Biomedical subjects
Publications and source records attributed to Stefan Benz.
BACKGROUND: Due to the complex embryologic development, pancreatic anatomy can be very variable. DISCUSSION: The authors present the second ever reported case in the literature of a complete pancreatic encasement of the portal vein which forced us to alter the standard operative procedure of pancreatic head resection, thus enabling possible dangerous complications.
BACKGROUND: Spontaneous or iatrogenic esophageal perforations after endoscopic procedures are potentially life-threatening events with a considerable mortality rate. The aim of this study was to demonstrate that a nonoperative endoscopic treatment with self-expanding metal stents may have a lower morbidity and mortality rate compared with surgical treatment. METHODS: A nonrandomized observational study was conducted with 15 consecutive patients between January 1997 and June 2004. Benign spontaneous and iatrogenic esophageal perforations after endoscopic procedures were treated with self-expandable metal stents. RESULTS: Seven patients (group 1) underwent stent insertion with an average time delay of 45 minutes. In 8 patients (group 2), the median delay was 123 hours. All patients in group 1 had an uneventful recovery and left hospital 5 days (range, 3 to 9) after stent insertion. One patient in group 2 (1 of 8) died of pneumonia after 6 days. In any other cases, perforations healed successfully after stent placement, but the clinical course was generally complicated with sepsis and multiple organ failure. The average hospital stay was 44 days (range, 15 to 70). CONCLUSIONS: Immediate insertion of a self-expandable metal stent enables an excellent outcome with minimal mortality and morbidity without the need for operation. Even in cases of old esophageal perforations, sealing with self-expandable metal stents is still a good option although the clinical course is much less impressive than in early treated perforations.
Complex refractive indices of supercooled liquid water have been retrieved at 269, 258, 252, and 238 K in the 4500-1100 cm(-1) wavenumber regime from series of infrared extinction spectra of micron-sized water droplets. The spectra collection was recorded during expansion experiments in the large coolable aerosol chamber AIDA of Forschungszentrum Karlsruhe. A Mie inversion technique was applied to derive the low-temperature refractive index data sets by iteratively adjusting the room-temperature optical constants of liquid water until obtaining the best agreement between measured and calculated infrared spectra of the supercooled water droplets. The new optical constants, revealing significant temperature-induced spectral variations in comparison with the room-temperature refractive indices, proved to be in good agreement with data sets obtained in a recent study. A detailed analysis was performed to elaborate potential inaccuracies in the retrieval results when deriving optical constants from particle extinction spectra using an iterative procedure.
BACKGROUND: Neutrophil-mediated tissue injury in acute pancreatitis includes a severe reduction of the functional microcirculation via interaction of adhesion molecules on leukocytes (MAC-1) and endothelium (ICAM-1). The hypothesis of the study was that trypsin and elastase in serum alone lead to the expression of these complementary adhesion molecules and result in increased leukocyte-endothelial interaction (LEI). In addition we evaluated the preventative benefit of protease inhibition on these mechanisms. MATERIALS AND METHODS: In vitro: Cultured endothelial cells (HUVEC) and human leukocytes (PMN) were stimulated with increasing doses of trypsin and elastase. In addition, pre-treatment of PMN or HUVEC was performed with protease inhibitors (Nafamostat mesilate, FUT and gabexate mesilate, FOY). The expression of ICAM-1 or MAC-1 was evaluated by flow cytometry. In vivo: Severe pancreatitis was induced in rats. Microcirculatory disturbances were evaluated by real-time confocal microscopy at 9 h in controls and acute pancreatitis with or without anti-protease treatment. Additionally, the effect of continuous trypsin and elastase infusion on pancreatic microcirculation and LEI were evaluated by intravital fluorescence videomicroscopy. RESULTS: Up-regulation of MAC-1 and ICAM-1 expression requires the presence of serum. The maximal increase of MAC-1 and ICAM-1 expression was found at concentrations of trypsin or elastase characteristic for acute pancreatitis. FUT or FOY significantly reduced protease-induced expression of MAC-1 and ICAM-1. Real-time in-vivo microscopy revealed that functional capillary density in acute pancreatitis was significantly reduced (267.1 +/- 2.95/mm2 vs. 91.29 +/- 12.81/mm2) and treatment with FUT significantly reduced this effect (134.6 +/- 4.6/mm2; p < 0.05 vs. untreated pancreatitis). Infusion of trypsin or elastase alone increased LEI in vivo and reduced pancreatic perfusion. CONCLUSION: Both trypsin and elastase up-regulate the expression of adhesion molecules on leukocytes and endothelial cells in the presence of serum. Increased LEI and reduced perfusion of the pancreas, characteristic of acute pancreatitis, is induced in vivo by infusion of pancreatic proteases and this effect is partially abrogated by their inhibitors. These results support the role of circulating trypsin and elastase in promoting pancreatic microcirculatory failure in experimental acute pancreatitis.
