Showing papers by "Ulrich T. Hopt published in 2010"

A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively

Abstract: Background Postoperative pancreatic fistula (POPF) is regarded as the most serious complication of pancreatic surgery. The preoperative risk stratification of patients by simple means is of interest in perioperative clinical management. Methods Based on prospective data, we performed a risk factor analysis for POPF after pancreatoduodenectomy in 62 patients operated between 2006 and 2008 with special focus on clinical parameters that might serve to predict POPF. A predictive score was developed and validated in an independent second dataset of 279 patients operated between 2001 and 2010. Results Several pre- and intraoperative factors, as well as underlying pathology, showed significant univariate correlation with rate of POPF. Multivariate analysis (binary logistic regression) disclosed soft pancreatic texture (odds ratio [OR] 10.80, 95% confidence interval [CI] 1.80–62.20) and history of weight loss (OR 0.15, 95% CI 0.04–0.66) to be the only independent preoperative clinical factors influencing POPF rate. The subjective assessment of pancreatic hardness by the surgeon correlated highly with objective assessment of pancreatic fibrosis by the pathologist ( r = −0.68, P Conclusions Preoperative stratification of patients regarding risk for POPF by simple clinical parameters is feasible. Pancreatic texture, as evaluated intraoperatively by the surgeon, is the strongest single predictive factor of POPF. The findings of the study may have important implications for perioperative risk assessment and patient care, as well as for the choice of anastomotic techniques.

Subcutaneous Redon drains do not reduce the incidence of surgical site infections after laparotomy. A randomized controlled trial on 200 patients

Abstract: Surgical site infections (SSI) cause excess morbidity and mortality in modern surgery. Several different approaches to reduce the incidence of SSI have been investigated with variable results. This is to our knowledge the first systematic randomized evaluation in patients undergoing laparotomy in visceral surgery to clarify whether widely used subcutaneous drains (Redon) affect wound infection as the primary outcome measure. In 200 patients, we were unable to show a statistically significant impact on the postoperative healing process in patients with the full variety of abdominal surgical interventions. Overall, we observed surgical site infection in 9.5% of all patients (n = 19), of these n = 9 (47.4%) were in the control group without a drain, and 10 (52.6%) were in the experimental group with a Redon drain (not significant). As this study could not demonstrate a reduction of SSI by the use of Redon drains, there is no indication for prophylactic subcutaneous suction drains after laparotomy.

Effects of antipsychotics and vitamin C on the formation of reactive oxygen species

Abstract: There is evidence that reactive oxygen species (ROS) are involved in the pathophysiology of psychiatric disorders such as schizophrenia. Indirect biochemical alterations of ROS formation have been shown for patients treated with antipsychotics as well as for untreated patients. Only one study measured directly the ROS formation after treatment with antipsychotics by using electron spin resonance spectroscopy. The aim of the present examination was to demonstrate the effects of haloperidol, clozapine and olanzapine in concentrations of 18, 90 and 180 μg/mL on the formation of ROS in the whole blood of rats by using electron spin resonance spectroscopy after incubation for 30 min. To test the protective capacity of vitamin C we incubated the highest concentration of each drug with vitamin C (1 mM). Under all treatment conditions, olanzapine led to a significantly higher formation of ROS compared with control conditions, whereas in the cases of haloperidol and clozapine the two higher concentrations induced a significantly enhanced formation of ROS. Vitamin C reduced the ROS production of all drugs tested and for haloperidol and clozapine the level of significance was reached. Our study demonstrated that antipsychotics induce the formation of ROS in the whole blood of rats, which can be reduced by the application of vitamin C.

Lipopolysaccharide-induced radical formation in the striatum is abolished in Nox2 gp91phox-deficient mice.

Abstract: Encephalopathy associated with septic shock as well as psychiatric disorders can be caused by the central nervous formation of reactive oxygen species (ROS) associated with inflammation. The systemic application of lipopolysaccharide (LPS, 100 μg/kg i.p.) also serves as a model for major depression and results in enhanced inflammatory processes. which are characterized by the stimulation of microglia or macrophages that then impair normal brain function. The aim of the present study was to analyze the effect of peripherally applied LPS on the central nervous formation of ROS and IL-6 in wild-type mice and in mice lacking the NADPH oxidase Nox2 subunit gp91phox. Microdialysis was performed in the striatum of the mice. Central nervous ROS were detected by electron spin resonance spectroscopy using 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) as reactant, which was infused via a microdialysis probe. IL-6 was measured in microdialysis samples by an immunoassay. Finally, blood samples were taken by heart puncture to detect IL-6 in plasma. In the wild-type mice, LPS significantly increased the ROS formation in the striatum of wild-type mice and resulted in a significantly enhanced IL-6 production. In the mice lacking the NADPH oxidase Nox2 subunit gp91phox, LPS did not enhance ROS formation, while central IL-6 was significantly increased. IL-6 plasma values were enhanced in both types of mice. In conclusion, the gp91phox-containing NADPH oxidase complex is involved in the central nervous ROS formation after peripheral LPS stimulation and might be a pharmacological target in patients with septic shock.

