Lawrence Hookey

A Dual-Action, Low-Volume Bowel Cleanser Administered the Day Before Colonoscopy: Results From the SEE CLEAR II Study

OBJECTIVES:Optimal bowel preparation is vital for the efficacy and safety of colonoscopy. The inconvenience, discomfort, required consumption of large volumes of product, and potential adverse effects associated with some bowel preparations deter patients from colonoscopy and may provide inadequate cleansing. A dual-action, non-phosphate, natural orange-flavored, low-volume preparation containing sodium picosulfate and magnesium citrate (P/MC) is currently being reviewed for bowel cleansing.METHODS:This was a phase 3, randomized, multicenter, assessor-blinded, prespecified non-inferiority, head-to-head study to investigate the efficacy, safety, and tolerability of day-before administration of P/MC vs. 2L polyethylene glycol solution and two 5-mg bisacodyl tablets (2L PEG-3350 and bisacodyl tablets (HalfLytely and Bisacodyl Tablets Bowel Prep Kit)) in adult patients preparing for colonoscopy (SEE CLEAR II Study). The primary objective of the study was to demonstrate the non-inferiority of P/MC to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing using a modified Aronchick scale. In addition, efficacy in the ascending, mid (transverse and descending), and recto-sigmoid segments of colon was evaluated using a modified Ottawa scale. Patient acceptability and tolerability of the bowel preparations were assessed via a standard questionnaire. Safety was assessed based on the monitoring of adverse events (AEs) and meaningful findings on clinical evaluations including physical examinations, vital sign measurements, and electrocardiograms (ECGs).RESULTS:A total of 603 patients were randomized to receive either P/MC (n=300) or 2L PEG-3350 and bisacodyl tablets (n=303). Based on the Aronchick scale, successful overall cleansing was similar in patients receiving P/MC (83.0%) and patients receiving 2L PEG-3350 and bisacodyl tablets (79.7%). P/MC demonstrated non-inferiority to 2L PEG-3350 and bisacodyl tablets in overall cleansing of the colon, as measured by the Aronchick scale. Similarly, the efficacy of P/MC, as measured by the Ottawa scale, was non-inferior to 2L PEG-3350 and bisacodyl tablets in cleansing the ascending, mid, and recto-sigmoid segments of the colon. Patient-reported acceptability and tolerability for each item examined on the questionnaire was significantly greater for P/MC compared with 2L PEG-3350 and bisacodyl tablets (P<0.0001).Treatment-emergent AEs related to the bowel preparation reported by 1% of patients receiving P/MC or 2L PEG-3350 and bisacodyl tablets were nausea (3.0% vs. 4.3%), vomiting (1.4% vs. 2.0%), and headache (2.7% vs. 1.7%). No clinically meaningful changes were noted in either treatment arm in data collected from physical examinations, vital sign measurements, and ECGs.CONCLUSIONS:When administered as a day-before dose, the bowel cleansing effects of P/MC were non-inferior compared with 2L PEG-3350 and bisacodyl tablets using the clinician-rated Aronchick and Ottawa scales. Treatment acceptability was significantly more favorable in patients receiving P/MC than in patients receiving 2L PEG-3350 and bisacodyl tablets.

A prospective randomized trial comparing low-dose oral sodium phosphate plus stimulant laxatives with large volume polyethylene glycol solution for colon cleansing.

This study examined whether the combination of a single dose (45 ml) oral sodium phosphate (NaP), four bisacodyl tablets (5 mg), and one bisacodyl enema (10 mg) preparation, Fleet Prep Kit 3 (FPK #3), was better tolerated and more efficacious than 4 L polyethylene glycol solution (PEG) for colonic cleansing prior to colonoscopy. One hundred and seventy-one patients were enrolled in this prospective, randomized, single-blinded study designed to detect a 20% or greater difference in patient tolerance and effectiveness in colonic cleansing between the two agents. The single dose of NaP and the bisacodyl tablets were administered at 1900 h and at 2100 h, respectively, the evening prior to colonoscopy and the bisacodyl enema 2 h before the procedure. PEG was consumed over 1–2 h the evening prior to colonoscopy. Most patients (84%) found the FPK #3 easy or tolerable compared to only 33% receiving PEG (p < 0.001). Over 40% could not complete the PEG. There was no detectable difference in the efficacy between the two preparations (p = 0.74). Comparison of biochemical and hemodynamic values obtained before and after colonic cleansing did not reveal any significant differences apart from hyperphosphatemia in a few patients (16%) receiving FPK #3 and minor changes in blood urea nitrogen and chloride. These findings suggest that FPK #3 is better tolerated and as safe as PEG but does not provide more efficacious cleansing of the colon.

