Colorectal cancer and cholangiocarcinoma in patients with primary sclerosing cholangitis and inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal cancer (CRC) and cholangiocarcinoma (CCA). We evaluated the relative risk of these malignancies in IBD patients with PSC, who had been under regular surveillance. MATERIAL AND METHODS: The survey involved a cohort of 51 patients with IBD and concomitant PSC. All patients had been under regular surveillance for a median of 19 years. The standardized incidence ratios (SIRs) of CRC and CCA were estimated between 1986 and 2007. RESULTS: During the follow up, three patients (5.9%) developed CRC and five patients (9.8%) developed CCA. SIRs were 20.71 (95% confidence interval [CI]: 5.62-79.70) and 916.63 (95% CI: 297.88-2140.99), respectively. The median age at diagnosis of CRC was 39.5 years. All patients with PSC were <45 years of age at the time of detecting CRC and had other risk factors for CRC. The median age at the time of the CCA diagnosis was 54.0 years. CONCLUSION: Despite regular surveillance, the relative risks of CCA and CRC remained increased in patients with IBD and PSC. A rigorous endoscopic surveillance is maintained for all patients with PSC, but better indicators of the development of CCA are urgently needed.

Histopathology of gastric erosions. Association with etiological factors and chronicity.

BACKGROUND: The histopathologic characteristics of the antral erosions, and a comparison with samples systematically collected from the background antral mucosa, have not been studied previously. Similarly, unknown is the association of these features with suspected etiological factors and chronicity of erosion. MATERIAL AND METHODS: We studied 117 patients with gastric erosions in the absence of peptic ulcer disease. With 28 patients available for a follow-up 19 years later, sites of erosions and background mucosa were biopsied and histopathology of both independently assessed at both visits. Helicobacter pylori status was examined from the biopsies taken in the initial and follow-up gastroscopies. Only subjects originally displaying antral erosions were included. The presence of Herpes simplex virus (HSV) antibodies was analyzed and use of nonsteroidal anti-inflammatory drug (NSAID) was inquired. RESULTS: Initially, the inflammation was more active in the region of erosions than elsewhere in antral mucosa. More active inflammation in the erosion was associated with HSV seropositivity, Helicobacter pylori infection, and the recent use of NSAIDs. In the follow-up visit, antral erosions were present in 38% (3/8) of Helicobacter pylori negatives and in 35% (7/20) of positives (p = ns). The Helicobacter pylori positive subjects with chronic or recurrent erosions had initially higher scores of neutrophils compared to subjects with nonrecurrent or nonchronic erosions (2.7 ± 0.5 vs 1.2 ± 1.0; p = .002). CONCLUSIONS: Focally enhanced inflammation is characteristic for gastric erosions. This focal inflammation was associated with HSV seropositivity or NSAID use suggesting that such inflammation may be important in the pathogenesis of gastric antral erosions. Highly active inflammation in the erosions associates with their chronicity.

The epidemiology of inflammatory bowel diseases in Finland.

OBJECTIVE: There is evidence that the incidence of inflammatory bowel diseases is increasing, but the data are inconsistent. For appropriate allocation of health care resources, knowledge of the actual occurrence of diseases is important. We here conducted an epidemiological survey using a population-based register in a well-defined area representative of the whole Finnish population. MATERIAL AND METHODS: The collection of cases took place in 1986-1999 in the Tampere region, which comprised 363,000 adults in 1999. All municipal centers detecting and managing inflammatory bowel diseases participated in the study. Particular effort was made to register all cases. RESULTS: The total number of patients was 1691. The prevalence per 100,000 inhabitants in 1986 was 119 for ulcerative colitis (UC), 40 for Crohn's disease (CD) and 9 for inflammatory bowel disease unclassified (IBDU); in 1999 the respective figures were 291, 124 and 27. During the study period, the annual incidence of UC increased from 13.3 to 19.6 per 100,000, and that of CD from 5.0 to 9.4, whereas the incidence of IBDU decreased from 1.2 to 0.3. The extent of the diseases remained by and large unaltered over the time of survey. CONCLUSIONS: An increasing trend was observed in the number of patients with inflammatory bowel disease, and the frequency was higher than that reported in most surveys. This increase constitutes a challenge for the health care system.

Ascites: aetiology, mortality and the prevalence of spontaneous bacterial peritonitis.

