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Abstract Objective Orthotopic-liver-transplantation (OLT) in patients with Human-Immunodeficiency-Virus infection (HIV) and end-stage-liver-disease (ESDL) is rarely reported. The purpose of this study is to describe our institutional experience on OLT for HIV positive patients. Material and methods This is a retrospective study of all HIV-infected patients who underwent OLT at the University Hospital of Essen, from January 1996 to December 2009. Age, sex, HIV transmission-way, CDC-stage, etiology of ESDL, concomitant liver disease, last CD4cell count and HIV-viral load prior to OLT were collected and analysed. Standard calcineurin-inhibitors-based immunosuppression was applied. All patients received anti-fungal and anti-pneumocystis carinii pneumonia prophylaxis post-OLT. Results Eight transplanted HIV-infected patients with a median age of 46 years (range 35-61 years) were included. OLT indications were HCV (n = 5), HBV (n = 2), HCV/HBV/HDV-related cirrhosis (n = 1) and acute liver-failure (n = 1). At OLT, CD4 cell-counts ranged from 113-621 cells/μl, and HIV viral-loads from < 50-175,000 copies/ml. Seven of eight patients were exposed to HAART before OLT. Patients were followed-up between 1-145 months. Five died 1, 3, 10, 31 and 34 months after OLT due to sepsis and graftfailure respectively. Graft-failure causes were recurrent hepatic-artery thrombosis, HCV-associated hepatitis, and chemotherapy-induced liver damage due to Hodgkin-disease. One survivor is relisted for OLT due to recurrent chronic HCV-disease but non-progredient HIV-infection 145 months post-OLT. Two other survivors show stable liver function and non-progredient HIV-disease under HAART 21 and 58 months post-OLT. Conclusions OLT in HIV-infected patients and ESLD is an acceptable therapeutic option in selected patients. Long-term survival can be achieved without HIV disease-progression under antiretroviral therapy and management of the viral hepatitis co-infection.

Abstract Objective Hilar cholangiocarcinoma is the fourth most common gastrointestinal malignancy. CA19-9 and CEA are helpful devices in the management of gastrointestinal malignancies and belong to clinical routine in surgical oncology. But the validity of these parameters in terms of tumor extension and prognosis of bile duct malignancies still remains unclear. Methods From 1998 to 2008, we obtained preoperative CA19-9 and CEA serum levels in 136 patients with hilar cholangiocarcinoma. We correlated tumor stage, resectability rate and survival with preoperative CA 19-9 and CEA serum levels. Results CA19-9 (UICC I: 253 ± 561 U/ml; UICC II: 742 ± 1572 U/ml; UICC III: 906 ± 1708 U/ml; UICC IV: 1707 ± 3053 U/ml) and CEA levels (UICC I: 2.9 ± 3.8 U/ml; UICC II: 4.6 ± 6.5 U/ml; UICC III: 18.1 ± 29.6 U/ml; UICC IV: 22.7 ± 53.9 U/ml) increase significantly with rising tumor stage. Patients with pre operative serum levels of CA19-9 (> 1000 U/ml) and CEA (> 14.4 ng/ml) showed a significant poorer resectability rate and survival than patients with lower CA19-9 and CEA serum levels respectively. Conclusion CA19-9 and CEA serum levels are associated with the tumor stage. If preoperatively obtained CA19-9 and CEA serum levels are highly elevated patients have an even worse survival and the frequency of irresectability is significantly higher.

Abstract Objective Non-operative management of blunt splenic injury in adults has been applied increasingly at the end of the last century. Therefore, the lifelong risk of overwhelming post-splenectomy infection has been the major impetus for preservation of the spleen. However, the prevalence of posttraumatic infection after splenectomy in contrast to a conservative management is still unknown. Objective was to determine if splenectomy is an independent risk factor for the development of posttraumatic sepsis and multi-organ failure. Methods 13,433 patients from 113 hospitals were prospective collected from 1993 to 2005. Patients with an injury severity score > 16, no isolated head injury, primary admission to a trauma center and splenic injury were included. Data were allocated according to the operative management into 2 groups (splenectomy (I) and conservative managed patients (II)). Results From 1,630 patients with splenic injury 758 patients undergoing splenectomy compared with 872 non-splenectomized patients. 96 (18.3%) of the patients with splenectomy and 102 (18.5%) without splenectomy had apparent infection after operation. Additionally, there was no difference in mortality (24.8% versus 22.2%) in both groups. After massive transfusion of red blood cells (> 10) non-splenectomy patients showed a significant increase of multi-organ failure (46% vs. 40%) and sepsis (38% vs. 25%). Conclusions Non-operative management leads to lower systemic infection rates and mortality in adult patients with moderate blunt splenic injury (grade 1-3) and should therefore be advocated. Patients with grade 4 and 5 injury, patients with massive transfusion of red blood cells and unstable patients should be managed operatively.

