Biomedical subjects

Tobias Keck

Publications and source records attributed to Tobias Keck.

12 recordsLinked to original sources

PubMed2006

Postoperative lymphoceles: detection with high-resolution MR lymphangiography.

Lymphoceles that do not resolve spontaneously or with treatment may be a major problem associated with a high degree of morbidity. Several imaging studies, including ultrasonography, computed tomography, magnetic resonance (MR) imaging, lymphography, lymphoscintigraphy, and intraoperative lymphatic mapping have been proposed to delineate lymphoceles before treatment. The present report describes the successful detection of three lymphoceles of the inguinal region with leaking lymphatic vessels by means of high-resolution MR lymphangiography.

Contrast Media↗

PubMed2005

Pancreatic proteases in serum induce leukocyte-endothelial adhesion and pancreatic microcirculatory failure.

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.

Animals↗

PubMed2005

Risk factors for the intermediate outcome of morbid obesity after laparoscopically placed adjustable gastric banding.

BACKGROUND: The overall long-term results of medical treatment for morbid obesity are poor. Surgery is the only treatment option to obtain long-term weight reduction. Analysis of risk factors for treatment success of laparoscopically placed gastric banding (LGB) has not been available until now. METHODS: Prospective study with 99 patients with LGB between January 1997 and July 2003. The parameters assessed as risk factors included onset of obesity, feeling of postprandial satiety, and initial body mass index (BMI). RESULTS: Median follow-up was 36 months (3 to 72). Independent prognostic factors of excess body weight reduction (>25%) were for the first postoperative year: onset of obesity as an adolescent (relative risk [RR] 0.21), an initial BMI <45 kg/m(2) (RR 4.76), and a BMI between 45.1 and 50 kg/m(2) (RR 3.23). After the second year, independent prognostic factors were as follows: feeling of postprandial satiety (RR 5.26) and an initial BMI <45 kg/m(2) (RR 3.03). CONCLUSION: LGB is suitable to achieve intermediate weight reduction in patients with morbid obesity. To obtain the best results, patients should be treated before they achieve a BMI >45 kg/m(2). Additionally a postprandial feeling of satiety after LGB is mandatory for good long-term results.

Adult↗

PubMed2005

Pelvic and acetabular fractures in childhood.

In pediatric pelvic fractures and acetabular fractures, the treating physician is confronted with a unique pattern of injuries. Throughout the literature, pediatric pelvic fractures are rare, but acetabular fractures are even rarer. The lack of experience with this type of fracture, due to their infrequency, leads to unavailability of standardized protocols for specific diagnosis and therapy. Anatomical differences and various stages of skeletal maturation between children and adults lead to different causes, patterns, and associated injuries. In this article, we review the epidemiology and pathophysiology of this entity of fractures and provide current algorithms for diagnosis and therapy. Both operative and nonoperative treatments have been advocated in the literature, and in this article we define indications for both approaches and review the current literature.

Acetabulum↗

PubMed2005

Serous cystadenocarcinoma of the pancreas: management of a rare entity.

Whereas mucinous cystadenomas of the pancreas are considered premalignant, serous cystadenomas are believed to remain benign. We present a case of an 80-year-old woman with a primary tumor of the pancreas that was histologically classified as serous cystadenocarcinoma. Because preoperatively available criteria that determine malignancy in serous lesions are lacking, observation is the preferred option in serous cystadenomas. Operating every serous lesion is not justified. Reviewing all reports of serous cystadenocarcinomas that have been published to date, we are providing recommendations for the management of this rare entity.

Aged, 80 and over↗

PubMed2004

Pancreatic head resection for chronic pancreatitis in patients with extrahepatic generalized portal hypertension.

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.

Adult↗

PubMed2004

Brain death impairs pancreatic microcirculation.

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.

Amylases↗

PubMed2003

Characterization of ischemia/reperfusion injury after pancreas transplantation and reduction by application of monoclonal antibodies against ICAM-1 in the rat.

