Sabine Richter

Risk factors and complications following percutaneous endoscopic gastrostomy: a case series of 1041 patients.

BACKGROUNDnMost studies exclude patients with severe coagulation disorders or those taking anticoagulants when evaluating the outcomes of percutaneous endoscopic gastrostomy (PEG).nnnOBJECTIVEnTo investigate complications and risk factors of PEG in a large clinical series including patients undergoing antiplatelet and anticoagulant therapy.nnnMETHODSnDuring a six-year period, 1057 patients referred for PEG placement were prospectively audited for clinical outcome. Exclusion criteria and follow-up care were defined. Complications were defined as minor or severe. Uni- and multivariate analyses were used to evaluate 14 risk factors. No standardized antibiotic prophylaxis was given.nnnRESULTSnA total of 1041 patients (66% male, 34% female) with the following conditions underwent PEG: neurogenic dysphagia (n=450), cancer (n=385) and others (n=206). No anticoagulants were administered to 351 patients, thrombosis prophylaxis was given to 348 while full therapeutic anticoagulation was received by 313. No increased bleeding risk was associated with patients who had above-normal international normalized ratio values (OR 0.79 [95% CI 0.08 to 7.64]; P=1.00). The total infection rate was 20.5% in patients with malignant disease, and 5.5% in those with nonmalignant disease. Severe complications occurred in 19 patients (bleeding 0.5%, peritonitis 1.3%). Cirrhosis (OR 2.91 [95% CI 1.31 to 6.54]; P=0.008), cancer (OR 2.34 [95% CI 1.33 to 4.12]; P=0.003) and radiation therapy (OR 2.34 [95% CI 1.35 to 4.05]; P=0.002) were significant predictors of post-PEG infection. The 30-day mortality rate was 5.8%. There were no procedure-related deaths.nnnCONCLUSIONSnCancer, cirrhosis and radiation therapy were predictors of infection. Post-PEG bleeding and other complications were rare events. Collectively, the data suggested that patients taking concurrent anticoagulants had no elevated risk of post-PEG bleeding.

Inhibition of matrix metalloproteinase-9 with doxycycline reduces pancreatitis-associated lung injury.

Background/Aims: Severe lung injury, responsible for up to 15% of mortality in acute necrotizing pancreatitis patients, is promoted by neutrophil (PMN) migration into the lung. We have previously demonstrated that pulmonary injury in acute pancreatitis is mediated by PMN-derived matrix metalloproteinase-9 (MMP-9). This study was conducted to evaluate the ability of the broad-spectrum MMP inhibitor doxycycline to prevent secondary pulmonary injury in acute pancreatitis. Methods: Eighteen rats were randomized into three groups: severe pancreatitis (SAP), severe pancreatitis + doxycycline (SAP+Dox) (30 mg/kg body mass) or control. Acute pancreatitis was induced by intraductal glycodesoxycholic acid and i.v. stimulation with cerulein. Lung sections were histologically graded for edema, microthrombi, atelectasis and hemorrhage. Active MMP-9 in lung tissue was measured with fluorescent assay (ELISA). Naphtol-AS-D-chloroacetate esterase staining was used to determine pulmonary PMN infiltration. The inhibitory effect of doxycycline on MMP-9-induced transmigration was confirmed in a Matrigel transmigration assay. Results: Addition of doxycycline significantly reduced TNF-α-induced PMN transmigration across Matrigel membrane (12.6 ± 2.6 vs. 20.1 ± 3.9 PMNs; p < 0.05). SAP+Dox showed decreased concentration of active MMP-9 in lung tissue (37.89 ± 1.75 vs. 46.29 ± 3.68 ng/ml; p < 0.05) and as a result decreased pulmonary infiltration of PMNs (21.2 ± 5.1 vs. 32.5 ± 6.8; p < 0.05). Histological evaluation revealed decreased pulmonary edema (1.83 ± 0.41 vs. 2.33 ± 0.51, p < 0.05), atelectasis (1.67 ± 0.52 vs. 2.33 ± 0.52; p < 0.05) and pulmonary hemorrhage (2.5 ± 0.55 vs. 1.83 ± 0.41; p < 0.05) in SAP+Dox vs. SAP. These findings were paralleled by reduced pulmonary expression of active MMP-9. Conclusions: Inhibition of MMP-9 activity with doxycycline reduced pancreatitis-associated lung injury and expression of MMP-9 in pulmonary tissue. Doxycycline reduced PMN migration in vitro and in vivo and therefore might represent a novel strategy for the prevention of secondary pulmonary complications in acute pancreatitis.

