Publications by authors named "Peter Neuhaus"

427 Publications

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

Ann Surg 2020 11;272(5):855-862

University Hospital Regensburg, Department of Surgery and Section of Experimental Surgery, Franz-Josef-Strauss-Allee 11, Regensburg, Germany.

Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial).

Summary And Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data.

Patients And Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence.

Results: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245).

Conclusions: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients.

Clinical Trial Registration: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004280DOI Listing
November 2020

Stability of Mina v2 for Robot-Assisted Balance and Locomotion.

Front Neurorobot 2018 15;12:62. Epub 2018 Oct 15.

Department of Mechanical and Aerospace Engineering, New York University, Brooklyn, NY, United States.

The assessment of the risk of falling during robot-assisted locomotion is critical for gait control and operator safety, but has not yet been addressed through a systematic and quantitative approach. In this study, the balance stability of Mina v2, a recently developed powered lower-limb robotic exoskeleton, is evaluated using an algorithmic framework based on center of mass (COM)- and joint-space dynamics. The equivalent mechanical model of the combined human-exoskeleton system in the sagittal plane is established and used for balance stability analysis. The properties of the Linear Linkage Actuator, which is custom-designed for Mina v2, are analyzed to obtain mathematical models of torque-velocity limits, and are implemented as constraint functions in the optimization formulation. For given feet configurations of the robotic exoskeleton during flat ground walking, the algorithm evaluates the maximum allowable COM velocity perturbations along the fore-aft directions at each COM position of the system. The resulting velocity extrema form the contact-specific balance stability boundaries (BSBs) of the combined system in the COM state space, which represent the thresholds between balanced and unbalanced states for given contact configurations. The BSBs are obtained for the operation of Mina v2 without crutches, thus quantifying Mina v2's capability of maintaining balance through the support of the leg(s). Stability boundaries in single and double leg supports are used to analyze the robot's stability performance during flat ground walking experiments, and provide design and control implications for future development of crutch-less robotic exoskeletons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbot.2018.00062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196256PMC
October 2018

COMPARISON OF THE EFFICACY AND SAFETY OF MEDETOMIDINE-KETAMINE VERSUS MEDETOMIDINE-AZAPERONE-ALFAXALONE COMBINATION IN FREE-RANGING ROCKY MOUNTAIN BIGHORN SHEEP ( OVIS CANADENSIS).

J Zoo Wildl Med 2018 Sep;49(3):662-670

Chemical immobilization is a key aspect of wildlife management. To minimize dose-dependent adverse effects, immobilization protocols often include two or more synergistic agents, which allows for reductions in individual drug dosages. Free-ranging bighorn sheep ( Ovis canadensis) in Canada ( n = 74) were remotely injected with a combination of medetomidine (0.16 ± 0.04 mg/kg) and ketamine (4.0 ± 1.4 mg/kg) (MK), or combination of medetomidine (0.14 ± 0.06 mg/kg), azaperone (0.21 ± 0.11 mg/kg), and alfaxalone (0.45 ± 0.21 mg/kg) (MAA). Once recumbency was achieved, arterial blood samples were collected and immediately analyzed for blood gas and acid-base status. Rectal temperature, heart rate, and respiratory rate were recorded upon recumbency and throughout anesthesia at 5-15 min intervals. At conclusion of the procedures, medetomidine was reversed by intramuscular atipamezole at five times the medetomidine dose. Induction times (mean ± standard deviation) of animals that became immobilized with one dart (8.7 ± 3.2 min, 7.3 ± 3.9 min) and recovery times of all animals (3.4 ± 1.5 min, 3.9 ± 1.6 min) were not significantly different between MK and MAA groups, respectively. Both MK and MAA groups experienced severe hypoxemia (PaO 42 ± 9 mmHg, 40 ± 10 mmHg, respectively). PaCO was significantly higher ( P = 0.0248) in the MK group (median 54 mmHg) than the MAA group (median 48 mmHg) with a trend towards lower pH (7.40 vs 7.42, respectively, P = 0.07). Initially, MK animals had higher heart rates than MAA animals (median 49 vs 40 beats/min), which decreased over time. In bighorn sheep, both MK and MAA produced reliable, reversible immobilization with smooth inductions and recoveries. However, less respiratory depression was seen with MAA than MK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1638/2017-0161.1DOI Listing
September 2018

IHMC's experience competing in the Cybathlon compared to the DARPA robotics challenge.

Authors:
Peter Neuhaus

J Neuroeng Rehabil 2017 Nov 9;14(1):112. Epub 2017 Nov 9.

IHMC, 40 S. Alcaniz St, Pensacola, FL, 32502, USA.

Background: As a research scientist, my work tends to focus on scientific investigations. Our group occasionally makes discoveries or has a successful demonstration, and sometimes we can even repeatedly demonstrate something working on the hardware. This mode of operation works for research, but not for competitions. In the past few years, I have participated in two international robotics competitions, the DARPA Robotics Challenge (DRC) and the Cybathlon; the research and development process for these competitions is significantly different from our typical research work. This commentary discusses our experience preparing for the Cybathlon, and contrasts it with our experience with the DRC.

