Details of a Researcher - Obara, Hideaki

Papers - Obara, Hideaki

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Impact of Stent Graft Design on External Iliac Artery Limb Occlusion Rates After Endovascular Aneurysm Repair: Post-hoc Analysis of a Japanese Multicentre Database

Shintani T., Obara H., Matsubara K., Hayashi K., Hayashi M., Ono S., Shimogawara T., Shibutani S., Watada S., Sekimoto Y., Uchida N., Asami A., Fujii T., Harada H., Fujimura N., Sato Y., Kitagawa Y.

European Journal of Vascular and Endovascular Surgery (European Journal of Vascular and Endovascular Surgery) 58 ( 6 ) 839 - 847 2019.12

ISSN 10785884

Objective/Background: It was hypothesised that a helical stent with expanded polytetrafluoroethylene (ePTFE) grafts could provide a preventive effect for external iliac artery (EIA) limb occlusion following endovascular aortic aneurysm repair (EVAR). Therefore, a post-hoc analysis of a Japanese multicentre database was conducted to assess the impact of the stent graft design on EIA limb occlusion rates. Methods: Patients who underwent EVAR with EIA limb deployment between 2008 and 2016 were evaluated. The stent graft limbs were divided into two groups: group A comprised stent graft limbs made of a helical stent with ePTFE grafts (Excluder; n = 255), and group B comprised stent graft limbs made of a Z stent with polyester grafts (Zenith, Flex and Endurant; n = 173). The main outcome was the incidence of limb occlusion and severe limb stenosis (EIA related limb complications). The risk factors for EIA related limb complications were analysed and the midterm results between groups A and B compared. Fine–Gray generalisation of the proportional hazards model was used after propensity score matching to calculate the hazard ratio (HR). Results: One complication occurred in group A and 10 complications occurred in group B. The risk factors for EIA related limb complications for the entire group were a stent graft limb size ≤10 mm (HR 5.41; p = .01) and inclusion in group B (HR 14.9; p = .009). After propensity matching, group A (n = 159) was matched with group B (n = 159). The cumulative incidence function of EIA related limb complications at five years was 0.66% in group A and 7.8% in group B (HR 8.67; p = .039). Conclusion: Stent graft design can affect limb patency in EIA limb deployment. When EIA limb deployment is necessary for patients with a small EIA, such as Japanese patients, stent graft limbs made of a helical stent with ePTFE should be used to reduce the risk of limb occlusion.

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Achievement of Durable and Complete Remission of Graft-versus-host Disease After Liver Transplantation With Ruxolitinib: A Case Report

Endo Y., Oshima G., Hibi T., Shinoda M., Sakurai M., Koda Y., Izawa Y., Obara H., Kitago M., Yagi H., Abe Y., Matsubara K., Yamada Y., Fukushima A., Yokose T., Mori T., Kuroda T., Kitagawa Y.

Transplantation (Transplantation) 103 ( 11 ) e375 - e377 2019.11

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Type IIIb Endoleak Is Not Extremely Rare and May Be Underdiagnosed after Endovascular Aneurysm Repair

Fujimura N., Ichihashi S., Matsubara K., Shibutani S., Harada H., Obara H., Kichikawa K., Kitagawa Y.

Journal of Vascular and Interventional Radiology (Journal of Vascular and Interventional Radiology) 30 ( 9 ) 1393 - 1399.e1 2019.09

