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  • 1
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    Incidence and long‐term survival of patients with de novo head and neck carcinoma after liver transplantation
    Wiley ; 2016
    In:  Head & Neck Vol. 38, No. 5 ( 2016-05), p. 707-714
    Details
    In: Head & Neck, Wiley, Vol. 38, No. 5 ( 2016-05), p. 707-714
    Abstract: Liver transplant recipients have an increased risk of developing de novo malignancies. Methods We conducted a prospective evaluation of clinicopathological data and predictors for overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) after liver transplantation (1988 to 2010). Results Thirty‐three of 2040 patients who underwent liver transplantation (1.6%) developed de novo HNSCC. The incidence of HNSCC in liver transplant recipients with end‐stage alcoholic liver disease (26) was 5%. After a median follow‐up of 9 years, 1‐year, 3‐year, and 5‐year OS rates were 74%, 47%, and 34%, respectively. Tumor size, cervical lymph node metastases, tumor site, and therapy (surgery only vs surgery and adjuvant radiotherapy [RT]/chemoradiotherapy [CRT] vs RT/CRT only; p   〈  .0001) were significantly associated with OS in univariate analysis. However, surgery only predicted OS independently in multivariate analysis. Conclusion Early diagnosis and surgical treatment of de novo HNSCC are crucial to the outcome. HNSCC risk should be taken into close consideration during posttransplantation follow‐up examinations, especially among patients with a positive history of smoking and alcohol consumption. © 2015 Wiley Periodicals, Inc. Head Neck 38: 707–714, 2016
    Type of Medium: Online Resource
    ISSN: 1043-3074 , 1097-0347
    URL: Issue
    URL: Article
    DOI: 10.1002/hed.v38.5
    DOI: 10.1002/hed.23943
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2001440-5
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  • 2
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    A socio‐ecological model for predicting impacts of land‐use and climate change on regional plant diversity in the Austrian Alps
    Wiley ; 2020
    In:  Global Change Biology Vol. 26, No. 4 ( 2020-04), p. 2336-2352
    Details
    In: Global Change Biology, Wiley, Vol. 26, No. 4 ( 2020-04), p. 2336-2352
    Abstract: Climate and land‐use change jointly affect the future of biodiversity. Yet, biodiversity scenarios have so far concentrated on climatic effects because forecasts of land use are rarely available at appropriate spatial and thematic scales. Agent‐based models (ABMs) represent a potentially powerful but little explored tool for establishing thematically and spatially fine‐grained land‐use scenarios. Here, we use an ABM parameterized for 1,329 agents, mostly farmers, in a Central European model region, and simulate the changes to land‐use patterns resulting from their response to three scenarios of changing socio‐economic conditions and three scenarios of climate change until the mid of the century. Subsequently, we use species distribution models to, first, analyse relationships between the realized niches of 832 plant species and climatic gradients or land‐use types, respectively, and, second, to project consequent changes in potential regional ranges of these species as triggered by changes in both the altered land‐use patterns and the changing climate. We find that both drivers determine the realized niches of the studied plants, with land use having a stronger effect than any single climatic variable in the model. Nevertheless, the plants' future distributions appear much more responsive to climate than to land‐use changes because alternative future socio‐economic backgrounds have only modest impact on land‐use decisions in the model region. However, relative effects of climate and land‐use changes on biodiversity may differ drastically in other regions, especially where landscapes are still dominated by natural or semi‐natural habitat. We conclude that agent‐based modelling of land use is able to provide scenarios at scales relevant to individual species distribution and suggest that coupling ABMs with models of species' range change should be intensified to provide more realistic biodiversity forecasts.