The first teleautomatic low-voltage prosthesis with multiple therapeutic applications: a new version of the German artificial sphincter system.

Abstract: To date, there are no artificial sphincter prostheses for urinary or fecal incontinence that may be implemented elsewhere instead, for example, in the upper gastrointestinal tract. Conventional systems are conceptually similar but are constructed specifically for distinct applications and are manual in operation. The German Artificial Sphincter System (GASS) II is the evolution of a highly integrative, modular, telemetric sphincter prosthesis with more than one application. Redesigning and integrating multilayer actuators into the pump allows us to reduce the input voltage to -10 to +20 V (V(PP) = 30 V). This provides for a flow rate of 2.23 mL/min and a counterpressure stability of 260 mbar. Furthermore, multiple applications have become feasible due to our standardized connection system, therapy-specific compression units, and application-specific software. These innovations allow us to integrate not only severe fecal and urinary incontinence, erectile dysfunction, and therapy-resistant reflux disease, but also morbid adiposity into the gamut of therapeutic GASS applications.

Colloid vs. crystalloid infusions in gastrointestinal surgery and their different impact on the healing of intestinal anastomoses.

Abstract: The aim of this study was to investigate if colloid infusions have different effects on intestinal anastomotic healing when compared to crystalloid infusions depending on the amount of the administered volume. Twenty-eight Wistar rats were randomly assigned to four groups receiving different amounts of either a crystalloid (Cry) or a colloid (Col) infusion solution. Animals with volume restriction (Cry (−) or Col (−)) were treated with a low and animals with volume overcharge (Cry (+) or Col (+)) with a high flow rate. All animals received an infusion for a 60-min period, while an end-to-end small bowel anastomosis was performed. At reoperation, the anastomotic bursting pressure (millimeters of mercury) was measured, as well as anastomotic hydroxyproline concentration. The presence of bowel wall edema was assessed histologically. Median bursting pressures were comparable in the Col (−) [118 mm Hg (range 113–170)], the Cry (−) [118 mm Hg (78–139)], and the Col (+) [97 mm Hg (65–152)] group. A significantly lower median bursting pressure was found in animals with crystalloid volume overload Cry (+) [73 mm Hg (60–101)]. Corresponding results were found for hydroxyproline concentration. Histology revealed submucosal edema in Cry (+) animals. In case of a fixed, high-volume load, colloids seem to have benefits on intestinal anastomotic healing when compared to crystalloid infusions.

Percutaneous endoscopic gastrostomy. Complications with and without anticoagulation

Abstract: Background Percutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation. Methods Between 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given. Results The average hospitalization time was 27.4 days (range 1-268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications. Conclusion Complications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.

Pitfalls and Technical Aspects during the Research of Intestinal Anastomotic Healing in Rats

Abstract: Background: Fundamental experimental research into intestinal anastomotic healing in rodent models will gain increasing interest in the future. Methods: The aim of this study was to describe our 5-year experience with a standardized experimental setup of small and large bowel anastomoses in a rodent model and present a basic set of assessment tools investigating anastomotic healing. Anastomotic technique, perioperative complications such as anastomotic insufficiency (AI) and obstructive ileus were in the focus. Results: During different studies with varying study patterns, 167 rat small bowel anastomoses and 120 colonic anastomoses were performed. Overall mortality was 3.6% in small bowel and 2.5% in colonic anastomoses, AI occurred in 2.9 and 4%, respectively. A postoperative obstructive ileus was seen in 3/167 small bowel anastomoses and none in the colonic group. Conclusion: When performing experimental intestinal anastomoses in a standardized operative setting and critically considering special perioperative issues, the incidence of relevant complications can be maintained at an adequately low level.

Perkutane endoskopische Gastrostomie

Abstract: Hintergrund Die perkutane endoskopische Gastrostomie (PEG) wird bislang als Hochrisikoeingriff klassifiziert (ASGE-Leitlinien). Koagulopathien, Thrombozytenaggregationshemmer (Aspirin, Clopidogrel u.a.) und Phenprocoumon bzw. Wafarine gelten als Kontraindikationen. Die Studie untersucht erstmals Komplikationen und Risikofaktoren bei Patienten mit und ohne Antikoagulation.

