The prevalence of celiac disease and the appropriateness of the diagnosis in family medicine setting could be lower than expected.

OBJECTIVE: To assess the prevalence of celiac disease (CD) and the appropriateness of this diagnosis in the family medicine setting in Italy. PATIENTS AND METHODS: The electronic databases of 16 general practitioners working in Rome (Italy) were analyzed. The prevalence of CD according to the Italian pathology identification code issued by the Italian National Health System was assessed. In addition, patients registered as having celiac disease without being assigned a pathology identification code were interviewed. RESULTS: Overall, a population of 22,064 patients was analyzed. 91 patients had a diagnosis of CD (0.41%), 60 of whom had a pathology identification code (0.27%), and 31 did not (0.14%). 29 of these patients were interviewed, 16 (17.58% of the CD recorded patients) of whom reported being on a gluten-free or gluten restricted diet, with reported improvement in their clinical symptoms. Half of them further stated that they would not agree to resume a restriction free diet in order to make a definitive CD diagnosis, due to the risk of symptom recurrence. CONCLUSIONS: In a family medicine setting, the prevalence of CD seems to be lower than expected, and one third of patients diagnosed with CD do not fulfill all diagnostic criteria. Any effort to improve the diagnostic work-up for CD should also be made in this setting.

Recognizing megatsunamis in Mediterranean deep sea sediments based on the massive deposits of the 365 CE Crete event.

The Mediterranean Sea hosts two subduction systems along the convergent Africa-Eurasia plate boundary that have produced strong ground shaking and generated tsunamis. Based on historical descriptions and sedimentary records, one of these events, in 365 CE, impacted a broad geographical area, including tsunami evidence for distances of 700-800 km from the source event, qualifying it as a 'megatsunami'. Understanding how megatsunamis are produced, and where they are more likely, requires a better understanding of the different secondary processes linked to these events such as massive slope failures, multiple turbidity current generation, and basin seiching. Our sedimentary records from an extensive collection of cores located in distal and disconnected basins, identify turbidites which are analyzed using granulometry, elemental (XRF), micropaleontological, and geochemical data in order to reconstruct their coastal or marine source. The results show that the 365 CE basin floor sediments are a mixture of inner shelf and slope materials. The tsunami wave produced multiple far-field slope failures that resulted in stacked basal turbidites. It also caused transport of continent-derived organic carbon and deposition over basal turbidites and into isolated basins of the deep ocean. The composition of sediment in isolated basins suggests their deposition by large-scale sheet like flows similar to what has been caused by the Tohoku earthquake associated tsunamis. This is significant for rectifying and resolving where risk is greatest and how cross-basin tsunamis are generated. Based on these results, estimates of the underlying deposits from the same locations were interpreted as possible older megatsunamis.

From hazardous asbestos containing wastes (ACW) to new secondary raw material through a new sustainable inertization process: A multimethodological mineralogical study.

Nowadays, asbestos-containing wastes (ACW) still represent an important environmental problem and a severe health hazard due to the well known pulmonary diseases derived from asbestos fibers inhalation. Except for a very few cases, ACW are currently confined in controlled landfills, giving rise to increasingly high amounts of still hazardous wastes. A promising alternative to landfill confinement is represented by ACW inertization, but the high cost of the inertization processes so far proposed by the scientific community have hampered the creation of actually operative plants. In this paper, we explore the possibility to use an innovative process that ensures the obtainment of asbestos-free inert material in an exceptionally short processing time, thus greatly reducing cost-related problems. The efficacy of the inertization process has been verified through accurate mineralogical investigations on both chrysotile and crocidolite de-activated fibers, through X-ray diffraction, scanning and transmission electron microscopy. Overall mineralogical, microstructural and granulometric characteristics of the inert bulk material suggest that it could be successfully re-used as a secondary raw material in ceramic industries. This innovative inertization procedure could therefore provide an effective and economically sustainable solution for ACW management.

Impact of treatments on fecal microbiota and fecal metabolome in symptomatic uncomplicated diverticular disease of the colon: a pilot study.

