Factors associated with switching and combination use of antidepressants in young Swedish adults.

AIMS: Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20-34 years. METHODS: Individuals, aged 20-34 years, who purchased an antidepressant in January-June 2006, and who had not purchased any antidepressant in the preceding 6 months (n = 24,897) were followed from 6 up to 12 months. Among those who purchased ≥ 2 antidepressant substances, switchers were defined as those who did not fulfil the requirements for combination use. Data on purchased antidepressants and socioeconomic characteristics were obtained from the Swedish Prescribed Drug Register and Statistics Sweden. The association between (i) ≥ 2 antidepressants or (ii) switching, respectively, and socioeconomic factors as well as level of care was analysed with multiple logistic regression. RESULTS: A total of 4254 individuals (17%) purchased ≥ 2 antidepressant substances, and the remaining 20,643 (83%) purchased one antidepressant. The adjusted odds ratio (OR) for purchase of ≥ 2 antidepressants (vs. purchase of one antidepressant only) was higher among those who started on mirtazapine compared with selective serotonin re-uptake inhibitors: 2.23 (95% confidence interval: 1.93-2.57), and lower in individuals with high education: 0.64 (0.54-0.75), and shorter length of follow-up: 0.73 (0.62-0.85). Among those with ≥ 2 antidepressants, 71.6% were classified as switchers. The adjusted OR for switching (vs. combination use) were higher among divorced/widows/widowers: 1.61 (1.05-2.49), and lower among individuals with short university education: 0.58 (0.43-0.78), those starting on mirtazapine: 0.78 (0.62-0.97), and when treatment was initiated in psychiatric care: 0.75 (0.63-0.88). CONCLUSIONS: One of six new users purchased at least two antidepressants, the majority were classified as switchers. Purchase patterns were associated with socioeconomic characteristics, in particular level of education, type of first purchased antidepressant, and level of care initiating treatment.

The epidemiology and clinical features of portal vein thrombosis: a multicentre study.

BACKGROUND: Reliable epidemiological data for portal vein thrombosis are lacking. AIMS: To investigate the incidence, prevalence and survival rates for patients with portal vein thrombosis. METHODS: Retrospective multicentre study of all patients registered with the diagnosis of portal vein thrombosis between 1995 and 2004. RESULTS: A total of 173 patients (median age 57 years, 93 men) with portal vein thrombosis were identified and followed up for a median of 2.5 years (range 0-9.7). The mean age-standardized incidence and prevalence rates were 0.7 per 100,000 per year and 3.7 per 100,000 inhabitants, respectively. Liver disease was present in 70 patients (40%), malignancy in 27%, thrombophilic factors in 22% and myeloproliferative disorders in 11%. Two or more risk factors were identified in 80 patients (46%). At diagnosis, 65% were put on anticoagulant therapy. Thrombolysis, TIPS, surgical shunting and liver transplantation were performed in 6, 3, 2 and 8 patients, respectively. The overall survival at 1 year and 5 years was 69% and 54%. In the absence of malignancy and cirrhosis, the survival was 92% and 76%, respectively. CONCLUSIONS: The incidence and prevalence rates of portal vein thrombosis were 0.7 per 100,000 inhabitants per year and 3.7 per 100,000 inhabitants, respectively. Concurrent prothrombotic risk factors are common. The prognosis is variable and highly dependent on underlying disease.

The use of complementary and alternative medicine in outpatients with inflammatory rheumatic diseases in Sweden.

OBJECTIVES: To study the use of complementary and alternative medicine (CAM) drugs and methods in patients with inflammatory rheumatic diseases, at rheumatology clinics in western Sweden, and to investigate possible associations between CAM-using habits and other characteristics of the patients. METHODS: Randomly selected rheumatology outpatients were asked to complete questionnaires about CAM usage, diagnoses, medication, quality of life (using the 36-item Short Form Health Survey, SF-36), fatigue (using the 20-item Multiple Fatigue Inventory, MFI-20), the Health Assessment Questionnaire (HAQ), and visual analogue scales (VAS) for global health, pain, and fatigue. RESULT: A total of 200 patients were included, 137 women and 63 men, mean age 55+/-16 and 54+/-15 years, respectively. Ongoing CAM use was reported by 58 patients (29%): 45 (22.5%) were taking CAM drugs, 20 (10%) were using CAM methods. Altogether 130 patients (65%) had used CAM at some time of their lives; 103 patients (51%) had used CAM drugs ever and 90 patients (45%) had used CAM methods ever. Women used more CAM drugs compared with men. Younger patients used more CAM. CAM use was associated with parameters indicating poorer health, mental component score (MCS) and physical component score (PCS) of SF-36, and VAS for global health and fatigue. Ongoing CAM method was associated with less use of immunomodulatory drugs. CONCLUSION: CAM use is widespread among rheumatology patients in Sweden. A total of 65% of the patients had experience of CAM treatment. Female sex, younger age, and poor health were associated with CAM utilization.

