Capsule endoscopic findings correlate with fecal calprotectin and C-reactive protein in patients with suspected small-bowel Crohn's disease.

OBJECTIVE: Capsule endoscopy (CE) is a sensitive method for detecting inflammatory lesions in the small bowel. Such lesions may be due to Crohn's disease but also to other causes and a histological diagnosis may be difficult to achieve in the small bowel. The aim of the study was to find a possible correlation between capsule endoscopic findings, biochemical parameters, and symptoms in patients with suspected or known small-bowel Crohn´s disease. MATERIALS AND METHODS: Thirty patients with inflammatory lesions in the small bowel diagnosed by CE were included. CE findings of inflammation were graded using the Lewis score. C-reactive protein (CRP) and fecal calprotectin were used as biochemical parameters. Symptoms were graded using the Harvey-Bradshaw index. The patients were followed up after 9 months with a second CE, CRP, fecal calprotectin, and Harvey-Bradshaw index. RESULTS: There was a significant persistent correlation between endoscopic inflammation and fecal calprotectin (p = 0.003 at inclusion and p < 0.001 at follow-up). CRP was correlated to endoscopic inflammation at inclusion (p = 0.006), but not at follow-up. Symptoms were not correlated with endoscopic inflammation. CONCLUSION: Inflammatory lesions in the small bowel diagnosed by CE in patients with suspected Crohn´s disease are correlated to fecal calprotectin and CRP, but not to symptoms.

Eosinophil associated genes in the inflammatory bowel disease 4 region: correlation to inflammatory bowel disease revealed.

AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP). METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP(®) system as described by the manufacturer. Statistical tests for calculations of results were χ(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant. RESULTS: The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in µg/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes. CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

Capsule retentions and incomplete capsule endoscopy examinations: an analysis of 2300 examinations.

UNLABELLED: Aim. To evaluate capsule endoscopy in terms of incomplete examinations and capsule retentions and to find risk factors for these events. Material and Methods. This retrospective and consecutive study includes data from 2300 capsule enteroscopy examinations, performed at four different hospitals in Stockholm, Sweden from 2003 to 2009. Results. The frequency of incomplete examinations was 20%. Older age, male gender, suspected, and known Crohn's disease were risk factors for an incomplete examination. The PillCam capsule had the highest rate of completed examinations. Capsule retention occurred in 1.3% (n = 31). Risk factors for capsule retention were known Crohn's disease and suspected tumor. Complications of capsule retention were acute obstructive symptoms in six patients and one death related to complications after acute surgical capsule retrieval. CONCLUSION: Capsule endoscopy is considered a safe procedure, although obstructive symptoms and serious complications due to capsule retention can be found in a large series of patients.

Colitis-associated DNA aneuploidy and dysplasia in Crohn's disease and risk of colorectal cancer.

BACKGROUND: There is uncertainty about how patients with Crohn's colitis should be monitored for colorectal cancer (CRC). By analogy to ulcerative colitis, regular colonoscopy with biopsies for dysplasia has been used. We describe the occurrence of dysplasia and DNA aneuploidy in a cohort of patients with Crohn's colitis. METHODS: In all, 245 patients with extensive colitis (225 with a firm diagnosis of Crohn's disease, and 20 diagnosed as indeterminate colitis) at Stockholm Söder Hospital and Karolinska University Hospital, Huddinge were included. They were followed with regular colonoscopies with biopsies both for dysplasia and DNA aneuploidy. The cumulative occurrence of DNA aneuploidy and dysplasia was estimated using Kaplan-Meier curves. Time sequences and interactions between DNA aneuploidy, dysplasia, and CRC were studied using Cox regression analysis, adjusted for age, sex, and age at diagnosis. RESULTS: During a median follow-up time of 9.2 person-years, DNA aneuploidy was found in 53 patients (22%), with 10 patients having multifocal aneuploidy and high S-phase values. Dysplasia was found in 42 patients (17%), 10 having multifocal dysplasia. Relative risk (RR) of dysplasia given DNA aneuploidy was 5.3 (95% confidence interval [CI] 2.3-12). RR of CRC given dysplasia was 10 (95% CI 2-50), and RR of CRC given aneuploidy was 1.5 (95% CI 0.3-9.3). CONCLUSIONS: Dysplasia and DNA aneuploidy including S-phase analysis may complement stratification of patients with Crohn's

Bleeding from gastrointestinal angioectasias is not related to bleeding disorders - a case control study.

