Split-dose preparation for colonoscopy increases adenoma detection rate: a randomised controlled trial in an organised screening programme.

OBJECTIVE: Although a split regimen of bowel preparation has been associated with higher levels of bowel cleansing, it is still uncertain whether it has a favourable effect on the adenoma detection rate (ADR). The present study was aimed at evaluating whether a split regimen was superior to the traditional 'full-dose, day-before' regimen in terms of ADR. DESIGN: In a multicentre, randomised, endoscopist-blinded study, 50-69-year-old subjects undergoing first colonoscopy after positive-faecal immunochemical test within an organised colorectal cancer organised screening programmes were 1:1 randomised to receive low-volume 2-L polyethylene glycol (PEG)-ascorbate solution in a 'split-dose' (Split-Dose Group, SDG) or 'day-before' regimen (Day-Before Group, DBG). The primary endpoint was the proportion of subjects with at least one adenoma. Secondary endpoints were the detection rates of advanced adenomas and serrated lesions at per-patient analysis and the total number of lesions. RESULTS: 690 subjects were included in the study. At per-patient analysis, the proportion of subjects with at least one adenoma was significantly higher in the SDG than in the DBG (183/345, 53.0% vs 141/345, 40.9%, relative risk (RR) 1.22, 95% CI 1.03 to 1.46); corresponding figures for advanced adenomas were 26.4% (91/345) versus 20.0% (69/345, RR 1.35, 95% CI 1.06 to 1.73). At per-polyp analysis, the total numbers of both adenomas and advanced adenomas per subject were significantly higher in the SDG (1.15 vs 0.8, p <0.001; 0.36 vs 0.22, p<0.001). CONCLUSIONS: In an organised screening setting, the adoption of a split regimen resulted into a higher detection rate of clinically relevant neoplastic lesions, thus improving the effectiveness of colonoscopy. Based on such evidence, the adoption of a split regimen for colonoscopy should be strongly recommended. CLINICAL TRIAL REGISTRATION NUMBER: NCT02178033.

Barriers against split-dose bowel preparation for colonoscopy.

OBJECTIVE: Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake. DESIGN: In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4 L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. RESULTS: Of the 1447 patients (mean age 59.2±13.5 years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p<0.001, χ2 for linear trend). At multivariate analysis, colonoscopy appointment before 10:00 (OR 0.14, 95% CI 0.11 to 0.18), travel time to endoscopy service >1 h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). CONCLUSION: Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. TRIAL REGISTRATION NUMBER: NCT02287051; pre-result.

Does asymmetric dimethylarginine (ADMA) plasma concentration predict esophageal varices in patients with cirrhosis?

BACKGROUND: In previous studies elevated Asymmetric NG, NG - dimethylarginine (ADMA) plasma levels, an endogenous nitric oxide synthase inhibitor, correlated with the severity of hepatic venous pressure gradient measurement, both in peripheral and in hepatic veins. The aim of this study was to explore whether elevated ADMA plasma levels were able to predict the presence of esophageal varices (EV) and/or large EV in patients with cirrhosis. METHODS: 74 cirrhotic patients who had undergone elective upper gastrointestinal endoscopy in order to assess the presence of portal hypertension and predictors of EV and/or large EV. ADMA levels were assayed by an ELISA test (Immundiagnostik AG, Germany). RESULTS: 53 patients had EV (26/53 had large EV). Univariate analysis of low hemoglobin (p = 0.045), PT-INR (p = 0.003), albumin (p = 0.024), bilirubin (p = 0.036), Child-Pugh score (p = 0.026), and ascites (p = 0.036) predicted the presence of EV. Multivariate analysis predicted EV for only PT-INR. The presence of large EV was predicted with univariate analysis of ADMA plasma levels (p = 0.013), low hemoglobin (p < 0.001), PT-INR (p = 0.001), albumin (p = 0.001), bilirubin (p = 0.026), Child-Pugh score (p < 0.001), ascites (p = 0.004). Sensitivity, specificity, predictive positive and negative values of ADMA plasma level > 0.5 micromol/L(-1) in predicting large EV were 0.69 (95% CI 0.53 - 0.82), 0.51 (95% CI 0.40 - 0.62), 0.43 (95% CI 0.31 - 0.56), 0.76 (95% CI 0.62 - 0.86), while the area under the ROC curve was 0.65 (95% CI 0.51 - 0.79). CONCLUSIONS: ADMA plasma levels were increased in cirrhotics with more advanced liver failure but did not prove to be a useful clinical tool for predicting the presence of esophageal varices or large esophageal varices.