Symptomatic uncomplicated diverticular disease (SUDD) affects 50% of people having diverticulosis. We performed a pilot study assessing the effect of current treatments on fecal microbiota and metabolome in SUDD. Thirteen consecutive females with SUDD were treated with a 2-week therapeutic trial of 30 g/day fiber supplementation (3 patients), 1.6 g/day of mesalazine (3 patients), 900 billion/day of probiotic mixture VivoMixx® (3 patients), or 800 mg/day of rifaximin (4 patients). Stool samples were collected at entry (T0), at the end of the 2-week therapeutic course (T1), and 30 (T2) and 60 days (T3) after the end of the therapeutic course. Real-time PCR quantified targeted microorganisms. Fecal metabolome patterns were studied by high-resolution proton NMR spectroscopy. At cumulative analysis, symptoms significantly decreased at each time point during follow-up (p less than 0.0001), and only left-lower quadrant pain increased again at T3. The overall bacterial quantity was not altered by the treatments. The amount of Akkermansia muciniphila species was significantly reduced at T1 (p=0.017) and at T2 (p=0.026), while at T3 the reduction was not significant in comparison to enrollment (p=0.090). Fecal molecular profile showed significant changes at T1 and T2, while at T3 it became similar to that of T0. Differences were found for 18 of the quantified molecules (tryptophan, phenylalanine, tyrosine, 4-hydroxyphenylacetate, urocanate, X-6.363, X-5.779, uridylate, galactose, X-4.197, threonine, sarcosine, methionine, 2-oxoisocaproate, 5-aminolevulinate, alanine, leucine, valerate). Metabolome and microbiota changed in patients with SUDD under treatment, confirming a possible role of dysbiosis/dysmetabolome in the pathology.

Assessment of nutritional status and therapy in emergency Medicine settings.

Hospital malnutrition is becoming a clinical concern. Our aim was to determine the prevalence of hospital malnutrition through Nutritional Risk Screening 2002 (NRS) and to evaluate nutritional risk through a prospective study. Nutritional status was assessed collecting anthropometric parameters together with the data relating to the diseases in the medical records of patients admitted to the Department of Emergency Medicine of the "Sant'Eugenio" Hospital. One hundred and sixty patients were retrospectively enrolled during a 3-month observational period. The risk of malnutrition was detected in 52% of patients (of whom 38% at risk and 62% at serious risk). The NRS score was positively correlated with patient age, days between hospital admission and nutritional assessment, disease severity, length of hospital stay and catabolism (p less than 0.05); Basal Energy Expenditure (BEE) and mean arm circumference (MUAC) were negatively correlated with positive outcome (p less than 0.05). No correlations were found in the NRS score, gender, height, weight, Body Mass Index (BMI) and Total Energetic Expenditure (TEE) (p=n.s). A high prevalence of the risk of malnutrition may be detected in the emergency medicine setting, particularly in the geriatric population. The NRS score is not strictly related to BMI, but rather is an excellent tool for disease prognosis, as well as nutritional screening.

Decreasing efficacy of the standard seven-day triple therapy containing amoxycillin and clarithromycin in curing Helicobacter pylori infection in clinical setting in Italy: a 10-year follow-up study.

AIM: The aim of the present study was to assess the efficacy of the standard triple therapy containing PPI plus amoxycillin and clarithromycin in curing Helicobacter pylori (H. pylori) infection during a long-term period. METHODS: A retrospective analysis was conducted on 1497 consecutive dyspeptic patients with proven H. pylori infection and enrolled from 1996 to 2006. Patients received a standard triple therapy with proton pump inhibitor (PPI) plus amoxicillin 1 g and clarithromycin 500 mg for 7 days (all twice daily) plus PPI every day for further 4 weeks in case of active peptic ulcer or severe gastritis detected at endoscopy. One month after conclusion of therapy, endoscopy was performed in those patients for whom the examinations were clinically relevant. The remaining patients were checked by ¹³C-urea breath test. RESULTS: The overall H. pylori eradication rate was 70.41% (on intention-to-treat analysis). However, it decreased significantly during the observation period, ranging from 90% (95% CI 87.14% to 93.91%) in 1996 to 51.11% (95% CI 48.14% to 55.91%) in 2006 (on i-t-t analysis) (P=0.001). No difference in eradicating the was found infection between Puglia and Lazio (1996: P=0.39; 2006: P=0.64). CONCLUSION: Standard triple therapy does not appear anymore a valid therapeutic strategy for the management of H. pylori infection in clinical practice.

