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.taiichi
jichi.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
研究分野
4経歴
1-
2022年10月
受賞
4主要な論文
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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 < 0.001), correlating positively with increasing hepatic vein diameter (Rs = 0.67, p < 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.
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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.
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A case of serous cystic neoplasm with tumor growth acceleration leading to extrapancreatic invasion.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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Annals of surgical oncology 29(2) 1294-1295 2022年2月
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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ANZ Journal of Surgery 88(9) E654-E658 2018年9月 査読有り
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Clinical nutrition ESPEN 23 54-60 2018年2月 査読有り
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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。
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Long-term Changes in Spleen Volume After Living Donor Liver Transplantation in Pediatric Recipients.Transplantation proceedings 50(9) 2723-2725 2018年 査読有り
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Transplantation proceedings 50(9) 2593-2596 2018年 査読有り
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Mol Clin Oncol 8(1) 54-60 2018年 査読有り
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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)
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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)
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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)
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Gan to kagaku ryoho. Cancer & chemotherapy 44(12) 1683-1685 2017年11月 査読有り
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Gan to kagaku ryoho. Cancer & chemotherapy 44(12) 1120-1122 2017年11月 査読有り
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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.
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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)
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Mol Clin Oncol 7(2) 200-204 2017年8月 査読有り
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Mol Clin Oncol 6(6) 963-967 2017年6月 査読有り
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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.
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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.
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Japanese Journal of Gastroenterological Surgery 50(8) 664-672 2017年 査読有りA 68-year-old man was admitted to our hospital with a diagnosis of resectable perihilar cholangiocarcinoma. In a preoperative indocyanine green (ICG) test, the ICG retention rate at 15 minutes (ICG R15) was more than 100%. Despite this finding, Child-Pugh classification and 99m-Tc-galactosyl-human serum albumin (GSA) liver scintigraphy did not show any abnormal findings and there was no background disease. Thus, we diagnosed constitutional ICG excretory defect and decided to perform radical surgery. We performed right hemihepatectomy extending to segment 1, extrahepatic bile duct resection and portal vein resection, and there were no postoperative complications. For patients requiring hepatectomy with this disease, it was concluded that the indications for surgery and the surgical procedure should be considered comprehensively, based on findings of liver function tests other than the ICG test, such as a general liver function test and GSA liver scintigraphy.
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Gan to kagaku ryoho. Cancer & chemotherapy 44(12) 1098-1100 2017年 査読有り
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ANTICANCER RESEARCH 37(1) 183-190 2017年1月 査読有りAim: The aim of this study was to examine the clinicopathological influence of tumor-infiltrating cluster of differentiation (CD) 163(+) macrophages and CD8(+) T-cells, and to clarify the prognostic effects of these cells in patients with invasive extrahepatic bile duct cancer (EHBC). Materials and Methods: The numbers of CD8(+) T-cells in cancer cell nests and CD163(+) macrophages in tumor stroma were evaluated using immunohistochemistry in 101 resected EHBC specimens. Correlations with clinicopathological variables and overall survival were analyzed. Results: Perihilar EHBC and perineural invasion were significantly associated with a low number of tumor-infiltrating CD8(+) T-cells. Poorly-differentiated histology and nodal metastasis were significantly associated with a high number of tumor-infiltrating CD163(+) macrophages. A combination of high number of CD8(+) T-cells and low number of CD163(+) macrophages was independently related to better overall survival in the whole patient cohort (hazard ratio=0.127, p<0.001) and in patients treated with adjuvant chemotherapy (hazard ratio=0.139, p=0.021). Conclusion: Infiltrating CD163(+) macrophages in tumor stroma and CD8(+) T-cells in cancer cell nests have a prognostic impact in patients with EHBC following resection and also after adjuvant chemotherapy.
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日本消化器外科学会雑誌 49(12) 1214-1221 2016年12月症例は65歳の女性で,2014年6月に前医で肝外胆管,総肝動脈,および膵頭部への浸潤を有する切除不能局所進行胆嚢癌の診断となり,gemcitabine+S-1併用療法が開始された.8コース施行後の腹部CTで上記浸潤所見が消失したため,2015年1月手術目的に当科紹介となった.拡大肝右葉切除術,肝外胆管切除術,総肝動脈合併切除術を施行し,病理組織学的診断は胆嚢体部を主座とする中〜高分化型管状線癌で,pT3N1M0,Stage IIIB,R0切除を達成した.S-1による術後補助化学療法を施行し,術後8ヵ月間の無再発生存が得られている.化学療法が奏効し非切除因子が消失した局所進行胆嚢癌の治療法について一定の見解は存在しない.しかし,conversion surgeryにより良好な予後を得られる可能性があり,化学療法中も外科的切除の可能性を定期的に追求することが重要であると思われた.(著者抄録)
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Japanese Journal of Gastroenterological Surgery 49(12) 1214-1221 2016年 査読有りA 65-year-old woman was diagnosed as having initially unresectable locally advanced gallbladder cancer (LAGBC) with direct invasion to the liver, the extra hepatic bile duct, the common hepatic artery, and the head of the pancreas. She received chemotherapy with gemcitabine and S-1. After 8 courses of chemotherapy, the size of the main lesion decreased and the invasion to the adjacent organs disappeared. We performed extended right hepatectomy and extrahepatic bile duct resection with combined resection of the common hepatic artery. Pathological investigation confirmed moderately differentiated tubular adenocarcinoma of the gallbladder, pT3N1M0, Stage IIIB, and R0 resection margins. The patient received adjuvant chemotherapy with S-1. Eight months after the surgery, she was alive with no signs of recurrence. The efficacy of conversion surgery for unresectable LAGBC has not been determined. Further studies are required to establish treatment strategy for unresectable LAGBC. However, it is important to pursue the feasibility of conversion surgery for patients with unresectable LAGBC.
