Publications by authors named "Shigehito Miyagi"

67 Publications

The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.

Med Oncol 2021 Apr 21;38(6):60. Epub 2021 Apr 21.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.
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http://dx.doi.org/10.1007/s12032-021-01503-zDOI Listing
April 2021

Surgical resection for liver metastasis and local recurrence of pheochromocytoma 16 years after primary surgery: A case report.

Int J Surg Case Rep 2021 Apr 27;81:105712. Epub 2021 Feb 27.

Department of Surgery, Graduate School of Medicine, Tohoku University, Japan.

Introduction And Importance: Pheochromocytomas arise from the adrenal medulla and are rare. Pheochromocytomas metastasize to bone, lung and liver, and surgery might be the curative treatment. However, few cases are detected when they are resectable lesions because of difficulty in diagnosis and rapid growth. We herein report a patient who underwent resection of liver metastasis and local recurrence of pheochromocytoma.

Case Presentation: A 74-year-old woman visited our hospital for treatment for liver and retroperitoneal tumors. She had undergone left adrenal gland resection for pheochromocytoma 16 years earlier. Eleven years after primary surgery, breast cancer was diagnosed and resected. During the breast cancer follow-up, a liver tumor was identified with computed tomography. Breast cancer recurrence and metastasis were considered, so chemotherapy was administered first. However, the liver tumor gradually enlarged, and another lesion appeared in the retroperitoneum. The tumors were diagnosed as pheochromocytoma recurrence using I-metaiodobenzylguanidine scintigraphy, and she underwent resection of the local recurrence and liver metastasis. She was discharged on postoperative day 25 without complications, and no evidence of recurrence occurred more than 3.5 years postoperatively.

Clinical Discussion: All pheochromocytomas have metastatic potential; however, there are no reliable markers to predict malignancy. Early detection of recurrence by regular imaging and complete resection are important in the treatment. If the recurrence was oligometastasis and tumor growth is slow, surgical resection may be eligible.

Conclusion: A favorable outcome resulted from complete resection for liver metastasis and local recurrence of pheochromocytoma.
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http://dx.doi.org/10.1016/j.ijscr.2021.105712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941035PMC
April 2021

Bleeding from jejunal varices formed at the Roux-en-Y jejunum site caused by the compression of the left renal vein after living donor liver transplantation with renoportal anastomosis.

Surg Case Rep 2021 Feb 6;7(1):43. Epub 2021 Feb 6.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.

Background: Renoportal anastomosis is an option for the portal vein reconstruction of a liver transplantation with grade 4 portal vein thrombosis and a splenorenal shunt. Here, we report the case of gastrointestinal bleeding who underwent living donor liver transplantation (LDLT) with renoportal anastomosis.

Case Presentation: Six-year-old female patient who underwent LDLT with renoportal anastomosis at 1 year of age had severe anemia with normal liver function during the follow-up period. The varices at the Roux-en-Y jejunum were considered the source of bleeding, and the compression of the left renal vein, which is known as a cause of Nutcracker syndrome, seemed to induce venous hypertension through the splenorenal shunt, which might induce the formation of the varices. She underwent percutaneous transhepatic sclerotherapy of the varices, and the anemia improved at her last follow-up, 6 months after sclerotherapy. This is the first reported case of Roux-en-Y jejunal varices bleeding related to the compression of the left renal vein after LDLT was performed with renoportal anastomosis.

Conclusions: Although renoportal anastomosis should be cautiously performed when there are no options for severe portal vein thrombosis, the status of the left renal vein and new collateral formation should be observed carefully during the follow-up period in pediatric cases of renoportal anastomosis.
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http://dx.doi.org/10.1186/s40792-021-01129-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867670PMC
February 2021

Improvement of hepatocyte engraftment by co-transplantation with pancreatic islets in hepatocyte transplantation.

J Tissue Eng Regen Med 2021 Apr 19;15(4):361-374. Epub 2021 Feb 19.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Because of the fragility of isolated hepatocytes, extremely poor engraftment of transplanted hepatocytes remains a severe issue in hepatocyte transplantation. Therefore, improving hepatocyte engraftment is necessary to establish hepatocyte transplantation as a standard therapy. Since the pancreatic islets are known to have favorable autocrine effects, we hypothesized that the transplanted islets might influence not only the islets but also the nearby hepatocytes, subsequently promoting engraftment. We evaluated the effects of islet co-transplantation using an analbuminemic rat model (in vivo model). Furthermore, we established a mimicking in vitro model to investigate the underlying mechanisms. In an in vivo model, the hepatocyte engraftment was significantly improved only when the islets were co-transplanted to the nearby hepatocytes (p < 0.001). Moreover, the transplanted hepatocytes appeared to penetrate the renal parenchyma together with the co-transplanted islets. In an in vitro model, the viability of cultured hepatocytes was also improved by coculture with pancreatic islets. Of particular interest, the coculture supernatant alone could also exert beneficial effects comparable to islet coculture. Although insulin, VEGF, and GLP-1 were selected as candidate crucial factors using the Bio-Plex system, beneficial effects were partially counteracted by anti-insulin receptor antibodies. In conclusion, this study demonstrated that islet co-transplantation improves hepatocyte engraftment, most likely due to continuously secreted crucial factors, such as insulin, in combination with providing favorable circumstances for hepatocyte engraftment. Further refinements of this approach, especially regarding substitutes for islets, could be a promising strategy for improving the outcomes of hepatocyte transplantation.
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http://dx.doi.org/10.1002/term.3170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048420PMC
April 2021

Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model.