BACKGROUND: Reperfusion injury contributes to early organ malfunction after transplantation. The aim of this study was to characterize the ischemia-reperfusion injury after pancreas transplantation and to evaluate the effect of monoclonal antibody therapy against ICAM-1. METHODS: Twenty-five heterotopic pancreas transplantations were performed in syngenic rats in a no-touch technique. Microcirculation and leukocyte-endothelial interaction in the grafts were evaluated by intravital microscopy at 1 hour (I), 6 hours (II), 12 hours (III), and 24 hours (IV) after reperfusion, and 12 hours after reperfusion (V) in the therapeutic group. In (V) antibodies against ICAM-1 were applied as bolus at reperfusion and continuously for 6 hours. Next to intravital microscopy, histologic scores, myeloperoxidase levels, and ICAM-1 expression were determined. RESULTS: Microcirculation was significantly reduced in capillaries and postcapillary venules in the time course after reperfusion (capillary: 0.96 +/- 0.08 mm/s [I] to 0.45 +/- 0.07 mm/s [IV] [P <.01]) and was improved significantly by therapy with ICAM-1 antibodies (0.98 +/- 0.06 mm/s, (P <.01). Leukocyte-endothelial interaction significantly increased 6 hours after reperfusion (II) (P <.01). These changes were paralleled by an increased endothelial expression of ICAM-1 in immunohistochemistry. Histologic evaluation showed increased inflammation at 12 hours after reperfusion (P <.01), which could be diminished by the administration of ICAM-1 antibodies (P <.05). CONCLUSION: Increased endothelial expression of ICAM-1 after pancreas transplantation is positively correlated with microcirculatory impairment. Important steps of pancreatic inflammation take place approximately 6 hours after reperfusion. Prophylactic application of monoclonal antibodies against ICAM-1 reduces reperfusion injury and successfully prevents the occurrence of graft pancreatitis.

Animals↗

PubMed2003

Oxygen radicals promote ICAM-1 expression and microcirculatory disturbances in experimental acute pancreatitis.

BACKGROUND/AIMS: The course of pancreatitis is paralleled by a drastic reduction in organ perfusion and increased ICAM-1-mediated leukocyte-endothelial interaction. We aimed to evaluate the effect of oxygen radicals on ICAM-1 expression and the microcirculation in severe acute pancreatitis using the oxygen radical scavenger dimethylsulfoxide (DMSO). MATERIALS AND METHODS: Severe pancreatitis was induced in rats (n = 32) who were randomly assigned to one of two groups: either 4 ml/kg 50% DMSO/saline (v/v) started 3 h after induction of pancreatitis or 4 ml/kg saline (control). Microcirculation was evaluated by intermittent intravital microscopy. Serum amylase and lipase, histomorphometric changes, immunohistochemistry for ICAM-1 expression and 24-hour survival were investigated. RESULTS: Leukocyte adherence was significantly reduced (4.4 +/- 0.47 vs. 5.58 +/- 0.69 sticker/100 micro m, p < 0.05), and mean capillary (0.96 +/- 0.06 vs. 0.45 +/- 0.13 mm/s; p < 0.01) and venous erythrocyte velocity (1.16 +/- 0.12 vs. 0.58 +/- 0.16 mm/s, p < 0.01) were significantly increased by DMSO treatment. Microcirculatory disturbances were paralleled by an increase in endothelial ICAM-1 expression, whereas DMSO reduced ICAM-1 expression. CONCLUSION: DMSO improves pancreatic microcirculation and reduces ICAM-1 expression and subsequent leukocyte adhesion, suggesting an important role of oxygen free radicals in the pathway of endothelial ICAM-1 expression and microcirculatory disturbances in acute pancreatitis.

Acute Disease↗

PubMed2002

Prevention of pancreatic fistula with a new synthetic, absorbable sealant: evaluation in a dog model.

