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1.
Chirurg ; 90(4): 307-317, 2019 Apr.
Article in German | MEDLINE | ID: mdl-30255373

ABSTRACT

AIM: To investigate the perioperative management and outcome of patients undergoing abdominal surgery with additional vascular (comorbid) alterations for internal quality assurance of the clinical results. METHODS: Over a defined study period all consecutive cases of the aforementioned profile were documented and retrospectively analyzed as part of an ongoing prospective monocentric observational study to reflect the daily surgical practice. RESULTS: Over 10 years (from January 1999 to December 2008), a total of 113 cases were registered. Pancreas resection including vascular reconstruction showed the highest percentage (30.1%). Within the target patient groups, similar outcome data were found compared with international reports. An exception was in the case of mesenteric ischemia, where open surgery was more frequently used in comparison to the study situation (included together were patients treated by surgery and interventions). The majority of vascular alterations during the postoperative course and iatrogenic lesions occurred following pancreas resection. In the therapeutic profile there are two particularly important measures, namely open surgery on one hand and image-guided radiology as well as endoscopy on the other hand. The majority of patients with a rare visceral artery aneurysm (considerable potential for rupture or erosion) were more frequently treated with image-guided interventional radiology versus open surgery. This conforms to the current well-established sequential patient (individual), results, and, in particular, risk-adapted staged treatment approach. CONCLUSION: Additional vascular surgical treatment of problematic situations during abdominal surgery or in emergency cases is not daily routine; however, it is a challenging field including a considerable potential for complications (morbidity) and definitely mortality. This requires an experienced surgeon with high expertise, if possible in a center for vascular medicine.


Subject(s)
Aneurysm , Vascular Surgical Procedures , Aneurysm/surgery , Humans , Prospective Studies , Retrospective Studies , Tertiary Care Centers
2.
Dtsch Med Wochenschr ; 138(27): 1406-9, 2013 Jul.
Article in German | MEDLINE | ID: mdl-23801262

ABSTRACT

UNLABELLED: HISTORY AND INTERVENTION: A 52-year-old female patient underwent open abdominothoracic cardia and esophageal resection with gastric transposition because of histologically diagnosed Barrett metaplasia with "high-grade" intraepithelial neoplasia (HGIEN) and parts of an invasive adenocarcinoma. The anastomotic insufficiency on the 10th postoperative day including an esophagobronchial fistula prompted to a subsequent surgical re-intervention with suture of the fistula, lavage and additional drainage, an endoscopic stenting of the fistula from esophageal site, as well as repeated (n = 22) bronchoscopic applications of fibrin glue (1-3 ml each) into the lumen of the fistula after each bronchoscopic lavage of the fistula until the complete closure was achieved. The changeful clinical course of 77 days on the surgical ICU was characterized by secondary complications such as pneumonia, mediastinitis and respiratory insufficiency with long-term artificial respiration and creation of a percutaneous dilatation tracheotomy. CONCLUSION: The application of fibrin glue can be considered a promising, minimally invasive therapeutic option in the management of postoperative fistula after esophageal resection, which requires expertise in decision-making and the finding-specific approach, in particular, if indicated inital steps of the sequential complication management such as surgical re-intervention and conventional endoscopic measures (stenting, Endo-VAC[-sponge]) do not provide great therapeutic potential any more due to the prolonged postoperative time course and the unfavorable local findings. In the presented case, modes of an assisted artificial respiration with low pressure and short phases of apnoe after fibrin glue application were the crucial predictions for an initial and favorable adhesion of this glue and finally for a successful sealing resulting in a sufficient closure of the fistula.


Subject(s)
Bronchial Fistula/therapy , Esophageal Fistula/therapy , Esophagectomy/methods , Fibrin Tissue Adhesive/administration & dosage , Wound Closure Techniques , Wound Healing/drug effects , Female , Humans , Middle Aged , Tissue Adhesives/administration & dosage , Treatment Outcome
4.
Z Gastroenterol ; 50(11): 1166-70, 2012 Nov.
Article in German | MEDLINE | ID: mdl-23150109

ABSTRACT

Obstruction of bile flow following pancreatoduodenectomy can be caused by stenosis of the hepaticojejunostomy created at the time of surgery, obstruction of the bile-draining jejunal loop, stones or, very rarely, ingested foreign bodies in the common hepatic duct. In analogy with endoscopic sphincterotomy or the once popular side-to-side-choledochduodenostomy, the creation of a hepaticojejunostomy eliminates the barrier of the sphincter Oddi, enabling intestinal content such as ingested foreign bodies or food fibers to migrate into the bile duct. We report on the case of a patient developing biliary tract obstruction due to fibrous material in the common hepatic duct 15 years after pancreatoduodenectomy. In addition, an overview of the literature on the rare phenomenon of foreign body-associated obstructive jaundice is given.


