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Biomedical subjects

O Søreide

Publications and source records attributed to O Søreide.

At least 19 recordsLinked to original sources

Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer.

BACKGROUND: Knowledge of prognostic factors following resection of rectal cancer may be used in the selection of patients for adjuvant therapy. This study examined the prognostic impact of the circumferential resection margin on local recurrence, distant metastasis and survival rates. METHODS: A national population-based rectal cancer registry included all 3319 new patients from November 1993 to August 1997. Some 686 patients underwent total mesorectal excision with a known circumferential margin. This shortest radial resection margin was measured in fixed specimens. None of the patients had adjuvant radiotherapy. RESULTS: Following potentially curative resection and after a median follow-up of 29 (range 14--60) months, the overall local recurrence rate was 7 per cent (46 of 686 patients): 22 per cent among patients with a positive resection margin and 5 per cent in those with a negative margin (margin greater than 1 mm). Forty per cent of patients with a positive margin developed distant metastasis, compared with 12 per cent of those with a negative margin. With decreasing circumferential margin there was an exponential increase in the rates of local recurrence, metastasis and death. CONCLUSION: The circumferential margin has a significant and major prognostic impact on the rates of local recurrence, distant metastasis and survival. Information on circumferential margin is important in the selection of patients for postoperative adjuvant therapy.

Adenocarcinoma↗

Laparoscopic cholecystectomy: bile duct and vascular injuries: management and outcome.

BACKGROUND: This is a retrospective study of 32 consecutive patients referred in the period 1992-2000 for management of serious bile duct injuries caused by elective laparoscopic cholecystectomy. METHODS: The patients were referred on median 29 days (0 days to 34 months). Only 7 patients were referred immediately after discovery of the injury. At the local hospital, 25 patients underwent various procedures in attempts at repair. Ten of the patients were treated for bile duct strictures after previous repairs in other hospitals. RESULTS: At referral, 23 patients (72%) had complete transection of the bile duct, while 9 had bile leakage injuries. Additional complications were occlusion of the right hepatic artery in 8 patients (24%) and occlusion of the mesenteric superior artery in 1 patient. Infectious complications were prominent in 21 patients (70%), 6 of whom had septicaemia. Operative management with hepaticojejunostomy Roux-Y was employed in 22 patients. Various non-operative strategies were chosen, including endoscopically or transhepatic stenting of the bile duct and embolization of the right hepatic artery. There was no difference in hospital stay between operative and non-operative procedures which on median was 16 days ( range 7-69 days). Three patients died: one had thrombosis of the superior mesenteric artery, while the other two died of complications to bile peritonitis. Median observation period is 5 years (5 months to 8 years). Two patients have cholangitis; both had injury to the right hepatic artery. The other patients all had normal ultrasonograms of the liver and normal/almost normal liver function tests. CONCLUSIONS: Bile duct injuries continue to occur, are serious and may result in death. Injury to the right hepatic artery is present in many cases. Patients are referred late to a competent center, resulting in serious infection in 70%.

Adolescent↗

[Cryoablation--a treatment option for inoperable liver tumors?].

BACKGROUND: Most patients with primary and secondary liver tumours are inoperable by conventional surgery. This has prompted the development of different techniques of local destruction of liver tumours, i.e. cryosurgical ablation radiofrequency, laser, and microwave ablation. MATERIAL AND METHODS: On the basis of relevant literature and our own experience we describe the principles of local destruction by cryoablation of colorectal metastases. RESULTS: Indications for ablation are mainly colorectal metastases and hepatocellular carcinoma. Mechanisms for tumour destruction include intra- and extracellular ice crystal formation, cellular membrane rupture, cellular dehydration and ischaemic damage. Ablation is regularly monitored by ultrasonography, which is suboptimal because of inadequate visualisation of the iceball. Long-term outcome of local destruction of liver tumours is not documented and randomized trials are not ethically acceptable. This complicates analyses of patient outcomes. INTERPRETATION: Local ablation of liver tumours is experimental therapy and should only be performed as a part of prospective trials.

Carcinoma, Hepatocellular↗

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma.