BACKGROUND: Angioectasias in the gastrointestinal tract can be found in up to 3% of the population. They are typically asymptomatic but may sometimes result in severe bleeding. The reasons for why some patients bleed from their angioectasias are not fully understood but it has been reported that it may be explained by an acquired von Willebrand syndrome (AVWS). This condition has similar laboratory findings to congenital von Willebrand disease with selective loss of large von Willebrand multimers. The aim of this study was to find out if AVWS or any other bleeding disorder was more common in patients with bleeding from angioectasias than in a control group. METHODS: We compared bleeding tests and coagulation parameters, including von Willebrand multimers, from a group of 23 patients with anemia caused by bleeding from angioectasias, with the results from a control group lacking angioectasias. RESULTS: No significant differences between the two groups were found in coagulation parameters, bleeding time or von Willebrand multimer levels. CONCLUSION: These results do not support a need for routine bleeding tests in cases of bleeding from angioectasias and do not show an overall increased risk of AVWS among these patients.

DNA adducts in normal colonic mucosa from healthy controls and patients with colon polyps and colorectal carcinomas.

Colon cancer is a multistage process where adenomatous polyps developing in a normal mucosa may further progress to neoplasia. DNA adducts are biomarkers linked to exposure to carcinogenic compounds, tumour formation and clinically observed cancer. Such DNA adducts have been detected in the mucosa of colon cancer patients. The aim of this study was to investigate whether there are differences in DNA adduct levels and patterns in mucosa from patients with colon cancer, polyps and non-cancerous controls and whether some DNA adducts could be markers for colon cancer development. Human colonic biopsies were collected from healthy controls (n = 10), polyp patients (n = 22) (from both normal and polyp tissue) and colon cancer patients (n = 32) (from both tumour tissue and adjacent normal mucosa). In 150 tissues specimens (when small amount of tissue, the same type of tissues were pooled from each patient), DNA adduct levels and patterns were analysed by the (32)P-high-performance liquid chromatography method. There were no significant difference in the total levels of DNA adducts between any of the groups. Levels of two single DNA adducts were decreased in mucosa adjacent to tumours as compared to mucosa from healthy controls. One DNA adduct was found only in tumour tissue and adjacent mucosa from the colon cancer patients. A food derived, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-related DNA adduct was detected in 106 of the 150 tissues analysed, but in similar levels in tissues from controls, polyp patients or cancer patients. In conclusion, three individual DNA adducts may be interesting candidates for further evaluation of their possible role as biomarkers in human carcinogenesis. Furthermore, a food-derived PhIP-related adduct contributes to the general DNA adduct pattern in most individuals, indicating a minor role of this adduct in human colon carcinogenesis.

Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn's disease in Swedish men.

