Publications by authors named "Karolin Thiel"

32 Publications

Comparison of Two Endoscopic Therapeutic Interventions as Primary Treatment for Anastomotic Leakages after Total Gastrectomy.

Cancers (Basel) 2022 Jun 16;14(12). Epub 2022 Jun 16.

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

Introduction: An esophagojejunal anastomotic leak following an oncological gastrectomy is a life-threatening complication, and its management is challenging. A stent application and endoscopic negative pressure therapy are possible therapeutic options. A clinical comparison of these strategies has been missing until now.

Methods: A retrospective analysis of 14 consecutive patients endoscopically treated for an anastomotic leak after a gastrectomy between June 2014 and December 2019 was performed.

Results: The mean time of the diagnosis of the leakage was 7.14 days after surgery. Five patients were selected for a covered stent, and nine patients received endoscopic negative pressure therapy. In the stent group, the mean number of endoscopies was 2.4, the mean duration of therapy was 26 days, and the mean time of hospitalization was 30 days. In patients treated with endoscopic negative pressure therapy, the mean number of endoscopies was 6.0, the mean days of therapy duration was 14.78, and the mean days of hospitalization was 38.11. Treatment was successful in all patients in the stent-based therapy group and in eight of nine patients in the negative pressure therapy group.

Discussion: Good clinical results in preserving the anastomosis and providing sepsis control was achieved in all patients. Stent therapy resulted in anastomosis healing with a lower number of endoscopies, a shorter time of hospitalization, and rapid oral nutrition.
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http://dx.doi.org/10.3390/cancers14122982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220783PMC
June 2022

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

Prolonged Exposure to Oxaliplatin during HIPEC Improves Effectiveness in a Preclinical Micrometastasis Model.

Cancers (Basel) 2022 Feb 24;14(5). Epub 2022 Feb 24.

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

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 µm thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients' samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.
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http://dx.doi.org/10.3390/cancers14051158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909393PMC
February 2022

Endoscopic Management for Post-Surgical Complications after Resection of Esophageal Cancer.

Cancers (Basel) 2022 Feb 15;14(4). Epub 2022 Feb 15.

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

Background: Esophageal cancer (EC) is the sixth-leading cause of cancer-related deaths in the world. Esophagectomy is the most effective treatment for patients without invasion of adjacent organs or distant metastasis. Complications and relevant problems may occur in the early post-operative course or in a delayed fashion. Here, innovative endoscopic techniques for the treatment of postsurgical problems were developed during the past 20 years.

Methods: Endoscopic treatment strategies for the following postoperative complications are presented: anastomotic bleeding, anastomotic insufficiency, delayed gastric passage and anastomotic stenosis. Based on a literature review covering the last two decades, therapeutic procedures are presented and analyzed.

Results: Addressing the four complications mentioned, clipping, stenting, injection therapy, dilatation, and negative pressure therapy are successfully utilized as endoscopic treatment techniques today.

Conclusion: Endoscopic treatment plays a major role in both early-postoperative and long-term aftercare. During the past 20 years, essential therapeutic measures have been established. A continuous development of these techniques in the field of endoscopy can be expected.
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http://dx.doi.org/10.3390/cancers14040980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870330PMC
February 2022

Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy.

J Immunother Cancer 2021 12;9(12)

Department of Dermatology, University Medical Center, Tübingen, Germany

Background: Anti-programmed cell death protein 1 (PD-1) antibodies are now routinely administered for metastatic melanoma and for increasing numbers of other cancers, but still only a fraction of patients respond. Better understanding of the modes of action and predictive biomarkers for clinical outcome is urgently required. Cancer rejection is mostly T cell-mediated. We previously showed that the presence of NY-ESO-1-reactive and/or Melan-A-reactive T cells in the blood correlated with prolonged overall survival (OS) of patients with melanoma with a heterogeneous treatment background. Here, we investigated whether such reactive T cells can also be informative for clinical outcomes in metastatic melanoma under PD-1 immune-checkpoint blockade (ICB).

