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2. Carbon dioxide embolism associated with transanal total mesorectal excision surgery: A report from the international registries

Author

Dickson, E. A., Penna, M., Cunningham, C., Ratcliffe, F. M., Chantler, J., Crabtree, N. A., Tuynman, J. B., Albert, M. R., Monson, J. R. T., Hompes, R., Abdelmoaty, W., Adamina, M., Aigner, F., Alavi, K., Albers, B., Al Furajii, H., Allison, A., Eduardo, S., Araujo, A., Apostolides, G. Y., Arezzo, A., Arnold, S. J., Aryal, K., Ashamalla, S., Ashraf, Sana, Attaluri, V., Austin, R., Barugo-La, G., Beggs, A., Belgers, H. J., Bell, S., Bemelman, W., Berti, S., Biebl, M., Blondeel, J., Binky, B., Baloyiannis, I. -N., Bandyopadhyay, D., Boni, L., Bordeianou, L., Box, B., Boyce, S., Brokelman, W., Brown, C. J., Bruegger, L., Buchli, C., Christian Buchs, N., Bulut, O., Burt, C., Bursics, A., Cahill, R. A., Pablo Campana, J., Caricato, M., Caro-Tar-Rago, A., Casans, F., Cassinotti, E., Caycedo-Marulan-Da, A., Chadi, S. A., Chandrasinghe, P., Chaudhri, S., Chaumont, N., Chitsabesan, P., Coget, J., Collera, P., Coleman, M., Courtney, E. D., Dagbert, F., Dalton, S. J., Daniel, G., Clark, D. A., De-Drye, L., De La Torre, J., Dapri, G., Dayal, S. P., De Chaisemartin, C., Borja De Lacy, F., Blasco Delgado, O., Di Candido, F., Diaz Del Gobbo, G., De Graaf, E. J. R., Delrio, P., De Pooter, K., D'Hooge, P., Doornebosch, P., Duff, S., Du Jardin, P., Dzhumabaev, K. E., Tom Edwards, M., Egenvall, I., Espin, E., Eugenio, M., Egenvall, M. -I., Ravn Eriksen, J., Faerden, A. E., Faes, S., Simo Fernandez, V., Fichera, A., Fierens, J., Fierens, K., Forgan, T., Francis, N., Francombe, J., Francone, E., Francone, T., Gamage, B., Perez Garcia, J. A., Ethem Gecim, I., Van Geluwe, B., Gin-Gert, C., George, V., Gloeckler, M., Gogenur, I., Goulart, A., Grolich, T., Haas, E., Hameed, U., Hahnloser, D., Harikrishnan, A., Harris, G., Haunold, I., Hendrickse, C., Hendrickx, T., Heyns, M., Horwood, J., Huerga, D., Ito, M., Jarimba, A., Joeng, H. K. M., Jones, O., Jutten, G., Kala, Z., Kita, Y., Knol, J., Thengugal Kochupapy, R., Kneist, W., Kok, A. S. Y., Kusters, M., Lacy, A. M., Laka-Tos, M., Lal, R., Lakkis, Z., Leao, P., Lambrechts, A., Lee, L., Lelong, B., Leung, E., Lezoche, E., Sender Liberman, A., Lidder, P., An-Drade Lima, M., Loganathan, A., Lombana, L. J., Lorenzon, Laura, Loriz, H., Lukas, M., Lutrin, D., Mackey, P., Mamedli, Z. Z., Mansfield, S., Marcello, P., Marcoen, S., Romero Marcos, J. M., Marcy, T., Marecik, S., Marks, J., Marsanic, P., Mattacheo, A., Maun, D., May, D., Maykel, J. A., Mcarthur, D., Mccallum, I., Mccarthy, K., Mclemore, E. C., Ramon Sil-Viera Mendes, C., Messaris, E., Michalopoulos, A., Mikalauskas, S., Miles, A., Millan, M., Mills, S., Miskovic, D., Montroni, I., Moore, E., Moore, T., Mori, Simona, Morino, M., Muratore, A., Mutafchiyski, V., Myers, A., Van