René W. van der Hulst

Treatment of Helicobacter pylori Infection: A Review of the World Literature

Background.None of the currently used anti‐Helicobacter pylori drug regimens cures the infection 100%, and cure results still vary considerably. The present article reviews the effectiveness of currently used antimicrobial regimens, aimed to cure H. pylori infection.

Helicobacter pylori Reinfection Is Virtually Absent after Successful Eradication

This study examined whether reinfection or recrudescence accounts for the reappearance of Helicobacter pylori infection after apparent successful eradication. In a prospective study, 173 patients cured from H. pylori infection underwent follow-up endoscopies, with biopsies for culture and histopathology, every 3 months during the first year after treatment. Subsequently, elective half-yearly endoscopies were performed in 124 patients; the remaining 49 underwent follow-up endoscopy only in 1995. At reappearing infection, DNA profiles of pretreatment and recurrent strains were compared. After 3.5 years (range, 1.0-9.2), H. pylori infection recurred in 9 patients (5.2%). Reappearing infections were classified as endoscopically transmitted reinfection (n = 2), unclassified because of loss of pretreatment isolate (n = 1), or recrudescence (identical DNA patterns before and after treatment; n = 6). The reappearance rate of infection, discarding endoscopic transmission, was 1.2% (7/601 H. pylori-negative patient-years). There was virtually no reinfection with H. pylori after eradication in this adult Western population. These data do not rule out acquisition of H. pylori.

Acute Pancreatitis and Concomitant Use of Pancreatitis-Associated Drugs

OBJECTIVES:Drug-induced pancreatitis (DIP) is considered a relative rare disease entity, perhaps due to lack of recognition. The objective of this study was to evaluate the prevalence of pancreatitis-associated drugs in a Dutch cohort of patients admitted for acute pancreatitis (AP) and to identify the proportion AP possibly attributable to the use of drugs.METHODS:This was a multicenter observational study (EARL study). Etiology, disease course, use of pancreatitis-associated drugs at hospital admittance, and discontinuation of these drugs were evaluated. Drugs were scored by means of an evidence-based DIP classification system.RESULTS:The first documented hospital admissions of 168 patients were analyzed. In all, 70 out of 168 (41.6%; 95% confidence interval (CI): 34.5–49.2%) patients used pancreatitis-associated drugs at admission. In 26.2% (44/168; 95% CI: 20.1–33.3%) of cases, at least one class I pancreatitis-associated drug was used. Possibly DIP was present in 12.5% (21/168; 95% CI: 8.3–18.4%); in less than half of these patients (9/21 or 42.9%; 95% CI: 24.5–63.5%), the prescribed drugs were actually discontinued, with no recurrence of AP later on. Among the remaining 12 patients without discontinuation of their drugs use and in absence of an alternative etiologic cause of AP, 8 patients used a class I pancreatitis-associated drug, representing 4.8% (8/168, 95% CI: 2.4–9.1%) of the total study population.CONCLUSIONS:In this series, a remarkably high percentage of patients who were admitted because of an attack of AP used pancreatitis-associated drugs. Physicians should be more aware of the possibility of DIP in patients with otherwise unexplained AP and act appropriately by discontinuation of the drug.

Prevalence of Helicobacter pylori infection in stress-induced gastric mucosal injury

Objective: To determine the role of Helicobacter pylori infection in critically ill patients admitted to the intensive care unit in the formation of gastric and duodenal mucosal injury in these patients. Design and setting: Prospective cohort analysis in an 18-bed mixed medical and surgical closed format ICU in a teaching hospital. Patients: Fifty consecutive patients admitted to the intensive care unit for emergency reasons and requiring mechanical ventilation were included. Interventions: H. pylori infection was detected by the laser-assisted ratio analyzer [13C]urea breath test (UBT). Gastric and duodenal mucosal lesions were assessed by upper gastrointestinal endoscopy and classified as minor (up to five erosions or submucosal hemorrhages) or major (more than five erosions or submucosal hemorrhages) mucosal injury. Measurements and main results: Six patients were not eligible because the UBT could not be processed. Of the 44 eligible patients 22 were H. pylori positive by UBT and 22 H. pylori negative. Either minor or major gastric mucosal injury was found on endoscopy in 66%. Of the 29 patients with minor mucosal injury 10 (34.5%) were infected with H. pylori as indicated by positive LARA 13C-UBT. In contrast, of the 15 patients with major mucosal injury 12 (80%) were infected with H. pylori (p=0.004). H. pylori was the only risk factor significantly associated with major mucosal injury in a multiple regression analysis (p=0.019). Conclusion: The severity of gastric and duodenal mucosal injury in critically ill patients during mechanical ventilation is significantly correlated with the presence of H. pylori infection.

Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results

BACKGROUND Colorectal cancer screening by fecal immunochemical tests (FITs) is hampered by frequent false-positive (FP) results and thereby the risk of complications and strain on colonoscopy capacity. Hemorrhoids might be a plausible cause of FP results. OBJECTIVE To determine the contribution of hemorrhoids to the frequency of FP FIT results. DESIGN Retrospective analysis from prospective cohort study. SETTING Five large teaching hospitals, including 1 academic hospital. PATIENTS All subjects scheduled for elective colonoscopy. INTERVENTIONS FIT before bowel preparation. MAIN OUTCOME MEASUREMENTS Frequency of FP FIT results in subjects with hemorrhoids as the only relevant abnormality compared with FP FIT results in subjects with no relevant abnormalities. Logistic regression analysis to determine colonic abnormalities influencing FP results. RESULTS In 2855 patients, 434 had positive FIT results: 213 had advanced neoplasia and 221 had FP results. In 9 individuals (4.1%; 95% CI, 1.4-6.8) with an FP FIT result, hemorrhoids were the only abnormality. In univariate unadjusted analysis, subjects with hemorrhoids as the only abnormality did not have more positive results (9/134; 6.7%) compared with subjects without any abnormalities (43/886; 4.9%; P = .396). Logistic regression identified hemorrhoids, nonadvanced polyps, and a group of miscellaneous abnormalities, all significantly influencing false positivity. Of 1000 subjects with hemorrhoids, 67 would have FP results, of whom 18 would have FP results because of hemorrhoids only. LIMITATIONS Potential underreporting of hemorrhoids; high-risk individuals. CONCLUSIONS Hemorrhoids in individuals participating in colorectal cancer screening will probably not lead to a substantial number of false-positive test results.

