Mikael Öman

First attack of acute pancreatitis in Sweden 1988-2003: incidence, aetiological classification, procedures and mortality - a register study.

BackgroundPopulation-based studies suggest that the incidence of first attack of acute pancreatitis (FAAP) is increasing and that old age is associated with increased mortality. Beacuse nationwide data are limited and information on standardized mortality ratio (SMR) versus age is lacking, we wanted to describe incidence and mortality of first attack acute pancreatitis (FAAP) in Sweden.MethodsHospital discharge data concerning diagnoses and surgical procedures and death certificate data were linked for patients with FAAP in Sweden. Mortality was calculated as case fatality rate (CFR), i.e. deaths per 1000 patients and SMR using age-, gender- and calendar year-specific expected survival estimates, and is given as mean with 95% confidence intervals. Data are presented as median values with 25% and 75% percentiles, means and standard deviations, or proportions. Proportions have been compared using the chi square test, Poisson-regression test or Fisher exact test. Location of two groups of ratio scale variables were compared using independent samples t-test or Mann-Whitney U-test.ResultsFrom 1988 through 2003, 43415 patients (23801 men and 19614 women) were admitted for FAAP. Age adjusted incidence rose from 27.0 to 32.0 per 100000 individuals and year. Incidence increased with age for both men and women. At index stay 19.7% of men and 35.4% of women had biliary diagnoses, and 7.1% of men and 2.1% of women alcohol-related diagnoses. Of 10072 patients who underwent cholecystectomy, 7521 (74.7%) did so after index stay within the audit period. With increasing age CFR increased and SMR decreased. For the whole period studied SMR was 11.75 (11.34–12.17) within 90 days of index admission and 2.03 (1.93–2.13) from 91 to 365 days. Alcohol-related diagnoses and young age was associated with increased SMR. Length of stay and SMR decreased significantly during the audit period.ConclusionIncidence of FAAP increased slightly from 1988 to 2003. Incidence increased and SMR declined with increasing patient age. Although the prognosis for patients with FAAP has improved it remains an important health problem. Aetiological classification at index stay and timing of cholecystectomy should be improved.

Cholecystectomy and sphincterotomy in patients with mild acute biliary pancreatitis in Sweden 1988 - 2003: a nationwide register study

BackgroundGallstones represent the most common cause of acute pancreatitis in Sweden. Epidemiological data concerning timing of cholecystectomy and sphincterotomy in patients with first attack of mild acute biliary pancreatitis (MABP) are scarce. Our aim was to analyse readmissions for biliary disease, cholecystectomy within one year, and mortality within 90 days of index admission for MABP.MethodsHospital discharge and death certificate data were linked for patients with first attack acute pancreatitis in Sweden 1988-2003. Mortality was calculated as case fatality rate (CFR) and standardized mortality ratio (SMR). MABP was defined as acute pancreatitis of biliary aetiology without mortality during an index stay of 10 days or shorter. Patients were analysed according to four different treatment policies: Cholecystectomy during index stay (group 1), no cholecystectomy during index stay but within 30 days of index admission (group 2), sphincterotomy but not cholecystectomy within 30 days of index admission (group 3), and neither cholecystectomy nor sphincterotomy within 30 days of index admission (group 4).ResultsOf 11636 patients with acute biliary pancreatitis, 8631 patients (74%) met the criteria for MABP. After exclusion of those with cholecystectomy or sphincterotomy during the year before index admission (N = 212), 8419 patients with MABP remained for analysis. Patients in group 1 and 2 were significantly younger than patients in group 3 and 4. Length of index stay differed significantly between the groups, from 4 (3-6) days, (representing median, 25 and 75 percentiles) in group 2 to 7 (5-8) days in groups 1. In group 1, 4.9% of patients were readmitted at least once for biliary disease within one year after index admission, compared to 100% in group 2, 62.5% in group 3, and 76.3% in group 4. One year after index admission, 30.8% of patients in group 3 and 47.7% of patients in group 4 had undergone cholecystectomy. SMR did not differ between the four groups.ConclusionCholecystectomy during index stay slightly prolongs this stay, but drastically reduces readmissions for biliary indications.

Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer

Background:Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients.Methods:The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques.Results:Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival.Conclusion:Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.

Expression pattern and circulating levels of endostatin in patients with pancreas cancer

Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up‐regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP‐3, MMP‐9 and MMP‐13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5‐FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.

Surgery for acute gallbladder disease in Sweden 1989-2006 : A register study

Abstract Objective. Since early 1970s, prospective randomized controlled trials have emphasized the advantages of early cholecystectomy in patients with acute cholecystitis, compared to elective delayed cholecystectomy. The aim of this investigation was to study surgery for acute gallbladder disease in Sweden during a 15-year period when open cholecystectomy was replaced by a laparoscopic procedure. Material and methods. Data from the Swedish National Patient Register and the Cause of Death Register 1988–2006 comprising hospital stays with a primary diagnosis of gallbladder/gallstone disease in Sweden were retrieved. Patients were analyzed with reference to timing of cholecystectomy, length of hospital stay, and mortality. Results. Emergency cholecystectomy at index (first) admission or at readmission within 2 years of index admission was performed in 32.2% and 6.1% of patients, respectively. Elective cholecystectomy within 2 years of index admission was performed in 20.3% patients, whereas 41.3% of all patients did not undergo cholecystectomy within 2 years. Standardized mortality ratio did not significantly change during the audit period. Total hospital stay (days at index stay and subsequent stay(s) for biliary diagnoses within 2 years) was shorter for patients who had emergency cholecystectomy at first admission compared to patients with later or no cholecystectomy within 2 years. Conclusions. Around 30% of patients with acute gallbladder disease were operated with cholecystectomy during the first admission with no time trend from 1990 through 2004. A total of 40% of patients with acute gallbladder disease were not cholecystectomized within 2 years. Analysis of outcome of long-term conservative treatment is warranted.