    Type of Medium: Online Resource
    ISSN: 1354-1013 , 1365-2486
    URL: Issue
    URL: Article
    DOI: 10.1111/gcb.v26.4
    DOI: 10.1111/gcb.14977
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2020313-5
    SSG: 12
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  • 3
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    Prognostic significance of TIE2‐expressing monocytes in hilar cholangiocarcinoma
    Wiley ; 2016
    In:  Journal of Surgical Oncology Vol. 114, No. 1 ( 2016-07), p. 91-98
    Details
    In: Journal of Surgical Oncology, Wiley, Vol. 114, No. 1 ( 2016-07), p. 91-98
    Abstract: Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang‐receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2‐expressing monocytes (TEMs) in cholangiocarcinoma. Methods We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co‐expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. Results High Ang 1 expression correlated with reduced metastasis ( P   〈  0.05). Patients characterized by invading Ang‐receptor bearing TEMs in tumor showed lower tumor recurrence ( P   〈  0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival ( P   〈  0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis ( P   〈  0.05). Conclusions High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91–98 . © 2016 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 0022-4790 , 1096-9098
    URL: Issue
    URL: Article
    DOI: 10.1002/jso.v114.1
    DOI: 10.1002/jso.24249
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 1475314-5
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  • 4
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    Cardiovascular risk and events after liver transplantation. Experiences from 313 consecutive transplants with a follow‐up of 20 years
    Wiley ; 2015
    In:  Clinical Transplantation Vol. 29, No. 4 ( 2015-04), p. 343-350
    Details
    In: Clinical Transplantation, Wiley, Vol. 29, No. 4 ( 2015-04), p. 343-350
    Abstract: Cardiovascular diseases ( CVD ) are the third leading cause of late death after liver transplantation ( LT ). The old PROCAM score was described in males (aged 35–65 yr) to estimate cardiovascular events after LT . New PROCAM is now available to estimate risks for cardiovascular events in both genders and for a wider age range (25–75 yr). We tested old and new PROCAM in long‐term follow‐up (10 and 20 yr) and described CVD risk factors, kidney function, and immunosuppression over two decades. A retrospective study of 313 consecutive LT s was conducted. At 10 (T2) and 20 (T3) yr, patients were screened for cardiovascular events, and for T1 (0.5 yr) and T2, CVD risk factors were recorded and old and new PROCAM calculated. PROCAM estimates were compared with observed events. CVD risk factors increased significantly over time and kidney function decreased. Between T1 and T2 in males, fewer events were observed (o) than estimated (e) (males: o: 3 vs. e: 6.05–9.88; females o: 2 vs. e: 1.35–4.21). For both genders, new PROCAM was appropriate between T2 and T3 (males o: 8; e: 4.5–8.57; females o: 2; e: 1.2–4.46). New PROCAM sufficiently estimates cardiovascular risk after LT , while overestimation in T1‐T2 may be due to strict surveillance.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2015.29.issue-4
    DOI: 10.1111/ctr.12520
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2739458-X
    detail.hit.zdb_id: 2004801-4
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  • 5
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    Eurotransplant donor‐risk‐index and recipient factors: influence on long‐term outcome after liver transplantation – A large single‐center experience
    Wiley ; 2016
    In:  Clinical Transplantation Vol. 30, No. 5 ( 2016-05), p. 508-517
    Details
    In: Clinical Transplantation, Wiley, Vol. 30, No. 5 ( 2016-05), p. 508-517
