Accuracy of colon capsule endoscopy for advanced neoplasia.

BACKGROUND AND AIMS: Second-generation colon capsule endoscopy (CCE-2) has shown promising accuracy for the diagnosis of overall neoplasia. Advanced neoplasia (AN) represents the main target of colorectal cancer screening programs. Our aim was to assess the diagnostic accuracy of CCE-2 for the detection of AN in patients with a positive result for the fecal immunochemical test (FIT) who are undergoing screening. METHODS: Patients aged 50 to 69 years with a positive result for the FIT in 4 population screening programs in Italy and Spain were enrolled. Screenees were asked to undergo CCE-2, followed by traditional colonoscopy (TC). TC was performed the same day or the following morning. Bowel preparation included a split-dose polyethylene glycol-based regimen, with sodium phosphate (NaP) with gastrografin as boosters. The CCE-2 video was read by an endoscopist blinded to the results of TC. The main outcomes were CCE-2 accuracy in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for AN when using 2 different size thresholds for TC referral (ie, polyps ≥6 mm and ≥10 mm). RESULTS: Two hundred twenty-two patients were enrolled, and 178 patients completed both CCE-2 and TC (87.7%). Overall, 59 cases of AN were detected at TC. CCE-2 sensitivity was 90%, specificity was 66.1%, PPV was 57.4%, and NPV was 92.9% for AN when using a 6-mm cut-off (TC referral rate, 52.8%) and 76.7%, 90.7%, 80.7%, and 88.4% when using a 10-mm cut-off (TC referral rate, 32%), respectively. CCE-2 detected that 8 of 9 already developed colorectal cancers. Among the 41 false positives at the 6-mm cut-off, 34 (82.9%) presented with a nonadvanced adenoma at TC. Mean transit time was 4 hours and 4 minutes, and ≥70% of patients excreted the capsule within 5 hours. CONCLUSIONS: In an enriched disease setting, we showed the high sensitivity of CCE-2 for the diagnosis of AN at a 6-mm cut-off. The apparently low CCE-2 specificity is related to the choice of AN as the main outcome. (Clinical trial registration number: ISRCTN 62158762.).

Effects of a Gluten-Containing Meal on Gastric Emptying and Gallbladder Contraction.

The ingestion of gluten has been associated with gastrointestinal symptoms even in the absence of detectable immune responses. Little is known about the pathophysiological effects of gluten on the upper gastrointestinal tract. We aimed to assess whether the ingestion of gluten leads to an impairment of the physiological mechanisms of gastric emptying, gallbladder contraction and relaxation. A total of 17 healthy subjects underwent ultrasound evaluation of gastric emptying dynamics and gallbladder contractions at baseline and every 30 min after a standard gluten-containing and gluten-free meal (250 kcal, 70% carbohydrates). The pattern of gastric emptying was similar after a standard meal with or without gluten, but differed in terms of the peak of the antral filling curve, which was wider (mean area 5.69, median 4.70, range 3.71‒9.27 cm² vs. mean 4.89, median 4.57, 2.27‒10.22 cm², p = 0.023) after the gluten-containing meal. The pattern of gallbladder contractions was different after the gluten-free meal (p < 0.05), with higher gallbladder volumes in the late refilling phases. The results of this study show that gluten ingestion exerts objective effects on gastric and gallbladder motility. Although the underlying pathophysiological mechanism remains unknown, these results could account for some of the gluten-related symptoms reported by patients with celiac disease and non-celiac gluten sensitivity.

Point shear-wave elastography in chronic pancreatitis: A promising tool for staging disease severity.

