Leo G. van Rossum

Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper

Several randomized controlled trials have shown that population‐based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high‐risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population‐based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic‐based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.

High Abstinence Rates in Heroin Addicts by a New Comprehensive Treatment Approach

In this multi-center, naturalistic study, the effectiveness of naltrexone maintenance combined with the Community Reinforcement Approach (CRA) was investigated in detoxified, opioid-dependent patients (N=272). Patients were recruited from methadone maintenance programs. With intention-to-treat analysis, 10 months of treatment yielded abstinence rates of 28% and 32% at 10 and 16 months after detoxification. The cumulative abstinence rate at 16 months was 24%. Quality of life, craving, general psychopathology, use of other psychoactive substances, and addiction severity of the abstinent group significantly improved when compared to the relapsed group. This abstinence-oriented approach appears to be a feasible goal, and remains an important option next to long-term methadone maintenance in the management of opioid dependence.

Alexithymia is associated with gastrointestinal symptoms, but does not predict endoscopy outcome in patients with gastrointestinal symptoms.

Background Alexithymia, where a person has difficulty in distinguishing between emotions and bodily sensations, is considered to be a character trait and a vulnerability factor for various psychosomatic disorders. Assessing alexithymia in patients with gastrointestinal (GI) symptoms before endoscopy might therefore be useful in selecting patients who are more prone to functional GI disorders. Goal To determine whether alexithymia might be a useful factor in predicting GI endoscopy outcomes. Study Patients referred for endoscopy between February 2002 and February 2004 were enrolled. They were asked to report alexithymia on the Toronto Alexithymia Scale-20 2 weeks before endoscopy. Information about endoscopic diagnoses was obtained from medical files. Results A total of 1141 subjects was included (49% male), of whom 245 (21%) reported alexithymia. There was no difference in mean±SD alexithymia scores between patients with (51±12) and without (50±12) an endoscopic organic abnormality at GI endoscopy. When divided into subgroups, according to the most prominent finding at either upper or lower GI endoscopy, there was no association with alexithymia. Patients with alexithymia reported a worse sensation of GI symptoms during the last weeks before enrollment in the study (mean±SD symptom severity score: 42±34 vs. 34±30, respectively; P<0.01). Conclusions Alexithymia is not associated with endoscopic findings, and has therefore no additive value in predicting endoscopy outcomes. Patients with alexithymia more often present with a higher number and more severe GI symptoms.

Comparison of guaiac and immunological fecal occult blood tests in colorectal cancer screening: the patient perspective.

Abstract Objective. Colorectal cancer (CRC) screening programs can decide upon the type of fecal occult blood test (FOBT): the guaiac FOBT (g-FOBT) or the immunological FOBT (i-FOBT). The effectiveness of any screening program depends not only on the diagnostic performance of the screening test but also on the compliance and general acceptance of the test by the public. Any decision on the type of FOBT for CRC screening should also take acceptation and perception into account. The aim of the present study was to study differences in patient perception between i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups in a population based study. Material and methods. Differences in patient perception of i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups were investigated (n = 20,623) by sending a short questionnaire to all invited to the first Dutch CRC screening trial. Results. i-FOBT was perceived significantly more favorable than g-FOBT. About 1275 (32%) participants reported the g-FOBT not easy to use, not easy to perform, disgusting or shameful compared to 742 (16%) for the i-FOBT (p < 0.001). The participation rate was significantly higher in those who received i-FOBT compared to the g-FOBT group: 6159 of 10,322 (60%) versus 4839 of 10,301 (47%) (p < 0.001). Conclusions. These findings support the selection of i-FOBT as the more appropriate test for population screening programs.

