Publications by authors named "Martin Schenk"

52 Publications

Retrospective analysis of different therapeutic approaches for retroperitoneal duodenal perforations.

Sci Rep 2022 Jun 17;12(1):10243. Epub 2022 Jun 17.

Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Surgical therapy of duodenal perforation into the retroperitoneum entails high morbidity. Conservative treatment and endoscopic negative pressure therapy have been suggested as promising therapeutic alternatives. We aimed to retrospectively assess outcomes of patients treated for duodenal perforation to the retroperitoneum at our department. A retrospective analysis of all patients that were treated for duodenal perforation to the retroperitoneum at our institution between 2010 and 2021 was conducted. Different therapeutic approaches with associated complications within 30 days, length of in-hospital stay, number of readmissions and necessity of parenteral nutrition were assessed. We included thirteen patients in our final analysis. Six patients underwent surgery, five patients were treated conservatively and two patients received interventional treatment by endoscopic negative pressure therapy. Length of stay was shorter in patients treated conservatively. One patient following conservative and surgical treatment each was readmitted to hospital within 30 days after initial therapy whereas no readmissions after interventional treatment occurred. There was no failure of therapy in patients treated without surgery whereas four (66.7%) of six patients required revision surgery following primary surgical therapy. Conservative and interventional treatment were associated with fewer complications than surgical therapy which involves high morbidity. Conservative and interventional treatment using endoscopic negative pressure therapy in selected patients might constitute appropriate therapeutic alternatives for duodenal perforations to the retroperitoneum.
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http://dx.doi.org/10.1038/s41598-022-14278-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205956PMC
June 2022

Replacing Needle Injection by a Novel Waterjet Technology Grants Improved Muscle Cell Delivery in Target Tissues.

Cell Transplant 2022 Jan-Dec;31:9636897221080943

Department of Urology, Center for Medical Research, Eberhard Karl University of Tübingen, Tübingen, Germany.

Current regimen to treat patients suffering from stress urinary incontinence often seems not to yield satisfactory improvement or may come with severe side effects. To overcome these hurdles, preclinical studies and clinical feasibility studies explored the potential of cell therapies successfully and raised high hopes for better outcome. However, other studies were rather disappointing. We therefore developed a novel cell injection technology to deliver viable cells in the urethral sphincter complex by waterjet instead of using injection needles. We hypothesized that the risk of tissue injury and loss of cells could be reduced by a needle-free injection technology. Muscle-derived cells were obtained from young male piglets and characterized. Upon expansion and fluorescent labeling, cells were injected into cadaveric tissue samples by either waterjet or injection needle. In other experiments, labeled cells were injected by waterjet in the urethra of living pigs and incubated for up to 7 days of follow-up. The analyses documented that the cells injected by waterjet were viable and proliferated well. Upon injection in live animals, cells appeared undamaged, showed defined cellular somata with distinct nuclei, and contained intact chromosomal DNA. Most importantly, by waterjet injections, a significantly wider cell distribution was observed when compared with needle injections ( < .05, ≥ 12 samples). The success rates of waterjet cell application in living animals were significantly higher (≥95%, = 24) when compared with needle injections, and the injection depth of cells in the urethra could be adapted to the need by adjusting waterjet pressures. We conclude that the novel waterjet technology injects viable muscle cells in tissues at distinct and predetermined depth depending on the injection pressure employed. After waterjet injection, loss of cells by full penetration or injury of the tissue targeted was reduced significantly in comparison with our previous studies employing needle injections.
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http://dx.doi.org/10.1177/09636897221080943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036380PMC
April 2022

Investigation of Crystallization and Relaxation Effects in Coarse-Grained Polyethylene Systems after Uniaxial Stretching.

Polymers (Basel) 2021 Dec 20;13(24). Epub 2021 Dec 20.

Institute of Technology, Resource and Energy-Efficient Engineering (TREE), Bonn-Rhein-Sieg University of Applied Sciences, Grantham-Allee 20, 53757 Sankt Augustin, Germany.

In this study, we investigate the thermo-mechanical relaxation and crystallization behavior of polyethylene using mesoscale molecular dynamics simulations. Our models specifically mimic constraints that occur in real-life polymer processing: After strong uniaxial stretching of the melt, we quench and release the polymer chains at different loading conditions. These conditions allow for free or hindered shrinkage, respectively. We present the shrinkage and swelling behavior as well as the crystallization kinetics over up to 600 ns simulation time. We are able to precisely evaluate how the interplay of chain length, temperature, local entanglements and orientation of chain segments influences crystallization and relaxation behavior. From our models, we determine the temperature dependent crystallization rate of polyethylene, including crystallization onset temperature.
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http://dx.doi.org/10.3390/polym13244466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703326PMC
December 2021

Intraperitoneal extension of the peritoneal dialysis catheter-a new technique for catheter implantation in patients with obesity.

J Nephrol 2022 Jan 8;35(1):311-316. Epub 2021 Jul 8.

Department of General, Visceral and Transplant Surgery, Tübingen University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany.

Background: In patients with obesity and end-stage kidney disease, implantation of the peritoneal dialysis (PD) catheter may be complicated by increased abdominal circumference or skin folds. Relocation of the implantation site to the upper abdomen could solve this problem. However, this would require an extended catheter.

Methods: We developed an extended PD catheter based on a swan neck Missouri PD catheter with the help of two adaptors and a straight intraperitoneal extension segment. The extended catheter was assembled intraoperatively, and its length was adjusted individually to ensure correct positioning. After the operation, PD was commenced and handled as usual.

Results: In the period from 2011 to 2021, we implanted 31 extended PD catheters in 29 patients (38% men) with end-stage renal failure and obesity. Median age was 53 (range 28-77) years and body mass index was 35.5 (range 26.4-46.9) kg/m. The postoperative course was unremarkable except for seroma formation in one patient and dialysate leakage in another. Continuous ambulatory peritoneal dialysis (CAPD) was initiated in 20 and APD in 9 patients. The achieved median Kt/V was 2.10 (range 1.50-3.10). During the follow-up period lasting up to 51 months, there was one case of intraperitoneal catheter disconnection due to an avoidable handling error. The peritonitis rate was 1:40 months. The 1- and 2-year catheter survival was 92% and 67%, respectively, and paralleled patient survival.

Conclusions: When using a PD catheter with an intraperitoneal extension, PD catheter implantation can be relocated to the upper abdomen in patients with obesity, thus providing optimal position and easy surgical access.
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http://dx.doi.org/10.1007/s40620-021-01077-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803766PMC
January 2022

Safety and effectiveness of a novel generator algorithm for bipolar vessel sealing: a randomised controlled chronic animal study.

BMC Surg 2019 Nov 5;19(1):160. Epub 2019 Nov 5.