Abstract Objective Liver injury due to trauma is a rare indication for transplantation. The main indications in such cases were uncontrollable bleeding and insufficient hepatic function. Because of poor results, liver transplantation in these patients is occasionally described as "waste of organs", however based on insufficient data. This study aims to report our experience and to critically question the indication of transplantation in these patients. Methods All liver transplantations at our institution were reviewed retrospectively. This covered 1,529 liver transplants between September 1987 and December 2008. Of them, 6 transplants were performed due to motor-vehicle accidents which caused uncontrollable acute liver trauma in 4 patients. The patients' peri-operative course, short- and long-term outcomes were analyzed. Results Five deceased-donor liver transplantations (4 full size, 1 split) and 1 living donor (right) transplantation were performed. The median GCS score was 9/15; the median MELD score was 15. Postoperative complications were observed in 3 patients, requiring re-operation in 2. After a median (range) follow-up of 32.95 (10.3-55.6) months, 2 patients are alive and remain well on immunosuppression. Conclusion Liver transplantation in patients with otherwise surgically uncontrollable acute liver injury can be indicated as a life saving procedure and can be performed successfully in highly selected cases.

Abstract Objective Due to organ shortage, average waiting time for a kidney in Germany is about 4 years after start of dialysis. Number of kidney grafts recovered can only be maintained by accepting older and expanded criteria donors. The aim of this study was to analyse the impact of donor and recipient risk on kidney long-term function. Methods All deceased kidney transplantations were considered. We retrospectively studied 332 patients between 2002 and 2006; divided in 4 groups reflecting donor and recipient risk. Results Non-marginal recipients were less likely to receive a marginal organ (69 of 207, 33%) as compared to marginal recipients, of whom two-thirds received a marginal organ (p < 0.0001). Graft function significantly differed between the groups, but detrimental effect of marginal recipient status on eGFR after 12 months (-6 ml/min/1.73 qm, 95% CI -2 to -9) was clearly smaller than the effect of marginal donor status (-10 ml/min/1.73 qm, 95% CI -7 to -14). Conclusions As we were able to show expanded criteria donor has a far bigger effect on long-term graft function than the "extra risk" recipient. Although there have been attempts to define groups of recipients who should be offered ECD kidneys primarily the discussion is still ongoing.

Background: The intraperitoneal onlay mesh (IPOM) is for many surgeons a pragmatic solution for the operative treatment of extensive and complex abdominal wall hernias. A few years after mesh implantation we are now faced with a number of late complications of the IPOM procedure. Chronic septic complications, such as mesh infections and fistula formation have an outstanding position., Objective: With this case series we would like to share our experiences with the operative treatment of severe late onset septic complications after abdominal wall augmentation with IPOM. Furthermore, the current indications for the IPOM procedure are discussed., Material and Methods: For the period February 2016-July 2019 a total of 10 patients with late septic complications after IPOM implantation were treated in our clinic. The index interventions took place between 2010 and 2017. The clinical picture varied from mesh infections with only minor symptoms to formation of multiple intestinal fistulas., Results: Multiple stage procedures were required in 9 out of the 10 patients in order to achieve sufficient decontamination of the surgical field. Due to enterocutaneous fistulas, bowel resection was performed in 5 patients. The mesh could be preserved in situ in only one patient. For the reconstruction of the abdominal wall, both plastic surgical methods and implantation of absorbable and non-absorbable meshes were used., Conclusion: A consistent treatment with great effort is required for septic complications of the IPOM procedure. The interventions are often associated with extensive adhesiolysis and intestinal resection. Therefore, the indications for intraperitoneal mesh implantation should be handled with caution and an alternative surgical procedure should be considered. There are still special cases, such as hernias with very large abdominal wall defects in which the IPOM method is a suitable treatment option for tension-free reconstruction.