Severe hepatotoxic adverse reaction in a healthy schoolgirl after treatment with flucloxacillin.

This is the first detailed description of a severe hepatotoxic reaction in a previously healthy 9-year-old schoolgirl after ingestion of some flucloxacillin tablets. She was clinically well within one week and alanine aminotransferase in serum was normalized in one month. Follow up for more than one year was normal.

Acute liver failure in Sweden: etiology and outcome.

OBJECTIVE: To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994-2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score with transplant-free deaths as a positive outcome. RESEARCH DESIGN AND METHODS: Adult patients in Sweden with international normalized ratio (INR) of >or=1.5 due to severe liver injury with and without encephalopathy at admission between 1994-2003 were included. RESULTS: A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive-predictive value (PPV) of 67%, negative-predictive value (NPV) of 84% in the acetaminophen group. Positive-predictive value and negative-predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score>30 had a positive-predictive value of 21%, negative-predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively. CONCLUSIONS: Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score<30 predicts a good prognosis in acetaminophen patients without transplantation.

Haplotype association analysis of the polymorphisms Arg16Gly and Gln27Glu of the adrenergic beta2 receptor in a Swedish hypertensive population.

The Arg16Gly and the Gln27Glu polymorphisms in the gene for the beta2-adrenergic receptor (beta2AR) have been linked to an increased risk for cardiovascular disease. The aim of the present study was to evaluate the significance of these haplotypes for development of myocardial infarction (MI) as well as other cardiovascular phenotypes. In a prospective study cohort (CAPPP), 522 hypertensive patients (174 MI and 348 matched controls) were analysed for the Arg16Gly and the Gln27Glu polymorphisms by dynamic allele-specific hybridisation. The haplotype could successfully be determined in 516 patients. Haplotype was not significantly associated with MI. Systolic blood pressure (SBP) was higher in patients with Arg16Gly+Gln27Gln and lower in patients with Arg16Gly+Gln27Glu as compared with the other haplotypes. Haplotype was not associated with body mass index, diastolic blood pressure, cholesterol, LDL, HDL triglycerides or a diagnosis of diabetes mellitus. The present study found no evidence that haplotype for the two most common polymorphisms in the beta2AR are associated with development of MI in a Swedish hypertensive population, but haplotype may be associated with SBP.

Elevation of cytokines in peritoneal fluid and blood in patients with liver cirrhosis.

BACKGROUND/AIMS: Liver cirrhosis, described as the endstage of a necroinflammatory process, is often accompanied by ascites formation. The rationale for this study was the hypothesis that patients with liver cirrhosis have a low-grade chronic inflammatory response, which leads to an increased amount of proinflammatory cytokines accumulated in ascites. Twenty-five patients with liver cirrhosis complicated by ascites and twelve healthy volunteers were prospectively included in the study. METHODOLOGY: Ascites and blood samples from the patients were obtained for analysis of inflammatory cytokines using enzyme-linked immunosorbent assay methodology. Blood samples were taken from the healthy volunteers to obtain reference values. RESULTS: Plasma and ascites concentrations of interleukin-1alpha, interleukin-6, and tumor necrosis factor-alpha were significantly elevated in the patients compared with plasma levels in the group of healthy controls. Significant elevation of interleukin-10 concentrations was found in ascites but not in plasma in the patients. There was no significant difference in interleukin-10 levels between patient and control plasma. CONCLUSIONS: The findings suggest that elevated cytokine concentrations in ascites and serum could perpetuate an inflammatory reaction that may be a source of preservation of an ongoing systemic inflammatory reaction. This may contribute to the maintenance, and even progress, of the liver dysfunction, leading to exaggerated ascites development.

Subjects with essential hypertension are more sensitive to the inhibition of 11 beta-HSD by liquorice.

