Details of a Researcher - Obara, Hideaki

Papers - Obara, Hideaki

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Severity of early diagnosed organ/space surgical site infection in elective gastrointestinal and hepatopancreatobiliary surgery

Okui J., Obara H., Shimane G., Sato Y., Kawakubo H., Kitago M., Okabayashi K., Kitagawa Y.

Annals of Gastroenterological Surgery 6 ( 3 ) 445 - 453 2022.05

ISSN 2475-0328

Background: Organ/space surgical site infection (SSI) is a significant clinical problem. The postdiagnosis course of organ/space SSIs and the impact of its early diagnosis on clinical outcomes are yet to be clarified. Thus, we aimed to investigate the association between the timing of diagnosis and the clinical outcome of organ/space SSI. Methods: This retrospective, single-center cohort study evaluated patients who underwent elective gastrointestinal or hepatopancreatobiliary surgery between 2016 and 2020. Clinical outcomes were compared between the early group (ie, SSI diagnosed until postoperative day [POD] 4) and normal-late group (ie, SSI diagnosed after POD 5). The primary outcome was the final C-reactive protein (CRP) level within 14 d after organ/space SSI diagnosis. Results: In total, 110 patients were evaluated. The median time of diagnosis was 7 d postoperatively (interquartile range, 5–9 d postoperatively). Compared with the normal-late group, the early group included a higher proportion of patients with Clavien–Dindo grade ≥IIIb (8/21 vs 11/89, P =.01), higher final CRP value within 14 d after SSI diagnosis (mean, 4.49 mg/dL vs 2.27 mg/dL, P =.01), longer postoperative length of hospitalization (median, 45.0 d vs 33.0 d; P =.028), and worse 1-y overall survival rate (74.8% vs 89.3%, P =.08). Conclusion: Early diagnosed organ/space SSI are originally severe and may therefore be detected earlier. Importantly, early diagnosed organ/space SSI is likely to be severe and refractory.

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Comparative Study of S2-Alar-Iliac Screw Trajectories between Males and Females Using Three-Dimensional Computed Tomography Analysis: The True Lateral Angulation of the S2-Alar-Iliac Screw in the Axial Plane

Funao H., Yamanouchi K., Fujita N., Kado Y., Kato S., Otomo N., Isogai N., Sasao Y., Ebata S., Kitagawa Y., Watanabe K., Obara H., Ishii K.

Journal of Clinical Medicine 11 ( 9 ) 2022.05

ISSN 2077-0383

The S2 alar-iliac screw (S2AIS) is commonly used for long spinal fusion as a rigid distal foundation in spinal deformity surgeries, and it is also used in percutaneous sacropelvic fixation for providing an in-line connection to the proximal spinal constructs without using offset connectors. Although the pelvic shape is different between males and females, reports on S2AIS trajectories according to gender have been scarce in the literature. In this paper, S2AIS trajectories are compared between males and females using pelvic three-dimensional computed tomography (3D-CT) in a normal Japanese population. After resetting the caudal angulation in CT-imaging plane manipulation, the angulation of S2AIS was more lateral in the axial plane and more horizontal in the coronal plane in females. Mean distances from the midline to starting points of S2AIS tended to be shorter in females, whereas mean distances from the midline to the posterior superior iliac spine was significantly longer in females. We also found that there were positive correlations between the patients’ height and the maximal lengths of S2AISs, and the patients’ height and minimal areas of S2AIS pathways. Our results are useful not only for conventional open spinal surgery, but also for minimally invasive spine surgery.

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Patients with liver cirrhosis due to nonalcoholic steatohepatitis have lesser chances for liver transplantation

Hasegawa Y., Obara H., Chu P.S., Shinoda M., Kitago M., Abe Y., Yagi H., Matsubara K., Nakamoto N., Kitagawa Y.

