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  • MDPI AG  (11)
  • Becker, Felix  (11)
  • 1
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    Liver Resection for Primary Hepatic Angiosarcoma: Bicentric Analysis of a Challenging Entity
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 11 ( 2022-05-25), p. 2990-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 11 ( 2022-05-25), p. 2990-
    Abstract: Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of the liver, and data on patient outcome after surgical treatment are scarce. The aim of this study was to evaluate postoperative morbidity and overall survival (OS) of patients who underwent hepatectomy for PHA. This is a bicentric retrospective analysis of all consecutive patients who underwent liver resection in curative intent for PHA between 2012 and 2019 at the University Hospital of Muenster and the University Hospital of Bern. Nine patients (five female, four male) were included from both centers. Median age was 72 years (44–82). Most lesions (77.8%) were larger than 5 cm, and mean size of the biggest lesion was 9.4 ± 4.5 cm. Major hepatectomy was performed in four (44.4%), and radical resection (R0) was achieved in six (66.7%) patients. Postoperative complication rate was 88.8%, including 44.4% higher than 3a in the Clavien–Dindo classification. OS survival rates at 1, 2, and 3 years were 44.4%, 22.2%, and 12.5%, respectively, and median OS was 5 months. OS was significantly better after radical resection (R0: 15 months vs. R1: 0 months, p = 0.04), whereas presentation with tumor rupture at diagnosis was associated with the worst OS (0 months vs. 15 months, p = 0.005). Disease recurrence occurred in three patients (33.3%) between three and seven months after surgery. Radical resection remains the only potentially curative treatment option for PHA. However, postoperative morbidity is high, and the overall prognosis remains poor. Multimodal therapy options and management strategies are urgently needed and could improve the prognosis of patients suffering from PHA in the future.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11112990
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 2
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    The Influence of Apremilast-Induced Macrophage Polarization on Intestinal Wound Healing
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 10 ( 2023-05-09), p. 3359-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 10 ( 2023-05-09), p. 3359-
    Abstract: There is compelling evidence suggesting a pivotal role played by macrophages in orchestrating intestinal wound healing. Since macrophages display significant plasticity and heterogeneity, exhibiting an either classically activated (M1-like) or alternatively activated (M2-like) phenotype, they can aggravate or attenuate intestinal wound healing. Growing evidence also demonstrates a causal link between impaired mucosal healing in inflammatory bowel disease (IBD) and defects in the polarization of pro-resolving macrophages. By targeting the switch from M1 to M2 macrophages, the phosphodiesterase-4 inhibitor Apremilast has gained recent attention as a potential IBD drug. However, there is a gap in our current knowledge regarding the impact of Apremilast-induced macrophages’ polarization on intestinal wound healing. The THP-1 cells were differentiated and polarized into M1 and M2 macrophages, and subsequently treated with Apremilast. Gene expression analysis was performed to characterize macrophage M1 and M2 phenotypes, and to identify possible target genes of Apremilast and the involved pathways. Next, intestinal fibroblast (CCD-18) and epithelial (CaCo-2) cell lines were scratch-wounded and exposed to a conditioned medium of Apremilast-treated macrophages. Apremilast had a clear effect on macrophage polarization, inducing an M1 to M2 phenotype switch, which was associated with NF-κB signaling. In addition, the wound-healing assays revealed an indirect influence of Apremilast on fibroblast migration. Our results support the hypothesis of Apremilast acting through the NF-κB-pathway and provide new insights into the interaction with fibroblast during intestinal wound healing.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12103359
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 3
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    Sulforaphane Elicits Protective Effects in Intestinal Ischemia Reperfusion Injury
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 15 ( 2020-07-22), p. 5189-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 15 ( 2020-07-22), p. 5189-
    Abstract: Intestinal ischemia reperfusion injury (IRI) is an inherent, unavoidable event of intestinal transplantation, contributing to allograft failure and rejection. The inflammatory state elicited by intestinal IRI is characterized by heightened leukocyte recruitment to the gut, which is amplified by a cross-talk with platelets at the endothelial border. Sulforaphane (SFN), a naturally occurring isothiocyanate, exhibits anti-inflammatory characteristics and has been shown to reduce platelet activation and block leukocyte adhesion. Thus, the aim of this study was to investigate protective effects and mechanism of action of SFN in a murine model of intestinal IRI. Intestinal IRI was induced by superior mesenteric artery occlusion for 30 min, followed by reperfusion for 2 h, 8 h or 24 h. To investigate cellular interactions, leukocytes were in vivo stained with rhodamine and platelets were harvested from donor animals and ex vivo stained. Mice (C57BL/6J) were divided into three groups: (1) control, (2) SFN treatment 24 h prior to reperfusion and (3) SFN treatment 24 h prior to platelet donation. Leukocyte and platelet recruitment was analyzed via intravital microscopy. Tissue was analyzed for morphological alterations in intestinal mucosa, barrier permeability, and leukocyte infiltration. Leukocyte rolling and adhesion was significantly reduced 2 h and 8 h after reperfusion. Mice receiving SFN treated platelets exhibited significantly decreased leukocyte and platelet recruitment. SFN showed protection for intestinal tissue with less damage observed in histopathological and ultrastructural evaluation. In summary, the data presented provide evidence for SFN as a potential therapeutic strategy against intestinal IRI.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21155189
