pancreatic strain. Pancreatic strain due to hepatectomy occurs in a resection/remnant liver volume-dependent manner. It would be beneficial to closely monitor pancreatic function in patients undergoing a major hepatectomy.
  • Taishu Kanda, Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Eri Yoshida, Junichi Nakagawa, Masashi Matsuzaka, Takenori Niioka, Yoshihiro Sasaki, Kenichi Hakamada
    Pancreas 53(1) e55-e61 2023年11月27日  
    OBJECTIVES: We aimed to predict in vitro chemosensitivity assay results from computed tomography (CT) images by applying deep learning (DL) to optimize chemotherapy for pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Preoperative enhanced abdominal CT images and the histoculture drug response assay (HDRA) results were collected from 33 PDAC patients undergoing surgery. Deep learning was performed using CT images of both the HDRA-positive and HDRA-negative groups. We trimmed small patches from the entire tumor area. We established various prediction labels for HDRA results with 5-fluorouracil (FU), gemcitabine (GEM), and paclitaxel (PTX). We built a predictive model using a residual convolutional neural network and used 3-fold cross-validation. RESULTS: Of the 33 patients, effective response to FU, GEM, and PTX by HDRA was observed in 19 (57.6%), 11 (33.3%), and 23 (88.5%) patients, respectively. The average accuracy and the area under the receiver operating characteristic curve (AUC) of the model for predicting the effective response to FU were 93.4% and 0.979, respectively. In the prediction of GEM, the models demonstrated high accuracy (92.8%) and AUC (0.969). Likewise, the model for predicting response to PTX had a high performance (accuracy, 95.9%; AUC, 0.979). CONCLUSIONS: Our CT patch-based DL model exhibited high predictive performance in projecting HDRA results. Our study suggests that the DL approach could possibly provide a noninvasive means for the optimization of chemotherapy.
  • Shunsuke Kubota, Takuya Miura, Taiichi Wakiya, Tadashi Yoshizawa, Shintaro Goto, Hajime Morohashi, Yoshiyuki Sakamoto, Yota Tatara, Hiroshi Kijima, Kenichi Hakamada
    Annals of surgical oncology 30(12) 7612-7623 2023年8月7日  
    BACKGROUND: Extramural vascular invasion (EMVI) and tumor deposits (TD) are poor prognostic factors in rectal cancer (RC), especially when resistant to neoadjuvant chemotherapy (NAC). We aimed to define differential expression in NAC responders and non-responders with concomitant EMVI and TD. METHODS: From 52 RC surgical patients, post-NAC resected specimens were extracted, comprising two groups: cases with residual EMVI and TD (NAC-resistant) and cases without (NAC-effective). Proteomic analysis was conducted to define differential protein expression in the two groups. To validate the findings, immunohistochemistry was performed in another cohort that included 58 RC surgical patients. Based on the findings, chemosensitivity and prognosis were compared. RESULTS: The NAC-resistant group was associated with a lower 3-year disease-free survival rate than the NAC-effective group (p = 0.041). Discriminative proteins in the NAC-resistant group were highly associated with the sulfur metabolism pathway. Among these pathway constituents, selenium-binding protein 1 (SELENBP1) expression in the NAC-resistant group decreased to less than one-third of that of the NAC-effective group. Immunohistochemistry in another RC cohort consistently validated the relationship between decreased SELENBP1 and poorer NAC sensitivity, in both pre-NAC biopsy and post-NAC surgery specimens. Furthermore, decrease in SELENBP1 was associated with a lower 3-year disease-free survival rate (p = 0.047). CONCLUSIONS: We defined one of the differentially expressed proteins in NAC responders and non-responders, concomitant with EMVI and TD. SELENBP1 was suspected to contribute to NAC resistance and poor prognosis in RC.
  • Kotaro Umemura, Hiroshi Shimoda, Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Takuji Kagiya, Kentaro Sato, Yuto Mitsuhashi, Seiji Watanabe, Hirokazu Narita, Tomohiro Chiba, Kenichi Hakamada
    PLOS ONE 18(5) e0286316-e0286316 2023年5月25日  
    Lymphatic fluid drains from the liver via the periportal lymphatic, hepatic venous lymphatic, and superficial lymphatic systems. We performed a postmortem study to clarify the three-dimensional structure and flow dynamics of the human hepatic venous lymphatic system, as it still remains unclear. Livers were excised whole from three human cadavers, injected with India ink, and sliced into 1-cm sections from which veins were harvested. The distribution of lymphatic vessels was observed in 5 μm sections immunostained for lymphatic and vascular markers (podoplanin and CD31, respectively) using light microscopy. Continuity and density of lymphatic vessel distribution were assessed in en-face whole-mount preparations of veins using stereomicroscopy. The structure of the external hepatic vein wall was assessed with scanning electron microscopy (SEM). The lymphatic dynamics study suggested that lymphatic fluid flows through an extravascular pathway around the central and sublobular veins. A lymphatic vessel network originates in the wall of sublobular veins, with a diameter greater than 110 μm, and the peripheral portions of hepatic veins and continues to the inferior vena cava. The density distribution of lymphatic vessels is smallest in the peripheral portion of the hepatic vein (0.03%) and increases to the proximal portion (0.22%, p = 0.012) and the main trunk (1.01%, p &lt; 0.001), correlating positively with increasing hepatic vein diameter (Rs = 0.67, p &lt; 0.001). We revealed the three-dimensional structure of the human hepatic venous lymphatic system. The results could improve the understanding of lymphatic physiology and liver pathology.