Erbe Elektromedizin GmbH, Waldhoernlestrasse 17, 72072, Tuebingen, Germany.

Background: Electrosurgical vessel sealers are gradually replacing conventional techniques such as ligation and clipping. Algorithms that control electrosurgical units (ESU), known as modes, are important for applications in different surgical disciplines. This chronic porcine animal study aimed to evaluate the safety and effectiveness of the novel thermoSEAL electrosurgical vessel sealing mode (TSM). The BiClamp® mode (BCM) of the renowned VIO® 300 D ESU served as control. BCM has been widely available since 2002 and has since been successfully used in many surgical disciplines. The TSM, for the novel VIO® 3 ESU, was developed to reduce sealing time and/or thermal lateral spread adjacent to the seal while maintaining clinical success rates. The primary aim of this study was to investigate the long-term and intraoperative seal quality of TSM.

Methods: The BiCision® device was used for vessel sealing with TSM and BCM in ten German Landrace pigs which underwent splenectomy and unilateral nephrectomy during the first intervention of the study. The seals were cut with the BiCision® knife. Ninety-nine arteries, veins and vascular bundles were chronically sealed for 5 or 21 days. Thereafter, during the second and terminal intervention of the study, 97 additional arteries and veins were sealed. The carotid arteries were used for histological evaluation of thermal spread.

Results: After each survival period, no long-term complications occurred with either mode. The intraoperative seal failure rates, i.e. vessel leaking or residual blood flow after the first sealing activation, were 2% with TSM versus 6% with BCM (p = 0.28). The sealing time was significantly shorter with TSM (3.5 ± 0.69 s vs. 7.3 ± 1.3 s, p < 0.0001). The thermal spread and burst pressure of arteries sealed with both modes were similar (p = 0.18 and p = 0.61) and corresponded to the histological evaluation. The measured tissue sticking parameter was rare with both modes (p = 0.33). Tissue charring did not occur. Regarding the cut quality, 97% of the seals were severed in the first and 3% in the second attempt (both with TSM and BCM).

Conclusions: The novel TSM seals blood vessels twice as fast as the BCM while maintaining excellent tissue effect and clinical success rates.

Trial Registration: Not applicable.
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http://dx.doi.org/10.1186/s12893-019-0625-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833204PMC
November 2019

A real-time model (eIBUB) for optimizing intraperitoneal drug delivery as an alternative to living animal models.

Pleura Peritoneum 2019 Sep 15;4(3):20190017. Epub 2019 Aug 15.

National Center for Pleura and Peritoneum, University of Tübingen, Tübingen, Germany.

Background: Optimization of intraperitoneal drug delivery systems requires functional models. We proposed the Inverted Bovine Urinary Bladder Model (IBUB), but IBUB does not allow repeated measurements over time and there is a significant biological variability between organs.

Methods: A further development of IBUB is presented, based on the physical principle of communicating vessels. Fresh bovine bladders were inverted so that the peritoneum lines up the inner surface. The IBUB and a second vessel were then interconnected under the same CO pressure and placed on two scales. The therapeutic solution (Doxorubicin 2.7 mg and Cisplatin 13.5 mg) was delivered via an aerosolizer. All experiments were in triplicate and blinded to the origin of samples, measurements in a GLP-certified laboratory.

Results: The enhanced IBUB (eIBUB) model allows measurements of tissue drug concentration, depth of tissue penetration and spatial distribution. The homogeneous morphology of the peritoneum enables standardized, multiple tissue sampling. eIBUB minimizes biological variability between different bladders and eliminates the bias caused by the liquid collecting at the bottom of the model. Concentration of doxorubicin in the eIBUB (mean ± STDV: 18.5 ± 22.6 ng/mg) were comparable to clinical peritoneal biopsies (19.2 ± 38.6 ng/mg), as was depth of drug penetration (eIBUB: mean (min-max) 433 (381-486) µm, clinical ~ 500 µm).

Conclusions: The eIBUB model is a simple and powerful model for optimizing intraperitoneal drug delivery and represents an attractive alternative to animal models. Results obtained are similar to those obtained in the human patient.
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http://dx.doi.org/10.1515/pp-2019-0017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812219PMC
September 2019

Automated closed-loop management of body temperature using forced-air blankets: preliminary feasibility study in a porcine model.

BMC Anesthesiol 2018 07 3;18(1):80. Epub 2018 Jul 3.

Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Paul-Ehrlich-Straße 36, Tübingen, 72076, Germany.

Background: Management of a patient's body temperature is an important aspect of care that should be addressed by targeted temperature management (TTM). Often, non-invasive methods like forced-air blankets are used. Especially in the operating room this management may be a subsidiary and repetitive task requiring constant observation of the patient's body temperature and adaption using the limited set of available settings. Thus, automation of TTM is a feasible target to improve patient outcome and reduce caregiver workload.

Methods: A Philips IntelliVue MP 50 patient monitor with an arterial PiCCO catheter system was used to measure patient blood temperature. Thermal management was performed with a 3M Bair Hugger 755 warming unit with forced air blankets. The warming unit was extended by a computer interface to allow for remote and automated control. A proposed closed-loop algorithm reads the measured temperature and performs automated control of the 3M Bair Hugger. Evaluation was performed in an experimental intensive care setting for animal studies. Two fully automated trials are compared with two manual and two uncontrolled trials in the same study setting using six female pigs for prolonged observation times of up to 90 hours in each trial.

Results: The developed system and proposed algorithm allow more precise temperature management by keeping a set target temperature within a range of ± 0.5 °C in 88% of the observation time and within a range of ± 1.0 °C at all times. The proposed algorithm yielded better performance than did manual control or uncontrolled trials. It was able to adapt to individual patient needs as it is more dynamic than look-up table approaches with fixed settings for various temperatures.

Conclusions: Closed-loop TTM using non-invasive forced-air warming blankets was successfully tested in a porcine study with the proposed hardware interface and control algorithm. This automation can be beneficial for patient outcome and can reduce caregiver workload and patient risk in clinical settings. As temperature readings are most often available, existing devices like the 3M Bair Hugger can easily be expanded. However, even if clinical application is feasible, open questions regarding approval and certification of such automated systems within the current legal situation still need to be answered.
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http://dx.doi.org/10.1186/s12871-018-0542-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029032PMC
July 2018

Fully automated life support: an implementation and feasibility pilot study in healthy pigs.

Intensive Care Med Exp 2018 Jan 16;6(1). Epub 2018 Jan 16.

Department of General, Visceral and Transplant Surgery, Tübingen University Hospital, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.

Background: Automated systems are available in various application areas all over the world for the purpose of reducing workload and increasing safety. However, such support systems that would aid caregivers are still lacking in the medical sector. With respect to workload and safety, especially, the intensive care unit appears to be an important and challenging application field. Whereas many closed-loop subsystems for single applications already exist, no comprehensive system covering multiple therapeutic aspects and interactions is available yet. This paper describes a fully closed-loop intensive care therapy and presents a feasibility analysis performed in three healthy pigs over a period of 72 h each to demonstrate the technical and practical implementation of automated intensive care therapy.

