The WD40-domain containing protein CORO2B is specifically enriched in glomerular podocytes and regulates the ventral actin cytoskeleton.

Podocytes are highly specialized epithelial cells essentially required to establish and maintain the kidney filtration barrier. Due to their complex cellular architecture these cells rely on an elaborated cytoskeletal apparatus providing plasticity as well as adaptive adhesion properties to withstand significant physical filtration forces. However, our knowledge about podocyte specific components of the cytoskeletal machinery is still incomplete. Employing cross-analysis of various quantitative omics-data sets we identify the WD40-domain containing protein CORO2B as a podocyte enriched protein. Furthermore, we demonstrate the distinct localization pattern of CORO2B to the ventral actin cytoskeleton serving as a physical linkage module to cell-matrix adhesion sites. Analysis of a novel Coro2b knockout mouse revealed that CORO2B modulates stress response of podocytes in an experimental nephropathy model. Using quantitative focal adhesome proteomics we identify the recruitment of CFL1 via CORO2B to focal adhesions as an underlying mechanism. Thus, we describe CORO2B as a novel podocyte enriched protein influencing cytoskeletal plasticity and stress adaptation.

A phase II study of high-dose octreotide in patients with unresectable pancreatic carcinoma.

This report describes the results of a phase II trial to evaluate the safety, feasibility and response of patients with irresectable, histologically proven, stage II-IV adenocarcinoma of the pancreas receiving high-dose octreotide treatment. Octreotide was self-administered subcutaneously (3 x 2000 micrograms per day) by 49 patients. Therapy was discontinued after progression of the disease. Due to the subseqment diagnosis of bile duct carcinoma and stage I disease, 2 patients were excluded, leaving 47 evaluable patients with measurable disease. The median Karnofsky score was 80%. 3 patients had stage II (6%), 19 stage III (40%), and 25 (53%) stage IV disease. Octreotide treatment resulted in stable disease in 9 patients (19%) for more than 12 weeks. No complete or partial response was observed. The median overall survival was 21.4 weeks and the median progression-free survival 9.0 weeks. Therapy with high-dose octreotide is feasible, well tolerated and might prolong survival. In a placebo-controlled phase III study the effects of octreotide in patients with pancreatic cancer will be confirmed.

[Acute pancreatitis. Classification, diagnosis, therapy]. / Die akute Pankreatitis. Klassifikation-Diagnostik-Therapie.

Acute pancreatitis is a multietiologic entity with rather diverse clinical courses. Whereas edematous pancreatitis has a mortality of less than 1%, nowadays; still approximately 20% of all patients with the necrotizing form succumb to the disease. To further improve therapeutic results a standardized approach should be used. For effective treatment the differentiation between edematous and necrotizing pancreatitis is crucial. All patients with signs of pancreatic necroses during abdominal ultrasound and patients with organ insufficiencies should undergo a CT-scan to define exactly the nature and the extent of the disease. Primarily all patients are treated conservatively. Main indications for operative intervention are signs for infection of pancreatic necroses and an acute abdomen due to local complications of acute pancreatitis. In cases of biliary origin an elective cholecystectomy has to be performed during a free interval to prevent a recurrence.

Regression of a distal bile duct carcinoma after treatment with octreotide for 6 months.

We report the case of a 66-year-old male who was admitted for obstructive jaundice presenting with an enlargement of the pancreatic head on CT scan. During exploratory laparotomy an invasion of the retropancreatic mesenteric vessels was found. Subsequently, the patient was included in a multi-center trial of subcutaneous high-dose octreotide in irresectable pancreatic cancer. After 6 months there was no tumour detectable on routine CT follow-up. One year after commencing octreotide treatment the patient underwent Whipple resection; the specimen showing a small T1N0M0 distal bile duct carcinoma. Taking into account that somatostatin receptors have been found on bile duct cancer cells our observation might warrant a controlled clinical trial.

[The value of 3-phase spiral CT and magnetic resonance tomography in preoperative diagnosis of pancreatic carcinoma]. / Die Wertigkeit der 3-Phasen-Spiral-CT und der Magnetresonanztomographie in der präoperativen Diagnostik des Pankreaskarzinoms.

UNLABELLED: The purpose of this study was to assess the role of spiral computed tomography (SCT) and magnetic resonance imaging (MRI) in the preoperative work-up of patients with pancreatic carcinoma, regarding local resectability and vascular involvement. METHODS AND MATERIALS: A total of 28 patients (19 men and 9 women; mean age 58 years) with known or highly suspected carcinoma of the pancreas were included in this study. All patients prospectively underwent MRI ( +/- gadolinium-DTPA ) and SCT (3-phase examination) as preoperative diagnostic imaging studies, and laparotomy was carried out within 7 days, irrespective of the MRI or SCT findings. SCT and MR studies were reviewed independently by two radiologists, without knowing the results of the surgical exploration. Standardized image analysis was correlated with findings at laparatomy. RESULTS: Laparotomy identified 10 patients to be suitable for surgical resection and 18 pancreatic carcinomas to be unresectable. In 17 of 18 non-resectable carcinomas MRI and SCT were able to obtain correct information about unresectability (sensitivity 94%), in 7 (MRI), resp. 8 (SCT) carcinomas were correctly considered to be resectable (sensitivity 70% of MRI and 80% for SCT). The presence of vascular involvement was depicted by SCT with a sensitivity of 82-100% and 62-100% by MRI. The specificity varied between 85-100% for SCT and 77-100% for MRI. CONCLUSION: Both MRI and SCT are good techniques for the preoperative work-up of pancreatic carcinomas in order to obtain a correct assessment of local resectability.

[Injuries of the extrahepatic bile ducts. Clinical aspects, diagnosis and therapy]. / Verletzungen der extrahepatischen Gallenwege. Klinik, Diagnostik und Therapie.

From 1990 to 1995, 27 patients with biliary injuries were treated at the Department of General Surgery of Münster University Hospitals. All lesions occurred during cholecystectomy, either via laparoscopy (n = 17) or via laparotomy (n = 10). Ten patients were male and 17 female. The mean age was 51.2 years. In all cases a preoperative ERCP was performed. Based on the ERCP status a new classification was developed taking into account the type and location of the injury, as well as the opportunity for endoscopic treatment. Twenty-two patients underwent surgical bile duct reconstructions (12 hepaticojejunostomies, 3 choledochojejunostomies, 7 direct reconstructions). In five cases endoscopic therapy alone was successful. The perioperative mortality was 7.4% (2/27). Three of the surviving 25 had to be readmitted for recurrent cholangitis. Only 15 feel well without any limitations on everyday activities.