Risk of Cancer in Patients With Crohn's Disease 30 Years After Diagnosis (the IBSEN Study).

Background: Patients with Crohn's disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types. Methods: The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population. Results: In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06-2.28), particularly male patients (HR = 1.85, 95% CI: 1.08-3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92-4.27 and SIR = 2.45, 95% CI: 0.67-5.37, respectively). Conclusions: After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.

Incidence of cancer in patients with ulcerative colitis 30 years after diagnosis (the IBSEN study).

OBJECTIVES: Patients with ulcerative colitis (UC) have shown an increased risk for colorectal cancer, hepatobiliary, hematologic, and skin cancers, but updated long-term data is needed. This study aimed to estimate the risk of cancer in patients with UC compared to the general Norwegian population, in a population-based cohort (the IBSEN study), 30 years after diagnosis; and to identify possible risk factors associated with cancer. METHODS: The IBSEN cohort prospectively included all incident patients between 1990 and 1993. Cancer incidence data were obtained from the Cancer Registry of Norway. The overall and cancer-specific hazard ratios (HR) were modelled using Cox regression. Standardized incidence ratios were estimated compared to the general population. RESULTS: In total, the cohort included 519 patients, and 83 cases were diagnosed with cancer. There was no statistically significant difference in the overall cancer risk (HR = 1.01, 95% CI: [0.79-1.29]) and colorectal cancer risk (HR = 1.37, 95% CI: [0.75-2.47]) between patients and controls. The incidence of biliary tract cancer was higher than expected (SIR = 9.84, 95%CI: [3.19-20.15]), especially when UC patients suffered from primary sclerosing cholangitis. Male UC patients were also more at risk of being diagnosed with hematologic malignancies (HR = 3.48, 95% CI: [1.55-7.82]). Being prescribed thiopurines was associated with a higher risk of cancer (HR = 2.03, 95% CI: [1.02-4.01]). CONCLUSIONS: At 30 years after diagnosis, the risk of all cancer in patients with UC was not significantly increased compared with the general population. However, the risks of biliary tract cancer and hematologic cancers were increased, particularly in male patients.

Mortality in Patients with Inflammatory Bowel Disease: Results from 30 Years of Follow-up in a Norwegian Inception Cohort (the IBSEN study).

BACKGROUND AND AIMS: Patients with longstanding inflammatory bowel disease [IBD] may be at an increased risk of death compared to the general population, especially elderly patients. The Inflammatory Bowel South-Eastern Norway [IBSEN] study has previously detected a small but not statistically significant increase in mortality 20 years after diagnosis. The aim of this study was to evaluate the overall and cause-specific mortality at 30 years of follow-up. METHODS: The IBSEN cohort included 519 incident patients with ulcerative colitis [UC] and 237 patients with Crohn's disease [CD] between 1990 and 1993, each matched with five controls. Death certificate data were obtained from the Norwegian Cause of Death Registry. The underlying causes of death were categorized into five groups: all cancers, gastrointestinal cancers, cardiovascular diseases, infections and all other causes. Hazard ratios [HRs] were modelled using Cox regression. RESULTS: There was no statistically significant difference in the overall mortality rates. However, in patients with CD, male sex (HR = 1.65 [95% CI: 1.04-2.62]), onset after 40 years of age (HR = 1.72 [1.19-2.48]), colonic disease (HR = 1.57 [1.05-2.35]) and penetrating behaviour (HR = 3.3 [1.41-7.76]) were clinical factors associated with an increased mortality. IBD patients were at a higher risk of death due to cardiovascular disease: HR = 1.51 [1.10-2.08] for UC and 2.04 [1.11-3.77] for CD. When taking into account both the underlying and the immediate cause of death, infection was more frequent in patients with IBD. CONCLUSIONS: Overall, all-cause mortality rates were similar between patients with IBD and controls. However, clinicians should remain alert to cardiovascular diseases and infections, particularly in specific subgroups of CD patients.

Helicobacter pylori was not detected in oral squamous cell carcinomas from cohorts of Norwegian and Nepalese patients.

Helicobacter pylori (HP) infection is an established causative agent for gastric cancer. Although the oral cavity is a part of the gastrointestinal system, the presence and possible causative role of HP in oral squamous cell carcinoma (OSCC) is a subject of controversy. Therefore, the current study aimed to investigate HP infection in two cohorts of OSCC patients with different demographic characteristics, lifestyles and habitual risk factors. A total of 242 formalin-fixed paraffin-embedded OSCC specimens from two different patient cohorts (Norway, n = 171 and Nepal, n = 71) were used to examine HP using immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR). Two different HP specific genes (23S rRNA and ureA) were used for TaqMan-based qPCR, and for subsequent verification using HP specific RIDAGENE HP kit and SYBR Green based qPCR. All of the OSCC specimens from both cohorts were found to be negative for HP infection with IHC and qPCR, although the positive control specimens tested positive. Our findings suggest that HP is absent in the examined OSCC cohorts, irrespective of race, lifestyle and habitual risk factors. This indicates that, in contrast to gastric cancer, HP is an unlikely contributing factor for OSCC pathogenesis.