Methods: The study was performed in three healthy, female German Landrace pigs under general anesthesia with endotracheal intubation. An arterial and a central venous line were implemented, and a suprapubic urinary catheter was inserted. Electrolytes, glucose levels, acid-base balance, and respiratory management were completely controlled by an automated fuzzy logic system based on individual targets. Fluid management by adaption of the respective infusion rates for the individual parameters was included.

Results: During the study, no manual modification of the device settings was allowed or required. Homoeostasis in all animals was kept stable during the entire observation period. All remote-controlled parameters were maintained within physiological ranges for most of the time (free arterial calcium 73%, glucose 98%, arterial base excess 89%, and etCO 98%). Subsystem interaction was analyzed.

Conclusions: In the presented study, we demonstrate the feasibility of a fully closed-loop system, for which we collected high-resolution data on the interaction and response of the different subsystems. Further studies should use big data approaches to analyze and investigate the interactions between the subsystems in more detail.
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http://dx.doi.org/10.1186/s40635-018-0168-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770352PMC
January 2018

Pathophysiological central nervous system changes in a porcine model of acetaminophen-induced acute liver failure.

Toxicol Lett 2017 Nov 27;281:119-126. Epub 2017 Sep 27.

Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tuebingen, Germany. Electronic address:

Background: Critical care management of patients suffering from acute liver failure (ALF) continues to be challenging. Animal models studying the pathophysiological central nervous system alterations during the course of ALF provide an opportunity to improve diagnostic and therapeutic strategies. The aim of this study was to analyse the course of cerebral oxygenation in addition to conventional neuromonitoring during the course of acetaminophen-induced ALF.

Methods: ALF was induced by intrajejunal acetaminophen administration in 20 German landrace pigs. All animals underwent invasive hemodynamic and neuromonitoring and were maintained under standardized intensive care support. Neuromonitoring consisted of continuous intraparenchymatous recording of intracranial pressure and brain partial oxygen pressure. Hemodynamic and ventilation parameters were continuously recorded; laboratory parameters were analysed every eight hours. Mean values were compared using the Wilcoxon test.

Results: Acute liver failure occurred in all intoxicated animals after 23±2h, resulting in death due to ALF after further 15±2h. Continuous neuromonitoring was performed in all animals during the whole experiment without observing signs of intracranial haemorrhage. Two hours after manifestation of ALF an increase in brain tissue oxygen (PtiO2) was observed. Brain oxygenation stayed stable until nine hours before death. Intracranial pressure (ICP) remained basically at a plateau level until manifestation of ALF. In the following ten hours a linear and slow increase was observed until five hours before death, followed by a fast and continuous rise in ICP to a final level of 35±1mmHg. Cerebral perfusion pressure (CPP) began to decrease 25h prior to exitus, further decreasing to 18±2mmHg at the end of the experiment. A strong negative linear correlation was found between PtiO2 and ICP (R=0.97). Arterial partial pressure of oxygen (PaO2) below 100mmHg was associated with lower PtiO2 levels. Changes in arterial partial pressure of carbon dioxide (PaC02) did not influence PtiO2 values. Hemoglobin values below 7g/dl were associated with lower PtiO2 values.

Conclusions: The results of our experiments demonstrate that ICP and PtiO2 measurements indicate impending damage well before serious complications occur and their use should be considered in order to protect endangered brain function in the presence of acetaminophen-induced ALF.
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http://dx.doi.org/10.1016/j.toxlet.2017.09.018DOI Listing
November 2017

Evaluation of a novel electrosurgical sealing mode in an ex vivo and in vivo porcine model.

Surg Endosc 2018 03 18;32(3):1456-1463. Epub 2017 Sep 18.

Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Hoppe-Seyler Strasse 3, 72076, Tuebingen, Germany.

Background: Bipolar vessel sealing has been successfully introduced in a variety of procedures like prostatectomy, hysterectomy, and nephrectomy. In this study, we evaluated a new sealing mode-the thermoSEAL mode (TSM)-operated with the VIO3 generator in an ex vivo and in vivo animal study and compared the results with the commercially available BiClamp mode (BCM), operated with the VIO300D generator. Two different instruments were used in combination with both modes, BiCision and BiClamp 201T (Erbe Elektromedizin GmbH).

Methods: In the ex vivo experiment, the sealing of renal arteries was evaluated using both instruments and modes. For the in vivo study, different types of arteries and veins were sealed using both modes and instruments in a side-by-side comparison for acute complications in a total of four animals.

Results: Mean burst pressure was in all cases significantly above 360 mmHg (p < 0.001). Sealing time during the ex vivo setting was significantly shorter for TSM compared to BCM: BiCision (3.7 ± 0.4 vs. 7.1 ± 0.3 s; p < 0.0001); BiClamp 201T (3.9 ± 0.3 vs. 5.1 ± 1.1 s; p < 0.0015). Lateral thermal damage was more pronounced for BCM: BiCision (TSM 1.4 ± 0.3 mm vs. BCM 1.9 ± 0.2 mm; p < 0.0001); BiClamp 201T (TSM 1.9 ± 0.6 mm vs. BCM 3.1 ± 0.6 mm; p < 0.0001). The sealing time during the in vivo study was significantly shorter for TSM in combination with BiCision for arteries [TSM 3.0 ± 0.7 s vs. BCM 6.5 ± 1.3 s, (p < 0.0001) and veins 3.2 ± 1.1 vs. 5.8 ± 1.8 s, (p < 0.0001)]. No significant differences were seen for the two modes used with BiClamp 201T [artery: TSM 3.3 ± 0.7 s vs. BCM 3.4 ± 0.9 s, (p = 0.891)]. High sealing rates for arteries (100%) and veins (>90%) were noted for both instruments and modes.

Conclusions: While both modes used with two different instruments reveal high safety characterized by a high burst pressure, low thermal damage (ex vivo) zones, and high sealing rates (in vivo), the thermoSEAL mode convinces by its fast sealing speed probably helping to reduce operation time.
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http://dx.doi.org/10.1007/s00464-017-5832-2DOI Listing
March 2018

Algorithm-based arterial blood sampling recognition increasing safety in point-of-care diagnostics.

World J Crit Care Med 2017 Aug 4;6(3):172-178. Epub 2017 Aug 4.

Jörg Peter, Wolfgang Rosenstiel, Department of Computer Engineering, University of Tübingen, 72076 Tübingen, Germany.

Aim: To detect blood withdrawal for patients with arterial blood pressure monitoring to increase patient safety and provide better sample dating.

