Åke Andrén-Sandberg

K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16INK4A, p21WAF-1, cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma

Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. Our aim was to undertake a comprehensive analysis of potentially useful molecular markers in a large, multicentre patient population and to compare these markers with standard pathological prognostic variables. Formalin‐fixed, paraffin‐embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients [100 men and 57 women with a median (range) age of 60 (33–77) years] who had undergone pancreatectomy. Immunohistochemistry was used to detect expression of p16INK4, p53, p21WAF1, cyclin D1, erbB‐2 and erbB‐3. Mutations in codons 12 and 13 of the K‐ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median (range) survival post‐resection was 12.5 (3–83) months. Abnormalities of p16INK4, p53, p21WAF1, cyclin D1, erbB‐2 and erbB‐3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K‐ras mutations were found in 73 (75%) of 97 cases with amplifiable DNA. The presence of K‐ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K‐ras mutation (p = 0.0007). Reduced survival was found in patients with GaT, cGT and GcT K‐ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K‐ras mutation but not expression of p16INK4, p53, p21WAF1, cyclin D1, erbB‐2 and erbB‐3. Int. J. Cancer 89:469–474, 2000.

Acute pancreatitis in Bergen, Norway. A study on incidence, etiology and severity.

Background: Studies on the incidence and etiology of acute pancreatitis show large regional differences. This study was performed to establish incidence, etiology and severity of acute pancreatitis in the population of Bergen, Norway. Methods: A study of all patients with acute pancreatitis admitted to Haukeland University Hospital over a 10-year period was performed. Information was obtained about the number of patients with acute pancreatitis admitted to the Deaconess Hospital in Bergen. Results: A total of 978 admissions of acute pancreatitis were recorded in these two hospitals giving an incidence of 30.6 per 100 000. Haukeland University Hospital had 757 admissions of acute pancreatitis in 487 patients. Pancreatitis was severe in 20 % (96/ 487) of patients, more often in males (25 %) than in females (14 %). Mortality due to acute pancreatitis was 3 % (16/487). Gallstones were found to be an etiological factor in 48.5 % and alcohol consumption in 19 % of patients. The risk of recurrent pancreatitis was 47 % in alcohol induced and 17 % in gallstone induced pancreatitis. The last five years of the study period, endoscopic sphincterotomy of patients with gallstone pancreatitis, resulted in drop in relapse rate from 33 % to 1.6 %. Conclusion: The incidence of acute pancreatitis was found to be 30.6 per 100 000 with 48.5 % associated with gallstones and 17 % alcohol induced. Incidence of first attack was 20/100 000. Pancreatitis was classified as severe in 20 % of cases with a mortality of 3 %.

Resection for pancreatic cancer in the new millennium.

Background and Aim of the Study: Complications of pancreatic resections are dangerous and costly. A literature review was therefore done to investigate the evidence for improving the results by regionalizing this demanding surgery. Results: Studies from four countries (USA, UK, the Netherlands and Finland) with advanced health care systems have shown a significant inverse correlation between case volume for pancreatic cancer resection and post-operative mortality. Further analysis reveals lower complications, reduced hospital stay, reduced hospital costs and improved survival of patients treated in high-volume hospitals. The relationship volume and outcome is with institutional volume rather than single surgeon caseload. The evidence therefore strongly supports the regionalization of pancreatic cancer surgery into large specialized multi-disciplinary units. In the UK, the National Health Service Executive has instructed Regional Health Authorities to concentrate pancreatic cancer surgery into designated Regional Centres ideally with catchment populations of 2–4 million. There is now considerable pressure to adopt a similar policy in all countries with advanced health care systems. Conclusion: There is today enough evidence to advocate the regionalization of pancreatic cancer resections.

Endoscopic sphincterotomy in acute gallstone pancreatitis: a prospective study of the late outcome

OBJECTIVE To describe the outcome after acute biliary pancreatitis in patients treated during the acute attack by endoscopic sphincterotomy without cholecystectomy. DESIGN Prospective observational study. SETTING University hospital, Norway. SUBJECTS 130 patients with gallstones and acute pancreatitis. In 62 patients with common bile duct stones the bile duct was cleared by sphincterotomy and stone extraction. The remaining 68 patients had prophylactic sphincterotomy. Cholecystectomy was not planned later. MAIN OUTCOME MEASURES Incidence of recurrent acute pancreatitis and need for cholecystectomy. RESULTS 21 patients were dead or not available for the follow-up. Consequently 109 patients were followed-up for a median of 39 months (range 23-62). One patient had recurrent pancreatitis. 20 patients had a cholecystectomy later for symptoms related to gallstone disease. Of the rest, 25 patients had moderate or mild gallstone-related symptoms. There was no difference in gallstone-related symptoms between those who had had stones in the bile duct and those who had not. 63 patients had no symptoms related to gallstones. CONCLUSION Endoscopic sphincterotomy during or immediately after acute gallstone pancreatitis resulted in half the patients being free of symptoms during the next three years.