K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte-macrophage colony-stimulating factor. Forty-eight patients (10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide-specific immunity was induced in 25 of 43 (58%) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end-stage disease. Patients followed-up for longer periods showed evidence of induction of long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras-specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non-responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients.

Adenocarcinoma↗

Magnetic resonance imaging-estimated three-dimensional temperature distribution in liver cryolesions: a study of cryolesion characteristics assumed necessary for tumor ablation.

The goal of this study was to estimate the three-dimensional (3D) temperature distribution in liver cryolesions and assess the margin of the transition zone between the tumoricidal core of the lesion and the surrounding unfrozen tissue, using criteria proposed in the literature. Local recurrences after liver tumor cryoablation are frequent. Temperatures below -40 degrees C and a 1-cm zone of normal tissue included in the cryolesion are considered necessary for adequate ablation. The 3D temperature distribution in 10 pig cryolesions was estimated by numerical solution of a simplified bioheat equation using magnetic resonance imaging data to establish cryolesion border conditions. Volumes encompassed by the -20, -40, and -60 degrees C isotherms were estimated. The shortest distance from every voxel on the -40 degrees C isotherm to the cryolesion edge was calculated and the mean and the maximal of these distances were defined for each cryolesion. Median cryolesion volumes with temperatures of -20, -40, and -60 degrees C or colder were 53, 26, and 14% of the total cryolesion volume, respectively. The median cryolesion volume was 12.3 cm(3). The median of the mean distances calculated between the -40 degrees C isotherm and the cryolesion edge was 4.1 mm and increased with increasing cryolesion volume. The median of the largest of these distances calculated for each cryolesion was 8.1 mm. Temperatures claimed to be adequate for tumor destruction were obtained only in parts of the cryolesion. The adequacy of a 1-cm zone of normal liver tissue included in the cryolesion to ensure tumor ablation is questioned.

Animals↗

Validation of estimated 3D temperature maps during hepatic cryo surgery.

A simple model for estimating temperature distribution within the frozen region during cryo ablation was tested for accuracy. Freezing experiments were conducted in both ex vivo and in vivo porcine livers. Temperature was measured during freezing using a fiber-optic temperature sensor. Three-dimensional MR images were obtained at the end of each freezing cycle. From the MR image volumes, three-dimensional temperature maps were calculated numerically using a simplified bio-heat model. Estimated temperatures were compared to measured temperatures. The median difference between measured and estimated temperature was 3.03 degrees C. The median distance from a sensor element to the closest point on a isotherm surface with the corresponding estimated temperature was 0.70 mm. The accuracy of this model is acceptable. Temperature maps as outlined here may be used for monitoring of cryotherapy in order to increase clinical effectiveness.

Animals↗

Plasma exchange and heart-liver transplantation in a patient with homozygous familial hypercholesterolemia.

A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. Plasma exchange reduced total cholesterol levels from 25-30 mmol/L (967-1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long-term treatment. Due to end-stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart-liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.

Cholesterol↗

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.

Acute Disease↗

Magnetic-resonance-guided percutaneous cryoablation of hepatic tumours.

OBJECTIVE: To study the feasibility of percutaneous cryoablation of hepatic tumours monitored by magnetic resonance imaging (MRI). DESIGN: Prospective study SETTING: University hospital, Norway PATIENTS: Six patients with hepatic metastases from colorectal cancer. INTERVENTIONS: Percutaneous cryoprobe positioning under general anaesthesia. Positioning and freezing monitored by near-real-time MRI using an open 0.5 Tesla MRI configuration system. MAIN OUTCOME MEASURES: Safety and feasibility of the procedure. Measurement of volumes of cryolesions. RESULTS: One patient developed a biliary leakage that had to be drained. Four patients developed pleural fluid. Two small tumours were adequately cryoablated. In the remaining 4 patients with large (>4 cm) tumours, an adequate cryolesion could not be formed. Cryolesion volumes larger than 105 cm3 were not produced even using 3-4 probes. MRI visualised the growing cryolesion well, but positioning of the cryoprobes was time-consuming. CONCLUSION: MR guided cryoablation is clinically feasible and gives good visualisation of the procedure. Patients with small tumours (<3 cm) seem to be best suited to this percutaneous approach as cryolesion volumes claimed to be adequate for tumour destruction can be produced. Measurement of tumour volume preoperatively may help to select patients who will respond.