Journal of Hepato Biliary Pancreatic Sciences 29 ( 5 ) 562 - 569 2022.05

ISSN 18686974

Background: The main causes of liver cirrhosis have changed over the past decade. In Japan, the number of deceased donors is increasing but is still insufficient relative to the number of patients awaiting a liver transplant. In the present study we aimed to assess the outcomes of candidates for liver transplantation. Methods: This was a retrospective study of adult patients who visited our department for consultation regarding liver transplantation from January 2009 to December 2020. Of a total of 601 patients, 336 were followed-up. The following data were collected and analyzed: patient's characteristics, liver etiology, Child-Pugh and MELD scores, and the eventual outcome, that is, whether liver transplantation was performed. Results: Only 153 of 336 (45.5%) patients underwent liver transplantation, of which 42 (27.5%) received deceased donor liver transplantation, and 129 (38.4%) died without transplantation. The proportion of patients who underwent liver transplantation was low among patients with nonalcoholic steatohepatitis (NASH) (10.7%) (P <.001). The rate of qualified living donors was the lowest for patients with NASH (28.6%) and that for the other etiologies ranged from 55.6% to 67.4% (P =.050). Conclusion: Patients with liver cirrhosis due to NASH may have a lesser chance of undergoing liver transplantation from both living and deceased donors.

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Adipose-Derived Mesenchymal Stromal/Stem Cell Line Prevents Hepatic Ischemia/Reperfusion Injury in Rats by Inhibiting Inflammasome Activation

Chen K., Obara H., Matsubara Y., Fukuda K., Yagi H., Ono-Uruga Y., Matsubara K., Kitagawa Y.

Cell Transplantation 31 9636897221089629 2022.04

ISSN 09636897

Mesenchymal stromal/stem cells (MSCs) have shown potential in the treatment of degenerative diseases, including ischemia/reperfusion injury (IRI), which occurs during organ transplantation and represents the main cause of post-transplant graft dysfunction. However, MSCs have heterogeneous characteristics, and studies of MSCs therapy have shown a variety of outcomes. To establish a new effective MSCs therapy, we developed an adipose-derived mesenchymal stromal/stem cell line (ASCL) and compared its therapeutic effects on primary adipose-derived MSCs (ASCs) using a hepatocyte co-culture model of hypoxia/reoxygenation in vitro and a rat model of hepatic IRI in vivo. The results showed that both ASCL and ASCs protect against hypoxia by improving hepatocyte viability, inhibiting reactive oxygen species release, and upregulating transforming growth factor-β in vitro. In vivo, ASCL or ASCs were infused into the spleen 24 h before the induction of rat hepatic IRI. The results showed that ASCL significantly improved the survival outcomes compared with the control (normal saline infusion) with the significantly decreased serum levels of liver enzymes and less damage to liver tissues compared with ASCs. Both ASCL and ASCs suppressed NOD-like receptor family pyrin domain-containing 3 inflammasome activation and subsequently reduced the release of activated IL-1β and IL-18, which is considered an important mechanism underlying ASCL and ASCs infusion in hepatic IRI. In addition, ASCL can promote the release of interleukin-1 receptor antagonist, which was previously reported as a key factor in hampering the inflammatory cascade during hepatic IRI. Our results suggest ASCL as a new candidate for hepatic IRI treatment due to its relatively homogeneous characteristics.

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Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model

Higashi H., Yagi H., Kuroda K., Tajima K., Kojima H., Nishi K., Morisaku T., Hirukawa K., Fukuda K., Matsubara K., Kitago M., Shinoda M., Obara H., Adachi S., Nishimura K., Natsume T., Tomi M., Soto-Gutierrez A., Kitagawa Y.

American Journal of Transplantation 22 ( 3 ) 731 - 744 2022.03

ISSN 16006135

Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.

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Carotid body tumor with neck metastasis due to germline SDHB variant: a case report and literature review

Mikoshiba, T; Yoshihama, K; Ito, F; Sekimizu, M; Nakamura, S; Nagai, R; Akiyama, T; Matsubara, K; Obara, H; Ozawa, H

INTERNATIONAL CANCER CONFERENCE JOURNAL 11 ( 1 ) 6 - 11 2022.01

ISSN 2192-3183

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Keio Uterus Transplantation Research: From Basic Research toward Future Clinical Application

Kisu I., Banno K., Matoba Y., Yamada Y., Emoto K., Masugi Y., Matsubara K., Obara H., Aoki D.