Am J Transplant 2020 Dec 22. Epub 2020 Dec 22.

Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Small-for-size syndrome (SFSS) has a poor prognosis due to excessive shear stress and sinusoidal microcirculatory disturbances in the acute phase after living-donor liver transplantation (LDLT). Multilineage-differentiating stress enduring (Muse) cells are reparative stem cells found in various tissues and currently under clinical trials. These cells selectively home to damaged sites via the sphingosine-1-phosphate (S1P)-S1P receptor 2 system and repair damaged tissue by pleiotropic effects, including tissue protection and damaged/apoptotic cell replacement by differentiating into tissue-constituent cells. The effects of intravenously administered human bone marrow-Muse cells and -mesenchymal stem cells (MSCs) (4 × 10 ) on liver sinusoidal endothelial cells (LSECs) were examined in a rat SFSS model without immunosuppression. Compared with MSCs, Muse cells intensively homed to the grafted liver, distributed to the sinusoids and vessels, and delivered improved blood chemistry and Ki-67(+) proliferative hepatocytes and -LSECs within 3 days. Tissue clearing and three-dimensional imaging by multiphoton laser confocal microscopy revealed maintenance of the sinusoid continuity, organization, and surface area, as well as decreased sinusoid interruption in the Muse group. Small-interfering RNA-induced knockdown of hepatocyte growth factor and vascular endothelial growth factor-A impaired the protective effect of Muse cells on LSECs. Intravenous injection of Muse cells might be a feasible approach for LDLT with less recipient burden.
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http://dx.doi.org/10.1111/ajt.16461DOI Listing
December 2020

Effect of enhanced recovery after surgery protocol on recovery after open hepatectomy: a randomized clinical trial.

Ann Surg Treat Res 2020 Dec 26;99(6):320-328. Epub 2020 Nov 26.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Purpose: Enhanced recovery after surgery (ERAS) is beneficial to patients undergoing digestive surgery. However, its efficacy in patients undergoing open hepatectomy remains unclear.

Methods: Consecutive patients scheduled for open hepatectomy were randomly assigned to undergo either ERAS or conventional postoperative management. The primary endpoint was the amount of time that elapsed before patients were considered medically fit for discharge (MFD) and length of hospital stay (LOHS). Secondary endpoints included morbidity, mortality, the time to first flatus, defecation, first walk, and freedom from infusion. Perioperative serum nutritional markers, insulin resistance, respiratory quotient (RQ), and resting energy expenditure (REE) were also assessed.

Results: Between August 2014 and March 2017, 57 patients were randomized into 2 groups; ERAS group (n = 29) and conventional management (n = 28). The median MFD was not significantly different between the ERAS and conventional management groups (6.5 7 days; P = 0.381). Recovery from gastrointestinal paresis was significantly quicker in the ERAS group (1.8 2.4 days; P = 0.004). There were no significant differences in serum markers, insulin resistance, RQ, and REE.

Conclusion: This trial did not demonstrate greater efficacy of the ERAS protocol following open hepatectomy in terms of the MFD and LOHS. However, the ERAS protocol was associated with better recovery from postoperative gastrointestinal paresis, suggesting that it is useful for patients undergoing open hepatectomy.
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http://dx.doi.org/10.4174/astr.2020.99.6.320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704272PMC
December 2020

Effects of re-augmenting maintenance immunosuppression on post-transplant donor-specific HLA antibodies in liver transplantation.

Transpl Immunol 2020 12 10;63:101334. Epub 2020 Sep 10.

Department of Surgery, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.

Background: Donor-specific antibodies (DSAs) have various negative short- and long-term effects after organ transplantation. DSAs are prevalent in patients with insufficient immunosuppression; thus, even patients with stable conditions after liver transplantation should be under optimized immunosuppression. However, the effect of re-augmenting immunosuppression therapy for patients with insufficient immunosuppression remains unclear. In this study, we investigated the long-term changes and the effects of immunosuppression (IS) re-augmentation on the DSA status.

Methods: Two DSA screenings were performed in 67 patients during long-term follow-up after liver transplantation. After the first screening, IS re-augmentation was performed in patients with consent. The effects of IS re-augmentation on the DSA status were analyzed using data of the serial DSA screenings. Negative conversion was defined as DSA positivity with MFI > 1000 converted to MFI < 1000. Improvement of DSA status was defined as either a 50% reduction of MFI or negative conversion.

Results: The median interval between the first and second DSA screening was 50 months. Among 67 patients, 43 were positive for DSAs on the first screening. Among these 43 patients, 30 had minimal to no IS therapy at the time of the first screening. Among the 30 patients, IS re-augmentation was conducted in 19. A comparison between the patients with a re-augmented IS and those with a sustained minimized IS showed that the DSA levels significantly decreased in the former (63% (12/19) vs. 18% (2/11), p = 0.02).

Conclusions: The results of this study indicate that post-liver transplant IS re-augmentation had suppressive effects on the DSA status. However, the clinical significance of DSA-negative conversion and/or mean fluorescence intensity reduction needs to be further investigated through histological evaluation and/or graft survival during longer follow-up periods.
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http://dx.doi.org/10.1016/j.trim.2020.101334DOI Listing
December 2020

Chronic Active Antibody-Mediated Rejection With Donor-Specific Anti-HLA-DP Antibodies Following Living Donor Kidney Transplantation: A Case Report.

Transplant Proc 2020 Jul - Aug;52(6):1937-1939. Epub 2020 Jun 23.

Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan.