Split-dose picosulfate, magnesium oxide, and citric acid solution markedly enhances colon cleansing before colonoscopy: a randomized, controlled trial.

BACKGROUND Picosulfate, magnesium oxide, and citric acid solution is a small-volume agent for colon cleansing before colonoscopy that is extremely well tolerated by patients, safe, and efficacious. Studies of other cleansing agents have suggested that split-dose regimens may further enhance efficacy. OBJECTIVE To examine whether split-dosing of picosulfate, magnesium oxide, and citric acid solution increases bowel cleansing efficacy while maintaining tolerability and safety. DESIGN Prospective, randomized, single-blinded, controlled trial. SETTING Outpatient tertiary care center. PATIENTS A total of 236 patients underwent colonoscopy (mean age 56 years, 53.8% female). INTERVENTIONS Patients in the traditional arm (n = 123) consumed 1 sachet of solution at 5:00 pm and 10:00 pm the night before the colonoscopy. Patients in the split-dose arm (n = 127) consumed 1 sachet at 7:00 pm the night before and another sachet 4 hours before their colonoscopy appointment. MAIN OUTCOME MEASUREMENTS Ottawa Bowel Preparation Scale (OBPS) score, Aronchick score, safety, tolerability. RESULTS The 113 and 109 patients in the split-dose and traditional arms, respectively, had OBPS scores for analysis. Overall, the OBPS scores in the split-dose group were significantly improved compared with the traditional dose group (4.05 vs 5.51, P < .001). This was mostly attributed to improvements in right-sided colon cleansing (1.22 in split-dose vs 2.14 in traditional arm, P < .001). Both regimens were well tolerated by patients, and no safety issues were identified. LIMITATIONS This was a single-center study. Disturbances in sleep related to the preparation were not assessed. CONCLUSIONS The split-dose regimen of picosulfate, magnesium oxide, and citric acid solution is superior to the traditional dosing regimen for colon cleansing before colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00885274.).

Pico-Salax Plus Two-Day Bisacodyl Is Superior to Pico-Salax Alone or Oral Sodium Phosphate for Colon Cleansing Before Colonoscopy

OBJECTIVES:This study examined whether Pico-Salax alone or Pico-Salax plus bisacodyl tablets for two nights before colonoscopy afford superior efficacy, patient tolerance, and safety compared with oral sodium phosphate.METHODS:Patients undergoing outpatient colonoscopy were randomized to receive either Pico-Salax at 5 and 10 PM the night before colonoscopy plus bisacodyl 10 mg at 5 PM in the two earlier evenings (n=105), Pico-Salax alone at 5 and 10 PM the night before colonoscopy (n=109), or oral sodium phosphate at 5 and 10 PM the night (n=101) before colonoscopy. All groups were encouraged to drink 3–4 l of Gatorade or other clear fluids the night before the colonoscopy.RESULTS:Global scoring of cleansing efficacy using the Ottawa scale did not reveal differences among groups, but Pico-Salax plus bisacodyl was superior in cleansing the right colon compared with the other regimens (P=0.003), providing almost 50% improvement over oral sodium phosphate. Patient tolerance of Pico-Salax plus bisacodyl did not differ from Pico-Salax alone but was much better than oral sodium phosphate (P<0.0001). Hemodynamic and biochemical monitoring of patients on Pico-Salax plus bisacodyl suggests this regimen has a very strong safety profile. It does not differ from Pico-Salax alone, which lacks the hyperphosphatemia and hypocalcemia associated with oral sodium phosphate.CONCLUSIONS:Together, these data suggest that Pico-Salax plus bisacodyl provides enhanced colon cleansing in the right colon compared with Pico-Salax alone or oral sodium phosphate, but this finding does not compromise the much greater tolerability or the safety profile of Pico-Salax alone.