OBJECTIVES: Crohn's disease (CD) is characterized by overproduction of proinflammatory cytokines like interleukin (IL)-1beta. Production of mature IL-1beta is dependent on a caspase-1-activating protein complex called the NALP3 inflammasome, composed of NALP3, ASC, and CARD8. NALP3 shares structural similarities with Nod2, and both of these proteins are required for bacteria-induced IL-1beta secretion. The combination of the polymorphisms CARD8 (C10X)and NALP3 (Q705K) was recently shown to be associated with rheumatoid arthritis.Our aim was to investigate whether these combined polymorphisms play a role in the susceptibility to CD. METHODS: The study included 498 CD patients in two cohorts from different regions and 742 control individuals from a Swedish population. DNA was isolated from whole blood. Polymorphisms of (Q705K) NALP3 and (C10X) CARD8, as well as the Nod2 variants, R702W and G908R, were genotyped using the Taqman single nucleotide polymorphism assay. The Nod2 frameshift mutation, L1007fs, was detected by Megabace SNuPe genotyping. RESULTS: Our results show that men who have both the C10X and Q705K alleles in CARD8 and NALP3, and who express wild-type alleles of Nod2 are at an increased risk of developing CD (odds ratio, OR: 3.40 range: 1.32-8.76); P = 0.011). No association with these polymorphisms was found in women (OR: 0.89 (range: 0.44-1.77); P = 0.74). CONCLUSIONS: We suggest a role for combined polymorphisms in CARD8 and NALP3 in the development of CD in men, with obvious sex differences in the genetic susceptibility pattern. These findings give further support to the importance of innate immune responses in CD.

Findings in patients with chronic intestinal dysmotility investigated by capsule endoscopy.

BACKGROUND: Capsule endoscopy (CE) is a unique tool to visualize the mucosa of the small intestine. Chronic intestinal dysmotility (CID) is a group of rare disorders of gastrointestinal motility that often are complicated by bacterial overgrowth. The aim of this study was to determine the prevalence of small bowel mucosal abnormalities in patients with CID. We also studied the usefulness of CE in the diagnosis of intestinal dysmotility. METHODS: We conducted a prospective study using CE in 18 patients; six with myopathic, 11 with neuropathic and one with indeterminate CID. A control group was used for comparison of small bowel transit. RESULTS: Mucosal breaks (erosions and ulcerations) were found in 16/18 (89%) patients. The capsule reached the caecum in 11/18 (61%) patients with a median transit time of 346 minutes. In the control group the capsule reached the caecum in 29/36 (81%) cases with a median transit time of 241 minutes. The difference in transit time was not significant (p = 0.061) in this material. The capsule was retained in the stomach in 3/18 patients. None of the patients developed symptoms or signs of mechanical obstruction. CONCLUSION: A high frequency of mucosal breaks and signs of motility disturbances were seen in CID patients. CE is feasible for the examination of small bowel mucosa in patients with CID. The relevance of observed mucosal abnormalities in CID remains uncertain.

Contribution of the IBD5 locus to Crohn's disease in the Swedish population.

OBJECTIVE: Recent data have controversially suggested that variants of the organic cation transport genes SLC22A4 (OCTN1) and SLC22A5 (OCTN2) are responsible for the contribution of IBD5 to disease susceptibility in Crohn's disease (CD). The objective of this study was to assess the contribution of the SLC22A4 variant (1672T) and SLC22A5 variant (-207C) together with three IBD5 haplotype markers in the previously uninvestigated Swedish CD population. MATERIAL AND METHODS: The study comprised 178 CD patients and 143 healthy controls (HC). Genotyping for IBD5 single nucleotide polymorphisms (SNPs) IGR2096a_1, IGR2198a_1, IGR2230a_1, SLC22A4 1672T and SLC22A5 -207C was carried out using the TaqMan system. Associations with disease susceptibility and disease phenotype were investigated. RESULTS: Strong linkage disequilibrium was observed between the investigated SNPs (D prime >0.92). IGR2096a_1 allelic frequency and homozygosity rates were associated with CD (44% CD versus 33.8% HC, p=0.008, OR=1.55 and 20% CD versus 12% HC, p=0.04, OR=1.93, respectively). Variant allelic frequency of SLC22A4, 1672T (44% versus 36%, p=0.03, OR=1.4) and homozygosity for the SLC22A4, SLC22A5 TC haplotype (1672T, -207C) (21.3% versus 12%, p=0.03, OR=1.78, population attributable risk (PAR)=11%) were associated with CD. There was no association between the allelic frequency of SLC22A5 and CD (46.6% CD versus 41.5% HC, p=0.82). The association of the TC haplotype with CD was not independent of the SNPs representing the extended IBD5 linkage interval. CONCLUSIONS: The IBD5 locus is associated with CD in the Swedish population. The strongest association is with the marker SNP IGR2096a_1, lying p-telomeric to SLC22A4 and SLC22A5. The effect of the TC haplotype was not an independent determinant in this population.