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

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

Percutaneous endoscopic gastrostomy. Complications with and without anticoagulation

BACKGROUNDnPercutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation.nnnMETHODSnBetween 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given.nnnRESULTSnThe average hospitalization time was 27.4 days (range 1-268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications.nnnCONCLUSIONnComplications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.ZusammenfassungHintergrundDie perkutane endoskopische Gastrostomie (PEG) wird bislang als Hochrisikoeingriff klassifiziert (ASGE-Leitlinien). Koagulopathien, Thrombozytenaggregationshemmer (Aspirin, Clopidogrel u.a.) und Phenprocoumon bzw. Wafarine gelten als Kontraindikationen. Die Studie untersucht erstmals Komplikationen und Risikofaktoren bei Patienten mit und ohne Antikoagulation.Material und MethodenAn der Klinik für Allgemein- und Viszeralchirurgie der Universität Freiburg wurden zwischen 2001 and 2007 insgesamt 450xa0Patienten mit neurologischer Dysphagie mit einer PEG versorgt und prospektiv während des stationären Aufenthalts untersucht. Die Patienten wurden drei Gruppen zugewiesen: Gruppexa01: keine Antikoagulation (n=50), Gruppexa02: Prophylaxe mit niedermolekularem Heparin (NMH, n=152), Gruppexa03: therapeutische Antikoagulation und Thrombozytenaggregationshemmer (UFH, NMH, Phenprocoumon, Acetysalicylsäure, Clopidogrel und Kombinationen, n=248). 11 Risikofaktoren und die Komplikationen Infektion, Blutung und Peritonitis wurden univariat analysiert (p-Wert, Odds Ratio [OR], 95%-Konfidenzintervall [KI]).ErgebnisseDer mittlere stationäre Aufenthalt betrug 27,4 Tage (1–268). Die Krankenhausmortalität betrug 6%. Ein PEG-abhängiger Todesfall trat nicht auf. Es zeigten sich 6,6% peristomale Infekte (n=30) und 1,3% Peritonitiden (n=6). Eine Post-PEG-Blutung wurde weder mit noch ohne Antikoagulation beobachtet. Die untersuchten Risikofaktoren zeigten sich in der Vorhersage auf o.g. Komplikationen statistisch nicht signifikant und konnten aufgrund der geringen Anzahl nicht multivariat getestet werden.SchlussfolgerungKomplikationen der PEG mit der Fadendurchzugsmethode sind per se selten. Ein erhöhtes PEG-assoziiertes Blutungsrisiko unter therapeutischer Antikoagulation wurde nicht beobachtet. Unseres Erachtens kann nach den vorliegenden Daten bei ausgewählten Patienten mit hohen Thromboembolierisiken eine PEG-Anlage auch ohne Absetzen der Antikoagulation erfolgen.AbstractBackgroundPercutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation.MethodsBetween 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given.ResultsThe average hospitalization time was 27.4 days (range 1–268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications. ConclusionComplications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.