Main Body: The human in the loop for the Cybathlon was the biggest differentiator between the DRC and the Cybathlon. Having the human at the center of the competition not only changed the way we developed, but changed how we viewed the impact of our work. For the DRC, a physics based dynamic simulation was a powerful, and invaluable, tool for not only the algorithm developers, but the robot operator as well. For the Cybathlon, simulation was of little use because the all of closed-loop control was performed by the pilot. In the software development cycle for the Cybathlon, the push was to just come up with something that works and "lock it down" and do not change it, so that the pilot could train with a given set of motions that would not change and make up for any deficiencies with his own abilities. The Cybathlon was more of an athletic challenge for the human who was assisted by technology. The DRC was the opposite, it was a robotics challenge assisted by a human. This commentary focuses on describing the Florida Institute for Human and Machine Cognition's (IHMC) experience leading up to and at the Cybathlon, with some comparisons to the DRC experience.

Conclusion: The Cybathlon was a very worthwhile experience me, my team, and of course our pilot. Knowing that our development could improve the quality of life and health for a group of people was very motivating and rewarding. Engineering competitions accelerate development, engage the public, and in the case of the Cybathlon, increase public awareness of issues for people with disabilities. The Cybathlon also revealed that the powered exoskeleton technology is still nascent in its ability to be a viable alternative to the wheelchair. But with continued developments toward the 2020 Cybathlon, we hope the capabilities of these devices can offer will be significantly improved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12984-017-0324-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680763PMC
November 2017

Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study.

Transplant Direct 2017 Jul 26;3(7):e183. Epub 2017 Jun 26.

Interdisciplinary Center for Clinical Trials Mainz and Surgical Trial Network; University Medical Center, Johannes Gutenberg University, Mainz, Germany.

Background: Arterial ex situ back-table perfusion (BP reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation.

Methods: Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation.

Results: A total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms.

Conclusions: Contrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TXD.0000000000000686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498024PMC
July 2017

The 28-year incidence of de novo malignancies after liver transplantation: A single-center analysis of risk factors and mortality in 1616 patients.

Liver Transpl 2017 11;23(11):1404-1414

Departments of Surgery, Campus Charité Mitte and Campus Virchow Klinikum.

De novo malignancies (DNMs) are one of the leading causes of late mortality after liver transplantation (LT). We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow-up data were available for 96% of patients, 3% were incomplete, and only 1% were lost to follow-up. The median follow-up of the patients was 14.1 years. Variables with possible prognostic impact on the development of DNMs were analyzed, as was the incidence of malignancies compared with the nontransplant population by using standardized incidence ratios. In total, 266 (16.5%) patients developed 322 DNMs of the following subgroups: hematological malignancies (n = 49), skin cancer (n = 83), and nonskin solid organ tumors (SOT; n = 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18.3-81.1 years). In the multivariate analysis, an increased recipient age (hazard ratio [HR], 1.03; P < 0.001) and a history of smoking (HR, 1.92; P < 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A-treated compared with tacrolimus-treated patients (HR, 1.53; P = 0.03). The present analysis shows a disproportionate increase of de novo SOT with an increasing follow-up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. Liver Transplantation 23 1404-1414 2017 AASLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lt.24795DOI Listing
November 2017

Discovery of herpesviruses in Canadian wildlife.

Arch Virol 2017 Feb 24;162(2):449-456. Epub 2016 Oct 24.

Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada.

Herpesviruses (HVs) have a wide range of hosts in the animal kingdom. The result of infection with HVs can vary from asymptomatic to fatal diseases depending on subtype, strain, and host. To date, little is known about HVs naturally circulating in wildlife species and the impact of these viruses on other species. In our study, we used genetic and comparative approaches to increase our understanding of circulating HVs in Canadian wildlife. Using nested polymerase chain reaction targeting a conserved region of the HV DNA polymerase gene, we analyzed material derived from wildlife of western and northern Canada collected between February 2009 and Sept 2014. For classification of new virus sequences, we compared our viral sequences with published sequences in GenBank to identify conserved residues and motifs that are unique to each subfamily, alongside phylogenetic analysis. All alphaherpesviruses shared a conserved tryptophan (W856) and tyrosine (Y880), betaherpesviruses all shared a serine (S836), and gammaherpesviruses had a conserved glutamic acid (E835). Most of our wildlife HV sequences grouped together with HVs from taxonomically related host species. From Martes americana, we detected previously uncharacterized alpha- and beta-herpesviruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00705-016-3126-yDOI Listing
February 2017

Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering.

Cells Tissues Organs 2015 -2016;201(6):399-411. Epub 2016 May 20.

General, Visceral and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Campus Virchow-Klinikum, Berlin, Germany.

Objectives: Stable long-term functioning of liver cells after transplantation in humans is still not achieved successfully. A new approach for successful engraftment of liver cells may be the transplantation of syngeneic cells into an allogeneic liver graft. We therefore developed a new rat model for combined liver and liver cell transplantation (cLCTx) under stable immunosuppression.

Materials And Methods: After inducing a mitotic block, liver grafts from female donor rats (Dark Agouti) were transplanted into female recipients (Lewis). In male Lewis rats, liver cell proliferation was induced with subsequent cell isolation and transplantation into female recipients after organ transplantation. Y-chromosome detection of the transplanted male cells was performed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FisH) with localization of transplanted cells by immunohistochemistry.

Results: Immunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by FisH, showing repopulation of the liver graft with 15.6% male cells (± 1.8 SEM) at day 90. qPCR revealed 14.15% (± 5.09 SEM) male DNA at day 90.

Conclusion: Engraftment of transplanted syngeneic cells after cLCTx was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the FisH results were partly confirmed by qPCR. This new protocol in rats appears feasible for addressing long-term functioning and eventually the induction of operational tolerance in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000445792DOI Listing
May 2016

Clinical application of modern ultrasound techniques after liver transplantation.