Methods: Blood pressure information obtained from a patient monitor was fed as a real-time data stream to an experimental medical framework. This framework was connected to an analytical application which observes changes in systolic, diastolic and mean pressure to determine anomalies in the continuous data stream. Detection was based on an increased mean blood pressure caused by the closing of the withdrawal three-way tap and an absence of systolic and diastolic measurements during this manipulation. For evaluation of the proposed algorithm, measured data from animal studies in healthy pigs were used.

Results: Using this novel approach for processing real-time measurement data of arterial pressure monitoring, the exact time of blood withdrawal could be successfully detected retrospectively and in real-time. The algorithm was able to detect 422 of 434 (97%) blood withdrawals for blood gas analysis in the retrospective analysis of 7 study trials. Additionally, 64 sampling events for other procedures like laboratory and activated clotting time analyses were detected. The proposed algorithm achieved a sensitivity of 0.97, a precision of 0.96 and an F1 score of 0.97.

Conclusion: Arterial blood pressure monitoring data can be used to perform an accurate identification of individual blood samplings in order to reduce sample mix-ups and thereby increase patient safety.
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http://dx.doi.org/10.5492/wjccm.v6.i3.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547431PMC
August 2017

Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure.

World J Gastroenterol 2017 Mar;23(9):1576-1585

Karolin Thiel, Wilfried Klingert, Alfred Königsrainer, Martin Schenk, Christian Thiel, Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen 72076, Germany.

Aim: To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose.

Methods: Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy.

Results: Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 mL/min) increased to a maximum flow of 1873 ± 175 mL/min at manifestation of ALF, which was significantly elevated ( < 0.01). Immediately after peaking, portal flow declined rapidly to 283 ± 135 mL/min at study end. Thrombocyte values (baseline 307 × 10/µL ± 34 × 10/µL) of intoxicated animals declined slowly to values of 145 × 10/µL ± 46 × 10/µL when liver failure occurred. Subsequent appearance of severe thrombocytopenia in liver failure resulted in values of 11 × 10/µL ± 3 × 10/µL preceding fatality within few hours which was significant ( > 0.01).

Conclusion: Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.
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http://dx.doi.org/10.3748/wjg.v23.i9.1576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340809PMC
March 2017

Functional vascular anatomy of the peritoneum in health and disease.

Pleura Peritoneum 2016 Sep 4;1(3):145-158. Epub 2016 Oct 4.

Department of General, Visceral and Transplant Surgery, Eberhard-Karls-Universitat Tubingen Medizinische Fakultat, Tuebingen, Germany.

The peritoneum consists of a layer of mesothelial cells on a connective tissue base which is perfused with circulatory and lymphatic vessels. Total effective blood flow to the human peritoneum is estimated between 60 and 100 mL/min, representing 1-2 % of the cardiac outflow. The parietal peritoneum accounts for about 30 % of the peritoneal surface (anterior abdominal wall 4 %) and is vascularized from the circumflex, iliac, lumbar, intercostal, and epigastric arteries, giving rise to a quadrangular network of large, parallel blood vessels and their perpendicular offshoots. Parietal vessels drain into the inferior vena cava. The visceral peritoneum accounts for 70 % of the peritoneal surface and derives its blood supply from the three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric. These vessels give rise to smaller arteries that anastomose extensively. The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to first-pass hepatic metabolism. Peritoneal inflammation and cancer invasion induce neoangiogenesis, leading to the development of an important microvascular network. Anatomy of neovessels is abnormal and characterized by large size, varying diameter, convolution and blood extravasation. Neovessels have a defective ultrastructure: formation of large "mother vessels" requires degradation of venular and capillary basement membranes. Mother vessels give birth to numerous "daughter vessels". Diffuse neoangiogenesis can be observed before appearance of macroscopic peritoneal metastasis. Multiplication of the peritoneal capillary surface by neoangiogenesis surface increases the part of cardiac outflow directed to the peritoneum.
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http://dx.doi.org/10.1515/pp-2016-0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328070PMC
September 2016

Pull-off characteristics of double-shanked compared to single-shanked ligation clips: an animal study.

Innov Surg Sci 2016 Sep 15;1(1):41-46. Epub 2016 Jun 15.

Universitätsklinikum Tübingen, Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Institut für Experimentelle Chirurgie, Tübingen, Germany.

Background: The use of surgical ligation clips is considered as the gold standard for the closure of vessels, particularly in laparoscopic surgery. The safety of clips is mainly achieved by the deep indentation of the metal bar with a high retention force. A novel double-shanked (DS) titanium clip was compared to two single-shanked clips with respect to axial and radial pull-off forces.

Methods: In a porcine model (8 animals, 51±1 kg), arteries were prepared immediately after euthanisation, assigned to either a medium (2-4 mm; n=120) or a medium-large (3.5-7 mm; n=120) clip size group, and clipped with the appropriate clip size. After dissection, axial and radial pull-off forces were measured.

Results: The axial pull-off force of the DS-Clip was higher than one single-shanked clip and comparable to the other single-shanked clip, and overall was linearly correlated to the cross-sectional area of the clip. The radial pull-off force of the DS-Clip was significantly higher than both single-shanked clips and, for the single-shanked clips, was correlated to the total clip thickness. The variation of radial pull-off force was lower for the DS-Clip due to a defined catch in the clip applier.

Conclusions: The radial pull-off force was lower than the axial pull-off force in total and therefore appears to be the critical point of dislocation. Due to the higher total holding mass, the DS-Clip provided a clear advantage in this regard and might therefore decrease the dislocation rate. The catch in the applier increases the reproducibility in clip placement.
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http://dx.doi.org/10.1515/iss-2016-0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753983PMC
September 2016

Quantitative Assessment of Iron-Labeled Stem-Cell Adhesion at the Vessel Wall in a Vascular Flow Model: Correlation of T2*-Weighted Imaging at 3 T and Histology.

J Vasc Interv Radiol 2015 Nov 29;26(11):1728-34.e1-3. Epub 2015 Jul 29.

Division of Diagnostic Radiology, Department of Diagnostic and Interventional Radiology, Section of Experimental Radiology, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany.

Purpose: To evaluate the distribution of superparamagnetic iron oxide (SPIO)-labeled cells in a perfused segment of a porcine artery and to estimate the number of adherent cells by means of magnetic resonance (MR) imaging.

Materials And Methods: Six vessel specimens (diameters between 0.8 and 1.2 cm) were placed in a bioreactor system, and 2 × 10(4) to 1 × 10(6) SPIO-labeled endothelial colony-forming cells were injected into the artery within the perfused reactor. The area of resulting signal extinctions at the inner wall of the vessels was quantified on MR images by using a high-resolution T2*-weighted sequence with a slice-by-slice approach. After imaging, the labeled cells were quantified histologically.