A comparison between hepatic artery ligation and portal 5-Fu infusion versus 5-Fu intra arterial infusion for colorectal liver metastases.

AIM A prospective randomized study was executed comparing two regimens of regional therapy for liver metastases from colorectal cancer. METHODS Eighteen patients were allocated to hepatic artery occlusion for 16 h followed by intraportal 5-fluorouracil (5-Fu) infusion (1000 mg/m(2)) for 5 days every sixth week (HAO). Twenty-one patients received intra-arterial 5-Fu infusion+Leucovorin (100 mg) i.v. for 2 days every second week (HAI). The follow up every third month included CT and CEA. Thirteen patients had limited extrahepatic cancer. At tumor progression regional therapy was stopped and systemic chemotherapy or the best supportive care was administered. RESULTS The study was discontinued after randomization of 39 patients. No significant difference in survival within patients with and without extrahepatic cancer was present. The mean survival was longer in the HAI group than for the HAO group (19 months versus 13 months, p=0.0147) (median 18 (8-37) versus 12 (2-26). PR and SD were registered in 8/18 in the HAO group and 17/21 patients in HAI group. The median time to progress was 4 (1-22) months versus 7 (1-23) months for the HAO and HAI group, respectively. CONCLUSION Regional intraarterial infusion with 5-Fu gives significantly better survival than hepatic artery occlusion followed by portal infusion. A limited amount of extrahepatic cancer does not influence survival time. A trial comparing hepatic artery 5-FU infusion and Leucovorin versus the most effective systemic therapy is warranted.

Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma

BACKGROUND A lack of disease-specific symptoms and good tumour markers makes early detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC) challenging. OBJECTIVE To analyse the tissue expression and circulating levels of four stroma-derived substances (type IV collagen, endostatin/type XVIII collagen, osteopontin and tenascin C) and four conventional tumour markers (CA 19-9, TPS, CEA and Ca 125) in a PDAC cohort. METHODS Tissue expression of markers in normal pancreas and PDAC tissue was analysed with immunofluorescence. Plasma concentrations of markers were measured before and after surgery. Patients with non-malignant disorders served as controls. RESULTS The conventional and stromal substances were expressed in the cancer cell compartment and the stroma, respectively. Although most patients had increased levels of many markers before surgery, 2/12 (17%) of patients had normal levels of Ca 19-9 at this stage. High preoperative endostatin/type XVIII collagen, and postoperative type IV collagen was associated with short survival. Neither the pre- nor postoperative levels of TPS, Ca 125 or CA 19-9 were associated to survival. CONCLUSIONS PDAC is characterized by an abundant stroma. These initial observations indicate that the stroma can be a source of PDAC tumour markers that are found in different compartments of the cancer, thus reflecting different aspects of tumour biology.

Analysis of the mechanism of injury in non-fatal vehicle-to-pedestrian and vehicle-to-bicyclist frontal crashes in Sweden

The aim of this paper is to analyse and compare injuries and injury sources in pedestrian and bicyclist non-fatal real-life frontal passengercar crashes, considering in what way pedestrian injury mitigation systems also might be adequate for bicyclists. Data from 203 non-fatal vehicle-to-pedestrian and vehicle-to-bicyclist crashes from 1997 through 2006 in a city in northern Sweden were analysed by use of the hospitals injury data base in addition to interviews with the injured. In vehicle-to-pedestrian crashes (n = 103) head and neck injuries were in general due to hitting the windscreen frame, while in vehicle-to-bicycle crashes (n = 100) head and neck injuries were typically sustained by ground impact. Abdominal, pelvic and thoracic injuries in pedestrians and thoracic injuries in bicyclists were in general caused by impacting the bonnet. In vehicle-to-pedestrian crashes, energy reducing airbags at critical impact points with low yielding ability on the car, as the bonnet and the windscreen frame, might reduce injuries. As vehicle-to-bicyclist crashes occurred mostly in good lighting conditions and visibility and the ground impact causing almost four times as many injuries as an impact to the different regions of the car, crash avoidance systems as well as separating bicyclists from motor traffic, may contribute to mitigate these injuries.

Mesenteric Vein Thrombosis Following Platelet Transfusion in a Patient with Hemorrhagic Fever with Renal Syndrome: A Case Report

Viral hemorrhagic fevers (VHFs) are typically characterized by life-threatening thrombocytopenia and tendency to bleed. Still, there are gaps of knowledge regarding risks and benefits of platelet transfusion for patients with severe thrombocytopenia during VHF and other infectious diseases. 1 2 3 4 Hemorrhagic fever with renal syndrome (HFRS) is a mild rodent-borne VHF, caused by Puumala virus, endemic in central and northern Europe. The infection is characterized by fever, nausea, back- and headache, thrombocytopenia, and transient renal impairment. We have shown that HFRS is a risk factor for both arterial and venous thrombosis. 5 6 We here report a case of a patient with HFRS with prolonged thrombocytopenia who developed thrombosis shortly after receiving platelet transfusion.