Acta Radiol 2016 Oct 27;57(10):1161-70. Epub 2016 Feb 27.

Charité, Berlin, Germany.

Liver transplantation has been established as a first-line therapy for a number of indications. Conventional ultrasound and contrast-enhanced ultrasound (CEUS) are methods of choice during the postoperative period as a safe and fast tool to detect potential complications and to enable early intervention if necessary. CEUS increases diagnostic quality and is an appropriate procedure for the examination of vessels and possibly bile ducts. This article presents the state of the art of ultrasound application during the early period after liver transplantation. It addresses common vascular complications and describes the identification of postoperative abnormal findings using ultrasound and CEUS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0284185116633910DOI Listing
October 2016

CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma.

Nat Med 2016 Mar 8;22(3):278-87. Epub 2016 Feb 8.

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Heidelberg, Germany.

Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and identify two markers--HNF1A and KRT81--that enable stratification of tumors into different subtypes by using immunohistochemistry. Individuals with tumors of these subtypes showed substantial differences in overall survival, and their tumors differed in drug sensitivity, with the exocrine-like subtype being resistant to tyrosine kinase inhibitors and paclitaxel. Cytochrome P450 3A5 (CYP3A5) metabolizes these compounds in tumors of the exocrine-like subtype, and pharmacological or short hairpin RNA (shRNA)-mediated CYP3A5 inhibition sensitizes tumor cells to these drugs. Whereas hepatocyte nuclear factor 4, alpha (HNF4A) controls basal expression of CYP3A5, drug-induced CYP3A5 upregulation is mediated by the nuclear receptor NR1I2. CYP3A5 also contributes to acquired drug resistance in QM-PDA and classical PDAC, and it is highly expressed in several additional malignancies. These findings designate CYP3A5 as a predictor of therapy response and as a tumor cell-autonomous detoxification mechanism that must be overcome to prevent drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nm.4038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780258PMC
March 2016

Preliminary study on liver function changes after trisectionectomy with versus without prior portal vein embolization.

Surg Today 2016 Sep 31;46(9):1053-61. Epub 2015 Dec 31.

Department of General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.

Purpose: Post-hepatectomy liver failure (PHLF) is the major risk factor for mortality after hepatectomy. Preoperative planning of the future liver remnant volume reduces PHLF rates; however, future liver remnant function (FLR-F) might have an even stronger predictive value. In this preliminary study, we used a new method to calculate FLR-F by the LiMAx test and computer tomography-assisted volumetric-analysis to visualize liver function changes after portal vein embolization (PVE) before extended hepatectomy.

Methods: The subjects included patients undergoing extended right hepatectomy either directly (NO-PVE group) or after PVE (PVE group). Computed tomography (CT) scan and liver function tests (LiMAx) were done before PVE and preoperatively. FLR-F was calculated and correlated with the postoperative liver function.

Results: There were 12 patients in the NO-PVE group and 19 patients in the PVE group. FLR-F and postoperative liver function correlated significantly in both groups (p = 0.036, p = 0.011), although postoperative liver function was slightly overestimated, at 32 and 45 µg/kg/min, in the NO-PVE and PVE groups, respectively. LiMAx value did not change after PVE.

Conclusions: Volume-function analysis using LiMAx and CT scan enables us to reliably predict early postoperative liver function. Global enzymatic liver function measured by the LiMAx test did not change after PVE, confirming that liver function distribution in the liver stays constant after PVE. An overestimation of FLR-F is needed to compensate for the intraoperative liver injury that occurs in patients undergoing extended hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00595-015-1293-1DOI Listing
September 2016

Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation.

Hepatobiliary Pancreat Dis Int 2015 Dec;14(6):596-602

Allgemein-, Visceral- & Transplantationschirurgie, Charite Campus Virchow Klinikum, Berlin 13353, Germany.

Background: Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.

Methods: Male inbred Wistar rats (weighing 230-260 g) served as donors and recipients (n=6/group). Donors of treatment groups received i.v. 0.01 mL/g body weight (BW) warm (21 degree centigrade) HTK systemically 15 minutes prior to cold perfusion. Control groups received 0.01 mL/g BW warm (21 degree centigrade) NaCl 0.9%. Following pretreatment, donors were flushed with 4 degree centigrade cold HTK, livers were explanted and stored in 4 degree centigrade HTK for six hours. Thereafter orthotopic liver transplantation was performed. Recipients were harvested four hours, two and five days after reperfusion and blood and liver tissue samples were obtained. Blood samples were analyzed for AST, ALT, lactate dehydrogenase and bilirubin. Liver histological analysis as well as tissue analysis for pro-MMP2, MMP2 and pro-MMP9 using zymography was conducted.

Results: Treatment groups showed significantly lower ALT and lactate dehydrogenase levels as well as significantly lower activities of pro-MMP2, MMP2 and pro-MMP9. Histological analysis revealed only minor damage in all groups.

Conclusions: The new concept of warm HTK pretreatment significantly reduced ischemia-reperfusion injury. The reduced ischemia-reperfusion injury was due to MMP inhibition. Warm HTK donor pretreatment is easy to handle and could further improve HTK's potency in liver preservation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s1499-3872(15)60426-xDOI Listing
December 2015

Secondary Sclerosing Cholangitis in Critically Ill Patients: Clinical Presentation, Cholangiographic Features, Natural History, and Outcome: A Series of 16 Cases.