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LIVER TRANSPLANTATION 21(11) 1419-1427 2015年11月 査読有りThe serum ferritin (SF) concentration is a widely available and objective laboratory parameter. SF is also widely recognized as an acute-phase reactant. The purpose of the present study was to identify the chronological changes in the recipient's SF concentration during liver transplantation (LT) and to clarify factors having an effect on the recipient's intraoperative SF level. In addition, the study retrospectively evaluated the usefulness of measuring SF during LT. Ninety-eight pediatric recipients were retrospectively analyzed. The data were analyzed and compared according to the SF level in the recipient. Patients were classified into 2 groups based on the intraoperative peak SF levels of 1000 ng/mL (low-SF group) or >1000 ng/mL (high-SF group). The SF value increased dramatically after reperfusion and fell to normal levels within the early postoperative period. The warm ischemia time (WIT) was significantly longer in the high-SF group (47.0 versus 58.5 minutes; P = 0.003). In addition, a significant positive correlation was observed between the peak SF value and WIT (r = 0.35; P < 0.001). There were significant positive correlations between the peak SF value and the donors' preoperative laboratory data, including transaminases, cholinesterase, hemoglobin, transferrin saturation, and SF, of which SF showed the strongest positive correlation (r = 0.74; P < 0.001). The multivariate analysis revealed that WIT and donor's SF level were a significant risk factor for high SF level in the recipient (P = 0.007 and 0.02, respectively). In conclusion, the SF measurement can suggest the degree of ischemia/reperfusion injury (IRI). A high SF level in the donor is associated with the risk of further acute reactions, such as IRI, in the recipient. Liver Transpl 21:1419-1427, 2015. (c) 2015 AASLD.
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PEDIATRIC TRANSPLANTATION 19(6) 595-604 2015年9月 査読有りStudies suggest that prophylactic intra-abdominal drains are unnecessary for cadaveric liver transplantation using whole liver grafts because there is no benefit from drainage. However, no studies have investigated on the necessity of prophylactic drains after LDLT using split-liver grafts or reduced-liver grafts, which may present a high risk of post-transplant intra-abdominal infections. This retrospective study investigated whether the ascitic data on POD 5 after LDLT can predict intra-abdominal infections and on the post-transplant management of prophylactic drains. Between March 2008 and March 2013, 90 LDLTs were performed. We assessed the number of ascitic cells, biochemical examinations, and cultivation tests at POD1 and POD5. The incidence rates of post-transplant intra-abdominal infections were 24.4%. The multivariate analysis showed that left lobe and S2 monosegment grafts were a significant risk factor for intra-abdominal infections (p=0.006). The patients with intra-abdominal infections had significantly higher acsitic LDH levels and the positive rate of ascitic culture at POD5 in comparison with patients without infections (p<0.001 and p=0.014, respectively). LDLT using left lobe and S2 monosegment grafts yields a high risk for post-transplant intra-abdominal infections, and ascitic LDH and cultivation tests at POD5 via prophylactic drains can predict intra-abdominal infections.
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VIROLOGY JOURNAL 12 91-91 2015年6月 査読有りA 12-year-old female patient with biliary atresia underwent living donor liver transplantation (LDLT). Twelve months after the LDLT, she developed acute hepatitis (alanine aminotransferase 584 IU/L) and was diagnosed with disseminated varicella-zoster virus (VZV) infection with high level of serum VZV-DNA (1.5 x 10(5) copies/mL) and generalized vesicular rash. She had received the VZV vaccination when she was 5-years-old and had not been exposed to chicken pox before the LDLT, and her serum was positive for VZV immunoglobulin G at the time of the LDLT. Although she underwent treatment with intravenous acyclovir, intravenous immunoglobulin, and withdrawal of immunosuppressants, her symptoms worsened and were accompanied by disseminated intravascular coagulation, pneumonia, and encephalitis. These complications required treatment in the intensive care unit for 16 days. Five weeks later, her clinical findings improved, although her VZV-DNA levels remained high (8.5 x 10(3) copies/mL). Oral acyclovir was added for 2 weeks, and she was eventually discharged from our hospital on day 86 after admission; she has not experienced a recurrence. In conclusion, although disseminated VZV infection with multiple organ failure after pediatric LDLT is a life-threatening disease, it can be cured via an early diagnosis and intensive treatment.
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JOURNAL OF GASTROINTESTINAL SURGERY 19(5) 866-879 2015年5月 査読有りBlood transfusion is linked to a negative outcome for malignant tumors. The aim of this study was to evaluate aggressive surgical resection for hilar cholangiocarcinoma (HCCA) and assess the impact of perioperative blood transfusion on long-term survival. Sixty-six consecutive major hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for HCCA were performed using macroscopically curative resection at our institute from 2002 to 2012. Clinicopathologic factors for recurrence and survival were retrospectively assessed. Overall survival rates at 1, 3, and 5 years were 86.7, 47.3, and 35.7 %, respectively. In univariate analysis, perioperative blood transfusion and a histological positive margin were two of several variables found to be significant prognostic factors for recurrence or survival (P < 0.05). In multivariate analysis, only perioperative blood transfusion was independently associated with recurrence (hazard ratio (HR) = 2.839 (95 % confidence interval (CI), 1.370-5.884), P = 0.005), while perioperative blood transfusion (HR = 3.383 (95 % CI, 1.499-7.637), P = 0.003) and R1 resection (HR = 3.125 (95 % CI, 1.025-9.530), P = 0.045) were independent risk factors for poor survival. Perioperative blood transfusion is a strong predictor of poor survival after radical hepatectomy for HCCA. We suggest that circumvention of perioperative blood transfusion can play an important role in long-term survival for patients with HCCA.
