Biomedical subjects
Publications and source records attributed to Ulrich T Hopt.
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.
OBJECTIVES: Failure to prevent secondary infectious complications in acute necrotizing pancreatitis (ANP) is attributable in part to the limited penetration of antimicrobial drugs. As newer quinolones are particularly attractive owing to their antimicrobial activity, for the first time we studied the penetration of moxifloxacin into pancreatic tissue in patients. PATIENTS AND METHODS: In this prospective, non-comparative clinical trial, 60 patients undergoing elective pancreas resection received a single oral or intravenous (iv) dose of 400 mg moxifloxacin for perioperative antimicrobial prophylaxis. The concentration of moxifloxacin was measured in samples taken from blood and from pancreatic tissue at the beginning and at the end of resection. RESULTS: Mean moxifloxacin concentrations in pancreatic tissue following iv or oral administration were 3.1+/-0.9 and 2.7+/-1.4 mg/kg at 3-3.7 h post-dose (first sampling) and 3.6+/-1.5 and 3.1+/-1.8 mg/kg at 4.3-5.3 h post-dose (second sampling), respectively. Corresponding mean plasma concentrations of moxifloxacin were 1.8+/-0.5 and 1.2+/-0.6 mg/L (first sampling) and 1.5+/-0.4 and 1.0+/-0.5 mg/L (second sampling), respectively. From first to second sampling, the mean tissue-to-plasma ratios varied from 1.8+/-0.6 to 2.6+/-1.2 (iv) and from 2.4+/-0.8 to 3.1+/-1.2 (oral). Pancreatic tissue concentrations of moxifloxacin exceeded the MIC90 for the relevant pathogens covered by moxifloxacin for at least 5 h after dosing. CONCLUSIONS: Moxifloxacin has been demonstrated to penetrate efficiently into human pancreatic tissue following iv or oral administration. From a pharmacological perspective, moxifloxacin appears to be promising for prophylaxis and treatment of local pancreas infections. Whether it is beneficial in the prevention and therapy of infectious complications in patients with ANP should be investigated in a controlled clinical trial.
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.
OBJECTIVES: Enzymatic digestion of donor pancreas is a vital step in islet isolation process. Recently, human and large mammalian islet isolation has been improved by Liberase. However, there are no data to show the improvement of rat islet isolation with Liberase. We hypothesized that commercially available Liberase has variable activities from batch to batch and that a short culture period might improve the function of isolated islets in vivo. We therefore isolated islets with Liberase and cultured them for a short period before transplantation to reverse diabetes in a syngenic rat model. METHODS: Islets of high inbred Lewis rats were isolated with Liberase, purified by discontinuous density gradients, hand-picked, and cultured at 37 degrees C for 24 hours. The same batch of Liberase was used for all experiments in this study. Freshly isolated and cultured islets were implanted intraportally into rats rendered diabetic by streptozotocin. RESULTS: In this study, we were not able to reverse diabetes by syngenic transplantation of freshly isolated islets from 2 donors with Liberase in the rat model. Surprisingly, for the first time, we successfully achieved normoglycemia for more than 100 days in the diabetic rats by syngenic transplantation of the cultured islets isolated with Liberase. These normoglycemic diabetic rats showed normal glucose tolerance curves. Histologic examination of the livers of the islet recipients revealed intact islets, with numerous well-granulated insulin-containing cells and only few glucagon-expressing cells. In islets of the recipients' pancreata, the remaining native islets consisted mainly of glucagon-expressing cells, with few insulin-expressing cells in the center. CONCLUSIONS: We conclude that Liberase isolation followed by a short culture period may be a good substitute for collagenase in rats. Islet culture before transplantation can promote the success of single-donor-single-recipient islet transplantation to reverse diabetes in the rat model.
