High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking. AIM: To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD. METHODS: From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia. RESULTS: The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo- (n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia. CONCLUSIONS: Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.

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.

Non-invasive resting magnetocardiographic imaging for the rapid detection of ischemia in subjects presenting with chest pain.

BACKGROUND: Early diagnosis of ischemia is complicated by the poor sensitivity of standard tests and contraindication for stress testing in unstable angina patients. Magnetocardiography (MCG) imaging can be used for the rapid, non-invasive detection of ischemia at rest. METHODS: We studied 125 patients with presumed ischemic chest pain. All were chest pain free at the time of scanning. A 6-minute resting MCG scan (CardioMag Imaging, Inc., New York, 9-channel system) was performed. Following the MCG scan, automated software data analysis was performed, and quantitative scores were automatically calculated for each subject. The presence of ischemia was determined after testing with serial troponins, stress testing, and/or coronary angiography. RESULTS: The mean age was 59.4 +/- 13.6 years. Most patients (86.4%) had non-ischemic 12-lead ECG and normal troponin (86.2%). Fifty-five patients (44.0%) were determined to be ischemic. The MCG sensitivity, specificity, positive and negative predictive value was 76.4, 74.3, 70.0 and 80.0%, respectively, for the detection of ischemia (p < 0.0001). CONCLUSIONS: MCG is a new rapid, non-invasive imaging tool able to detect repolarization abnormalities at rest consistent with ischemia in patients presenting with chest pain syndrome and normal or non-specific 12-lead ECG and normal troponin.

No association between the use of cellular or cordless telephones and salivary gland tumours.

AIM: To investigate the association between the use of cellular or cordless telephones and the risk for salivary gland tumours. METHODS: Cases were assessed from the six regional cancer registries in Sweden. Four controls matched for sex and age in five year age groups were selected for each case. A total of 293 living cases and 1172 controls were included. RESULTS: There were 267 (91%) participating cases and 1053 (90%) controls. Overall no significantly increased risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI 0.68 to 1.43) for use of cordless phones. Similar results were found for different salivary gland localisations. No effect of tumour induction period or latency was seen, although few subjects reported use for more than 10 years. CONCLUSIONS: No association between the use of cellular or cordless phones and salivary gland tumours was found, although this study does not permit conclusions for long term heavy use.

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.

Validation of the inflammatory bowel disease questionnaire in Swedish patients with ulcerative colitis.

BACKGROUND: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease-specific health-related quality of life (HRQOL) questionnaire including four dimensions and a sum score. The aim of this study was to assess the internal and external validity, reliability, and sensitivity of a Swedish version of the IBDQ. METHODS: Three hundred consecutive patients with ulcerative colitis completed the IBDQ and three other health-related quality of life questionnaires (the Rating Form of IBD Patient Concerns (RFIPC), the Short Form-36 (SF-36) and the Psychological General Well-Being (PGWB) index). Disease activity was evaluated using a 1-week symptom diary, blood tests and rigid sigmoidoscopy. One hundred and fourteen patients filled in the questionnaire a second time, of whom 75 had been in stable remission for over 6 months and 39 had a significant clinical change in disease activity. RESULTS: Factor analysis of the 32 IBDQ items did not support the four dimensional scores. The dimensional scores had sufficient convergent validity, but low discriminative validity and homogeneity. The homogeneity was also low for the sum score. The inter-dimensional correlations were high. The concurrent validity was supported by correlations between the dimensional scores and other measures of disease activity and HRQOL. Patients in relapse scored significantly less on the sum score and the four dimensions compared to patients in remission. The test-retest correlations for the dimensional scores were 0.40-0.76. Patients with a change in disease activity during the 6-month follow-up period had a significant change in IBDQ scores not found in those who remained in remission. CONCLUSIONS: The Swedish version of the IBDQ had external validity and was shown to be a reliable and sensitive measure of HRQOL in ulcerative colitis, though there are some concerns regarding the internal validity. The use of a sum score was not supported and the questionnaire may benefit from a redivision of items into dimensions with better homogeneity and discriminative validity.

Hermansky-Pudlak syndrome with colitis and pulmonary fibrosis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessively inherited disease with oculocutaneous albinism, hemorrhagic diathesis, and multisystemic deposition of ceroid lipofuscin. We report a case with all symptoms characteristic of HPS. The patient was a mentally retarded albino with mild bleeding diathesis, and her course was complicated by granulomatous colitis refractory to medical treatment and progressive, fatal pulmonary fibrosis.

Primary amyloidosis with spontaneous splenic rupture, cholestasis, and liver failure treated with emergency liver transplantation.

A 61-yr-old man with cholestatic jaundice soon after presentation had an emergency operation because of spontaneous rupture of the spleen. This was found to be caused by primary systemic amyloidosis. After the splenectomy, the patient deteriorated with liver failure and was successfully treated with liver transplantation. Osteopenic fractures of the thoracic columna developed after transplantation. Except for this, the patient is well 18 months after transplantation.

Medical therapy of active Crohn's disease.