In this intervention study, we have investigated if hypertensive patients are more sensitive to liquorice-induced inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 2 than normotensive (NT) subjects and if the response depends on gender. Healthy volunteers and patients with essential hypertension (HT), consumed 100 g of liquorice daily, for 4 weeks, corresponding to a daily intake of 150 mg glycyrrhetinic acid. Office, 24-h ambulatory blood pressure (BP) and blood samples were measured before, during and after liquorice consumption. Effect on cortisol metabolism was evaluated by determining the urinary total cortisol metabolites and urinary free cortisol/free cortisone quotient (Q). The mean rise in systolic BP with office measurements after 4 weeks of liquorice consumption was 3.5 mmHg (p<0.06) in NT and 15.3 mmHg (p=0.003) in hypertensive subjects, the response being different (p=0.004). The mean rise in diastolic BP was 3.6 mmHg (p=0.01) in NT and 9.3 mmHg (p<0.001) in hypertensive subjects, the response also being different (p=0.03). Liquorice induced more pronounced clinical symptoms in women than in men (p=0.0008), although the difference in the effect on the BP was not significant. The increase in Q was prominent (p<0.0001) and correlated to the rise in BP (p=0.02). The rise in BP was not dependant on age, the change in plasma renin activity or weight. We conclude that patients with essential HT are more sensitive to the inhibition of 11 beta-HSD by liquorice than NT subjects, and that this inhibition causes more clinical symptoms in women than in men.

HLA class II markers and clinical heterogeneity in Swedish patients with primary biliary cirrhosis.

Genetic susceptibility to PBC can, at least in part, be ascribed to the major histocompatibility complex. The relevance of immunogenetic markers for the clinical presentation and course, however, is unclear. Thus, the aim of this study was to investigate the contribution of HLA class II genes to susceptibility, clinical presentation and course of disease in PBC patients. HLA genotyping for HLA-DRB1, -DQB1 and -DPB1 was carried out in a total of 99 Swedish PBC patients and 158 controls. Clinical parameters including epidemiologic variables, signs and symptoms of PBC-related liver disease and histologic data were collected and analyzed in 92 patients at study entry and at follow-up five years later. Significant clinical heterogeneity was seen among PBC patients upon study entry. Although a significant disease association was seen for HLA DRB1*08 and DQB1*0402, immunogenetic markers identified neither a particular subset of patients nor an association with the clinical course of the disease. HLA-DRB1*08 and DQB1*0402 provide the strongest immunogenetic influence in PBC. However, this association is not restricted to any particular, clinically defined subgroup of patients and it is not predictive for the course of the disease.

Usefulness of serial electrocardiograms for diagnosis of acute myocardial infarction.

The purpose of this study was to determine whether the automated detection of acute myocardial infarction (AMI) by utilizing artificial neural networks was improved by using a previous electrocardiogram (ECG) in addition to the current ECG. A total of 4,691 ECGs were recorded from patients admitted to an emergency department due to suspected AMI. Of these, 902 ECGs, in which diagnoses of AMI were later confirmed, formed the study group, whereas the remaining 3,789 ECGS comprised the control group. For each ECG recorded, a previous ECG of the same patient was selected from the clinical electrocardiographic database. Artificial neural networks were then programmed to detect AMI based on either the current ECG only or on the combination of the previous and the current ECGs. On this basis, 3 assessors--a neural network, an experienced cardiologist, and an intern--separately classified the ECGs of the test group, with and without access to the previous ECG. The detection performance, as measured by the area under the receiver operating characteristic curve, showed an increase for all assessors with access to previous ECGs. The neural network improved from 0.85 to 0.88 (p = 0.02), the cardiologist from 0.79 to 0.81 (p = 0.36), and the intern from 0.71 to 0.78 (p <0.001). Thus, the performance of a neural network, detecting AMI in an ECG, is improved when a previous ECG is used as an additional input.

Liquorice-induced rise in blood pressure: a linear dose-response relationship.

To clarify the dose-response and the time-response relationship between liquorice consumption and rise in blood pressure and explore the inter-individual variance this intervention study was designed and executed in research laboratories at University hospitals in Iceland and Sweden. Healthy, Caucasian volunteers who also served as a control for himself/herself consumed liquorice in various doses, 50-200 g/day, for 2-4 weeks, corresponding to a daily intake of 75-540 mg glycyrrhetinic acid, the active substance in liquorice. Blood pressure was measured before, during and after liquorice consumption. Systolic blood pressure increased by 3.1-14.4 mm Hg (P < 0.05 for all), demonstrating a dose-response but not a time-response relationship. The individual response to liquorice followed the normal distribution. Since liquorice raised the blood pressure with a linear dose-response relationship, even doses as low as 50 g of liquorice (75 mg glycyrrhetinic acid) consumed daily for 2 weeks can cause a significant rise in blood pressure. The finding of a maximal effect of liquorice after only 2 weeks has important implications for all doctors dealing with hypertension. There does not seem to be a special group of responders since the degree of individual response to liquorice consumption followed the normal distribution curve.