BACKGROUND: Pancreatic fistula complicates up to 15% to 25% of pancreatic resections, especially with soft, normal pancreas, and is most common after distal pancreatectomy. A new synthetic, absorbable hydrogel sealant has recently been developed and tested for sealing of human aorta, bronchi, and dura; it is FDA approved as a lung sealant in humans. Our objective was to test the efficacy of the sealant in preventing pancreatic leaks in a dog model of distal pancreatectomy. STUDY DESIGN: Ten dogs underwent bilateral distal pancreatectomy under general anesthesia. Animals were randomized to receive application of the sealant to the pancreatic stumps (n = 5) or no treatment (n = 5). The transected pancreatic duct was not ligated, and the end of the pancreas was neither oversewn nor stapled; closed-suction drains were placed in proximity to the pancreatic stumps before abdominal closure. All animals received normal chow starting on the second postoperative day. Drainage was collected for volume and amylase determination twice daily for 14 days, after which the animals were sacrificed. Pancreatic tissue was collected from the area of transection and was formalin fixed for histopathology. RESULTS: There was no perioperative mortality. Fluid recovered from closed-suction drains in all animals was uniformly amylase-rich. Over the 14-day study period, daily volume of pancreatic drainage was significantly different between control animals and animals treated with sealant (p < 0.001). By postoperative day 6, the total mean pancreatic drainage in dogs treated with sealant was 25 +/- 5 mL/drain (versus 91 +/- 26 mL/drain in untreated dogs; p < 0.05). This is the point at which we remove the drains in our clinical practice. Examination at 14 days revealed intact sealant at the pancreatic stumps in the treatment group, and histopathology showed a characteristic benign histiocyte reaction to the sealant but no other qualitative differences in the degree of inflammation between control and treatment animals. There were no undrained collections or abscesses. CONCLUSIONS: A new synthetic hydrogel sealant prevents the formation of significant pancreatic fistulae after distal pancreatectomy in the dog and may be suitable for clinical application.

Absorption↗

PubMed2002

Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat.

BACKGROUND & AIMS: In pancreatitis-associated lung injury, neutrophils (PMN) access the lung by migration through endothelial basement membranes. We hypothesize that degeneration of the basement membrane by specific PMN-produced matrix metalloproteinases (MMPs) may facilitate this process. METHODS: Mild or severe pancreatitis was induced in rats and the consequent pulmonary injury characterized. MMP-2 and MMP-9 activity in supernatant of PMN cultures and homogenates of lungs were assessed by zymography and Western blot. Congruence of PMN and MMP expression in lung tissue was evaluated by neutrophil depletion and fluorescent immunohistochemistry (IHC). The contribution of MMPs to PMN transmigration and lung injury was tested with the MMP inhibitor batimastat (BB-94) in vitro (PMN transmigration across matrigel chambers) and in vivo (myeloperoxidase activity and Evans blue in broncho-alveolar lavage fluid). RESULTS: MMP-9 was highly expressed in lungs and supernatant of neutrophil cultures in severe pancreatitis, and, to a lesser degree, in mild pancreatitis. Lung IHC showed colocalization of MMP-9 and PMN. PMN depletion simultaneously reduced neutrophil infiltration and MMP-9 levels in lung tissue. Trypsin, interleukin 1 beta, and tumor necrosis factor (TNF)-alpha all potently stimulated MMP-9 release from PMN. BB-94 significantly reduced TNF-alpha-induced PMN transmigration across matrigel and ameliorated transendothelial PMN migration and protein leak in severe pancreatitis. CONCLUSIONS: MMP-9 secretion by PMN can be stimulated by trypsin and proinflammatory cytokines and increases in pancreatitis in proportion to its severity. MMP inhibition reduces PMN transmigration and reduces resultant alveolar-capillary leakage. These findings suggest an important role for MMP-9 from PMN in the pathogenesis of pancreatitis-associated lung injury.

Acute Disease↗

PubMedDate not supplied

Perioperative matrix metalloproteinase inhibition therapy does not impair wound or anastomotic healing.

Matrix metalloproteinases (MMPs) catalyze the degradation of collagen and extracellular matrix. They play a role in pathologic states including malignancy, in which they facilitate invasion and metastasis. MMP inhibition has been shown to block neoplastic invasion and improve survival in animal models of malignancy. Concern about the effects of MMP inhibitors on wound and anastomotic healing may limit their potential use in the perioperative period to prevent local and systemic showering of cancer cells from surgical manipulation. We sought to assess the safety of perioperative administration of an MMP inhibitor (BB-94) with respect to skin and bowel healing in a rat model. Absorption of BB-94 was confirmed through high-pressure liquid chromatography and mass spectroscopy of sera from treated animals. Bowel bursting pressure in all animals increased almost 10-fold between 4 and 14 days. Two-way analysis of variance showed no significant difference in bowel bursting pressure between control and treatment animals over time. There was a significant increase in the collagen content of skin specimens of all animals combined between 4 and 28 days. Similarly, all animals showed an increase in bowel collagen between 4 and 28 days. There was no significant difference in skin or bowel collagen concentrations between control and treatment animals over time. Perioperative treatment with MMP inhibition does not impair wound or enteric healing in a rat model of laparotomy and small bowel resection. MMP inhibitors are safe for use as adjuvant therapy after resection for cancer.

Anastomosis, Surgical↗