Posttransplant donor-specific anti-HLA antibodies (DSA) cause chronic antibody-mediated rejection. Anti-DR and anti-DQ DSAs have especially been shown to be associated with negative graft function. In contrast, the prevalence and significance of anti-DP DSA have not been well established and remain unclear. We report a case of living donor kidney transplantation. The level of serum creatinine gradually became elevated because of chronic active antibody-mediated rejection, which was considered to be caused by anti-DP DSA. In this report, we indicate the significance of pretransplant screening for HLA-DP in donors to evaluate more comprehensively the donor specificity of posttransplant HLA antibodies.
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http://dx.doi.org/10.1016/j.transproceed.2020.02.130DOI Listing
November 2020

Effects of Short-Term Normothermic and Subnormothermic Perfusion After Cold Preservation on Liver Transplantation From Donors After Cardiac Death.

Transplant Proc 2020 Jul - Aug;52(6):1639-1642. Epub 2020 May 26.

Department of Transplantation and Regenerative Medicine, Tohoku University, Graduate School of Medicine, Sendai, Japan.

Background: Liver transplantation from donors after cardiac death (DCD) could increase the pool of organs. We previously reported that oxygenated subnormothermic (20°C-25°C) ex vivo liver perfusion (SELP) improved the graft viability in rats. This study aimed to compare the effectiveness of SELP and normothermic (37°C) ex vivo liver perfusion (NELP) after cold storage (CS) in DCD liver grafts.

Methods: Male Wistar rats were used, and grafts were retrieved 30 minutes after cardiac arrest. We performed oxygenated NELP and SELP with a Krebs-Henseleit buffer for different time points and durations: Group 0, donation performed from heart-beating donors (control); Group 1 (DCD group), donation performed from DCD donors with no treatments; Group 2, NELP performed before CS (30 minutes); Group 3, NELP performed after CS (30 minutes); Group 4, SELP performed after CS (30 minutes); Group 5, SELP performed after CS (60 minutes); and Group 6, SELP performed after CS (90 minutes). After 15 minutes of incubation at room temperature, the grafts were reperfused under normothermic conditions for 60 minutes as a model of liver transplantation.

Results: No significant differences in body and liver weight were observed between all groups. In the SELP after CS groups, even 30 minutes of perfusion improved bile production, tumor necrosis factor-α, and interleukin-1β significantly compared with the DCD group (P < .05), comparable with NELP groups.

Conclusion: SELP rescued DCD livers from ischemia-reperfusion injury the same as the normothermic perfusion before or after CS groups. SELP after CS is more convenient than normothermic perfusion; hence, this technique may increase the organ pool.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.147DOI Listing
November 2020

Risks of Living Donor Liver Transplantation Using Small-For-Size Grafts.

Transplant Proc 2020 Jul - Aug;52(6):1825-1828. Epub 2020 May 21.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: In living donor liver transplantation (LDLT), a graft-to-recipient weight ratio (GRWR) of under 0.8 is recognized as the critical graft size. Our aim was to compare the survival rates of recipients with small-for-size grafts (SFSG: GRWR <0.8), normal-sized grafts (NSG), and large-for-size grafts (LFSG: GRWR ≥ 3.5) and to investigate the mortality risk with SFSG.

Methods: Between 1991 and April 2019, we performed 188 LDLT surgeries. Recently, we added splenectomy when portal vein pressure is high (>17 mm Hg) to interrupt the splenic bloodstream. We divided all LDLT cases retrospectively into 3 groups: an SFSG group (n = 22), NSG group (n = 154), and LFSG group (n = 12). We investigated the survival rates in these groups. Furthermore, we divided the SFSG group into 2 subgroups: an SFSG with splenectomy (SFSG+S) group (n = 7) and an SFSG without splenectomy group. We investigated the occurrence rates of lethal complications such as portal vein thrombosis, hepatic artery thrombosis, and hepatic vein thrombosis.

Results: The 5-year survival rate in the SFSG group was significantly lower (52.8%) than in the other groups (NSG: 84.5%; LFSG: 83.3%), but that of the SFSG+S group was similar (80.0%) to that of other groups. There was no difference in the occurrence of postoperative complications such as portal vein thrombosis, hepatic artery thrombosis, or hepatic vein thrombosis between the SFSG+S group and other groups.

Conclusions: Graft survival of LDLT using SFSG+S was as good as that of normal-sized grafts. Reducing portal vein pressure was important for SFSG.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.136DOI Listing
November 2020

Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation From Donors After Cardiac Death in Swine.

Transplant Proc 2020 Jul - Aug;52(6):1891-1900. Epub 2020 May 7.

Division of Transplantation and Regenerative Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Liver transplantation from donors after cardiac death (DCDs) can increase the pool of available organs. Recently, mesenchymal stem cells (MSCs) have been used to treat various diseases. Some studies have reported that MSCs improve the outcome of liver transplantation from DCDs in mice. The aim of this study was to evaluate the cytoprotective effects and safety of MSC transplantation on liver grafts from DCDs in swine.

Methods: For the MSCs, we used swine adipose-derived stem cells (ADSCs). Landrace swine were divided into 3 groups (n = 5) as follows: 1. the heart-beating (HB) group, from which liver grafts were retrieved and transplanted; 2. the DCD group, from which liver grafts were retrieved 10 minutes after apnea-induced cardiac arrest and transplanted; and 3. the ADSC group, from which liver grafts were retrieved as with the DCD group, transplanted, and then infused with 1.0 × 10 ADSCs 2 hours after reperfusion.