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Pediatric transplantation 19(3) 279-86 2015年5月 査読有り
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Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 21(2) 233-8 2015年2月 査読有り
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Gan to kagaku ryoho. Cancer & chemotherapy 41(12) 2396-8 2014年11月A man in his seventies presented with a stomach abnormality that was revealed upon physical examination.Following workup, he was diagnosed with gastric diffuse large B-cell lymphoma (DLBCL)StageII1 (Lugano staging system for gastrointestinal lymphoma) with low risk as defined by the International Prognostic Index criteria.The entire stomach showed an intense, abnormal FDG uptake by FDG-PET evaluation.He was treated with rituximab plus CHOP (R-CHOP).The patient's body weight decreased by 12 kg during the treatment period.Post -treatment evaluation by gastroscopy and FDG-PET following 5 courses of R-CHOP therapy revealed a residual lesion in the stomach.Total gastrectomy was performed for R-CHOP refractory gastric DLBCL.The pathological diagnosis was DLBCL, and the pathological therapeutic effect was Grade 1a.Lymphoma cells were detected at the duodenal margin of the resected specimen, and an FDG-PET scan showed abnormal FDG uptake in the duodenal stump necessitating salvage chemotherapy (DeVIC therapy)and radiotherapy.The patient's body weight increased by 5 kg after gastrectomy and there were no signs of relapse for 14 months after the operation.Salvage therapy including gastrectomy may be effective for chemotherapy-resistant gastric DLBCL.
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Gan to kagaku ryoho. Cancer & chemotherapy 41(12) 2453-5 2014年11月Perforation, bleeding, and ileus are known complications of small intestinal lymphoma and can occur either at diagnosis or during the course of treatment. Surgery is an important component in the management of these gastrointestinal complications. However, there is no consensus regarding the indications for and timing of surgery in small intestinal lymphoma. We herein present our experience with a case of small intestinal lymphoma with ileus that required surgery during chemotherapy. A 69-year-old man developed abdominal pain. Computed tomography revealed lower right jaw lymphadenopathy, small intestinal wall thickening, and mesenteric lymphadenopathy. Malignant lymphoma (diffuse large B-cell type) was diagnosed on the basis of a lower jaw lymph node biopsy. The patient was initially administered chemotherapy. After the third cycle of chemotherapy, the patient developed small intestinal obstruction detected upon abdominal computed tomography. Because a stricture persisted despite medical treatment, we performed partial resection of the small intestine. The postoperative course was good, and the patient rapidly resumed chemotherapy. Currently, 6 months after the surgery, the patient is alive without any progression of the lymphoma. A multidisciplinary treatment strategy, including surgery, is desirable to achieve a safe but radical cure for small intestinal lymphoma.
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A case of metastatic liver tumor arising from gastric cancer resected after second-line chemotherapyJapanese Journal of Cancer and Chemotherapy 41(12) 2355-2357 2014年11月1日 査読有りA man in his 60s was diagnosed with gastric cancer and underwent distal gastrectomy and D2 lymph node dissection. The histological diagnosis was adenocarcinoma (T3, N1, Stage IIB). He was treated with S-1 as adjuvant chemotherapy for 1 year. One year and 2 months after gastrectomy, a computed tomography (CT) scan revealed liver metastasis (S8, 38 mm). The patient was diagnosed with liver metastasis (refractory to S-1), and administered combination chemotherapy with irinotecan and cisplatin. After 4 courses of treatment, a CT scan detected a progressive liver tumor (55 mm). Combination chemotherapy with docetaxel and S-1 was selected as second-line chemotherapy. After 6 courses of treatment, the tumor size reduced to 40 mm in diameter, and no other metastasis was detected. Nine months after the diagnosis of liver metastasis, partial resection of the liver (S8) was performed. A pathological diagnosis of metastatic adenocarcinoma was determined, and the pathological therapeutic effect was rated as Grade 1b. Combination chemotherapy with docetaxel and S-1 was found to be effective, and was thus administrated after the operation. There have been no signs of recurrence for 6 months after the operation. Surgery with perioperative chemotherapy can be an effective treatment for liver metastasis from gastric cancer.
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HEPATO-GASTROENTEROLOGY 61(133) 1368-1373 2014年7月 査読有りBackground/Aims: (beta-D glucan in the portal vein blood is processed by the hepatic reticuloendothelial system, and therefore, it is possible that the beta-D glucan kinetics of the peripheral vein blood may be useful as a biological index. In this study, the beta-D glucan levels in the peripheral and portal vein blood during liver transplantation were measured in order to study the clinical significance of the molecule. Methodology: The subjects comprised 20 patients who underwent living donor liver transplantation. In the perioperative period, the beta-D glucan levels were measured before liver transplantation, during surgical procedure, then on postoperative days 5, 14, and 21. Results: The portal vein blood showed a significantly higher level beta-D glucan than the peripheral blood (p<0.001). A significant difference of beta-D glucan levels was observed between the pre-liver transplantation and postoperative days 5 (p=0.048). There was a significant positive correlation between the preoperative beta-D glucan level and the period of postoperative hospitalization (p<0.001). The patients with fungal infections (35.0%) had a significantly longer period of hospitalization.(p=0.019). Conclusions: The beta-D glucan kinetics accurately reflects the liver function and fungal infections. The beta-D glucan level before liver transplantation can be used to predict the period of hospitalization.
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Journal of hepato-biliary-pancreatic sciences 21(7) 463-472 2014年7月 査読有り
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Hepatogastroenterology 61(133) 1368-1373 2014年7月 査読有り
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World journal of gastroenterology : WJG 20(21) 6638-6650 2014年6月 査読有り
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TRANSPLANT INTERNATIONAL 27(4) 383-390 2014年4月 査読有りSome studies have found that gender mismatch between donors and recipients are related to poor graft prognosis after liver transplantation. However, few studies have investigated the impact of gender mismatch on acute cellular rejection (ACR) in pediatric living donor liver transplantation (LDLT). This retrospective study investigated the clinical significance of these factors in ACR after pediatric LDLT. Between November 2001 and February 2012, 114 LDLTs were performed for recipients with biliary atresia (BA) using parental grafts. We performed univariate and multivariate analyses to identify the factors associated with ACR. The donor-recipient classifications included mother donor to daughter recipient (MD; n=43), mother to son (n=18), father to daughter (FD; n=33), and father to son (n=20) groups. The overall incidence rate of ACR in the recipients was 36.8%. Multivariate analysis showed that gender mismatch alone was an independent risk factor for ACR (P=0.012). The FD group had a higher incidence of ACR than the MD group (P=0.002). In LDLT, paternal grafts with gender mismatch were associated with a higher increased incidence of ACR than maternal grafts with gender match. Our findings support the possibility that maternal antigens may have an important clinical impact on graft tolerance in LDLT for patients with BA.