BACKGROUND: Objectives: ElastPQ®-pSWE is an ultrasound technique developed to stage disease severity in patients with chronic liver diseases. Little data is available about its application to the pancreas. We aimed to assess the feasibility and reproducibility of pancreatic stiffness (PS) measurements in patients with chronic pancreatitis and their relationship with clinical and laboratory data. MATERIAL AND METHODS: 52 consecutive patients with chronic pancreatitis (CP) (40 males; median age 60 years) underwent hepatic and pancreatic pSWE. Liver stiffness was measured by transient elastography, 42 healthy subjects being controls (25 males; median age 54 years). Pancreatic pSWE inter-observer agreement was analyzed by intraclass correlation coefficient (ICC). The effects of clinical, laboratory and US data on PS measurements were evaluated by linear regression. RESULTS: pSWE was feasible in all the CP patients, but one. Pancreatic stiffness was significantly higher in CP patients than healthy controls (4.3 ± SD 2.4 vs. 2.8 ± SD 1.1 kPa, respectively, p = 0.001). Significantly higher values in the CP group were observed in patients with longer disease duration (>10 vs. ≤10 years) (5.8 ± SD 4 vs. 3.9 ± SD 1.5 kPa, respectively, p = 0.01), on chronic analgesic drugs (6.0 vs. 3.5 kPa, p < 0.05) and with lower body weight (p < 0.05, r = -0.38). At multivariate analysis all the three variables resulted independently associated to the pancreatic stiffness value. The ICC for PS was 0.77. CONCLUSIONS: ElastPQ®-pSWE is promising and reproducible in assessing pancreatic stiffness, which mainly reflects disease length and severity. Accordingly, its use is of potential value in stratifying CP patients by identifying those with a more serious degree of disease.

Bowel ultrasound imaging in patients with cystic fibrosis: Relationship with clinical symptoms and CFTR genotype.

BACKGROUND: Ultrasound imaging is used to assess bowel abnormalities in gastrointestinal diseases. We aimed to assess the rate of predefined bowel ultrasound signs and their relationship with gastrointestinal symptoms and the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in cystic fibrosis patients in regular follow-up. METHODS: Prospective study of 70 consecutive patients with cystic fibrosis and 45 controls who underwent abdominal ultrasound; pertinent findings were related to gastrointestinal symptoms and, in cystic fibrosis patients, to pancreatic status, malabsorption degree, lipase intake, CFTR genotype (classified as severe or mild against functional class of CFTR mutations). RESULTS: 96% patients showed at least one abnormal bowel ultrasound sign. Most frequent signs were lymph node enlargement (64%), bowel loop dilatation (55%), thick corpuscular intraluminal content (49%), bowel wall hypervascularization (26%), thickened bowel wall (22%) and intussusception (17%). Patients with recurrent abdominal pain showed more bowel wall hypervascularization than patients without recurrent pain (47% vs. 19%, respectively; p = 0.02) and intussusception (58% vs. 17%, respectively; p < 0.01). Genotype was not associated to specific bowel ultrasound signs. Patients with bowel loop intussusception showed greater lipase intake than those without intussusception (8.118 ± 2.083 vs. 5.994 ± 4.187, respectively; p < 0.01). CONCLUSION: Cystic fibrosis patients present a higher rate of bowel ultrasound abnormalities than controls. Bowel ultrasound abnormalities are associated with abdominal symptoms.

2-Litre polyethylene glycol-citrate-simethicone plus bisacodyl versus 4-litre polyethylene glycol as preparation for colonoscopy in chronic constipation.