Keio Journal of Medicine 71 ( 2 ) 33 - 43 2022

ISSN 00229717

Uterus transplantation (UTx) is now a potential option to allow women with uterine factor infertility to give birth. However, UTx is still at an experimental stage, and basic animal studies, including in nonhuman primates, are needed for the accumulation of data prior to clinical application. Considering that UTx may provide new hope to Japanese women, we launched UTx research in 2009 and have since accumulated a large archive of results in the UTx research field. Furthermore, we have carried out various activities aimed at the implementation of clinical applications of UTx in Japan while clarifying the ethical and social issues involved. Currently, the clinical application of UTx in Japan is just around the corner, and it is expected that UTx research will develop further in the future. Herein, we summarize our basic experiences using non-human primates and our activities with the goal of future clinical applications.

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Dynamic contrast-enhanced CT at the early stage confirms two cases of acute liver failure due to acute-onset autoimmune hepatitis with extensive liver necrosis

Watanabe T., Chu P.S., Ehira T., Hasegawa Y., Hattori N., Shinoda M., Ikeda H., Tsujikawa H., Obara H., Hara M., Suzuki T., Matsunaga K., Okuse C., Itoh F.

Kanzo Acta Hepatologica Japonica 63 ( 3 ) 158 - 169 2022

ISSN 04514203

[Case 1] A 54-year-old female presented with severe liver damage. During diagnosis, contrast-enhanced CT enhanced the area of hypoattenuation on unenhanced CT in the arterial phase, after which the enhanced effect was prolonged to the equilibrium phase. Then, we started immunosuppressive therapy based on the results, including corticosteroid administration, and her hepatitis subsided. [Case 2] A 57-year-old female also presented with severe hepatitis. Contrast-enhanced CT findings were similar to those of Case 1. Since hepatic encephalo-pathy developed and worsened to degree IV, a brain-dead liver transplant was conducted on the 21st day. Nev-ertheless, histological diagnosis was challenging in both cases. Therefore, when unenhanced CT shows hetero-geneous hypoattenuation in the liver and contrast-enhanced CT shows a characteristic blood flow disorder, acute-onset autoimmune hepatitis and corticosteroid treatment should be considered, including in complex se-rological or histological case diagnoses.

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Efficacy of Early Closed Toe Amputation for Toe Ulcers with Suspected Osteomyelitis after Revascularization for Chronic Limb-Threatening Ischemia

Shintani, T; Suzuki, S; Kikuchi, N; Ariya, T; Natsume, K; Ookura, K; Okui, J; Sato, Y; Obara, H

ANNALS OF VASCULAR DISEASES 15 ( 2 ) 126 - 133 2022

ISSN 1881-641X

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Contemporary Outcomes After Partial Resection of Infected Aortic Grafts

Janko M., Hubbard G., Woo K., Kashyap V.S., Mitchell M., Murugesan A., Chen L., Gardner R., Baril D., Hacker R.I., Szeberin Z., ElSayed R., Magee G.A., Motta F., Zhou W., Lemmon G., Coleman D., Behrendt C.A., Aziz F., Black J.H., Tran K., Dao A., Shutze W., Garrett H.E., De Caridi G., Patel R., Liapis C.D., Geroulakos G., Kakisis J., Moulakakis K., Kakkos S.K., Obara H., Wang G., Stoecker J., Rhéaume P., Davila V., Ravin R., DeMartino R., Milner R., Shalhub S., Jim J., Lee J., Dubuis C., Ricco J.B., Coselli J., Lemaire S., Fatima J., Sanford J., Yoshida W., Schermerhorn M.L., Menard M., Belkin M., Blackwood S., Conrad M., Wang L., Crofts S., Nixon T., Wu T., Chiesa R., Bose S., Turner J., Moore R., Smith J., Irshad A., Hsu J., Czerny M., Cullen J., Kahlberg A., Setacci C., Joh J.H., Senneville E., Garrido P., Sarac T.P., Rizzo A., Go M.R., Bjorck M., Gavali H., Wanhainen A., D'Oria M., Lepidi S., Mastrorilli D., Veraldi G., Piazza M., Squizzato F., Beck A., St. John R., Wishy A., Humphries M., Shah S.K., Back M., Chung J., Lawrence P.F., Bath J., Smeds M.R.