Reinforcement of Colonic Anastomoses with a Collagenous Double-Layer Matrix Extracted from Porcine Dermis

Abstract: Background: Anastomotic leakage is a major factor for morbidity in colorectal surgery. Anastomotic reinforcement with biological or synthetic materials has been claimed to be useful

Extracellular matrices for gastrointestinal surgery: ex vivo testing and current applications.

Abstract: AIM: To assess the effects of bile and pancreatic juice on structural and mechanical resistance of extracellular matrices (ECMs) in vitro. METHODS: Small-intestinal submucosa (SIS), porcine dermal matrix (PDM), porcine pericardial matrix (PPM) and bovine pericardial matrix (BPM) were incubated in human bile and pancreatic juice in vitro. ECMs were examined by macroscopic observation, scanning electron microscopy (SEM) and testing of mechanical resistance. RESULTS: PDM dissolved within 4 d after exposure to bile or pancreatic juice. SIS, PPM and PDM retained their integrity for > 60 d when incubated in either digestive juice. The effect of bile was found to be far more detrimental to mechanical stability than pancreatic juice in all tested materials. In SIS, the loss of mechanical stability after incubation in either of the digestive secretions was less distinct than in PPM and BPM [mFmax 4.01/14.27 N (SIS) vs 2.08/5.23 N (PPM) vs 1.48/7.89 N (BPM)]. In SIS, the extent of structural damage revealed by SEM was more evident in bile than in pancreatic juice. In PPM and BPM, structural damage was comparable in both media. CONCLUSION: PDM is less suitable for support of gastrointestinal healing. Besides SIS, PPM and BPM should also be evaluated experimentally for gastrointestinal indications.

[Postoperative sepsis: diagnosis, special features, management].

Abstract: A high level of suspicion is necessary to detect postoperative sepsis in good time. It may be difficult to differentiate sepsis from normal SIRS in the postoperative setting. Early signs and symptoms include delirium and respiratory compromise. These should trigger the search for a septic focus aggressively with special attention to the original site of surgery. Key recommendations include early goal-directed resuscitation of the septic patient, administration of broad-spectrum antibiotic therapy within 1 hour of diagnosis, and source control with attention to the balance of risks and benefits of the chosen method. In cases of severe abdominal sepsis the concept of relaparotomy on-demand has become most popular.

Consensus statement on the adoption of the COPE guidelines

Abstract: We the undersigned editors of the member journals of the Surgery Journal Editors Group (SJEG), in the furtherance of integrity in surgical and scientific publication, agree to adopt the guidelines established by the Committee on Publication Ethics (COPE) [1]. The COPE guidelines represent a means of addressing a variety of ethical concerns, including duplicate publication and authorship misconduct issues, which have, unfortunately, become more prevalent. This statement is being simultaneously published in the respective journals of the members of the Surgery Journal Editors Group, as follows:

Short-and long-term health implications of surgical intensive care in the elderly

Abstract: Background: Treatment of elderly patients on intensive care units is an increasing challenge all over the world. Objectives: To evaluate short- term survival and long-term quality of life im-plications of intensive care for the elderly. Methods: Retrospective analysis of 314 patients 75 years of age or more requiring over 48 hours of intensive care. Results: In multivariate analy-sis, significant risk factors for mortality were chronic renal impairment (OR for survival .30, p 24 h (OR 4.5), hemodialysis (OR 6.8), and vasopressor therapy (OR 2.5, p < 0.001 for each). A health survey questionnaire in an up to 60-month follow-up of 28 patients revealed considerably lower physi-cal subscores of our patients compared to the general elderly population. Conclusions: Elderly patients benefit from intensive care in terms of survival. Complications are frequent, as are severe consequences for long-term quality of life. Short-term mortality in elderly intensive care patients correlates most closely to pre- existing disease, not age.

Immunsuppression bei Pankreasorgan-, Insel(zell)- und Nierentransplantation

Abstract: Nach Organtransplantation sind die Empfanger ein Leben lang auf die Einnahme von immunsuppressiven Medikamenten angewiesen, um eine Abstosungsreaktion und somit einen Verlust des Transplantates zu verhindern. Der vorliegende Beitrag zeigt aktuelle Standards auf und diskutiert neue Erkenntnisse der letzten Jahre. Gerade der Bereich der Immunsuppression steht im standigen Wandel. Ziele der intensiven klinischen Forschungsbemuhungen sind nicht nur die Wahl der richtigen Kombination verschiedener Wirkstoffe, sondern ebenso die Findung eines adaquaten therapeutischen Wirkspiegels, um eine Uberimmunsuppression, welche mit einer erheblichen Steigerung des Auftretens von Nebenwirkungen einhergeht, zu vermeiden.