Women represent the majority of medical students in several countries. In any surgical specialty and above all in surgical leadership positions, women still remain disproportionally underrepresented. The objective of this study was to investigate female surgeons' career advancement and satisfaction with training. A standardized questionnaire was devised and sent out via the web-based survey tool SurveyMonkey ® to female surgeons in the German federal state of North Rhine-Westphalia. A total of 125 completed questionnaires were analyzed (response rate 40.8%). Female surgeons are at least largely (76%) satisfied with their surgical training. Increased time (>5 h/week) as the principal surgeon in the operating room significantly stimulates the satisfaction with the surgical training (86% vs. 68%, p = 0.0384). At the participants' current workplace, the heads of departments are predominantly male surgeons (91%). Respondents not satisfied with their surgical training prefer a female head of department more frequently (24% vs. 2%, p = 0.0085). The majority of the respondents themselves aspire to become a consultant surgeon (56%), while only 12% intend to become a head of a department. Female surgeons aiming at leadership positions work overtime (≥50 h/week) significantly more frequently (81% vs. 57%, p = 0.0041). Favoritism of male colleagues is perceived by 34%. Respondents who do not perceive any preferential treatment are significantly more satisfied with their surgical training (88% vs. 57%, p = 0.0004). In conclusion, female surgeons seem positive about their career choice, once in the surgical profession, and aptly fill upcoming positions. Women interested in surgery are likely to pursue a surgical career despite the alleged workload, demonstrating the importance of professional self-fulfillment among female surgeons., (©2020 Radunz S., et al., published by De Gruyter, Berlin/Boston.)

Background: The worldwide dissemination of the coronavirus disease 2019 (COVID-19) pandemic has become a relevant problem for the German healthcare system and the whole of society within only a few weeks. Because visceral medicine is at the focal point many adjustments in procedures are necessary., Material and Methods: Necessary organizational structures and challenges in visceral medicine are described for urgent abdominal surgery after screening and for patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, an analysis of the current and relevant literature was performed and changes in the procedures in a hospital for basic and standard healthcare in Lower Rhine are described., Results: This article describes the organizational structures and changes in a German hospital facing the crisis and management during the pandemic. These include establishment of a corona screening center at the hospital's main entrance and a multidisciplinary crisis management team. Specific internal guidelines were formulated for the management, confirmed by international experience and studies and regularly changed due to the requirements of the situation., Conclusion: In comparison to other countries the crisis reached hospitals in Germany with a clear delay and a relatively mild course. In order to be prepared for severely ill patients, adequate preparations could be made to meet the challenges on intensive care units, isolation wards, operating theaters and in endoscopy. The primary goal was the safeguarding of patients and employees. In the light of the pandemic medical rituals and habits need to be reconsidered., (© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020.)

Background/aims: Perihilar cholangiocarcinoma is a rare disease with unfavorable prognosis resulting in low survival rates. This study aims to retrospectively assess the beneficial histopathological features and surgical procedures in long-term survivors (i.e., patients surviving perihilar cholangiocarcinoma for at least 2 y)., Material and Methods: In total, 322 patients with perihilar cholangiocarcinoma underwent surgery at our center. The follow-up ended in 2017; 76 patients survived for >2 y. The type of resection, UICC stage, and histopathological features were compared between three survival groups (>2-3, >3-5, and >5 y)., Results: The >5-year-survival rate in our selected study cohort was 43.4% (>3-5 y,31.6% and >2-3 y, 25.0%), and 14.5% of the patients survived for >10 y after surgery. Patients with non-regional lymph node positive tumors and/or distant metastasis (i.e., UICC stage IVb; p=0.0112), R2 status (p=0.0288), and exploratory laparotomy only (p=0.0157) showed the poorest survival rates. Perineural invasion had no significant impact on the overall survival. However, 29.0% patients surviving for >5 y displayed the lowest perineural infiltration prevalence. Interestingly, Bismuth-Corlette stage IIIa (p=0.0467), especially caudate lobectomy (p=0.0034), was associated with disease-specific overall survival of >5y., Conclusion: Complete/extended tumor resection with additional caudate lobe resection is strongly associated with long-term survival. Perineural infiltration as a negative prognostic marker for prolonged survival needs to be evaluated in larger study cohorts.