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Transplant international : official journal of the European Society for Organ Transplantation 27(3) 322-329 2014年3月 査読有り
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Transplantation proceedings 46(3) 999-1000 2014年Anastomotic stricture of the choledochojejunostomy is a common complication after living donor liver transplantation. Most anastomotic strictures can be treated by percutaneous transhepatic cholangiodrainage and/or double balloon endoscopy. However, in severe cases and/or in small infants, neither of these is possible. Our new technique, cholangiography accompanied by cholangioscopy, enabled successful guidewire placement and balloon dilatation in cases with severe anastomotic stricture. © 2014 by Elsevier Inc. All rights reserved.
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American journal of transplantation 2014年
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Transplantation proceedings 46(3) 2014年
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Transplantation proceedings 46(3) 2014年
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ANNALS OF SURGICAL ONCOLOGY 21(1) 167-172 2014年1月 査読有りBackground. The indocyanine green (ICG) clearance test is reported to be useful for the preoperative evaluation of hepatic functional reserve. However, the ICG clearance test has not been sufficiently investigated in patients with colorectal liver metastasis after chemotherapy. The aim of the present study was to evaluate whether the ICG clearance test is a useful parameter for the preoperative detection of chemotherapy-associated liver injury. Methods. Ninety-four patients undergoing liver resection for colorectal liver metastasis after chemotherapy were studied. The medical records for each case were retrospectively reviewed. They underwent pathological assessment to clarify the degree of histopathological liver injury of the nontumoral liver parenchyma. In addition, the correlation between the pathological score and the ICG retention rate at 15 min (ICG-R15) was analyzed. Results. Sinusoidal injury was observed in the 31 of 94 patients. Steatohepatitis was observed in the 40 of 94 patients. There was no strong correlation between the preoperative ICG-R15 value and the sinusoidal pathological score (r = 0.117, P = 0.261). There was no strong correlation between the ICG-R15 and the nonalcoholic fatty liver disease activity score (r = 0.215, P = 0.037). Conclusions. It was difficult to predict the degree of chemotherapy-associated liver injury by the preoperative ICG-R15 value. It is necessary to estimate the hepatic functional reserve based on a combination of several clinical indicators without relying on the ICG test, in order to perform a safe radical liver resection.
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Surgery today 44(1) 180-184 2014年1月 査読有り
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Pediatrics international : official journal of the Japan Pediatric Society 55(5) e119-22 2013年10月 査読有り
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Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 11(3) 259-263 2013年6月 査読有り
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JOURNAL OF SURGICAL RESEARCH 180(2) 349-355 2013年4月 査読有りBackground: Endotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system. Thus, it is possible that the Et kinetics of the peripheral venous blood may be useful as a biological index that can be used to evaluate liver function. In this study, we measured Et using the endotoxin activity assay in peripheral venous blood during living donor liver transplantation (LDLT), to study its clinical significance. Methods: Subjects were 17 patients who underwent LDLT. In the perioperative peripheral venous blood, was measured Et activity (EA) using the endotoxin activity assay at 1 or 2 d before LT, and then on 1, 5, 7, 14, and 21 postoperative days. Results: Patients with infections had significantly higher EA levels compared with those without complications before LDLT and 14 postoperative days (P = 0.038 and 0.027, respectively). The average EA level of patients with infections and without complications before LT was 0.22 and 0.08, respectively (P = 0.038). Patients with an EA level higher than 0.20 before LDLT had a significantly longer period of hospitalization compared with those without complications (P = 0.038). Conclusions: A preoperative EA level more than 0.20 is a high risk factor for post-transplant infection and a prolonged period of hospitalization. Crown Copyright (c) 2013 Published by Elsevier Inc. All rights reserved.
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Clinical transplantation 26(6) 816-819 2012年11月 査読有りTo improve the processes used for perfusion of the explanted graft and measuring the portal venous pressure (PVP) in adult living donor transplantation (LDLT), we performed transumbilical portal venous catheterization (TPVC) to reopen the umbilical vein and insert the catheter for seven adult patients undergoing left lobe LDLT. There were no major complications as a result of this procedure. This procedure prior to implanting the graft was derived from our experience and is a classic diagnostic technique used during liver surgery. It is a simple and effective procedure for perfusion and washout of the graft and for the safe monitoring of the intraoperative PVP. We hope that this technique for left lobe LDLT will be helpful to others using postoperative PVP monitoring, administration of therapeutic drugs through the portal vein, and temporal portal decompression by preparation of extracorporeal shunting in patients with a small-for-size graft.
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Pediatric transplantation 16(7) 783-787 2012年11月 査読有り
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HEPATOLOGY INTERNATIONAL 6(4) 778-782 2012年10月 査読有りEndotoxin (Et) in the portal vein blood is processed by the hepatic reticuloendothelial system, and therefore, it is possible that the hepatic clearance of Et may become a biological index for liver function. In this study, Et levels of preoperative peripheral and portal vein blood at the time of liver transplantation (LT) were measured in order to study the meaning. The study population comprised 19 patients in whom pediatric living donor LT was performed. In the preoperative peripheral and the portal vein blood at the time of LT, we measured Et activity (EA) by the Et activity assay (EAA) and the Limulus amebocyte lysate (LAL) method. The preoperative peripheral vein blood showed a low EA in all cases. In the EA of the peripheral and the portal vein blood, the latter showed a significantly high level (p = 0.049). With the LAL method, 5.3% (2/38) of patients were positive for Et. The EAA is considered to be superior to the LAL method for the detection of Et, even in low endotoxinemia, and is also capable of elucidating the Et kinetics by accurately reflecting hepatic clearance.