Results: The total iron load of each cell was 56.5 pg ± 14.4. In the applied range of 2 × 10(4) to 1 × 10(6) cells per vessel, the area of iron-induced signal extinction at the vessel wall on T2*-weighted imaging corresponded to the histologically detected cell number (r = 0.98, P < .001).

Conclusions: A correlation between the area of signal extinction and the number of labeled cells at the vessel wall was found. This might help to evaluate dose rates in further clinical applications of intravascular cell-based therapies.
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http://dx.doi.org/10.1016/j.jvir.2015.06.018DOI Listing
November 2015

First In Vivo Results of a Novel Pediatric Oxygenator with an Integrated Pulsatile Pump.

ASAIO J 2015 Sep-Oct;61(5):574-82

From the *Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Tuebingen, Germany; †Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute, Aachen University, Aachen, Germany; ‡Department of General, Visceral and Transplant Surgery, University Hospital of Tuebingen, Tuebingen, Germany; and §Herold-Consulting, Business center, Heidelberg, Germany.

Extracorporeal membrane oxygenation (ECMO) is a pivotal bridge to recovery for cardiopulmonary failure in children. Besides its life-saving quality, it is often associated with severe system-related complications, such as hemolysis, inflammation, and thromboembolism. Novel oxygenator and pump systems may reduce such ECMO-related complications. The ExMeTrA oxygenator is a newly designed pediatric oxygenator with an integrated pulsatile pump minimizing the priming volume and reducing the surface area of blood contact. The aim of our study was to investigate the feasibility and safety of this new ExMeTrA (expansion mediated transport and accumulation) oxygenator in an animal model. During 6 h of extracorporeal circulation (ECC) in pigs, parameters of the hemostatic system including coagulation, platelets and complement activation, and flow rates were investigated. A nonsignificant trend in C3 consumption, thrombin-antithrombin-III (TAT) complex formation and a slight trend in hemolysis were detected. During the ECC, the blood flow was constantly at 500 ml/min using only flexible silicone tubes inside the oxygenator as pulsatile pump. Our data clearly indicate that the hemostatic markers were only slightly influenced by the ExMeTrA oxygenator. Additionally, the oxygenator showed a constant quality of blood flow. Therefore, this novel pediatric oxygenator shows the potential to be used in pediatric and neonatal support with ECMO.
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http://dx.doi.org/10.1097/MAT.0000000000000256DOI Listing
July 2016

Retinal output changes qualitatively with every change in ambient illuminance.

Nat Neurosci 2015 Jan 8;18(1):66-74. Epub 2014 Dec 8.

Retinal Circuits and Optogenetics, Centre for Integrative Neuroscience and Bernstein Center for Computational Neuroscience, University of Tübingen, Germany.

The collective activity pattern of retinal ganglion cells, the retinal code, underlies higher visual processing. How does the ambient illuminance of the visual scene influence this retinal output? We recorded from isolated mouse and pig retina and from mouse dorsal lateral geniculate nucleus in vivo at up to seven ambient light levels covering the scotopic to photopic regimes. Across each luminance transition, most ganglion cells exhibited qualitative response changes, whereas they maintained stable responses within each luminance. We commonly observed the appearance and disappearance of ON responses in OFF cells and vice versa. Such qualitative response changes occurred for a variety of stimuli, including full-field and localized contrast steps and naturalistic movies. Our results suggest that the retinal code is not fixed but varies with every change of ambient luminance. This finding raises questions about signal processing within the retina and has implications for visual processing in higher brain areas.
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http://dx.doi.org/10.1038/nn.3891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338531PMC
January 2015

Controlled processing of a full-sized porcine liver to a decellularized matrix in 24 h.

J Biosci Bioeng 2015 May 21;119(5):609-13. Epub 2014 Nov 21.

Department of General, Visceral, and Transplant Surgery, University of Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany.

The generation of full-sized humanized organs based on animal matrix scaffolds is a promising approach to overcome the shortage of transplant organs. Recent decellularization methods are mostly time-consuming and associated with large rinsing volumes and poorly standardized procedures. In this study we developed an optimized rapid and standardized decellularization method to obtain a functional porcine liver matrix within 24 h. Full porcine livers (n = 10) were decellularized by flushing with 3 L of an isotonic sodium chloride solution and controlled portal perfusion (20 mmHg) with 2 × 10 L of a 1% sodium dodecyl sulphate (SDS) solution at 37°C and a final perfusion with DNase (n = 5). Protein concentrations were continuously monitored by optical density (280 nm). DNA, glycosaminoglycans, and collagen contents were assessed and a haematoxylin and eosin (H&E) staining was performed. After 24 h of perfusion, the liver had a white and translucent appearance, and no further protein was eluted. Histological staining showed an intact extracellular matrix with no nuclear residuals. Moreover, only trace amounts of DNA were detectable in the decellularized tissue (p < 0.001), while glycosaminoglycans and about 60% of collagen levels could be preserved. Thus, we demonstrate that human-scale porcine livers can be successfully decellularized with small volumes of an SDS solution and DNase in a standardized process within 24 h to obtain a clinically relevant organ scaffold suitable for further tissue engineering.
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http://dx.doi.org/10.1016/j.jbiosc.2014.10.019DOI Listing
May 2015

Acute liver failure after amanitin poisoning: a porcine model to detect prognostic markers for liver regeneration.

Hepatol Int 2014 Jan 4;8(1):128-36. Epub 2013 Dec 4.

Department of General, Visceral and Transplant Surgery, University Hospital, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany.

Purpose: Over 90 % of fatal mushroom poisoning occurs after ingestion of amanitin-containing species. This study aimed to investigate markers indicating spontaneous liver regeneration in a porcine acute liver failure (ALF) model after α-amanitin intoxication.

Methods: German landrace pigs received either 0.15 mg/kg (n = 5) α-amanitin intravenously or 0.35 mg/kg (n = 5) intraportally. Pigs were invasively monitored and kept under general anesthesia throughout the experiment. Laboratory parameters were analyzed every 8 h.

Results: ALF occurred in all animals (10/10) 41 ± 3 h after intoxication. All pigs receiving 0.35 mg/kg α-amanitin and one pig receiving 0.15 mg/kg α-amanitin died 57 ± 16 h after the primary onset of ALF. Four pigs of the 0.15 mg/kg intoxication group recovered spontaneously from ALF after 56 ± 6 h. Starting at 32 h after intoxication, significantly higher values of albumin and total plasma protein could be measured in surviving animals (p < 0.05). A significant temporary increase in the tumor necrosis factor alpha (TNF-α) plasma concentration was detected 40-80 h after intoxication in recovering animals (p < 0.05).