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
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    Hyperspectral Imaging for Assessment of Initial Graft Function in Human Kidney Transplantation
    MDPI AG ; 2022
    In:  Diagnostics Vol. 12, No. 5 ( 2022-05-10), p. 1194-
    Details
    In: Diagnostics, MDPI AG, Vol. 12, No. 5 ( 2022-05-10), p. 1194-
    Abstract: The aim of our study was to evaluate hyperspectral imaging (HSI) as a rapid, non-ionizing technique for the assessment of organ quality and the prediction of delayed graft function (DGF) in kidney transplantation after static cold storage (SCS, n = 20), as well as hypothermic machine perfusion (HMP, n = 18). HSI assessment of the kidney parenchyma was performed during organ preservation and at 10 and 30 min after reperfusion using the TIVITA® Tissue System (Diaspective Vision GmbH, Am Salzhaff, Germany), calculating oxygen saturation (StO2), near-infrared perfusion index (NIR), tissue haemoglobin index (THI), and tissue water index (TWI). Recipient and donor characteristics were comparable between organ preservation groups. Cold ischemic time was significantly longer in the HMP group (14.1 h [3.6–23.1] vs. 8.7h [2.2–17.0] , p = 0.002). The overall presence of DGF was comparable between groups (HMP group n = 10 (55.6%), SCS group n = 10 (50.0%)). Prediction of DGF was possible in SCS and HMP kidneys; StO2 at 10 (50.00 [17.75–76.25] vs. 63.17 [27.00–77.75] %, p = 0.0467) and 30 min (57.63 [18.25–78.25] vs. 65.38 [21.25–83.33] %, p = 0.0323) after reperfusion, as well as NIR at 10 (41.75 [1.0–58.00] vs. 48.63 [12.25–69.50] , p = 0.0137) and 30 min (49.63 [8.50–66.75] vs. 55.80 [14.75–73.25] , p = 0.0261) after reperfusion were significantly lower in DGF kidneys, independent of the organ preservation method. In conclusion, HSI is a reliable method for intraoperative assessment of renal microperfusion, applicable after organ preservation through SCS and HMP, and predicts the development of DGF.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics12051194
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662336-5
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  • 5
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    Surgery for Liver Metastasis of Non-Colorectal and Non-Neuroendocrine Tumors
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 7 ( 2022-03-29), p. 1906-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 7 ( 2022-03-29), p. 1906-
    Abstract: Surgery has become well established for patients with colorectal and neuroendocrine liver metastases. However, the value of this procedure in non-colorectal and non-neuroendocrine metastases (NCRNNELMs) remains unclear. We analyzed the outcomes of patients that underwent liver surgery for NCRNNELMs and for colorectal liver metastases (CRLMs) between 2012 and 2017 at our institution. Prognostic factors of overall and recurrence-free survival were analyzed, and a comparison of survival between two groups was performed. Seventy-three patients (30 NCRNNELM and 43 CRLM) were included in this study. Although the mean age, extrahepatic metastases, and rate of reoperation were significantly different between the groups, recurrence-free survival was comparable. The 5-year overall survival rates were 38% for NCRNNELM and 55% for CRLM. In univariate analysis, a patient age of ≥60 years, endodermal origin of the primary tumor, and major complications were negative prognostic factors. Resection for NCRNNELM showed comparable results to resection for CRLM. Age, the embryological origin of the primary tumor, and the number of metastases might be the criteria for patient selection.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11071906
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Tumor Recurrence and Graft Survival in Renal Transplant Recipients with a History of Pretransplant Malignancy: A Matched Pair Analysis
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 11 ( 2021-05-27), p. 2349-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 11 ( 2021-05-27), p. 2349-
    Abstract: Organ scarcity demands critical decision-making regarding eligible transplant candidates and graft allocation to ensure best benefit from renal transplantation (RTx). Among the controversial relative contraindications is a history of pretransplant malignancy (PTM). While oncological outcomes of PTM-RTx recipients are well described, data on graft-specific outcome are scarce. A retrospective double case control matched pair analysis (60 months follow-up) was carried out and RTx-recipients were stratified for history of PTM. First, PTM-RTx recipients were matched according to age, sex and duration of immunosuppressive therapy. Next, PTM-RTx recipients were matched 1:1 for age, sex and cause of end-stage renal disease. Five-year patient and graft survival as well as oncological outcomes were analyzed. A total of 65 PTM-RTx recipients were identified. Post-RTx recurrence rate was 5%, while 20% developed second de novo malignancy, comparable to 14% in the control group. PTM-RTx recipients had a noticeable lower five-year death-censored as well as overall graft survival and Cox proportional hazard modeling showed a correlation between PTM and inferior graft survival. Although underlying reasons remain not fully understood, this study is the first to show inferior graft survival in PTM-RTx recipients and advocates necessity to focus on more meticulous graft monitoring in PTM recipients in addition to heightened surveillance for cancer recurrence.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10112349