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World journal of surgery 36(10) 2449-2454 2012年10月 査読有り
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Pediatric surgery international 28(10) 993-996 2012年10月 査読有り
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Pediatric transplantation 16(6) E193-5 2012年9月 査読有り
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THERAPEUTIC APHERESIS AND DIALYSIS 16(4) 368-375 2012年8月 査読有りIn the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible-liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type-incompatible liver transplantation was 128 and eight, respectively (P < 0.05). Eleven courses of apheresis and dialysis were performed post liver transplantation for 10 patients. The median PaO2/FiO2 ratio before and after dialysis for fluid overload was 159 and 339, respectively (P < 0.05). No bleeding or technical complications attributable to apheresis and dialysis occurred. The 1-year survival rate of the patients was 100%. Apheresis and dialysis in pediatric living donor liver transplantation are effective for antibody removal in ABO-incompatible liver transplantation, and fluid management for acute respiratory failure.
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Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 10(4) 350-355 2012年8月 査読有り
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WORLD JOURNAL OF SURGERY 36(4) 908-916 2012年4月 査読有りLiver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity. Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed. The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001). Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.
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Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 10(2) 176-179 2012年4月 査読有り
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SURGERY 151(3) 404-411 2012年3月 査読有りBackground and Aims. Congenital extrahepatic portosystemic shunt (CEPS) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. It is still a matter of debate whether conservative or operative strategies should be used to treat symptomatic CEPS. The aim of this study was to evaluate the role of operative intervention in the management of CEPS. Methods. Between June 2004 and August 2010, 6 consecutive patients with symptomatic CEPS were treated in our department. There were 3 male and 3 female patients, with a median age of 3.5 years (range, 1-8). Their demographic, clinical, and laboratory data were analyzed. All patients were scheduled to undergo shunt ligation or liver transplantation Results. Living donor LT was carried out in 4 patients, and shunt ligation in 2. After a median follow-up of 25 months, all the patients are alive currently with marked relief of symptoms. Conclusion. Shunt ligation or LT for symptomatic CEPS is potentially curative. (Surgery 2012;151:404-11.)
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MOLECULAR GENETICS AND METABOLISM 105(3) 404-407 2012年3月 査読有りThere are no objective and concrete guidelines for the management of Ornithine transcarbamylase deficiency (OTCD). Based on previous findings, we hypothesized that patients with OTCD have a low Ornithine transcarbamylase (OTC) activity in the liver, and therefore it would be better to determine the appropriate indications and optimal timing for liver transplantation (LT) based on the OTC activity. However, few data have so far been accumulated on the OTC activity in cases that are indicated for LT. The purpose of the present study was to clarify the OTC activity in cases that were indicated for LT. This study involved thirteen children with OTCD (8 males and 5 females) who underwent LT, and two females with OTCD who did not require LT. The OTC activity of the neonatal onset type ranged from 0% to 7.2%, while that of the late onset type who underwent LT ranged from 4.4% to 18.7%. The OTC activity of the late onset type which did not require LT was 33-38% based on a preoperative needle liver biopsy. Some late onset patients that underwent LT, showed an activity that was as low as that observed in the neonatal onset cases. This is the first report to show the results of measuring the OTC activity for serial OTCD cases indicated for LT. OTC activity might be an indicator to determine the indications for and the timing of LT in the late onset type, however, further investigations are necessary. (C) 2011 Elsevier Inc. All rights reserved.
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PEDIATRICS INTERNATIONAL 53(6) 1077-1081 2011年12月 査読有り
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ANNALS OF TRANSPLANTATION 16(4) 7-11 2011年10月 査読有りBackground: At the present time, indications of liver transplantation (LT) for jaundice-free biliary atresia (BA) patients include intractable cholangitis, portal hypertension and pulmonary vascular disorders. However, the timing of LT remains unclear. In the current study, we describe the therapeutic strategies for jaundice-free BA patients. Material/Methods: 129 BA patients were undergone LDLT between May, 2001 and April, 2010 in the Department of Transplant Surgery, Jichi Medical University, Japan. Results: The indications of LDLT for jaundice-free BA patients was 30 patients (30/129, 23%), and included portal hypertension (16 patients, 53%). Among the 16 patients with portal hypertension, there were 7 patients (7/16, 23%) in which uncontrollable gastrointestinal bleeding was an indication of LDLT. There were 5 patients (5/7; 71%) in which bleeding sites were not identified, and 3 patients (3/7; 43%) in which supportive treatments against collateral vessels were performed as a previous treatment. Conclusions: Even in jaundice-free BA patients, after supportive treatments for portal hypertension are performed, it is necessary to assess the esophageal and gastrointestinal varices regularly and to also prepare for LT simultaneously because there is a probability of the complication of uncontrollable gastrointestinal bleeding.