Conclusions: This porcine model represents a novel tool to analyse multiple aspects of liver regeneration following α-amanitin poisoning to allow early discrimination between a fatal course and survivors. Decreased albumin and total plasma protein concentrations in the early intoxication phase indicated a lethal outcome, while an increase in the TNF-α plasma concentration was identified as the earliest prognostic plasma marker detecting liver regeneration a long time before liver function was biochemically and clinically impaired.
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http://dx.doi.org/10.1007/s12072-013-9491-7DOI Listing
January 2014

Differential induction of apoptosis and senescence by the DNA methyltransferase inhibitors 5-azacytidine and 5-aza-2'-deoxycytidine in solid tumor cells.

Mol Cancer Ther 2013 Oct 7;12(10):2226-36. Epub 2013 Aug 7.

Corresponding Author: Michael Bitzer, Medical University Hospital, University of Tuebingen, Otfried-Mueller-Str. 10, Tuebingen D-72076, Germany.

Epigenetic alterations are a hallmark of cancer that govern the silencing of genes. Up to now, 5-azacytidine (5-aza-CR, Vidaza) and 5-aza-2'-deoxycytidine (5-aza-dC, Dacogen) are the only clinically approved DNA methyltransferase inhibitors (DNMTi). Current effort tries to exploit DNMTi application beyond acute leukemia or myelodysplastic syndrome, especially to solid tumors. Although both drugs only differ by a minimal structural difference, they trigger distinct molecular mechanisms that are highly relevant for a rational choice of new combination therapies. Therefore, we investigated cell death pathways in vitro in human hepatoma, colon, renal, and lung cancer cells and in vivo in chorioallantoic membrane and xenograft models. Real-time cancer cell monitoring and cytokine profiling revealed a profoundly distinct response pattern to both drugs. 5-aza-dC induced p53-dependent tumor cell senescence and a high number of DNA double-strand breaks. In contrast, 5-aza-CR downregulated p53, induced caspase activation and apoptosis. These individual response patterns of tumor cells could be verified in vivo in chorioallantoic membrane assays and in a hepatoma xenograft model. Although 5-aza-CR and 5-aza-dC are viewed as drugs with similar therapeutic activity, they induce a diverse molecular response in tumor cells. These findings together with other reported differences enable and facilitate a rational design of new combination strategies to further exploit the epigenetic mode of action of these two drugs in different areas of clinical oncology.
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http://dx.doi.org/10.1158/1535-7163.MCT-13-0137DOI Listing
October 2013

Internally gas-cooled radiofrequency applicators as an alternative to conventional radiofrequency and microwave ablation devices: an in vivo comparison.

Eur J Radiol 2013 Aug 20;82(8):e350-5. Epub 2013 Mar 20.

Eberhard Karls University of Tübingen, Tübingen University Hospital, Department of Diagnostic and Interventional Radiology, Hoppe-Seyler-Straße 3, Tübingen 72076, Germany.

Purpose: To test the efficacy of internally CO2-cooled radiofrequency (RF) ablation in vivo and to compare its effectiveness to a standard water-cooled RF probe and to a gas-cooled microwave (MW) device.

Method And Materials: 49 ablations were performed on 15 pigs under general anesthesia using 15G monopolar CO2-cooled RF applicators, 17G monopolar water-cooled RF applicators and 15G internally CO2-cooled microwave devices. The power of the MW device was 45W, the current of the gas-cooled RF device was 1200-1600mA. At the water-cooled RF probe, maximum power of 200W was set. Ablation time was 15min. The short and long axes of the ablation zone were measured. Histological analyses and NADH-staining were performed. The diameters and the ablation volumes were compared using an analysis of variance.

Results: No spots of untreated tissue were observed close to the cooled needle track in any of the ablation zones. The largest short axis diameter was 3.4±0.5cm achieved with the gas-cooled monopolar applicator. With the water-cooled applicators, short axis diameter was significantly smaller, reaching 2.5±0.4cm. Gas-cooled MW probes achieved 2.9±1.0cm. The largest ablation volume was 31.5±12ml (gas-cooled RF), and the smallest was 12.7±4ml (water-cooled RF). Short/long axis ratio was largest for gas-cooled RF probes with 0.73±0.08 versus 0.64±0.04 for the water-cooled probes and 0.49±0.25 for the microwave applicator.

Conclusion: Gas-cooled RF applicators may have a higher potential for effective destruction of liver lesions than comparable water-cooled RF systems, and may be an alternative to standard RF and MW ablation devices.
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http://dx.doi.org/10.1016/j.ejrad.2013.02.029DOI Listing
August 2013

Selective protection of human liver tissue in TNF-targeting of cancers of the liver by transient depletion of adenosine triphosphate.

PLoS One 2012 18;7(12):e52496. Epub 2012 Dec 18.

Department of Internal Medicine I, Medical University Hospital, Tuebingen, Germany.

Background: Tumor necrosis factor alpha (TNF) is able to kill cancer cells via receptor-mediated cell death requiring adenosine triphosphate (ATP). Clinical usage of TNF so far is largely limited by its profound hepatotoxicity. Recently, it was found in the murine system that specific protection of hepatocytes against TNF's detrimental effects can be achieved by fructose-mediated ATP depletion therein. Before employing this quite attractive selection principle in a first clinical trial, we here comprehensively investigated the interdependence between ATP depletion and TNF hepatotoxicity in both in vitro and ex vivo experiments based on usage of primary patient tissue materials.

Methods: Primary human hepatocytes, and both non-tumorous and tumorous patient-derived primary liver tissue slices were used to elucidate fructose-induced ATP depletion and TNF-induced cytotoxicity.

Results: PHH as well as tissue slices prepared from non-malignant human liver specimen undergoing a fructose-mediated ATP depletion were both demonstrated to be protected against TNF-induced cell death. In contrast, due to tumor-specific overexpression of hexokinase II, which imposes a profound bypass on hepatocytic-specific fructose catabolism, this was not the case for human tumorous liver tissues.

Conclusion: Normal human liver tissues can be protected transiently against TNF-induced cell death by systemic pretreatment with fructose used in non-toxic/physiologic concentrations. Selective TNF-targeting of primary and secondary tumors of the liver by transient and specific depletion of hepatocytic ATP opens up a new clinical avenue for the TNF-based treatment of liver cancers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052496PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525543PMC
June 2013

In vitro comparison of hypericin and 5-aminolevulinic acid-derived protoporphyrin IX for photodynamic inactivation of medulloblastoma cells.

PLoS One 2012 14;7(12):e51974. Epub 2012 Dec 14.

Department of Neurosurgery, Eberhard Karls University Tübingen, Tübingen, Germany.

Background: Hypericin (HYP) is a naturally occurring photosensitizer. Cellular uptake and photodynamic inactivation after incubation with this photosensitizer have neither been examined in medulloblastoma cells in vitro, nor compared with 5-aminolevulinic acid-derived protoporphyrin IX (5-ALA-derived PpIX).