Methods: Peripheral blood T cell stimulation by NY-ESO-1 and Melan-A overlapping peptide libraries was assessed before and during ICB in two independent cohorts of a total of 111 patients with stage IV melanoma. In certain cases, tumor-infiltrating lymphocytes could also be assessed for such responses. These were characterized using intracellular cytokine staining for interferon gamma (IFN-γ), tumor negrosis factor (TNF) and CD107a. Digital pathology analysis was performed to quantify NY-ESO-1 and Melan-A expression by tumors. Endpoints were OS and progression-free survival (PFS).

Results: The initial presence in the circulation of NY-ESO-1- or Melan-A-reactive T cells which became no longer detectable during ICB correlated with validated, prolonged PFS (HR:0.1; p>0.0001) and OS (HR:0.2; p=0.021). An evaluation of melanoma tissue from selected cases suggested a correlation between tumor-resident NY-ESO-1- and Melan-A-reactive T cells and disease control, supporting the notion of a therapy-associated sequestration of cells from the periphery to the tumor predominantly in those patients benefitting from ICB.

Conclusions: Our findings suggest a PD-1 blockade-dependent infiltration of melanoma-reactive T cells from the periphery into the tumor and imply that this seminally contributes to effective treatment.
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http://dx.doi.org/10.1136/jitc-2021-003439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693089PMC
December 2021

Endoscopic negative pressure therapy as stand-alone treatment for perforated duodenal diverticulum: presentation of two cases.

BMC Gastroenterol 2021 Nov 21;21(1):436. Epub 2021 Nov 21.

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

Background: Endoscopic negative pressure therapy is a novel and successful treatment method for a variety of gastrointestinal leaks. This therapy mode has been frequently described for rectal and esophageal leakages. Duodenal diverticular perforations are rare but life-threatening events. The early diagnosis of duodenal diverticular perforation is often complicated by inconclusive symptoms. This is the first report about endoscopic negative pressure therapy in patients with perforated duodenal diverticula.

Case Presentation: We present two cases of duodenal diverticula perforations treated with endoscopic negative pressure therapy as stand-alone treatment. Start of symptoms varied from one to three days before hospital admission. Early sectional imaging led to the diagnosis of duodenal diverticular perforation. Both patients were treated with endoluminal endoscopic negative pressure therapy with simultaneous feeding option. Three respective changes of the suction device were performed. Both patients were treated with antibiotics and antimycotics during their hospital stay and be discharged from hospital after 20 days.

Conclusions: This is the first description of successful stand-alone treatment by endoscopic negative pressure therapy in two patients with perforated duodenal diverticulum. We thus strongly recommend to attempt interventional therapy with endoluminal endoscopic negative pressure therapy in patients with duodenal diverticular perforations upfront to surgery.
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http://dx.doi.org/10.1186/s12876-021-02018-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607673PMC
November 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

Endoscopic Negative Pressure Therapy (ENPT) Is Superior to Stent Therapy for Staple Line Leak After Sleeve Gastrectomy: a Single-Center Cohort Study.

Obes Surg 2021 06 1;31(6):2511-2519. Epub 2021 Mar 1.

Department for General, Visceral and Transplant Surgery, Eberhard-Karls-University Hospital, Hoppe-Seyler-Str. 3-5, 72076, Tuebingen, Germany.

Purpose: Staple line leak (SLL) is a serious complication after sleeve gastrectomy (SG). Common endoscopic treatment options include self-expandable metallic stent (SEMS), endoscopic internal drainage (EID), and endoscopic closure. The endoscopic negative pressure therapy (ENPT) is a promising treatment option combining temporary sealing of the defect with drainage of the inflammatory bed. In this study, we compare the outcome of ENPT and SEMS for the treatment of SLL following SG.

Materials And Methods: A retrospective cohort of 27 patients (21 females) treated at a single center for SLL after SG was included. ENPT was primary therapy for 14 patients and compared with 13 patients treated primarily using SEMS.