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Transplant international : official journal of the European Society for Organ Transplantation 24(10) 984-990 2011年10月 査読有り
MISC
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PEDIATRIC TRANSPLANTATION 17(3) 316-317 2013年5月
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JOURNAL OF CLINICAL ONCOLOGY 31(15) 2013年5月
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GASTROENTEROLOGY 144(5) S794-S794 2013年5月
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日本外科学会雑誌 114(2) 652-652 2013年3月5日
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日本外科学会雑誌 114(2) 854-854 2013年3月5日
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日本外科学会雑誌 114(2) 820-820 2013年3月5日
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日本外科学会雑誌 114(2) 1031-1031 2013年3月5日
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日本外科学会雑誌 114(2) 996-996 2013年3月5日
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日本外科学会雑誌 114(2) 1001-1001 2013年3月5日
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移植 47(4-5) 326-334 2012年9月実験用ブタを用いた多内臓移植と小腸移植の手術経験について報告した。実験用ブタを用いて異所性自己小腸移植9回と多内臓移植2回を施行した。異所性自己小腸移植と多内臓移植の手術時間は、それぞれ平均300分、334分であった。また、冷阻血時間は、平均53分、116分で、温阻血時間は平均38分、40分であり、バックテーブル時間は、平均29分、17分であった。異所性自己小腸移植におけるグラフト小腸摘出時間は平均90分であった。また、グラフト血管の動脈径、静脈径は平均4.2mm、9.8mmで、吻合時間は平均動脈16分、静脈13分であった。また、多内臓移植におけるグラフト多内臓摘出時間は平均129分であった。吻合時間は平均動脈12分、静脈7分であった。全例で再灌流後30分間、良好な臓器血流が得られた。
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移植 47(4-5) 320-325 2012年9月9歳男児。日齢76に胆道閉塞症に対し葛西手術を施行した。今回、黄疸の進行で生体肝移植目的に入院となった。45歳の父親をドナーとした拡大左葉グラフトによる生体肝移植を行った。術後早期より肝機能障害を伴わない5000〜10000ml/dayの大量腹水が出現し、肝生検で急性拒絶反応(P3B3V3)を認め、類洞および中心静脈周囲の線維化を伴い、ステロイドパルス療法および腹水濃縮還流を開始した。腹水は改善せず、急性拒絶反応(P1B1V3)は改善したが、中心静脈内皮炎と周囲の線維化が高度で、拒絶反応は遷延していると判断した。肝静脈狭窄を疑い、腹部造影CTおよび経内頸静脈的肝静脈造影を行ったが、肝静脈吻合部の狭窄は認めなかった。3回のステロイド療法でも腹水は減少せず、ステロイド抵抗性拒絶反応と診断し、第62病日よりOKT3の10日間使用により徐々に腹水は減少した。第75病日に急性拒絶反応(P0B0V0)の改善、中心静脈周囲および類洞線維化の改善を確認し、第94病日に腹腔ドレーン抜去となり第108病日に退院した。肝移植後2年を経て経過は良好である。
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移植 47(2-3) 224-228 2012年6月症例は9歳男児で、生後3ヵ月に先天性門脈欠損症と診断され、治療抵抗性の抗アンモニア血症、多発肝腫瘍のため8歳時に父親をドナーとするABO血液型適合生体肝移植を施行した。術前cytomegalovirus(CMV)抗体検査ではドナー既感染/レシピエント未感染であった。術後30日目に急性胃腸炎で入院し、いったん改善後に貧血、大量下血を認め、hypovolemic shockの状態となった。更に40℃台の発熱を認め、CMV腸炎による消化管出血の可能性を考え、免疫抑制剤を中止し、γ-globulin、ganciclovirの点滴治療を開始した。下部消化管内視鏡で回盲弁から10cm口側の回腸に出血源と考えられる多発潰瘍を認め、術後41日目のCMV抗原が陽性であり、CMV腸炎を疑った。その後CMV抗原値は減少し、解熱傾向となって免疫抑制剤を再開し、valganciclovir hydrochloride経口投与に変更し退院となった。以後CMV感染症の再燃はなく、術後2年6ヵ月で経過良好である。
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今日の移植 25(3) 193-195 2012年5月当院では2009年1月からグラセプターの使用を開始し、その使用基準は「移植後3年以上経過した5歳以上の症例」としている。今回、具体的な使用方法を紹介し、これまでに使用した28例について報告した。28例の内訳は男性7例、女性21例、年齢5〜19歳(中央値12歳)、移植後年数は4〜18年(中央値9年)であった。グラセプターを導入した理由は「家族や患者の希望」が最も多く13例(46%)、次いで「免疫抑制剤を増量・再開時」11例(39%)、「服薬コンプライアンス不良」4例(14%)であった。グラセプターへの切り替え・導入パターンの内訳は、プログラフ顆粒剤からの切り替え10例(36%)、プログラフカプセル剤からの切り替え10例(36%)、シクロスポリンからの切り替え1例(4%)、カルシニューリン阻害剤(CNI)を中止してからの再開7例(25%)であった。グラセプターの継続使用が可能であった症例の割合は89%であり、CNI中止から再開した症例ではグラセプター導入後に肝機能や病理所見の改善が認められ、服薬コンプライアンス不良に対してグラセプターを導入した症例ではいずれも飲み忘れが減少した。
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自治医科大学紀要 35 81-85 2012年胆道閉鎖症による肝不全に対して生体肝移植を施行し,免疫抑制療法としてタクロリムスを内服中に川崎病を発症した1歳女児例を経験した。血液検査上,白血球の増加がなくCRP の上昇も軽度で,診断に苦慮した。炎症反応の上昇が軽度であった理由として,タクロリムス内服による炎症性サイトカインの抑制が推測される。また,川崎病が原因と考えられる門脈吻合部狭窄の増悪を認めた。川崎病の剖検例では血管壁の炎症により門脈の拡大が生じると報告されているが,本症例では門脈吻合部の線維化のため内径が拡大せず,門脈域の細胞浸潤を伴った炎症と浮腫により吻合部狭窄が生じたと推測される。Here we report a case of Kawasaki disease( KD) in a 1-year-old female patient treated with tacrolimus( FK506) following liver transplantation for hepatic failure secondary to congenital biliary atresia. At the onset of KD, laboratory data included a normal white blood cell count and slightly increased C reactive protein, making the diagnosis of KD difficult. This mild inflammatory reaction could have been due to cytokine suppression by FK506. The portal vein became stenotic, possibly due to KD-associated phlebitis. Portal vein dilatation caused by inflammation in KD patients was previously reported; however, to our knowledge, there is no previous report of the occurrence of portal vein stenosis in this setting. In patients who have undergone liver transplantation, the anastomosis site can become non-elastic due to fibrosis, which, in the setting of KD-induced inflammation of the vein, can lead to portal vein stenosis.