  • Akiko Suto, Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Hidezumi Kikuchi, Chikara Iino, Go Igarashi, Satoshi Sato, Hirotake Sakuraba, Kenichi Hakamada
    Clinical journal of gastroenterology 16(5) 726-731 2023年5月11日  
    A 65-year-old woman underwent living-donor liver transplantation (left-lobe graft: GWRW ratio, 0.54) for cirrhosis caused by autoimmune hepatitis. At 68 years, she was diagnosed with obstructive cholangitis due to stricture during a hepaticojejunostomy following impaired liver function. Endoscopic balloon dilation of anastomosis and placement of a plastic stent resulted in improved liver function. However, at 72 years, the patient experienced a flare-up of liver damage. The plastic stent had fallen out, and although endoscopic stenotic dilation was attempted, the anastomotic site was obstructed completely. Therefore, recanalization of the hepaticojejunostomy was attempted using a rendezvous technique. A percutaneous transhepatic biliary drainage tube was inserted through the B3 bile duct, and the complete obstructed anastomosis was confirmed by percutaneous transhepatic and transjejunal approaches. The anastomosis was reopened by excising the scarred tissues from the jejunal side using a 1.5-mm high-frequency knife. A 14-Fr. catheter for the internal fistula tube was percutaneously placed at the opened anastomosis to achieve anastomotic site recanalization. The patient's liver damage improved after the re-internalization, and no symptom recurrence such as obstructive cholangitis developed for 1 year. There are few reports of recanalization of the hepaticojejunostomy with a high-frequency knife. Herein, we report the case with a literature review.
  • Keisuke Yamazaki, Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Daichi Ichinohe, Yoshiya Takahashi, Tadashi Yoshizawa, Hiroshi Kijima, Kenichi Hakamada
    Clinical journal of gastroenterology 16(2) 289-296 2023年4月  
    Serous cystic neoplasm (SCN) is a potentially malignant and invasive disease. However, there are no established guidelines regarding the surgical management of SCN. Here, we report a case of SCN with jejunal invasion that ultimately required a distal pancreatectomy with partial resection of the jejunum. The patient was a 65-year-old female who was referred to our department after a diagnosis of SCN in the pancreatic tail. CT and MRI showed a 75-mm multifocal cystic mass with calcifications; the splenic vein and left adrenal vein were entrapped within the tumor. Furthermore, the tumor was in contact with the beginning of the jejunum. Finally, she underwent a posterior radical antegrade modular pancreatosplenectomy with a partial wedge-shaped resection of the jejunum. Histological findings indicated serous cystadenoma. In addition, the tumor cells were found to have infiltrated the jejunal muscularis propria in some areas, suggesting that the tumor had malignant potential. Currently, 14 months have passed since surgery and there is no evidence of metastasis or recurrence. Surveillance and the decision to perform surgical resection should be made based on tumor size and growth rate to avoid malignant transformation as well as to provide SCN patients with organ-sparing, less invasive surgery.
  • Hirokazu Ogasawara, Tadashi Yoshizawa, Kiyoko Oshima, Kenta Ogasawara, Shunsuke Kubota, Shintaro Goto, Satoko Morohashi, Taiichi Wakiya, Norihisa Kimura, Keinosuke Ishido, Hiroshi Kijima, Kenichi Hakamada
    Pathology oncology research : POR 29 1611284-1611284 2023年  
    Perineural invasion (PNI) is a characteristic invasion pattern of distal cholangiocarcinoma (DCC). Conventional histopathologic examination is a challenging approach to analyze the spatial relationship between cancer and neural tissue in full-thickness bile duct specimens. Therefore, we used a tissue clearing method to examine PNI in DCC with three-dimensional (3D) structural analysis. The immunolabeling-enabled 3D imaging of solvent-cleared organs method was performed to examine 20 DCC specimens from five patients and 8 non-neoplastic bile duct specimens from two controls. The bile duct epithelium and neural tissue were labeled with CK19 and S100 antibodies, respectively. Two-dimensional hematoxylin/eosin staining revealed only PNI around thick nerve fibers in the deep layer of the bile duct, whereas PNI was not identified in the superficial layer. 3D analysis revealed that the parts of DCC closer to the mucosa exhibited more nerves than the normal bile duct. The nerve fibers were continuously branched and connected with thick nerve fibers in the deep layer of the bile duct. DCC formed a tubular structure invading from the epithelium and extending around thin nerve fibers in the superficial layer. DCC exhibited continuous infiltration around the thick nerve fibers in the deep layer. This is the first study using a tissue clearing method to examine the PNI of DCC, providing new insights into the underlying mechanisms.
  • Hiroaki Fujita, Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Taishu Kanda, Masashi Matsuzaka, Yoshihiro Sasaki, Kenichi Hakamada
    Annals of gastroenterological surgery 6(6) 823-832 2022年11月  
    BACKGROUND: The differential diagnosis between gallbladder cancer (GBC) and xanthogranulomatous cholecystitis (XGC) remains quite challenging, and can possibly lead to improper surgery. This study aimed to distinguish between XGC and GBC by combining computed tomography (CT) images and deep learning (DL) to maximize the therapeutic success of surgery. METHODS: We collected a dataset, including preoperative CT images, from 28 cases of GBC and 21 XGC patients undergoing surgery at our facility. It was subdivided into training and validation (n = 40), and test (n = 9) datasets. We built a CT patch-based discriminating model using a residual convolutional neural network and employed 5-fold cross-validation. The discriminating performance of the model was analyzed in the test dataset. RESULTS: Of the 40 patients in the training dataset, GBC and XGC were observed in 21 (52.5%), and 19 (47.5%) patients, respectively. A total of 61 126 patches were extracted from the 40 patients. In the validation dataset, the average sensitivity, specificity, and accuracy were 98.8%, 98.0%, and 98.5%, respectively. Furthermore, the area under the receiver operating characteristic curve (AUC) was 0.9985. In the test dataset, which included 11 738 patches, the discriminating accuracy for GBC patients after neoadjuvant chemotherapy (NAC) (n = 3) was insufficient (61.8%). However, the discriminating model demonstrated high accuracy (98.2%) and AUC (0.9893) for cases other than those receiving NAC. CONCLUSION: Our CT-based DL model exhibited high discriminating performance in patients with GBC and XGC. Our study proposes a novel concept for selecting the appropriate procedure and avoiding unnecessary invasive measures.