Expression of basic fibroblastic growth factor, syndecan 1 and tumour necrosis factor α in resected acute colonic diverticulitis.

AIM: Inflammation and fibrosis are present in both colonic diverticulitis and Crohn's disease (CD). The molecular pattern of basic fibroblastic growth factor (bFGF) and syndecan 1 (SD1) expression is altered in stenosing CD, but their expression in resected complicated colonic diverticulitis (ACD) is unknown. METHOD: The expression of bFGF, SD1 and tumour necrosis factor α (TNF-α) in 20 patients after resection of ACD was compared with 15 patients having a resection for CD. Analysis was conducted using real-time reverse transcriptase polymerase chain reaction in biopsy samples. RESULTS: Lymphocytic and neutrophil inflammation scores were similar in both groups (P = 0.771 and P = 0.562). TNF-α and bFGF expression was significantly higher in ACD than in CD (P < 0.0001 and P = 0.009). SD1 expression was similar in both groups (P = 0.841). CONCLUSION: TNF-α and bFGF are significantly overexpressed in ACD with respect to CD, whilst SD1 levels do not differ. The findings confirm that inflammation and its association with altered molecular patterns of mucosal healing may play an important role in the phenotype of the diseases.

Randomised clinical trial: mesalazine and/or probiotics in maintaining remission of symptomatic uncomplicated diverticular disease--a double-blind, randomised, placebo-controlled study.

BACKGROUND: Placebo-controlled studies in maintaining remission of symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking. AIM: To assess the effectiveness of mesalazine and/or probiotics in maintaining remission in SUDD. METHODS: A multicentre, double-blind, placebo-controlled study was conducted. Two hundred and ten patients were randomly enrolled in a double-blind fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24 billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp. DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG placebo plus mesalazine placebo). Patients received treatment for 10 days/month for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal pain during follow-up, scored as ≥5 (0: best; 10: worst) for at least 24 consecutive hours. RESULTS: Recurrence of SUDD occurred in no (0%) patient in group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs. L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P = 0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six group P cases and in one group L case (P = 0.003). CONCLUSION: Both cyclic mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given in combination, appear to be better than placebo for maintaining remission of symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov: NCT01534754).

Effectiveness of different therapeutic strategies in preventing diverticulitis recurrence.

BACKGROUND: Colonic diverticulitis shows a high recurrence rate. AIMS: To assess the efficacy of three different therapeutic strategies in preventing diverticulitis recurrence. MATERIALS AND METHODS: One hundred thirty patients suffering from Acute Uncomplicated Diverticulitis (AUD) (81 males, 49 females, mean age 64.71 years, range 40-85) were prospectively assessed. After obtaining remission, considered present when both endoscopic and histological damage were absent, the patients were treated with mesalazine 1.6 g/day (59 patients, group A), or rifaximin 800 mg/day for 7 days every month (52 patients, group B). Clinical, endoscopic and histological follow-up was performed after 6, 12 and thereafter every 12 months after diagnosis of AUD. RESULTS: Seven patients were excluded from final evaluation because they were lost to follow-up. Fifty-five group A patients and 49 group B patients patients were available for the final assessment at the end of a 24-month follow-up. Sustained remission was significantly higher in group A with respect to group B. CONCLUSIONS: Patients taking mesalazine have lower risk of diverticulitis recurrence than patients taking rifaximin because of the lower prevalence of persisting endoscopic and histological inflammation.

Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

BACKGROUND: Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). METHODS: Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. KEY RESULTS: The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. CONCLUSIONS & INFERENCES: Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD.

Musosal tumour necrosis factor α in diverticular disease of the colon is overexpressed with disease severity.

AIM: Inflammation occurs in diverticular disease (DD), but there is little information on inflammatory cytokines such as tumour necrosis factor α (TNF-α). The aim of this study was to assess TNF-α expression in DD and to see whether it is related to the severity of the disease. METHOD: Twenty-four patients with symptomatic DD were divided into those with acute uncomplicated diverticulitis (AUD) (12 patients) and those with symptomatic uncomplicated diverticular disease (SUDD) (12 patients). Twelve further patients with asymptomatic diverticulosis (AD), six with segmental colitis associated with diverticulosis (SCAD), with ulcerative colitis (UC) and six healthy individuals (HC) were enrolled as controls. TNF-α expression in the colonic mucosa was assessed by the amount of mRNA codifying for the synthesis of TNF-α. RESULTS: TNF-α expression was significantly higher in AUD than in HC (P=0.0007), in AD (P=0.0001) and in SUDD (P=0.0179). It was significantly higher also in SUDD than in HC (P=0.0007) and in AD (P=0.0001). TNF-α expression in AUD did not differ significantly from that in UC (P=0.0678) and SCAD (P=0.0610). It was significantly higher in UC, SCAD and AUD than in SUDD (P=0.0007, P=0.0001, P=0.0179). CONCLUSION: TNF-α expression in DD seems to be related to the severity of the disease. In particular, it appears to be overexpressed in DD with inflammation (AUD and SUDD) compared with DD without (AD).

Role of fecal calprotectin in the diagnosis and treatment of segmental colitis associated with diverticulosis.

AIM: Information about fecal calprotectin (FC) in segmental colitis associated with diverticulosis (SCAD) is lacking. We assessed FC in SCAD, comparing it healthy controls (HC), irritable bowel syndrome (IBS), diverticular disease (DD), ulcerative colitis (UC). Moreover, we compared FC levels in different degrees of SCAD and assessed FC SCAD before and after treatment. METHODS: Twenty-seven consecutive patients with a new endoscopic diagnosis of SCAD, and 16 patients for each control group, underwent to FC assessment. FC was assessed by semi-quantitative method. RESULTS: FC was not increased in HC and in IBS patients, whilst it was increased in DD, SCAD, and UC. FC concentration was higher in SCAD and UC than in DD (SCAD vs. DD, P=0.05). No difference was found in FC concentration between SCAD and UC (P=0.213), as well as between different degree of SCAD (P= 0.178). After treatment, FC values decreased to normal values in all patients obtaining remission (P<0.0005). Three patients experienced still symptoms (one SCAD type B and two SCAD type D patients), and in all of them FC was still detectable. CONCLUSION: FC may be useful in differentiating SCAD from functional syndromes. Moreover, it may be useful in assessing response to therapy.

Inflammatory manifestations at colonoscopy in patients with colonic diverticular disease.

BACKGROUND: Ulcerative colitis with diverticulosis (UCD), segmental colitis associated with diverticulosis (SCAD) and acute uncomplicated diverticulitis (AUD) may affect the same colonic regions, but the real incidence of these entities in clinical practice is unknown. AIM: To assess the incidence and the endoscopic findings of UCD, SCAD and AUD. METHODS: From January 2004 to June 2009, 8525 consecutive colonoscopies were performed. Diagnosis of the diseases was based on specific endoscopic and histological (UCD and SCAD), and on endoscopic and radiological (AUD) patterns. RESULTS: Ulcerative colitis with diverticulosis was diagnosed in 25 patients (0.3%), SCAD was diagnosed in 129 patients (2%) and AUD was diagnosed in 130 patients (2%). In UCD, the inflammation in colonic area harbouring diverticula always affects the overall colonic mucosa in all cases, involving also diverticular orifices. The endoscopic characteristic of SCAD is that inflammation is mainly detected within the inter-diverticular mucosa without involvement of the diverticular orifices. In AUD, the inflammation affects primarily diverticular orifice and peri-diverticular mucosa. CONCLUSIONS: In clinical practice, the incidence of mucosal inflammation in the presence of colonic diverticular disease is low and endoscopy is the mainstay of differential diagnosis.