ISSN 10510443

Purpose: To investigate the real incidence of type IIIb endoleaks associated with the Zenith stent graft, currently the most widely used third-generation polyester stent graft, in a Japanese multicenter database. Materials and Methods: Retrospective analysis was conducted of 433 patients who underwent endovascular aneurysm repair (EVAR) of aortoiliac aneurysms with the use of Zenith stent grafts from 2007 to 2016. The mean age of patients was 75.6 y ± 7.8, and 85.2% of patients were men. Mean transverse diameters of abdominal aortic aneurysms and common iliac artery aneurysms were 50.8 mm ± 9.9 and 42.2 mm ± 10.3, respectively. Results: During a mean follow-up period of 41.9 mo, 7 type IIIb endoleaks (1.6%) were identified. Four patients were definitively diagnosed during repeat intervention, and 3 were diagnosed based on postoperative CT images. Three patients were treated surgically, 2 were treated by relining with an additional stent graft, and 2 were conservatively followed with CT imaging. Only 1 of 5 patients who underwent repeat intervention had a preoperative diagnosis of type IIIb endoleak, reflecting the difficulty in its diagnosis. Conclusions: The incidence of type IIIb endoleak in Zenith stent grafts was 1.6% in this study, suggesting that type IIIb endoleaks are not extremely rare. In addition, type IIIb endoleak may be underdiagnosed or misdiagnosed as a different type of endoleak. Type IIIb endoleaks should always be considered in patients with sac expansion after EVAR.

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Comparison of olanexidine versus povidone-iodine for preventing surgical site infection in gastrointestinal surgery: Study protocol for a multicentre, single-blind, randomised controlled clinical trial

Takeuchi M., Obara H., Kawakubo H., Shinoda M., Okabayashi K., Mayanagi S., Irino T., Fukuda K., Nakamura R., Wada N., Kitago M., Yagi H., Abe Y., Oshima G., Hori S., Tsuruta M., Ishida T., Yokose T., Hirukawa K., Isobe Y., Sekimoto Y., Harada H., Maeda Y., Shito M., Kondo T., Sato Y., Kitagawa Y.

BMJ Open (BMJ Open) 9 ( 5 ) 2019.05

Introduction: The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries. Methods and analysis: We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method. Ethics and dissemination: The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals.

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Living donor liver re-transplantation for recurrent hepatoblastoma in the liver graft following complete eradication of peritoneal metastases under indocyanine green fluorescence imaging

Takahashi N., Yamada Y., Hoshino K., Kawaida M., Mori T., Abe K., Fujimura T., Matsubara K., Hibi T., Shinoda M., Obara H., Isshiki K., Shima H., Shimada H., Kameyama K., Fuchimoto Y., Kitagawa Y., Kuroda T.

Cancers (Cancers) 11 ( 5 ) 2019.05

The curability of chemotherapy-resistant hepatoblastoma (HB) largely depends on the achievement of radical surgical resection. Navigation techniques utilizing indocyanine green (ICG) are a powerful tool for detecting small metastatic lesions. We herein report a patient who underwent a second living donor liver transplantation (LDLTx) for multiple recurrent HBs in the liver graft following metastasectomy for peritoneal dissemination with ICG navigation. The patient initially presented with ruptured HB at 6 years of age and underwent 3 liver resections followed by the first LDLTx with multiple sessions of chemotherapy at 11 years of age. His alpha-fetoprotein (AFP) level increased above the normal limit, and metastases were noted in the transplanted liver and peritoneum four years after the first LDLTx. The patient underwent metastasectomy of the peritoneally disseminated HBs with ICG navigation followed by the second LDLTx for multiple metastases in the transplanted liver. The patient has been recurrence-free with a normal AFP for 30 months since the second LDLTx. To our knowledge, this report is the first successful case of re-LDLTx for recurrent HBs. Re-LDLTx for recurrent HB can be performed in highly select patients, and ICG navigation is a powerful surgical tool for achieving tumor clearance.

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A Hybrid Technique to Manage a Large Perigraft Seroma after an Open Abdominal Aortic Aneurysm Repair: A Case Report

Ono S., Obara H., Hagiwara K., Saida F., Oshiro K., Matsubara K., Shibutani S., Kitagawa Y.