Subject(s)
Bezoars/diagnosis , Bezoars/etiology , Hepatic Duct, Common , Jaundice, Obstructive/diagnosis , Jaundice, Obstructive/etiology , Pancreatic Pseudocyst/surgery , Pancreaticoduodenectomy , Pancreatitis, Chronic/surgery , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Bezoars/surgery , Diagnosis, Differential , Follow-Up Studies , Hepatic Duct, Common/surgery , Humans , Image Processing, Computer-Assisted , Jaundice, Obstructive/surgery , Male , Middle Aged , Postoperative Complications/surgery , Recurrence , Reoperation , Tomography, X-Ray Computed
5.
Zentralbl Chir ; 136(2): 152-8, 2011 Apr.
Article in German | MEDLINE | ID: mdl-21425047

ABSTRACT

INTRODUCTION: Knowledge on potentially pathogenic microbes including characteristics of their antibiotic resistance in septic patients as well as on the ward- and department-specific microbial spectrum can be considered essential for an efficient initiation of an adequate antimicrobial treatment, which turns out to become pivotal for patient outcome. Permanent changes in microbial patterns and antibiotic resistance can only be identified by a continuous investigation of various microbiological specimens. AIM: Based on the retrospective evaluation of prospectively collected data on microbiological investigations of the surgical ICU in 1996, 2002, 2004 and 2005, the short- and long-term changes by trend of microbial spectrum and antibiotic resistance following reorganisation and restructuring of the University Hospital from the more traditional pavillon-based system to a multidisciplinary complex building in 2003 were investigated. MATERIAL AND METHODS: Twice a week, routine microbiological testing of blood and urinary cultures as well as swabs from wound areas and endotracheal swabs were initiated in septic patients (suspect, manifestation) or in case of their clinical impairment. The microbial spectrum was sub-divided according to Gram-staining (Gram-positive/ -negative), various species and fungi with descriptive absolute and relative data values. -Various groups and time periods were statistically compared using χ² test as appropriate. P values < 0.05 were considered statistically significant. RESULTS: In total (n (Total) = 4 899), microbiological testing resulted in the detection of microbes in 699 and 833 blood and urinary cultures (14.3 % and 17 %, respectively) as well as 1 232 wound swabs (25.1 %) together with 2 135 samples from the endotracheal sites (43.6 %). During the short- (2002 vs. 2004) and long-term analyses (1996 vs. 2005), the proportion of Gram-positive microbes increased. Al-though Gram-positive bacteria can be considered the most frequent microbes for bacteriemia, there was a shift onto urinary and wound infections as well as pneumonias through the observation period. Despite the decreasing incidence of Enterococcus and the consistent proportion of MRSA, the increase of resistant Enterococcus strains (0 % vs. 43.2 %; P < 0.05) is critical. However, in the Gram-negative microbial spectrum there was an increase of the bacteraemia rate but a fall of the detection rate in wound and endotracheal swabs. In parallel, an increase of the detection rate of E. coli in blood (6.5 % vs. 45.5 %; P < 0.05) and endotracheal swabs (9.2 % vs. 16.2 %; P < 0.05) is associated with an increase of multiresistant Enterobacteriaceae strains (0 % vs. 30.7 %; P < 0.05). The portion of multiresistant strains of Pseudomonas with 31 % stayed the same through the 10-year time period. While Candida-based colonisation showed a decreased incidence (25 % vs. 15 %; P < 0.05) during the whole investigation period, there was a relative rise in the frequency of candidemia. CONCLUSION: ICU relocation from the pavillon-based system to a new complex clinic building was not associated with any significant alteration of the microbial spectrum on the surgical ICU. Increasing incidences of resistant Enterococcus and Gram-negative problematic microbes may indicate a general spread of multi-resistant microbes under the steady selecting pressure of a not always adequately initiated antibiotic / antimicrobial therapeutic regimen and underline the required but specific and selected microbiological screening.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Critical Care , Cross Infection/drug therapy , Cross Infection/microbiology , Drug Resistance, Microbial , Antifungal Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/epidemiology , Bacteremia/microbiology , Bacterial Infections/epidemiology , Bacteriuria/drug therapy , Bacteriuria/epidemiology , Bacteriuria/microbiology , Cross Infection/epidemiology , Cross-Sectional Studies , Drug Resistance, Multiple, Bacterial , Germany , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Humans , Microbial Sensitivity Tests , Mycoses/drug therapy , Mycoses/microbiology , Retrospective Studies , Sepsis/drug therapy , Sepsis/microbiology , Surgical Wound Infection/drug therapy , Surgical Wound Infection/epidemiology , Surgical Wound Infection/microbiology , Trachea/microbiology
6.
Dig Dis ; 28(2): 373-8, 2010.
Article in English | MEDLINE | ID: mdl-20814215