Introduction: Organ procurement from deceased donors has been steadily augmented over the last 20 years. With a more aged donor population, a higher incidence of intraabdominal pathologies, including abdominal aortic aneurysms and atherosclerotic aortic disease, is commonly being encountered. The objective of our study was to report our institutional experience with abdominal aortic grafts during solid organ harvesting., Patients and Methods: Data concerning the presence of aortic grafts in deceased solid organ donors during a 36-month period were retrospectively reviewed., Results: During the study period, the organ retrieval team of our institution performed 246 multiorgan retrievals from deceased donors. More specifically, we harvested 6 livers and 12 kidneys from 6 donors with abdominal aortic grafts, which were not known/diagnosed to the organ retrieving team prior to the harvesting procedure. Severe atherosclerosis was present in all these donors. All 18 harvested organs were successfully transplanted. Apart of the absence of the aortic patch in 5 kidney grafts, no further special technical difficulties have been reported by the transplant teams. Data analysis of the recipient and graft outcome was performed through the Eurotransplant database., Conclusion: There are so far no literature data on the outcome of recipients and grafts from deceased donors with abdominal aortic grafts. Although retrieval of such organs is very challenging and requires a very experienced team, the transplantation of the corresponding organs can be performed without special technical problems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The number of patients on waiting lists for repeated kidney transplantation has increased. However, retransplanted patients have a greater surgical and immunological risk than first-time kidney recipients., Methods: We retrospectively analysed all kidney recipients that underwent third, fourth or fifth kidney transplantation (Group 3+) at the University Hospital Essen, Essen, Germany from October 1973 to January 2017. A historical cohort of recipients retransplanted with a second kidney (Group 2) served as the control. Donor and recipient demographic data, cold ischaemia time (CIT), warm ischaemia time, overall operation time and methods, transplantectomy of previous kidney grafts, incidence of surgical and immunological complications as well as patient- and death-censored survival were analysed., Results: We identified 108 recipients transplanted with the third, fourth or fifth renal allograft. Patients with more than one transplantation had significantly higher surgical risk due to atherosclerosis (P = 0.002) and higher immunological risk due to higher panel reactive antibody levels preoperatively (current panel reactive antibody P = 0.004; highest panel reactive antibody value P = 0.0001). Group 3+ patients had more often undergone previous transplant nephrectomy (P = 0.0001). There was a significant difference in CIT (P = 0.009), overall operative time (P = 0.0001) and post-transplantation thrombotic events (P = 0.02). We could not demonstrate any differences in graft and patient survival., Conclusion: Third, fourth and fifth transplant recipients are a high-risk patient cohort. Our results suggest that patient survival after more than three renal transplantations is similar to that of second graft recipients. This supports the concept of repeated kidney retransplantations., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Introduction: The overall increase in life expectancy causes a rapid increase in number of elderly patients needing colorectal surgery. It remains unclear if there is a significant risk factor in patients over 80 years of age for postoperative morbidity and mortality. For this reason we investigated the perioperative, outcome and long-term survival after surgery for colorectal cancer in our hospital., Materials and Methods: We retrospectively analysed a database containing information about patients who underwent surgery for colorectal cancer from January 2010 to December 2015 at the St. Bernhard Hospital in Kamp-Lintfort, Germany. The last follow-up date was 31th of December 2017., Results: A total of 232 patients were enrolled and analysed in this study. All patients were separated in tow groups depending in age. The first group was ≥80 years old (n=49). The second group was <80 years old (n=183). High ASA-Scores (≥3) were detectable more often in elderly patients (p<0,05). Elderly and young patients had a similar risk for postoperative anastomosic leakages (p=0,047). Likewise there were no significant differences regarding the Dindo-Clavien-Classification (p=0,13). The mortality within the first 30 days after surgery was significant elevated for elderly patients compared to younger patients (p=0,04). Also the overall 1-year survival was 90% for the younger and 73,5% for the older study group (p<0,05) Conclusion. Both the short-term outcome and long-term survival rate after colorectal surgery for cancer are worse for patients older than 80 years of age. After interpretation of all data it remains unclear if the age itself is still the biggest risk factor. When old patients have a good ASA-Score and no severe comorbidities, colorectal surgery remains safe even for patients older than 80 years.