Wirsung and Santorini: The Men Behind the Ducts

During the 16th and 17th centuries, several important discoveries were accomplished by anatomists whose contribution has enlightened the most important anatomic structures of the pancreas. Following the earliest discoveries, researchers of several medical specialities further investigated the ductal pancreatic system. The accessory pancreatic duct with its minor papilla, the main pancreatic duct and the papilla major along with the confluence of the main pancreatic duct with the bile duct and pancreas divisum, have been the objects of interest of several personalities of the medical history. Eponyms in pancreatic anatomy were given to remember some of them, although anatomical misattributions are frequent and controversial. The aim of the authors was to dedicate a small tribute to the researchers who have written, during the last 500 years, important chapters of the medical history and who dedicated their lives to study the pancreatic ducts and their duodenal endings. Furthermore, a brief outlook was dedicated to the impact of anatomic variations and of embryologic anomalies of the pancreatic ducts in our clinical practice and in our actual understanding of duct-related diseases. The authors are confident that the genial curiosity of few extraordinary personalities of the past and the opportunities provided by modern technology continue to play a major role that may finally add wisdom to decision-making in dealing with duct-related biliopancreatic diseases and safety to diagnostic and therapeutic procedures employed.

Influence of laparoscopic cholecystectomy on the prevalence of operations for gallstones in Norway

OBJECTIVE To assess trends in the treatment of gallstone disease, by recording the number of admissions to hospital and operations; to find out if there are regional differences in the number of operations for gallstone disease; to compare these with those of other countries, and to discuss possible causative factors with special reference to introduction of laparocopic cholecystectomy. DESIGN Study of medical records. SETTING University hospital, Norway. SUBJECTS A total of 55,622 hospital stays and 28,048 operations for gallstone disease were recorded in a national registry for the 8-year period 1992-9, which comprise 99% of all admissions for gallstone disease. INTERVENTIONS Data were compared for number of admissions to hospitals for gallstone disease, incidence of different operations, and trends in treatment. Different regions in Norway were also compared. RESULTS Both the number of hospital stays and the number of gallstone operations increased slightly over the period. Compared with 1992, the open cholecystectomy rate was reduced to 25%, and laparoscopic operations increased more than four times. The incidence of endoscopic procedures showed an annual increase from 1992-9, followed by a fall in 1999 to the 1992 level. CONCLUSION Treatment trends show a pronounced increase in laparoscopic operations, and at the same time fewer open operations. The total number of operations has increased slightly in Norway. The prevalence of operations for gallstones in Norway is the lowest reported in Western Europe. The overall number of gallstone operations in Norway is relatively small. The increase in the number of operations for gallstones in Norway was mainly caused by the increase in laparoscopic cholecystectomies. After a steady rise, there was a fall in the number of endoscopic procedures for common bile duct stones during the last year. At the same time, however, magnetic resonance cholangiopancreatography was introduced in Norway. The prevalence of gallstone disease in the population studied seems to have had little influence on the incidence of operations. Many Norwegian patients with gallstone disease who could benefit from operation are probably not being offered surgical treatment today, but are treated in an expectant manner instead.

Theodor Kocher (1841–1917) – A Surgical Maestro

Accessible online at: www.karger.com/journals/dsu The name Theodor Kocher (fig. 1) is obviously known to surgeons working not only in his hometown Bern, Switzerland, but also in the rest of the world. Outside Bern, probably, his name today is usually connected to ‘the Kocher maneuver’, or to some instrument, rather than to the 1909 Nobel laureate. Bern’s doctors and surgeons are proud of Theodor Kocher. There is a street and a park named after him and there are two statues of him set up in central positions in the city. Furthermore, he has been pictured on a postage stamp from 1967. It should also be mentioned as a curiosity that a grateful Russian patient named a volcano in Manchuria after him.

Non-adhesive organ culture of human biliary epithelium with stroma

Objective. Explanted tissue has been shown to keep adult human cells in organ culture with a preserved morphology for at least one month as spheres in a non-adhesive organ culture. In the present study, we explored whether also human biliary epithelium can be grown in this manner, because the result may be of interest in studies of hepato-biliary-pancreatic carciogenesis. Material and methods. Small tissue samples were obtained from the gallbladder wall of patients who had been operated upon with cholecystectomy. Fragments of about 300 µm in diameter from each patient were cultured and investigated with light microscopy at the time of explantation and after 5, 10, 20, 30 and 40 days of culture. Scanning and transmission electron microscopy were performed to demonstrate the ultrastructure. Incubation of cultured fragments with the vital dyes revealed a viable epithelium. Results. At the time of explantation, all the tissue fragments had a rough appearance with an uneven, torn periphery, while during the first few days of culture they became rounder with a smooth-looking surface covering the entire circumference. This spheroid morphology persisted for the remainder of the culture period. The core of the fragments harboured connective tissue with vascular elements, fibroblasts and leucocytes. Immunostaining for cytokeratin 7, 19 and 20 revealed a strong positive staining of the epithelium. Conclusions. These results show that biliary epithelium can be grown in vitro in a non-adhesive organ culture with their stroma.