Open-Access Upper Gastrointestinal Endoscopy a Decade after the Introduction of Proton Pump Inhibitors and Helicobacter pylori Eradication: A Shift in Endoscopic Findings

Background/Aim: Over the past 15 years, there were considerable changes in factors associated with the development and treatment of upper gastrointestinal symptoms, of which the introduction of proton pump inhibitors and Helicobacter pylori eradication in guidelines for treatment of patients with dyspepsia are the most prominent: findings at open-access upper gastrointestinal endoscopy have not been evaluated properly ever since. This study aims to compare the current prevalence of upper gastrointestinal endoscopic findings to the prevalence 15 years ago. Methods: Data about endoscopic findings of consecutive patients for the first time referred for open-access upper gastrointestinal endoscopy between January 2002 and December 2004 was collected from medical files. The prevalence of each specific finding was compared with data described in three historical populations about 15 years ago. Results: The current and historical study population consisted of 1,286 and 3,062 subjects, respectively. The prevalence of peptic ulcer disease and duodenitis significantly decreased by 12.6% (95% CI: 14.5–10.7) and 2.9% (95% CI: 4.5–1.3), respectively. On the other hand, the prevalence of reflux esophagitis and Barrett’s esophagus both significantly increased by 6.9% (95% CI: 4.2–9.6) and 2.1% (95% CI: 0.8–4.4), respectively. Conclusions: Compared to 15 years ago, the prevalence of specific findings at open-access upper gastrointestinal endoscopy has changed considerably.

Prevalence of gastrointestinal symptoms in alcoholics and the relationship with alexithymia.

Alcohol abuse coincides with a wide variety of clinical, sociological and psychological features and symptoms. Gastrointestinal symptoms are also very common in alcoholics, but the reason is unclear. We aimed to determine the prevalence of alexithymia in alcoholics and furthermore if gastrointestinal symptoms were associated with alexithymia. Out of the 84 alcoholics who completed the alexithymia questionnaire (Toronto Alexithymia Scale, TAS20) and the standard gastrointestinal symptoms questionnaire, 92% reported gastrointestinal symptoms and 54% were alexithymic. Alcoholics above age 43 had more difficulty describing feelings (odds ratio=4.1, confidence interval=1.5-11.4). Almost all measured gastrointestinal symptoms in alcoholics were associated with scores on an alexithymia questionnaire.

Similar fecal immunochemical test results in screening and referral colorectal cancer

AIM To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.

Withdrawal of Personal Genome Service

quency questionnaire. No significant differences between the intervention and control groups were found for key indicators of nutritional status, including the intake of calories, protein, or vitamin D. Successful randomization within clinical trials addresses the equal distribution of known and unknown covariates. Thus, these findings make it unlikely that there were substantial between-group differences in these unmeasured variables at baseline. The variables included (and excluded) from the trial were carefully considered when the protocol was developed. The trial was designed to accommodate the needs of older people after hip fracture who had functional limitations at enrollment. Recruitment and retention of participants is challenging in hip fracture clinical trials.2 Our priority was to design a trial to reliably measure the key outcome variables but minimize the burden of the assessments on the participants as much as possible to ensure adequate recruitment, full completion of assessments, and long-term retention of participants. All assessments were conducted in the patients’ homes, which would have made it difficult to conduct dual-energy X-ray absorptiometry testing for sarcopenia. We recognize that the control group did receive in-person and telephone-based nutritional education that may improve dietary behaviors and increase consumption of protein and vitamin D, whereas the intervention group did not receive this nutritional education. However, it would be expected that if this did have a clinical effect, it would have biased our findings toward the null hypothesis. Combining the exercise program with a nutrition intervention might have increased the treatment effect, but our intent in this trial was to investigate the efficacy of a homebased program with minimal supervision. A combined intervention would have increased the cost and complexity of the intervention and limited its ability to be easily and widely disseminated.

Su1642 Over a Quarter of the General Adult Population Experiences Gastrointestinal Symptoms Influencing Health-Related Quality of Life: Results of 50,000 Questionnaires