Carbohydrate-deficient transferrin in vitreous humour: a marker of possible withdrawal-related death in alcoholics.

The possibility of performing reliable post-mortem analysis of carbohydrate-deficient transferrin (CDT) concentration in vitreous humour (VH) by using a commercial assay designed for serum analysis (CDTect(TM)) as well as the usefulness of VH-CDT as a marker of alcohol misuse and possible withdrawal-related death were evaluated in a forensic sample. Detectable VH-CDT was found in 20 of 21 alcoholic subjects and in two of seven controls. By using the detection limit of the CDTect(TM) method (VH-CDT = 5 U/l) as cut-off level for a positive test, the alcoholic group was significantly separated from the control group (P = 0.0024, Fisher's exact test). The sensitivity and specificity of the test was 95% and 71%, giving a positive and a negative predictive value of 91% and 83%, respectively. Time-dependent changes of VH-CDT in the dead body could not unequivocally be excluded, which must be considered when selecting cases suitable for VH-CDT analysis. We conclude that adding VH-CDT analysis to ordinary alcohol tests may become useful in forensic medicine for establishing the so-called 'alcoholic state', which may provide a tool in research dealing with the relation between alcohol withdrawal and various causes of death in alcoholics.

[Therapeutic program for ascites. Recommendations from the Swedish Society of Gastroenterology and Gastrointestinal Endoscopy]. / Behandlingsprogram vid ascites. Rekommendationer från Svensk förening för gastroenterologi och gastrointestinal endoskopi.

As ascites is related to liver cirrhosis in 80% of the patients, the present therapeutic guidelines are focused on ascites in liver cirrhosis. A combination of spironolactone and furosemide is recommended as first line therapy in patients with mild to moderate ascites and is effective in 90% of patients. In patients with pronounced or tense ascites, first line treatment is total paracentesis with intravenous infusion of human albumin as colloid replacement. Maintenance therapy for the prevention of recurrent ascites is based on spironolactone with or without furosemide. The indications for peritoneovenous shunt, or transjugular intrahepatic stent-shunt (TIPSS), are limited and only recommended in strictly selected patients with refractory ascites. Ascites in liver cirrhosis is a symptom of advanced liver disease, and liver transplantation should always be considered in eligible patients.

Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins.

To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.

Effects of propofol on desipramine-sensitive [3H]-noradrenaline uptake kinetics in rat femoral artery.

BACKGROUND: The intravenous anaesthetic propofol inhibits the neuronal uptake of noradrenaline (uptake1) from the vascular sympathetic neuromuscular junction, resulting in an enhancement of the sympathetic neurotransmission. This could be important for maintenance of blood pressure during propofol anaesthesia. The aim of the present study was to determine how propofol influences the kinetics of uptake1. METHODS: Isolated segments of rat femoral arteries were incubated with [3H]-noradrenaline in the presence or absence of propofol and the radioactivity taken up was measured in a scintillation counter. The uptake1 inhibitor, desipramine, was used to delineate the specific neuronal uptake. RESULTS: Desipramine and 10 microM propofol significantly reduced the uptake in segments incubated with 0.1 microM [3H]-noradrenaline. Propofol at 1 microM and 100 microM did not affect the uptake. Non-linear regression analysis of specific uptake yielded Km 0.50 microM, Vmax 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 microM) increased the Km value and propofol (10-100 microM) increased the Vmax value concentration-dependently, while the Hill coefficient was not affected. CONCLUSION: Propofol seems to have a biphasic effect on the uptake of noradrenaline in the vascular sympathetic neuromuscular junction. At lower propofol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher propofol concentrations by an increase in the efficacy of the uptake.

Hepatocellular carcinoma in Sweden: its association with viral hepatitis, especially with hepatitis C viral genotypes.

Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malmö, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malmö, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p = 0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p < 0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p < 0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.

Effects of propofol on isolated human pial arteries.