ABSTRACT

BACKGROUND: In human acute pancreatitis (AP) the local anaesthetic procainhydrochloride (procain-HCl) is given intravenously for pain treatment. Procain has been shown to inhibit catalytic activity of pancreatic (group I) phospholipase A2 (PLA2) and non-pancreatic (group II) PLA2. Both enzymes are important mediators for the local and systemic inflammatory process in AP. To determine the effect of procain, we examined serum and tissue levels of both types of PLA2 activity in the experimental rodent taurocholate model of AP. METHODS: In 60 rats, severe pancreatitis was induced by taurocholate. Forty rats were treated with procain-HCl intravenously at a dosage of 2 mg/kg body weight/h either at or 1 h after induction of pancreatitis. Twenty rats served as controls. We measured catalytic activities of group I and group II PLA2 in serum and tissue samples of lung and pancreas. RESULTS: Serum group II PLA2 catalytic activity was significantly reduced 3 and 6 h after AP induction in rats treated with procain-HCl (p < 0.001) in both treatment groups. In pancreatic and lung tissue, group II PLA2 catalytic activity was significantly reduced compared with normal values (p < 0.001). CONCLUSION: Procain-HCl given intravenously either at or 1 h after induction of necrotizing pancreatitis significantly inhibits group II PLA2 catalytic activity in serum and tissues.


Subject(s)
Biocatalysis/drug effects , Pancreatitis/drug therapy , Pancreatitis/enzymology , Phospholipases A2/metabolism , Procaine/pharmacology , Procaine/therapeutic use , Animals , Group II Phospholipases A2/blood , Lung/drug effects , Lung/enzymology , Male , Pancreatitis/blood , Pancreatitis/chemically induced , Phospholipases A2/blood , Rats , Rats, Wistar , Taurocholic Acid
7.
Zentralbl Chir ; 135(6): 564-74, 2010 Dec.
Article in German | MEDLINE | ID: mdl-20645249

ABSTRACT

INTRODUCTION: Retroperitoneal soft-tissue sarcomas (RSTS) represent a rare and heterogeneous class of diseases for which the clinical management is still largely non-standardised. Based on a selective review of recent publications, it was the purpose of the present review article to summarize the current concepts of disease classification, diagnostics and surgical as well as multimodal therapy for these tumors. METHOD: A clinically based empirical review derived from a literature search focusing on publications from the past 5  years was carried out. RESULTS: Due to the paucity of randomised-controlled trials, therapy for RSTS is largely based on personal experience, retrospectively gathered data and historical controls. Pre-therapeutic planning requires precise information on the localisation, extension, and texture of the tumor through cross-sectional imaging (CT, MRI) as well as histological diagnosis through percutaneous or open biopsy. Complete tumor resection is crucial. Recent studies have confirmed the importance of microscopically negative resection margins which has subsequently led to a trend towards more radical resection. Chemotherapy does not play a role in the adjuvant setting except in clinical trials; however, radiotherapy has been controversely debated in adjuvant RSTS therapy. Efforts to limit radiation toxicity include modern techniques as well as a strategy of using pre-resection radiotherapy instead of postoperative radiation. Surgery is also the treatment of choice for locally recurrent RSTS and pulmonary metastases. The prognosis of RSTS depends on the quality of surgical care and several disease-specific factors (histological type, grading). CONCLUSION: The clinical management of RSTS is complex and can only partly be considered as evidence-based. Due to the required level of experience in the treatment of these tumor lesions and the involvement of several subspecialties, pre-therapeutic planning, treatment and follow-up should be limited to high-volume surgical centres. In order to achieve microscopically negative resection margins, multivisceral resections are a valuable option after thorough consideration of the risks and benefits. Adjuvant radiotherapy needs to be decided upon on an individual basis, taking into account patient- and tumor-specific factors as well as resection status.