Combined Low-Volume Polyethylene Glycol Solution Plus Stimulant Laxatives versus Standard-Volume Polyethylene Glycol Solution: A Prospective, Randomized Study of Colon Cleansing before Colonoscopy

INTRODUCTION The effectiveness of polyethylene glycol solutions (PEG) for colon cleansing is often limited by the inability of patients to drink adequate portions of the 4 L solution. The aim of the present study was to determine whether a reduced volume of PEG combined with stimulant laxatives would be better tolerated and as or more effective than the standard dose. METHODS Patients undergoing outpatient colonoscopy were randomly assigned to receive either low-volume PEG plus sennosides (120 mg oral sennosides syrup followed by 2 L PEG) or the standard volume preparation (4 L PEG). The subjects rated the tolerability of the preparations and their symptoms. Colonoscopists were blind to the colonic cleansing preparation and graded the cleansing efficacy using a validated tool (the Ottawa scale). RESULTS The low-volume PEG plus sennosides preparation was significantly better tolerated than the standard large volume PEG (P<0.001) but was less efficacious (P=0.03). Thirty-eight per cent of patients in the large volume PEG group were unable to finish the preparation, compared with only 6% in the reduced volume group. There were no adverse events reported. CONCLUSIONS Although the low-volume PEG plus sennosides preparation was better tolerated, it was not as effective as standard large-volume PEG. However, in view of the significant difference in tolerance, further research investigating possible improvements in the reduced-volume regimen seems warranted.

Risk Factors for Early Colonoscopic Perforation Include Non-Gastroenterologist Endoscopists: A Multivariable Analysis

BACKGROUND & AIMS Bowel perforation is a rare but serious complication of colonoscopy. Its prevalence is increasing with the rapidly growing volume of procedures performed. Although colonoscopies have been performed for decades, the risk factors for perforation are not completely understood. We investigated risk factors for perforation during colonoscopy by assessing variables that included sedation type and endoscopist specialty and level of training. METHODS We performed a retrospective multivariate analysis of risk factors for early perforation (occurring at any point during the colonoscopy but recognized during or immediately after the procedure) in adult patients by using the Clinical Outcomes Research Initiative National Endoscopic Database. Risk factors were determined from published articles. Additional variables assessed included endoscopist specialty and years of experience, trainee involvement, and sedation with propofol. RESULTS We identified 192 perforation events during 1,144,900 colonoscopies from 85 centers entered into the database from January 2000-March 2011. On multivariate analysis, increasing age, American Society of Anesthesia class, female sex, hospital setting, any therapy, and polyps >10 mm were significantly associated with increased risk of early perforation. Colonoscopies performed by surgeons and endoscopists of unknown specialty had higher rates of perforation than those performed by gastroenterologists (odds ratio, 2.00; 95% confidence interval, 1.30-3.08). Propofol sedation did not significantly affect risk for perforation. CONCLUSIONS In addition to previously established risk factors, non-gastroenterologist specialty was found to affect risk for perforations detected during or immediately after colonoscopy. This finding could result from differences in volume and style of endoscopy training. Further investigation into these observed associations is warranted.

Intraductal optical coherence tomography during endoscopic retrograde cholangiopancreatography for investigation of biliary strictures