Medicine (Baltimore) 2015 Dec;94(49):e2188

From the Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany (SL, DE, WF, PN, DS); Endoscopy Unit, Department of Gastroenterology and Hepatology, Endocrinology, Diabetes and Metabolic Diseases, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany (WV-S, AA, ES); and Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, Düsseldorf, Germany (SL).

Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is an important differential diagnosis in patients presenting with cholestasis and PSC-like cholangiographic changes in endoscopic retrograde cholangiography (ERC). As a relatively newly described entity, SSC-CIP is still underdiagnosed, and the diagnosis is often delayed. The present study aims to improve the early detection of SSC-CIP and the identification of its complications.A total of 2633 records of patients who underwent or were listed for orthotopic liver transplantation at the University Hospital Charité, Berlin, were analyzed retrospectively. The clinical presentation and outcome (mean follow-up 62.7 months) of the 16 identified SSC-CIP cases were reviewed.Cholestasis was the first sign of SSC-CIP. GGT was the predominant enzyme of cholestasis. Hypercholesterolemia occurred in at least 75% of the patients. SSC-CIP provoked a profound weight loss (mean 18 kg) in 94% of our patients. SSC-CIP was diagnosed by ERC in all patients. The 3 different cholangiographic features detected correspond roughly to the following stages: (I) evidence of biliary casts, (II) progressive destruction of intrahepatic bile ducts, and (III) picture of pruned tree. Biliary cast formation is a hallmark of SSC-CIP and was seen in 87% of our cases. In 75% of the patients, the clinical course was complicated by cholangiosepsis, cholangitic liver abscesses, acalculous cholecystitis, or gallbladder perforation. SSC-CIP was associated with worse prognosis; transplant-free survival was ∼40 months (mean).Because of its high rate of serious complications and unfavorable prognosis, it is imperative to diagnose SSC-CIP early and to differentiate SSC-CIP from other types of sclerosing cholangitis. Specific characteristics enable identification of SSC-CIP. Early cooperation with a transplant center and special attention to biliary complications are required after diagnosis of SSC-CIP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000002188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008492PMC
December 2015

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

Transplantation 2016 Jan;100(1):116-25

1 Department of Surgery and Section of Experimental Surgery, University Hospital Regensburg, Regensburg, Germany. 2 Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany. 3 Unite d'Hepatologie et de Transplantation Hepatique, Centre Hospitalier Universitaire Henri-Mondor, Service d'Hepatologie et de Gastroenterologie, Université Paris-Est Créteil Val-de-Marne, Paris, France. 4 Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche (DiSCOG), Università degli Studi di Padova, Padova, Italy. 5 Klinik für Allgemeine, Viszeral, Transplantations- Gefäß- und Thoraxchirurgie, Klinikum der Ludwig-Maximilians-Universität München-Großhadern, München, Germany. 6 Innere Medizin IV, Sektion Lebertransplantation, Universitätsklinikum Heidelberg, Heidelberg, Germany. 7 Klinik für Allgemein-, Viszeral- und Gefässchirurgie, Universitätsklinikum Jena, Jena, Germany. 8 Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany. 9 Centro Trapianti Fegato, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico IRCCS di Milano, Milan, Italy. 10 Chirurgia Epatobiliare e Trapianto Epatico, Azienda Ospedaliera di Padova, Università di Padova, Padova, Italy. 11 Alberta Health Services Liver Transplant Program, University of Alberta, Edmonton, Alberta, Canada. 12 Centre Hépato Biliaire, Hôpital Paul Brousse, Villejuif Cedex, Paris, France. 13 Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, Netherlands. 14 Service de Chirurgie Générale, Hépatique, Endocrinienne, et Transplantation, Hôpital de Hautepierre, Les Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 15 Service de Néphrologie-HTA-Dialyse-Transplantation, CHU Toulouse-Rangueil, Toulouse, France. 16 Department of Surgery and Transplantation, Sahlgrenska University Hospital, Göteborg, Sweden. 17 Hepatic-Pa

Background: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC).

Methods: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint.

Results: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874).

Conclusions: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000000965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683033PMC
January 2016

Sex-specific demography and generalization of the Trivers-Willard theory.

Nature 2015 Oct 21;526(7572):249-52. Epub 2015 Sep 21.

University of Oxford, Department of Zoology, Oxford OX1 3PS, UK.

The Trivers-Willard theory proposes that the sex ratio of offspring should vary with maternal condition when it has sex-specific influences on offspring fitness. In particular, mothers in good condition in polygynous and dimorphic species are predicted to produce an excess of sons, whereas mothers in poor condition should do the opposite. Despite the elegance of the theory, support for it has been limited. Here we extend and generalize the Trivers-Willard theory to explain the disparity between predictions and observations of offspring sex ratio. In polygynous species, males typically have higher mortality rates, different age-specific reproductive schedules and more risk-prone life history tactics than females; however, these differences are not currently incorporated into the Trivers-Willard theory. Using two-sex models parameterized with data from free-living mammal populations with contrasting levels of sex differences in demography, we demonstrate how sex differences in life history traits over the entire lifespan can lead to a wide range of sex allocation tactics, and show that correlations between maternal condition and offspring sex ratio alone are insufficient to conclude that mothers adaptively adjust offspring sex ratio.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature14968DOI Listing
October 2015

Patterns of ectoparasitism in North American red squirrels (Tamiasciurus hudsonicus): Sex-biases, seasonality, age, and effects on male body condition.