  • Kohei Chida, Keinosuke Ishido, Yoshiyuki Sakamoto, Norihisa Kimura, Hajime Morohashi, Takuya Miura, Taiichi Wakiya, Hiroshi Yokoyama, Hayato Nagase, Daichi Ichinohe, Akiko Suto, Daisuke Kuwata, Aika Ichisawa, Akie Nakamura, Daiki Kasai, Kenichi Hakamada
    Surgical case reports 8(1) 183-183 2022年9月27日  
    BACKGROUND: Emphysematous pancreatitis is acute pancreatitis associated with emphysema based on imaging studies and has been considered a subtype of necrotizing pancreatitis. Although some recent studies have reported the successful use of conservative treatment, it is still considered a serious condition. Computed tomography (CT) scan is useful in identifying emphysema associated with acute pancreatitis; however, whether the presence of emphysema correlates with the severity of pancreatitis remains controversial. In this study, we managed two cases of severe acute pancreatitis complicated with retroperitoneal emphysema successfully by treatment with lavage and drainage. CASE PRESENTATION: Case 1: A 76-year-old man was referred to our hospital after being diagnosed with acute pancreatitis. At post-admission, his abdominal symptoms worsened, and a repeat CT scan revealed increased retroperitoneal gas. Due to the high risk for gastrointestinal tract perforation, emergent laparotomy was performed. Fat necrosis was observed on the anterior surface of the pancreas, and a diagnosis of acute necrotizing pancreatitis with retroperitoneal emphysema was made. Thus, retroperitoneal drainage was performed. Case 2: A 50-year-old woman developed anaphylactic shock during the induction of general anesthesia for lumbar spine surgery, and peritoneal irritation symptoms and hypotension occurred on the same day. Contrast-enhanced CT scan showed necrotic changes in the pancreatic body and emphysema surrounding the pancreas. Therefore, she was diagnosed with acute necrotizing pancreatitis with retroperitoneal emphysema, and retroperitoneal cavity lavage and drainage were performed. In the second case, the intraperitoneal abscess occurred postoperatively, requiring time for drainage treatment. Both patients showed no significant postoperative course problems and were discharged on postoperative days 18 and 108, respectively. CONCLUSION: Acute pancreatitis with emphysema from the acute phase highly indicates severe necrotizing pancreatitis. Surgical drainage should be chosen without hesitation in necrotizing pancreatitis with emphysema from early onset.
  • Taishu Kanda, Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hiroaki Fujita, Tadashi Yoshizawa, Shintaro Goto, Yota Tatara, Hiroshi Kijima, Kenichi Hakamada
    Journal of gastroenterology 57(10) 798-811 2022年7月3日  
    BACKGROUND: Evolutionary cancer has a supply mechanism to satisfy higher energy demands even in poor-nutrient conditions. Metabolic reprogramming is essential to supply sufficient energy. The relationship between metabolic reprogramming and the clinical course of pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to clarify the differences in metabolic status among PDAC patients. METHODS: We collected clinical data from 128 cases of resectable PDAC patients undergoing surgery. Sixty-three resected tissues, 15 tissues from the low carbohydrate antigen 19-9 (CA19-9), 38-100 U/mL, and high CA19-9, > 500 U/mL groups, and 33 non-tumor control parts, were subjected to tandem mass spectrometry workflow to systematically explore metabolic status. Clinical and proteomic data were compared on the most used PDAC biomarker, preoperative CA19-9 value. RESULTS: Higher CA19-9 levels were clearly associated with higher early recurrence (p < 0.001), decreased RFS (p < 0.001), and decreased DSS (p = 0.025). From proteomic analysis, we discovered that cancer evolution-related as well as various metabolism-related pathways were more notable in the high group. Using resected tissue immunohistochemical staining, we learned that high CA19-9 PDAC demonstrated aerobic glycolysis enhancement, yet no decrease in protein synthesis. We found a heterogeneity of various metabolic processes, including carbohydrates, proteins, amino acids, lipids, and nucleic acids, between the low and the high groups, suggesting differences in metabolic adaptive capacity. CONCLUSIONS: Our study found metabolic adaptation differences among PDAC cases, pertaining to both cancer evolution and the prognosis. CA19-9 can help estimate the metabolic adaptive capacity of energy supply for PDAC evolution.
  • Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Taishu Kanda, Sotaro Ichiyama, Kenji Soma, Masashi Matsuzaka, Yoshihiro Sasaki, Shunsuke Kubota, Hiroaki Fujita, Takeyuki Sawano, Yutaka Umehara, Yusuke Wakasa, Yoshikazu Toyoki, Kenichi Hakamada
    Scientific reports 12(1) 8428-8428 2022年5月19日  
    Preoperatively accurate evaluation of risk for early postoperative recurrence contributes to maximizing the therapeutic success for intrahepatic cholangiocarcinoma (iCCA) patients. This study aimed to investigate the potential of deep learning (DL) algorithms for predicting postoperative early recurrence through the use of preoperative images. We collected the dataset, including preoperative plain computed tomography (CT) images, from 41 patients undergoing curative surgery for iCCA at multiple institutions. We built a CT patch-based predictive model using a residual convolutional neural network and used fivefold cross-validation. The prediction accuracy of the model was analyzed. We defined early recurrence as recurrence within a year after surgical resection. Of the 41 patients, early recurrence was observed in 20 (48.8%). A total of 71,081 patches were extracted from the entire segmented tumor area of each patient. The average accuracy of the ResNet model for predicting early recurrence was 98.2% for the training dataset. In the validation dataset, the average sensitivity, specificity, and accuracy were 97.8%, 94.0%, and 96.5%, respectively. Furthermore, the area under the receiver operating characteristic curve was 0.994. Our CT-based DL model exhibited high predictive performance in projecting postoperative early recurrence, proposing a novel insight into iCCA management.
  • Hajime Morohashi, Yoshiyuki Sakamoto, Takuya Miura, Daichi Ichinohe, Shunsuke Kubota, Keisuke Yamazaki, Aika Ichisawa, Yuto Mitsuhashi, Taiichi Wakiya, Kenichi Hakamada
    Asian journal of endoscopic surgery 15(3) 577-584 2022年3月18日  
    INTRODUCTION: There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery. METHODS: From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC. RESULTS: The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P = .024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P < .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P < .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group. CONCLUSIONS: Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.
  • Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Hayato Nagase, Yutaro Hara, Taishu Kanda, Hiroaki Fujita, Kenichi Hakamada
    Annals of surgical oncology 29(2) 1281-1293 2022年2月  
    BACKGROUND: Resectable pancreatic ductal adenocarcinoma (R-PDAC) often recurs early after radical resection, which is associated with poor prognosis. Predicting early recurrence preoperatively is useful for determining the optimal treatment. PATIENTS AND METHODS: One hundred and seventy-eight patients diagnosed with R-PDAC on computed tomography (CT) imaging and undergoing radical resection at Hirosaki University Hospital from 2005 to 2019 were retrospectively analyzed. Patients with recurrence within 6 months after resection formed the early recurrence (ER) group, while other patients constituted the non-early recurrence (non-ER) group. Early recurrence prediction score (ERP score) was developed using preoperative parameters. RESULTS: ER was observed in 45 patients (25.3%). The ER group had significantly higher preoperative CA19-9 (p = 0.03), serum SPan-1 (p = 0.006), and CT tumor diameter (p = 0.01) compared with the non-ER group. The receiver operating characteristic (ROC) curve analysis identified cutoff values for CA19-9 (133 U/mL), SPan-1 (78.2 U/mL), and preoperative tumor diameter (23 mm). When the parameter exceeded the cutoff level, 1 point was given, and the total score of the three factors was defined as the ERP score. The group with an ERP score of 3 had postoperative recurrence-free survival (RFS) of 5.5 months (95% CI 3.02-7.98). Multivariate analysis for ER-related perioperative and surgical factors identified ERP score of 3 [odds ratio (OR) 4.63 (95% CI 1.82-11.78), p = 0.0013] and R1 resection [OR 3.20 (95% CI 1.01-10.17), p = 0.049] as independent predictors of ER. CONCLUSIONS: For R-PDAC, ER could be predicted by the scoring system using preoperative serum CA19-9 and SPan-1 levels and CT tumor diameter, which may have great significance in identifying patients with poor prognoses and avoiding unnecessary surgery.
  • Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Hayato Nagase, Yutaro Hara, Taishu Kanda, Hiroaki Fujita, Kenichi Hakamada
    Annals of surgical oncology 29(2) 1294-1295 2022年2月  
  • Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Tadashi Yoshizawa, Satoko Morohashi, Hiroaki Fujita, Taishu Kanda, Yota Tatara, Junji Saruwatari, Hiroshi Kijima, Kenichi Hakamada
    Scientific reports 11(1) 21197-21197 2021年10月27日  
    Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P < 0.001), and decreased DSS (P < 0.001). The severity of lymphatic (r = 0.440, P = 0.042) and venous (r = 0.610, P = 0.002) invasions was positively correlated with the ne score. Tumors having abundant stroma often displayed severe ne. Proteomics identified eukaryotic initiation factor 2 (EIF2) signaling as the most significantly enriched pathway in high-grade ne PDAC. Additionally, EIF2 signaling-related ribosome proteins decreased according to severity. Results showed that PNI is linked with lymphatic and vascular invasion in early-stage PDAC. Furthermore, the dysregulation of proteostasis and ribosome biogenesis can yield a difference in PNI severity.
  • Taishu Kanda, Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Shunsuke Kubota, Hiroaki Fujita, Yusuke Hagiwara, Kenichi Hakamada
    Pancreas 50(9) 1314-1325 2021年10月1日  
    OBJECTIVE: We aimed to investigate the real impact of allogeneic red blood cell transfusion (ABT) on postoperative outcomes in resectable pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: Of 128 patients undergoing resectable PDAC surgery at our facility, 24 (18.8%) received ABT. Recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ABT. RESULTS: In the entire cohort, ABT was significantly associated with decreased RFS (P = 0.002) and DSS (P = 0.014) before PSM. Cox regression analysis identified ABT (risk ratio, 1.884; 95% confidence interval, 1.015-3.497; P = 0.045) as an independent prognostic factor for RFS. Univariate and multivariate analysis identified preoperative hemoglobin value, preoperative total bilirubin value, and intraoperative blood loss as significant independent risk factors for ABT. Using these 3 variables, PSM analysis created 16 pairs of patients. After PSM, the ABT group had significantly poorer RFS rates than the non-ABT group (median, 9.8 vs 15.8 months, P = 0.022). Similar tendencies were found in DSS rates (median, 19.4 vs 40.0 months, P = 0.071). CONCLUSIONS: This study revealed certain negative effects of intraoperative ABT on postoperative survival outcomes in patients with resectable PDAC.
  • Taiichi Wakiya, Keinosuke Ishido, Tadashi Yoshizawa, Taishu Kanda, Kenichi Hakamada
    Annals of gastroenterological surgery 5(5) 623-633 2021年9月  
    Pancreatic ductal adenocarcinoma (PDAC), with its extremely poor prognosis, presents a substantial health problem worldwide. Outcomes have improved thanks to progress in surgical technique, chemotherapy, pre-/postoperative management, and centralization of patient care to high-volume centers. However, our goals are yet to be met. Recently, exome sequencing using PDAC surgical specimens has demonstrated that the most frequently altered genes were the axon guidance genes, indicating involvement of the nervous system in PDAC carcinogenesis. Moreover, perineural invasion has been widely identified as one poor prognostic factor. The combination of innovative technologies and extensive clinician experience with the nervous system come together here to create a new treatment option. However, evidence has emerged that suggests that the relationship between cancer and nerves in PDAC, the underlying mechanism, is not fully understood. In an attempt to tackle this lethal cancer, this review summarizes the anatomy and physiology of the pancreas and discusses the role of the nervous system in the pathophysiology of PDAC.