BACKGROUND: Chronic constipation is a risk factor of inadequate bowel preparation for colonoscopy; however, no large clinical trials have been performed in this subgroup of patients. AIMS: To compare bowel cleansing efficacy, tolerability and acceptability of 2-L polyethylene-glycol-citrate-simethicone (PEG-CS) plus 2-day bisacodyl (reinforced regimen) vs. 4-L PEG in patients with chronic constipation undergoing colonoscopy. METHODS: Randomized, observer-blind, parallel group study. Adult outpatients undergoing colonoscopy were randomly allocated to 2-L PEG-CS/bisacodyl or 4-L PEG, taken as split regimens before colonoscopy. Quality of bowel preparation was assessed by the Ottawa Bowel Cleansing Scale (OBCS). The amount of foam/bubble interfering with colonic visualization was also measured. RESULTS: 400 patients were enrolled. There was no significant difference in successful cleansing (OBCS score ≤6): 80.2% in the 2-L PEG-CS/bisacodyl vs. 81.4% in the 4-L PEG group. Significantly more patients taking 2L PEG-CS/bisacodyl showed no or minimal foam/bubbles in all colonic segments (80% vs. 63%; p<0.001). 2-L PEG-CS/bisacodyl was significantly more acceptable for ease of administration (p<0.001), willingness to repeat (p<0.001) and showed better compliance (p=0.002). CONCLUSION: Split 2-L PEG-CS plus bisacodyl was not superior to split 4-L PEG for colonoscopy bowel cleansing in patients with chronic constipation; however, it performed better than the standard regimen in terms of colonic mucosa visualization, patient acceptance and compliance.

Decreasing iron-related indexes without anaemia in a patient with genetic haemochromatosis.

Present case report refers to a 48-year-old man with genetic haemochromatosis (C282Y mut/mut) diagnosed at the age of 26. After aggressive iron depleting regimen carried out up to normalization of iron-related indexes, he received a maintenance regimen based on regular phlebotomies for about 20 years. In 2014, a marked reduction of both serum ferritin and transferrin saturation percent, without concomitant anaemia, was noted on two different occasions at 5-month interval. An obscure occult GI bleeding was suspected, but both upper and lower GI tract endoscopy were negative for abnormal findings, as also was a detailed abdominal US scan. The persistence of low iron-related indexes prompted the physicians to perform a videocapsule endoscopy, which showed an ulcerative bleeding lesion in the small bowel, not confirmed however by both anterograde and retrograde double-balloon enteroscopy. Further MRI and PET allowed the identification of a 3.5 cm large lesion, located outside the small bowel wall, suspected to be a gastrointestinal stromal tumour (GIST). A further laparoscopic procedure allowed the resection of 10 cm of midileum, which included the mass, fully consistent with GIST at pathology.

Non-invasive assessment of liver fibrosis in chronic hepatitis B.

The goal of this review is to provide a comprehensive picture of the role, clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus (HBV) infection. During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility, poor acceptance by patients. Elastographic techniques conceived to assess liver stiffness, in particular transient elastography, and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis. Recent evidence highlights that both liver stiffness and some bio-chemical markers correlate with survival and major clinical end-points such as liver decompensation, development of hepatocellular carcinoma and portal hypertension. Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis. Given their prognostic value, transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes. Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

The impact of hyoscine-N-butylbromide on adenoma detection during colonoscopy: meta-analysis of randomized, controlled studies.

BACKGROUND: Hyoscine-N-butylbromide (HBB) can induce flattening of colon folds through inhibition of smooth muscle activity, which improves mucosal visualization. Whether this affects polyp detection is controversial. OBJECTIVE: To evaluate whether HBB, administered during colonoscopy, improves polyp and adenoma detection. DESIGN: We performed a comprehensive search in MEDLINE and EMBASE databases to identify randomized, placebo-controlled trials (RCTs) in which HBB was administered during colonoscopy and which also reported the detection rate for polyps and/or adenomas (PDR and/or ADR, respectively). SETTING: Meta-analysis of 5 RCTs. PATIENTS: A total of 1998 patients (1006 receiving HBB) were included in the study. INTERVENTIONS: Intravenous administration of 20 mg (2 mL) HBB or 2 mL saline solution at the time of cecal intubation. MAIN OUTCOME MEASUREMENTS: The PDR was the primary outcome variable. Secondary outcomes included the ADR, the advanced adenoma detection rate (adv-ADR), and the mean number of polyps and adenomas per patient (PPP and APP, respectively). RESULTS: The PDR, ADR, and adv-ADR did not differ significantly between the 2 groups. The odds ratios (95% confidence interval [CI]) for PDR, ADR, and adv-ADR were 1.09, 95% CI, 0.91-1.31; 1.13, 95% CI, 0.92-1.38; and 0.9, 95% CI, 0.63-1.30, respectively. In addition, no significant differences were observed in PPP and APP between the 2 groups. LIMITATIONS: Small number of studies included. Limited data about secondary outcomes and safety. CONCLUSION: Our meta-analysis does not provide evidence that routine HBB administration at cecal intubation improves PDR or ADR. More studies are needed for final conclusions, particularly on HBB's effect on PPP and APP.