Subject(s)
Retroperitoneal Neoplasms/surgery , Sarcoma/surgery , Biopsy , Combined Modality Therapy , Evidence-Based Medicine , Humans , Magnetic Resonance Imaging , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Radiotherapy, Adjuvant , Randomized Controlled Trials as Topic , Retroperitoneal Neoplasms/pathology , Retroperitoneal Neoplasms/radiotherapy , Sarcoma/pathology , Sarcoma/radiotherapy , Tomography, X-Ray Computed
8.
Langenbecks Arch Surg ; 394(2): 363-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18690472

ABSTRACT

BACKGROUND: Early events in the pathogenesis of experimental acute pancreatitis are intensively studied using isolated cells or animal models. However, the results and their interpretations are dependent on the complexity of biological structures. Therefore, we proposed that studies on isolated perfused pancreas can give additional information about processes leading to acinar cell injury. This hypothesis was examined adapting the well-established caerulein hyperstimulation model and the taurocholate model of acute pancreatitis to the extracorporeal perfused isolated rat pancreas. MATERIALS AND METHODS: The pancreas was removed with the duodenum including the arterial supply. A continuous perfusion of the organ was performed with a modified Krebs-Ringer bicarbonate buffer. Intraarterial caerulein application or an intraductal taurocholate (3.5%) application were used to induce acinar cell injury which was determined as the release of amylase, lipase and lactate dehydrogenase into the portal outflow medium and into the transudation fluid and by examination of histological alterations. Trypsinogen release and activation was followed by analysis of trypsinogen activation peptide (TAP) in the transudation fluid and in pancreatic tissue. RESULTS: Perfusion of isolated rat pancreas with supramaximal concentrations of caerulein or retrograde injection of taurocholate (3.5%) resulted in acinar cell injury indicated by elevated levels of amylase and lipase into the perfusate and into the transudation fluid. TAP levels in the transudation fluid significantly increased after perfusion with caerulein or retrograde injection of taurocholate (3.5%). The histological alterations after taurocholate application include oedema and necrosis and show significant differences to the control perfusion. Extensive pancreatic necroses were not observed after caerulein hyperstimulation. CONCLUSIONS: The isolated perfused rat pancreas is a useful model to investigate pathophysiological mechanisms which are relevant for the early phase of acute pancreatitis. The caerulein and the taurocholate models are transferable to the isolated rat pancreas. Studies on isolated perfused rat pancreas enable pathophysiological investigations of the exocrine pancreas without influence of systemic components, but with preserved morphology.


Subject(s)
Ceruletide/pharmacology , Cholagogues and Choleretics/pharmacology , Disease Models, Animal , Gastrointestinal Agents/pharmacology , Pancreatitis, Acute Necrotizing/chemically induced , Taurocholic Acid/pharmacology , Amylases/metabolism , Animals , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Lipase/metabolism , Male , Pancreas/drug effects , Pancreas/pathology , Pancreatitis, Acute Necrotizing/pathology , Perfusion , Rats , Rats, Wistar
9.
Pharmacogenomics J ; 8(1): 34-41, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17325733

ABSTRACT

UDP-glucuronosyltransferases (UGT) catalyze the glucuronidation of various compounds and thus inactivate toxic substrates. Genetic variations reducing the activity of UGT1A7 have been associated with various gastrointestinal cancers. Most recently, the UGT1A7*3 allele has been reported as a significant risk factor for pancreatic disorders, but we could not confirm these data. This study focused on the possible causes for the noted discrepancy. UGT1A7 genotypes were assessed in 37 samples, which were previously analyzed for UGT1A7 polymorphisms by others. We determined genotypes by melting curve analysis and by DNA sequencing. Additionally, we produced UGT1A7*1 and *3 constructs with or without a mutation at position - 57 of UGT1A7 and analyzed various combinations of these constructs. In 14/37 samples UGT1A7 genotyping results differed. The discrepancy could be explained by polymerase chain reaction bias owing to an unbalanced allelic amplification which was caused by a -57T>G variant located within the sequence of the chosen primer template in previous studies. Our findings indicate that most of the previously reported genetic associations between UGT1A7 and gastrointestinal cancers are based on primer-dependent genotyping errors.


Subject(s)
Glucuronosyltransferase/genetics , Pancreatitis, Chronic/enzymology , Pancreatitis, Chronic/genetics , Polymorphism, Genetic/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Cloning, Molecular , Codon , DNA/genetics , DNA Primers , Fluorescence Resonance Energy Transfer , Genotype , Humans , Polymorphism, Restriction Fragment Length , Reverse Transcriptase Polymerase Chain Reaction/standards , Temperature
10.
Z Gastroenterol ; 45(11): 1180-4, 2007 Nov.
Article in English | MEDLINE | ID: mdl-18027320