Nieuwenhove, Y., Nishizawa, Y., Ng, P., John Nolan, G., Obias, V., Ochsner, A., Hwan Oh, J., Onghena, T., Oommen, S., Orkin, B. A., Osman, K., Ouro, S., Panis, Y., Papavramidis, T., Von Papen, M., Papp, G., Paquette, I., Paraoan, M. T., Paredes, J. P., Pastor, C., Pattyn, P. R. L., Karim Perdawood, S., Wan Pei, C. F., Piehslinger, J., Penchev, D., Oliva Perez, R., Persiani, Roberto, Pfeffer, F., Terry Phang, P., Pokela, V., Picchetto, A., Poskus, E., Prieto, D., Que-Reshy, F. A., Ramcharan, S., Rauch, S., Rega, D., Reyes, J. C., Ris, F., Delgado Rivilla, S., Alexander Rockall, T., Roquete, P., Rossi, G., Ruffo, G., Sakai, Y. -S., Sands, D., Sao Juliao, G. P., Scala, Alessandro, Scala, D., Estevez Schwarz, L., Edmond Seid, V., Seitinger, G., Shaikh, I. A., Sharma, A., Siet-Ses, C., Singh, B., Helmer Sjo, O., Kyung Sohn, D., Sora-Via, C., Sosef, M. N., Spinelli, A., Speakman, C., Steele, S., Stephan, V., Stevenson, A. R. L., Stotland, P., Studer, P., Strypstein, S., Sylla, P., Szyszkowitz, A., Talwar, A., Tanis, P., Tejedor, P., Pastor Teso, E., Tognelli, J., Torkington, J., Tschann, P., Tuech, J. -J., Tuerler, A., Tzovaras, G., Ugolini, G., Vallribera, F., Vansteenkiste, F., Vangenechten, E., Verdaasdonk, E. G. G., Vilela, N., Walter, B., Warren, O. J., Visser, T., Warrier, S., Warner, M., Waru-Savitarne, J., Whiteford, M. H., Andreas Wik, T., Witzig, J. -A., Wolff, T., Wolthuis, A. M., Wynn, G., Ashraf S., Lorenzon L. (ORCID:0000-0001-6736-0383), Mori S., Persiani R. (ORCID:0000-0002-1537-5097), Scala A., Dickson, E. A., Penna, M., Cunningham, C., Ratcliffe, F. M., Chantler, J., Crabtree, N. A., Tuynman, J. B., Albert, M. R., Monson, J. R. T., Hompes, R., Abdelmoaty, W., Adamina, M., Aigner, F., Alavi, K., Albers, B., Al Furajii, H., Allison, A., Eduardo, S., Araujo, A., Apostolides, G. Y., Arezzo, A., Arnold, S. J., Aryal, K., Ashamalla, S., Ashraf, Sana, Attaluri, V., Austin, R., Barugo-La, G., Beggs, A., Belgers, H. J., Bell, S., Bemelman, W., Berti, S., Biebl, M., Blondeel, J., Binky, B., Baloyiannis, I. -N., Bandyopadhyay, D., Boni, L., Bordeianou, L., Box, B., Boyce, S., Brokelman, W., Brown, C. J., Bruegger, L., Buchli, C., Christian Buchs, N., Bulut, O., Burt, C., Bursics, A., Cahill, R. A., Pablo Campana, J., Caricato, M., Caro-Tar-Rago, A., Casans, F., Cassinotti, E., Caycedo-Marulan-Da, A., Chadi, S. A., Chandrasinghe, P., Chaudhri, S., Chaumont, N., Chitsabesan, P., Coget, J., Collera, P., Coleman, M., Courtney, E. D., Dagbert, F., Dalton, S. J., Daniel, G., Clark, D. A., De-Drye, L., De La Torre, J., Dapri, G., Dayal, S. P., De Chaisemartin, C., Borja De Lacy, F., Blasco Delgado, O., Di Candido, F., Diaz Del Gobbo, G., De Graaf, E. J. R., Delrio, P., De Pooter, K., D'Hooge, P., Doornebosch, P., Duff, S., Du Jardin, P., Dzhumabaev, K. E., Tom Edwards, M., Egenvall, I., Espin, E., Eugenio, M., Egenvall, M. -I., Ravn