Background: The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated., Methods: Between 03/2001 and 02/2013, 98 patients with the diagnosis of an ICC were surgically treated at our center. Median survival times were calculated for these patients after separate classification by both sixth and seventh editions., Results: Median overall survival was increased in patients classified to the lower tumor stages I and II using the seventh as compared to the sixth edition: stage I (54.9 vs. 47.3 months), stage II (19.9 vs. 18.9 months), stage III (17.2 vs. 19.9 months), and stage IV (23.2 vs. 15.3 months), respectively. The seventh edition definition of the T category resulted in an increased median survival regarding the T1 (50.4 vs. 47.3 months) as well as the T2 category (19.9 vs. 15.6 months) and revealed a reduced median survival of patients within the T3 (21.6 vs. 24.8 months) as well as the T4 category (19.9 vs. 27.0 months)., Conclusions: The UICC seventh edition TNM classification for ICC improves separation of patients with intermediate stage tumors as compared to the sixth edition. The prognostic value of the UICC staging system has been improved by the seventh edition. Trial registration The data for this study have been retrospectively registered and the study has been approved by the ethic committee of the medical faculty of the University Hospital of Essen, Germany (license number 15-6353-BO).

Background: Intrahepatic cholangiocarcinomas are the second most common malignant tumors of the liver with an unfavorable prognosis. The role of CA19-9 in terms of patient prognosis is still under debate in the literature., Objective: The aim of the present study was to investigate the prognostic value of preoperatively assessed CA19-9 levels in patients with intrahepatic cholangiocarcinoma after surgery., Material and Methods: A total of 63 patients suffering from intrahepatic cholangiocarcinoma underwent surgery between March 2001 and February 2013 at the West German Cancer Center in Essen, Germany. The follow-up ended in December 2017. The UICC stages, clinicopathological parameters and postoperative tumor-specific survival rates were analyzed with respect to preoperatively measured CA19-9 serum levels., Results: Increased CA19-9 serum levels correlated with higher UICC tumor stages and other unfavorable clinicopathological parameters. Moreover, patients with preoperative elevated CA19-9 serum levels displayed significantly reduced overall survival rates (especially >1000 U/ml vs. ≤1000 U/ml; median overall survival: 14.05 months vs. 42.40 months; p = 0.0003)., Conclusion: Preoperatively assessed CA19-9 levels >1000 U/ml are a strong negative prognostic factor of postoperative disease-specific survival in patients suffering from intrahepatic cholangiocarcinoma. Future studies are necessary to evaluate if patients with highly elevated CA19-9 serum levels should be considered for modified treatment strategies (e. g. neoadjuvant or adjuvant therapy).

Purpose: Women represent up to 60 % of students entering the medical profession in many countries in the world. However, the proportion of women to men is not accordingly balanced among surgical residents and especially in leadership positions in surgery. Therefore, we investigated the career goals as well as family and lifestyle priorities of female surgeons in German liver transplant centers., Methods: A standardized questionnaire was developed using the web-based survey tool SurveyMonkey®. Questionnaires were distributed electronically to 180 female surgeons in 24 German liver transplant centers. A total of 81 completed questionnaires were analyzed., Results: Female surgeons in German liver transplant centers are eager to assume leadership positions and do not wish to follow traditional role models. After finishing training, most female surgeons plan to continue working at a university hospital. About 80 % of the respondents intend to continue working full time and wish to combine career and family., Conclusions: This is the first survey on career intentions of female surgeons in Germany. In the face of gender changes in the medical profession, we were able to demonstrate that female surgeons are willing to fill leadership positions. Individual and institutional creative modifications are necessary if the advancement of women in surgery is to be promoted.

The sequelae of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in organ donors potentially results in ischemic organ injury and graft dysfunction after transplantation. Thresholds of resuscitation times in brain dead liver donors have not been established so far. We report the case of a brain dead liver donor who experienced 2.5 hours of CPR whose liver was successfully transplanted. A 75-year-old male experienced CA and was treated by CPR with streptokinase application for 2.5 hours until stabilization of cardiac function. Brain death was diagnosed at the day of admission and organ donation carried out within 24 hours. The DRI was 2.2 with a CIT of 8.8 hours. The liver was transplanted into a 64-year-old recipient suffering from alcoholic liver cirrhosis and a MELD-score of 10 non representative for severity of disease. During follow up of 4 years ERCP and stenting was performed regularly for biliary anastomosis stenosis. The patient remained in a very good overall state of health without any signs of liver dysfunction. This case demonstrates that an extensive period of CPR is not an obligatory exclusion criterion for liver donation. Thresholds of CPR times as well as predictive factors in donors with CA should be established., (Celsius.)