ABSTRACT

BACKGROUND: Esophageal dilatation is performed for the treatment of anatomic and sometimes functional narrowing of the esophageal lumen caused by a variety of benign and malignant conditions. Esophageal perforation is the major complication associated with endoscopic dilatation. AIM: The object of this study was to assess the incidence of perforation, management and outcomes after endoscopic esophageal dilatation. METHODS: All patients who underwent endoscopic esophageal dilatation at our institution from June 2001 to December 2006 were identified. Data were obtained by searching our prospectively collected electronic database (MEDOS AG, Langenselbold, Germany), which includes all endoscopic reports as well as discharge summaries of patients who have undergone endoscopy in our department. RESULTS: 248 patients (148 male, 100 female, mean age 58 years, range 14-87 years) underwent 365 esophageal dilatations: 74 pneumatic balloon dilatations for achalasia, 79 balloon dilatations for other reasons such as tumors, peptic stenosis, or post-radiotherapy stenosis and 212 dilatations with Savary bougies. The overall incidence of perforation based on the number of procedures was 2.2% (8 perforations/365 procedures) and 3.2% (8/248 patients) based on the number of patients. The perforation rate was 1.9% for bougie dilatation, 0% for balloon dilatation and 5-4% for pneumatic balloon dilatation for achalasia. Five patients were treated surgically and 3 patients were managed conservatively. The mean hospital stay was 14 days (7-33 days). One patient in whom the perforation was recognized 16 days after the dilatation died. CONCLUSIONS: Endoscopic esophageal dilatation is a safe procedure for the palliation of malignant strictures, for the management of benign strictures as well as for the therapy of achalasia. The perforation rate after these procedures is low. Early recognition of the perforation is associated with a good outcome. Small perforations can be treated conservatively.


Subject(s)
Dilatation/statistics & numerical data , Esophageal Perforation/epidemiology , Esophageal Perforation/therapy , Esophagoscopy/statistics & numerical data , Risk Assessment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome
11.
Dig Liver Dis ; 38(6): 423-8, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16627015

ABSTRACT

BACKGROUND: Bacterial infection of the pancreas aggravates the course of acute pancreatitis. Since bacterial translocation from the gut is likely to be an early event, in an animal model of pancreatitis, we investigated the effect of early bacterial supra-infection of the pancreas on the course of the disease. METHODS: Six hours after the induction of acute pancreatitis in male Wistar rats (n = 180) by supramaximal stimulation with cerulein (or placebo in a control group), the animals were operated and a suspension of Helicobacter pylori, Escherichia coli or saline were introduced either in the pancreatic duct or interstitium (12 groups of 15 rats each); after 24 h, animals were killed and the following parameters analysed: macroscopic and histologic appearance of the pancreas (score), wet-to-dry weight ratio, pancreas trypsinogen activation peptide level, serum amylase, interleukin-6 and phospholipase A2 activity. RESULTS: All parameters were increased in rats with cerulein-induced pancreatitis in comparison to placebo. Interstitial and intraductal application of bacteria increased the pancreatic damage. This effect was more evident with the application of E. coli in both cerulein and placebo groups. Application of E. coli but not of H. pylori determined pancreatic activation of trypsinogen, increased mortality and induced the production of interleukin-6. CONCLUSIONS: Bacterial invasion of the pancreas worsens the histologic and clinical picture of disease and induces a systemic inflammatory response.


Subject(s)
Bacterial Infections/complications , Pancreas/pathology , Pancreatitis/microbiology , Pancreatitis/pathology , Acute Disease , Amylases/metabolism , Animals , Ceruletide , Disease Models, Animal , Interleukin-6/metabolism , Male , Organ Size , Pancreatitis/chemically induced , Pancreatitis, Acute Necrotizing/pathology , Phospholipases A/metabolism , Phospholipases A2 , Rats , Rats, Wistar , Systemic Inflammatory Response Syndrome/pathology
12.
Int J Colorectal Dis ; 21(4): 314-20, 2006 May.
Article in English | MEDLINE | ID: mdl-16205930