Annals of Vascular Surgery 76 202 - 210 2021.10

ISSN 08905096

Introduction: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection. Methods: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed. Results: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01) Conclusion: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.

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Advantages of extrahepatic glissonean approach in the donor operation in living donor liver transplantation

Hirukawa, K; Yagi, H; Hibi, T; Masuda, Y; Shinoda, M; Obara, H; Kitago, M; Abe, Y; Oshima, G; Hori, S; Kuroda, T; Kitagawa, Y

TRANSPLANTATION 105 ( 8 ) 107 - 107 2021.08

ISSN 0041-1337

HONEDRA® (CLBS12) AUTOLOGOUS CD34+CELLS IMPROVE OUTCOMES IN PATIENTS WITH BUERGER'S DISEASE

Kawamoto, A; Furukawa, Y; Fujita, Y; Kobayashi, S; Tobita, K; Yamaguchi, J; Shimizu, W; Takagi, G; Matsumura, H; Murata, N; Nakamura, M; Kitano, I; Yokoi, H; Azuma, N; Kozuki, A; Obara, H; Furukawa, M; Sietsema, WK; Takagi, H; Wang, J; Bartel, R; Losordo, DW

CYTOTHERAPY 23 ( 5 ) S80 - S81 2021.05

ISSN 1465-3249

Nationwide study of surgery for primary infected abdominal aortic and common iliac artery aneurysms

Hosaka A., Kumamaru H., Takahashi A., Azuma N., Obara H., Miyata T., Obitsu Y., Zempo N., Miyata H., Komori K., Shigematsu K., Inoue Y., Okazaki J., Obara H., Satokawa H., Sugimoto I., Banno H., Fujimura N., Mii S., Morikage N., Yamaoka T.

British Journal of Surgery 108 ( 3 ) 286 - 295 2021.03

ISSN 00071323

Background: Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy remain poorly defined. Methods: A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR). Results: Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P<0.001). Propensity score-matched analyses demonstrated no significant differences between EVAR and in situ graft replacement in terms of 3-year all-cause and aorta-related mortality rates (P=0.093 and P =0.472 respectively). Conclusion: In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.

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Long-term outcomes of living donor liver transplantation after locoregional treatment for hepatocellular carcinoma: an experience from a single institute

Inomata K., Yagi H., Hibi T., Shinoda M., Matsubara K., Abe Y., Kitago M., Obara H., Itano O., Kawachi S., Tanabe M., Wakabayashi G., Shimazu M., Kitagawa Y.

Surgery Today (Surgery Today) 51 ( 3 ) 350 - 357 2021.03

ISSN 09411291

Purpose: The precise role of downstaging or bridge therapy for cirrhotic patients with hepatocellular carcinoma (HCC) beyond or within the Milan criteria (MC) before living donor liver transplantation (LDLT) remains undefined. Methods: We conducted a single-center, retrospective cohort study of 40 cirrhotic patients with HCC who underwent LDLT from 2000 to 2018. Dynamic computed tomography images at the initial presentation and immediately before LDLT as well as the final histopathological findings were reviewed to determine whether they met or exceeded MC. Results: Overall, 29 patients underwent various pre-transplant HCC treatments, including ablation and embolization (bridge therapy, n = 20; downstaging, n = 9). Of the 9 patients who were initially beyond the MC, 4 (44.4%) were successfully downstaged to within the MC. Five patients beyond the MC immediately before LDLT demonstrated a significantly worse 5-year overall survival rate than patients within the MC (16.7% vs. 82.2%, P = 0.004), regardless of the radiological HCC stage at presentation or the final pathological tumor status. All 3 recurrent patients had HCC beyond the MC immediately before transplant and died of their disease at 13, 24, and 50 months after transplantation. Conclusions: Successful downstaging for HCC cases beyond the MC provides similar outcomes to those within the MC at presentation, regardless of the histopathological findings.

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CT screening for COVID-19 in asymptomatic patients before hospital admission

Uchida S., Uno S., Uwamino Y., Hashimoto M., Matsumoto S., Obara H., Jinzaki M., Kitagawa Y., Hasegawa N.

Journal of Infection and Chemotherapy (Journal of Infection and Chemotherapy) 27 ( 2 ) 232 - 236 2021.02

ISSN 1341321X

Introduction: In the novel coronavirus disease (COVID-19) pandemic era, it is essential to rule out COVID-19 effectively to prevent transmission in both communities and medical facilities. According to previous reports in high prevalence areas, CT screening may be useful in the diagnosis of COVID-19. However, the value of CT screening in low prevalence areas has scarcely been reported. Methods: This report examines the diagnostic efficacy of CT screening before admission to a hospital in Tokyo. We conducted a retrospective analysis at Keio University Hospital from April 6, 2020, through May 29, 2020. We set up an outpatient screening clinic on April 6 for COVID-19, administering both PCR with nasopharyngeal swabs and chest CT for all patients scheduled for surgery under general anesthesia. Results: A total of 292 asymptomatic patients were included in this study. There were three PCR-positive patients, and they all had negative CT findings, which revealed that both the sensitivity and positive predictive value of CT (PPV) were 0%. There were nine CT-positive patients; the specificity and the negative predictive value (NPV) were 96.9% and 98.9%, respectively. Conclusion: CT screening was not useful in low prevalence areas at this time in Tokyo, even with the inclusion of the most prevalent phase. Given that the utility of CT screening depends on disease prevalence, the criteria for performing CT screening based on the prevalence of COVID-19 should be established.

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In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas

Janko M.R., Woo K., Hacker R.I., Baril D., Bath J., Smeds M.R., Kashyap V.S., Szeberin Z., Magee G.A., Elsayed R., Wishy A., St. John R., Beck A., Farber M., Motta F., Zhou W., Lemmon G., Coleman D., Behrendt C.A., Aziz F., Black J., Shutze W., Garrett H.E., De Caridi G., Liapis C.D., Geroulakos G., Kakisis J., Moulakakis K., Kakkos S.K., Obara H., Wang G., Rhéaume P., Davila V., Ravin R., DeMartino R., Milner R., Shalhub S., Jim J., Lee J., Dubuis C., Ricco J.B., Coselli J., Lemaire S., Fatima J., Sanford J., Yoshida W., Schermerhorn M.L., Menard M., Belkin M., Blackwood S., Conrad M., Wang L., Crofts S., Nixon T., Wu T., Chiesa R., Bose S., Turner J., Moore R., Smith J., Ciocca R., Hsu J., Czerny M., Cullen J., Kahlberg A., Setacci C., Joh J.H., Senneville E., Garrido P., Sarac T.P., Rizzo A., Go M.R., Bjorck M., Gavali H., Wanhainen A., Lawrence P.F., Chung J.

Journal of Vascular Surgery (Journal of Vascular Surgery) 73 ( 1 ) 210 - 221.e1 2021.01

ISSN 07415214

Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. Results: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P =.82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P =.01), had less operative hemorrhage (1200 mL vs 2000 mL; P =.04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P =.02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P =.03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P =.01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P =.03) independently decreased mortality. Conclusions: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10 months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population.

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Invasive pulmonary aspergillosis after liver transplantation: lessons from successfully treated cases and review of the literature

Abe K., Shinoda M., Uno S., Obara H., Kitago M., Abe Y., Hishida T., Yagi H., Hasegawa Y., Kitagawa Y.

Surgery Today (Surgery Today) 51 ( 8 ) 1361 - 1370 2021

ISSN 09411291

Purpose: Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center. Methods: We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully. Results: Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized. Conclusions: Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.

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Diagnostic utility of presepsin in infections after liver transplantation: A preliminary study

Yokose T., Takeuchi M., Obara H., Shinoda M., Kawakubo H., Kitago M., Yagi H., Abe Y., Yamada Y., Matsubara K., Oshima G., Hori S., Fujimura T., Takemura R., Ishii R., Kuroda T., Kitagawa Y.