Results: In the HB group, all 5 recipients survived for >7 days, whereas all 5 recipients in the DCD group died within 24 hours after transplantation. In the ADSC group, 3 recipients survived for >7 days, whereas 2 recipients died within 4 days after transplantation. The survival rate was significantly higher in the ADSC group than in the DCD group.

Conclusions: MSCs could protect the function of liver grafts from warm ischemia-reperfusion injury and improve the viability of DCD liver grafts.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.165DOI Listing
November 2020

Diabetic Muscle Infarction with High Fever.

Am J Med 2020 10 11;133(10):e594-e595. Epub 2020 Apr 11.

Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Miyagi Japan. Electronic address:

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http://dx.doi.org/10.1016/j.amjmed.2020.03.021DOI Listing
October 2020

Characteristics and predictive value for graft fibrosis of the complement-binding capacity of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation.

Pediatr Transplant 2020 02 29;24(1):e13648. Epub 2019 Dec 29.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Donor-specific HLA antibodies (DSAs) have detrimental effects on short- and long-term outcomes after organ transplantation. Despite evidence that the complement-binding capacity of DSAs has predictive power in kidney transplantation, its clinical impact during long-term follow-up after LT remains unclear. In this study, we assessed the complement-binding capacities of DSAs and their association with histological findings.

Methods: In total, 72 patients who underwent pediatric LT at our institution between July 1991 and October 2013 were retrospectively reviewed. A subgroup analysis of histological findings was performed for 37 subjects who underwent liver graft biopsy. Patients were divided into two groups based on the degree of graft fibrosis, and clinical characteristics were assessed.

Results: All anti-class I DSAs were C1q-negative. Anti-DR and anti-DQ DSAs were identified in 34% and 41% of patients, respectively; however, only three of 25 patients with anti-DR DSAs exhibited a positive C1q-binding assay, whereas, 25 of 29 anti-DQ DSAs showed C1q-binding capacity. MFI values for DSA were significantly higher for patients with C1q-binding capacity than for those without (P < .0001). Complement-binding anti-DR DSA was relatively rare in both groups. Regarding anti-DQ DSA, there were no differences between fibrosis and non-fibrosis groups, irrespective of complement-binding capacity.

Conclusions: The association between anti-DR DSA and liver fibrosis, which was supported in this cohort, was not strengthened but rather impaired when accounting for complement-binding capacity due to low positive detection. Further studies of the association between complement-binding anti-DQ DSA and histological findings in LT are needed.
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http://dx.doi.org/10.1111/petr.13648DOI Listing
February 2020

Effects of a new perioperative enhanced recovery after surgery protocol in hepatectomy for hepatocellular carcinoma.

Surg Today 2020 Jun 3;50(6):615-622. Epub 2019 Dec 3.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-0872, Japan.

Purpose: Enhanced recovery after surgery (ERAS) protocols are becoming the standard of care in many surgical procedures, although data on their use following hepatectomy for hepatocellular carcinoma (HCC) are scarce. This study aimed to evaluate the effects of a new ERAS pathway in terms of the patient nutrition status after hepatectomy for HCC.

Methods: This is a retrospective analysis of 97 consecutive patients treated with open or laparoscopic hepatectomy for HCC between January 2011 and August 2014. We compared the perioperative outcomes between patients whose treatment incorporated the ERAS pathway and control patients. The nutritional status was evaluated using the controlling nutritional status score.

Results: The length of hospital stay (LOS) after both open and laparoscopic hepatectomy was shorter for the ERAS group than the control group. The days of ambulation and cessation of intravenous infusion were earlier and the postoperative nutrition status was statistically better in the ERAS group than in the control group. A multivariate analysis showed that being in the non-ERAS group was a risk factor of delayed discharge. There were no marked differences in the rate of severe complications between the two groups.

Conclusions: The ERAS pathway seems feasible and safe and results in a faster recovery, reduced LOS, improved nutrition status, and fewer severe complications.
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http://dx.doi.org/10.1007/s00595-019-01930-6DOI Listing
June 2020

Long-Term Outcomes of Acute Limb Ischemia: A Retrospective Analysis of 93 Consecutive Limbs.

Ann Vasc Dis 2019 Sep;12(3):347-353

Department of Surgery, Tohoku University Hospital, Sendai, Miyagi, Japan.

: To examine the medium- to long-term outcomes of acute limb ischemia (ALI), which are unclear at present. : We analyzed 93 consecutive limbs in 77 patients with ALI between January 2005 and December 2015 treated at our vascular center. We categorized the cases into four groups according to etiology (embolism, thrombosis, graft thrombosis, and dissection groups) to assess survival, limb salvage, and freedom from re-intervention rates. : The mean age at onset was 72±15 years. The median follow-up length was 2.90 years. The Rutherford categories I, IIa, IIb, and III included 1, 38, 51, and 3 cases, respectively. Thromboembolectomy was performed in all patients in the embolism and thrombosis groups. In addition, endovascular treatment was performed in 25 (37.3%) patients, especially in the thrombosis group (81.3%). A major amputation could not be avoided in 10 patients. The 5-year limb salvage rates for categories IIa and IIb were 97.1% and 83.1%, respectively. The 5-year freedom from re-intervention rate was 89.2%. The survival rates at 1, 3, and 5 years were 87.9%, 75.2%, and 60.6%, respectively. : The 5-year survival rates of patients with ALI were equivalent to those with chronic limb threatening ischemia (CLTI). The intervention and long-term outcomes were distinguishable according to etiology.
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http://dx.doi.org/10.3400/avd.oa.19-00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766766PMC
September 2019

Intraoperative modulation of arterial blood flow in a hybrid operating room: A report of three cases.