    Abstract: The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor‐Risk‐Index ( ET ‐ DRI ) was established to estimate outcome after Liver Transplantation ( LT ). Currently, data on impact of ET ‐ DRI on long‐term outcome for different indications and recipient conditions are missing. Retrospective, single‐center analysis of long‐term graft survival ( GS ) of 1767 adult primary LT s according to indication, lab MELD category ( 1 : ≤18; 2 : 〉 18–25; 3 : 〉 25–35; 4 : 〉 35), and ET ‐ DRI . Mean ET ‐ DRI in our cohort was 1.63 (±0.43). One‐, 10, and 15‐yr GS was 83.5%, 63.3%, and 54.8%. Long‐term GS was significantly influenced by ET ‐ DRI . Accordingly, four ET ‐ DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases ( CD / AIH ), and HCV , but not for HCC , HBV , cryptogenic cirrhosis, and acute liver failure. lab MELD categories showed no significant influence on graft, but on patient survival. Matching ET ‐ DRI categories with lab MELD revealed significant differences in long‐term GS for lab MELD categories 1 , 2 , and 3 , but not 4 . In multivariate analysis, HCV combined with ET ‐ DRI 〉 2 and lab MELD category 3 combined with ET ‐ DRI 〉 2 emerged as negative predictors. To achieve excellent long‐term graft survival, higher risk organs ( ET ‐ DRI 〉 1.4) should be used restrictively for patients with CD / AIH or HCV . Organs with ET‐DRI 〉 2 should be avoided in patients with a lab MELD of 〉 25–35.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2016.30.issue-5
    DOI: 10.1111/ctr.12714
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 6
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    Selection and use of immunosuppressive therapies after liver transplantation: current German practice
    Wiley ; 2016
    In:  Clinical Transplantation Vol. 30, No. 5 ( 2016-05), p. 487-501
    Details
    In: Clinical Transplantation, Wiley, Vol. 30, No. 5 ( 2016-05), p. 487-501
    Abstract: In recent years, immunosuppression ( IS ) after liver transplantation ( LT ) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors ( CNI s) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin‐2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil ( MMF ) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus‐based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3–6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult‐to‐treat patient subpopulations.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2016.30.issue-5
    DOI: 10.1111/ctr.12708
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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  • 7
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    Predictive factors for extrahepatic recurrence of hepatocellular carcinoma following liver transplantation
    Wiley ; 2016
    In:  Clinical Transplantation Vol. 30, No. 7 ( 2016-07), p. 819-827
    Details
    In: Clinical Transplantation, Wiley, Vol. 30, No. 7 ( 2016-07), p. 819-827
    Abstract: Recurrence of hepatocellular carcinoma ( HCC ) in patients treated with liver transplantation ( LT ) is associated with diminished survival. Particularly, extrahepatic localization of HCC recurrence contributes to poor prognosis. Patients and methods Clinicopathological data of patients who underwent LT for HCC between 1989 and 2010 in a high‐volume transplant center were retrospectively evaluated, and predictors of extrahepatic recurrence were identified. Results Three hundred and sixty‐four patients underwent LT for HCC . After a median follow‐up time of 78 months, 93 patients (25%) were diagnosed with a recurrence. Median time to recurrence was 19 months. Recurrence was located exclusively in the liver in 19 cases (20%), and 74 patients (80%) had extrahepatic recurrence. Factors associated with extrahepatic recurrence in multivariate analysis included HCC beyond the Milan criteria (p 〈 0.0001) and the presence of macrovascular tumor invasion (p = 0.035). In patients with HCC beyond the Milan criteria who developed a recurrence (N = 73), macrovascular invasion was the only positive predictor of extrahepatic recurrence in multivariate analysis (p 〈 0.0001). In patients with HCC within the Milan criteria who recurred after LT (N = 20), DNA ‐index 〉 1.5 (p = 0.013) was the only predictive factor for extrahepatic recurrence in multivariate analysis. Conclusions Advanced HCC beyond the Milan criteria and the presence of macrovascular invasion are associated with an increased risk for extrahepatic recurrence and are currently considered as relative contraindications to LT . In patients with HCC within the Milan criteria, the DNA ‐index represents a valuable prognostic marker for the development of extrahepatic recurrence and may support the selection of patients for intensified postoperative tumor surveillance.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2016.30.issue-7
    DOI: 10.1111/ctr.12755
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2739458-X
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  • 8
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    Cerebrovascular events in 20 years of follow‐up after liver transplantation: an underestimated issue?