Is interferon-alpha therapy safe and effective for patients with chronic hepatitis C and inflammatory bowel disease? A case-control study.

BACKGROUND: Hepatitis C virus infection is more common in patients with inflammatory bowel disease than in general population. Limited data are available as to the safety and efficacy of alpha-interferon therapy for chronic active hepatitis C in patients with concomitant inflammatory bowel disease. AIM: To evaluate the efficacy and safety of alpha-interferon monotherapy in patients with chronic active hepatitis C and inactive or mildly active inflammatory bowel disease. METHODS: A total of 513 consecutive inflammatory bowel disease patients at a single centre were tested for antibodies to hepatitis C virus (anti-hepatitis C virus) between 1995 and 2000. Twenty-one patients had detectable anti-hepatitis C virus Ab and were hepatitis C virus-RNA positive with histologically proved chronic active hepatitis. Each of these patients, whose inflammatory bowel disease was in clinical remission or mildly active, was sex- and age-matched to three controls with similar histological grade and stage of chronic hepatitis C virus but without inflammatory bowel disease; and all were treated with human leucocyte alpha-interferon 6 million units given thrice weekly for 12 months. Responses to treatment were classified as follows: complete response--persistently normal alanine aminotransferase and viral clearance (hepatitis C virus-RNA-ve) at the end-of-treatment, incomplete response--alanine aminotransferase normalization without viral clearance (hepatitis C virus-RNA+ve), and sustained response--alanine aminotransferase normalization and hepatitis C virus clearance 12 months after the end-of-treatment. RESULTS: Twenty-one patients with chronic active hepatitis C and inflammatory bowel disease (10 with Crohn's disease and 11 with ulcerative colitis) and 63 sex- and age-matched controls with chronic hepatitis C virus alone received alpha-interferon monotherapy. Response rates to interferon were similar for inflammatory bowel disease patients compared with controls [CR 42% vs. 35% and SR 24% vs. 18% (P, not significant), respectively]. None of the 21 inflammatory bowel disease patients had severe adverse effects and the mild ones observed were comparable with those seen in the control group. No patients developed an inflammatory bowel disease relapse during the interferon treatment period or in the 12 months thereafter. CONCLUSIONS: The biochemical and virological response to a 12-month human leucocyte alpha-interferon treatment in patients with chronic active hepatitis C are similar to that observed in matched controls with chronic hepatitis C virus without inflammatory bowel disease. Adverse effects are similar in both groups of patients and unrelated to the underlying inflammatory bowel condition. This provides hepatologists with evidence that alpha-interferon can be safely administered to patients with chronic hepatitis C virus and inflammatory bowel disease provided that the inflammatory bowel condition is in clinical remission.

Different effects of short-term omeprazole, lansoprazole or pantoprazole on the accuracy of the (13)C-urea breath test.

BACKGROUND: Proton pump inhibitors may interfere with the accuracy of the (13)C-urea breath test, but little information is available on the effect of standard doses of various proton pump inhibitors on this test. AIM: To evaluate the effect of short-term standard doses of omeprazole, lansoprazole and pantoprazole on the accuracy of the standardized (13)C-urea breath test. METHODS: A total of 124 patients with Helicobacter pylori infection, diagnosed on the basis of gastric histology, rapid urease test and (13)C-urea breath test, were studied. These patients received omeprazole, 20 mg/day, lansoprazole, 30 mg/day, or pantoprazole, 40 mg/day, for 2 weeks according to a randomized protocol. (13)C-Urea breath test was repeated on days 4, 7 and 14 while on therapy and 7 days after proton pump inhibitor withdrawal. RESULTS: Of the patients receiving omeprazole and lansoprazole, 30% (12/40) and 20% (8/41), respectively, became (13)C-urea breath test negative during therapy, compared with none of the 42 patients treated with pantoprazole (P < 0.05). All the false negative (13)C-urea breath test results returned to positive within 1 week of drug withdrawal, with a mean recovery to 84.7 +/- 15.6% of baseline delta(13)CO(2). CONCLUSIONS: Short-term omeprazole and lansoprazole interfere with the 13C-urea breath test, although a return to positive test results invariably occurs within 1 week of proton pump inhibitor withdrawal. In contrast, the accuracy of the (13)C-urea breath test does not appear to be significantly impaired by short-term pantoprazole, which therefore may not necessarily be withdrawn before this test.