Contribution of CARD15 variants in determining susceptibility to Crohn's disease in Sweden.

OBJECTIVE: Crohn's disease (CD) is a chronic inflammatory bowel disorder caused by environmental and genetic factors. Mutations in the CARD15 gene have been associated with CD. No previous case-control CARD15 study has been performed in the Swedish population. MATERIAL AND METHODS: The study comprised of 321 individuals: 178 with CD and 143 healthy controls (HCs), all from Stockholm County. All were genotyped for the three main CD-associated CARD15 variants (R702W, G908R and 1007fs) and phenotypic associations were investigated. RESULTS: The allele frequencies of the R702W variant (4.5% CD versus 0.7% HC, p=0.008, OR = 6.8) and the G908R variant (2.0% CD versus 0% HC, p=0.045) were more common in CD patients than in controls. No significant difference in1007fs variant allele frequency was found between CD patients and controls (2.0% CD versus 1.7% HC, p = 0.8, OR = 1.1). Carriage of CARD15 variants was more common in the CD patients than in controls (15.2% CD versus 4.2% HC, p = 0.001, OR = 4.1, population attributable risk (PAR) = 11.4%). Genotype-phenotype analysis demonstrated that CARD15 variants were associated with ileal disease (p=0.0006, OR = 9.3, CI = 2.2-34) and protective for colonic CD (p = 0.01, OR = 0.18). An association between CARD15 variants and ileal CD (p=0.004, OR = 6.6) was confirmed by multivariate analyses. CONCLUSIONS: The CARD15 variants R702W and G908R, but not 1007fs, are associated with susceptibility to CD in Stockholm County. Genotype-phenotype analysis shows an association with ileal CD. The contribution of these CARD15 mutations in Swedish CD patients overall is low in relation to studies elsewhere in Central Europe and North America, but is consistent with emerging data from elsewhere in Scandinavia and in Northern Europe.

Experience of endoscopic transanal resections with a urologic resectoscope in 131 patients.

PURPOSE: Endoscopic transanal resection of rectal adenomas and other presumably benign lesions is not widespread. The purpose of this study was to evaluate the efficacy and the safety of endoscopic transanal resection. METHODS: Patients who underwent endoscopic transanal resection at three Stockholm hospitals between 1993 and 2004 were studied retrospectively with respect to patient and lesion characteristics, complications, follow-up time, and recurrence rates. RESULTS: One hundred eighty endoscopic transanal resection procedures were performed in 131 patients. The tissue diagnosis was adenoma in 160 operative cases, cancer in 12 operative cases, and hyperplasia, fibrosis, or normal mucosa in the remaining 8 operative cases. Among the patients with rectal adenomas, one endoscopic transanal resection was sufficient in 77 cases and in 16 cases the surgery was performed in more than one session because of the large size of the adenoma. In 27 cases there were recurrences that needed additional endoscopic transanal resection or other surgery. The median time until recurrence was seven months, but there were no recurrent rectal carcinomas. In 16 operative cases there were complications. Two patients had to undergo a Hartman's procedure as a result of a bowel perforation, and one patient had to be reoperated on because of bleeding. There were no perioperative deaths. The median follow-up time without recurrence was 32 (range, 0-67) months. CONCLUSIONS: Endoscopic transanal resection is a feasible and oncologically safe option for treatment of rectal adenomas, especially in cases where conventional transanal resection or transanal endoscopic microsurgery are unavailable or unsuitable because of the characteristics and localization of the lesion.