BACKGROUND: The intravenous anaesthetic propofol has been reported to increase cerebral vascular resistance in vivo. The underlying mechanisms are not fully understood, but may include effects on metabolism and direct effects on the vascular smooth muscle. The present study was designed to evaluate the direct effects of propofol on human pial arteries. METHODS: We investigated the direct effect of propofol (10(-6)-10(-4) M) on isolated human pial arteries at basal tension as well as the influence on contractions induced by 5-hydroxytryptamine, prostaglandin F2alpha, noradrenaline and potassium chloride. RESULTS: Propofol did not change the basal tension. Propofol at 10(-6) and 10(-5) M did not affect the concentration-response curves of any of the contractile agents tested. Propofol at the supraclinical concentration 10(-4) M reduced the contractions induced by all contractile agents. CONCLUSION: Propofol reduces the tone of human pial arteries in vitro at supraclinical concentrations, but has no effect on the tone at clinically relevant concentrations.

Differential effect of propofol on sympathetic neurotransmission in isolated human omental arteries and veins.

1. The present study was undertaken to elucidate the effect of propofol on sympathetic neurotransmission in isolated human omental vessels. 2. Segments of both arteries and veins were exposed to 0, 10(-7), 10(-6), 10(-5) or 10(-4)M propofol, and studied in vitro to determine effects on: (i) isometric tension after electrical field stimulation (EFS) or after exogenous administration of noradrenaline (NA); (ii) EFS-stimulated release of [3H]-NA from vessel segments preincubated with [3H]-NA; (iii) uptake of [3H]-NA. 3. Propofol at 10(-6) M enhanced EFS-induced contraction in artery segments, 10(-7) and 10(-5) M had no effect, and 10(-4) M propofol depressed EFS-induced contraction in both artery and vein segments. 4. Propofol did not affect the response to exogenous NA in artery and vein segments. 5. EFS-stimulated release of [3H]-NA was depressed by 10(-5) and 10(-4) M propofol in artery segments, and by 10(-4) M in vein segments. 6. Uptake of [3H]-NA was depressed by 10(-6)-10(-4) M propofol in artery but not in vein segments. 7. The results suggest that sympathetic neurotransmission is enhanced at clinical concentrations (10(-6) M) of propofol in human omental arteries, but not veins. This may be due to an increased availability of NA in the neuromuscular junction resulting from a reduced presynaptic reuptake. Propofol at probably supraclinical concentrations (10(-5)-10(-4) M) impairs the sympathetic neurotransmission in both human omental arteries and veins, probably due to an inhibitory effect on the NA release from the sympathetic nerves.

Relaxant effects of propofol on human omental arteries and veins.

We have investigated the relaxant effects of propofol on smooth muscle tension in human omental arteries and veins to determine if endothelium-related mechanisms are involved. Isolated vessel segments were precontracted with endothelin-1 and propofol was added cumulatively (10(-7)-10(-4) mol litre-1). In both artery and vein segments, propofol induced relaxation, which was not dependent on an intact endothelium. Relaxation was reduced when the extracellular K+ concentration was increased and in the presence of tetraethylammonium chloride (TEA). In intact segments, N-nitro-L-arginine methyl ester (L-NAME), indomethacin, glibenclamide, 4-aminopyridine, clotrimazole and atropine did not affect the concentration-response curve of propofol. This indicates that propofol relaxes human omental arteries and veins in an endothelium independent manner, and that hyperpolarization caused by activation of the K+ channel, BKCa, may be involved.

Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma--a study of 51 cases from a low-endemicity area.

A total of 51 cases (19 males and 32 females) of intrahepatic cholangiocellular carcinoma (CCC) from a low-endemicity area of primary liver cancer was analyzed during the periods from 1958 to 1979 and from 1984 to 1991. The mean annual age-adjusted incidence rate was 0.44 for males and 0.56 for females per 100,000 inhabitants. CCC was diagnosed before death in only 31%. There was a female predominance in patients over 70 years of age (p < 0.05). At presentation, malaise (85%), weight loss (73%) abdominal pain (50%) and hepatomegaly (80%) were common. The median survival time from diagnosis was 2 months. The mean age at the time of death was 72 years (range 41-92). At autopsy, cholelithiasis was found in 61% (81% in patients older than 70 years) and cirrhosis in 30% of patients. Cholelithiasis was more common in CCC (p < 0.01) than in hepatocellular carcinoma cases with the same mean age. Not one case of inflammatory bowel disease was found. The gross appearance of the tumor was predominantly massive (49%) or multinodular (35%). The most common histological features were tubular pattern of growth (82%) and abundant fibrous stroma. Metastases were particularly associated with the lymph nodes (41%), skeleton (26%) and lungs (16%).