A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study.

BACKGROUND & AIMS: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. METHODS: A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. RESULTS: Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. CONCLUSIONS: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.

BACKGROUND: The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain. METHODS: Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy. RESULTS: Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P= 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P= 0.32). Mean units of blood transfused were 1.7 +/- 2.1 in the intensive and 1.5 +/- 2.1 in the standard regimen group (P= 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P= 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died. CONCLUSIONS: Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).

Digestive endoscopy is not a major risk factor for transmitting hepatitis C virus.

BACKGROUND: The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial. OBJECTIVE: To evaluate the role of digestive endoscopy in transmitting HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors. DESIGN: Prospective cohort study. SETTING: 3 endoscopic units and 2 blood banks in northwestern Italy. PATIENTS: The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51,230 healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38,280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95,317 person-years of observation). MEASUREMENTS: Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction. RESULTS: All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test. LIMITATIONS: In the endoscopy cohort, 8.3% of patients were lost to follow-up. CONCLUSIONS: These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.

Interobserver agreement in staging gastric malt lymphoma by EUS.

BACKGROUND: EUS is highly accurate for staging gastric lymphoma. Because stage correlates to outcome, interobserver agreement is mandatory. However, previous studies suggest that interobserver agreement might vary according to T-stage. A multicenter evaluation of observer agreement with respect to endosonographic staging of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was therefore conducted. METHODS: Fifty-four patients were studied; 42 were also evaluated after eradication of Helicobacter pylori infection. EUS was performed at different institutions by 10 experienced endosonographers who collected the best photographs for each examination. Interobserver agreement was estimated with kappa statistics. RESULTS: Overall interobserver agreement for T-stage was fair, both before and after treatment (kappa = 0.38 and kappa = 0.37, respectively). Overall interobserver agreement for N-stage was substantial before treatment, but only fair after treatment (kappa = 0.63 and kappa = 0.34, respectively). The lowest values of agreement occurred with T1sm (submucosa) and T2 stage lesions. CONCLUSIONS: Interobserver agreement for staging of gastric MALT lymphoma by EUS is suboptimal before as well as after treatment of H pylori infection. This evidence suggests that gastric EUS may be more difficult technically compared with EUS of other organs. Lack of agreement is crucial because it influences the choice of therapy and assessment of response to treatment. Good interobserver agreement would permit better communication concerning the clinical status of patients, comparison of the results of different studies, and stratification of patients within clinical trials.