One or two operator technique and quality performance of colonoscopy: a randomised controlled trial.

BACKGROUND: The two-operator technique for colonoscopy, with the endoscopy assistant actively advancing and withdrawing the scope, is still commonly practiced in Europe. As uncontrolled data has suggested that the one-operator technique is associated with a higher adenoma detection rate, we tested the hypothesis that the two-operator-technique can achieve comparable performances in terms of adenoma detection. METHODS: Non-inferiority trial in which consecutive adult outpatients were randomised to undergo colonoscopy by one (one-operator) or by four endoscopists. Each performed half the procedures by one-operator and half by two-operator technique independently of routine clinical practice. Main outcome measure was adenoma detection rate. RESULTS: 352 subjects (49% males, mean age 60 ± 12.1 years) were randomised to one (n=176) or to two-operator technique (n=176) colonoscopy. No significant differences were found in adenoma detection (33% vs. 30.7%, p=0.65), or cecal intubation rate, procedure times, and patient tolerability. No differences were found in the subgroup analysis according to routinely adopted colonoscopy technique. CONCLUSIONS: This study does not confirm a higher adenoma detection rate for one-operator technique colonoscopy. Changing current practice to improve adenoma detection rate for endoscopists routinely using two-operator technique is not warranted.

Accuracy of capsule colonoscopy and computed tomographic colonography in individuals with positive results from the fecal occult blood test.

BACKGROUND & AIMS: Computed tomographic colonography (CTC) is a reliable option for screening subjects who are unable or unwilling to undergo optical colonoscopy (OC). A colon capsule (PillCam Colon2 [CC2]; GivenImaging Ltd., Yokneam, Israel) has shown promising results in detecting polyps larger than 6 mm. We compared the accuracy of CC2 and CTC in identifying individuals with at least 1 polyp greater than 6 mm and subjects' attitude toward the procedures. METHODS: Fifty individuals (mean age, 59.2 ± 5.8 y; 58% male) with positive results from the immunochemical fecal occult blood test (iFOBT-positive) underwent CC2, CTC, and OC. The unblinded colonoscopy, integrating OC, CTC, and CC2 results, was used as the reference standard. In a per-patient analysis, the accuracy of CC2 and CTC were assessed for individuals with at least 1 polyp 6 mm or larger. Individuals were asked to choose which procedure they would be willing to repeat between CTC and CC2. RESULTS: The combination of OC, CTC, and CC2 identified 16 cases with at least 1 polyp 6 mm or larger (reference standard). CTC identified the polyps with 88.2% sensitivity, 84.8% specificity, a 3.0 positive likelihood ratio, and a 0.07 negative likelihood ratio. CC2 identified the polyps with 88.2% sensitivity, 87.8% specificity, a 3.75 positive likelihood ratio, and a 0.06 negative likelihood ratio. Thirty-nine subjects (78%) said they preferred CC2 to CTC. CONCLUSIONS: CC2 and CTC detect polyps 6 mm and larger with high levels of accuracy; these techniques are effective in selecting iFOBT-positive individuals who do not need to be referred for colonoscopy. CC2 seems to be better tolerated than CTC, and could be a reliable alternative to CTC for iFOBT-positive individuals who are unable or unwilling to undergo OC. ClinicalTrials.gov number: NCT01744509.