ABSTRACT

BACKGROUND: As angiogenesis is one of the key steps in tumor growth, invasion, and metastasis, antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. We investigated the cytotoxic, anti-adhesive, and anti-invasive effects of angiostatin in vitro and on intraperitoneal tumor growth in a laparoscopic rat model of peritoneal carcinomatosis using CC531 colon adenocarcinoma cells. METHODS: The in vitro adhesion and cytotoxicity assays were performed with microtiter plates, and the invasion assay with Transwell dual chambers. Normal saline was used as control. In in vivo experiments, CC531 adenocarcinoma cells were intraperitoneally given to Wistar Albino Glaxo rats after the establishment of a pneumoperitoneum. The animals received angiostatin in different doses intraperitoneally, and in some, angiostatin was additionally administered subcutaneously. Saline was used as control. After 21 days, the animals were euthanized to determine the intra-abdominal tumor weight. RESULTS: In in vitro experiments, there was no effect of angiostatin on the viability of tumor cells in the cytotoxicity assay, but there was a significant inhibition of tumor cell adhesion and invasion (p<0.05 and p<0.01) in all angiostatin concentrations. In in vivo experiments, an intraperitoneal application of 20 microg angiostatin, but not 10 microg, significantly (p<0.005) decreased the intraperitoneal tumor weight compared with controls. This effect was most pronounced after the combined intraperitoneal and subcutaneous applications. CONCLUSION: Angiostatin given intraperitoneally at a dose of 20 microg alone or in combination with subcutaneous application significantly diminishes intraperitoneal tumor growth in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic surgery for colorectal cancer.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Angiostatins/pharmacology , Neovascularization, Pathologic/prevention & control , Peritoneal Neoplasms/pathology , Adenocarcinoma/pathology , Animals , Cell Adhesion/drug effects , Cell Line, Tumor/drug effects , Colonic Neoplasms/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Injections, Intraperitoneal , Injections, Subcutaneous , Laparoscopy , Male , Neoplasm Transplantation , Peritoneal Neoplasms/blood supply , Pneumoperitoneum, Artificial , Random Allocation , Rats , Rats, Wistar
13.
J Med Genet ; 42(10): e62, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16199544

ABSTRACT

BACKGROUND: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. OBJECTIVE: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. METHODS: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany (n = 638), Netherlands (n = 136), and Switzerland (n = 106), and in healthy (n = 1409) and alcoholic (n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. RESULTS: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. CONCLUSIONS: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.


Subject(s)
Genetic Predisposition to Disease , Glucuronosyltransferase/genetics , Pancreatic Diseases/enzymology , Polymorphism, Genetic , Adenocarcinoma/metabolism , Adult , Cohort Studies , Female , Gene Frequency , Humans , Male , Middle Aged , Pancreatitis/enzymology , Xenobiotics
14.
Surg Endosc ; 19(2): 280-4, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15870965

ABSTRACT

BACKGROUND: The object of this study was to examine the effect of taurolidine on intraabdominal tumor growth in a laparoscopic animal model. We tested the cytotoxic, antiadhesive, and anti-invasive effects of this substance on CC531 adenocarcinoma cells in vitro and in vivo using WAG rats. METHODS: For in vitro experiments, Transwell dual chambers with polycarbonate filters coated with 100 microg/cm2 Matrigel were used to investigate the effects of 5, 10, and 20 microl of 2.0% taurolidine on the invasion of 1 x 10(5) CC531 adenocarcinoma cells. For the adhesion assays, tumor cells were applied onto microtiter plates coated with 5, 10, and 20 microl taurolidine and 0.9% NaCl solution for the control group subsequently. For in vivo experiments, 40 WAG rats were randomized into three therapy groups and one control group. All animals underwent laparoscopy and received 1 ml of CC531 adenocarcinoma cells (5 x 10(6) cells/ml) intraabdominally at the beginning of the procedure. According to the randomization, the rats were administered taurolidine with different concentrations or 1 ml of 0.9% NaCl solution for the control group. After 21 days, the animals were killed and the intraabdominal tumor weight was determined. RESULTS: For the in vitro experiments, we found a moderate cytotoxicity and a significant inhibition of tumor cell adhesion and invasion (p < 0.01) by all taurolidine concentrations used in the assay. For in vivo experiments, the application of all concentrations of taurolidine significantly decreased the intraperitoneal tumor weight (p < 0.001). CONCLUSION: Taurolidine significantly decreases adhesion and invasion of CC531 adenocarcinoma cells in vitro and significantly diminishes tumor growth in vivo. This may offer additional therapeutic options for laparoscopic surgery for colorectal cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/pharmacology , Colonic Neoplasms/drug therapy , Taurine/analogs & derivatives , Thiadiazines/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Cell Adhesion/drug effects , Cell Line, Tumor , Disease Models, Animal , Dose-Response Relationship, Drug , In Vitro Techniques , Laparoscopy , Male , Neoplasm Invasiveness , Rats , Rats, Inbred Strains , Taurine/administration & dosage , Taurine/pharmacology , Thiadiazines/administration & dosage
16.
Int J Clin Pharmacol Ther ; 42(9): 481-7, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15487806