Current guidelines for the eradication of Helicobacter pylori in peptic ulcer disease

SummaryPharmacological suppression of gastric acid secretion has traditionally been the most rational approach to healing ulcers successfully. However, ulcers initially healed using antisecretory therapy have a tendency to relapse after treatment is withdrawn. This tendency is altered definitively by eradication of Helicobacter pylori. Antimicrobial therapy should be given to all patients with documented duodenal and gastric ulcer associated with H. pylori infection.The optimal therapeutic regimen to eradicate, H. pylori is still not completely clear. The requirement for treatment to be effective in more than 90% of patients makes monotherapy and dual therapy inappropriate. Bismuth-based triple therapy (bismuth, tetracycline and metronidazole) is highly efficacious if the H. pylori strain is sensitive to metronidazole and the patient is compliant, but adverse effects often occur. Triple therapy consisting of omeprazole and 2 antimicrobials (clarithromycin and/or amoxicillin and/or metronidazole) and quadruple therapy (bismuth-based triple therapy plus omeprazole) are both very effective and patient compliance may be better because of the shortened (1 week) course. Preliminary data indicate that the efficacy of the regimen is not influenced by imidazole resistance.Eradication of H. pylori prevents complications and relapses of peptic ulcer disease and is a cost-effective option compared with maintenance acid-suppressive therapy.

Faecal immunochemical test accuracy in patients referred for surveillance colonoscopy: a multi-centre cohort study

BackgroundGiven the increasing burden on colonoscopy capacity, it has been suggested that faecal immunochemical test (FIT) results could guide surveillance colonoscopy intervals. Against this background, we have evaluated the test accuracy of single and double FIT sampling to detect colorectal cancer (CRC) and/or advanced adenomas in an asymptomatic colonoscopy-controlled high-risk population.MethodsCohort study of asymptomatic high-risk patients (personal history of adenomas/CRC or family history of CRC), who provided one or two FITs before elective colonoscopy. Test accuracy of FIT for detection of CRC and advanced adenomas was determined (cut-off level 50 ng/ml).Results1,041 patients provided a FIT (516 personal history of adenomas, 172 personal history of CRC and 353 family history of CRC). Five CRCs (0.5%) and 101 advanced adenomas (9.7%) were detected by colonoscopy. Single FIT sampling resulted in a sensitivity, specificity, PPV and NPV for CRC of 80%, 89%, 3% and 99.9%, respectively, and for advanced adenoma of 28%, 91%, 24% and 92%, respectively. Double FIT sampling did not result in a significantly higher sensitivity for advanced neoplasia. Simulation of multiple screening rounds indicated that sensitivity of FIT for advanced adenoma could reach 81% after 5 screening rounds.ConclusionsIn once-only FIT sampling before surveillance colonoscopy, 70% of advanced neoplasia were missed. A simulation approach indicates that multiple screening rounds may be more promising in detecting advanced neoplasia and could potentially alleviate endoscopic burden.

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.

S1123 Double Versus Single Sampling of Fecal Immunochemical Tests for Colorectal Cancer Screening; Added Value or Added Costs?

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

930 Comparing Three Different Strategies of Double Sampling by Fecal Immunochemical Tests for Detection of Advanced Colorectal Neoplasm's

Background Fecal Immunochemical Tests (FITs) are widely used for Colorectal Cancer (CRC) screening. Some sampling schemes use one-day FIT testing, whereas others use twoday FIT testing. Data on sensitivity and specificity of two-day FIT testing are lacking. This study aims to compare the difference in sensitivity and specificity of three different strategies of two-day FIT sampling, at different cut-off values. Methods In three hospitals in the Amsterdam area, all subjects ≥18 years who were referred for elective colonoscopy were asked to perform a FIT (OC sensor®) on two consecutive days. Colonoscopy and histology were considered as gold standard. Two-day FIT sampling was defined positive in three different ways: 1) when at least one of two FITs was above the cut-off value (FIT+), 2) when both FITs were above the cut-off value(FIT++), and 3) when the geometric mean of two FITs was above the cut-off value (FITmean). Test performance of all three strategies was evaluated at cut-off values of 50, 75 and 100ng/ml. Results In 1105 subjects with complete colonoscopy, 140 (9,4%) AN were found (34 CRCs and 106 advanced adenomas). Of the CRC cases, 70% were Dukes stage A or B (stage unknown in 2). Positivity rates for FIT+ ranged from 16-23%, for FIT++ from 10-13% and for FITmean from 13-17% (see table). At any cut-off level, FIT++ resulted in the lowest and FIT+ in the highest sensitivity. FIT++ showed a higher specificity than both other strategies (see table). Conclusions The most sensitive strategy in two-day FIT sampling is defining the test positive when at least one of both FITs passes the cut off (FIT+), whereas the highest specificity is obtained when both FITs need to be positive for calling the tests positive (FIT++). At all cut-off values, FITmean offers substantially better specificity than FIT+, while sensitivity is substantially higher than FIT++. Sensitivity and specificity of three methods to use two-day FIT sampling for the detection of advanced neoplasia