Carbon dioxide insufflation or warm-water infusion versus standard air insufflation for unsedated colonoscopy: a randomized controlled trial.

BACKGROUND: The increasing demand for colonoscopy has renewed the interest for unsedated procedures. Alternative techniques, such as carbon dioxide insufflation and warm-water infusion, have been advocated to improve patient tolerance for colonoscopy in comparison with air insufflation. OBJECTIVE: The aim of this study was to evaluate the benefits of carbon dioxide insufflation and warm-water irrigation over air insufflation in unsedated patients. DESIGN: This study was a randomized, controlled trial. SETTING: This study was conducted at a nonacademic single center. PATIENTS: Consecutive outpatients agreeing to start colonoscopy without premedication were included. INTERVENTIONS: Patients were assigned to either carbon dioxide insufflation, warm-water irrigation, or air insufflation colonoscopy insertion phase. Sedation/analgesia were administered on patient request if significant pain or discomfort occurred. MAIN OUTCOME MEASURES: The primary outcome measured was the percentage of patients requiring sedation/analgesia. Pain and tolerance scores were assessed at discharge by using a 100-mm visual analog scale. RESULTS: Three hundred forty-one subjects (115 in the carbon dioxide, 113 in the warm-water, and 113 in the air group) were enrolled. Intention-to-treat analysis showed that the proportion of patients requesting sedation/analgesia during colonoscopy was 15.5% in the carbon dioxide group, 13.2% in the warm-water group, and 25.6% in the air group (p = 0.04 carbon dioxide vs air; p = 0.03 warm water vs air). Median (interquartile range) scores for pain were 30 (10-50), 28 (15-50), and 46 (22-62) in the carbon dioxide, warm-water, and air groups (carbon dioxide vs air, p < 0.01; warm water vs air, p < 0.01); corresponding figures for tolerance were 20 (5-30), 19 (5-36), and 28 (10-50) (carbon dioxide vs air, p < 0.01; warm water vs air, p < 0.01). LIMITATIONS: This investigation was limited because it was a single-center study and the endoscopists were not blinded to randomization. CONCLUSIONS: Carbon dioxide insufflation was associated with a decrease in the proportion of patients requesting on-demand sedation, improved patient tolerance, and decreased colonoscopy-related pain in comparison with air insufflation. The findings regarding warm-water irrigation confirmed the previously reported advantages, so that warm-water irrigation and carbon dioxide insufflation could represent competitive strategies for colonoscopy in unsedated patients.

Hyoscine N-butylbromide for adenoma detection during colonoscopy: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Hyoscine N-butylbromide (HBB), commonly used during colonoscopy to facilitate cecal intubation, has been proposed to increase the adenoma detection rate (ADR). AIMS: To evaluate whether HBB administration increases the adenoma detection rate and influences patients' tolerance. METHODS: Consecutive colonoscopy outpatients were randomized after cecal intubation to receive either 20mg HBB or placebo i.v. The number, size, histology and location of polyps were recorded. The air retained in the abdomen was either indirectly estimated by ΔAC (difference in the abdominal circumference measured before and after colonoscopy) or directly evaluated by patients' perception (visual analogic scale, range 0-100). RESULTS: 402 patients (44% male; mean age 57.7±12.5years) received either HBB or placebo. No differences in ADR (31.7% vs. 28%, p=0.48), advanced-ADR (7.4% vs. 10.5%, p=0.35) were observed between HBB and placebo group, respectively. A significantly lower detection rate of flat/depressed lesions was observed in the HBB group (0.5% vs. 5.5%, p=0.003). The ΔAC and the bloating perception were comparable between the two groups (p=0.22 and p=0.48, respectively). CONCLUSIONS: HBB administered before colonoscope withdrawal does not increase adenoma detection rate and seems to hamper the visualization of flat/depressed lesions. This finding raises concerns on the indiscriminate use of HBB during colonoscopy.