Prevalence of celiac disease and symptoms in relatives of patients with celiac disease.

BACKGROUND AND OBJECTIVES: We determined the prevalence and clinical features of celiac disease (CD) in family-members (FMs) of a population-based cohort of index cases. MATERIALS AND METHODS: We recruited 108 CD index cases: mean age at diagnosis, 23.0 years (range, 1.5-45.2 years); 81 (75%) female. Three-hundred twelve (mean age, 41.6 years; 219 [70%] female) of FMs were analyzed. 153 (49%) were parents, 24 (7.7%) were children, 69 (22.2%) were siblings, 66 (21.1%) were second degree FMs. RESULTS: CD was diagnosed in 63 subjects (20.1%, 21 males and 42 females, mean age 34.24 years, range 2-81 years). Classic, subclinical, and silent forms of CD were recognized in 18 [28.6% (6 siblings, 6 parents, 3 child, 3 second-degree FMs)], in 27 [45.8% (9 siblings, 3 parent, 15 second-degree FMs)], and in 18 [28.6% (6 siblings, 6 parents, 6 second-degree FMs)] cases, respectively. Most of patients suffering from "classical" (18/63 patients, 28.7%) and "subclinical" (27/63 patients, 42.9%) form of CD were older than patients suffering from "silent " CD (18/63 patients, 28.7%) (p=0.01). Most of patients suffering from subclinical disease showed autoimmune diseases (Hashimoto's thyroiditis, and psoriasis), and other atypical symptoms, as gastroesophageal reflux disease (GERD), were also recorded. CONCLUSIONS: We found an high-prevalence of CD between CD FMs, and most of them were olygo- or asymptomatic.

Safety and effectiveness of infliximab for inflammatory bowel diseases in clinical practice.

BACKGROUND AND OBJECTIVES: Our aim was to assess the efficacy and safety of infliximab (IFX) in clinical practice in three Primary Care, Hospital Centers. MATERIAL AND METHODS: From September 2004 to December 2008 62 patients (28 males, 34 females, mean age 30.25 years, range 15-55 years), affected by ulcerative colitis (UC) (23 pts) or by Crohn's disease (CD) (39 patients) were treated. Clinical efficacy, safety, mucosal healing and quality of life were assessed both in UC and CD. RESULTS: A total of 746 infusions were performed. IFX was administered for a mean of 26 months (range 8-44 months). 33/39 (84.61%) pts with CD were in remission under treatment with IFX for a mean time of 19 months (range 12-44 months). Mean Crohn Disease Activity Index (CDAI) score decreased from 295 (range 258-346) to 136 (range 98-136) (p < 0.005). Inflammatory Bowel Disease Quality of Life (IBDQL) improved from 48 (at entry) to 198 (at the end of the study) (p < 0.005). 20/23 (86.95%) patients with UC were in remission under treatment with IFX for a mean of 18 months (range 8-34 months). Mean Disease Activity Index (DAI) decreased from 11 (range 9-12) to < 3 (range 2-3) (p < 0.05). Mean Mayo Subscore for Endoscopy decreased from 3 to < 1 (range 0-1). IBDQL improved from 56 (at entry) to 194 (at the end of the study) (p < 0.005). Only 5 patients (8.06%) experienced side-effects. CONCLUSIONS: Long-term outpatients treatment with IFX seems to be safe and effective in managing patients affected by IBD in clinical practice.

The endoscopic spectrum of segmental colitis associated with diverticulosis.

OBJECTIVE: An endoscopic classification of 'Segmental colitis associated with diverticulosis' (SCAD) is lacking. Our aim was therefore to assess the endoscopic spectrum of SCAD, comparing it with the histological and clinical features. METHOD: A prospective study was performed from January 2004 to October 2007. Diagnosis of SCAD was made on the basis of specific endoscopic and histological patterns. RESULTS: A total of 6230 consecutive colonoscopies were performed during the study period. SCAD was diagnosed in 92 (1.48%) patients, with four endoscopic patterns: pattern A, 'crescentic fold disease' (52.20%); pattern B, 'Mild-to moderate ulcerative colitis-like' pattern (30.40%); pattern C, 'Crohn's disease colitis-like' pattern (10.90%); pattern D, 'Severe ulcerative colitis-like' pattern (6.50%). Most patients with patterns A (58.33%, P < 0.018) and B (89.29%, P < 0.00001) showed histological alterations resembling moderate ulcerative colitis (UC). In pattern C, larger histological variability was found (P < 0.01). All patients showing pattern D showed the typical histological alteration changes of severe UC (P < 0.0001). In pattern A (60.42%, P = n.s.) and pattern B (46.43%, P = n.s.), diarrhoea was the most common symptom whilst abdominal pain was the most frequent in pattern C (50%, P = n.s.) and pattern D (83.33%, P = n.s.) patients. CONCLUSIONS: Endoscopic patterns of SCAD may range from mild to severe inflammation. The histopathological findings but not clinical features showed a statistically significant association with the degree of endoscopic severity.

Effect of mesalazine on epithelial cell proliferation in colonic diverticular disease.

BACKGROUND AND AIMS: Increased epithelial cell proliferation may be detected in diverticular disease, but antibiotics have failed in reducing it. We assess therefore the effect of mesalazine on epithelial cell proliferation in diverticular disease. METHODS: A prospective study was conducted on 20 consecutive patients with a new endoscopic diagnosis of symptomatic uncomplicated diverticular disease. The patients were treated with mesalazine 1.6 mg/day for 1 year. The Ki-67 antigen index of the whole crypt and in the upper third was separately evaluated before and after starting the treatment. RESULTS: Cell proliferation index was higher in diverticular disease patients than healthy controls both in the whole crypt (median 6.7%, range 2-9% vs. median 1.6%, range 1-3%, p=0.001) and in the upper third of the crypt (median 6.8%, range 2-8% vs. median 1.8%, range 1-3%, p=0.001). Cell proliferation decreased throughout the follow-up. In the whole crypt it was 6.7% at entry and 3.8% at the end of treatment (p<0.005), whereas it was 6.8% at entry and 2.9% at the end of treatment in the upper third of the crypt (p<0.005). CONCLUSIONS: We found mesalazine effective in reducing the colonic cell proliferation in long-term treatment for colonic diverticular disease.

Effectiveness of the CRCAPRO program in identifying patients suspected for HNPCC.

Subjects affected by hereditary non-polyposis colorectal cancer exhibit a high susceptibility to colon and extracolonic tumours, due to MMR gene defects. Revised Bethesda criteria are used to select patients as candidates for genetic tests. Recently, the CRCAPRO model has been developed, based on family history of colorectal and endometrial cancers. Our study aims to evaluate the reliability of CRCAPRO in identifying mutation carriers. We used the CRCAPRO program to evaluate carrier probability risk in 99 patients fulfilling Amsterdam or Bethesda guidelines. MLH1 and MSH2 were studied by direct sequencing in all the 99 patients, and the study of microsatellite instability and of MMR proteins expression was performed. Nine MLH1 and nine MSH2 germline mutations were identified. Five out of the nine patients with MLH1 mutation showed a CRCAPRO risk evaluation of less than 20%. The same happened for four out of nine patients with MSH2 mutation. Of the 17 patients with an estimated risk of more than 80%, only four harboured a mutation, all in the MSH2 gene. The highest risk calculated by the CRCAPRO system in the nine carriers of a MLH1 mutation has been 31.7%. In our experience, the CRCAPRO program sensitivity and specificity appears to be low but needs to be further evaluated in larger samples.