Results: ENPT was associated with a significant reduction of hospital stay (19 ± 15.1 vs. 56.69 ± 47.21 days, p = 0.027), reduced duration of endoscopic treatment (9.8 ± 8.6 vs. 44.92 ± 60.98 days, p = 0.009), and shorter transabdominal drain dwell time (15 (5-96) vs. 45 (12-162) days, p = 0.014) when compared to SEMS. Whereas endoscopic management was successful in 12/14 (85.7%) of patients from the ENPT group, SEMS was successful in only 5/13 (38.5%) of patients (p = 0.015). Furthermore, ENPT was associated with a significant reduction of endoscopic adverse events compared with SEMS (14.3% vs. 76.92% p = 0.001).

Conclusion: Compared with SEMS, ENPT is effective and safe in treating SLL after SG providing higher success rates, shorter treatment duration, and lower adverse events rates.
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http://dx.doi.org/10.1007/s11695-021-05287-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113301PMC
June 2021

Incidence of Perforated Appendicitis during the COVID-19 Pandemic: Lessons to Be Considered in the Second Wave.

J Gastrointest Surg 2021 09 8;25(9):2404-2406. Epub 2021 Feb 8.

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

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http://dx.doi.org/10.1007/s11605-021-04915-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869768PMC
September 2021

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

Implementation of Urgent Start Peritoneal Dialysis Reduces Hemodialysis Catheter Use and Hospital Stay in Patients with Unplanned Dialysis Start.

Kidney Blood Press Res 2019 16;44(6):1383-1391. Epub 2019 Oct 16.

Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, University Hospital Tübingen, Tübingen, Germany.

Background: Unplanned start of renal replacement therapy is common in patients with end-stage renal disease and often accomplished by hemodialysis (HD) using a central venous catheter (CVC). Urgent start using peritoneal dialysis (PD) could be an alternative for some of the patients; however, this requires a hospital-based PD center that offers a structured urgent start PD (usPD) program.

Methods: In this prospective study, we describe the implementation of an usPD program at our university hospital by structuring the process from presentation to PD catheter implantation and start of PD within a few days. For clinical validation, we compared the patient flow before (2013-2015) and after (2016-2018) availability of usPD.

Results: In the 3 years before the availability of usPD, 14% (n = 12) of incident PD patients (n = 87) presented in an unplanned situation and were initially treated with HD using a CVC. In the 3 years after implementation of the usPD program, 18% (n = 18) of all incident PD patients (n = 103) presented in an unplanned situation of whom n = 12 (12%) were treated with usPD and n = 6 (6%) with initial HD. usPD significantly reduced the use of HD by 57% (p = 0.0005). Hospital stay was similar in patients treated with usPD (median 9 days) compared to those with elective PD (8 days), and significantly lower than in patients with initial HD (26 days, p = 0.0056).

Conclusions: Implementation of an usPD program reduces HD catheter use and hospital stay in the unplanned situation.
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http://dx.doi.org/10.1159/000503288DOI Listing
June 2020

Multi-omics discovery of exome-derived neoantigens in hepatocellular carcinoma.

Genome Med 2019 04 30;11(1):28. Epub 2019 Apr 30.

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

Background: Although mutated HLA ligands are considered ideal cancer-specific immunotherapy targets, evidence for their presentation is lacking in hepatocellular carcinomas (HCCs). Employing a unique multi-omics approach comprising a neoepitope identification pipeline, we assessed exome-derived mutations naturally presented as HLA class I ligands in HCCs.

Methods: In-depth multi-omics analyses included whole exome and transcriptome sequencing to define individual patient-specific search spaces of neoepitope candidates. Evidence for the natural presentation of mutated HLA ligands was investigated through an in silico pipeline integrating proteome and HLA ligandome profiling data.

Results: The approach was successfully validated in a state-of-the-art dataset from malignant melanoma, and despite multi-omics evidence for somatic mutations, mutated naturally presented HLA ligands remained elusive in HCCs. An analysis of extensive cancer datasets confirmed fundamental differences of tumor mutational burden in HCC and malignant melanoma, challenging the notion that exome-derived mutations contribute relevantly to the expectable neoepitope pool in malignancies with only few mutations.