Annals of Transplantation 26 e933774 2021

ISSN 14259524

Background: Infectious complications after solid organ transplantation can be fatal, and early diagnosis and intervention are important. To the best of our knowledge, no study has examined the diagnostic utility of presepsin, a known accurate biomarker, for infectious complications after liver transplantation. This study aimed to evaluate the utility of presepsin for detecting infection and perioperative kinetics of presepsin after liver transplantation. Material/Methods: This single-institutional prospective, observational study included 13 patients who underwent living-donor or de-ceased-donor liver transplantation. Perioperative serum presepsin level was measured 6 times within a week to evaluate its association with infectious complications and compare it with procalcitonin and C-reactive protein levels and leukocyte count. Postoperatively, patients were followed up for 15 days for infectious complications. Results: Five of the 13 patients developed infectious complications after liver transplantation. The median time for infection diagnosis was 9 postoperative days (25th-75th percentile, 7-10). Presepsin levels on 5 and 7 postoperative days were significantly higher in patients with infection than in those without (P=0.019 and P=0.011, re-spectively). In receiver operating characteristic analysis, area under the curve values of presepsin on 5 and 7 postoperative days (0.881 and 0.905, respectively) were higher than those of other biomarkers. The optimal cut-off value of presepsin was 1361 pg/mL on postoperative day 5 and 1375 pg/mL on postoperative day 7. Conclusions: Although this study included a small number of patients, presepsin levels on postoperative days 5 and 7 may be useful indicators for infectious complications after liver transplantation.

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Maintenance treatment with infliximab for ulcerative ileitis after intestinal transplantation: A case report

Fujimura T., Yamada Y., Umeyama T., Kudo Y., Kanamori H., Mori T., Shimizu T., Kato M., Shimojima N., Hoshino K., Kuroda T., Kawaida M., Hosoe N., Hasegawa Y., Matsubara K., Shinoda M., Obara H., Kitagawa Y., Naganuma M.

World Journal of Clinical Cases 9 ( 19 ) 5270 - 5279 2021

ISSN 2307-8960

BACKGROUND Evidence has been published on the successful applications of the anti-tumor necrosis factor alpha antibody infliximab, such as induction therapy, salvage treatment for acute cellular rejection, and treatment for chronic ulcerative inflammation, in intestinal transplant recipients. However, the optimal protocol for the effective use of infliximab remains largely undetermined due to scarcity of available clinical data. We report a continuative application of infliximab as maintenance therapy for recurrent chronic ulcerative ileitis in a recipient of isolated intestinal transplantation (ITx). CASE SUMMARY The patient was a 11-year-old boy with intestinal motility disorder classified as a hypogenic type of intestinal dysganglionosis. The patient underwent living-donor related intestinal transplant. His immunosuppression regimen consisted of daclizumab, tacrolimus, and steroids. Although he did not show rejection while on tacrolimus monotherapy, routine screening endoscopy showed several ulcerative lesions in the distal end of the graft 2 years after the intestinal transplant. Endoscopic work up to evaluate the progression of anemia revealed stenosis with ulcerative inflammatory changes and multiple longitudinal ulcers in the graft. Since the endoscopic findings suggested ulcerative lesions in Crohn's disease, infliximab treatment was considered. Treatment with infliximab and a small dose of oral prednisolone afforded successful withdrawal of total parenteral nutrition and maintenance of a well-functioning graft without infectious complications for 5 years since the administration of the first dose of infliximab. CONCLUSION Infliximab is effective as maintenance therapy for recurrent chronic ulcerative ileitis in an isolated ITx patient.

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The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure

Mizota T., Hishiki T., Shinoda M., Naito Y., Hirukawa K., Masugi Y., Itano O., Obara H., Kitago M., Yagi H., Abe Y., Matsubara K., Suematsu M., Kitagawa Y.

Journal of Clinical Biochemistry and Nutrition 70 ( 1 ) 54 - 63 2021

ISSN 09120009

The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S-adenosyl-L-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH<inf>3</inf> levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms.

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