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移植 46(6) 592-598 2011年12月10日1歳3ヵ月女児。生後7ヵ月時、胆道閉鎖症に対して父をドナーとする生体肝移植を施行した。術後3日目、門脈血流低下に対し、門脈バルーン拡張術を試みるも不成功であったため、開腹門脈血栓除去術を施行した。その後、肝動脈吻合部狭窄と難治性急性拒絶反応を合併したが、術後71日目に退院した。術後4ヵ月時、再発門脈狭窄に対し、経皮経肝的門脈バルーン拡張術を施行した。手術時脾静脈血栓を合併し、ワーファリンによる抗凝固療法を施行した。術後5ヵ月時、胆管空腸吻合部狭窄に対し、経皮経肝的胆道ドレナージ術を施行した。術後6ヵ月時、定期腹部超音波検査にて、門脈血流の流速の低下を認め、再々発門脈狭窄の診断で入院となった。全身麻酔下にて、経皮経肝的ステント留置術を施行した施行した。ステント留置術後1年6ヵ月の現在、ステントの逸脱やstent edge stenosisなどは認めず、門脈血流も良好である。
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移植 46(6) 599-605 2011年12月10日15歳女児。日齢38、胆道閉鎖症に対し葛西手術を施行した。9歳時、脾機能亢進症に対し部分的脾動脈塞栓術を施行した。11歳6ヵ月時に脳膿瘍を契機に肺血流シンチで肝肺症候群と診断した。12歳1ヵ月時、母親の肝左葉をグラフトとする生体肝移植術を施行した。術後58日目に門脈血栓を認め、抗凝固療法と血栓溶解療法を施行したが、門脈狭窄を認めたため、術後63日目に経皮経肝的門脈バルーン拡張術を施行した。移植後36ヵ月時、定期外来検査にて門脈吻合部狭窄の再々発を認めたため、経皮経肝的門脈バルーン拡張術目的に入院となった。吻合部狭窄はやや改善したが残存し、造影剤のwashoutは依然として遅延したままであった。脾腎シャントに対してはコイル塞栓による経皮経肝的塞栓術を行い、難治性吻合部狭窄に対してはステント留置を行う方針とした。術後6ヵ月時現在、ステントの位置は問題なく、門脈血流は良好である。
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血管外科 30(1) 22-25 2011年11月小児生体肝移植における血行再建の手術手技と成績について報告した。小児生体肝移植170例(176回)で、原疾患は、胆道閉鎖症129例、OTC欠損症12例、劇症肝不全9例、アラジール症候群8例、グラフト肝不全(再移植)7例、先天性門脈欠損症3例、その他7例であった。ドナーは、父親84例、母親86例、祖父母5例、叔父1例、グラフトは、外側区域129例、左葉41例、左葉+尾状葉7例、単亜区域3例であった。血管合併症は、肝動脈血流障害14例、門脈狭窄21例、肝静脈狭窄9例に認めた。治療は、いずれもinterventional radiologyを第1選択とした。肝静脈狭窄の3例は後に再移植を必要としたが、血管合併症による死亡例は認めなかった。グラフト生存率、患者生存率は、それぞれ91%、95%であった。
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移植 46(4) 365-374 2011年9月10日症例1:日齢0男児。在胎37週4日胎児機能不全で緊急帝王切開にて出生後、劇症肝不全で交換輸血を行い、MRI所見・フェリチン高値で新生児ヘモクロマトーシス(NH)と診断、内科的治療抵抗性から肝移植目的で当院に転院した。日齢27父親ドナーの生体肝移植を行った。症例2:日齢1女児。在胎38週経腟分娩で出生、日齢2劇症肝不全によるDICで交換輸血を行い、フェリチン高値でNHを疑い、内科的治療抵抗性から肝移植目的で当院に転院した。日齢13日父親ドナーの生体肝移植を行った。症例3:日齢7女児。在胎36週帝王切開にて出生、日齢3心エコーで動脈管開存症(PDA)の指摘。日齢6退院後哺乳不良、傾眠傾向からNICUに搬送、劇症肝不全で交換輸血を行い、MRI所見・フェリチン高値でNHと診断、内科的治療抵抗性から肝移植目的で当院に転院した。心不全悪化でPDA結紮術を行い、劇症肝不全の改善傾向を認め、内科的治療継続で諸検査値は安定し前医に転院した。
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日本小児栄養消化器肝臓学会雑誌 = Japanese journal of pediatric gastroenterology, hepatology and nutrition 25(1) 13-18 2011年4月27日新生児ヘモクロマトーシス(NH)は、肝細胞内外の広範囲な鉄沈着により生後数時間から数週間以内に急性肝不全を発症する予後不良な疾患である。内科的治療抵抗性の場合は肝移植の適応となる。今回、内科的治療で救命したNHを経験したので報告する。症例は日齢7に哺乳不良を初発症状とする急性肝不全を発症した女児。急性肝不全に対し交換輸血を施行し、精査にてNHを疑い、鉄キレート療法と抗酸化療法を開始したが、内科的治療抵抗性と判断され、日齢13に肝移植目的で当院へ転院した。転院後、交換輸血や鉄キレート療法などの治療を継続し、徐々に急性肝不全は改善した。日齢17の肝生検では肝再生が期待されたため、肝移植を回避した。現在経過良好である。NHは新生児期に肝移植を必要とする疾患であるが、日齢3以降に発症するNHは、内科的治療により新生児期の肝移植を回避できる可能性があるため、肝生検による確定診断と肝再生の評価が重要である。(著者抄録)
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移植 46(1) 64-70 2011年3月10日5歳9ヵ月女児。7ヵ月時、胆道閉鎖症術後肝硬変に対して母親の外側区域をグラフトとする生体部分肝移植術を施行し、術後にタクロリムスとメチルプレドニソロンによる免疫抑制療法を施行した。1年6ヵ月後にメチルプレドニソロンを漸減中止し、5年時はタクロリムス単剤で行っていた。今回、プロトコール肝生検で門脈域の拡大と形質細胞の浸潤を認めinterface hepatitisを呈し、門脈域の線維性拡大を認めbridging fibrosisへの進行が懸念され、タクロリムス増量、mycophenolate mofetil(MMF)を導入して免疫抑制療法を強化した。5年6ヵ月後のフォローアップ肝生検でinterface hepatitisと門脈域の形質細胞浸潤は改善傾向を認めたが、一部線維化を認めtacrolimusの継続とMMFの増量を行った。6年6ヵ月後のフォローアップ肝生検で門脈域の形質細胞浸潤は消失し、bridging fibrosisも改善したため、免疫抑制療法は変更せずに継続した。