Annals of Vascular Surgery (Annals of Vascular Surgery) 56 352.e1 - 352.e4 2019.04

ISSN 08905096

Perigraft seroma (PGS) is a relatively rare complication of aortoiliac reconstructive surgery. We, herein, describe a case of a large PGS that was managed by using a hybrid technique of relining the original graft with simultaneous open drainage. An 86-year-old man with a 17.3-cm diameter PGS after prosthetic bifurcated graft replacement for abdominal aortic aneurysm was admitted to our hospital. He presented with abdominal distension and discomfort and had difficulty in taking food. The entire relining of the original covered stent graft with GORE EXCLUDER using aortic extension cuff and iliac extenders and simultaneous open evacuation of PGS were successfully performed. The symptoms of the patient totally improved, and no recurrence was detected at 2 years after the operation. This technique would be a feasible treatment option for this rare complication. ® ®

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Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

Wakabayashi T., Obara H., Seki M., Shinoda M., Kitago M., Yagi H., Abe Y., Matsubara K., Yamada Y., Oshima G., Oki K., Nagoshi N., Watanabe K., Hibi T., Itano O., Hoshino K., Suzuki N., Kuroda T., Kitagawa Y.

Annals of Hepatology (Annals of Hepatology) 18 ( 2 ) 397 - 401 2019.03

ISSN 16652681

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.

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Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature

Yokose T., Obara H., Shinoda M., Nakano Y., Kitago M., Yagi H., Abe Y., Yamada Y., Matsubara K., Oshima G., Hori S., Ibuki S., Higashi H., Masuda Y., Hayashi M., Mori T., Kawaida M., Fujimura T., Hoshino K., Kameyama K., Kuroda T., Kitagawa Y.

World Journal of Gastroenterology (World Journal of Gastroenterology) 25 ( 15 ) 1899 - 1906 2019

ISSN 10079327

BACKGROUND Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT). CASE SUMMARY The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE. CONCLUSION This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation.

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A Pre-Clinical Large Animal Model of Sustained Liver Injury and Regeneration Stimulus

Inomata K., Tajima K., Yagi H., Higashi H., Shimoda H., Matsubara K., Hibi T., Abe Y., Tsujikawa H., Kitago M., Shinoda M., Obara H., Itano O., Soto-Gutierrez A., Kitagawa Y.

Scientific Reports (Scientific Reports) 8 ( 1 ) 2018.12

A feasible large animal model to evaluate regenerative medicine techniques is vital for developing clinical applications. One such appropriate model could be to use retrorsine (RS) together with partial hepatectomy (PH). Here, we have developed the first porcine model using RS and PH. RS or saline control was administered intraperitoneally to Göttingen miniature pigs twice, two weeks apart. Four weeks after the second dose, animals underwent PH. Initially, we tested different doses of RS and resection of different amounts of liver, and selected 50 mg/kg RS with 60% hepatectomy as our model for further testing. Treated animals were sacrificed 3, 10, 17 or 28 days after PH. Blood samples and resected liver were collected. Serum and liver RS content was determined by Liquid Chromatograph-tandem Mass Spectrometer. Blood analyses demonstrated liver dysfunction after PH. Liver regeneration was significantly inhibited 10 and 17 days after PH in RS-treated animals, to the extent of 20%. Histological examination indicated hepatic injury and regenerative responses after PH. Immunohistochemical staining demonstrated accumulation of Cyclin D1 and suppression of Ki-67 and PCNA in RS-treated animals. We report the development of the first large animal model of sustained liver injury with suppression of hepatic regeneration.

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Decreased Incidence of Acute Cellular Rejection in Low-Muscle-Mass Recipients After Living-donor Liver Transplantation

Wakabayashi T., Shinoda M., Obara H., Kitago M., Yagi H., Abe Y., Matsubara K., Yamada Y., Oshima G., Hirukawa K., Mizota T., Hibi T., Itano O., Hoshino K., Kuroda T., Kitagawa Y.