An artificial sphincter prototype has been developed, specifically designed for comfortable remote control by fecally incontinent patients. The artificial sphincter includes a fluid reservoir, an occlusive cuff, and a micropump based on piezo-technology in a single unit. Continence and implantation management were evaluated around isolated porcine anal canals and in vivo. The design of the prosthesis reduces the occlusion pressure and allows low inflation volumes (6.5-16 mL). Operating pressures between 24 and 58 mm Hg indicate a minor risk of ischemic injury to the bowel. The operation time is estimated at about 7 days with no recharging of the battery. The novel prototype is a highly integrated prosthesis for placement around the anal canal or lower rectum, effecting continence with comfortable control.
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.
Despite decreasing mortality rates, morbidity is still high after pancreatic head resection. Comparative data in the United States and Europe show a relationship between hospital volume and mortality. Treatment strategies vary frequently, partially because of the lack of evidence-based data. We performed a multi-institutional analysis in Germany evaluating current numbers, indications, techniques, and complication rates of pancreatic head resection. Questionnaires were completed by seven high-volume surgical departments regarding quantitative and qualitative aspects of pancreatic head resections in the period from 1999 to 2004 (five prospective and two retrospective institutional databases). A total of 1454 pancreatic head resections (944 for malignancy) were reported. Mean annual hospital volume ranged from 14 to 52 (10 to 43 in malignancy). Mortality was between 1.1% and 4.8%, morbidity was between 24% and 46%, and pancreatic leakage was between 9% and 20%. In malignant disease, all centers perform standard lymphadenectomy and regard arterial infiltration as a contraindication for resection. However, the rate of portal vein resection varied from 0% to 28%. No consensus is seen on the type of surgery for malignancy and chronic pancreatitis. After resection for pancreatic cancer less than one fourth of the patients receive adjuvant therapy. The results of our analysis in Germany confirm that pancreatic head resection can be performed with low mortality in specialized units. Variations in indications, operative technique, and perioperative care may demonstrate the lack of evidence-based data and/or personal and institutional experience. The low number of patients receiving adjuvant therapy after resection of pancreatic cancer suggests that more efforts must be made to establish novel adjuvant therapies under randomized study conditions.
Despite low mortality, postoperative complications are still relatively frequent after pancreatic head resection. The occurrence of delayed visceral arterial bleeding from erosions or pseudoaneurysms of branches of the celiac trunk or from the stump of the gastroduodenal artery is a rare but life-threatening complication and is probably underreported in the literature. During a 10-year period, we diagnosed and treated 12 patients (three referred from other hospitals) with severe visceral arterial bleeding, presenting 7 to 85 days after pancreatic head resection. Clinical presentation was gastrointestinal bleeding (seven patients) or abdominal bleeding (five patients). The bleeding source was identified by angiography in 10 of the 12 cases. Definitive bleeding control was achieved by angiography in six of the 12 patients (stent 2, coiling 4), or by surgery in five patients. None of the six patients with successful angiographic intervention required further surgery for bleeding control. One patient died due to hemorrhage before bleeding was controlled. Median transfusion requirement was 12.5 (range 3-37) units. Of five patients with interventional or surgical occlusion of the common hepatic artery, three developed hepatic abscesses and two had complications of the hepaticojejunostomy. One of those five patients died four months after definitive bleeding control because of recurrent hepatic abscesses. All other patients eventually recovered completely. We conclude that delayed arterial bleeding from visceral arteries is a rare but life-threatening complication after pancreatic head resection. Angiographic stenting with preservation of hepatic blood flow, if technically possible, represents the best treatment option.
We report a case of a 55-year-old woman who was transferred from another center to our university clinic after diagnostic laparotomy with a pancreatic head tumor which was seen to encase the portal vein. Although intraoperative biopsies were performed, a histologic diagnosis of the tumor was not possible before giving suspect to a malignant tumor being resectable only with a vascular resection. In a second operation we performed a pylorus-preserving pancreatoduodenectomy. Due to adhesion of the tumor to the portal vein, a segmental resection and end-to-end anastomosis of the portal vein was necessary. Postoperative histologic diagnosis revealed an ancient schwannoma which was removed in toto being a rare report of this benign tumor in the pancreatic head. Ten months after the operation the patient is without any health problems. Partial resection of the portal vein, which is considered to be a safe procedure in high volume centers, stands in contrary to surgical nihilism of pancreatic head tumors suspecting advanced tumors with vascular involvement.