Experiences from multiplex PCR diagnostics of faeces in hospitalised patients: clinical significance of Enteropathogenic Escherichia coli (EPEC) and culture negative campylobacter.

BACKGROUND: In hospitalised patients with diarrhoea a positive campylobacter stool Polymerase Chain Reaction (PCR) test with negative culture results as well as Enteropathogenic Escherichia coli (EPEC) positive stool PCRs, challenges the clinician and may lead the unexperienced clinician astray. The aim of the study was to elucidate the clinical significance of positive Campylobacter and/or EPEC test results in hospitalised patients with diarrhoea. METHODS: We conducted a retrospective case-case study. Case groups with 1) EPEC only and 2) EPEC in combination with any other pathogen in the PCR multiplex array, 3) PCR positive/culture negative Campylobacter, and 4) PCR positive/culture positive Campylobacter were compared. Medical records were reviewed and cases classified according to pre-specified clinical criteria as infectious gastroenteritis or non-infectious causes for diarrhoea. We analyzed the association between laboratory findings (the 4 subgroups) and the pre-specified clinical classification. We further sequenced culture negative campylobacter samples and tested EPEC for bundle forming pilus A (bfpA) gene, distinguishing typical from atypical EPEC. RESULTS: A total of 291 patients were included, 169 were PCR positive for Campylobacter and 122 for EPEC. For both pathogens, co-infections were more common in culture negative/PCR positive samples than in culture positive samples. Clinical characteristics differed significantly in and between groups. Campylobacter culture positive patients had very high prevalence of characteristics of acute infectious gastroenteritis, whereas patients with PCR positive test results only often had an alternative explanation for their diarrhoea. Culture positives were almost exclusively C. jejuni/coli, whereas in culture negatives, constituting a third of the total PCR positives, C. concisus was the most frequent species. The vast majority of EPEC only positives had documented non-infectious factors that could explain diarrhoea. The EPEC co-infected group mimicked the culture positive campylobacter group, with most patients fulfilling the infectious gastroenteritis criteria. CONCLUSIONS: In hospitalised patients, positive PCR results for campylobacter and EPEC should be interpreted in a clinical context after evaluation of non-infectious diarrhoea associated conditions, and cannot be used as a stand-alone diagnostic tool.

Fluoride: a risk factor for inflammatory bowel disease?

Although the association between inflammatory bowel disease (IBD) and oral hygiene has been noticed before, there has been little research on prolonged fluoride exposure as a possible risk factor. In the presented cases, exposure to fluoride seems indirectly associated with higher incidence of IBD. Fluoride toxicology and epidemiology documents frequent unspecific chronic gastrointestinal symptoms and intestinal inflammation. Efflux genes that confer resistance to environmental fluoride may select for IBD associated gut microbiota and therefore be involved in the pathogenesis. Together these multidisciplinary results argue for further investigation on the hypothesis of fluoride as a risk factor for IBD.

Suitability of stx-PCR directly from fecal samples in clinical diagnostics of STEC.

PCR-based testing for Shiga toxin producing Escherichia coli (STEC) directly from fecal samples is increasingly being implemented in routine diagnostic laboratories. These methods aim to detect clinically relevant amounts of microbes and not stx-carrying phages or low backgrounds of STEC. We present a diagnostic procedure and results from 1 year of stx-targeted real-time PCR of fecal samples from patients with gastrointestinal symptoms in Norway. A rapid stx2 subtyping strategy is described, which aims to quickly reveal the virulence potential of the microbe. stx was detected in 22 of 3320 samples, corresponding to a PCR positive rate of 0.66%. STEC were cultured from 72% of the PCR positive samples. Four stx1 isolates, eight stx2 isolates, and four isolates with both stx1 and stx2 were identified. With the method presented, stx-carrying phages are not commonly detected. Our results support the use of molecular testing combined with classical culture techniques for routine diagnostic purposes.

A rapid, high-throughput screening method for carriage of methicillin-resistant Staphylococcus aureus.

Rapid screening of methicillin-resistant Staphylococcus aureus (MRSA) colonization prior to hospital admittance is important to reduce nosocomial infections and health care costs. Molecular detection of mecA and S. aureus specific target genes has become widely established for this purpose. However, there are still limitations in potential for high-throughput screening in the methods described. We have compared the time aspects and workload of four different DNA preparation platforms, resulting in an automated and simple MRSA screening method which combines two liquid handling systems and a simple lysis buffer. We have further transferred our in-house dual real-time PCR to a fast-PCR protocol, reducing the time and labour spent on these samples to a minimum.