Transplantation Proceedings (Transplantation Proceedings) 50 ( 10 ) 3626 - 3634 2018.12

ISSN 00411345

Background: Sarcopenia has recently been studied as a potential risk factor for mortality and complications after liver transplantation. We investigated the impact of low muscle mass on postoperative outcomes after living-donor liver transplantation. Methods: Our study population consisted of 100 adult recipients who underwent living-donor liver transplantation in our department between 2005 and 2017. Recipients were divided into a low-muscle-mass group (L group) and a normal-muscle-mass group (N group) based on skeletal muscle index (SMI) values, and postoperative outcomes were compared between the groups. Regarding factors that were significantly different between the groups, multivariate analyses were performed to identify predictive factors. Results: Based on the SMI definition, 47 and 53 of the recipients were categorized as having low muscle mass (L group) and normal muscle mass (N group), respectively. Comparison between the groups revealed a significantly reduced incidence of rejection (10.6% in L group vs 30.2% in N group, P =.017) and increased incidences of bacterial infection (61.7% in L group vs 37.7% in N group, P =.017) in the L group compared with the N group. The survival rate did not differ significantly between the groups. Multivariate analyses indicated that muscle mass was a significant predictive factor for both rejection and bacterial infection. Conclusion: It is important to recognize that muscle mass has an impact not only on bacterial infection but also on rejection in recipients with low muscle mass in the postoperative course of living-donor liver transplantation.

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Contemporary critical limb ischemia: Asian multidisciplinary consensus statement on the collaboration between endovascular therapy and wound care

Kawarada O., Zen K., Hozawa K., Ayabe S., Huang H.L., Choi D., Kim S.H., Kim J., Kato T., Tsubakimoto Y., Nakama T., Ichihashi S., Fujimura N., Higashimori A., Fujihara M., Sato T., Yan B.P.Y., Pang S.Y.C., Wongwanit C., Leong Y.P., Chua B., George R.K., Yokoi Y., Motomura H., Obara H.

Cardiovascular Intervention and Therapeutics (Cardiovascular Intervention and Therapeutics) 33 ( 4 ) 297 - 312 2018.10

ISSN 18684300

The burden of peripheral artery disease (PAD) and diabetes in Asia is projected to increase. Asia also has the highest incidence and prevalence of end-stage renal disease (ESRD) in the world. Therefore, most Asian patients with PAD might have diabetic PAD or ESRD-related PAD. Given these pandemic conditions, critical limb ischemia (CLI) with diabetes or ESRD, the most advanced and challenging subset of PAD, is an emerging public health issue in Asian countries. Given that diabetic and ESRD-related CLI have complex pathophysiology that involve arterial insufficiency, bacterial infection, neuropathy, and foot deformity, a coordinated approach that involves endovascular therapy and wound care is vital. Recently, there is increasing interaction among cardiologists, vascular surgeons, radiologists, orthopedic surgeons, and plastic surgeons beyond specialty and country boundaries in Asia. This article is intended to share practical Asian multidisciplinary consensus statement on the collaboration between endovascular therapy and wound care for CLI.

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Retroperitoneal hematoma volume is a good predictor of perioperative mortality after endovascular aneurysm repair for ruptured abdominal aortic aneurysm

Fujimura N., Takahara M., Isogai N., Yashiro H., Shibutani S., Inoue M., Obara H., Ogino H.

Journal of Vascular Surgery (Journal of Vascular Surgery) 68 ( 4 ) 998 - 1006.e2 2018.10