Behaviour of the bowel wall during the first year after surgery is a strong predictor of symptomatic recurrence of Crohn's disease: a prospective study.

BACKGROUND: Recurrences after surgery for Crohn's disease are frequent and unpredictable. To date, there is little agreement as to which factors increase a patient risk of early recurrence. AIM: To assess whether the post-operative behaviour of diseased bowel walls, as determined by ultrasound, may be a useful predictor of relapse. METHODS: A total of 127 Crohn's disease patients were monitored after surgery by means of bowel ultrasound as well as by clinical and laboratory evaluations for a median follow-up of 41.0 months. Bowel wall thickness of diseased loops measured at ultrasound during follow-up was compared with the presurgery values. Multivariable survival analysis was performed to elucidate predictors of early post-operative recurrence. Receiver operating characteristic curves were also constructed taking into account bowel wall thickness for selecting Crohn's disease patients with high risk of clinical/surgical recurrence. RESULTS: The estimated 5 years survival probability of symptomatic Crohn's disease recurrence were 90% and 33%, respectively for unchanged/worsened bowel wall thickness vs. improved bowel wall thickness at 12 months from surgery. The hazard ratio for unchanged/worsened bowel wall thickness at 12 months was 8.9 (95% CI: 3.4-23.2). Receiver operating characteristic curve identified a bowel wall thickness > 6.0 mm at 12 months from surgery as directly associated with the risk of having a Crohn's disease recurrence (hazard ratio was 6.5, 95% CI: 2.8-15.4). CONCLUSIONS: Systematic ultrasound follow-up of diseased bowel walls after conservative surgery allows the early identification of patients at high risk of clinical/surgical recurrence.

The effects on gastroduodenal mucosa of a new nonsteroidal anti-inflammatory drug, amtolmetin-guacyl, versus piroxicam in healthy volunteers: a short-term, double-blind, endoscopically controlled study.

AIM: Amtolmetin-guacyl (AMG) (2-[2[1-methyl-5-(4-methylbenzoyl) pyrrol-2-yl] acetamido] acetic acid 2-methoxyphenyl ester) is a recent drug that, in preliminary studies, has shown effective anti-inflammatory properties with improved gastrointestinal safety. Our study was designed to investigate the effects of AMG and piroxicam on gastroduodenal mucosa in healthy volunteers. MATERIALS AND METHODS: Forty-two healthy volunteers aged 18--45 years were randomized in a double-blind manner to AMG 1200 mg for 2 days and 600 mg for 12 days, or piroxicam 40 mg for 2 days and 20 mg for 12 days. Endoscopic evaluation and laboratory tests were performed at baseline and at the end of the treatment. The mucosa was evaluated by endoscopy using a predefined scale: the score could range from 0 to 4. Only volunteers with endoscopy grade 0-1 entered the trial. RESULTS: The median post-treatment endoscopy gastric injury scores were 1 (range 0--4) in the AMG-treated volunteers and 3 (range 0--4) in the piroxicam-treated volunteers (P = 0.04). There were two cases with an endoscopic gastric score of 4 in the AMG group, and seven in the piroxicam group (P = 0.1). The corresponding values in the duodenum were 1/21 volunteers in the AMG group and 1/21 in the piroxicam group. Eight out of 11 subjects with an endoscopic score of 4 were Helicobacter pylori negative, and 3/11 were infected by the micro-organism. Different adverse reactions were reported by 15/21 volunteers (71%) in the AMG group and by 12/21 (57%) in the piroxicam group. None of these events resulted in interruption of the study. CONCLUSIONS: AMG is a new anti-inflammatory drug with limited gastric toxicity. If these findings are confirmed on a wider scale in long-term trials, then the drug might become a valid alternative to current treatments, especially for patients such as those with rheumatoid arthritis who need steroids and second-line drugs simultaneously.

An unusual cause of recurrent biliary colics.