Eriksen, J., Faerden, A. E., Faes, S., Simo Fernandez, V., Fichera, A., Fierens, J., Fierens, K., Forgan, T., Francis, N., Francombe, J., Francone, E., Francone, T., Gamage, B., Perez Garcia, J. A., Ethem Gecim, I., Van Geluwe, B., Gin-Gert, C., George, V., Gloeckler, M., Gogenur, I., Goulart, A., Grolich, T., Haas, E., Hameed, U., Hahnloser, D., Harikrishnan, A., Harris, G., Haunold, I., Hendrickse, C., Hendrickx, T., Heyns, M., Horwood, J., Huerga, D., Ito, M., Jarimba, A., Joeng, H. K. M., Jones, O., Jutten, G., Kala, Z., Kita, Y., Knol, J., Thengugal Kochupapy, R., Kneist, W., Kok, A. S. Y., Kusters, M., Lacy, A. M., Laka-Tos, M., Lal, R., Lakkis, Z., Leao, P., Lambrechts, A., Lee, L., Lelong, B., Leung, E., Lezoche, E., Sender Liberman, A., Lidder, P., An-Drade Lima, M., Loganathan, A., Lombana, L. J., Lorenzon, Laura, Loriz, H., Lukas, M., Lutrin, D., Mackey, P., Mamedli, Z. Z., Mansfield, S., Marcello, P., Marcoen, S., Romero Marcos, J. M., Marcy, T., Marecik, S., Marks, J., Marsanic, P., Mattacheo, A., Maun, D., May, D., Maykel, J. A., Mcarthur, D., Mccallum, I., Mccarthy, K., Mclemore, E. C., Ramon Sil-Viera Mendes, C., Messaris, E., Michalopoulos, A., Mikalauskas, S., Miles, A., Millan, M., Mills, S., Miskovic, D., Montroni, I., Moore, E., Moore, T., Mori, Simona, Morino, M., Muratore, A., Mutafchiyski, V., Myers, A., Van Nieuwenhove, Y., Nishizawa, Y., Ng, P., John Nolan, G., Obias, V., Ochsner, A., Hwan Oh, J., Onghena, T., Oommen, S., Orkin, B. A., Osman, K., Ouro, S., Panis, Y., Papavramidis, T., Von Papen, M., Papp, G., Paquette, I., Paraoan, M. T., Paredes, J. P., Pastor, C., Pattyn, P. R. L., Karim Perdawood, S., Wan Pei, C. F., Piehslinger, J., Penchev, D., Oliva Perez, R., Persiani, Roberto, Pfeffer, F., Terry Phang, P., Pokela, V., Picchetto, A., Poskus, E., Prieto, D., Que-Reshy, F. A., Ramcharan, S., Rauch, S., Rega, D., Reyes, J. C., Ris, F., Delgado Rivilla, S., Alexander Rockall, T., Roquete, P., Rossi, G., Ruffo, G., Sakai, Y. -S., Sands, D., Sao Juliao, G. P., Scala, Alessandro, Scala, D., Estevez Schwarz, L., Edmond Seid, V., Seitinger, G., Shaikh, I. A., Sharma, A., Siet-Ses, C., Singh, B., Helmer Sjo, O., Kyung Sohn, D., Sora-Via, C., Sosef, M. N., Spinelli, A., Speakman, C., Steele, S., Stephan, V., Stevenson, A. R. L., Stotland, P., Studer, P., Strypstein, S., Sylla, P., Szyszkowitz, A., Talwar, A., Tanis, P., Tejedor, P., Pastor Teso, E., Tognelli, J., Torkington, J., Tschann, P., Tuech, J. -J., Tuerler, A., Tzovaras, G., Ugolini, G., Vallribera, F., Vansteenkiste, F., Vangenechten, E., Verdaasdonk, E. G. G., Vilela, N., Walter, B., Warren, O. J., Visser, T., Warrier, S., Warner, M., Waru-Savitarne, J., Whiteford, M. H., Andreas Wik, T., Witzig, J. -A., Wolff, T., Wolthuis, A. M., Wynn, G., Ashraf S., Lorenzon L. (ORCID:0000-0001-6736-0383), Mori S., Persiani R. (ORCID:0000-0002-1537-5097), and Scala A. more...