BACKGROUND: The objective of this study was to determine the long-term results after simultaneous pancreas-kidney transplantation (SPK) at a single-center institution in Europe. PATIENTS AND METHODS: Seventy-eight consecutive patients with insulin-dependent diabetes mellitus and end-stage nephropathy were followed for a median of 7 years after SPK. Immunosuppressive protocol consisted of cyclosporine A, azathioprine, prednisone, and antithymocyte globulin. Multivariate Cox proportional hazard model was used to investigate the impact of different putative risk factors on long-term patient survival. Health-related quality of life was assessed by a validated questionnaire (SF-36). RESULTS: Patient survival at 5 and 10 years was 81% and 67%, respectively. Pancreas function rate was 73% and 60% and kidney function 67% and 44%, respectively. In multivariate analysis, preexisting myocardial infarction (relative risk [RR] 5.1, 95% confidence interval [CI] 1.5-16.6) and amputation (RR 3.7, 95% CI 1.1-12.9) were strongly associated with a diminished long-term patient survival. Analysis of patients with long-term functioning pancreas and kidney grafts revealed excellent results for quality of life posttransplant that were comparable with average scores of the normal German population. CONCLUSIONS: This series representing the largest experience with long-term follow-up in Europe confirms an excellent long-term survival and an exceptional quality of life after SPK.
Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia/reperfusion (I/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male Lewis rats served as donors and recipients of heterotopic syngeneic pancreaticoduodenal transplantation. Recipient animals were divided into two experimental groups: group Tx (n=7) received grafts without IPC, group Tx&IPC received grafts with IPC. Animals that had not undergone transplantation but whose pancreata had been exteriorized served as controls (n=5). All pancreatic grafts were preserved in University of Wisconsin solution for 6 h at 4 degrees C. IPC was induced by interruption of the arterial blood flow for 10 min followed by 10 min of reperfusion. One and two hours after reperfusion, graft microcirculation was assessed by means of intravital microscopy (IVM). Rats were immediately killed after the second measurement and DNA breaks of acinar cells were detected by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate digoxigenin nick end-labelling (TUNEL) assay and gel electrophoresis (laddering). The apoptotic index (AI) was defined as the number of apoptotic cells per high-power field. Analysis of both groups of transplanted grafts showed a significant decrease in functional capillary density (FCD) and a significant increase in leukocyte sticking to postcapillary venules (LAV) at 1 h and 2 h of reperfusion, compared with animals that had not undergone transplantation ( P<0.01). In parallel, AI was significantly increased in transplanted grafts compared to the controls ( P<0.01). Grafts subjected to IPC showed no significant differences, neither for FCD nor LAV, at both time points if compared with grafts of group Tx. However, IPC resulted in a significant increase in AI ( P<0.05). We can conclude that IPC has no effect on pancreatic microcirculation but enhances acinar cell apoptosis in experimental pancreas transplantation. These results indicate that IPC might increase I/R injury after pancreatic cold ischemia.
BACKGROUND: Postoperative morbidity is high after pancreatic head resections. Data about risk factors are controversial. The aim of this study was to evaluate risk factors for complications after pancreatic head resection and to assess whether the complication rate changed during the study period. METHODS: Data of 301 patients undergoing pancreatic head resection were recorded prospectively. Risk factors were assessed by multivariate analysis. The first and second part of the study period were compared. RESULTS: Mortality was 3%. Overall and surgery-related complications occurred in 42% and 28%, respectively. Independent risk factors for postoperative morbidity were impaired renal function (odds ratio [OR] 2.7), absence of preoperative biliary drainage (OR 1.9), and resection of other organs (OR 3.2). Complication rate, duration of surgery, amount of blood transfused, and length of hospital stay decreased during the study period. CONCLUSIONS: Increasing hospital experience decreased complication rates. Patients with risk factors should be considered for transferal to specialized centers.