Methods: In 3 medulloblastoma cell lines (D283 Med, Daoy, and D341 Med) the time- and concentration-dependent intracellular accumulation of HYP and 5-ALA-derived PpIX was analyzed by fluorescence microscopy (FM) and FACS. Photocytotoxicity was measured after illumination at 595 nm (HYP) and 635 nm (5-ALA-derived PpIX) in D283 Med cells and compared to U373 MG glioma cells.

Results: All medulloblastoma cell lines exhibited concentration- and time-dependent uptake of HYP. Incubation with HYP up to 10 µM resulted in a rapid increase in fluorescence intensity, which peaked between 2 and 4 hours. 5-ALA-derived PpIX accumulation increased in D283 Med cells by 22% over baseline after 5-ALA incubation up to 1.2 mM. Photocytotoxicity of 5-ALA-derived PpIX was higher in D283 Med medulloblastoma compared to U373MG glioma. The LD50 [lethal dose (light dose that is required to reduce cell survival to 50% of control)] of 5-ALA-derived PpIX was 3.8 J/cm(2) in D283 Med cells versus 5.7 J/cm2 in U373MG glioma cells. Photocytotoxicity of HYP in D283 Med cells was determined at 2.5 µM after an incubation time of 2 h and an illumination wavelength of 595 nm. The [Formula: see text] value was 0.47 J/cm(2).

Conclusion: By its 5-fold increase in fluorescence over autofluorescence levels HYP has excellent properties for tumor visualization in medulloblastomas. The high photocytotoxicity of HYP, compared to 5-ALA-derived PpIX, is convincingly demonstrated by its 8- to 13-fold lower LD50. Therefore HYP might be a promising molecule for intraoperative visualization and photodynamic treatment of medulloblastomas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051974PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522623PMC
September 2013

Contributors to individual quality of life after liver transplantation.

Eur J Clin Invest 2013 Jan 18;43(1):11-9. Epub 2012 Oct 18.

Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Tuebingen, Germany.

Background: With increasing improvements of patient survival after liver transplantation, the focus on outcome measures shifts from survival rate to quality of life. Individual quality of life is crucial to rehabilitate patients after transplantation. Therefore, it is important to identify specific issues that contribute to high individual quality of life. In contrast to the Short form 36 Health Survey (SF-36), the Schedule for the Evaluation of Individual aspects of Quality of Life-direct weighting (SEIQoL-DW) allows patients to name the areas of life, which are important to them.

Design: In a semi-structured interview style, 71 patients following liver transplant were asked to complete the SEIQoL-DW and the SF-36 in a cross-sectional design.

Results: We found five quality of life areas that were chosen by more than half of the patients: family, friends, sports, partnership and profession/occupation. Health was only mentioned by 45% of all patients. Individual quality of life did not differ from healthy population. In the SF-36, patients showed normal mental health parameters but reduced physical components. A strong correlation between SEIQoL-DW-Index and the mental component summary of the SF-36 was observed.

Conclusion: In addition to the widely used standardized SF-36, the individual measure SEIQoL-DW shows new aspects concerning the areas of quality of life, which are personally important to the participants. Less than half of our patients mentioned health and the five most nominated areas are not related to health. By focusing on health, the importance of health-related factors is overrated, and the impact of non-medical effects is underrepresented.
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http://dx.doi.org/10.1111/eci.12007DOI Listing
January 2013

The values of cerebrovascular pressure reactivity and brain tissue oxygen pressure reactivity in experimental anhepatic liver failure.

Neurocrit Care 2012 Oct;17(2):271-80

Department of General, Visceral and Transplant Surgery, Eberhard Karls University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany.

Background: We investigated in a porcine model of anhepatic acute liver failure (ALF), the value of two parameters describing cerebrovascular autoregulatory capacity, pressure reactivity index (PRx) and brain tissue oxygen pressure reactivity (ORx), regarding their power to predict the development of intracranial hypertension.

Methods: In six pigs, hepatectomy was performed. Only one animal was sham operated. All animals received neuromonitoring including arterial blood pressure, intracranial pressure (ICP), and brain tissue partial oxygen pressure (P(br)O(2)). The average time of neuromonitoring was 31.0 h. Cerebral perfusion pressures (CPP), cerebrovascular pressure reactivity index (PRx) and brain tissue oxygen reactivity index (ORx) were calculated.

Results: Perioperative disturbance of AR improved within 4 h after surgery. From 6 to 16 h post hepatectomy, ICP did slowly increase by 4 mmHg from baseline; CPP remained stable around 40 mmHg. PRx and ORx, however, indicated in this period a progressive loss of AR, reflected in a decrease of P(br)O(2) despite unchanged CPP. Beyond 16 h, ICP rose quickly. At CPP levels below 35 mmHg, P(br)O(2) fell to ischemic levels.

Conclusions: The loss of cerebrovascular autoregulatory capacity, indicated by a rise of PRx and ORx precedes the final crisis of uncontrollable intracranial hypertension in this animal model by hours. During this phase cerebral blood flow, as reflected in tissue oxygenation, deteriorates despite unchanged CPP. Monitoring of AR during ALF therefore seems to carry the power to identify a risk for development of critical CBF and intracranial hypertension.
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http://dx.doi.org/10.1007/s12028-012-9714-0DOI Listing
October 2012

Correlation of the intracranial pressure to the central venous pressure in the late phase of acute liver failure in a porcine model.

Acta Neurochir Suppl 2012 ;114:387-91

Department of General, Visceral Transplant Surgery, Tuebingen University Hospital, Tuebingen, Germany.

Volume loading is a common method used to ensure adequate circulation. However, in the late phase of acute liver failure complications that often lead to death are cerebral swelling and brainstem edema, which are considered to result from increasing intracranial pressure (ICP). In former studies cerebral venous pressure (CVP) and ICP were reported to be independent entities. Acute liver failure was induced in 25 German land race pigs by acetaminophen intoxication. CVP and ICP were measured continuously. Hydroxyethyl starch solution and noradrenalin were administered to stabilize the circulation at a mean arterial pressure above 60mmHg. There is an increasing correlation in quantity and quality between the CVP and ICP in the last 24 h before exitus. Beginning with a slope of 0.24 (ICP against CVP) and a low correlation coefficient of 0.08. 24h before exitus, this situation remained stable until 16 h to exitus (m = 0.22, r = 0.1). The correlation increased from 16 to 8 h prior to exitus to a slope of m = 0.5 and a correlation of r = 0.3 and remained until exitus. In late acute liver failure it seems therefore clinically reasonable to keep circulation within an adequate range by the use of noradrenalin and to avoid fluid overload.
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http://dx.doi.org/10.1007/978-3-7091-0956-4_75DOI Listing
May 2012

Is P(br)O (2) pressure reactivity index (ORx) dependent on the type of oxygen probe? An in vivo study.