Aged↗

Liver tumors and minimally invasive surgery: a feasibility study.

Laparoscopic liver resection has not yet been established, although recent reports document that liver resection can be performed safely by the laparoscopic approach. Other interventional procedures like cryoablation have also been introduced in treatment of liver metastases. In this report 11 liver resections performed laparoscopically in eight patients are presented. Six patients had colorectal metastases, one a metastases from a malignant melanoma, and one patient had focal nodular hyperplasia. Two patients received synchronous cryoablation of remaining liver metastases. During follow up, two patients received percutaneous cryoablation of liver recurrences monitored by an open configuration magnetic resonance scanner. All except one of the tumors we attempted to remove had free resection margins (re-resection of new metastasis). No complications occurred except an atelectasis of the left lower pulmonary lobe in one patient. Median postoperative hospital stay was 3 days, and median postoperative opioid-dependent days was 1. The report demonstrates that minimally invasive techniques may safely be combined in hepatic intervention, and that the advantages of minimally invasive surgery, such as reduced hospital stay and less patient discomfort, also applies to liver resections.

Adenocarcinoma↗

Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model.

We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (WBP) in orthotopic liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow (2 l/min) and at a constant temperature (37.5 degrees C) for 12 h. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubing was used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system were found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3h = 9* (6-14.4), 12h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3h = 5*(0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range (*: p < 0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TCC (NC vs. HC group): 3h, p < 0.001; 12 h, p < 0.001. Significant increases in the values of thrombin-antithrombin complexes (p = 0.003), prothrombin fragment 1 + 2 (p = 0.006) and plasmin-alpha2-antiplasmin complexes (p = 0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for WBP reduces activation of the plasma cascade systems in a closed venous system in vitro.

Blood Coagulation Factors↗

Structuring rectal cancer treatment in Scandinavia.

By focusing on surgical technique through special training courses, a significant improvement in outcome after surgery for rectal cancer is evident based on the Scandinavian experience. Overall results have improved because of systematic quality assurance of surgery by way of a national rectal cancer registry. Moreover, in Scandinavia, rectal cancer surgery has been taken out of the general surgeon's armamentarium and is performed only by surgeons who specialize in gastrointestinal (Denmark and Norway) or colorectal (Sweden) surgery.

Humans↗

Presence of choloyl- and chenodeoxycholoyl-coenzyme A thioesterase activity in human liver.

In human liver homogenate the formation of bile acid-CoA thioesters is localized both to the microsomal fraction catalysed by an ATP-dependent synthetase and to the peroxisomal fraction catalysed by the thiolase in the last step of the beta-oxidative cleavage of the 5beta-cholestanoyl side chain. The cytosolic bile acid-CoA:amino acid N-acyltransferase catalyse the conjugation of the CoA-activated bile acids with taurine or glycine prior to secretion into bile. The formation of bile acid-CoA esters is considered the rate-limiting step in bile acid amidation. So far, a bile acid-CoA cleaving activity has not been assessed in the research of bile acid amidation in human liver. In this work, a bile acid-CoA cleaving activity has been demonstrated at a rate that may influence the concentration of bile acid-CoA thioesters, free bile acids and amidated bile acids within the hepatocyte. Recently, it was shown that free chenodeoxycholic acid, formed by the thioesterase, is the physiological ligand of the farnesoid X receptor. A multiorganelle distribution of the bile acid-CoA hydrolytic activity was found. In the postnuclear fraction of human liver homogenate, apparent Km and Vmax for the cleavage of choloyl-CoA were 7.7 x 10-5 mol/L and 3.6 nmol x mg-1 x min-1 respectively. The corresponding values for chenodeoxycholoyl-CoA cleavage were 7.1 x 10-5 mol/L and 4.8 nmol x mg-1 x min-1. Hydrolytic activities were detected in the microsomal and the peroxisomal fractions where the bile acid-CoA esters are formed as well as in cytosol housing the N-acyltransferase activity. Compared to the bile acid-CoA synthetase activities, the hydrolytic activities were considerably higher, both in the postnuclear fraction and in the microsomal fraction. The thioesterase activities were in the same range as detected for the N-acyltransferase activities both in the postnuclear fraction and in the cytosolic fraction. The mere presence of thioesterase in microsomes, peroxisomes and cytosol seems counterproductive to bile acid amidation. The thioesterases may have an indirect regulatory function on the bile acid synthesis and are important for the regulation of bile acid synthesis by providing free chenodeoxycholic acid, the most potent activator of the farnesoid X receptor.