Background: International data on training, work, and lifestyle of transplant physicians and surgeons are scarce. Such data might help in development of uniform education paths and provide insights for young clinicians interested in this field. This study aimed at the evaluation of these data in all transplant-associated medical disciplines., Methods: A survey on professional and academic training, workload, and lifestyle was generated. The questionnaire was distributed to all members of the German Transplant Association (DTG), utilizing the tool SurveyMonkey(®) ., Results: A total of 127 members of the DTG responded (male/female 66.1%/33.9%, 45.8±10.3 years). The majority had been working in transplant medicine for more than 10 years (61.9%). Fifteen respondents (11.8%) obtained an official European certification (European Union of Medical Specialists). A total of 57 (48.3%) respondents worked full time on research during training. The research focus was clinical for most respondents (n=72, 61.5%). An average working time of 62±1.5 h/wk was reported. Fifty-eight percent of all respondents complained of inadequate remuneration and 50% reported inadequate acknowledgment of their professional performance., Conclusion: This is the first study reporting characteristics of training, work, and lifestyle in an interdisciplinary cohort of German transplant physicians and surgeons. Enormous efforts in clinical and research work were reported, associated with high rates of professional and financial dissatisfaction., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Perihilar cholangiocarcinoma (Klatskin tumor) is a rare tumor entity with an unfavorable prognosis despite optimal treatment., Objectives: The aim of the study is to investigate beneficial histopathological features and recommendations for surgery in perihilar cholangiocarcinoma to improve patients' long term survival., Material and Methods: 192 patients suffering from perihilar cholangiocarcinoma underwent attempted tumor resection between 1998 and 2008 at our clinic. 50 patients survived more than 2 years. The follow-up ended in December 2013. The resection type, the UICC stage and histopathological features were compared between three groups (2-3-year, 3-5-year and > 5-year survival groups)., Results: The overall 5‑year survival rate of the study groups was 32 %, and even 16 % survived more than 10 years after surgery. Patients with lymph node positive tumors (p = 0.0126) and distant metastasis (p = 0.0376) had the poorest survival rate. Perineural invasion had no significant impact on the overall survival, but patients surviving more than 5 years had the lowest incidence of perineural invasion with 18.75 %. Caudate lobectomy was significantly (p = 0.011) associated with a survival of more than 5 years in our study., Conclusions: Complete tumor resection with additional caudate lobe resection is associated with long-term survival. Perineural invasion seems to be a negative prognostic factor for long-term survival.

Background: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data., Methods: PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment., Results: A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively., Conclusion: Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology., Methods: We employed CCA samples from 73 patients and human HUCCT-1/Mz-CHA1/KMCH-1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas., Results: PLK1/2/3-immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival., Conclusions: The results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo-like kinase inhibitors (i.e., PLK1/2 specifity)., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen., Methods: Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity., Results: Cell preparation yielded the following cell counts per gram of liver tissue: 2.0 ± 0.4 × 10(7) hepatocytes, 1.8 ± 0.5 × 10(6 )Kupffer cells, 4.3 ± 1.9 × 10(5) liver sinusoidal endothelial cells, and 3.2 ± 0.5 × 10(5) stellate cells. Hepatocytes were identified by albumin (95.5 ± 1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5 ± 1.2%) and exhibited phagocytic activity, as determined with 1 μm latex beads. Endothelial cells were CD146(+) (97.8 ± 1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1 ± 1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence., Conclusions: Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.