Conclusions: This study suggests that exome-derived mutated HLA ligands appear to be rarely presented in HCCs, inter alia resulting from a low mutational burden as compared to other malignancies such as malignant melanoma. Our results therefore demand widening the target scope for personalized immunotherapy beyond this limited range of mutated neoepitopes, particularly for malignancies with similar or lower mutational burden.
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http://dx.doi.org/10.1186/s13073-019-0636-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492406PMC
April 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

CT-Guided Translumbar Placement of Permanent Catheters in the Inferior Vena Cava: Description of the Technique with Technical Success and Complications Data.

Cardiovasc Intervent Radiol 2018 Sep 19;41(9):1356-1362. Epub 2018 Apr 19.

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

Purpose: To evaluate indications, technical success rate and complications of CT-guided translumbar catheter placement in the inferior vena cava for long-term central venous access (Port and Hickman catheters) as a bail-out approach in patients with no alternative options for permanent central venous access.

Materials And Methods: This retrospective study included 12 patients with a total of 17 interventions. All patients suffered from bilaterally chronically occluded venous vessels of their upper extremities, without patent internal jugular and/or subclavian veins. Catheter implantation was performed as a hybrid procedure with CT-guided translumbar access into the inferior vena cava with subsequent angiography-guided catheter placement of a Hickman-type catheter (7×) or a Port catheter (10×).

Results: All interventions were technically successful. The total 30-day complication rate was 11.8% (n = 2). The two detected complications were bleeding at the subcutaneous port hub and subcutaneous kinking of the venous tube. Mean follow-up time was 68.4 ± 41.4 months (range 3.4-160 months). Six patients (50%) died during follow-up from non-procedure-related complications associated with the underlying disease. Late complications occurred in 8/17 (47.1%) cases and were infections of the catheter system in 35.3% (n = 6), mechanical defect of the catheter system in 5.8% (n = 1) and dislocation of the catheter system in 5.8% (n = 1). The overall infection rate was 0.77 per 1000 catheter days.

Conclusions: CT-guided translumbar placement of permanent catheters is a technically feasible and safe method for permanent central venous access as last resort in chronically occluded veins of the upper extremities.
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http://dx.doi.org/10.1007/s00270-018-1961-9DOI Listing
September 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

Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient.

J Hepatol 2016 10 7;65(4):849-855. Epub 2016 Jul 7.

University Hospital Tübingen, Department of General, Visceral and Transplant Surgery, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Germany.

Background & Aims: We report a novel experimental immunotherapeutic approach in a patient with metastatic intrahepatic cholangiocarcinoma. In the 5year course of the disease, the initial tumor mass, two local recurrences and a lung metastasis were surgically removed. Lacking alternative treatment options, aiming at the induction of anti-tumor T cells responses, we initiated a personalized multi-peptide vaccination, based on in-depth analysis of tumor antigens (immunopeptidome) and sequencing.

Methods: Tumors were characterized by immunohistochemistry, next-generation sequencing and mass spectrometry of HLA ligands.

Results: Although several tumor-specific neo-epitopes were predicted in silico, none could be validated by mass spectrometry. Instead, a personalized multi-peptide vaccine containing non-mutated tumor-associated epitopes was designed and applied. Immunomonitoring showed vaccine-induced T cell responses to three out of seven peptides administered. The pulmonary metastasis resected after start of vaccination showed strong immune cell infiltration and perforin positivity, in contrast to the previous lesions. The patient remains clinically healthy, without any radiologically detectable tumors since March 2013 and the vaccination is continued.

Conclusions: This remarkable clinical course encourages formal clinical studies on adjuvant personalized peptide vaccination in cholangiocarcinoma.

Lay Summary: Metastatic cholangiocarcinomas, cancers that originate from the liver bile ducts, have very limited treatment options and a fatal prognosis. We describe a novel therapeutic approach in such a patient using a personalized multi-peptide vaccine. This vaccine, developed based on the characterization of the patient's tumor, evoked detectable anti-tumor immune responses, associating with long-term tumor-free survival.
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http://dx.doi.org/10.1016/j.jhep.2016.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756536PMC
October 2016

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

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

[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

A simple dummy liver assist device prolongs anhepatic survival in a porcine model of total hepatectomy by slight hypothermia.