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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.
BACKGROUND: Five percent to 10% of chronic pancreatitis (CP) cases are complicated by portal venous occlusion leading to extrahepatic generalized portal hypertension (GPH). Pancreatic head resections (PHR) are regarded risky or contraindicated in patients with extrahepatic GPH. The aim of our study was to analyze the outcome of patients with extrahepatic GPH undergoing PHR for CP and to propose recommendations for surgical strategy. METHODS: Sixteen of 185 patients with PHR suffered from extrahepatic GPH. Perioperative and follow-up data were documented prospectively and analyzed to assess the outcome. RESULTS: Preoperative interventional thrombolysis of the portal vein was successfully performed in 5 patients and alleviated further PHR. Median operative time and blood transfusions were higher in patients with extrahepatic GPH compared with patients without extrahepatic GPH (P<.01). Overall complication rate was not statistically different (44% vs 34%). One death occurred in each group. At the end of follow-up (median, 18 months) 13 of 15 patients with extrahepatic GPH were free of pain. No variceal bleeding or cholestasis was documented. All patients judged their status as subjectively improved. CONCLUSION: Although technically demanding in the presence of extrahepatic GPH, PHR can be performed with an acceptable morbidity and mortality in an experienced center. Preoperative interventional recanalization of portal vein thrombosis may render PHR possible by restoring normal splanchnic blood flow in selected cases indicated for surgery.
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.
No highly integrated sphincter prosthesis for therapy of major fecal incontinence exists. Therefore, we developed a novel neosphincter, made of polyurethane. The GASS consists of a support ring (SR) which includes a fluid reservoir, fixed on the outer diameter of the SR, and a multi-chamber occluding cuff (C(int)) on the inside diameter. The total inflation volume of C(int) is about 23 cc. The integrated micropump based on piezotechnology measures 30x13x1 mm3 (flowrate 1.4 cc/min, max. backpressure 40,000 Pa) . GASS was evaluated around the external sphincter of isolated porcine anal canals. The threshold of continence was defined as the inflating volume which water ceased to leak through the area occluded by C(int) under an induced rectal pressure of 150 cm H2O. Minimal filling volumes maintained continence for liquids against high luminal pressures. A low intraanal resting pressure (delta p(anal)) induced by activated GASS indicates a little risk of ischemic injury of the anal canal in vivo (median delta p(anal) 24.1 mm hg:15 cc vs 46.9 mm hg:21 cc). In summary, a highly integrated and efficient high-tech neosphincter for the therapy of major fecal incontinence could be realized.
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.
BACKGROUND AND AIMS: To determine the outcome of pancreatic head resection for chronic pancreatitis in the presence of celiac axis stenosis or occlusion we analyzed the blood supply of the upper abdominal organs in 11 patients before and after surgery. PATIENTS AND METHODS: Between March 1994 and April 2000 we performed 145 pancreatic head resections for chronic pancreatitis. Preoperatively 11 patients showed celiac axis stenosis at angiography. All 11 patients underwent duplex ultrasonography postoperatively and 8 had magnetic resonance angiography during follow-up. RESULTS: In two cases division of the median arcuate ligament was performed to reestablish hepatic artery blood flow. No further revascularization procedures of the celiac axis were necessary. Postoperative duplex ultrasonography and magnetic resonance angiography showed normal blood flow in five patients. Four patients still had an occlusion or a significant celiac axis stenosis, and two had a stenosis only during expiration. At follow-up nine patients were completely free of abdominal pain (82%), and all had gained weight postoperatively, ranging from 5 to 16 kg. CONCLUSIONS: Our data suggest that celiac axis stenosis infrequently causes complications in pancreatic head resection for chronic pancreatitis and therefore does not represent a contraindication for this procedure. Nevertheless the hepatopedal blood flow must be confirmed by palpation or duplex ultrasonography after pancreatic head resection in these patients.
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.