Perkutane endoskopische Gastrostomie

BACKGROUNDnPercutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation.nnnMETHODSnBetween 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given.nnnRESULTSnThe average hospitalization time was 27.4 days (range 1-268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications.nnnCONCLUSIONnComplications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.ZusammenfassungHintergrundDie perkutane endoskopische Gastrostomie (PEG) wird bislang als Hochrisikoeingriff klassifiziert (ASGE-Leitlinien). Koagulopathien, Thrombozytenaggregationshemmer (Aspirin, Clopidogrel u.a.) und Phenprocoumon bzw. Wafarine gelten als Kontraindikationen. Die Studie untersucht erstmals Komplikationen und Risikofaktoren bei Patienten mit und ohne Antikoagulation.Material und MethodenAn der Klinik für Allgemein- und Viszeralchirurgie der Universität Freiburg wurden zwischen 2001 and 2007 insgesamt 450xa0Patienten mit neurologischer Dysphagie mit einer PEG versorgt und prospektiv während des stationären Aufenthalts untersucht. Die Patienten wurden drei Gruppen zugewiesen: Gruppexa01: keine Antikoagulation (n=50), Gruppexa02: Prophylaxe mit niedermolekularem Heparin (NMH, n=152), Gruppexa03: therapeutische Antikoagulation und Thrombozytenaggregationshemmer (UFH, NMH, Phenprocoumon, Acetysalicylsäure, Clopidogrel und Kombinationen, n=248). 11 Risikofaktoren und die Komplikationen Infektion, Blutung und Peritonitis wurden univariat analysiert (p-Wert, Odds Ratio [OR], 95%-Konfidenzintervall [KI]).ErgebnisseDer mittlere stationäre Aufenthalt betrug 27,4 Tage (1–268). Die Krankenhausmortalität betrug 6%. Ein PEG-abhängiger Todesfall trat nicht auf. Es zeigten sich 6,6% peristomale Infekte (n=30) und 1,3% Peritonitiden (n=6). Eine Post-PEG-Blutung wurde weder mit noch ohne Antikoagulation beobachtet. Die untersuchten Risikofaktoren zeigten sich in der Vorhersage auf o.g. Komplikationen statistisch nicht signifikant und konnten aufgrund der geringen Anzahl nicht multivariat getestet werden.SchlussfolgerungKomplikationen der PEG mit der Fadendurchzugsmethode sind per se selten. Ein erhöhtes PEG-assoziiertes Blutungsrisiko unter therapeutischer Antikoagulation wurde nicht beobachtet. Unseres Erachtens kann nach den vorliegenden Daten bei ausgewählten Patienten mit hohen Thromboembolierisiken eine PEG-Anlage auch ohne Absetzen der Antikoagulation erfolgen.AbstractBackgroundPercutaneous endoscopic gastrostomy (PEG) has been classified to date as a high-risk procedure (ASGE guidelines). Coagulopathies, thrombocyte aggregation inhibitors (Aspirin, clopidogrel etc.) and phenprocoumone or warfarin are considered to be contraindications. The study examined for the first time the risk factors in patients with and without concurrent anticoagulation.MethodsBetween 2001 and 2007 PEGs were placed in 450 patients with neurological diseases at the University Hospital for General and Visceral Surgery in Freiburg and studied prospectively during hospitalization. The patients were divided into 3 groups: group 1 controls (n=50, no anticoagulation), group 2 low-molecular-weight heparin (LMWH) prophylaxis (n=152) and group 3 therapeutic anticoagulation (unfractionated heparin, phenprocoumone, therapeutic LMWH, aspirin, clopidorel and combinations, n=248). Univariate analyses were performed to determine risk factors for the occurrence of infection, bleeding and peritonitis. The p-values (p), odds ratios (OR) and 95% confidence intervals (CI) are given.ResultsThe average hospitalization time was 27.4 days (range 1–268 days) and hospital mortality was 6%. There were no cases of death due to the PEG. Complications included peristomal infections (n=30, 6.6%) and peritonitis (n=6, 1.3%). Post-PEG bleeding did not occur either with or without anticoagulation. The investigated risk factors showed no statistically significant values with respect to prognosis for these complications. Multivariate testing could not be carried out due to the low number of complications. ConclusionComplications of PEG placement with the method used here are rare. An increased risk of bleeding during therapeutic anticoagulation was not observed. In our opinion the present data indicate that PEG placement can be carried out in selected patients with increased risk of thromboembolism without discontinuation of anticoagulation.

MMP-9 in Serum Correlates with the Development of Pulmonary Complications in Experimental Acute Pancreatitis

Introduction: The prediction of the course of acute pancreatitis and its arising complications is of clinical importance. The aim of this study was to judge the time course and relevance of matrix metalloproteinase-9 (MMP-9), a PMN-derived protease, for the development of pulmonary complications in two models of acute pancreatitis. Methods: MMP-9 was evaluated in a standardized experimental model of acute pancreatitis. Mild edematous (n = 12) and severe necrotizing pancreatitis (n = 48) were induced by intravenous cerulein or intravenous cerulein and intraductal application of glycodeoxycholic acid and compared to control animals. 1, 6, 9, 12, 24 and 72 h after induction, rats were sacrificed and damage to the lung and the pancreas was quantified by histology and extravasation of Evans blue. At 1, 6, 9, 12, 24 and 72 h, we determined MMP-9 in serum by ELISA. Results: In our model, MMP-9 in serum was increased in the group with severe acute pancreatitis in comparison to mild edematous pancreatitis and controls at each evaluated time point (p < 0.05). The maximum release of MMP-9 preceded the development of pulmonary complications, verified by histology and extravasation of Evans blue. MMP-9 showed a negative predictive value of 96.2% and a positive predictive value of 100% for the development of pulmonary complications. Conclusion: MMP-9 in serum allows a valid grouping to severe and mild courses of experimental acute pancreatitis with a good predictive value for the development of pulmonary complications. MMP-9 should be evaluated as a valid single marker for the prediction of progression and the development of pulmonary complications in acute pancreatitis in clinical studies.

Infected pancreatic necrosis increases the severity of experimental necrotizing pancreatitis in mice.