  • Hajime Morohashi, Yoshiyuki Sakamoto, Takuya Miura, Daichi Ichinohe, Kotaro Umemura, Takanobu Akaishi, Kentaro Sato, Daisuke Kuwata, Keisuke Yamazaki, Taiichi Wakiya, Kenichi Hakamada
    International journal of colorectal disease 36(6) 1251-1261 2021年6月  
    PURPOSE: There are no reports showing the significance and effective range of dissection for patients with lateral lymph node metastasis (LLNM). This study aimed to investigate the indications for lateral lymph node dissection (LLND) in patients with LLNM based on prognostic factors and recurrence types. METHODS: We reviewed 379 patients with advanced rectal cancer who were treated with total mesorectal excision plus LLND. We analyzed background factors and survival times of patients who had LLNM to determine prognostic factors and recurrence types. RESULTS: Pathological LLNM occurred in 44 (11.6%). Among patients with LLNM, the predictors of poor prognoses, according to univariate analysis, were > 3 node metastases, the presence of node metastasis on both sides, and spreading beyond the internal iliac lymph nodes. Moreover, LLNM beyond the internal iliac region was found to be an independent prognostic risk factor. Twenty-eight of the 44 patients with lateral lymph node metastasis (64%) relapsed, 22 of whom had distant metastases and 11 of whom experienced local recurrences. Among the latter group, nine (20%) and two (5%) had recurrences in the central and lateral pelvis, respectively. CONCLUSION: The therapeutic benefit of resection was high, especially in patients with ≤ 3 positive lateral lymph nodes, one-sided bilateral lymph node areas, and positive nodes localized near the internal iliac artery.
  • Yoshiyuki Sakamoto, Hajime Morohashi, Takuya Miura, Shinji Tsutsumi, Seiji Takahashi, Kimiaki Hirama, Taiichi Wakiya, Kenichi Hakamada
    Diseases of the colon and rectum 65(5) 663-671 2021年4月5日  
    BACKGROUND: Neoadjuvant chemoradiotherapy and total mesorectal excision comprise the standard of care for rectal cancer in multiple guidelines. However, neoadjuvant chemoradiotherapy has not exhibited clear survival benefits, but rather has led to an increase in adverse events. Conversely, neoadjuvant chemotherapy is expected to prevent adverse events caused by radiation, yet this treatment is still controversial. OBJECTIVE: To evaluate the feasibility and efficacy of S-1 and oxaliplatin neoadjuvant chemotherapy together with total mesorectal excision for resectable locally advanced rectal cancer. DESIGN: The study was a prospective, single-arm phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Fifty-eight patients with resectable locally advanced rectal cancer were enrolled. INTERVENTION: Three cycles of S-1 and oxaliplatin were administered before surgery. S-1 was administered orally at 80 mg/m2/day for 14 consecutive days, followed by a 7-day resting period. Oxaliplatin was given intravenously on the first day at a dose of 130 mg/m2/day. The duration of one cycle was considered to be 21 days. Total mesorectal excision with bilateral lymph node dissection was carried out after neoadjuvant chemotherapy. MAIN OUTCOME MEASURES: The study was designed to detect the feasibility and efficacy of S-1 and oxaliplatin as neoadjuvant chemotherapy. RESULTS: The completion rate of three courses of S-1 and oxaliplatin as neoadjuvant chemotherapy was 94.8% (55/58). The reasons for discontinuation were thrombocytopenia (3.4%) and liver injury (1.7%). The most common severe (grade ≥ 3) adverse effect of neoadjuvant chemotherapy was thrombocytopenia (3.4%). There were no severe adverse clinical symptoms. Consequently, R0 resection was achieved in 51 of 52 patients (98.1%). Pathological complete response occurred in 10 patients (19.2%). LIMITATIONS: This was a single-arm, nonrandomized phase II study. CONCLUSIONS: The combination of S-1 and oxaliplatin neoadjuvant chemotherapy and total mesorectal excision is a feasible and promising treatment option for resectable locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B555.
  • Hiroaki Fujita, Keinosuke Ishido, Norihisa Kimura, Taiichi Wakiya, Hayato Nagase, Tadashi Yoshizawa, Toshihiro Haga, Shintaro Goto, Hiroshi Kijima, Kenichi Hakamada
    Surgical case reports 7(1) 25-25 2021年1月15日  
    BACKGROUND: Intra-ampullary papillary-tubular neoplasm (IAPN) has been classified as a Vater papillary tumor. The prognosis of IAPN is generally relatively good. Here, we describe a patient with a mucinous adenocarcinoma cluster in the Vater papilla of IAPN origin. CLINICAL PRESENTATION: The patient was a 66-year-old man who was admitted to our hospital after a diagnosis of pancreatic head carcinoma based on a pancreatic duct dilatation found on abdominal ultrasound. CT showed a 40 mm lesion in the pancreatic head and expansion of the main pancreatic duct to a maximum diameter of 9 mm on the caudal side of the lesion. The extrahepatic bile duct had also expanded to a maximum diameter of 8 mm. PET/CT showed fluorodeoxyglucose (FDG) accumulation of SUVmax 6.02 that corresponded to the tumor in the pancreatic head, though it did not suggest distant metastasis. The patient was diagnosed with pancreatic head carcinoma T3 N0 M0 Stage IIA and underwent a pancreaticoduodenectomy. Pathology indicated that the tumor in the pancreatic head was a benign inflammatory lesion. On the other hand, the papillotubular tumor pervading the lumen in the duodenal papillary common channel met the criteria for IAPN, and a mucinous adenocarcinoma cluster found in the surrounding stroma suggested malignant transformation of IAPN. No metastasis to lymph nodes was demonstrated. With regard to the mucus phenotype of each lesion, the IAPN was MUC2 and MUC5AC positive, while the mucinous adenocarcinoma was MUC2-positive and MUC5AC-negative. In addition, CD10 was negative in both lesions, suggesting that mucus transformation from the gastric type to the intestinal type was a key element. A blood test 10 months after surgery showed increased CA19-9 (105 U/mL) and CEA (7.1 ng/mL). Abdominal CT showed multiple cystoid nodes in the liver, which were diagnosed as multiple liver metastases of mucinous adenocarcinoma transformed from the IAPN. CONCLUSIONS: We reported a case with IAPN that developed in the Vater papilla, which took an extremely malignant course. IAPN generally has a good prognosis, but it is important to understand that a malignant course may occur.
  • Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Shunsuke Kubota, Hiroaki Fujita, Yusuke Hagiwara, Taishu Kanda, Masashi Matsuzaka, Yoshihiro Sasaki, Kenichi Hakamada
    PloS one 16(11) e0259682 2021年  
    Massive intraoperative blood loss (IBL) negatively influence outcomes after surgery for pancreatic ductal adenocarcinoma (PDAC). However, few data or predictive models are available for the identification of patients with a high risk for massive IBL. This study aimed to build a model for massive IBL prediction using a decision tree algorithm, which is one machine learning method. One hundred and seventy-five patients undergoing curative surgery for resectable PDAC at our facility between January 2007 and October 2020 were allocated to training (n = 128) and testing (n = 47) sets. Using the preoperatively available data of the patients (34 variables), we built a decision tree classification algorithm. Of the 175 patients, massive IBL occurred in 88 patients (50.3%). Binary logistic regression analysis indicated that alanine aminotransferase and distal pancreatectomy were significant predictors of massive IBL occurrence with an overall correct prediction rate of 70.3%. Decision tree analysis automatically selected 14 predictive variables. The best predictor was the surgical procedure. Though massive IBL was not common, the outcome of patients with distal pancreatectomy was secondarily split by glutamyl transpeptidase. Among patients who underwent PD (n = 83), diabetes mellitus (DM) was selected as the variable in the second split. Of the 21 patients with DM, massive IBL occurred in 85.7%. Decision tree sensitivity was 98.5% in the training data set and 100% in the testing data set. Our findings suggested that a decision tree can provide a new potential approach to predict massive IBL in surgery for resectable PDAC.
  • Keinosuke Ishido, Kenichi Hakamada, Norihisa Kimura, Takuya Miura, Taiichi Wakiya
    Annals of gastroenterological surgery 5(1) 7-23 2021年1月  
    Pancreatic ductal adenocarcinoma (PDAC) is highly malignant. While cancers in other organs have shown clear improvements in 5-year survival, the 5-year survival rate of pancreatic cancer is approximately 10%. Early relapse and metastasis are not uncommon, making it difficult to achieve an acceptable prognosis even after complete surgical resection of the pancreas. Studies have been performed on various treatments to improve the prognosis of PDAC, and multidisciplinary approaches including non-surgical treatments have led to gradual improvement. In the present literature review, we have described the significance of anatomical and biological resectability criteria, the concept of R0 resection in surgical treatment, the feasibility of minimally invasive surgery, the remarkable development of perioperative chemotherapy, the effectiveness of conversion surgery for unresectable PDAC, and ongoing challenges in PDAC treatment. We also provide an essential update on these subjects by focusing on recent trends and topics.
  • Junichi Nakagawa, Keinosuke Ishido, Yuka Tono, Norihisa Kimura, Taiichi Wakiya, Yuji Okamura, Kenichi Hakamada, Takenori Niioka
    European journal of drug metabolism and pharmacokinetics 45(5) 619-626 2020年10月  
    BACKGROUND AND OBJECTIVE: Tacrolimus clearance (CL) is significantly altered according to recovery of liver function at an early stage after living donor liver transplantation (LDLT). In this study, we aimed to examine the impact of the change rate from postoperative day (POD) 1 in CL (ΔCL) of tacrolimus during continuous intravenous infusion (CIVI) on recipient recovery. METHODS: A tacrolimus population pharmacokinetic model on POD1 after LDLT was developed using Phoenix NLME 1.3. The CLPOD1 was calculated using the final model. The CLPOD4-7 was calculated by dividing total daily tacrolimus dose by the area under the concentration-time curve from 0 to 24 h. RESULTS: Data were obtained from 57 LDLT recipients, along with 540 points (177 points on POD1, 363 points on POD4-7) of tacrolimus whole blood concentrations at CIVI. The median tacrolimus CL decreased from POD1 to POD4 (from 2.73 to 1.40 L/h) and was then stable until POD7. Stepwise Cox proportional hazards regression analyses showed that the graft volume (GV)/standard liver volume (SLV) ratio (GV/SLV) and the tacrolimus ΔCLPOD6 were independent factors predicting early discharge (within 64 days median value) of recipients after LDLT [hazard ratio (HR) = 1.041, P = 0.001 and HR = 1.023, P = 0.004]. CONCLUSIONS: The tacrolimus ΔCL during CIVI immediately after LDLT in each recipient was a useful indicator for evaluation of recovery at an early stage after LDLT.
  • Naoya Yamada, Tadayoshi Karasawa, Taiichi Wakiya, Ai Sadatomo, Homare Ito, Ryo Kamata, Sachiko Watanabe, Takanori Komada, Hiroaki Kimura, Yukihiro Sanada, Yasunaru Sakuma, Koichi Mizuta, Nobuhiko Ohno, Naohiro Sata, Masafumi Takahashi
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20(6) 1606-1618 2020年1月7日  査読有り
    Hepatic ischemia-reperfusion (I/R) injury is a major problem in liver transplantation (LT). Although hepatocyte cell death is the initial event in hepatic I/R injury, the underlying mechanism remains unclear. In the present study, we retrospectively analyzed the clinical data of 202 pediatric living donor LT and found that a high serum ferritin level, a marker of iron overload, of the donor is an independent risk factor for liver damage after LT. Since ferroptosis has been recently discovered as an iron-dependent cell death that is triggered by a loss of cellular redox homeostasis, we investigated the role of ferroptosis in a murine model of hepatic I/R injury, and found that liver damage, lipid peroxidation, and upregulation of the ferroptosis marker Ptgs2 were induced by I/R, and all of these manifestations were markedly prevented by the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or α-tocopherol. Fer-1 also inhibited hepatic I/R-induced inflammatory responses. Furthermore, hepatic I/R injury was attenuated by iron chelation by deferoxamine and exacerbated by iron overload with a high iron diet. These findings demonstrate that iron overload is a novel risk factor for hepatic I/R injury in LT, and ferroptosis contributes to the pathogenesis of hepatic I/R injury.