Int J Parasitol Parasites Wildl 2015 Dec 10;4(3):301-6. Epub 2015 Jun 10.

Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T6E6V6, Canada.

Within many species, males are often more heavily parasitised than females. Several hypotheses have been proposed to explain this phenomenon, including immunocompetence handicaps, sexual size dimorphism and behavioural differences. Here we set out to test the latter two hypotheses and make inferences about the former by assessing patterns of ectoparasitism across various life-history stages in a population of North American red squirrels (Tamiasciurus hudsonicus). We also conducted an ectoparasite removal experiment to investigate the effects of ectoparasites on male body condition. We found that males were more intensely parasitized than females, but only during the mating period. There was no difference in ectoparasite intensity between male and female juveniles at birth or at emergence, suggesting that ectoparasites do not exploit male red squirrels for longer-range natal dispersal. Male red squirrels in our population were slightly heavier than females, however we did not find any evidence that this dimorphism drives male-biased ectoparasitism. Finally, we could not detect an effect of ectoparasite removal on male body mass. Our results lend support to the hypothesis that ectoparasites exploit their male hosts for transmission and that male red squirrels are important for the transmission dynamics of ectoparasites in this population; however, the mechanisms (i.e., immunocompetence, testosterone) are not known.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijppaw.2015.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501535PMC
December 2015

The DNA index as a prognostic tool in hilar cholangiocarcinoma.

J Surg Oncol 2015 Aug 29;112(2):214-8. Epub 2015 Jul 29.

Department of General, Visceral and Transplantation Surgery, Charité, Campus Virchow Klinikum, Berlin, Germany.

Background And Objectives: Due to the devastating prognosis of patients suffering from hilar cholangiocarcinoma (HCCA) valid prognostic factors are urgently needed to guide treatment decisions in a personalized concept. The aim of this study was to analyze the predictive value of the DNA index in a large single-center cohort of patients undergoing resection of HCCA.

Methods: A total of 154 patients who underwent resection of HCCA were included in this prospective study. The DNA index was assessed by image cytometry of fresh tumor samples and correlated, as well as standard histopathological parameters, with patient survival.

Results: The median DNA index was 1.61 ± 0.32. Univariate survival analysis identified eight parameters including DNA index, but not DNA ploidy as prognostic markers. In the Cox proportional hazard model DNA index (P = 0.021), tumor size (P = 0.029) and lymph nodes status (P = 0.039) could be shown to be independent predictors of patient survival.

Conclusion: The DNA index represents an independent prognostic marker in HCCA which is superior to most standard histopathological factors. Since the DNA index can be assessed not only post- but also preoperatively, it might be a potential tool in the preoperative decision-making process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.23977DOI Listing
August 2015

Reductions in post-hepatectomy liver failure and related mortality after implementation of the LiMAx algorithm in preoperative work-up: a single-centre analysis of 1170 hepatectomies of one or more segments.

HPB (Oxford) 2015 Jul;17(7):651-8

Department for General, Visceral and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Objectives: Post-hepatectomy liver failure has a major impact on patient outcome. This study aims to explore the impact of the integration of a novel patient-centred evaluation, the LiMAx algorithm, on perioperative patient outcome after hepatectomy.

Methods: Trends in perioperative variables and morbidity and mortality rates in 1170 consecutive patients undergoing elective hepatectomy between January 2006 and December 2011 were analysed retrospectively. Propensity score matching was used to compare the effects on morbidity and mortality of the integration of the LiMAx algorithm into clinical practice.

Results: Over the study period, the proportion of complex hepatectomies increased from 29.1% in 2006 to 37.7% in 2011 (P = 0.034). Similarly, the proportion of patients with liver cirrhosis selected for hepatic surgery rose from 6.9% in 2006 to 11.3% in 2011 (P = 0.039). Despite these increases, rates of post-hepatectomy liver failure fell from 24.7% in 2006 to 9.0% in 2011 (P < 0.001) and liver failure-related postoperative mortality decreased from 4.0% in 2006 to 0.9% in 2011 (P = 0.014). Propensity score matching was associated with reduced rates of post-hepatectomy liver failure [24.7% (n = 77) versus 11.2% (n = 35); P < 0.001] and related mortality [3.8% (n = 12) versus 1.0% (n = 3); P = 0.035].

Conclusions: Postoperative liver failure and postoperative liver failure-related mortality decreased in patients undergoing hepatectomy following the implementation of the LiMAx algorithm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hpb.12424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474514PMC
July 2015

Cytoreductive Surgery for Pancreatic Cancer Improves Overall Outcome of Gemcitabine-Based Chemotherapy.

Pancreas 2015 Aug;44(6):930-6

From the *Department of General, Visceral, and Transplantation Surgery; †Department of Diagnostic and Interventional Radiology; and ‡Department of Hematology and Oncology, Charité Campus Virchow, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Objectives: Pancreatoduodenectomy is feasible also in patients with locally advanced pancreatic adenocarcinoma (PA) nowadays. Data on risk and survival analysis of palliative pancreatic resections followed by gemcitabine-based chemotherapy (Cx) are limited.

Methods: Between 2000 and 2009, a total of 45 patients had primary cytoreductive surgery (cS) (pancreaticoduodenectomy or total pancreatectomy) followed by gemcitabine-based Cx (cS + Cx) for advanced PA. We matched 1:1 the cS + Cx group with 45 contemporaneous patients who primarily started palliative gemcitabine-based Cx for age, sex, performance status, and body mass index. Overall, survival was evaluated.

