Guido Alsfasser

Imaging of Acute Mesenteric Ischemia Using Multidetector CT and CT Angiography in a Porcine Model

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findingsd—compared with pathologic diagnosesd—predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.

Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis

Background: Release of TNFα is thought to play an important role in mediating systemic effects in acute pancreatitis (AP). We have been unable to find an elevation of plasma TNFα in AP and hypothesize that it is susceptible to catabolism by circulating pancreatic proteases. Methods: (1) AP was induced in Sprague-Dawley rats by cerulein hyperstimulation preceded by intraductal infusion of saline (mild) or glycodeoxycholic acid (severe). Healthy and sham-operated animals served as controls. Severity of pancreatitis was confirmed by histology. Plasma TNFα levels were measured at various time points after induction of AP with competitive ELISA. (2) Recombinant rat TNFα (rrTNFα) was incubated with trypsin, elastase, chymotrypsin and pepsin. Western Blot was performed to visualize TNF degradation. (3) RrTNFα was incubated in a concentration and time-dependant manner with proteases and TNF bioactivity was evaluated with a cytotoxicity assay. Results: (1) Plasma TNFα levels in severe pancreatitis were significantly lower than in sham-operated controls after 0.5 and 6 h. (2) Incubation with proteases showed degradation in the presence of trypsin, elastase and chymotrypsin and no effect of pepsin. (3) There was a concentration dependent inactivation of rrTNFα in the presence of pancreatic proteases and a complete time-dependent inactivation in the presence of trypsin. Conclusion: Plasma TNFα does not rise in experimental AP, and levels are significantly lower in severe pancreatitis compared to sham-operated controls. Our study demonstrates degradation and inactivation of TNFα by pancreatic proteases, suggesting that it is unlikely it plays an important role in the development of distant organ failure.

478 Surgical Endoscopic Vacuum Therapy for Defects of the Upper GI Tract

S A T A b st ra ct s of esophagogastric junction (EGJ) relaxation. Indeed, the diagnosis of achalasia is established by HRM on the basis of an IRP>15mmHg and absence of normal peristalsis in the esophageal body. Our aim was to assess the effect of Heller myotomy on IRP in achalasia patients. Patients and Methods: We evaluated all consecutive patients who underwent laparoscopic Heller myotomy as first treatment from 2009-2014 and had a HRM evaluation before and after surgery. Patients who had already been treated for achalasia (with Heller myotomy, endoscopic treatment) were excluded from the study. The diagnosis of primary achalasia was established by esophageal manometry on the basis of accepted esophageal motility characteristics (i.e. absence of normal peristalsis in the esophageal body). Symptoms were collected and scored using a detailed questionnaire for dysphagia, regurgitation, and chest pain; barium swallow, endoscopy, HRM were performed, before and 6 months after surgical treatment. Treatment failure was defined as a postoperative symptom score >10th percentile of the preoperative score (i.e. > 10). Results: 139 consecutive achalasia patients (M:F= 72:67) represented the study population. All the patients had 100% simultaneous waves but 11 had a IRP<15 mmHg. According to the HRM classification, patients were classified as having: 58 (42.3%) type I, 63 (46%) type II and 16 (11.7%) type III. At a median follow-up of 24 months, the symptom score was significantly lower after surgery (median preoperative score 18 [IQR 11-20] vs median postoperative score 0 [IQR 0-3]; p<0.0001). The resting LES pressure (median preoperatively 27 [IQR 19-36] vs median postoperatively 11 [IQR 8-14]; p<0.001) and IRP (median preoperatively 27.4 [IQR 20.4-35] vs median postoperatively 7.1 [IQR: 4.4-9.8]; p<0.001). The surgical procedure was completed laparoscopically in all the patients. The failures of surgical treatment were 7 (5%). At univariate analysis IRP was correlated with the gender, LES basal and resting pressure, and the dysphagia score. Conclusion: This is the first study evaluating the role of IRP in achalasia and its modifications after surgery. An increased preoperative IRP directly correlated with dysphagia severity in achalasia patients. Heller myotomy was able to resolve this symptom by reducing the IRP to a value lower than 10 mmHg.

Aktiviertes Protein C hemmt die Entzündungsreaktion und verbessert das Überleben bei experimenteller akuter Pankreatitis

Objective: To evaluate the effect of Drotrecogin alfa (activated) (DrotAA) in experimental acute pancreatitis (AP). Summary Background Data: DrotAA is the pharmacological form of activated protein C (APC) and is the first FDA-approved drug for treatment of severe sepsis. It has not been evaluated in acute pancreatitis. Methods: Safety of i. v. DrotAA was assessed in healthy animals with different dosages. Mild (iv cerulein) or severe (iv cerulein + intraductal glycodeoxycholic-acid) AP was induced in 72 rats and coagulation parameters were compared to 42 healthy and sham-operated animals. Rats with severe AP were randomized to treatment with 100 μg/kg/h DrotAA or saline. End-points included histologic scoring of pancreatic necrosis, inflammation of pancreas and lung (measured by myeloperoxidase (MPO)), coagulation parameters, and 24h survival. Results: Severe consumptive coagulopathy, disseminated intravascular coagulation (DIC), hemoconcentration, and leukocytosis were observed six hours after induction of severe AP, but not in mild AP. Treatment of AP with 100 μg/kg/h DrotAA did not worsen coagulation parameters. While the degree of pancreatic necrosis was comparable in treated and untreated animals with severe AP, APC significantly reduced MPO levels in pancreas (p = 0.009) and lungs (p = 0.03). 24 h survival in severe AP was markedly improved in animals treated with APC (86% vs. 38%, p < 0.05 ). Conclusion: Animals with severe AP suffer from severe consumptive coagulopathy and DIC, but administration of 100 μ/kg/h DrotAA does not worsen coagulation abnormalities. DrotAA treatment reduces inflammation in the pancreas and lungs and significantly improves survival. These results encourage clinical investigation of DrotAA in treatment of severe acute pancreatitis.

Konfokale Laser Reflektanz Mikroskopie in vivo: eine neue Methode zur Beurteilung der pankreatischen Mikrozirkulation bei akut nekrotisierender Pankreatitis

Konfokale Laser Reflektanz Mikroskopie (CM) liefert in Echtzeit nicht invasive Bilder von dunnen virtuellen Schnitten durch Gewebe in hoher Auflosung und Kontrast. Wir haben vor kurzem die in vivo Anwendbarkeit dieser neuen Technik erstmals fur die Beurteilung der Mikrozirkulation des Pankreas und die Evaluierung der Leukozyten-Endothel Interaktion in postkapillaren Venolen des Pankreas bei der Ratte demonstriert. Ziel dieser Studie war es, die Mikrozirkulation des Pankreas bei akuter Pankreatitis im Vergleich zu gesunden Tieren und einer Therapiegruppe zu evaluieren.