OBJECTIVE: To assess the aetiology, prognosis and prevalence of spontaneous bacterial peritonitis (SBP) in patients hospitalized for ascites. The validity of an elevated (>11 g/l) serum-ascites albumin gradient (SAAG) in the diagnostic work-up was evaluated. Mortality trends were observed over two periods of time. MATERIAL AND METHODS: A total of 231 consecutive patients who underwent diagnostic paracentesis between February 1994 and December 1998 and January 2005 and March 2007 were included in the study. The definition of SBP comprised polymorphonuclear cell count >250/mm(3) without evidence of other intra-abdominal source of infection. SAAG was obtained and the Child-Pugh classification applied. Survival rates were obtained from medical records. RESULTS: The most common causes of ascites were alcohol liver cirrhosis (n=143; 62%), malignancy (n=30; 13%), non-alcoholic cirrhosis (n=11; 5%) and malignancy with cirrhosis (n=11; 5%). The prevalence of SBP in cirrhosis was 6.7% (95% CI 2.8-10.5%). Overall mortality rates at 1 month, 6 months and 1 year were 22%, 40% and 48%, respectively, and remained unchanged between the intervals. Patients with grade C liver disease had higher 1-month (26% versus 6%), and 6-month (44% versus 27%) mortality rates than grade B patients, but commensurate 1-year mortality (49% versus 47%). SAAG was >or=11 g/l in 85% of patients with obvious portal hypertension and in 30% with malignancy, ascites albumin level

[Update on current care guidelines. Safe use of non-steroidal anti-inflammatory drugs]. / Tulehduskipulääkkeiden turvallinen käyttö.

Pain medication should be based on patient's needs and risk profile. Age > 65 years, prior ulcer, co-morbidities, large daily dose, Helicobacter pylori infection, concurrent use of glucocorticoids, serotonin re-uptake inhibitors, or warfarin increase the risk of upper gastrointestinal bleeds. As a preventive strategy the use of concurrent proton pump inhibitors with non-selective NSAIDs is recommended. It is also possible to use COX-2 selective NSAIDs but they are contraindicated for persons with atherosclerotic diseases and special consideration is required for persons with risk factors of heart diseases. Paracetamol is the drug of choice for pain.

The risk of colorectal cancer in patients with inflammatory bowel diseases in Finland: a follow-up of 20 years.

BACKGROUND AND AIMS: Data on the relative risk of colorectal cancer in inflammatory bowel diseases (IBD) are inconsistent. To prevent the development of cancer, endoscopic facilities should be targeted correctly. We report here the results of a 20-year follow-up in Finland and evaluate the efficacy of endoscopic surveillance in cancer prevention. METHODS: The data were based on an IBD register in our catchment area in 1986-2007. The population-based cohort comprised 1915 patients, 1254 with ulcerative colitis, 550 with Crohn's disease and 111 with inflammatory bowel unclassified. Colorectal cancer cases were obtained from the IBD register; the colorectal cancer figures in the respective population were obtained from the Finnish Cancer Registry. RESULTS: Colorectal cancer was found in 21 patients, the standardized incidence ratio (SIR) being 1.83 (95% confidence interval (CI) 1.13-2.79) for IBD. Colorectal cancer risk was 3.09 (CI 1.50-5.75) for extensive UC, and 3.62 (CI 2.00-11.87) for Crohn's disease affecting the colon. Eleven (52%) of the colorectal cancer cases were TNM stage 3 or 4. In the same observation period 10 colectomies with ileoanal anastomosis were performed with the indication of cancer risk in ulcerative colitis; of these 10 patients only two had no additional risk factors for colorectal cancer, for example primary sclerosing cholangitis, pseudopolyposis or active disease. CONCLUSIONS: The risk of colorectal cancer in the cohort was only moderately increased. In the absence of additional risk factors, endoscopic surveillance was of limited benefit. We therefore suggest intensive endoscopy surveillance to be targeted on patients with definite risk factors.

Mortality in ulcerative colitis and Crohn's disease. A population-based study in Finland.

BACKGROUND: An increased mortality has been reported in patients with Crohn's disease (CD), while figures have remained similar or decreased in patients with ulcerative colitis (UC) compared to the population in general. We evaluated the long-term mortality risk of patients with inflammatory bowel diseases (IBD) in a well-defined population. METHODS: The data were based on a prospective IBD register in our catchment area; follow-up covered 1986-2007. The population based cohort comprised 1915 adult patients, 1254 with UC, 550 with CD, and 111 with inflammatory bowel disease unclassified (IBDU). The mortality rate and causes of death were obtained from Statistics Finland. RESULTS: We recorded 223 deaths among the 1915 patients with IBD within a follow-up of 29,644 person-years. The standardised mortality rate (SMR) was 1.14 in CD and 0.90 in UC. In cause-specific mortality; the risk of death in diseases of the digestive system was significantly increased in CD (SMR 5.38). The mortality in colorectal cancer was non-significantly increased in both UC and CD (SMR 1.80 and 1.88, respectively). Compared to the background population, there were significantly fewer deaths due to mental and behavioural disorders due to use of alcohol (0 observed, 10.2 expected in IBD). CONCLUSIONS: The overall mortality in CD and CU was not different from that in the population. In cause-specific mortality, diseases of the digestive system were significantly increased. Deaths due to mental and behavioural disorders resulting from alcohol consumption were less common in patients with IBD than in the population at large in Finland.