Abstract

BACKGROUND: Carbon dioxide embolus has been reported as a rare but clinically important risk associated with transanal total mesorectal excision surgery. To date, there exists limited data describing the incidence, risk factors, and management of carbon dioxide embolus in transanal total mesorectal excision. OBJECTIVE: This study aimed to obtain data from the transanal total mesorectal excision registries to identify trends and potential risk factors for carbon dioxide embolus specific to this surgical technique. DESIGN: Contributors to both the LOREC and OSTRiCh transanal total mesorectal excision registries were invited to report their incidence of carbon dioxide embolus. Case report forms were collected detailing the patient-specific and technical factors of each event. SETTINGS: The study was conducted at the collaborating centers from the international transanal total mesorectal excision registries. MAIN OUTCOME MEASURES: Characteristics and outcomes of patients with carbon dioxide embolus associated with transanal mesorectal excision were measured. RESULTS: Twenty-five cases were reported. The incidence of carbon dioxide embolus during transanal total mesorectal excision is estimated to be ≈0.4% (25/6375 cases). A fall in end tidal carbon dioxide was noted as the initial feature in 22 cases, with 13 (52%) developing signs of hemodynamic compromise. All of the events occurred in the transanal component of dissection, with mean (range) insufflation pressures of 15 mm Hg (12-20 mm Hg). Patients were predominantly (68%) in a Trendelenburg position, between 30° and 45°. Venous bleeding was reported in 20 cases at the time of carbon dioxide embolus, with periprostatic veins documented as the most common site (40%). After carbon dioxide embolus, 84% of cases were completed after hemodynamic stabilization. Two patients required cardiopulmonary resuscitation because of cardiovascular collapse. There were no deaths. LIMITATIONS: This is a retrospective study surveying r more...

Published
2019

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4. Laparoscopic common bile duct exploration for common bile duct stones after gastric surgery.

Author

De Raeymaeker X, Blondeel J, Houben B, Karimi A, Appeltans B, and Sergeant G

Abstract

Background: Gallstone disease is common after gastric surgery and especially after weight loss from bariatric surgery. In patients with normal gastroduodenal anatomy, treatment of common bile duct stones (CBS) generally consists of, endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic sphincterotomy (ES), followed by cholecystectomy in a second stage. However, after gastric surgery the papilla may not be easily accessible endoscopically. The aim of our study was to evaluate the therapeutic success of single-stage laparoscopic cholecystectomy and common bile duct exploration (LCBDE) after previous gastric surgery., Methods: In this observational cohort study, all LCBDE in patients with previous gastric surgery between January 2014 and July 2022 were retrospectively reviewed. Gastric surgery consisted of Roux-en-Y gastric bypass, BII subtotal gastrectomy, total gastrectomy and subtotal gastrectomy with Roux-en-Y reconstruction. Outcomes of interest consisted of successful duct clearance, postoperative adverse events and CBS recurrence., Results: Forty-four patients (M/F: 22/22) underwent LCBDE after previous gastric surgery, in which simultaneous cholecystectomy was performed in 38 cases. Median (range) age 68 (25-90) years. Presence of CBS was confirmed in 38 patients (85%), a choledochal polyp in one patient (2%) and recurrence of gastric cancer in another (2%). Duct clearance was successful in 37 out of 38 patients (97%). Median (range) length of stay after LCBDE was 1 (0-12) day(s). Eight patients developed a postoperative adverse event, of which three Clavien-Dindo > 3a complications. Three patients were readmitted. At a median (range) follow-up of 60 (24-120) months, no CBS recurrences were observed., Conclusions: LCBDE is a safe technique, with a high rate of successful duct clearance after previous gastric surgery, even after previous cholecystectomy. In experienced centers, LCBDE provides a valid alternative for complex interventional endoscopy, omitting the need for the creation of a gastro-gastric fistula., Competing Interests: Declarations. Disclosures: Xavier De Raeymaeker, Joris Blondeel, Bert Houben, Amine Karimi, Bart Appeltans and Gregory Sergeant have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

Published
2025
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5. Dynamic Preservation of Donation After Circulatory Death Liver Grafts From Donors Aged 60 y and Older.