BACKGROUND AND STUDY AIMS Optical coherence tomography (OCT) uses infrared light reflectance to produce high-resolution cross-sectional tissue images. The aim of this study was to demonstrate the feasibility of biliary intraductal OCT during endoscopic retrograde cholangiopancreatography (ERCP) and to assess the potential of the method to detect malignant biliary strictures. PATIENTS AND METHODS Thirty-seven patients with biliary strictures were studied during therapeutic ERCP. Malignant strictures were defined as those that demonstrated malignant cells in brushing and/or biopsy specimens, and/or endoscopic ultrasound-guided fine-needle aspiration and/or surgery. Strictures that did not have malignant cells in resected specimens and were without clinical/radiological evidence of disease progression for at least a 12-month follow-up period were considered as benign. Two OCT criteria for malignancy were considered: unrecognizable layer architecture; and presence of large, nonreflective areas compatible with tumor vessels. Sensitivity and specificity for brushings/biopsies as well as OCT criteria were calculated. RESULTS Nineteen patients had malignant and 16 had benign strictures. In two patients, OCT assessment could not be performed due to tight strictures. Malignancy was confirmed by biliary brushings/biopsies in 12/19 (63 %) patients. OCT revealed that two malignancy criteria were encountered in 10/19 (53 %) and at least one criterion in 15/19 (79 %) patients with malignant strictures. No patient with benign stricture met both criteria and 5/16 met one criterion (31 %). Combining brushings/biopsy with the observation of at least one OCT criterion resulted in the diagnosis of malignancy in 16/19 (84 %) patients. CONCLUSIONS OCT may improve the sensitivity and diagnostic accuracy of biliary brushings/biopsies alone.

Clinical Practice Guidelines for the Use of Video Capsule Endoscopy

BACKGROUND & AIMS Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. METHODS A systematic literature search identified studies on the use of CE in patients with Crohns disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. RESULTS The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohns disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohns disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohns disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. CONCLUSIONS CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohns disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.

A review of current issues underlying colon cleansing before colonoscopy

The present review examines four current issues related to the efficacy, patient tolerance and safety of the following bowel cleansing agents: oral sodium phosphate (NaP), polyethylene glycol (PEG) and magnesium citrate (Pico-Salax, Ferring Pharmaceuticals Inc, Canada), an agent recently made available in Canada. MedLine and PubMed databases were systematically searched to identify studies related to the efficacy of altered PEG solutions combined with adjunct treatments; the efficacy, tolerability and safety of Pico-Salax; the association between nephrocalcinosis, and chronic renal failure and oral NaP use; and the role of diet. Although lower volume PEG solutions combined with adjuvant agents were generally associated with better patient tolerance, their efficacy was varied and interpretation of this end point is complicated by study design issues. There are very few reported studies of Pico-Salax, and as a result, there are insufficient data to draw conclusions about the efficacy of this agent. The available data suggest that Pico-Salax may be better tolerated by patients, than oral NaP and PEG solutions. There is a paucity of hemodynamic monitoring data pre- and postadministration, but the available data suggests that this small-volume osmotic agent could cause subclinical contraction of the intravascular space. Recent case reports suggest an association between nephrocalcinosis and oral NaP ingestion, but to date, these reports have been confined to a single centre. Preliminary studies suggest that this is not a widespread problem, but more studies are needed. There are only a few studies examining diet and patient tolerability, but they do suggest that diet may be liberalized with some cleansing regimens to enhance tolerability without decreasing efficacy. The present review highlights current controversies and advances in colon cleansing before colonoscopy, and also identifies areas for further study.

The Queen’s closure: a novel technique for closure of endoscopic gastrotomy for natural-orifice transluminal endoscopic surgery

BACKGROUND AND AIMS Finding a reliable, safe, adaptable method of closing gastrotomies for natural-orifice transluminal endoscopic surgery (NOTES) procedures has been a major challenge facing this new clinical area. The Queens NOTES Group has designed a novel endoscopic method of closing gastrotomies which involved using PolyLoop polyp ligature devices and endoscopic clips. The current study describes the technique and a pilot study of leak testing it versus hand-sewn suture closure. METHODS Ten fresh pig stomachs were used, five for each technique. A 16-mm endoscopic gastrotomy was performed on the anterior wall of each. Five stomachs were then closed using the Queens closure technique, and five with a hand-sewn double-layer suture technique. The stomachs were then connected to a water infusion device with sensitive pressure monitoring and were filled until leakage was detected at the closure site. RESULTS The closures were all technically successful. The mean time for each gastrotomy and closure using the Queens closure technique was 1.2 hours. The mean leak pressure for the Queens closure was 51.8 mmHg and for the hand-sewn suture technique it was 80.8 mmHg ( P < 0.001). CONCLUSIONS The Queens closure technique holds promise as a reliable transferable technique for closing gastrotomies. Further study is necessary to evaluate its effects in live models.