Clin Case Rep 2019 Oct 15;7(10):1839-1843. Epub 2019 Aug 15.

Department of Surgery, Graduate School of Medicine Tohoku University Sendai Japan.

The preoperative modulation of arterial blood flow is widely performed to prevent massive intraoperative hemorrhage and unstable circulatory dynamics; however, this may cause complications. The intraoperative modulation of arterial blood flow can be performed with operation to reduce the physical and psychological stresses on the patients and improve intraoperative safety.
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http://dx.doi.org/10.1002/ccr3.2355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787820PMC
October 2019

Strategy towards tailored donor tissue-specific pancreatic islet isolation.

PLoS One 2019 10;14(5):e0216136. Epub 2019 May 10.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Background: Optimizing the collagenase G (ColG):collagenase H (ColH) ratio is a key strategy for achieving tailored donor-tissue specific islet isolation. Collagen V (Col V) and collagen III (Col III) are crucial target matrices of ColG and ColH, respectively. We herein investigated the relevance between the expression of target matrices in pancreatic tissues and influence of ColG:ColH ratio on islet isolation outcome.

Methods: Islet isolation was performed in Lewis and SD rats using different ColG:ColH ratios (5:1, 1:1 and 1:5; n = 7/group). The composition of Col III and Col V was examined using immunohistochemical staining, real-time polymerase chain reaction (PCR), Western blotting and mass spectrometry. Chain types in collagen I (Col I) were also assessed using mass spectrometry.

Results: No beneficial effects were observed by increasing the ColG amount, irrespective of the rat strain. In contrast, the islet yield in Lewis rats was considerably increased by high amounts of ColH but decreased in SD rats, suggesting that Lewis pancreas contains more Col III than SD pancreas. Neither immunohistochemical nor real-time PCR showed correlation with isolation outcome. However, Western blotting revealed that Lewis contained considerably higher amount of Col III than SD (p = 0.10). Likewise, Col-I(α1)/Col-III(α1) and Col-I(α2)/Col-III(α1) were significantly lower in Lewis than in SD rats (p = 0.007, respectively). Furthermore, the isolation outcome was considerably correlated with the composition of homotrimeric Col I.

Conclusions: The Col III expression and the composition of homotrimeric Col I in pancreatic tissues determined using mass analyses appeared useful for optimizing the ColG:ColH ratio in islet isolation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216136PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510438PMC
January 2020

A Simple and Useful Predictive Assay for Evaluating the Quality of Isolated Hepatocytes for Hepatocyte Transplantation.

Sci Rep 2019 04 16;9(1):6166. Epub 2019 Apr 16.

Department of Surgery, Tohoku University Graduate School of Medicine, 980-0872, Sendai, Japan.

No optimal assay for assessing isolated hepatocytes before hepatocyte transplantation (HTx) has been established, therefore reliable and rapid assays are warranted. Isolated rat hepatocytes were dipped in a water bath (necrosis model), and were also cultured with Okadaic acid (apoptosis model) or vehicle, followed by cellular assessment including trypan blue exclusion (TBE) viability, ADP /ATP ratio, plating efficiency (PE), DNA quantity and ammonia elimination. Hepatocytes were transplanted into the liver of analbuminemic rats, subsequently engraftment was assessed by serum albumin and the histology of transplanted grafts. In the necrosis model, the ADP/ATP ratio was strongly and negatively correlated with the TBE (R = 0.559, P < 0.001). In the apoptosis model, the ADP/ATP ratio assay, PE, DNA quantification and an ammonia elimination test clearly distinguished the groups (P < 0.001, respectively). The ADP/ATP ratio, PE and DNA quantity were well-correlated and the ammonia elimination was slightly correlated with the transplant outcome. TBE could not distinguish the groups and was not correlated with the outcome. The ADP/ATP ratio assay predicted the transplant outcome. PE and DNA quantification may improve the accuracy of the retrospective (evaluations require several days) quality assessment of hepatocytes. The ADP/ATP ratio assay, alone or with a short-term metabolic assay could improve the efficiency of HTx.
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http://dx.doi.org/10.1038/s41598-019-42720-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467914PMC
April 2019

Pediatric Living-Donor Liver Transplant Recipients without Transition After Reaching Adulthood.

Ann Transplant 2019 Jan 8;24:18-24. Epub 2019 Jan 8.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

BACKGROUND Transition to adult care can trigger certain problems for pediatric liver transplant recipients. At our institution, the same transplant team performs both adult and pediatric liver transplantation and post-transplant care; thus, pediatric liver transplant recipients do not have to be transferred. However, it is unclear whether this system affects the recipient's outcome during the transition period. Therefore, we retrospectively assessed pediatric liver transplant recipients who reached adulthood at our institution. MATERIAL AND METHODS This was a single-center, retrospective study involving consecutive pediatric living-donor liver transplant recipients who reached the age of 18 by October 2017. A total of 36 recipients, 20 females and 16 males, were included in the study. RESULTS The 5- and 10-year patient survival after reaching the age of 18 was 100% and 93%, respectively. All of the 3 patients who died had been suffering from secondary biliary cirrhosis due to biliary stricture. In 5 patients (13.9%), biliary stricture became symptomatic or recurred after reaching the age of 18 years. Late-onset acute rejection and chronic rejection developed in 2 (5.6%) and 4 patients (11.1%), respectively. Only 4 (11.1%) patients were obviously noncompliant. We found no significant association between compliance and rejection or survival. Among the patients who are 18 years old and older, 5 (13.9%) had a psychiatric diagnosis. CONCLUSIONS Pediatric liver transplant recipients who underwent transplant surgery and received post-transplant care at our institution have good long-term outcomes. This suggests that having the same team perform both adult and pediatric transplantation and post-transplant care is beneficial for young adult recipients.
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http://dx.doi.org/10.12659/AOT.911544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338013PMC
January 2019

Surgical strategy for an adult patient with a catecholamine-producing ganglioneuroblastoma and a cerebral aneurysm: a case report.