Abstract 4168: Comprehensive characterisation of a newly established patient-derived pancreatic adenocarcinoma xenograft collection

Abstract: There is a high medical need to identify new treatments for patients with pancreatic cancer, since in many cases only palliative treatment is possible. The standard 1st line chemotherapy in inoperable, locally advanced (stage II and III) and metastatic (stage IV) adenocarcinoma of the pancreas is Gemcitabine as a single agent with a median survival of about 6 month. In addition, Gemcitabine is indicated as adjuvant chemotherapy after surgery. Although the anti-metabolite 5-Flourouracil (5-FU) and the EGF-R inhibitor Tarceva (Erlotinib) have been approved for 2nd line treatment, new and more efficient drugs are urgently needed. In the present study, more than 60 samples of pancreatic carcinomas were transplanted subcutaneously (s.c.) into NMRI nude mice directly after tumor resection. In most cases, tumor material from chemonaive patients with defined histology and staging was used for implantation. Up to now, 17 tumor models were passaged in nude mice and characterized comprehensively. In general, the histology of the primary tumor was comparable to that of the established xenograft. Chemosensitivity in vivo was evaluated by treatment of tumor bearing nude mice with 5-FU (100 or 75mg/kg, q7dx3, i.p.), Gemcitabine (240mg/kg, q7dx3, i.v.) and Erlotinib (25 and 50mg/kg, qdx21, p.o.). In general, tumor growth was not inhibited with best T/C values >50% highlighting the general chemoresistance of pancreatic cancer. Only for two models (PAXF 1872 and PAXF 1998), a high sensitivity towards Gemcitabine was evident with best T/C values of 8% and 3.8%, respectively. There was no correlation to the transcriptional levels of proteins involved in transportation and metabolism of Gemcitabine. Concerning Erlotinib, best T/C values were ranging from 89.6% (PAXF 1876) to 38.5% (PAXF 1982) with no correlation to EGFR expression status. A more broad chemosensitivity profile was established with the ex-vivo clonogenic assay. Interestingly, several tumors responded strongly to treatment with Rapamycin (IC50 ≤ 10nM). Based on this data, in vivo treatment experiments with RAD001 (Everolimus) were done and data are presented. Mutational analysis of p53 (exons 4 to 10) revealed only 4 out of 13 models as p53 wild-type. Nevertheless, the p53 pathway is dysregulated in all tumor models and for selected tumors, an aneuploid cell population was identified by ex vivo cell cycle analysis. In summary, a unique collection of patient-derived pancreatic xenograft models of high clinical relevance has been established. These models are available for translational research studies including in-vivo efficacy testing of new investigational drugs. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4168.

[Patient assignment to a surgical intensive care unit - plea for a preoperative risk stratification].

Abstract: BACKGROUND: Surgical intensive care units (ICUs) have to meet the demands of caring for elective surgical patients, for surgical emergencies, and for trauma patients. To achieve this a high flexi-bil-ity and a high rate of admissions and discharges are needed. ICU beds are scant and expensive, so who is to be admitted? PATIENTS AND METHODS: All admissions and dis-charges of a 20-bed surgical ICU in a university hospital within one year have been analysed. RESULTS: During the analysed year 2524 patients were admitted to the surgical ICU (6.9 ± 3.1 per day). Of 1886 planned admissions (elective surgery) only 1234 were eventually admitted, but there were 1290 additional patients admitted as emergencies. Of all realised admissions only 49 % were planned. In 653 requested but refused elective admissions, the surgery was performed with-out intensive care admission in 432 patients (64.9 %). CONCLUSIONS: Half of the patients of the surgical ICU are electively surgical, half of them are emergencies. The limited number of ICU beds requires strict indications for admission. It turns out to be useful to create a category of patients in whom postoperative intensive care is desirable but not mandatory.

Laparoscopic Implantation and Evaluation of a Telemetric Sphincter Prosthesis for Urinary Incontinence in Pigs – Evaluation of First Results.

Abstract: Hypothesis / Study Objective The first artificial sphincter was implanted in 1947 by Foley. Since then, sphincter prostheses have become a crucial instrument in the therapy of high-grade urinary incontinence. In fact, the currently most widespread systems, i.e. the AMS 800 [1] and the FlowSecure System [2], have been implanted over 100.000 times. These systems both entail at least 3 components that are implanted in different anatomical compartments. Also both systems use hydraulic mechanisms and are manually controlled. In the past, we developed a fully telemetric sphincter prosthesis, the German Artificial Sphincter System (GASS). Here we report on the implantation of this prosthesis in two pigs. Our goal was to test whether continence can be achieved while at the same time providing adequate tissue protection. Furthermore, we tested a laparoscopic implantation technique.