Acyltransferases↗

The significance of personality in pain from gallbladder stones.

BACKGROUND: The aim of the study was to investigate the association between personality factors related to coping styles and reported pain due to gallstones. METHODS: Personality trait measures were completed by 28 consecutive gallstone patients to provide estimates of positive coping resources (Life Regard Index, Sense of Coherence Scale, Sense of Humor Questionnaire) and negative coping resources (Eysenck Personality Questionnaire on Neuroticism, Tension, and Effort Stress Inventory). An overall index of gallstone-related complaints (pain) over the past 7 days/6 months was also obtained. Ultrasonography confirmed the gallstone condition. Multiple regression analyses tested the hypothesis that pain would be moderated by positive coping resources and mediated by negative coping resources. RESULTS: Reported pain was less severe with positive coping resources (39% of pain variance explained) and more severe with negative coping resources (45% of pain variance explained). CONCLUSION: The results confirm that mental coping resources have a significant role in pain differences among gallstone patients.

Adaptation, Psychological↗

[Liver transplantation--development and experiences].

A liver transplant program was established in Norway in 1984, and until March 1999 200 liver transplantations have been carried out. Data for these 200 consecutive patients are briefly outlined with emphasis on survival. Relevant data are also given from the Nordic Liver Transplant Registry (NLTR), the European Liver Transplant Registry (ELTR) and from United Network for Organ Sharing (UNOS). Future trends and potential advances in liver transplantation are briefly discussed. One-year and three-year survival rates for Norwegian patients have increased markedly over the years and were 85% and 75% respectively for the 1995-98 period. The number of liver transplantations per million population per year was 3.4 in Norway, 7.8 in Sweden, 5.7 in Finland and 5.4 in Denmark (1990-98). The low number of liver transplantations in Norway warrants attention. It is possible that some patients with end stage liver disease have not been offered this treatment modality. Monitoring of results and active participation in international liver transplant registries like NLTR and ELTR is an important quality control instrument.

Contraindications↗

Causes of death in patients with peptic ulcer perforation: a long-term follow-up study.

BACKGROUND: Survival is lower in ulcer perforation patients than in the general population. This study assesses the causes of death in patients treated for peptic ulcer perforation. METHODS: Cause-specific mortality in a population-based cohort of 817 patients treated for ulcer perforation in western Norway during the period 1962-1990 was compared with cause-specific population death rates. Analyses were based on observed and expected mortality curves for major causes of death and on standardized mortality rates (SMRs). Cox regression models were used to analyse possible differences on the basis of sex, birth cohort, surgical procedure, and ulcer location. RESULTS: Ulcer perforation patients experienced increased mortality from neoplasms (SMR = 1.8; 95% confidence interval (CI) = 1.4-2.1), lung cancer (SMR = 3.6; 95% CI = 2.3-4.9), circulatory diseases (SMR = 1.3; 95% CI = 1.1-1.6), ischaemic heart disease (SMR = 1.3; 95% CI = 1.03-1.6), and respiratory diseases (SMR = 1.9; 95% CI = 1.3-2.6). Postoperative deaths accounted for 38% of all excess deaths. Death from recurrent peptic ulcer was increased also in subjects who survived the 1st year after the perforation (SMR = 5.8; 95% CI = 1.2-10.4) but accounted for only a few deaths. The increase in mortality from lung cancer was higher in subjects born after 1910 than in patients of older generations. Excess mortality from lung cancer and from circulatory diseases was higher in male than in female patients. CONCLUSIONS: Increased mortality in ulcer perforation patients could mainly be attributed to smoking-related diseases. This is indirect evidence that smoking may be an important aetiologic factor for ulcer perforation.

Cardiovascular Diseases↗