ABSTRACT

OBJECTIVE: This study investigated concentrations of ascorbic acid (ASC) in gastric mucosa, gastric juice, urine and plasma in healthy subjects under steady state and fasted conditions with and without concomitant administration of acetylsalicylic acid (ASA). MATERIAL AND METHODS: This was a prospective, randomized, double-blind, parallel-group study in healthy subjects. It has assessed the effects of a 6-day administration of 0.8 g ASA or 0.48 g ASC, 3 times daily and the combination of both on concentrations of ASC in gastric mucosa, gastric juice, urine and plasma. Treatments were switched after 6 days without any washout for assessment of compartment sensitivity to changes in study medication resulting in an overall 14-day study period. Each of the 3 treatment groups consisted of 15 subjects. RESULTS: ASC concentrations were highest in the gastric mucosa (251+/-11 microg/g), followed by gastric juice (29+/-6 microg/ml), plasma (10+/-0.2 microg/ml), and urine (5+/-1 microg/ml). On day 7, ASC concentrations in gastric mucosa, plasma and urine had increased in those groups receiving ASC and decreased in the group receiving ASA only. All differences were statistically significant and indicate an interaction with ASA. In gastric juice, differences in ASC concentrations between the treatment groups were not statistically significant between baseline and day 7. ASC concentrations in plasma were strongly correlated with corresponding ASC concentrations in gastric mucosa (r = 0.34) and urine (r = 0.83), as were ASC concentrations in gastric mucosa with ASC in urine (r = 0.28). CONCLUSIONS: The gastric mucosa is the largest depot of ASC in the human body with ASC concentrations 25 times higher than in plasma. In healthy subjects, clinically relevant doses of ASA reduced ASC concentrations in gastric mucosa by about 10% within 6 days resulting from antioxidative defense mechanisms. In patients with long-term ASA treatment or conditions with additional risks such as elderly subjects with unfavorable dietary conditions and impaired antioxidative protection, a protective adjunct administration of ASC appears to be beneficial.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Ascorbic Acid/pharmacokinetics , Aspirin/pharmacology , Adolescent , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Ascorbic Acid/administration & dosage , Ascorbic Acid/blood , Ascorbic Acid/metabolism , Ascorbic Acid/urine , Aspirin/administration & dosage , Double-Blind Method , Fasting , Female , Gastric Juice/metabolism , Gastric Mucosa/metabolism , Humans , Male , Middle Aged , Prospective Studies
17.
Chirurg ; 75(10): 1021-8, 2004 Oct.
Article in German | MEDLINE | ID: mdl-15138659

ABSTRACT

Spontaneous or postoperative hemorrhage into the abdominal cavity due to inflammatory vessel arrosion represents an uncommon but menacing situation. According to the literature, such hemorrhage is associated with a lethality of nearly 2%. Therapeutical options include reoperation and interventional radiological techniques such as endovascular catheter techniques with stent graft implantation or the embolization of vessels. We report on the management of seven cases with hemorrhage either from the gastroduodenal artery ( n=5) following pancreatic surgery for pancreatic carcinoma, liposarcoma, and chronic pancreatitis or from the common hepatic artery ( n=1) and the superior mesenteric artery ( n=1) following chronic pancreatitis. The present article describes our experiences with stent graft implantation (hemobahn prosthesis) in four cases. Based on these experiences, we see the advantages of stent grafts in primary hemostasis without any contact to infected tissue and the preservation of regular perfusion. However, further clinical data are required focussing on indication, technical success rates, stent-related complications, and long-term outcome.


Subject(s)
Blood Vessel Prosthesis Implantation , Gastrointestinal Hemorrhage/surgery , Hemostasis, Surgical/methods , Pancreas/surgery , Postoperative Complications/surgery , Stents , Adult , Aged , Angioplasty, Balloon , Chronic Disease , Follow-Up Studies , Gastrointestinal Hemorrhage/etiology , Humans , Male , Middle Aged , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Pancreatitis/surgery , Reoperation , Shock, Hemorrhagic/etiology , Time Factors
18.
Pancreas ; 28(4): 387-90, 2004 May.
Article in English | MEDLINE | ID: mdl-15097855

ABSTRACT

OBJECTIVE: To investigate the relationship of strictures of the common bile duct (CBD) with pain in patients with chronic pancreatitis (CP) and jaundice. METHODS: A total of 61 patients with CBD strictures caused by CP of alcoholic etiology were treated by endoscopic stent insertion for 1 year with scheduled stent exchanges. Pain was assessed using a visual analogue scale, and analgesic medication was recorded prior to and after endoscopic treatment. RESULTS: Endoscopic drainage was successful in all cases, with complete resolution of jaundice during the 1-year follow-up period. Prior to the endoscopic stent insertion, pain scores were 6.8 +/- 6.3. Following stent therapy pain scores were 7.7 +/- 7.7. Pain scores, the number of patients requiring analgesics, the required amount of analgesics, and the type of analgesic medication did not change following treatment of CBD stricture. CONCLUSION: Successful endoscopic drainage of biliary obstruction has no influence on pain pattern in patients with CP. CBD obstruction does not cause pain in patients with CP.