Results: Local R0 and R1 resection in metastatic patients was achieved in 27% and 27%, respectively. The R2 resection status without distant metastasis resulted in 33%, whereas 13% showed a local R2 status with additional metastasis (M1). Median overall survival was 10.4 months after cytoreductive pancreatic surgery and consecutive gemcitabine-based Cx versus 7.2 months after upfront gemcitabine-based Cx (P = 0.009). Median survival for R0/M1 patients was 14.4 months and 11.0 months for R2/M0 patients, whereas the median survival for R1/M1 and for R2/M1 patients was 7.3 months and 6.1 months, respectively.

Conclusions: Individual patients with advanced PA had a significantly longer overall survival after palliative pancreaticoduodenectomy followed by Cx than patients in a matched control group who underwent primarily palliative Cx.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000000365DOI Listing
August 2015

Trigger mechanisms of secondary sclerosing cholangitis in critically ill patients.

Crit Care 2015 Mar 31;19:131. Epub 2015 Mar 31.

Department of General, Visceral and Transplantation Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, 13353, Germany.

Introduction: In recent years the development of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has increasingly been perceived as a separate disease entity. About possible trigger mechanisms of SSC-CIP has been speculated, systematic investigations on this issue are still lacking. The purpose of this study was to evaluate the prevalence and influence of promoting factors.

Methods: Temporality, consistency and biological plausibility are essential prerequisites for causality. In this study, we investigated the temporality and consistency of possible triggers of SSC-CIP in a large case series. Biological plausibility of the individual triggers is discussed in a scientific context. SSC-CIP cases were recruited retrospectively from 2633 patients who underwent or were scheduled for liver transplantation at the University Hospital Charité, Berlin. All patients who developed secondary sclerosing cholangitis in association with intensive care treatment were included. Possible trigger factors during the course of the initial intensive care treatment were recorded.

Results: Sixteen patients (68% males, mean age 45.87 ± 14.64 years) with a confirmed diagnosis of SSC-CIP were identified. Of the 19 risk factors investigated, particularly severe hypotension with a prolonged decrease in mean arterial blood pressure (MAP) to <65 mmHg and systemic inflammatory response syndrome (SIRS) were established as possible triggers of SSC-CIP. The occurrence of severe hypotension appears to be the first and most significant step in the pathogenesis. It seems that severe hypotension has a critical effect on the blood supply of bile ducts when it occurs together with additional microcirculatory disturbances.

Conclusions: In critically ill patients with newly acquired cholestasis the differential diagnosis of SSC-CIP should be considered when they have had an episode of haemodynamic instability with a prolonged decrease in MAP, initial need for large amounts of blood transfusions or colloids, and early development of a SIRS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-015-0861-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407292PMC
March 2015

Ectoparasites and fitness of female Columbian ground squirrels.

Philos Trans R Soc Lond B Biol Sci 2015 May;370(1669)

Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA.

Parasites play an important role in the evolution of host traits via natural selection, coevolution and sexually selected ornaments used in mate choice. These evolutionary scenarios assume fitness costs for hosts. To test this assumption, we conducted an ectoparasite removal experiment in free-living Columbian ground squirrels (Urocittelus columbianus) in four populations over three years. Adult females were randomly chosen to be either experimentally treated with anti-parasite treatments (spot-on solution and flea powder, N = 61) or a sham treatment (control, N = 44). We expected that experimental females would show better body condition, increased reproductive success and enhanced survival. Contrary to our expectations, body mass was not significantly different between treatments at mating, birth of litter or weaning of young. Further, neither number nor size of young at weaning differed significantly between the two treatments. Survival to the next spring for adult females and juveniles was not significantly different between experimental and control treatments. Finally, annual fitness was not affected by the treatments. We concluded that females and their offspring were able compensate for the presence of ectoparasites, suggesting little or no fitness costs of parasites for females in the different colonies and during the years of our experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rstb.2014.0113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410379PMC
May 2015

CT-guided Interstitial Brachytherapy of Hepatocellular Carcinoma before Liver Transplantation: an Equivalent Alternative to Transarterial Chemoembolization?

Eur Radiol 2015 Sep 4;25(9):2608-16. Epub 2015 Mar 4.

Klinik für Radiologie, Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany,

Objectives: Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients.

Methods: Twelve patients with HCC received LT after CTB (minimal tumour dose, 15-20 Gy). Patients were matched (CTB:TACE, 1:2) by sex, age, number and size of lesions, and underlying liver disease with patients who received TACE before transplantation. Study endpoints were extent of necrosis at histopathology and recurrence rate after OLT.

Results: There were no significant differences between the CTB and TACE groups regarding Child-Pugh category (p = 0.732), AFP (0.765), time on waiting list (p = 0.659), number (p = 0.698) and size (p = 0.853) of HCC lesions, fulfilment of Milan-criteria (p = 0.638), or previous liver-specific treatments. CTB achieved higher tumour necrosis rates than TACE (p = 0.018). The 1- and 3-year recurrence rate in the CTB group was 10 and 10 % vs. TACE, 14 and 30 % (p = 0.292).

Conclusions: Our data show comparable or even better response and post-LT recurrence rates of CTB compared to TACE for treating HCC in patients prior to LT. CTB should be further evaluated as an alternative bridging modality, especially for patients not suited for TACE.