    Wiley ; 2016
    In:  Clinical Transplantation Vol. 30, No. 10 ( 2016-10), p. 1276-1282
    Details
    In: Clinical Transplantation, Wiley, Vol. 30, No. 10 ( 2016-10), p. 1276-1282
    Abstract: Cardio‐ and cerebrovascular diseases are the third leading cause of late death after liver transplantation ( LT ). A new score ( PROCAM ‐Stroke) has been established to estimate the 10‐year risk of cerebrovascular events ( CBVE ) in a German standard population. We evaluate the applicability of the PROCAM ‐Stroke for long‐term follow‐up after LT . Patients and Methods A retrospective study of 313 consecutive LT s was conducted. Six months after LT (T1) and 10 years after LT (T2), CBVE risk factors were recorded and PROCAM ‐Stroke was calculated. Ten (T2) and 20 years (T3) after LT , recipients were screened regarding CBVE . PROCAM ‐Stroke estimates of CBVE were compared with the incidence of observed CBVE . Results In both 10‐year time frames, the incidence of observed CBVE was higher than expected based on the PROCAM ‐Stroke estimates: 6 months—10 years after LT (T1–T2): observed: 11, expected: 3.2; 10 years—20 years after LT (T2–T3): observed: 7, expected: 3.4. Conclusion LT recipients seem to have a considerably increased risk of CBVE . Long‐term surveillance should take this into account, and screening may be extended accordingly. The progressive impairment of renal function in the long‐term LT survivors may be one reason for the underestimation of CBVE in this patient group.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2016.30.issue-10
    DOI: 10.1111/ctr.12819
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2739458-X
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  • 9
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    Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis
    Wiley ; 2011
    In:  Liver International Vol. 31, No. 10 ( 2011-11), p. 1574-1588
    Details
    In: Liver International, Wiley, Vol. 31, No. 10 ( 2011-11), p. 1574-1588
    Abstract: Pattern recognition receptors ( PRR s) orchestrate the innate immune defence in human biliary epithelial cells ( BEC s). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BEC s. Aims We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. Methods We examined PRR ‐mediated innate immune responses and protective endotoxin tolerance in primary BEC s isolated from patients with primary sclerosing cholangitis ( PSC ), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT ‐ PCR , Western blots and immunocytochemistry. Functional studies comprised immuno‐precipitation Western blots, FACS for endotoxin uptake, and NF ‐κB activation assays and ELISA for secreted IL ‐8 and tumour necrosis factor ( TNF )‐α. Results Primary BEC s from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/ IRAK signalling complex. Consecutively, PSC BEC s exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper‐responsiveness was probably because of the stimulatory effect of abundantly expressed IFN ‐γ and TNF ‐α in PSC livers, which stimulated TLR 4‐mediated endotoxin signalling in BEC s, leading to increased TLR 4‐mediated endotoxin incorporation and impaired inactivation of the TLR 4 signalling cascade. As TNF ‐α inhibition partly restored protective innate immune tolerance, endogenous TNF ‐α secretion probably contributed to inappropriate endotoxin responses in BEC s. Conclusion Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BEC s probably contribute to chronic cholangitis.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.2011.31.issue-10
    DOI: 10.1111/j.1478-3231.2011.02635.x
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2124684-1
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  • 10
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    Impaired psychosocial outcome of donors after living donor liver transplantation: a qualitative case study
    Wiley ; 2006
    In:  Clinical Transplantation Vol. 20, No. 4 ( 2006-07), p. 410-415
    Details
    In: Clinical Transplantation, Wiley, Vol. 20, No. 4 ( 2006-07), p. 410-415
    Abstract: Abstract:  Adult‐to‐adult living donor liver transplantation (LDLT) of the right hepatic lobe has been developing into an established therapy for treating pre‐terminal liver diseases. There is little experience available on the psychosocial outcome of living donors. The aim of this first qualitative case study was to investigate the patterns for impaired psychosocial outcome in donors after LDLT. Donor hepatectomies were performed in 30 donors at the Charité Berlin. Six months after surgery, the six of the 30 donors with negative moods and physical complaints in psychometric monitoring were examined. The post‐operative interviews were transcribed and analysed using current qualitative research methods. These six donors (20%) reported various unspecific complaints and psychological conflicts. Sadness was expressed about organ rejection and death of the recipient. Anxieties about the recipient and their own health were verbalized. Disappointment and anger refer to the experience that they were not as fully appreciated by the medical system and their social environment as expected. The negative emotions of donors with impaired psychosocial outcome could be related to a decrease in self‐esteem in the post‐operative course. Adequate medical and psychological treatment opportunities for these donors should be provided.
    Type of Medium: Online Resource
    ISSN: 0902-0063 , 1399-0012
    URL: Issue
    URL: Article
    DOI: 10.1111/ctr.2006.20.issue-4
    DOI: 10.1111/j.1399-0012.2006.00464.x
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2739458-X
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