Brain death (BD) influences the quality of donor grafts in transplantation. To evaluate the impact of BD on pancreas grafts, we investigated the influence of BD on the microcirculation and histology of the pancreas in a rat model of explosive BD. A group of Wistar rats (n=7), rendered brain dead by inflating an intracranially inserted Fogarty catheter was compared with controls (CO) using intravital epifluorescence-microscopy over 4 h after BD induction; functional capillary density (FCD), leukocyte adherence (AL) in post-capillary venules, histology and pancreatic enzymes were investigated. Four hours after BD, FCD decreased (333 +/- 11 vs. baseline 444 cm/cm2 +/- 5 SEM; p<0.01) and showed lower values than CO (388 +/- 9 p<0.01). In BD, AL was increased (628 cells/mm2 +/- 110 SEM vs. baseline 123 +/- 32, and vs. CO 180 +/- 33; p<0.001). BD caused increased histological damage (CO 1.6 score-points +/- 0.7 SD vs. BD 8.3 +/- 7.1; p<0.05). Amylase was higher in BD (p<0.05) but did not reach pathological values. We show for the first time that BD causes relevant changes in pancreatic microcirculation, histology and leukocyte endothelial interaction which might have a serious impact on the function of grafts. New strategies for preventing this damage are therefore highly desirable in order to improve the outcome of pancreas transplantation.
OBJECTIVES: Impairment of glucose tolerance is one of the leading clinical presentations in patients with pancreatic carcinoma. The mechanism of disturbed glucose metabolism, however, is still under debate. Using microarray technology, key mechanisms of deregulated molecular functions of cancer cell-specific mRNAs and tumor-induced mRNAs in peritumorous tissue should be identified in pancreatic ductal adenocarcinoma (PDAC) by comparison to chronic pancreatitis and normal pancreas. METHODS: Forty-three mRNAs were abundant in tissue specimens of patients operated due to pancreatic carcinoma but absent or of low abundance in chronic pancreatitis and normal pancreas. One of these mRNAs encodes the gap junction protein connexin26, known as a tumor suppressor, which was 10.8- and 6.9-fold more abundant in pancreatic carcinoma than in normal pancreas and chronic pancreatitis, respectively. Quantitative RT-PCR was performed for connexin26, with mRNA being expressed 26.7- and 2.9-fold more than in normal pancreas (n = 6), in pancreatic carcinoma (n = 7), and chronic pancreatitis (n = 8), respectively. RESULTS: By immunohistochemistry, connexin26 was predominantly localized to the islets in the vicinity of the pancreatic carcinoma tissue. Control sections of tissue with chronic pancreatitis and normal pancreas show connexin26 expression in the islets as well. Interestingly, the level of mRNA abundance (fold over normal pancreas) in RT-PCR correlates (r = 0.62) with the 2h value of the pre-operative oral glucose tolerance test of these patients. CONCLUSION: Whether overexpressed connexin26 in pancreatic cancer is a cause of impaired glucose tolerance remains to be elucidated in further experimental studies.
This study was undertaken to examine the impact of ischemia-reperfusion (I/R) injury on microcirculation and apoptosis in experimental pancreas transplantation. Pancreatic grafts were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-h CITs (group U6); UW, 18-h CITs (group U18); normal saline, 6-h CITs (group S6); and normal saline, 6-h CITs with Z-Asp-2,6-dichlorobenzoyloxymethylketone (pan-caspase inhibitor; group S6 & CI). Nontransplanted animals served as controls. At 1- and 2-h reperfusion microcirculation was assessed by means of intravital microscopy. Apoptosis was detected by in situ nick end-labeling method (TUNEL) at 2-h reperfusion. Deterioration of microcirculation was lowest in group U6 and highest in groups S6 and S6 & CI compared with controls. The apoptotic index (cells per high power fields) of groups U6, U18 and S6 correlated well with functional capillary density (r=- 0,70, p < 0.0001) and leucocyte sticking (r= 0,69, p < 0.0001) at 1-h reperfusion. Caspase inhibition had no impact on microcirculation but significantly reduced AI compared with group S6 (p < 0.001). These data suggest that pancreatic I/R injury-induced apoptotic cell death well predicts the extent of [corrected] microcirculatory impairment. Caspase inhibition might be a promising strategy in reducing I/R injury in pancreas transplantation.
BACKGROUND: After pancreas transplantation, endocrine function is determined by the insulin secretory capacity of the transplanted pancreas. The authors evaluated the predictive value of postoperative oral glucose tolerance test (OGTT) and stimulated insulin secretion on long-term endocrine function. METHODS: Forty-one patients after pancreas-kidney transplantation with systemic venous drainage were studied. Patients were categorized to have normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) (World Health Organization criteria: NGT, <7.8 mM; IGT, 7.8-11.1 mM 120 min after glucose intake) and high or low total insulin secretion. Mean follow-up of graft function and patient outcome was 10.2+/-0.5 years after OGTT. RESULTS: Patients with IGT had grafts with a longer ischemia time and a significantly worse urine amylase excretion as compared with patients with NGT. Using Kaplan-Meier survival analysis, patients with NGT had better long-term pancreatic function as compared with IGT in the follow-up after performing the first OGTT (mean, 10.9+/-0.2 vs. 8.8+/-0.9 years of graft function; P=0.02), but there was no difference in patient survival and kidney graft function. Also, high insulin secretion predicted significantly longer pancreas graft function as compared with low insulin secretion (P=0.04). CONCLUSIONS: Although IGT does not lead to poorer long-term patient survival and kidney graft function, it does predict compromised long-term endocrine function of the transplanted pancreas. Therefore, postoperative OGTT are useful tools for identification of patients at risk of long-term endocrine graft failure after pancreas transplantation.