Objective Infection of pancreatic necrosis in necrotizing pancreatitis increases the lethality of patients with acute pancreatitis. To examine mechanisms underlying this clinical observation, we developed and tested a model, in which primary infection of necrosis is achieved in taurocholate-induced pancreatitis in mice. Methods Sterile necrosis of acute necrotizing pancreatitis was induced by retrograde injection of 4% taurocholate into the common bile duct of Balb/c mice. Primary infection of pancreatic necrosis was induced by coinjecting 108 colony-forming units of Escherichia coli. Animals were killed after 6, 12, 24, 48, and 120 hours, and pancreatic damage and pancreatitis-associated systemic inflammatory response were assessed. Results Mice with pancreatic acinar cell necrosis had an increased bacterial concentration in all tissues and showed sustained bacteremia. Acute pancreatitis was induced only by coinjection of taurocholate and not by bacterial infection alone. Infection of pancreatic necrosis increased pancreatic damage and the pulmonary vascular leak. Serum glucose concentrations serving as a parameter of hepatic function were reduced in mice with infected pancreatic necrosis. Conclusions Primary infection of pancreatic necrosis with E. coli increases both pancreatic damage and pulmonary and hepatic complications in acute necrotizing pancreatitis in mice.

Dissecting the effect of moxifloxacin in mice with infected necrosis in taurocholate induced necrotizing pancreatitis

OBJECTIVESnTo investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events.nnnMETHODSnSterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10(8)xa0CFU/ml Escherichia coli. 10xa0mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24xa0h, animals were sacrificed to examine serum as well as organs for signs of SIRS.nnnRESULTSnMoxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10(7)xa0±xa02.4·10(7) vs. AN 4.9·10(4)xa0±xa02.6·10(4)xa0CFU/g; pxa0<xa00.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8xa0±xa02.7 vs. AN 22.6xa0±xa01.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5xa0±xa0336.6 vs. 38.7xa0±xa025.5xa0pg/ml; pxa0<xa00.001), hypoglycemia (serum glucose: IN 105.8xa0±xa012.7 vs. AN 155.7xa0±xa039.5xa0mg/dl; pxa0<xa00.001), and serum aspartate aminotransferase (IN 606xa0±xa089.7 vs. AN 255xa0±xa052.1; pxa0<xa00.05). These parameters were significantly increased in animals with necrotizing pancreatitis.nnnCONCLUSIONnIn the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.

Murine genotype impacts pancreatitis severity and systemic inflammation: An experimental study

Background Little is known regarding the impact of host response in acute pancreatitis. Here, we induce murine necrotizing pancreatitis in 9 different mouse strains. Materials and methods We examined 9 different mouse strains: Balb/CB4J, C3H/HEJ, NOD/SHILT, A/J, AKR/J, C57BI/6J, DBA/2J, FVB/NJ, 129S1/SvlmJ. 10 animals per strain were randomly allotted to two groups. Sterile necrotizing pancreatitis was induced by injection of taurocholate into the common bile duct. Control animals were injected with saline. Every 6 h, clinical parameters were examined and scored. After 24 h, animals were sacrificed to examine and compare serum enzymes, histology, bronchoalveolar lavage fluid, and serum IL-6. Results Histologically, taurocholate treated animals scored significantly higher than control animals. Concordantly, serum lipase and amylase were significantly elevated in pancreatitis animals in all strains. NOD/SHILT and AKR/J mice had the highest enzyme activity. 24 h after induction, there were no signs of increased pulmonary vascular leak in taurocholate animals. Remarkably, interleukin 6 was not increased at all in C57BL/6J, C3H/HeJ, and 129S1/SvlmJ mice compared to all other strains. Conclusion The genetic strain has an impact on pancreatitis severity and systemic inflammatory response in a murine taurocholate induction model. Analogous differences in humans may partially account for the disparity in post-ERCP pancreatitis.

Does the genetic strain influence severity of acute necrotizing pancreatitis and SIRS in a murine model

s / Pancreatology 14 (2014) S1eS129 S101 profiles measured. EAP severity was assessed by standard biochemical parameters and blinded histopathology. Results: GSK-7975A inhibited calcium influx and necrotic pathway activation inmurine (at 3, 10 or 30 mM, p<0.05) and human (at 10, 30 or 100 mM, p<0.05) PACs after toxin administration. TRPC3 inhibition did not further increase inhibition of calcium influx. PK confirmed GSK-6288B consistently achieved drug levels of GSK-7975A (circa 4.2 and 13.32 mM in blood or 8.87 and 49.31mM in pancreas at the dose of 28 and 110mg/kg/h, respectively). GSK-6288B significantly reduced all EAP severity parameters in both models (all p<0.05). Conclusion: Orai1 plays a major role in PAC Ca2+ entry and injury in response to toxins. This work confirms the role of calcium overload in EAP and suggests Orai1 inhibition has potential in the treatment of AP.