Author

Blondeel J, van Leeuwen OB, Schurink IJ, Lantinga VA, Gilbo N, de Goeij FHC, Pirenne J, Huurman VAL, de Meijer VE, de Jonge J, Porte RJ, and Monbaliu D

Abstract

Background: Donor livers from older donation after circulatory death (DCD) donors are frequently discarded for transplantation because of the high risk of graft failure. It is unknown whether DCD livers from older donors benefit from dynamic preservation., Methods: In a multicenter study, we retrospectively compared graft and patient outcomes after transplantation of livers from DCD donors older than 60 y, preserved with either static cold storage (SCS), ex situ sequential dual hypothermic perfusion, controlled oxygenated rewarming, and normothermic perfusion (DHOPE-COR-NMP), or in situ abdominal normothermic regional perfusion (aNRP)., Results: Fifty-six liver transplants were included in the SCS cohort, 33 in the DHOPE-COR-NMP cohort, and 27 in the aNRP cohort. Donor warm ischemia time was significantly shorter in the SCS group than in DHOPE-COR-NMP (P < 0.001) and aNRP (P < 0.001) groups. Cold ischemia times were similar. One-year incidence of nonanastomotic biliary strictures was lower after DHOPE-COR-NMP (3%, P = 0.03) or aNRP (7%, P = 0.13), compared with SCS alone (21%). Anastomotic strictures were less frequent in aNRP (19%) compared with DHOPE-COR-NMP (52%; P = 0.015). One-year graft and patient survival were similar., Conclusions: Dynamic preservation allows safe transplantation of livers from DCD donors aged 60 y or older. The risk of nonanastomotic strictures was significantly lower after DHOPE-COR-NMP than after SCS, despite longer donor warm ischemia times., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.) more...

Published
2024
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6. The dynamics of cytokine release during 24 hours continuous normothermic machine perfusion liver preservation: An explorative porcine study.

Author

Gilbo N, Blondeel J, Wylin T, Heedfeld V, Jochmans I, Pirenne J, Korf H, and Monbaliu D

Subjects
Animals, Swine, Reperfusion Injury prevention & control, Reperfusion Injury metabolism, Cytokines metabolism, Organ Preservation methods, Organ Preservation instrumentation, Perfusion methods, Perfusion instrumentation, Liver metabolism, Liver Transplantation methods
Abstract

Background: Normothermic machine perfusion (NMP) has been proposed to preserve liver grafts in a less pro-inflammatory environment. However, the effect of NMP on liver inflammation remains unclear. Therefore, we aimed at characterizing the inflammatory response during continuous NMP with a comprehensive investigation of cytokine release during perfusion., Methods: Ten porcine livers underwent either 24 h NMP or whole blood-based NMP (WB-NMP) immediately after procurement. WB-NMP was used as a positive control to mimic early post-reperfusion inflammation. High mobility group box-1 (HMGB1), interleukin 1-beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha), interleukin 6 (IL-6), 8 (IL-8), and 10 (IL-10), transforming growth factor-beta (TGFbeta), aspartate transferase (AST), and hyaluronic acid were measured in the perfusate. The area under the curve (AUC) of their perfusate concentration was compared between groups. Median (IQR) is given., Results: The AUC of HMGB1 and IL-1beta was similar between groups. Compared to WB-NMP, NMP inhibited the release of TNFalpha [NMP: 20275 (18402-32 152), WB-NMP: 242100 (203511-244 238); p = 0.01], IL-6 [NMP: 1206 (338.9-1686), WB-NMP: 8444 (7359-10 087); p = 0.03], and IL-8 [NMP: 1635 (106.90-2130), WB-NMP: 3951 (3090-4116); p = 0.008]. The release of TGFbeta remained unchanged but IL-10 release was lower in NMP [1612 (1313-1916), WB-NMP: 5591 (4312-6421); p = 0.01]. The ratios TGFbeta:TNFalpha and IL-10:TNFalpha were significantly higher in the NMP than in the WB-NMP group. Importantly, the AUC of AST was significantly lower during NMP [1960 (1950-2893)] than WB-NMP [6812 (6370-7916); p = 0.02]., Conclusions: Continuous NMP leads to the release of detectable levels of cytokines with a slow, linear increase over time and a shift toward anti-inflammatory signaling., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.) more...

Published
2024
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7. Simultaneous Lung-abdominal Organ Procurement From Donation After Circulatory Death Donors Reduces Donor Hepatectomy Time.