OBJECTIVES: Prospective organ donors are exposed to various stress types. The effect of endotoxin pretreatment (ETX) on pancreatic ischemia/reperfusion injury (IRI) is unclear. We investigated, using a rat model of pancreatic IRI of an in situ isolated pancreatic tail segment, the effect of ETX on postischemic microcirculation and organ damage. METHODS: Twenty-four hours before pancreatic dissection, either intraperitoneal application of ETX (1 mg/kg in 0.9% NaCl) or saline only (control) was performed. Two-hour normothermic ischemia of the pancreatic tail was induced by clamping the splenic vessels and was followed by a reperfusion period of 2 hours. Microcirculatory parameters were measured by intravital epifluorescence microscopy [functional capillary density (FCD), adherent leukocytes (ALs), and histology]. The presented data represent the mean +/- SEM/SD as appropriate. RESULTS: ETX pretreatment caused a significantly greater decrease in FCD (497 +/- 6 cm/cm2 baseline versus 326 +/- 15 cm/cm2 2 hours of reperfusion) compared with controls (498 +/- 8 versus 258 +/- 15 cm/cm2) 2 hours after reperfusion (P < 0.01). Two hours after reperfusion, ALs were significantly decreased in ETX animals compared with controls (ETX: 141 +/- 37 versus 273 +/- 36 cells/mm2, P < 0.05). Histologic damage was less in ETX (6.4 score points +/- 0.32 versus 8.8 +/- 0.33 control, P < 0.05). CONCLUSION: ETX preconditioning decreases microcirculatory deterioration caused by IRI by means of less loss of nutritive tissue perfusion, decrease in ALs, and less histologic damage. This indicates a protective effect of ETX preconditioning in pancreatic IRI.
BACKGROUND: The therapeutic efficacy of intratumoral instillation of genetically engineered, CYP2B1-expressing, microencapsulated cells in combination with ifosfamide had been previously demonstrated in xenografted human pancreatic ductal carcinomas [Gene Ther 1998;5:1070-1078]. Prior to a clinical study, the feasibility of an intra-arterial application of microencapsulated cells to the pancreas and its consequences to the organ had to be evaluated. MATERIAL AND METHODS: Microencapsulated, CYP2B1-producing cells were instilled both in vivo (transfemoral angiographical access) and in vitro (perfusion model) in the splenic lobe of the pig pancreas. In vivo, animals were monitored clinically for 7 days, then treated with ifosfamide and sacrificed. In vitro, ifosfamide was administered intra-arterially. RESULTS: In all animals, 100 microcapsules could be instilled safely via the femoral route without clinical, biochemical or histological signs of pancreatitis. Histological examination revealed partial obstruction of small arteries by the capsules, without causing any parenchymal damage. In vitro, instillation reduced blood flow by half. Ifosfamide, also in combination with the capsules, did not add any damage to the pancreas. CONCLUSION: Intra-arterial instillation of microencapsulated cells to the pig pancreas is feasible and safe. Neither pancreatitis, foreign body reactions nor circulatory disturbances were observed. Clinical application of this genetically enhanced chemotherapeutic method seems possible.
In ischemia/reperfusion of the pancreas impairment of microcirculation after reperfusion is believed to be of critical importance. The 'no-reflow' phenomenon is thought to cause persisting tissue ischemia, while the 'reflow-paradox' is defined as secondary impairment of nutritive perfusion. These phenomena have been shown by intravital microscopy but their effect on tissue oxygenation as assessed by continuous tissue oximetry has not been identified. In landrace pigs tissue oxygenation was investigated in warm ischemia/reperfusion of the pancreas by the use of continuous tissue oximetry. After reperfusion rapid reoxygenation occurred which was followed by a period of secondary hypoxia. Thereafter, secondary reoxygenation was found, and finally tertiary hypoxia with a gradual decline of tissue pO(2) was noted. The data show a relevant impairment of tissue oxygenation after reperfusion. However, 'no-reflow' seems not to be a primary failure of capillary reperfusion but the consequence of a short reperfusion period followed by secondary ischemia. The 'reflow-paradox' most likely corresponds to tertiary ischemia.