  • Umetsu S, Wakiya T, Ishido K, Kudo D, Kimura N, Miura T, Toyoki Y, Hakamada K
    ANZ Journal of Surgery 88(9) E654-E658 2018年9月  査読有り
  • Wakiya T, Ishido K, Kudo D, Kimura N, Sakuraba S, Tsutsumi S, Kagiya T, Uchida C, Hakamada K
    Clinical nutrition ESPEN 23 54-60 2018年2月  査読有り
  • 若狭 悠介, 石戸 圭之輔, 工藤 大輔, 木村 憲央, 脇屋 太一, 袴田 健一
    外科 80(1) 92-98 2018年1月  
    症例は72歳女性で、閉塞性黄疸を契機に膵頭部癌を指摘され、亜全胃温存膵頭十二指腸切除術(SSPPD)および門脈合併切除が施行された。術後S-1を用いた補助化学療法を施行していたが、下血が出現した。腹部CTでは門脈周囲に不整な軟部組織と門脈狭窄像を認め、上部消化管内視鏡検査で食道静脈瘤からの出血と判明したため内視鏡的静脈瘤結紮術を施行した。その後、化学療法を継続していたが吐血が出現した。腹部CT所見では、肝門部領域の門脈周囲に軟部組織陰影を認め、同組織により門脈の高度な狭窄を伴った。胃および食道への側副血行路の発達と脾腫を認めた。上部消化管内視鏡検査所見では、食道胃接合部より口側に食道静脈瘤を認めた。SSPPD術後の炎症性変化もしくは膵頭部癌局所再発による高度の門脈狭窄から門脈圧亢進をきたし、食道静脈瘤出血が出現していると判断した。症状およびADL改善を目的に門脈ステントを留置した。留置後は大きな合併症なく良好に経過し、術後3日目に退院した。術後3年3ヵ月目となる現在も門脈圧亢進症状や再発の出現を認めず、外来通院中である。
  • Mitsuhashi Y, Wakiya T, Ishido K, Kudo D, Kimura N, Sato K, Amagasa J, Shibazuka T, Toyoki Y, Hakamada K
    Transplantation proceedings 50(9) 2723-2725 2018年  査読有り
  • Wakiya T, Ishido K, Kudo D, Kimura N, Sato K, Mitsuhashi Y, Kagiya T, Uchida C, Umetsu S, Yoshida T, Wakasa Y, Toyoki Y, Hakamada K
    Transplantation proceedings 50(9) 2593-2596 2018年  査読有り
  • Okano K, Yoshizawa T, Miura T, Ishido K, Kudo D, Kimura N, Wakiya T. I, Wu Y, Morohashi S, Hakamada K, Kijima H
    Mol Clin Oncol 8(1) 54-60 2018年  査読有り
  • 三橋 佑人, 木村 憲央, 石戸 圭之輔, 工藤 大輔, 脇屋 太一, 矢越 雄太, 豊木 嘉一, 袴田 健一
    癌と化学療法 44(12) 1098-1100 2017年11月  
    症例は72歳、女性。平成某年2月、胆嚢癌の診断で拡大胆嚢摘出術、肝外胆管切除術を施行した。病理診断は、CGnBdGb、circ、nodular infiltrating type、20×10mm、tub2、pT3b、int、INFc、ly1、v1、ne3、pN0、pDM0、pHM0、pEM0、pPV0、pA0、R0、Stage IIIAであり、病変の主座が胆嚢管であったため、胆嚢管癌と診断した。術後7ヵ月、follow up CTで肝S7に10mm大の腫瘍を認め肝転移再発の診断となった。化学療法として、gemcitabine(GEM1,000mg/m2)を3週投与1週休薬で開始した。3コース施行した時点のCTで肝腫瘍は不明瞭化し、6コース目からはGEM(1,000mg/m2)を隔週投与とした。8コース施行した時点で肝腫瘍は指摘されずcomplete response(CR)が得られた。GEMは計21コース施行後に離脱し、術後4年4ヵ月現在、再発徴候なく経過している。(著者抄録)
  • 須藤 亜希子, 工藤 大輔, 石戸 圭之輔, 木村 憲央, 脇屋 太一, 諸橋 聡子, 鬼島 宏, 袴田 健一
    癌と化学療法 44(12) 1120-1122 2017年11月  
    症例は82歳、男性。貧血があり上部消化管内視鏡検査を施行したところ、十二指腸球部後壁に易出血性の1型腫瘍を認め、生検にて神経内分泌癌の診断を得た。その他の画像診断では遠隔転移を認めず、膵頭十二指腸切除術を施行した。病理所見より、neuroendocrine carcinoma(NEC)と診断した。術後補助化学療法は施行せず外来経過観察を行い、術後16ヵ月無再発生存中である。消化管原発NECのなかでも、乳頭部発生を除く十二指腸NECの報告例はまれであるので若干の文献的考察を加えて報告する。(著者抄録)
  • 谷地 孝文, 脇屋 太一, 石戸 圭之輔, 工藤 大輔, 木村 憲央, 袴田 健一
    癌と化学療法 44(12) 1683-1685 2017年11月  
    症例は34歳、男性。2011年9月に家族性大腸腺腫症の診断となり、多発十二指腸ポリープ、多発小腸ポリープに対し内視鏡的粘膜切除術(endoscopic mucosal resection:EMR)を施行された。同年12月に十二指腸乳頭部癌に対し内視鏡的十二指腸乳頭切除術を施行されるも、水平断端陽性のため2012年1月に再度EMRが施行された。同年12月に大腸全摘術および小腸部分切除術を施行した。その後は3ヵ月ないし6ヵ月ごとに内視鏡検査で観察し、計4回EMRを行った。2014年より6ヵ月ごとの経過観察としていたが、2016年1月に十二指腸乳頭部癌の再発を認め、膵頭十二指腸切除術を施行した。病理組織診はadenocarcinoma、tub2>tub1、pT1a、N0、M0、fStage IAの診断であった。十二指腸粘膜にはlow-high grade adenomaが多発していた。術後1年6ヵ月を経過した現在、無再発で経過している。(著者抄録)
  • Yachi T, Wakiya T, Ishido K, Kudo D, Kimura N, Hakamada K
    Gan to kagaku ryoho. Cancer &amp; chemotherapy 44(12) 1683-1685 2017年11月  査読有り
  • Suto A, Kudo D, Ishido K, Kimura N, Wakiya T, Morohashi S, Kijima H, Hakamada K
    Gan to kagaku ryoho. Cancer &amp; chemotherapy 44(12) 1120-1122 2017年11月  査読有り
  • Takuji Kagiya, Hiroshi Shimoda, Hirokazu Narita, Tadashi Odagiri, Seiji Watanabe, Keinosuke Ishido, Daisuke Kudo, Norihisa Kimura, Taiichi Wakiya, Kenichi Hakamada
    Journal of hepato-biliary-pancreatic sciences 24(10) 570-575 2017年10月  査読有り
    BACKGROUND: Little information is available regarding microanatomy of lymphatic system in the ampulla of Vater, though it is of critical importance for an understanding of tumor progression via the lymphatics and determination of surgical strategy. The present study, therefore, aimed to demonstrate the distribution and microanatomical profiles on the lymphatic system in the ampulla. METHODS: The fine distribution and structure of the lymphatic vessels were investigated in the ampulla and the stomach by immunohistochemistry for lymphatic- (D2-40) and blood vascular- (CD31) specific markers and scanning electron microscopy. The densities of lymphatic and blood vessels were also compared. RESULTS: The duodenal papilla densely developed the lymphatics with distinct aspects of lymphatic capillaries, together with blood vessels. The density of lymphatic capillaries in the extramuscular layer in the ampulla was higher than those of both the other ampullary layers and the gastric extramuscular (subserosal) layer. CONCLUSIONS: The ampulla of Vater showed widespread lymphatic capillaries throughout the entire wall. The specific vascular system is suited to produce lymph everywhere and drain without via such a large vessel as lymphatic collector. This suggests that tumor cells invade the lymphatics and metastasize more easily in the ampulla than in the other gastrointestinal regions.