ISSN 07415214

Objective: The objective of this study was to validate the usefulness of retroperitoneal hematoma volume as a predictor of perioperative mortality after endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA). Methods: We retrospectively reviewed consecutive patients with rAAA who underwent the unified EVAR first protocol between 2012 and 2016 at any one of three participating institutions in Japan and were prospectively registered in a dedicated database. Only patients with preoperative computed tomography scans adequate for three-dimensional volumetric analysis were included. Volumetry was used to measure the retroperitoneal hematoma volume. To adjust for body size differences between patients, the retroperitoneal hematoma volume was divided by the abdominal cavity volume, and the predictive power of this ratio was validated using appropriate statistical methods. Results: Of 114 patients with rAAA managed during the study period, 101 (88.6%) underwent EVAR, 9 (7.9%) underwent open surgical repair, and 4 (3.5%) did not undergo any repair. Finally, 82 of 101 patients treated with EVAR were included in the analysis. Within 30 days after EVAR, the mortality rates for the 82 patients included in the analysis and the 19 excluded patients were 24.4% and 31.6%, respectively, without statistically significant differences (P =.518). The retroperitoneal hematoma volume ratio was 3.59% ± 2.46% and 7.63% ± 3.45% in survivors and nonsurvivors, respectively (P <.001). Univariate analysis of other preoperative demographic and anatomic factors revealed that a Glasgow Aneurysm Score >85, systolic blood pressure <90 mm Hg, loss of consciousness, and mean minimum right external iliac artery diameter were statistically significant. Receiver operating characteristic curve analysis for the prediction of perioperative mortality revealed that retroperitoneal hematoma volume ratio was the best predictor of perioperative mortality in patients with rAAA of type >III in the Fitzgerald classification (area under the curve: retroperitoneal hematoma volume ratio, 0.880; Glasgow Aneurysm Score, 0.587; P <.001). Based on the Youden index, the optimal cutoff for the retroperitoneal hematoma volume ratio was 6.97%, providing a sensitivity of 0.833 and specificity of 0.860. Conclusions: Our study suggests that retroperitoneal hematoma volume may be a good predictor of perioperative mortality after EVAR for rAAA, especially for patients with Fitzgerald classification >III and a best cutoff value of 6.97%.

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Early sac shrinkage is a good surrogate marker of durable success after endovascular aneurysm repair in Japanese patients

Fujimura N., Matsubara K., Takahara M., Harada H., Asami A., Shibutani S., Watada S., Obara H., Kitagawa Y.

Journal of Vascular Surgery (Journal of Vascular Surgery) 67 ( 5 ) 1410 - 1418.e1 2018.05

ISSN 07415214

Objective: The applicability of early sac shrinkage as a predictor of a low risk of late complications after endovascular aneurysm repair (EVAR) in Asian populations has not been validated. This study aimed to analyze early sac shrinkage and its relationship with late complications in Asian people using a Japanese multicenter database. We also assessed the impact of endoleaks. Methods: A retrospective analysis of 697 patients who had undergone EVAR of abdominal aortic aneurysms from 2008 to 2015 and were followed up for at least 1 year was conducted. Late complications were defined as any aneurysm-related events occurring >1 year after EVAR, including >5-mm aneurysm sac enlargements and any reinterventions performed. Endoleaks without any evidence of sac enlargement or a requirement for additional treatment were not considered late complications. Results: Early sac shrinkage, defined as a >5-mm-diameter decrease within 1 year of EVAR, occurred in 335 patients (48.1%); type I endoleaks (T1ELs) and isolated type II endoleaks (iT2ELs; type II endoleaks without evidence of other endoleaks) were observed in 4.0% and 29.4%, respectively. During the mean follow-up period of 45.5 months, 93 late complications (13.3%) occurred. Kaplan-Meier curve and log-rank analyses showed that early sac shrinkage was a significant predictor for a lower risk of late complications (P <.001). Multivariate analysis revealed that early sac shrinkage was independently associated with a lower risk of late complications (adjusted hazard ratio, 0.425; P =.004). Conversely, T1ELs and iT2ELs were positively associated with late complication (adjusted hazard ratio, 11.774 and 5.137, respectively; both P <.001). Subsequent multivariate analysis demonstrated that T1ELs and iT2ELs were negatively associated with early sac shrinkage (adjusted odds ratio, 0.102 and 0.285, respectively; both P <.001). Conclusions: Early sac shrinkage was associated with a low risk of late complications in Asian people and may be a good surrogate marker of durable success after EVAR. T1ELs and iT2ELs were negatively associated with early sac shrinkage and positively associated with late complications. Along with the high incidence of iT2ELs observed, T2ELs may be an important condition to consider after EVAR in the Asian population.

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Successful management of living donor liver transplantation for biliary atresia with single ventricle physiology—from peri-transplant through total cavopulmonary connection: A case report

Yamada Y., Hoshino K., Oyanagi T., Gatayama R., Maeda J., Katori N., Fuchimoto Y., Hibi T., Shinoda M., Matsubara K., Obara H., Aeba R., Kitagawa Y., Yamagishi H., Kuroda T.