Surg Case Rep 2018 Sep 17;4(1):119. Epub 2018 Sep 17.

Department of Surgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryou-machi, Aobaku, Sendai, 980-8574, Japan.

Background: Ganglioneuroblastomas, particularly those that produce catecholamine, are extremely rare in adults. Here, we report an interesting surgical case of an adult patient with a catecholamine-producing ganglioneuroblastomas in her adrenal gland, suspected to be a pheochromocytoma, and with a cerebral aneurysm.

Case Presentation: The patient was a 73-year-old woman under treatment for hypertension. During a health check-up, a cystic retroperitoneal tumor was incidentally found in the superior pole of her right kidney. Her blood adrenaline level was slightly elevated, and her urinary adrenaline, noradrenaline, and dopamine levels were above the upper reference limits. In addition, 24-h urinary excretion of metanephrine, normetanephrine, and vanillylmandelic acid were all increased. 123I-Meta-iodobenzylguanidine scintigraphy showed an abnormal accumulation of the marker in the cyst wall. She was, therefore, diagnosed with a pheochromocytoma and scheduled for tumor resection. However, preoperatively, 8-mm-diameter cerebral aneurysm was incidentally found in her basilar artery. This required careful preoperative discussion. The aneurysm was difficult to approach and treat, and based on its position, shape, and size, the risk of rupture was low. Because hypertension is a major risk factor for aneurysmal rupture, we decided to proceed with the tumor resection. A lumbar catheter was placed to monitor the cerebral aneurysm for intraoperative rupture, and her transcranial motor-evoked potential and somatosensory-evoked potentials were monitored to track her intraoperative neurological function. During surgery, we carefully monitored fluctuations in blood pressure and resected the tumor with minimal mobilization. Postoperatively, head computed tomography confirmed that there was no sign of rupture. Histopathologically, the tumor was diagnosed as a catecholamine-producing ganglioneuroblastoma. The postoperative course was good, and the patient's blood pressure improved.

Conclusions: Careful perioperative management is needed for a patient with both a catecholamine-producing tumor and cerebral aneurysm.
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http://dx.doi.org/10.1186/s40792-018-0529-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141414PMC
September 2018

Classical Hodgkin lymphoma-type and monomorphic-type post-transplant lymphoproliferative disorder following liver transplantation: a case report.

Surg Case Rep 2018 Jul 6;4(1):72. Epub 2018 Jul 6.

Department of Pathology, Graduate School of Medicine, Tohoku University, 1-1 Seiryou-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan.

Background: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication that can be difficult to treat; moreover, determination of the pathophysiological type is difficult. We report a rare case of a patient who developed two types of Epstein-Barr virus (EBV)-negative PTLD following living donor liver transplantation (LDLT).

Case Presentation: A 64-year-old man underwent LDLT for acute fulminant hepatitis B. Sixty-five months later, he developed EBV-negative monomorphic B cell PTLD. Reduction of immunosuppressive therapy and chemotherapy with rituximab resulted in a partial response. He received radioimmunotherapy with yttrium-90-ibritumomab tiuxetan, which was effective for all lesions, except for the splenic hilar lesion, which enlarged and seemed to penetrate the stomach. Therefore, he underwent resection of the pancreatic tail with splenectomy and partial gastrectomy. The pathological diagnosis was EBV-negative classical Hodgkin lymphoma (cHL)-type PTLD.

Conclusions: This patient showed an unexpected course of PTLD, from both a clinical and pathological perspective. There are no prior reports of an adult case of EBV-negative cHL-type PTLD coexisting with EBV-negative monomorphic B cell PTLD. When a strange and refractory lesion persists despite effective therapy for PTLD, we must consider the possibility of another type of PTLD within the residual lesion.
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http://dx.doi.org/10.1186/s40792-018-0480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035123PMC
July 2018

Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms.

Hepatol Res 2018 Nov 16;48(12):989-999. Epub 2018 Jul 16.

Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Steroidogenesis In Hepatic Mucinous Cystic Neoplasm: Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.
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http://dx.doi.org/10.1111/hepr.13201DOI Listing
November 2018

Association of post-transplant donor-specific HLA antibody with liver graft fibrosis during long-term follow-up after pediatric liver transplantation.

Pediatr Transplant 2018 05 14;22(3):e13169. Epub 2018 Mar 14.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

The aim of this study was to evaluate the significance of post-transplant DSA as a predictor of liver fibrosis during long-term follow-up after pediatric LT. We evaluated the histological findings in 18 LT recipients who underwent liver biopsy after DSA screening. Liver fibrosis was scored based on the METAVIR fibrosis staging. Patients were divided into 2 groups based on histological findings, and clinical characteristics among patients with liver fibrosis were assessed. Of 18 patients, 7 were included in the fibrosis group. No significant between-group differences were found regarding peritransplant characteristics, including age, sex, primary disease, ABO incompatibility, and immunosuppressive regimen. Episodes of acute rejection and non-adherence to immunosuppressive drugs were comparable between both groups. The MFI for anti-DR DSA and positive rate were significantly higher in the fibrosis group (1655 vs 216; P = .019, 86% vs 27%; P = .012, respectively). MFI for anti-DQ DSA was higher in the fibrosis group, but non-significantly (2052 vs 384; P = .46). Post-transplant anti-DR DSA is associated with graft fibrosis during long-term follow-up. This finding seems useful for the implementation of valid histological examinations of liver grafts for patients with higher MFI, especially for anti-DR DSA, after pediatric LT.
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http://dx.doi.org/10.1111/petr.13169DOI Listing
May 2018

Natural History and Chronological Growth Rate of Renal Artery Aneurysms.