Prevalence and incidence of primary biliary cirrhosis are increasing in Finland.

OBJECTIVE: To examine the epidemiology of primary biliary cirrhosis (PBC) in Finland and to evaluate whether the possible increase in prevalence was attributable to the increasing incidence, better survival, or both. MATERIAL AND METHODS: The Hospital Discharge Register, pathology registers, and death certificates for the years 1988 99 were scrutinized, and the patients identified were followed-up for survival until 31 October 2004. The study area covered four university hospital districts: a total of 25 hospitals. The diagnosis of PBC was regarded as definite (or probable) if three (or two) of the following criteria were fulfilled: positive antimitochondrial antibodies, constantly elevated alkaline phosphatase, and compatible liver histology. RESULTS: In the total population of the study areas, the age-standardized prevalence of PBC increased during the study period from 103 (95% CI: 97-110) to 180 (172-189) per million inhabitants. Incidence increased from 12 (10-14) to 17 (15-20) per million inhabitants per year. The annual average increase in prevalence was 5.1% (4.2-5.9%, p <0.0001) and in incidence 3.5% (0.9%-6.0%, p =0.008). In gender-specific analyses among women, the prevalence of PBC increased from 161 (151-171) to 292 (277-207) per million during the study period and the incidence from 20 (16-24) to 27 (23-32) per million per year. The death rate was 4% per year and half the deaths were from liver-related causes. Survival after diagnosis during the study period lengthened. CONCLUSIONS: The prevalence of PBC increased in Finland during 1988-99, owing to both the increased incidence and the prolonged survival.

Comparison of three stool antigen tests in confirming Helicobacter pylori eradication in adults.

OBJECTIVE: Reliable and readily available non-invasive methods are needed for detection of Helicobacter pylori infection and assessment of eradication therapy. In H. pylori-positive subjects we compared three stool antigen tests (Premier Platinum HpSA, Amplified IDEIA HpStAR and ImmunoCard STAT!HpSA) with invasive tests before their eradication therapy, and with non-invasive diagnostic methods after their therapy. MATERIAL AND METHODS: A total of 82 adults with dyspepsia (aged 24-79 years) with an H. pylori-positive rapid urease test were enrolled in the study. Before therapy, H. pylori status was also confirmed with histology, culture and serology. After eradication, success was assessed with the [13C]-urea breath test (UBT) and usually also with serology. RESULTS: At baseline, sensitivities of these stool antigen tests were 90.2% for HpSA, 97.6% for HpStAR and 96.3% for ImmunoCard. Eradication therapy was successful in 66 patients and unsuccessful in 16. Sensitivity and specificity of the three stool antigen tests in the post-eradication setting were, respectively, 75.0% and 95.5% for HpSA, 93.8% and 98.5% for HpStAR and 87.5% and 95.5% for Immunocard. CONCLUSIONS: The performance of all three stool antigen tests in the post-treatment setting was slightly inferior to that of the UBT test and serology, with monoclonal antibody-based tests showing better results.

Evolution of gastritis in patients with gastric erosions.

OBJECTIVE: Gastric erosions are mainly associated with Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), but there has been no information available on the long-term evolution of gastritis in subjects with erosions. MATERIAL AND METHODS: A series of 117 patients with gastric erosions without peptic ulcer disease and matched controls without erosions or ulcers were studied. Available subjects underwent endoscopy and biopsy 17 years later. Parietal cell antibodies were analysed at the first visit. RESULTS: Fifty-two patients and 67 controls were available for follow-up. Since H. pylori was a major determinant of gastritis, only subjects with unchanged H. pylori status were included in the evaluation of gastritis progression. At the follow-up visit, gastric erosions were present in 38% (16/42) of the patients and 11% (5/46) of the controls (p=0.005). In H. pylori-negative subjects, no evolution of histological changes was seen. In H. pylori-positive subjects, body gastritis was initially less active in the erosion group. With time, antral gastritis worsened only in the erosion group. Parietal cell antibodies were more common in the control group (23%; erosion patients 0%; p=0.01), which also showed worsening of gastritis (p=0.003) and aggravation of atrophy (p=0.002) in the body mucosa. CONCLUSIONS: Gastritis in H. pylori-positive subjects with gastric erosions shows evolution of antral predominance, body predominance including development of atrophic changes being rare. Accordingly, patients with erosions share the characteristics of gastritis of the duodenal ulcer phenotype. These findings support the importance of H. pylori and acid in the pathogenesis of gastric erosions in H. pylori-positive patients.

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo-controlled trial.

No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases gamma-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (-337 +/- 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (-0.50 +/- 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated.