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45 Patienten wurden 1–37 Jahre nach distaler Magenresektion (B IIn = 34, B In = 11) einem indirekten Pankreasfunktionstest (PLT-Test) mit Fluoresceindilaurat als Substrat unterzogen. Bei 11 Patienten mit chronischer Pankreatitis wurde die Diagnose durch spezifische Untersuchungen gesichert, wobei alle einen pathologischen Pankreasfunktionstest aufwiesen. Die PLT-Testergebnisse waren in 69,7% pathologisch in der Gruppe nach B II-Resektion ohne primare Pankreaserkrankung und in 63,6% in der Gruppe nach B I-Resektion. Eine Malabsorption konnte bei allen Patienten durch die unveranderte Resorption von freiem Fluorescein ausgeschlossen werden. Die Ergebnisse sind Ausdruck einer sekundaren Pankreasinsuffizienz nach distaler Magenresektion. Bei Patienten mit Anzeichen einer Mangelernahrung nach Magenresektion sollte ein indirekter Pankreasfunktionstest durchgefuhrt werden und nach Evaluierung einer exokrinen Storung eine Substitution mit Pankreasfermenten erfolgen.

The value of a modified fluorescein dilaurate (FDL) serum test for the detection of pancreatic exocrine insufficiency was investigated in 89 patients with and without pancreatic disease. This test modification with fluorescein serum determination following metoclopramide (10 mg) and secretin (1 U/kg) i.v. injection appeared efficacious in a pilot study in six healthy volunteers. Individual peak fluorescein serum concentration was achieved within 180 min after the test meal in 96% of all subjects studied. Peak fluorescein serum concentration within this time period allowed the best discrimination between normal and abnormal pancreatic function. Sensitivity in detection of chronic pancreatitis was 86% (38 of 44 patients) when the lower normal fluorescein serum concentration was considered 4.5 micrograms/ml (this value corresponds to mean - 2 SD). The specificity of this test in detecting chronic pancreatitis was 100% when healthy controls were considered, but fell to 78% when patients with different gastrointestinal disorders, including those with secondary pancreatic insufficiency, were included. The correlation between serum and urinary fluorescein determination was significant (r = 0.61; p less than 0.01). Duodenal bicarbonate output/h after secretin also showed a significant correlation with peak fluorescein serum concentration (r = 0.79; p less than 0.001).

In 72 patients with tumours of the ampulla of Vater, the course of the disease was analysed. Surgical specimens were examined microscopically, and special attention was paid to the study of morphologi

The gastrointestinal system is substantially involved in the regulation of exocrine pancreatic secretion, and it is therefore not surprising that intestinal diseases have been shown to affect exocrine pancreatic function. In rat experiments gastrectomy, truncal vagotomy, and subtotal colectomy stimulated pancreatic growth and altered pancreatic enzyme composition. Focusing on two main hormones supposed to be involved in the regulation of pancreatic adaptation, we studied basal and stimulated gastrin and cholecystokinin (CCK) pattern after the operative procedures. After total gastrectomy basal CCK values were unchanged, whereas postprandial CCK plasma values and the integrated postprandial CCK release were significantly increased. After subtotal colectomy CCK levels, both basal and postprandial, were significantly increased. In both of these conditions gastrin levels were either decreased (total gastrectomy) or unchanged (subtotal colectomy). CCK may therefore be the major humoral candidate to promote the observed pancreatic adaptive response. After truncal vagotomy CCK values remained unchanged, whereas basal and postprandial gastrin was significantly increased. Gastrin may be a candidate involved in the stimulation of pancreatic trophism after vagisection.

One hundred and five of 395 patients with acute pancreatitis were surgically treated in our clinic from 1981 to 1984. Ninety three of these patients were examined with contrast enhanced computed tomography and/or ultrasound and were clinically assessed according to Ranson's objective criteria before operation. At operation, 77 patients showed necrotising pancreatitis and 16 showed biliary acute interstitial pancreatitis. Ninety per cent of the cases with extensive and 79% of those with minor necroses of the pancreas had been demonstrated with contrast enhanced computed tomography. Ultrasound failed to be diagnostic in 24% of the patients due to meteorism; the sensitivity of the diagnostic studies for pancreatic necrosis was 73% regardless of the extent of the process. Using the early objective signs, seven patients with acute interstitial pancreatitis were classified as having a severe attack, whereas 30 patients with necrotising pancreatitis were categorised as mild attacks. We conclude that the contrast enhanced computed tomography is an aid in deciding on conservative or surgical treatment in a case of acute pancreatitis. Ultrasound does not appear to be an adequate method for determining pancreatic necrosis. The early objective signs fail to sufficiently identify the necrotising form of acute pancreatitis.

The present case report demonstrates the history of a 50-year-old man with a mixed endocrine-neurogenous tumor of the ampulla of Vater. The tumor was localized endoscopically after an attack of melena. There were no signs of endocrinopathy. A local resection with suturing of the pancreatic duct was performed. Morphologically, there were two different tissue types (neurogenous and carcinoid-like) with numerous cells and nerve fibers reacting immunohistochemically with somatostatin and neurotensin antisera: some immunoreactivity to PP-antibodies was observed. Still, after 20 months, the patient seems to have been cured by local resection.

Subtotal colectomy was performed in 17 rats. After 2 or 4 weeks the entire pancreas was excised and isolated pancreatic lobules were incubated for 60 min in Krebs-Ringer-Hepes solution either with or without addition of ceruletide (5 X 10(-10) g/ml). Amylase was determined every 15 min in the supernatant medium. Amylase, trypsin, DNA and total protein were measured in homogenized pancreatic tissue. Morphology was performed via light-microscopy analysis. Two weeks after subtotal colectomy we found an increase in pancreatic wet weight, enzyme and protein content, cellular size and secretion capacity in vitro, whereas DNA concentration in relation to pancreatic tissue weight in grams decreased. These changes pointed to pancreatic hypertrophy. Four weeks after surgery, pancreatic wet weight, enzyme content and DNA content as well as in vitro amylase discharge increased, whereas cellular size remained unchanged compared to controls and sham-operated rats. These changes were indicative of pancreatic hyperplasia.

Background Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. Methods/design CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. Discussion As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice.

Background Surgical hepatic resection remains the treatment of choice for patients with liver metastases from colorectal cancer despite the use of alternative therapeutic strategies. Although this procedure provides long-term survival in a significant number of patients, 50–75% of the patients develop intra- and/or extrahepatic recurrence. One possible reason for tumor recurrence may be intraoperative hematogenous tumor cell dissemination due to mechanical manipulation of the tumor during hepatic resection. Surgical technique may have an influence on hematogenous tumor cell spread. We hypothesize that hematogenous tumor cell dissemination may be reduced by using the anterior approach technique compared to conventional liver resection. Methods/Design This is a multi-centre prospective randomized controlled, superiority trial to compare two liver resection techniques of liver metastases from colorectal cancer. 150 patients will be included and randomized intraoperatively after surgical exploration just prior to resection. The primary objective is to compare the anterior approach with the conventional liver resection technique with regard to intraoperative haematogenous tumor cell dissemination. As secondary objectives we examine five year survival rates (OS and DFS), blood loss, duration of operation, requirement of blood transfusions, morbidity rate, prognostic relevance of tumor cell detection in blood and bone marrow and the comparison of tumor cell detection by different detection methods. Conclusion This trial will answer the question whether there is an advantage for the anterior approach technique compared to the conventional resection group with regard to tumor cell dissemination. It will also add further information about prognostic differences, safety, advantages and disadvantages of each technique. Trial registration Current controlled trials – ISRCTN45066244

Pancreatic ductal adenocarcinoma (PDAC) presently has an incidence of approximately 8 to 10 cases per 100000 citizens in European countries, and the incidence has been increasing throughout the last decades. Approximately 30000 patients die every year from PDAC in Western Europe and most of the newly diagnosed patients present with an already unresectable tumor stage. Self-sufficiency in growth signals, insensitivity to antigrowth signals, and evasion of apoptosis are hallmarks of malignant growth. In PDAC a variety of growth factors are expressed at increased levels. For example, the concomitant presence of the EGF-receptor and its ligands EGF, TGF-alpha, and/or amphiregulin is associated with enhanced tumor aggressiveness and shorter survival periods following tumor resection. In addition, PDACs often exhibit alterations in growth inhibitory pathways such as Smad4 mutations and Smad6 and Smad7 overexpression, and evade apoptosis through p53 mutations and aberrant expression of apoptosis regulating genes such as members of the Bcl family. Taken together, the abundance of growth promoting factors and the disturbance of growth inhibitory and apoptotic pathways give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival prognosis.

Diagnosing and monitoring pancreatic cancer is an ongoing challenge. Conventional markers such as tumor-associated antigens might be supplemented by molecular markers such as gene mutations and growth factor/growth factor receptor alterations in the future. Tumor-associated antigens can easily be measured by different EIA/ELISA systems, but the analysis of gene mutations, growth factors and their receptors requires advanced molecular techniques. CA 19-9 is the most widely used conventional marker for pancreatic cancer and is a useful tool in the diagnosis and follow-up of patients after tumor resection. Nonetheless, its role in detecting early pancreatic cancer is limited. The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis. Growth factor and growth factor receptor alterations are often associated with increased tumor aggressiveness and shorter survival following tumor resection. To date the analysis of growth factors/growth factor receptors in pancreatic cancer has not entered clinical use, but further molecular characterization of pancreatic cancer is necessary for earlier and more accurate diagnosis and it may result in new treatment options.

At the joint International Association of Pancreatology and European Pancreatic Club meeting at King's College, London (July 9-12, 1997), a satellite meeting of the European Study Group for Pancreatic Cancer (ESPAC) met to discuss the progress of the ESPAC-1 trial. This study will address which, if any, of the following adjuvant treatments are of benefit in patients with resectable pancreatic cancer: radiotherapy (40 Gy with 5-fluorouracil as a sensitising agent); 6 months chemotherapy (5-fluorouracil and folinic acid), or a combination of these treatments. The study, which commenced in 1994, had already recruited 348 patients into the 3 treatment arms and 1 control arm of the study by May 31, 1997. This is the largest study of its kind in pancreatic cancer and should definitively address the question of the role of conventional methods of adjuvant treatment in pancreatic cancer.

No good evidence of benefit—trials needed

Background: Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized histomorphologically by progressive development of fibrosis and atrophy of the pancreatic parenchyma. Cartilage oligomeric matrix protein (COMP) is a member of the thrombospondin (TSP) family of extracellular glycoproteins that is expressed in CP tissues. In the present study, we characterized COMP mRNA and protein expression in the normal pancreas, chronic pancreatitis, and pancreatic cancer tissues. Methods: 15 normal pancreatic tissues, 14 CP tissues and 14 pancreatic cancer tissues were analyzed by Northern blotting, Western blotting, in situ hybridization and immunohistochemistry. Results: COMP mRNA and protein were detected at moderate to high levels in chronic pancreatitis tissues, at moderate levels in pancreatic cancer tissues, but at low levels in normal pancreatic tissues and in four pancreatic cancer cell lines. COMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. COMP protein was also present in the fibrotic tissue in CP. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues. Conclusion: COMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this gene in the course of acinar cell degeneration and dedifferentiation. COMP might thus serve as a marker for tissue destruction and disease activity in CP.

Bei 111 Patienten mit nekrotisierender Pankreatitis kamen zwischen 1974 und 1984 zwei verschiedene Therapieverfahren prospektiv zur Anwendung. Im Anschlus an eine Nekrotektomie wurden in Gruppe 1 mit 64 Patienten eine kontinuierliche Peritoneal-Lavage und in Gruppe II mit 47 Patienten eine Lavage der Bursa omentalis durchgefuhrt. Zusatzlich wurde bei 32 Patienten der Gruppe II mit extrapankreatischen Nekrosen und diffuser Peritonitis eine Peritoneal-Lavage vorgenommen. Die kontinuierliche postoperative Bursa-Lavage bei bestimmter Indikation in Kombination mit Peritoneal-Lavage ist der alleinigen Peritoneal-Lavage signifikant uberlegen.