Active Crohn's disease constitutes a major problem in gastroenterology. Symptoms vary with site, extent and local complications of the disease as well as with the absence or presence of extraintestinal manifestations. Due to the troublesome consequences of the disease new treatments have continuously been tried. However, the results have varied and no definite breakthrough has occurred in the medical treatment of active Crohn's disease during the last years. The new salicylates have shown some effect using higher doses, but have not fulfilled the expectations once connected with their development. The new steroids have compared well to, but not exceeded, the older corticosteroid preparations in terms of therapeutic efficacy but they have a better side-effect profile. The role of the purine analogs azathioprine/6-mercaptopurine has been further evaluated. The onset of their effect is slow, an intravenous loading dose might shorten this time span, and they are steroid sparing. The controlled data on methotrexate are limited and the long-term effects not well studied and there is concern about toxicity. Even the use of cyclosporine in active Crohn's disease is controversial and connected with serious adverse events. Studies on the new immune modulating therapies such as anti-TNF-alpha antibodies, anti-CD4 antibodies, interleukin-10 and interferon have been encouraging but large scale studies are still awaited before the effect and the spectra of side-effects can be fully evaluated. The aim of this chapter is to summarize the present knowledge of medical treatment of active Crohn's disease and to point towards the directions of new therapeutic options.

Cytogenetical observations in a cultured polymorphous low-grade adenocarcinoma originating from the minor salivary glands.

The cytogenetical findings in a cultured polymorphous low-grade adenocarcinoma (PLGA) of the minor salivary glands are reported. The deviations observed showed similarities to those found in the only hitherto studied case originating in the minor glands. Both these cases, however, showed a picture completely different from that in the two reported cases of parotid PLGA, constituting the malignant component in carcinomas ex pleomorphic adenoma. The most probably reasons are believed to be aetiological differences.

Platelet density and size in inflammatory bowel disease.

OBJECTIVE: The present study investigates platelet density and mean platelet volume (MPV) in active inflammatory bowel disease (IBD). EXPERIMENTAL PROTOCOL: 27 patients with IBD (18 ulcerative colitis and 9 Crohn's disease) were compared to 12 healthy volunteers. 18 subjects had active disease. Platelet counts and mean platelet volume (MPV) were determined. Thereafter, platelets were separated according to density on a linear preformed Percoll gradient. A computerized device was employed for scanning transmission variations and thus the platelet distribution in the gradient and the platelet peak were identified. RESULTS AND CONCLUSIONS: Subjects with active IBD had greater platelet density (p = 0.02) and lower MPVs (p < 0.001). These findings may indicate augmented platelet granule content. The study also demonstrates that a low MPV is associated with active IBD.

Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.

BACKGROUND/AIMS--The course of primary sclerosing cholangitis (PSC) is highly variable and unpredictable. This study describes the natural history and outcome of PSC. These data were used to construct a prognostic model for patients with PSC. METHODS--A total of 305 Swedish patients with PSC were studied. The median follow up time was 63 (1-194) months and all patients could be traced for follow up. Some 79 patients died or had a liver transplant. The prognostic significance of clinical, biochemical, and histological findings at the time of diagnosis were evaluated using multivariate analysis. RESULTS--The estimated median survival from time of diagnosis to death or liver transplantation was 12 years. Cholangiocarcinoma was found in 24 (8%) of the patients and 134 (44%) of the patients were asymptomatic at the time of diagnosis. The estimated survival rate was significantly higher in the asymptomatic group (p < 0.001). However, 29 (22%) of the asymptomatic patients became symptomatic during the study period. It was found that age, serum bilirubin concentration, and histological stage at the time of diagnosis were independent predictors of a bad prognosis. These variables were used to construct a prognostic model. CONCLUSIONS--This prognostic model developed from a large homogeneous population of PSC patients should be of value for the timing of transplantation and patient counselling in PSC.

Optimum dose of olsalazine for maintaining remission in ulcerative colitis.

To evaluate the optimum dose of olsalazine for maintaining remission in ulcerative colitis, 198 patients in remission for more than three months were randomly assigned to receive 0.5 g, 1.0 g, or 2.0 g/day for 12 months. A dose-ranging effect was detected in the per protocol analysis, with remission rates of 60% (0.5 g), 70% (1.0 g), and 78% (2.0 g) (p = 0.03, trend in proportions). The higher dose was most effective in patients with proctitis (90% remission on 2 g/day, p = 0.03) or those in remission for less than 12 months before the trial (88% remission on 2 g/day, p = 0.0006). There was little dose-ranging effect in patients with extensive colitis or those in remission for more than 12 months. Diarrhoea necessitated treatment withdrawal in 12%. The optimal dose of olsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferable, although the dose seems to be less important in patients with more extensive disease or those in long term remission.

Olsalazine does not increase the bile acid losses in subjects with a permanent ileostomy.

Olsalazine is a novel compound presently under development for the treatment of ulcerative colitis. Olsalazine sometimes causes diarrhoea; one of the possible explanations could be an increased load of bile acids in the colon. Bile acid ileostomy output was therefore measured enzymatically and after oral administration of tauro-23-[75Se]selena-25-homocholic acid (SeHCAT) in eight subjects during intake of placebo or olsalazine. The bile acid output showed great individual variations during both treatment periods, but there was no indication that olsalazine interfered with bile acid handling in the terminal ileum.