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日本小児外科学会雑誌 46(7) 1164-1170 2010年12月20日減黄した胆道閉鎖症において,門脈圧亢進症が肝移植の適応になることもあるが,葛西術後の術後管理法や肝移植の実施時期に関しては一定のコンセンサスは得られていない.今回,門脈圧亢進症を合併した胆道閉鎖症に対する肝移植の適応病態とその実施時期について考察した.14歳,胆道閉鎖症,女児.葛西手術後に減黄したが,年長児期に治療を要する門脈圧亢進症を合併した.内視鏡的静脈瘤結紮術や部分的脾動脈塞栓術が行われたが,その後治療抵抗性の挙上空腸出血を呈したため,準緊急的に生体肝移植を施行した.葛西手術後の門脈圧亢進症に対する対症療法後は逆に他の側副血行路の発達を誘発し,負に働くことがある.減黄した胆道閉鎖症であっても,門脈圧亢進症に対して対症療法を行った後は内科的治療抵抗性の消化管出血を合併する可能性があるため,静脈瘤の評価を行いながら肝移植の準備を進めるべきであると考えられた.
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日本小児外科学会雑誌 46(7) 1171-1177 2010年12月20日肝移植適応と判断された胆道閉鎖症(BA)乳児において,低体重の場合,肝移植後合併症のハイリスクであるため,成長を待って移植することが望ましいとされている.今回我々は急速に肝不全と門脈圧亢進症が進行したBA乳児に対して準緊急生体肝移植を施行したので報告する.11か月,女児,体重5.2kg.移植待機中にコントロール不良な感染症を合併し,急速に肝不全と門脈圧亢進症が進行した.また,肝腫大,脾腫大による腹部膨満から換気不全となり,挿管,人工呼吸管理が必要となった.これ以上の成長も期待できず,準緊急肝移植を施行した.待機可能な低体重のBA乳児おいては,多発性のbiliary cyst,コントロール不良な感染症,高サイトカイン血症,脾腫進行の有無を評価することが重要であり,いずれかに該当する場合,周術期合併症のハイリスクであるため,速やかに肝移植の準備を進め,施行すべきであると考えられた.
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肝臓 51(11) 652-663 2010年11月25日[背景] 先天性門脈体循環シャント(Congenital extrahepatic portosystemic shunt:CEPS)は,症候性CEPSにおいて内科的治療抵抗性の場合,外科的治療の適応となる.今回,2例の症候性CEPSに対しシャント血管結紮術を施行し,良好な結果を得たので報告する. [症例1] 8才,男児.検診による精査にて肝腫瘍を指摘され,増大傾向を認めたため,静脈管結紮切離術を施行した.術後1年6カ月,CT上多発性肝腫瘍は明らかに縮小した. [症例2] 1才4カ月,女児.出生後より腎静脈レベルの下大静脈に直接流入するシャント血管を認めており,肝肺症候群が悪化したため,シャント血管結紮切離術を施行した.術後6カ月で在宅酸素療法を離脱でき,レントゲン上も明らかに改善した. [考察] 症候性CEPSに対する外科的治療は,種々の合併症の根治的治療になるため,時期を逸せずに施行すべきである.外科的治療法の選択の際,術前の肝内門脈評価と門脈圧測定が重要である.
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移植 45(3) 259-262 2010年6月10日8歳女児。胆道閉鎖症術後胆汁うっ滞性肝硬変に対し、1歳時に父親をドナーとする生体肝移植術を施行した。術後経過は良好で、第65病日に退院となった。外来フォロー中に門脈吻合部の狭窄を合併し、2歳時と4歳時にバルーン拡張術を施行した。しかし、8歳頃から再々狭窄を認めるようになった。全身麻酔下にバルーン拡張術を施行し、門脈の狭窄を解除後、プロトコール肝生検を超音波ガイド下に実施した。手技中のトラブルはなかった。また、術直前と術後8時間時に、予防的に抗生を投与した。40℃台の発熱が出現し、肝胆道系酵素の上昇を認めた。敗血症と診断し抗生剤、γグロブリン製剤の投与を開始した。敗血症の原因は肝生検による胆管炎が考えられた。術後3日目には解熱傾向に転じ、炎症反応や黄疸の改善もみられ、その後は速やかに状態の改善を得て、術後10日目に退院となった。
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日本臨床外科学会雑誌 = The journal of the Japan Surgical Association 71(5) 1299-1304 2010年5月25日
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日本消化器外科学会雑誌 42(7) 1059-1059 2009年7月1日
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日本消化器外科学会雑誌 42(7) 1262-1262 2009年7月1日
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日本外科学会雑誌 110(2) 714-714 2009年2月25日
主要な講演・口頭発表等
311-
TRANSPLANTATION 2016年7月 LIPPINCOTT WILLIAMS & WILKINS
共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2018年4月 - 2021年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2016年4月 - 2020年3月
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日本学術振興会 科学研究費助成事業 若手研究(B) 2016年4月 - 2019年3月