Ann Vasc Dis 2017 Dec;10(4):411-416

Division of Vascular Surgery, Department of Surgery, Tohoku University, Sendai, Miyagi, Japan.

: Renal artery aneurysm (RAA) is an uncommon disease, the natural course of which is still not well known. The objective of this study is to define factors that affect the growth rate of RAAs. : We retrospectively reviewed 32 aneurysms in 26 patients at our institute between January 2010 and March 2016. Basal demographics, comorbidities, reason for diagnosis, and details of the aneurysms and interventions were recorded. The chronological changes in the diameter of the RAA using multiplanar reconstructions of computed tomography images were measured and analyzed. : The baseline mean diameter was 20.1±8.4 mm (range: 9.9-41). The mean follow-up period was 3.13±2.1 y (range: 0.5-7.1). The median growth rate was 0.35 mm/y (interquartile range: 0.05, 0.62). The growth rate was slower when the initial diameter was <20 mm than when it was >20 mm (p=0.036). Also, whole-completed calcification was a significant factor for slower growth (p=0.016). We performed ex-vivo surgery in two cases and coil packing with stenting in one. No ruptures occurred during the study period. : Our results suggest that cases with an RAA diameter <20 mm do not require intervention. The interval period can be longer in whole-completed calcification types.
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http://dx.doi.org/10.3400/avd.oa.17-00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835437PMC
December 2017

The Effects of Short-term Subnormothermic Perfusion After Cold Preservation on Liver Grafts From Donors After Circulatory Death: An Ex Vivo Rat Model.

Transplantation 2018 04;102(4):e147-e154

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: We previously reported that short oxygenated warm perfusion before cold storage (CS) had improved the graft viability of rat livers from donors after circulatory death (DCD). In this study, we investigated the effectiveness of short-term oxygenated subnormothermic perfusion for different durations after CS in a rat DCD model.

Methods: We used an isolated perfused rat liver system. In study 1: the grafts were retrieved from Wistar rats 30 minutes after cardiac arrest (thoracotomy), preserved in CS for 6 hours, and perfused with oxygenated subnormothermic (20-25°C) Krebs-Henseleit buffer for different durations (0, 15, 30, 60, and 90 minutes groups; n = 5 in each). In study 2: in addition to subnormothermic ex vivo liver perfusion (SELP), after 15-minute incubation at room temperature, the grafts were reperfused under normothermic condition for 60 minutes as a model of liver transplantation (0, 30, 60, and 90 minutes groups; n = 5 in each).

Results: In study 1, portal flow, bile production and tissue adenosine triphosphate increased with perfusion duration. In study 2, SELP significantly improved portal flow volume (P <0.05), and bile production (P <0.05), decreased liver enzymes (P <0.05) and cytokines (P <0.0001), and increased tissue adenosine triphosphate (P <0.01). Histological examinations showed that additional SELP ameliorated tissue deterioration, preserved the parenchymal structure, and decreased apoptosis (P <0.01). Furthermore, scanning electron microscopy revealed that additional SELP alleviated sinusoidal endothelial cells and hepatic microvasculature.

Conclusions: Even 30 minutes of SELP after CS rescued DCD livers from ischemia-reperfusion injury, which may help the viability of the grafts.
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http://dx.doi.org/10.1097/TP.0000000000002080DOI Listing
April 2018

The extra-anatomical jump graft reconstruction of the right hepatic artery after resection of a biliary tract malignancy with a common hepatic artery aneurysm: a case report.

Clin Case Rep 2017 11 26;5(11):1841-1846. Epub 2017 Sep 26.

Department of Surgery Tohoku University Sendai Japan.

Performing resection of a biliary tract malignancy with a hepatic artery aneurysm is very challenging. Resection of the extrahepatic bile duct and extra-anatomical reconstruction can be successfully performed using free radial artery autografts from the aorta to the right hepatic artery. Hepatic artery thrombosis can be prevented with intimal preservation.
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http://dx.doi.org/10.1002/ccr3.1200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676259PMC
November 2017

Renoportal Anastomosis in Left Lateral Lobe Living Donor Liver Transplantation: A Pediatric Case.

Case Rep Gastroenterol 2017 Sep-Dec;11(3):584-592. Epub 2017 Sep 27.

Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan.

In adult liver transplantation, renoportal anastomosis (RPA) has been introduced as a useful technique for patients with grade 4 portal vein thrombosis and a splenorenal shunt. Here, we report a pediatric case in which RPA allowed a left lateral lobe living donor liver transplantation (LDLT) despite portal vein thrombosis and a large splenorenal shunt. At 36 days old, the patient underwent a Kasai operation for biliary atresia. At 17 months old, she underwent LDLT because of repetitive cholangitis. Pretransplant examinations revealed a large splenorenal shunt and portal vein thrombosis. Simple end-to-end portal reconstruction and clamping of the collateral route after removing the thrombosis were unsuccessful. Thus, RPA was performed using a donor superficial femoral vein as an interpositional graft. The portal vein pressure was 20 mm Hg after arterial reperfusion. Ligation of the splenic artery reduced the portal vein pressure. Although she developed severe acute cellular rejection and chylous ascites, there were no signs of portal vein complications. She was discharged 73 days after transplantation without any signs of renal dysfunction. The patient's condition was good at her last follow-up, 22 months after transplantation. To our knowledge, this is the youngest case of RPA in pediatric left lateral lobe LDLT. Additionally, this is the first case of RPA with splenic artery ligation and using the donor's superficial femoral vein as the venous graft for RPA. Although long-term follow-up is necessary, RPA could be a salvage option in LDLT in infants if other methods are unsuccessful.
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http://dx.doi.org/10.1159/000481160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662992PMC
September 2017

The Optimization of the Prevascularization Procedures for Improving Subcutaneous Islet Engraftment.