Background: The significance of humoral immune response for allograft survival after liver transplantation (LT) is still a matter of debate. The aim of this cross-sectional study was to assess immunological and clinical factors associated with advanced fibrosis (F3-F4) and chronic graft failure in LT recipients., Methods: Serum samples from 174 patients prospectively enrolled and followed up for 12 months were tested for anti-HLA antibodies and compared against donor HLA types. Immunohistochemical C4d staining was performed on formalin-fixed, paraffin-embedded liver tissue., Results: Mean time period from LT to enrollment was 66.9 ± 51.9 months. Independent predictive factors for graft failure included donor-positive cytomegalovirus serostatus (P = 0.02), donor-specific antibodies (DSA) against HLA class II (P = 0.03), donor age (P = 0.01), hepatitis C virus allograft reinfection (P = 0.0008), and biliary complications (P = 0.003). HLA class II DSA and HLA class I antibody positivity, hepatitis C virus reinfection, and mycophenolate mofetil-free regimens were significant risk factors for advanced fibrosis after LT. There was a significant association between C4d deposition on allograft endothelial cells and presence of class II DSA (P < 0.0001). Patients with C4d deposits had a 4.3 times higher risk of graft failure than those with negative staining and a significantly lower median time to graft failure (94.6 months [range, 3.6-158.9 months] vs 176.4 months [range, 9.4-217.8 months], P < 0.0001)., Conclusions: Screening for HLA DSA might be useful for early identification of LT recipients at increased risk of graft failure who could benefit from closer surveillance and tailored immunosuppressive regimens.

Background: Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration., Methods: In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control)., Results: Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, -10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension., Conclusions: A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.

This manuscript reports the results of a nationwide survey of transplant surgeons in Germany, including the demographics, training, position, individual case loads, center volumes, program structure, professional practice, grade of specialization, workload, work hours, salary, and career expectations. We contacted all 32 German transplant centers that perform liver, kidney, and pancreas transplantation. Surgeons engaged in transplantation were asked to reply to the survey. Eighty-five surgeons responded, with a mean age of 44 ± 8 years, 13% of whom were female. The median transplant frequency per active transplant surgeon was relatively low, with 16 liver transplants, 15 kidney transplants, and three pancreas transplants. The median reported center volumes were 45 liver transplants, 90 kidney transplants, and five pancreas transplants per year. Most of the surgeons reported a primary focus on hepato-pancreato-biliary surgery, and only 10% of effective work time was actually dedicated to perform transplant surgeries. The majority of respondents estimated their weekly work hours to be between 55 and 66 h. When asked about their career satisfaction and expectations, most respondents characterized their salaries as inappropriately low and their career prospects as inadequate. This survey provides a first impression of the transplant surgery work force in Germany., (© 2015 Steunstichting ESOT.)

Background & Aims: Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors., Methods: We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest., Results: We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1-150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors., Conclusion: This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Infections are a major cause for morbidity and mortality in liver transplant recipients. So far there has been no study systematically investigating the correlation between the MELD (Model for End-Stage Liver Disease) scoring system and complications caused by infections. The aim of the present retrospective study was to evaluate the impact of the pretransplant MELD score on incidence and mortality of pneumonia and septicemia in liver transplant recipients., Material and Methods: The clinical courses of 201 liver transplant recipients between 12/2006 and 3/2009 were recorded and analyzed on the basis of chart review. Patients were stratified into three groups (pretransplant MELD score: group I 6-20, group II ≥ 21-30, group III ≥ 31-40) and compared in terms of incidence of infection and survival., Results: The mean pretransplant MELD score was 22 ± 12. There were 81 patients in group I, 65 patients in group II, and 55 patients in group III. There was no difference in incidence of infections between the MELD groups. However, septicemia-associated mortality was significantly higher in group III., Conclusions: A high MELD score is not associated with higher incidence of infections but it is associated with a significantly higher mortality in the case of septicemia. Prevention of infections is of utmost importance, especially in liver transplant recipients with high MELD scores.

Purpose: Severe bleeding after trauma frequently leads to a poor outcome. Prehospital fluid replacement therapy is considered an important primary treatment option. We conducted a retrospective matched pair analysis to assess the influence of prehospital fluid replacement volume on the clinical course of patients with solid abdominal organ trauma., Methods: Data were analyzed from 51,425 patients in TraumaRegister DGU® of the German Trauma Society. Inclusion criteria were as follows: injury severity score ≥ 16 points, primary admission, age ≥ 16 years, no isolated brain injury, transfusion of at least one unit of packed red blood cells (pRBCs), and systolic blood pressure ≥ 20 mmHg at the accident site. The patients were divided into "low-volume" (0-1000 ml) and "high-volume" (≥ 1,500 ml) groups according to the matched pair criteria. In each group, 68 patients met the inclusion criteria., Results: Higher volume in fluid replacement was associated with increased need for transfusion (pRBCs: low-volume: 7.71 units, high-volume: 9.16 units; p = 0.074) and with by trend reduced clotting ability (prothrombin time: low-volume: 71.47 %, high-volume: 66.47 %; p = 0.27). The percentage of patients in shock (systolic blood pressure <90 mmHg) upon admission was equal in the two groups (25.0 %; p = 1). The mortality rate was discretely higher in the high-volume group (low-volume: 11.8 %, high-volume: 19.1 %; p = 0.089)., Conclusions: Excessive prehospital fluid replacement is able to lead in an increased mortality rate in patients with solid abdominal organ injury. Our results support the concept of restrained fluid replacement in the preclinical treatment of severe trauma patients.