  • 若狭 悠介, 木村 憲央, 石戸 圭之輔, 工藤 大輔, 脇屋 太一, 中山 義人, 赤石 隆信, 吉田 達哉, 諸橋 聡子, 袴田 健一
    日本消化器外科学会雑誌 50(8) 664-672 2017年8月  
    患者は68歳の男性で,近医で肝門部腫瘍の診断で当科へ紹介され,肝門部領域胆管癌の診断で根治手術の適応と判断した.術前のindocyanine green(以下,ICGと略記)負荷試験でICG15分血中停滞率が100%以上と著明な高値が認められたが,Child-Pugh分類や99m-Tc-galactosyl-human serum albumin(以下,GSAと略記)肝シンチグラフィーでは異常所見は認められず,背景疾患を有さないことから体質性ICG排泄異常症と診断し手術の方針とした.手術は右肝切除術,尾状葉合併切除術,肝外胆管切除術および門脈合併切除術を施行した.術後は危惧された肝不全の発症を認めなかった.本症を伴った肝切除術を要する患者については,一般肝機能検査やGSA肝シンチグラフィーといったICG試験以外の肝機能検査結果を踏まえ総合的に手術適応や術式を検討すべきと考えられた.(著者抄録)
  • Wakiya T, Kudo D, Ishido K, Kimura N, Yakoshi Y, Toyoki Y, Kijima H, Hakamada K
    Mol Clin Oncol 7(2) 200-204 2017年8月  査読有り
  • Saito T, Ishido K, Kudo D, Kimura N, Wakiya T, Nakayama Y, Hakamada K
    Mol Clin Oncol 6(6) 963-967 2017年6月  査読有り
  • Taiichi Wakiya, Yoshikazu Toyoki, Keinosuke Ishido, Daisuke Kudo, Norihisa Kimura, Shinji Tsutsumi, Tadashi Odagiri, Akiko Suto, Chiaki Uchida, Kenichi Hakamada
    PEDIATRIC TRANSPLANTATION 21(2) 2017年3月  査読有り
    There is ongoing discussion regarding the indications and timing of LT for patients with a preexisting extrahepatic malignancy. We herein report a pediatric case that underwent LDLT after therapy for YST. The patient, a 13-year-old female with biliary atresia, had undergone portoenterostomy at 2 months of age. She developed a left ovarian tumor with a high serum alpha-fetoprotein concentration at 10 years of age. She underwent left oophorectomy and was diagnosed with ovarian YST (Stage I). After surgery, hepatopulmonary syndrome progressed gradually. She was examined carefully and exhibited no findings to suggest the recurrence of YST. We decided to perform LDLT at 3 years and 6 months of age after the surgery for YST. The patient is currently alive and doing well without recurrence of YST at approximately 2 years after transplantation. There is no significant difference between the recurrence rate of preexisting extrahepatic malignancy and the incidence of de novo malignancy if specific cases are selected. The indications and period from surgery for preexisting extrahepatic malignancy to LT should thus be determined according to the type and stage of cancer.
  • Y. Wakasa, D. Kudo, K. Ishido, N. Kimura, T. Wakiya, Y. Mitsuhashi, K. Hakamada
    Transplantation proceedings 49(7) 1615-1618 2017年  
    When there is an anatomic anomaly in the biliary tract of the donor for living-donor liver transplantation, the risk of postoperative biliary tract complications increases in both the donor and the recipient. We studied a case of living-donor liver transplantation with a left hepatic lobe graft that had anatomic anomalies, in which the medial segmental branch (B4) joined the anterior segmental branch and the posterior segmental branch formed a common trunk with the lateral segmental branch. A 40-year-old man visited our institution as a candidate organ donor for his mother, who had end-stage liver failure. An anomaly of B4 connecting the anterior segmental branch was suspected on magnetic resonance cholangiopancreatography. On intraoperative cholangiography, confluence of B4 with the anterior segmental branch and connection of the posterior and lateral segmental branches forming a common trunk were confirmed. Accordingly, individual anastomoses of the lateral segmental branch and B4 with the recipient jejunum were planned, and a left-lobe graft was excised. The postoperative recovery was smooth, and the donor was discharged with no complications. Even when an anatomic anomaly is present in the donor bile duct, in urgent cases, accurate evaluation through the use of various modalities may enable living-donor liver transplantation with the use of a graft with an anatomic anomaly.

MISC

 100

主要な講演・口頭発表等

 311

共同研究・競争的資金等の研究課題

 5