Author

Blondeel J, Blondeel M, Gilbo N, Vandervelde CM, Fieuws S, Jochmans I, Van Raemdonck D, Pirenne J, Ceulemans LJ, and Monbaliu D

Subjects
Humans, Hepatectomy adverse effects, Retrospective Studies, Constriction, Pathologic, Tissue Donors, Liver surgery, Graft Survival, Lung, Death, Brain Death, Primary Graft Dysfunction, Tissue and Organ Procurement
Abstract

Background: Prolonged organ procurement time impairs the outcome of donation after circulatory death (DCD) and liver transplantation (LiT). Our transplant team developed a simultaneous, rather than sequential, lung-abdominal organ explantation strategy for DCD donation to prioritize liver procurement. We evaluated whether this change in strategy effectively reduced donor hepatectomy time (dHT), without affecting donor pneumonectomy time (dPT), and influenced LiT and lung transplantation outcome., Methods: All lung-abdominal and abdominal-only transplant procedures between 2010 and 2020 were analyzed in this retrospective cohort study. Relationships were assessed between the year of transplant and dHT and dPT (univariate linear regression), 1-y patient and graft survival, primary graft dysfunction, and nonanastomotic biliary strictures (univariate logistic regression)., Results: Fifty-two lung-abdominal and 110 abdominal-only DCD procedures were analyzed. A significant decrease in dHT was noted in lung-abdominal (slope -1.14 [-2.14; -0.15], P = 0.026) but not in abdominal-only procedures; dPT did not increase. There were no significant associations between the year of transplant and nonanastomotic biliary strictures frequency, primary graft dysfunction incidence, 1-y patient, and graft survival., Conclusions: Simultaneous organ procurement in multiorgan lung-abdominal DCD procedures is feasible, and effectively shortened dHT without affecting lung transplantation outcome. No impact on LiT outcome was observed; however, larger multicenter studies are needed., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.) more...

Published
2024
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8. Organ Repair and Regeneration During Ex Situ Dynamic Preservation: The Future is Nano.

Author

Gilbo N, Blondeel J, Pirenne J, Romagnoli R, Camussi G, and Monbaliu D

Subjects
Humans, Organ Preservation methods, Regeneration, Perfusion methods, Organ Transplantation, Mesenchymal Stem Cell Transplantation methods
Abstract

Organ preservation and assessment with machine perfusion (MP) has provided transplant physicians with the ability to evaluate and select grafts suitable for transplantation. Nevertheless, the discard of organs considered too damaged still sustains the imbalance between donor organs supply and demands. Therefore, there is the pressing clinical need for strategies to repair and/or regenerate organs before transplantation, and MP is uniquely positioned to satisfy this need. The systemic administration of mesenchymal stromal cells (MSC) was shown to reduce ischemia-reperfusion injury in pre-clinical organ transplant models but could not be reproduced in clinical transplantation, largely because of inefficient cell delivery. The administration of MSC during MP is one strategy that recently gained much attention as an alternative delivery method to target MSC directly to the donor organ. However, careful reinterpretation of preliminary results reveals that this approach is equally limited by a suboptimal delivery of short-lived MSC to the target organ. In contrast, the use of MSC secretome and/or extracellular vesicles therapy during MP seems to be more efficient in harnessing MSC properties during MP. In this mini review we speculate on the future of the novel niche of ex situ organ repair and regeneration before transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gilbo, Blondeel, Pirenne, Romagnoli, Camussi and Monbaliu.) more...

Published
2023
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9. Stem cell Derived Extracellular Vesicles to Alleviate ischemia-reperfusion Injury of Transplantable Organs. A Systematic Review.

Author

Blondeel J, Gilbo N, De Bondt S, and Monbaliu D

Abstract

Background: The possible beneficial effects of stem cell-derived EV on ischemia-reperfusion injury (IRI) in organ transplantation have been frequently investigated; however, the source of EV, as well as the methods of isolation and administration vary widely. We conducted a systematic review to summarize current pre-clinical evidence on stem cell-derived EV therapy for IRI of transplantable organs., Methods: PubMed, Embase and Web of Science were searched from inception until August 19th, 2022, for studies on stem cell-derived EV therapy for IRI after heart, kidney, liver, pancreas, lung and intestine transplantation. The Systematic Review Center for Laboratory animal Experiments (SYRCLE) guidelines were followed to assess potential risk of bias., Results: The search yielded 4153 unique articles, of which 96 were retained. We identified 32 studies on cardiac IRI, 38 studies on renal IRI, 21 studies on liver IRI, four studies on lung IRI and one study on intestinal IRI. Most studies used rodent models of transient ischemic injury followed by in situ reperfusion. In all studies, EV therapy was associated with improved outcome albeit to a variable degree. EV-therapy reduced organ injury and improved function while displaying anti-inflammatory-, immunomodulatory- and pro-regenerative properties., Conclusion: A multitude of animal studies support the potential of stem cell-derived EV-therapy to alleviate IRI after solid organ transplantation but suffer from low reporting quality and wide methodological variability. Future studies should focus on determining optimal stem cell source, dosage, and timing of treatment, as well as long-term efficacy in transplant models., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

Published
2023
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10. The Distinct Innate Immune Response of Warm Ischemic Injured Livers during Continuous Normothermic Machine Perfusion.