Pediatric Transplantation (Pediatric Transplantation) 22 ( 3 ) 2018.05

ISSN 13973142

Children with single ventricle physiology have complete mixing of the pulmonary and systemic circulations, requiring staged procedures to achieve a separation of these circulations, or Fontan circulation. The single ventricle physiology significantly increases the risk of mortality in children undergoing non-cardiac surgery. As liver transplantation for patients with single ventricle physiology is particularly challenging, only a few reports have been published. We herein report a case of successful LDLTx for an 8-month-old pediatric patient with biliary atresia, heterotaxy, and complex heart disease of single ventricle physiology. The cardiac anomalies included total anomalous pulmonary venous return type IIb, intermediate atrioventricular septal defect, tricuspid regurgitation grade III, coarctation of aorta, interrupted inferior vena cava, bilateral superior vena cava, and polysplenia syndrome. Following LDLTx, the patient sequentially underwent total cavopulmonary shunt + Damus-Kaye-Stansel at 3 years of age and extracardiac total cavopulmonary connection (EC-TCPC) completion at 5 years of age; 7 years have now passed since LDLTx (2 years post–EC-TCPC). We describe the details of the management of LTx in the presence of cardiac anomalies and report the long-term cardiac and liver function, from peri-LDLTx through EC-TCPC completion.

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Concurrent presentation of an intraductal tubulopapillary neoplasm and intraductal papillary mucinous neoplasm in the branch duct of the pancreas, with a superior mesenteric artery aneurysm: A case report

Inomata K., Kitago M., Obara H., Fujii-Nishimura Y., Shinoda M., Yagi H., Abe Y., Hibi T., Matsubara K., Oshima G., Sekimoto Y., Inoue M., Itano O., Sakamoto M., Kitagawa Y.

World Journal of Surgical Oncology (World Journal of Surgical Oncology) 16 ( 1 ) 2018.04

Background: Since the concept of intraductal tubulopapillary neoplasm (ITPN) was introduced in the current World Health Organization classification of tumors, the number of reports of ITPN occurrence has increased gradually. However, ITPN is usually located in the main pancreatic duct, with few reports of a branch duct ITPN. As a result, imaging protocols for the diagnosis of a branch duct ITPN have not been established. Case presentation: We report a case of a concurrent presentation of a branch duct ITPN and intraductal papillary mucinous neoplasm (IPMN) in the head of the pancreas, with a superior mesenteric artery (SMA) aneurysm. Initially, the cystic masses in the pancreatic head were diagnosed as branch duct IPMNs, with treatment consisting of a pylorus-preserving pancreaticoduodenectomy, in combination with an aneurysmectomy performed for treatment of the SMA aneurysm. Pathological examination confirmed these cysts were a combination of branch-type ITPN and IPMN. The patient recovered from the treatment without complication, with no evidence of recurrence over a period of 34 months post-surgery. Conclusion: This case report of a synchronous presentation of an ITPN and IPMN indicates the difficulty in differentiating these two types of neoplasms in the branch duct of the pancreatic head.

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Hemoadsorption of high-mobilitygroup box 1 using a porous polymethylmethacrylate fiber in a swine acute liver failure model

Amemiya R., Shinoda M., Yamada M., Ueno Y., Shimada K., Fujieda H., Yagi H., Mizota T., Nishiyama R., Oshima G., Yamada S., Matsubara K., Abe Y., Hibi T., Kitago M., Obara H., Itano O., Kitagawa Y.

International Journal of Artificial Organs (International Journal of Artificial Organs) 41 ( 4 ) 190 - 200 2018.02

ISSN 03913988

Background: High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs highmobility- group box chromosomal protein 1 by altering the pore size of the fiber. Materials and methods: First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model. Results: Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column. Conclusion: The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.