Key Points: • CT-guided interstitial brachytherapy (CTB) is a promising alternative to transarterial chemoembolization (TACE). • CTB instead of TACE is possible for bridging to liver transplantation in HCC patients. • HCC recurrence was not associated with CTB despite potential tumour seeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-015-3660-0DOI Listing
September 2015

Patient age and extent of liver resection influence outcome of liver resection for hepatocellular carcinoma in non-cirrhotic liver.

Hepatogastroenterology 2014 Oct;61(135):1925-30

Background/aims: Data about the clinical course after liver resection for HCC in non-cirrhotic liver (NCL) is rare in western countries. Although the patients with HCC in NCL tolerate major liver resections, it is less clear if an underlying steatosis or NASH increase the perioperative and postoperative risk. The purpose of this study was to characterize the clinical course after hepatic resection in patients with HCC in the absence of liver cirrhosis and in the absence of viral hepatitis.

Methodology: The data of 148 patients with HCC in non-cirrhotic liver, who underwent curatively intented liver resection, were analyzed. Patients with hepatitis B or C infection were excluded. Patients with fibrolamellar HCC or liver cirrhosis or fibrosis higher than grade 2 according to the Desmet-Scheuer score were also excluded.

Results: The overall 1-, 3- and 5-year survival rates were 75.4%, 54.7% and 38.9%. Increased patient age (elder than 70 years) influenced the cumulative survival significantly. Especially the combination of increased patient age and major resection (>2 segments) at once influenced the cumulative survival. The overall postoperative morbidity was 37.8 %. No intraoperative death was observed. Postoperative increased leucocytes, urea and creatinin increased the postoperative complications. In the subgroup with major resection increased GGT correlated with steatosis, and raised AST correlated with elevated patient age.

Conclusions: In Western countries HCC in non-cirrhotic liver is rare. Liver resection is safe and is the only curative therapy option for the time by HCC without liver cirrhosis. Further studies are necessary for identification of more prognostic factors and optionally special treatment
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2014

Iloprost donor treatment reduces ischemia-reperfusion injury in an isolated extracorporeal pig liver perfusion model.

Exp Clin Transplant 2015 Feb;13(1):51-61

From the Transplant Surgery Charité Humboldt-University, Berlin, Germany.

Objectives: Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model.

Materials And Methods: German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2 L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 μg/kg body weight), (3) addition of iloprost to Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 μg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4).

Results: Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens. Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls.

Conclusions: Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2015

Factors influencing hypertrophy of the left lateral liver lobe after portal vein embolization.

Langenbecks Arch Surg 2015 Feb 6;400(2):237-46. Epub 2015 Jan 6.

Department of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany,

Purpose: Portal vein embolization (PVE) before extended right hepatectomy leads to an increase of the future liver remnant (FLR) volume, but predictive factors for sufficient hypertrophy are still unclear. The purpose of this study was to investigate parameters influencing the growth of FLR.

Methods: Patients undergoing PVE prior hepatic resection were evaluated. PVE was done using polyvinyl alcohol particles only. Volumetric analysis was performed before embolization and before hepatectomy. Success of PVE was determined as percental growth of the future liver remnant.

Results: Seventy-seven patients were included, and three cohorts were formed according to the hypertrophy of FLR. FLR increased from 448.2 ± 187 to 475.5 ± 191 in the poor, from 315.3 ± 86 to 469.1 ± 142 in the moderate, and from 283.4 ± 68 to 400.4 ± 110 in the good hypertrophy group. More cases of recanalization of the portal vein were observed in patients with poor hypertrophy (p = 0.016). Small FLR before PVE predict higher growth of the FLR (p = 0.006). Duration between PVE and surgery differed significantly: 22 (poor) vs. 32 (good) days (p = 0.040).

Discussion: No recanalization, small initial FLR and longer time were assessed with better FLR hypertrophy. More sufficient PVE techniques and postponed hepatectomy might improve the outcome. Small initial FLR should not be a disclosure for curative hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00423-014-1266-7DOI Listing
February 2015

Incidence and long-term survival of patients with de novo head and neck carcinoma after liver transplantation.

Head Neck 2016 May 25;38(5):707-14. Epub 2015 Jun 25.

Department of General, Visceral and Transplant Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.

Background: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.23943DOI Listing
May 2016

Ataxia-telangiectasia-mutated protein kinase levels stratify patients with pancreatic adenocarcinoma into prognostic subgroups with loss being a strong indicator of poor survival.

Pancreas 2015 Mar;44(2):296-301

From the *Department of General, Visceral and Transplantation Surgery, and †Institute of Pathology, Charité University Hospital, Berlin; ‡Institute of Pathology, University Hospital Heidelberg; and §National Center for Tumor Diseases, Heidelberg, Germany.

Objectives: Recently, aberrations in the gene encoding for ataxia-telangiectasia-mutated (ATM) protein kinase have been reported for pancreatic ductal adenocarcinomas (PDAC). These findings argue that ATM deficiency may play a role during carcinogenesis. Therefore, in this study, we investigated the clinical relevance of ATM expression and ATM activation in PDAC.

Methods: Both ATM expression and nuclear phosphoSer1981-ATM levels were assessed by immunohistochemistry in a cohort of 133 PDAC and correlated with clinicopathological parameters.

Results: We found stratification in prognostic subgroups. Complete loss of Ser1981-ATM was indicative of the worst prognosis (median survival, 10.8 vs 14.3 months [low expression] vs 31.1 months [high expression], P < 0.001). Similarly, analysis of ATM expression demonstrated absent expression levels of ATM to be associated with dismal prognosis (median survival, 9.6 months), whereas expression of ATM in general was associated with increased survival (17.7 months, P = 0.001).