Background: One of the main reasons for organ shortage is insufficient education on organ donation. Knowledgeable medical students could share the information with friends and families resulting in a positive attitude to organ donation of the general public., Methods: During six consecutive years (2009 to 2014), we conducted a voluntary, anonymous educational intervention study on organ donation among fourth year medical students in the course of the main surgery lecture at the University of Essen, Germany., Results: Questionnaires of 383 students were analyzed. Prior to the specific lecture on organ donation, 64% of the students carried a signed organ donor card with the intention to donate. Further information regarding organ donation was required by 37% of the students. The request for further information was statistically significantly higher among students without a donor card compared to organ donor card carriers (P < 0.0001). After the lecture, the number of students requiring further information decreased statistically significantly to 19% (P < 0.0001)., Conclusions: Already a 45-minute lecture for fourth year medical students significantly decreases their request for further information on organ donation and improves their attitude to organ donation. Continued training on organ donation will help medical students to become disseminators for this important topic in our society.

The proapoptotic molecule TNF-related apoptosis-inducing ligand (TRAIL) has earned attention because of its ability to induce apoptosis in liver cancer cells without damaging normal liver cells. It may play an important role in preventing the development and outgrowth of hepatocellular carcinoma (HCC). TRAIL expression was investigated in a large series of human HCCs. We analyzed liver tissue from 108 patients undergoing partial liver resection (PLR) or liver transplantation (LT) because of either HCC or other indications. TRAIL expression was correlated with the cause of liver disease, demographic and clinical variables and pathologic properties. Our analysis found that in 66% of HCCs TRAIL expression was significantly lower than in the surrounding non-cancerous liver tissue (p≤0.012). Separation by cause of disease showed that HCC TRAIL mRNA expression was lower in almost all groups than in non-cancerous tissue but most significantly lower in NASH-associated liver tumors. Interestingly, low HCC TRAIL expression was found to correlate with tumor size (p≤0.007) and stage, as well as with tumor recurrence after resection and poor survival rates. The results of this study suggest that low TRAIL mRNA levels may be both a dominant feature in HCC development and growth and a predictor of tumor recurrence and poorer survival rates., (© 2014 UICC.)

Background: We previously reported that the presence of steatosis did not adversely influence survival in patients undergoing resection for colorectal liver metastases (CLM) without pre-operative chemotherapy. Here, this hypothesis is tested in patients undergoing resection for CLM following pre-operative chemotherapy., Methods: We assessed the effects of background liver pathology, categorized as 'normal', 'steatosis' and 'other', on perioperative mortality, overall survival (OS) and cancer-specific survival (CSS) in LiverMetSurvey patients. Survival analyses included log-rank tests and multivariate Cox models, incorporating well-established prognosticators. In secondary analyses, re-populating the model with non-chemotherapy patients, the effect modification of chemotherapy on the impact of steatosis on survival was tested., Results: Of 4329 patients undergoing first-time liver resection following pre-operative chemotherapy, histologies were normal in 1913 (44%), steatosis in 1675 (39%), and other abnormal pathologies in 741 (17%). For normal, steatosis and other, 90-day mortalities were 2.1%, 2.3%, and 3.5% (P = 0.103). For the three histo-pathological groups, 5-year OS rates were 39%, 42%, and 36% (Plogrank = 0.363); 5-year CSS rates were 43%, 45% and 41% (Plogrank = 0.496), respectively. The associations of steatosis with OS and CSS were materially unchanged in the multivariate models. Chemotherapy did not interact with the effect of steatosis on survival., Conclusion: The findings of equivalent survivals challenge the common perception that steatosis in CLM patients after pre-operative chemotherapy is associated with increased peri-operative mortality and poorer long-term survival., (Copyright © 2014 Elsevier Ltd. All rights reserved.)