Dysplasia in ulcerative colitis--clinical consequences?

BACKGROUND: The overall absolute risk of colorectal cancer (CRC) in longstanding extensive or total ulcerative colitis (UC) is estimated to be 10%-15%. The size of this risk is 6- to 10-times that expected in the background population. By performing complete colonoscopies with multiple biopsies from the entire colon and rectum at regular intervals, surveillance programmes for high-risk UC patients aim at detecting mucosal dysplasia in order to select CRC-prone individuals for prophylactic colectomy. MATERIAL AND METHODS: In many of the hitherto reported surveillance programmes, the UC patients surveyed have a much lesser risk of dying from CRC than do non-surveyed patients, although randomized studies are lacking. The inter- and intra-observer variability of dysplasia among pathologists is a major pitfall in the surveillance of these patients, as well as the influence of active inflammation, making dysplasia assessment difficult. The practical issues discussed here are, to a large extent, based on the recommendations from the Swedish Gastroenterological Association. RESULTS: Screening colonoscopy should be performed approximately 8-10 years after onset of disease. After negative results for screening or surveillance colonoscopy, the intervals between colonoscopies should not exceed 2 years. Biannual investigations of between 8 and 20 years' duration have been adopted in the Swedish studies, with annual colonoscopies from that point. Findings of CRC, a dysplasia-associated lesion or mass (DALM) with high-grade dysplasia (HGD) or low-grade dysplasia (LGD), or HGD in flat mucosa, are considered as indications for proctocolectomy, as well as repeated, confirmed findings of multifocal LGD. The management of unifocal LGD in flat mucosa is controversial (e.g. proctocolectomy or increased surveillance). Polyps may be handled with snare polypectomy. CONCLUSIONS: The safest way of handling UC patients at high risk of developing CRC is by performing regular colonoscopic surveillance. Dysplasia is a useful prognostic marker for subsequent cancer development but has its limitations. A combination of enhanced colonoscopic surveillance using markers that are more sensitive than dysplasia might be the optimal way to manage the increased CRC risk in these patients.

Ursodeoxycholic acid treatment in IBD-patients with colorectal dysplasia and/or DNA-aneuploidy: a prospective, double-blind, randomized controlled pilot study.

BACKGROUND & AIMS: There is an increased risk of colorectal carcinoma (CRC) in patients with longstanding, extensive colonic inflammatory bowel disease (IBD). Primary sclerosing cholangitis, family history of CRC, mucosal dysplasia and DNA-aneuploidy are other risk factors. Recently, results from animal studies have shown that the bile acid ursodeoxycholic acid (UDCA) has a favourable impact on experimentally-induced CRC/neoplasia in rats. The aim of this proof of the concept study was to explore the possible preventive/reverting effects of UDCA in patients with colorectal IBD with existing findings of low grade dysplasia and/or DNA-aneuploidy. PATIENTS AND METHODS: Nineteen patients (13 UC, 6 CD, median age 43 years) with long-standing, extensive IBD (median duration 21 years), with previous findings of low-grade dysplasia and/or DNA-aneuploidy, were randomized to receive either UDCA (500 mg b.i.d) (n=10) or placebo (n=9) in a controlled, double-blind, two-year study. Colonoscopy with multiple biopsies for histopathology and for DNA-flow cytometry was performed at the start and at six-month intervals during the study period. The primary outcome was the need for colectomy due to progression of dysplasia. Changes in dysplasia and DNA-aneuploidy scores were also assessed. RESULTS: There were no significant differences in the overall composed score between the two groups, either at study start or during the study period. In the placebo group one patient had a progression of dysplasia into high-grade and one patient developed DALM with low-grade dysplasia; both had a colectomy. In contrast, no UDCA-treated patient had progression of dysplasia. CONCLUSION: UDCA may prevent further progression of manifest low-grade dysplasia in colorectal IBD. Prolonged treatment or an increased dose may be needed to fully exploit the chemopreventive properties of this compound.