Author

Blondeel J, Gilbo N, Heedfeld V, Wylin T, Libbrecht L, Jochmans I, Pirenne J, Korf H, and Monbaliu D

Subjects
Perfusion, Reperfusion, Cytokines, Liver, Immunity, Innate
Abstract

Although normothermic machine perfusion (NMP) provides superior preservation of liver grafts compared to static cold storage and allows for viability testing of high-risk grafts, its effect on the liver immune compartment remains unclear. We investigated the innate immune response during 6 h of continuous NMP (cNMP) of livers that were directly procured (DP, n = 5) or procured after 60 min warm ischemia (WI, n = 5), followed by 12 h of whole blood (WB) reperfusion. WI livers showed elevated transaminase levels during cNMP but not after WB reperfusion. Perfusate concentrations of TNF-α were lower in WI livers during cNMP and WB reperfusion, whereas IL-8 concentrations did not differ significantly. TGF-β concentrations were higher in WI livers during NMP but not after WB reperfusion, whereas IL-10 concentrations were similar. Endoplasmic stress and apoptotic signaling were increased in WI livers during cNMP but not after WB reperfusion. Additionally, neutrophil mobilization increased to a significantly lesser extent in WI livers at the end of NMP. In conclusion, WI livers exhibit a distinct innate immune response during cNMP compared to DP livers. The cytokine profile shifted towards an anti-inflammatory phenotype during cNMP and WB reperfusion, and pro-apoptotic signaling was stronger during cNMP. During WB reperfusion, livers exhibited a blunted cytokine release, regardless of ischemic damage, supporting the potential reconditioning effect of cNMP. more...

Published
2023
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11. Case report: Immediate revascularization for symptomatic hepatic artery pseudoaneurysm after orthotopic liver transplantation? A case series and literature review.

Author

Lerut AV, Pirenne J, Sainz-Barriga M, Blondeel J, Maleux G, and Monbaliu D

Abstract

Introduction: Hepatic artery pseudoaneurysm (HAPA), a rare vascular complication that can develop after liver transplantation, is associated with a high mortality rate and graft loss. To salvage the liver graft, immediate revascularization, either through surgical or endovascular intervention, is required. However, currently there is no consensus on the optimal strategy. Here, we report three cases of liver transplant recipients diagnosed with HAPA and treated with immediate revascularization. In addition, we present an overview of HAPA cases described in the literature and make recommendations on how to treat this rare complication., Methods: All adults transplanted in our center between 2005 and 2021 were retrospectively reviewed. Literature search was done in PubMed for original studies between 1980 and 2021 reporting early hepatic artery (pseudo) aneurysm after liver transplantation requiring either surgical or endovascular intervention., Results: From a total of 1,172, 3 liver transplant patients were identified with a symptomatic HAPA and treated with immediate revascularization. HAPA occurred 73, 27, and 8 days after liver transplantation and was treated with immediate revascularization (two surgical and one endovascular intervention). Literature review identified 127 cases of HAPA. HAPA was managed with endovascular therapy in 20 cases and by surgical intervention in 89 cases. Overall reported mortality rate was 39.6%, whereas overall graft survival was 45.2%., Conclusion: Immediate surgical or radiological interventional excision and prompt revascularization to salvage liver grafts is feasible but still associated with a high mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lerut, Pirenne, Sainz-Barriga, Blondeel, Maleux and Monbaliu.) more...

Published
2023
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12. Porcine Normothermic Isolated Liver Perfusion.