BACKGROUND: Esophago-gastrointestinal (EGI) symptoms are frequently reported by patients with eating disorders (ED), who tend to use somatic disturbances to justify modifications of alimentary behaviour. It is not clear if referred symptoms are real, whether they ameliorate after controlled diet or if there are related to psychopathogical traits. AIM: (i) to analyze the prevalence of moderate-severe EGI symptoms, either individual or pooled, and of Minnesota Multiphasic Personality Inventory (MMPI-2 or MMPI-A) scales in hospitalized ED patients and symptoms modifications after 6 months of follow-up; (ii) to correlate EGI symptoms and sds-body mass index (sdsBMI) changes with MMPI scales. METHODS: We enrolled 48 consecutive patients (41 F, median age 15) hospitalized with a diagnosis of ED. Thirty-nine patients (81%) were classified as AN and 9 (19%) as BN. At admission (T1) all patients completed MMPI-2 or MMPI-A and the italian version of a validated questionnaire on gastroesophageal (E) and gastrointestinal (GI) symptoms. EGI questionnaire was then completed at discharge (T2), at 1 month of follow up (T3) and after 6 months (T4). RESULTS: (i) the most frequently reported symptoms classified as moderate-severe were postprandial fullness (70%) and abdominal distention (57%). The most prevalent pychopathological trait with abnormal MMPI score (>55) was depression (67%). During observational period of 6 months (T1-T4), E and GI symptoms significantly decreased (IR 3-19 and 0.5-6.5, IR 1444 and 4-28, p<0.05 and p<0.0001, respectively), as well as sdsBMI (-3.4 -1.7 e -1.5 -0.4; p<0.001). Patients with abnormal scores of Hypochondriasis (HS) had significantly more severe abdominal distention and pooled GI symptoms than patients with normal HS scores (p<0.05 and p<0.005, respectively). (ii) sdsBMI change did not correlate with EGI symptoms improvement (p=NS). Normal HS, Hysteria (HY), Psychoastenia (PT), Schizophrenia (SC) scores were significantly correlated with reduction of postprandial fullness compared to abnormal scores (p<0.05). Abdominal distention improved in all patients, irrespectively of MMPI scores (p<0.05). Pooled E symptoms significantly diminished in patients with normal HY scores vs abnormal (p<0.05), whereas pooled GI symptoms improved irrespectively of high HS and HY scores (p<0.05). All patients showed a reduction in sdsBMI, irrespectively of MMPI scores (p<0.05). CONCLUSIONS: Postprandial fullness and abdominal distention are the most prevalent digestive complaints reported by ED patients. An improvement of sdsBMI is observed in controlled ED patients as well as EGI symptoms. Abnormal MMPI traits may interfere with amelioration of postprandial fullness, but has no influence on abdominal distention, nor on sdsBMI.

S1125 Differences in Fit Results Between Screening and Referred Colorectal Cancer Patients are Explained by Differences in Tissue Tumor Stage

Background Fecal immunochemical tests (FITs) are state of the art in colorectal cancer(CRC) screening. Sensitivity of a single FIT for advanced neoplasia is around 50%. Theoretically, as blood loss from colon tumors can be intermittent, sensitivity of FITs could improve by double sampling. This study aims to compare the sensitivity of single FIT sampling and double FIT sampling at different cut-off values, for the detection of advanced neoplasia. Methods All subjects (≥18 years) scheduled for elective colonoscopy in three participating centers in the Amsterdam area were asked to perform FITs (OC sensor®) on two consecutive days. FIT results were compared with colonoscopy and histology as gold standard. Test performance of single FIT was compared to the sensitivity of double FIT sampling. Double FIT sampling was considered positive if one of both FITs was higher than the cut-off value. Test performances were evaluated at cut-off values ranging from 50-150ng/ml (incremental steps of 25ng/ml). Results Of 1105 subjects who performed two FITs and underwent total colonoscopy, 140 (9,4%) had advanced neoplasia (AN), of which 34 were CRC and 106 were advanced adenomas (AA). Of the CRC cases, 70% were Dukes stage A or B (stage unknown in 2). Positivity rates for single FIT ranged from 11-17%, and for double FIT from 14-23%. At the same cut-off value for positivity, sensitivity of double FIT sampling was higher than sensitivity of single FIT sampling. For any particular specificity (e.g. 90%), the sensitivity of double FIT was slightly higher than that of single FIT at a lower cut-off value (see table), but these differences were not statistically significant. Conclusions Two fold sampling of FIT does increase sensitivity for advanced neoplasia. However, at a given specificity, sensitivity of double sampling is comparable to single sampling at a lower cutoff value. Sensitivity and specificity of single and double FIT testing for the detection of advanced neoplasia