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Successful living donor liver retransplantation for graft failure within 7 days due to acute de novo donor-specific anti-human leukocyte antigen antibody-mediated rejection

Yamada Y., Hoshino K., Mori T., Kawaida M., Abe K., Ishihama H., Shimizu T., Takahashi N., Matsubara K., Hibi T., Abe Y., Yagi H., Shimojima N., Shinoda M., Kitago M., Obara H., Fuchimoto Y., Kameyama K., Kitagawa Y., Kuroda T.

Hepatology Research (Hepatology Research) 48 ( 3 ) E360 - E366 2018.02

ISSN 13866346

Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.

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Rituximab induction to prevent the recurrence of PSC after liver transplantation—the lessons learned from ABO-incompatible living donor liver transplantation

Yamada Y., Hoshino K., Fuchimoto Y., Matsubara K., Hibi T., Yagi H., Abe Y., Shinoda M., Kitago M., Obara H., Yagi T., Okajima H., Kaido T., Uemoto S., Suzuki T., Kubota K., Yoshizumi T., Maehara Y., Inomata Y., Kitagawa Y., Egawa H., Kuroda T.

Transplantation Direct (Transplantation Direct) 4 ( 2 ) 2018.02

Background. Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods. We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results. All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions. The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.

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Tolvaptan for fluid management in living donor liver transplant recipients

Imai S., Shinoda M., Obara H., Kitago M., Hibi T., Abe Y., Yagi H., Matsubara K., Higashi H., Itano O., Kitagawa Y.

Annals of Transplantation (Annals of Transplantation) 23 25 - 33 2018

ISSN 14259524

Background: Tolvaptan, an antagonist of the vasopressin V2 receptor is a novel oral diuretic that promotes water excretion selectively. We have used furosemide as a primary diuretic and added human atrial natriuretic peptide (hANP) if necessary for fluid management postoperatively in living-donor liver transplantation (LDLT) recipients. Recently we introduced tolvaptan and used both tolvaptan and furosemide as primary diuretics. Material/Methods: Clinical outcomes were compared between LDLT recipients whose postoperative fluid management was performed before (control group, n=10) and after (tolvaptan group, n=16) introduction of tolvaptan. Results: Preoperative and intraoperative demographic data did not differ significantly between the groups except for the period of post-surgical follow-up and total ischemic time. Urine volume was 1,242±692, 2,240±1307, and 2,268±1262 mL on postoperative day 1, 3, and 7, respectively, in the tolvaptan group. These volumes did not significantly differ from those in control group (1,027±462, 1,788±909, and 2,057±1216 mL on day 1, 3, and 7 postoperatively, respectively). Body weight gain and fluid volume from abdominal drainage tubes postoperatively did not differ significantly between groups. The time from hANP initiation to discontinuation and the time to removal of central vein catheters were significantly reduced in tolvaptan-treated patients. No severe side effects directly related to tolvaptan were observed. The survival rate at month 6 was 90.0% in control patients versus 93.8% in tolvaptan-treated patients. Conclusions: The outcomes of this investigation indicate that tolvaptan in combination with furosemide provides an adequate diuretic for fluid management subsequent to LDLT without causing adverse effects.

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Outcome from a randomized controlled clinical trial ― Improvement of peripheral arterial disease by granulocyte colony-stimulating factor-mobilized autologous peripheral-blood-mononuclear cell transplantation (IMPACT) ―

Horie T., Yamazaki S., Hanada S., Kobayashi S., Tsukamoto T., Haruna T., Sakaguchi K., Sakai K., Obara H., Morishita K., Saigo K., Shintani Y., Kubo K., Hoshino J., Oda T., Kaneko E., Nishikido M., Ioji T., Kaneda H., Fukushima M., Akamatsu M., Ichikawa Y., Ishida A., Iwashita C., Kawamura A., Mizuiri K., Otake T., Sakata A.

Circulation Journal (Circulation Journal) 82 ( 8 ) 2165 - 2174 2018

ISSN 13469843

Background: The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified. Methods and Results: A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II–IV and Rutherford category 1–5) caused by arteriosclerosis obliterans or Buerger’s disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. Conclusions: In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

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