Subject(s)
Abdominal Pain/etiology , Common Bile Duct Diseases/complications , Pancreatitis/complications , Abdominal Pain/diagnosis , Adult , Aged , Chronic Disease , Common Bile Duct Diseases/surgery , Constriction, Pathologic/complications , Constriction, Pathologic/surgery , Female , Follow-Up Studies , Humans , Jaundice, Obstructive/etiology , Male , Middle Aged , Stents/adverse effects , Treatment Outcome
19.
Aliment Pharmacol Ther ; 19(3): 367-74, 2004 Feb 01.
Article in English | MEDLINE | ID: mdl-14984384

ABSTRACT

BACKGROUND: The most frequently reported adverse events associated with acetylsalicylic acid intake are minor gastrointestinal complaints. Galenic modifications, such as buffered formulations with or without ascorbic acid, may improve the benefit-risk ratio by decreasing the local mucosal side-effects of acetylsalicylic acid. AIM: To assess endoscopically-proven gastrointestinal lesions and the amount of gastric microbleeding of four different buffered and plain acetylsalicylic acid formulations, one containing paracetamol. METHODS: A randomized, four-fold cross-over study was performed in 17 healthy subjects who underwent serial oesophago-gastro-duodenoscopy before and after each course of 4-day dosing. Gastric aspirates were collected for the determination of haemoglobin concentrations to detect microbleeding. RESULTS: Buffered acetylsalicylic acid plus ascorbic acid yielded the lowest Lanza score, the lowest increase in the number of mucosal petechiae and the lowest increase in the amount of gastric microbleeding. Subjects receiving acetylsalicylic acid plus paracetamol plus caffeine showed the highest Lanza score of all treatments, and a considerably greater sum of petechiae in the oesophagus, stomach and duodenum compared with those receiving buffered acetylsalicylic acid plus ascorbic acid. CONCLUSIONS: The trial confirms that buffering of acetylsalicylic acid improves local gastric tolerability. Acetylsalicylic acid in combination with ascorbic acid shows significantly fewer gastric lesions and the lowest increase in gastric microbleeding compared with the other tested formulations.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Aspirin/adverse effects , Gastrointestinal Hemorrhage/chemically induced , Stomach Diseases/chemically induced , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Aspirin/administration & dosage , Cross-Over Studies , Female , Gastric Mucosa , Humans , Male , Prospective Studies , Risk Factors
20.
Int J Colorectal Dis ; 19(2): 143-6, 2004 Mar.
Article in English | MEDLINE | ID: mdl-12955418

ABSTRACT

BACKGROUND AND AIMS: Metastatization, adhesion, invasion, and growth of tumor cells involve a cascade of complex phenomena which may be affected. We investigated the effect of a low molecular weight heparin, reviparin, on intra-abdominal tumor growth and intra-abdominal metastasis in rats undergoing laparoscopy. METHODS: CC531 adenocarcinoma cells (5x10(6) cells/ml) were administered intraperitoneally to 150 Wistar Albino Glaxo rats, with 15 groups of animals each. During laparoscopy 1 ml saline containing 0.0, 0.5, 2.0,; 4.0, and 10 mg reviparin/kg b.w. was introduced intraperitoneally (i.p.), daily subcutaneously (s.c.), or combined. After 21 days the animals were killed and underwent autopsy, and the tumor weight and the number of metastases on the liver surface were determined. RESULTS: Tumor weight was significantly reduced by 4.0 and 10.0 mg/kg b.w. but not by 0.5 or 2.0 mg/kg b.w. compared to controls. Decreased metastatization was observed in all treated groups. These effects were most pronounced after the s.c. or combined i.p. and s.c. administration, whereas after a sole i.p. administration only the highest dose of 10 mg/kg b.w. induced a significant inhibition of tumor growth. CONCLUSION: Low molecular weight heparin given s.c. or in combination of i.p. lavage and s.c. injections significantly inhibits intra-abdominal tumor growth and intraperitoneal metastasis of CC531 adenocarcinoma cells in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic and also open cancer surgery.


Subject(s)
Abdominal Neoplasms/prevention & control , Adenocarcinoma/prevention & control , Anticoagulants/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Peritoneal Neoplasms/prevention & control , Abdominal Neoplasms/pathology , Adenocarcinoma/secondary , Animals , Anticoagulants/adverse effects , Disease Models, Animal , Dose-Response Relationship, Drug , Heparin, Low-Molecular-Weight/adverse effects , Injections, Intraperitoneal , Injections, Subcutaneous , Laparoscopy/methods , Peritoneal Neoplasms/secondary , Rats , Rats, Wistar , Tumor Cells, Cultured
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