Acta Neurochir Suppl 2012 ;114:173-6

Department of General and Transplantation Surgery, Eberhard-Karls-University Hospital, Tübingen, Germany.

Objective: To evaluate if ORx is dependent on the type of brain tissue O(2) (P(br)O(2)) probe in an in vivo setting.

Methods: In eight German landrace pigs two types of probes were implanted simultaneously in the same cerebral hemisphere. All pigs underwent hepatectomy and received neuromonitoring until death. A LICOX(®) probe CCI.S, representing a Clarke type electrode, was compared with a Raumedic Neurovent PTO, representing an optode. Data were sampled at 50 Hz. Average values were calculated every 30 s. Cerebral perfusion pressure (CPP) was averaged over 30 s. ORx was calculated for each probe. To increase the signal to noise ratio of the ORx, the ORx values, which had been assessed every minute, were averaged over 1 h.

Results: The overall measurement time was 145.1 h (8,703 data pairs). Despite a mean difference of 6.2 mmHg (p < 0.0001) in the measured values of P(br)O(2), the mean ORx(licox) was 0.139, mean ORx(raumedic) 0.146 (p = 0.2098). Correlation coefficient of ORx values assessed every minute and every hour was 0.52 and 0.58 respectively.

Conclusion: Despite this significant difference in absolute values of P(br)O(2) the derived mean ORx values were not different. Similar to the established Licox system, the Raumedic system seems to enable a valid ORx recording.
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http://dx.doi.org/10.1007/978-3-7091-0956-4_33DOI Listing
May 2012

Experimental comparison of the measurement accuracy of the Licox(®) and Raumedic (®) Neurovent-PTO brain tissue oxygen monitors.

Acta Neurochir Suppl 2012 ;114:169-72

Department of Neurosurgery, Eberhard Karls University Hospital, Tübingen, Germany.

Background: Only a few experimental reports are available on the direct comparison of Licox(®) and Raumedic(®)-Neurovent-PTO brain tissue oxygen pressure (P(br)O(2)) monitors. We compared the two systems regarding their measurement properties under experimental in vitro and in vivo conditions.

Materials And Methods: Eight Licox(®) and Raumedic(®) Neurovent-PTO(®) sensors were tested for 10 min at 37°C, atmospheric pressure, at an oxygen content of 0% and 100% before and after the in vivo test. The same probes were implanted in German landrace pigs, which underwent hepatectomy. The mean P(br)O(2) values were recorded every minute. An O(2) challenge with inhalation of 100% O(2) for 10 min was performed 2 h post-abdominal surgery.

Results: At 0% O(2) content values varied from 0.2 to 7 mmHg, at 100% O(2) content from 130 to 165 mmHg. No difference between probes was found. In vivo tests: Raumedic® showed higher P(br)O(2) values (mean +6.3 mmHg, p < 0.0001) compared with Licox®. During O(2) challenge, both probes responded similarly; however, Raumedic(®) had a 10% higher response amplitude (p < 0.005). After explantation there was again no difference between the two sensors.

Conclusion: Raumedic(®) sensors measured higher P(br)O(2) values. There was no significant difference regarding overall measurement of in vitro accuracy between the two probes, which proved to be robust when used consecutively for longer periods and in different environments.
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http://dx.doi.org/10.1007/978-3-7091-0956-4_32DOI Listing
May 2012

Evaluation of thermal damage in a pig model.

J Invest Surg 2012 Feb;25(1):43-50

Department of Gynaecology and Obstetrics, University of Tuebingen, Calwerstr. 7, D-72076 Tuebingen, Germany.

Background: Electrosurgical vessel sealing produces seals that can withstand intraluminal pressures well above the physiological range. In many cases it is more efficient than other methods, such as sutures, hemoclips, and ultrasonic coagulation devices, but bears lateral thermal damage as a side effect. The overall aim of this study was to compare the thermal lateral damage (TL) in vivo versus ex vivo using two different bipolar vessel sealing instruments in an epigastric vein animal model.

Material And Methods: A total of 96 thermofusions of bilateral epigastric veins were carried out in a prospective, randomized and controlled study design. The laparoscopic BiClamp (type Maryland) and the bipolar clamp Kelly model Clermont-Ferrand were used for ex vivo versus in vivo investigation. After exposure of the two bilateral epigastric veins the proximal sections were bilaterally coagulated in vivo with the two different instruments. For ex vivo coagulation, the uncoagulated section of the vein was removed and coagulated ex vivo. The TL was investigated by infrared measurement, light microscope and histological analysis.

Results: The comparison of the extent of coagulation damage between ex vivo and in vivo coagulation did not differ significantly: no differences between in vivo and ex vivo measurements were found for the Kelly clamp. In the case of the Maryland clamp only a significant greater TL in vivo was shown for stereomicroscopic measurements.

Conclusions: Ex vivo TL results are comparable with in vivo results. This might prospectively spare in vivo studies with respect to TL and might facilitate the design of future experiments for the development of bipolar electrocoagulation devices.
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http://dx.doi.org/10.3109/08941939.2011.591895DOI Listing
February 2012

[Is the traditional open donor nephrectomy in living donor renal transplantation still up to date?].

Wien Klin Wochenschr 2012 Jan 30;124(1-2):39-44. Epub 2011 Nov 30.

Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie, Tübingen, Germany.

Background: Living donor kidney transplantation is a well-established method to reduce time on the waiting list. Although the laparoscopic donor nephrectomy has already been established worldwide, more than 80% of the living donor nephrectomies are performed as a traditional open donor nephrectomy in Germany. The aim of our study was to analyze perioperative data and long-term outcome of donors and recipients following open donor nephrectomy.

Methods: From February 2004 to July 2008, a total of 51 open donor nephrectomies were performed in Tuebingen University Hospital. Forty-five data of corresponding transplant donors and recipients were analyzed. The Kocak classification which provides a format to compare postoperative complications after living donor nephrectomy was used.

Results: Five-year graft survival was 100%. No intraoperative complications occurred. Postoperatively Grad I complications were observed in 10 donors (22.2%). In the long term no major complications occurred. Two donors (4.4%) had newly diagnosed hypertension and required antihypertensive medication. None of the donors developed proteinuria. Right-sided transabdominal donor nephrectomy was associated with a shorter mean hospital stay compared to left-sided lumbar nephrectomy. (7.8 ± 2.4 vs. 9.2 ± 1.8 days, p < 0.05).

Conclusion: Open donor nephrectomy is a safe procedure with an excellent graft survival. Complication rates in our center are comparable to recent results in laparoscopic living donor nephrectomy. Therefore, the open donor nephrectomy remains important.
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http://dx.doi.org/10.1007/s00508-011-0094-9DOI Listing
January 2012
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