Transplantation 2018 03;102(3):387-395

Division of Advanced Surgical Science and Technology, Tohoku University School of Medicine, Sendai, Japan.

Background: Subcutaneous islet transplantation is associated with minimal invasiveness, but poor vascularization. Thus, the optimization of the prevascularization procedures is crucial for improving the outcomes. Although the effectiveness of basic fibroblast growth factor (bFGF) was reported, the optimal procedures remain unclear. We sought to optimize the prevascularization procedures including the use of a novel scaffold, recombinant peptide (RCP).

Methods: Devices containing various amount of bFGF with/without heparin or RCP were implanted into the subcutaneous space of diabetic C57BL/6 mice. Syngeneic islets were transplanted into the prevascularized space. Blood glucose, intraperitoneal glucose tolerance, and immunohistochemistry were evaluated.

Results: The cure rates in all the device groups irrespective of bFGF doses were considerably higher than in the nondevice group. The cure rate in the bFGF0 group was unexpectedly higher than that in the subcutaneous islet transplant alone group (the None group) (57.1% vs 28.6%). Glucose tolerance was ameliorated in the bFGF10(-), 10(+) and 15(-) groups. The number of von Willebrand factor-positive vessels in the bFGF10(+) group was significantly higher than that in the None and bFGF0 groups (P < 0.01). Taken together, the bFGF10(+) group was considered to have received optimized procedures. In a marginal graft model, the efficiency in the RCP group was better than that in the bFGF10(+) group, furthermore, comparable to that in the intraportal transplantation group. Unlike bFGF, no bleeding and effusion were observed in the RCP group.

Conclusions: These results suggest that optimizing biomaterials to induce efficient prevascularization could be a novel strategy for improving subcutaneous islet transplantation.
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http://dx.doi.org/10.1097/TP.0000000000001970DOI Listing
March 2018

Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability.

Transplant Direct 2017 Aug 11;3(8):e196. Epub 2017 Jul 11.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: In pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression.

Methods: We retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013. Patients were divided into 2 groups based on the CNI trough level. The cutoff trough levels were 3 and 30 ng/mL for tacrolimus and cyclosporine, respectively. Luminex single-antigen bead assays were performed, and the cutoff for a positive reaction was set at a mean fluorescence intensity (MFI) of at least 1000.

Results: The mean recipient ages at the time of LT were 29.1 and 77.2 months for the low and regular CNI groups, respectively ( = 0.0007). Univariate logistic regression analysis revealed that recipient age at LT younger than 3 years ( = 0.0099) and low CNI ( < 0.0001) were significantly associated with DSA development. In multivariate analysis, low CNI was an independent risk factor of DSA development ( = 0.0011). Of 15 high-MFI DSAs, 3 were anti-DR, and 12 were anti-DQ. Two of 3 anti-DR DSAs and 11 of 12 anti-DQ DSAs had complement-binding ability and high MFIs.

Conclusions: CNI minimization was an independent risk factor for posttransplant DSA during long-term follow-up after pediatric LT. Adjusting CNI to appropriate levels is a safe first step to prevent the immunological effects of DSA.
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http://dx.doi.org/10.1097/TXD.0000000000000713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540634PMC
August 2017

The Optimization of Short-Term Hepatocyte Preservation Before Transplantation.

Transplant Direct 2017 Jul 19;3(7):e176. Epub 2017 Jun 19.

Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: No optimal methods for short-term hepatocyte preservation have been established. We have recently developed a prominent oxygen-permeable bag (Tohoku Device [TD]) for pancreatic islet culture and transplantation. In this study, we investigated whether TD is also effective for hepatocyte preservation and tried to optimize other conditions.

Methods: Hepatocytes were preserved in the following conditions, and their outcomes were observed. First, the effectiveness of TD was investigated. Second, hepatocyte medium (HM) and organ preservation solutions with or without fetal bovine serum (FBS) were compared. Third, as supplementations, FBS and human serum albumin (HSA) were compared. Fourth, low, room and high temperature were compared. And finally, hepatocytes preserved in various conditions were transplanted into the subrenal capsule space of nonalbumin rats and engrafted areas were assessed.

Results: The survival rate of hepatocytes preserved in TD tended to be higher and their viability and function were maintained significantly greater than those of non-TD group. Irrespective of FBS supplementation, the survival rate of HM group was significantly higher than those of organ preservation solution group while viabilities and plating efficiency were similar among them. Although survival rates of groups without FBS were extremely low, results of HSA supplemented group were not inferior to FBS supplemented group. Hepatocytes preserved at high temperature had the worst results. The engrafted area of TD group tended to be higher than those of other groups.

Conclusions: TD is effective for short-term hepatocyte preservation. HSA is a useful substitute for FBS, and preserving in HM at low temperature is recommended.
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http://dx.doi.org/10.1097/TXD.0000000000000687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498017PMC
July 2017