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 7
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    Innate Immune Cells during Machine Perfusion of Liver Grafts—The Janus Face of Hepatic Macrophages
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 22 ( 2022-11-10), p. 6669-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 22 ( 2022-11-10), p. 6669-
    Abstract: Machine perfusion is an emerging technology in the field of liver transplantation. While machine perfusion has now been implemented in clinical routine throughout transplant centers around the world, a debate has arisen regarding its concurrent effect on the complex hepatic immune system during perfusion. Currently, our understanding of the perfusion-elicited processes involving innate immune cells remains incomplete. Hepatic macrophages (Kupffer cells) represent a special subset of hepatic immune cells with a dual pro-inflammatory, as well as a pro-resolving and anti-inflammatory, role in the sequence of ischemia–reperfusion injury. The purpose of this review is to provide an overview of the current data regarding the immunomodulatory role of machine perfusion and to emphasize the importance of macrophages for hepatic ischemia–reperfusion injury.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11226669
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 8
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    Dynamic Parameters of Hypothermic Machine Perfusion—An Image of Initial Graft Function in Adult Kidney Transplantation?
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 19 ( 2022-09-27), p. 5698-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 19 ( 2022-09-27), p. 5698-
    Abstract: Kidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS (n = 88) or HMP (n = 45). There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group (16.5 [8.5–28.5] vs. 11.3 [5.4–24.1] , p 〈 0.0001). The incidence of DGF as well as serum creatinine at discharge and at 1 year post transplant were comparable between groups. Duration of SCS prior to HMP was comparable among grafts with and without DGF. Flow rate and organ resistance at the start of HMP were significantly worse in DGF-kidney grafts (arterial flow 22.50 [18.00–48.00] vs. 51.83 [25.50–92.67] ml/min, p = 0.0256; organ resistance 123.33 [57.67–165.50] vs. 51.33 [28.17–111.50] mmHg/mL/min, p = 0.0050). Recipients with DGF had significantly worse creatinine levels at discharge (2.54 [1.08–7.64] vs. 1.67 [0.90–6.56] , p 〈 0.0001) and at 1 year post transplant (1.80 [1.09–7.95] vs. 1.59 [0.87–7.40] , p = 0.0105). In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11195698
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 9
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    How Old Is Old? An Age-Stratified Analysis of Elderly Liver Donors above 65
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 13 ( 2022-07-04), p. 3899-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 13 ( 2022-07-04), p. 3899-
    Abstract: In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65–69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65–69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65–69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65–69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65–70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11133899
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 10
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    Bryostatin-1 Attenuates Ischemia-Elicited Neutrophil Transmigration and Ameliorates Graft Injury after Kidney Transplantation
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 6 ( 2022-03-10), p. 948-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 6 ( 2022-03-10), p. 948-
    Abstract: Ischemia reperfusion injury (IRI) is a form of sterile inflammation whose severity determines short- and long-term graft fates in kidney transplantation. Neutrophils are now recognized as a key cell type mediating early graft injury, which activates further innate immune responses and intensifies acquired immunity and alloimmunity. Since the macrolide Bryostatin-1 has been shown to block neutrophil transmigration, we aimed to determine whether these findings could be translated to the field of kidney transplantation. To study the effects of Bryostatin-1 on ischemia-elicited neutrophil transmigration, an in vitro model of hypoxia and normoxia was equipped with human endothelial cells and neutrophils. To translate these findings, a porcine renal autotransplantation model with eight hours of reperfusion was used to study neutrophil infiltration in vivo. Graft-specific treatment using Bryostatin-1 (100 nM) was applied during static cold storage. Bryostatin-1 dose-dependently blocked neutrophil activation and transmigration over ischemically challenged endothelial cell monolayers. When applied to porcine renal autografts, Bryostatin-1 reduced neutrophil graft infiltration, attenuated histological and ultrastructural damage, and improved renal function. Our novel findings demonstrate that Bryostatin-1 is a promising pharmacological candidate for graft-specific treatment in kidney transplantation, as it provides protection by blocking neutrophil infiltration and attenuating functional graft injury.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11060948
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
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