Anxiety, functional health status, and coping ability in patients with ulcerative colitis who are undergoing colonoscopic surveillance.

BACKGROUND: Patients with long-standing extensive ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). High-risk UC patients are nowadays enrolled in surveillance programs to decrease CRC incidence and mortality, although little is known about patients' concerns and anxiety when subjected to colonoscopic surveillance. The aims of this study were to evaluate functional health status, general state of health, anxiety, and coping ability in patients with UC taking part in such a program in a university hospital setting. METHODS: Forty-one patients with long-standing, extensive/total UC in remission (median disease duration, 21.0 years) undergoing surveillance comprised the study group. Twenty patients with extensive disease but with shorter disease duration (median, 8.0 years) and 19 patients with only distal involvement UC acted as controls. Four different self-administered questionnaires (SAQs) were used. The SAQ assessments were made twice in the study group and once in the controls. RESULTS: No statistically significant differences were found in any of the SAQ assessments. The median scores obtained were well within the ranges seen in normal healthy subjects. CONCLUSIONS: Colonoscopic surveillance in long-standing UC does not seem to generate increased anxiety or impairment of functional or general health status among participating patients. Rather, UC patients in clinical remission seem to cope just as well as healthy individuals irrespective of the CRC risk or surveillance procedures.

[Capsule endoscopy is better than other methods. 66 examinations performed at Sodersjukhuset prove a high diagnostic yield]. / Kapselendoskopi slår ut andra metoder. 66 undersökningar vid Södersjukhuset visar på högt diagnostiskt utbyte.

Capsule endoscopy is a non-invasive method to investigate the small intestine by means of a swallowable videocapsule that takes pictures during its passage throughout the gut. The method has been proven to have a high diagnostic yield in obscure GI bleeding and suspected small bowel Crohn's disease in cases where traditional methods have failed. In 63 patients consecutively evaluated by capsule endoscopy pathological lesions were found in 39 (62%), of which angiodysplasias were the most common (33%). Inflammatory changes including Crohn's disease constituted 40% of the findings. Malignant tumors were found in two patients (5%). Half of the patients with patological findings were either medically treated or referred to surgery. Capsule endoscopy is a new method for small bowel examination that has a great potential to replace some older methods with lower diagnostic yield.

Chronic colitis is associated with a reduction of mucosal alkaline sphingomyelinase activity.

BACKGROUND AND AIMS: The hydrolysis of sphingomyelin (SM) generates key molecules regulating cell growth. Animal cancer studies support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. The activity of a specific intestinal alkaline sphingomyelinase (SMase), which hydrolyzes SM, is reduced in colorectal tumors. In this study we measured alkaline SMase activity in patients with longstanding colitis and assessed if a reduction can be used as a marker in surveillance of high risk patients. METHODS: Alkaline SMase activity was measured in 139 colonic biopsies from 34 patients with longstanding, extensive colitis and from 11 controls. Fifteen patients had earlier diagnosis of dysplasia or DNA aneuploidy. Alkaline SMase activity was related to histologic dysplasia and DNA aneuploidy assessed by flow cytometry, patient age, and duration of disease. RESULTS: Alkaline SMase activity was significantly lower in the patient group with and without dysplasia compared with controls (p = 0.006). In biopsies, an association was not found between alkaline SMase activity, dysplasia, or DNA ploidy. However, alkaline SMase activity decreased with age both in patients and controls (p = 0.008). CONCLUSIONS: Reduction of alkaline SMase activity seen in colorectal cancer and adenomas is also present in patients with chronic colitis. It is not complementary to dysplasia or DNA-aneuploidy in the identification of high risk patients. The age-associated decrease of alkaline SMase activity seems to be a general phenomenon indicating premature senescence of the mucosa in longstanding colitis.