Author

Blondeel J, Gilbo N, Wylin T, Heedfeld V, and Monbaliu D

Subjects
Humans, Swine, Animals, Liver surgery, Liver physiology, Perfusion, Warm Ischemia, Organ Preservation, Liver Transplantation
Abstract

Porcine models of liver ex situ normothermic machine perfusion (NMP) are increasingly being used in transplant research. Contrary to rodents, porcine livers are anatomically and physiologically close to humans, with similar organ size and bile composition. NMP preserves the liver graft at near-to-physiological conditions by recirculating a warm, oxygenated, and nutrient-enriched red blood cell-based perfusate through the liver vasculature. NMP can be used to study ischemia-reperfusion injury, preserve a liver ex situ before transplantation, assess the liver's function prior to implantation, and provide a platform for organ repair and regeneration. Alternatively, NMP with a whole blood-based perfusate can be used to mimic transplantation. Nevertheless, this model is labor-intensive, technically challenging, and carries a high financial cost. In this porcine NMP model, we use warm ischemic damaged livers (corresponding to donation after circulatory death). First, general anesthesia with mechanical ventilation is initiated, followed by the induction of warm ischemia by clamping the thoracic aorta for 60 min. Cannulas inserted in the abdominal aorta and portal vein allow flush-out of the liver with cold preservation solution. The flushed-out blood is washed with a cell saver to obtain concentrated red blood cells. Following hepatectomy, cannulas are inserted in the portal vein, hepatic artery, and infra-hepatic vena cava and connected to a closed perfusion circuit primed with a plasma expander and red blood cells. A hollow fiber oxygenator is included in the circuit and coupled to a heat exchanger to maintain a pO2 of 70-100 mmHg at 38 °C. NMP is achieved by a continuous flow directly through the artery and via a venous reservoir through the portal vein. Flows, pressures, and blood gas values are continuously monitored. To evaluate the liver injury, perfusate and tissue are sampled at predefined time points; bile is collected via a cannula in the common bile duct. more...

Published
2023
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13. Dynamic liver preservation: Are we still missing pieces of the puzzle?

Author

Blondeel J, Monbaliu D, and Gilbo N

Subjects
Humans, Organ Preservation adverse effects, Perfusion adverse effects, Liver surgery, Reperfusion Injury etiology, Reperfusion Injury prevention & control, Liver Transplantation adverse effects
Abstract

To alleviate the persistent shortage of donor livers, high-risk liver grafts are increasingly being considered for liver transplantation. Conventional preservation with static cold storage falls short in protecting these high-risk livers from ischemia-reperfusion injury, as evident from higher rates of post-transplant complications such as early allograft dysfunction and ischemic cholangiopathy. Moreover, static cold storage does not allow for a functional assessment of the liver prior to transplantation. To overcome these limitations, dynamic strategies of liver preservation have been proposed, designed to provide a protective effect while allowing pre-transplant functional assessment. In this review, we discuss how different dynamic preservation strategies exert their effects, where we stand in assessing liver function and what challenges are lying ahead., (© 2022 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.) more...

Published
2023
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15. Differences in ball speed and three-dimensional kinematics between male and female handball players during a standing throw with run-up.

Author

Serrien B, Clijsen R, Blondeel J, Goossens M, and Baeyens JP

Abstract

Background: The purpose of this paper was to examine differences in ball release speed and throwing kinematics between male and female team-handball players in a standing throw with run-up. Other research has shown that this throwing type produces the highest ball release speeds and comparing groups with differences in ball release speed can suggest where this difference might come from. If throwing technique differs, perhaps gender-specific coordination- and strength-training guidelines are in order., Methods: Measurements of three-dimensional kinematics were performed with a seven-camera VICON motion capture system and subsequent joint angles and angular velocities calculations were executed in Mathcad. Data-analysis with Statistical Parametric Mapping allowed us to examine the entire time-series of every variable without having to reduce the data to certain scalar values such as minima/maxima extracted from the time-series., Results: Statistical Parametric Mapping enabled us to detect several differences in the throwing kinematics (12 out of 20 variables had one or more differences somewhere during the motion). The results indicated two distinct strategies in generating and transferring momentum through the kinematic chain. Male team-handball players showed more activity in the transverse plane (pelvis and trunk rotation and shoulder horizontal abduction) whereas female team-handball players showed more activity in the sagital plane (trunk flexion). Also the arm cocking maneuver was quite different., Conclusions: The observed differences between male and female team handball players in the motions of pelvis, trunk and throwing arm can be important information for coaches to give feedback to athletes. Whether these differences contribute to the observed difference in ball release speed is at the present unclear and more research on the relation with anthropometric profile needs to be done. Kinematic differences might suggest gender-specific training guidelines in team-handball. more...

Published
2015
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