Hepato-biliary ascariasis is a rare condition in non-endemic areas; however, it should always be taken into account in patients with recurrent biliary colics and/or cholangitis, since these are among the most frequent modes of clinical presentation. We report a case of a young woman suffering from recurrent biliary colics in whom a diagnosis of biliary ascariasis was made. Endoscopic retrograde cholangiopancreatography with sphincterotomy and endoscopic extraction of the worm, using a Dormia basket, proved to be a safe and effective procedure for removing the living Ascaris from the biliary tree and relieving symptoms. In the era of worldwide travels, physicians in Western countries should be more aware of this infection especially in patients with biliary symptoms who have travelled to endemic areas or immigrant from endemic countries.

The cognitive development of children born preterm and affected by spastic diplegia.

In a prospective study the intellectual development of 20 premature children affected by spastic diplegia was compared with that of 10 preterm low-risk children. The assessment was carried out with the Griffiths scale at the age of 3 years and with the WPPSI scale at the age of 6 years. The analysis of data collected in the 2 psychometric evaluations of the preterm-born diplegic children showed a disharmonic profile of neuropsychological functions, already present at the age of 3 years and confirmed at the age of 6 years. The average scores in diplegic children were poorest in the subscales locomotor, eye-hand coordination, and performance on Griffiths scale, and in the performance subtests of the WPPSI scale. The mean scores of subscales for hearing and speech, and practical reasoning on the Griffiths scale and of the verbal subscale of the WPPSI were near to the lower range of the normal distribution. Significant differences in performance subtests were found between the groups of preterm diplegic children and the group of low-risk preterm children, both at 3 and 6 years of age.

Eye-movement disorders and visual-perceptual impairment in diplegic children born preterm: a clinical evaluation.

The visual-motor behaviour of 15 preterm diplegic children and 50 control children (age range 4 to 7 years) was recorded on video as they performed a visual-perceptual task (an adaptation of the Animal House subtest of the Wechsler Preschool Primary Scale of Intelligence). The following parameters were analysed and scored: time to perform task; omissions; figure-colour association; sequence direction; sequential scanning order; accuracy of fitting target; and number of anticipatory saccadic movements to next target. The ability of the control children to perform the task improved significantly with age, as measured by performance time, mistakes in sequence direction and scanning order, accuracy of target fitting, and number of anticipatory saccadic movements. The scores of children with diplegia were not related to age and were poorer overall than those of the control group. Children with diplegia made significantly more mistakes of sequence direction and scanning order, and significantly fewer anticipatory saccadic movements than the control group. These results indicate that visual-perceptual impairment in diplegic children born preterm is not attributable only to sensory visual loss and to fine manipulation difficulties but is also related to difficulties in eye movements and in using anticipatory control to process information.

Treatment of Helicobacter pylori infection using a novel antiadhesion compound (3'sialyllactose sodium salt). A double blind, placebo-controlled clinical study.

BACKGROUND AND AIM: 3' sialyllactose sodium salt (3'SL) is an oligosaccharide that occurs naturally in human and bovine milk. It can inhibit the adhesion of H. pylori to human epithelial cells in vitro. The aim of this study was to test whether this oligosaccharide can suppress or cure H. pylori colonization in vivo and to determine its safety in humans. METHODS: Seventy-one consecutive dyspeptic patients with H. pylori infection documented by histology and 13C-Urea Breath Test (UBT) were initially recruited to this study. Patients with UBT values <15 were excluded, thus reducing the enrollment to 65 patients. They were given two different dosages of 3'SL (10 g or 20 g/day) in three daily administrations before meals or placebo for 4 weeks, according to a randomised double-blind protocol. A standardized 13C-UBT (using 100 mg of 13C labelled urea) was repeated in all patients at fixed intervals during treatment (at the end of weeks 1, 2 and 4) and 4 weeks after treatment withdrawal. Patients compliance and side-effects were evaluated at each weekly visit. RESULTS: Five patients were excluded from the PP analysis due to violation of the protocol (noncompliance, lost to follow-up), whereas 61 patients completed correctly the study: 17 received 3'SL 10 g/day, 22 were treated with 3'SL 20 g/day and 21 were given placebo. The three treatment groups did not significantly differ in demographic or clinical patient characteristics. No serious adverse events were observed during therapy in any of the three groups. No patients became UBT negative (<4) during or after treatment but UBT values decreased significantly during the study period in both treatment groups and placebo. CONCLUSIONS: Antiadhesive therapy was safe and well tolerated but did not suppress or cure H. pylori colonization in humans. The observed decrease in UBT values could be explained by a regression towards the mean effect.

Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn's disease. A prospective comparison with conventional ultrasound, x ray studies, and ileocolonoscopy.

UNLABELLED: BACKGROUND/ AIM: Although ultrasound (US) has proved to be useful in intestinal diseases, barium enteroclysis (BE) remains the gold standard technique for assessing patients with small bowel Crohn's disease (CD). The ingestion of anechoic non-absorbable solutions has been recently proposed in order to distend intestinal loops and improve small bowel visualisation. The authors' aim was to evaluate the accuracy of oral contrast US in finding CD lesions, assessing their extent within the bowel, and detecting luminal complications, compared with BE and ileocolonoscopy. METHODS: 102 consecutive patients with proven CD, having undergone complete x ray and endoscopic evaluation, were enrolled in the study. Each US examination, before and after the ingestion of a polyethylene glycol (PEG) solution (500-800 ml), was performed independently by two sonographers unaware of the results of other diagnostic procedures. The accuracy of conventional and contrast enhanced US in detecting CD lesions and luminal complications, as well as the extent of bowel involvement, were determined. Interobserver agreement between sonographers with both US techniques was also estimated. RESULTS: After oral contrast, satisfactory distension of the intestinal lumen was obtained in all patients, with a mean time to reach the terminal ileum of 31.4 (SD 10.9) minutes. Overall sensitivity of conventional and oral contrast US in detecting CD lesions were 91.4% and 96.1%, respectively. The correlation coefficient between US and x ray extent of ileal disease was r1 = 0.83 (p<0.001) before and r2 = 0.94 (p<0.001) after PEG ingestion; r1 versus r2 p<0.01. Sensitivity in detecting strictures was 74% for conventional US and 89% for contrast US. Overall interobserver agreement for bowel wall thickness and disease location within the small bowel was already good before but significantly improved after PEG ingestion. CONCLUSIONS: Oral contrast bowel US is comparable with BE in defining anatomic location and extension of CD and superior to conventional US in detecting luminal complications, as well as reducing interobserver variability between sonographers. It may be therefore regarded as the first imaging procedure in the diagnostic work up and follow up of small intestine CD.

Bowel ultrasound in assessment of Crohn's disease and detection of related small bowel strictures: a prospective comparative study versus x ray and intraoperative findings.

BACKGROUND AND AIM: Despite the fact that bowel ultrasound (US) has recently been proved to be useful in the assessment of bowel diseases, uncertainty persists as to its diagnostic role in patients with complicated Crohn's disease (CD). Therefore, we have prospectively investigated the accuracy of US compared with x ray procedures and intraoperative findings in detecting small bowel strictures complicating CD as well as its reliability in assessing disease extent and location within the bowel. METHODS: A series of 296 consecutive patients with proven CD admitted to L Sacco University Hospital between 1997 and 1999, having undergone complete radiographic evaluation (including small bowel x ray, colonoscopy, or double contrast barium enema), were enrolled in the study. Bowel US was performed in each patient by two experienced operators unaware of the results of other diagnostic procedures. The accuracy of US in detecting strictures compared with x ray studies was determined separately in two different groups of patients: 211 patients treated conservatively (non-operative CD) and 85 patients who were candidates for surgery for CD complications or unresponsiveness to medical therapy (operative CD). RESULTS: Overall sensitivity and specificity of US in assessing the anatomical distribution of CD were 93% and 97%, respectively. The extent of ileal disease measured at US correlated well with that determined by x ray (r=0.52, p<0.001) in medically treated patients as well as with that measured intraoperatively in surgical patients (r=0.64, p<0.001). One or more stenoses were detected in 75 patients (35.5%) at small bowel enteroclysis in the non-operative CD group compared with 70 (82%) in the operative CD series. Sensitivity, specificity, and positive predictive values of bowel US in the detection of strictures were 79%, 98%, and 95% in non-operative CD patients and 90%, 100%, and 100% in operative CD cases, respectively. CONCLUSIONS: In experienced hands, bowel US is an accurate technique for assessing CD extent and location and is very helpful in detecting small bowel strictures, especially in very severe cases that are candidates for surgery. The use of bowel US is therefore justified as a primary investigation in CD patients in whom complications are suspected.