BMC Gastroenterol 2011 Jul 14;11:79. Epub 2011 Jul 14.

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

Background: Advances in intensive care support such as therapeutic hypothermia or new liver assist devices have been the mainstay of treatment attempting to bridge the gap from acute liver failure to liver transplantation, but the efficacy of the available devices in reducing mortality has been questioned. To address this issue, the present animal study was aimed to analyze the pure clinical effects of a simple extracorporeal dummy device in an anhepatic porcine model of acute liver failure.

Methods: Total hepatectomy was performed in ten female pigs followed by standardized intensive care support until death. Five animals (dummy group, n = 5) underwent additional cyclic connection to an extracorporeal dummy device which consisted of a plasma separation unit. The separated undetoxified plasma was completely returned to the pigs circulation without any plasma substitution or exchange in contrast to animals receiving intensive care support alone (control group, n = 5). All physiological parameters such as vital and ventilation parameters were monitored electronically; laboratory values and endotoxin levels were measured every 8 hours.

Results: Survival of the dummy device group was 74 ± 6 hours in contrast to 53 ± 5 hours of the control group which was statistically significant (p < 0.05). Body temperature 24 hours after hepatectomy was significantly lower (36.5 ± 0.5°C vs. 38.2 ± 0.7°C) in the dummy device group. Significant lower values were measured for blood lactate (1.9 ± 0.2 vs. 2.5 ± 0.5 mM/L) from 16 hours, creatinine (1.5 ± 0.2 vs. 2.0 ± 0.3 mg/dL) from 40 hours and ammonia (273 ± 122 vs. 1345 ± 700 μg/dL) from 48 hours after hepatectomy until death. A significant rise of endotoxin levels indicated the onset of sepsis at time of death in 60% (3/5) of the dummy device group animals surviving beyond 60 hours from hepatectomy.

Conclusions: Episodes of slight hypothermia induced by cyclic connection to the extracorporeal dummy device produced a significant survival benefit of more than 20 hours through organ protection and hemodynamic stabilisation. Animal studies which focus on a survival benefit generated by liver assist devices should especially address the aspect of slight transient hypothermia by extracorporeal cooling.
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http://dx.doi.org/10.1186/1471-230X-11-79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224123PMC
July 2011

The enterohepatic circulation of amanitin: kinetics and therapeutical implications.

Toxicol Lett 2011 Jun 21;203(2):142-6. Epub 2011 Mar 21.

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

Background: Amatoxin poisoning induces a delayed onset of acute liver failure which might be explained by the prolonged persistence of the toxin in the enterohepatic circulation. Aim of the study was to demonstrate amanitin kinetics in the enterohepatic circulation.

Methods: Four pigs underwent α-amanitin intoxication receiving 0.35 mg/kg (n=2) or 0.15 mg/kg (n=2) intraportally. All pigs remained under general anesthesia throughout the observation period of 72 h. Laboratory values and amanitin concentration in systemic and portal plasma, bile and urine samples were measured.

Results: Amanitin concentrations measured 5h after intoxication of 219±5ng/mL (0.35 mg/kg) and 64±3 (0.15 mg/kg) in systemic plasma and 201±8ng/mL, 80±13ng/mL in portal plasma declined to baseline levels within 24h. Bile concentrations simultaneously recorded showed 153±28ng/mL and 99±58ng/mL and decreased slightly delayed to baseline within 32 h. No difference between portal and systemic amanitin concentration was detected after 24h.

Conclusions: Amanitin disappeared almost completely from systemic and enterohepatic circulation within 24 h. Systemic detoxification and/or interrupting the enterohepatic circulation at a later date might be poorly effective.
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http://dx.doi.org/10.1016/j.toxlet.2011.03.016DOI Listing
June 2011
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