Conclusions: Our analysis shows that both ATM expression and activated ATM are prognostic markers in PDAC with respect to standard clinicopathological parameters. These results suggest that ATM should be further explored as prognostic as well as predictive factor with respect to conventional chemotherapies and for putative synthetic lethal approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000000248DOI Listing
March 2015

Nonalcoholic steatohepatits and liver steatosis modify partial hepatectomy recovery.

J Invest Surg 2015 Feb 13;28(1):24-31. Epub 2014 Nov 13.

1Department of General, Visceral and Transplantation Surgery, Charité - Universitaetsmedizin Berlin , Berlin , Germany.

Background: The impact of nonalcoholic fatty liver disease (NAFLD) comprising simple steatosis (NAFL) and steatohepatitis (NASH) on liver recovery after partial hepatectomy has not been evaluated. This pilot study investigated whether there is an effect of proven NAFLD on liver recovery.

Methods: Thirty-one patients elected for partial hepatectomy were characterized and included into a prospective study. Liver samples were staged according to the NAFLD activity score. Liver function was measured by using the LiMAx method on postoperative days (POD) 1, 3, 5, and 10.

Results: Nineteen patients were identified to suffer from NAFLD (NAFL, n = 11; NASH, n = 8). In NAFL, preoperative liver function (p = .48) and hepatic recovery on POD 1, 3, and 5 was comparable to controls (p > .05, respectively), while it was impaired on POD 10 (p = .022). NASH patients had preoperative enzymatic function comparable to controls (p = .10), but there was a trend to reduced levels on POD 1 (p = .082) and 5 (p = .062), which became significant on POD 10 (p = .003).

Conclusion: This study suggests that NAFLD impairs functional recovery assessed by LiMAx after partial hepatectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/08941939.2014.971206DOI Listing
February 2015

Independent effects of sham laparotomy and anesthesia on hepatic microRNA expression in rats.

BMC Res Notes 2014 Oct 8;7:702. Epub 2014 Oct 8.

General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: Studies on liver regeneration following partial hepatectomy (PH) have identified several microRNAs (miRNAs) that show a regulated expression pattern. These studies involve major surgery to access the liver, which is known to have intrinsic effects on hepatic gene expression and may also affect miRNA screening results. We performed two-third PH or sham laparotomy (SL) in Wistar rats to investigate the effect of both procedures on miRNA expression in liver tissue and corresponding plasma samples by microarray and qRT-PCR analyses. As control groups, non-treated rats and rats undergoing anesthesia only were used.

Results: We found that 49 out of 323 miRNAs (15%) were significantly deregulated after PH in liver tissue 12 to 48 hours postoperatively (>20% change), while 45 miRNAs (14%) were deregulated following SL. Out of these miRNAs, 10 miRNAs were similarly deregulated after PH and SL, while one miRNA showed opposite regulation. In plasma, miRNA upregulation was observed for miR-133a and miR-133b following PH and SL, whereas miR-100 and miR-466c were similarly downregulated following anesthesia and surgery.

Conclusions: We show that miRNAs are indeed regulated by sham laparotomy and anesthesia in rats. These findings illustrate the critical need for finding appropriate control groups in experimental surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1756-0500-7-702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198680PMC
October 2014

Single-incision versus multiport laparoscopic appendectomy: a case-matched comparative analysis.

Surg Endosc 2015 Jun 8;29(6):1530-6. Epub 2014 Oct 8.

Department of General, Visceral and Transplantation Surgery, Universitätsmedizin Berlin, Charité Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany,

Background: The multiport technique is the gold standard for laparoscopic appendectomy, but the use of single-incision laparoscopy is on the increase. The aim of the present study was to compare case-matched cohorts of patients who had undergone single-incision laparoscopic appendectomy (SILA) with those who had undergone conventional multiport laparoscopic appendectomy (MLA).

Methods: In a case-matched analysis, all single-incision laparoscopic appendectomies performed between July 2009 and December 2013 at one institution were reviewed and compared to multiport laparoscopic appendectomies performed during the same period. Patients who had undergone SILA were matched in terms of age, gender, body mass index (BMI), and American Society of Anesthesiologists (ASA) scores with the same number of patients who had undergone MLA. Statistical evaluation included the description and comparison of demographic factors, details of surgery, and histological data. A univariate analysis was performed to assess potential risk factors for morbidity after SILA.

Results: One hundred and fifty-six patients who had undergone SILA were reviewed, matched, and compared to the same number of patients who had undergone MLA. No significant difference was noted in mean operating times (50.83 vs. 50.61 min for SILA and MLA, respectively; p = 0.924) and the length of hospital stay (3.60 vs. 3.66 days; p = 0.704). No patient in either group required conversion to the open procedure while 6 (3.8 %) SILA patients were converted to multiport laparoscopy. SILA was not associated with significantly higher postoperative morbidity compared to MLA (9.6 % vs. 5.8 %; p = 0.288). Postoperative wound infection rates were higher after SILA (3.2 % vs. 0.6 %), but did not achieve statistical significance (p = 0.214). Statistical analysis revealed no risk factors for developing postoperative complications after the single-incision procedure.

Conclusion: SILA is a technically feasible and safe alternative to conventional MLA. The two procedures did not differ in terms of operating times, length of hospital stay, and postoperative outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-014-3837-7DOI Listing
June 2015