Felix W. Leung

Role of Blood Flow in Gastric and Duodenal Mucosal Injury in the Rat

The hemorrhagic hypotension model in anesthetized rats was used to study the relationship between gastric and duodenal mucosal blood flow and susceptibility to acid-induced injury. Mucosal blood flows measured by the hydrogen gas clearance technique in the corpus, antrum, and duodenum all showed a significant linear correlation with mean blood pressure, decreasing progressively as blood pressure fell. Significant gastric mucosal lesions occurred only after mean blood pressure and hence, mucosal blood flow was reduced to below 40% of baseline values. In contrast, duodenal mucosal lesion formation was related in a linear manner to decrease in mean blood pressure or blood flow. We conclude that mild reductions in blood flow are more important in the duodenum than in the stomach in increasing susceptibility of the mucosa to acid-induced injury.

A proof-of-principle, prospective, randomized, controlled trial demonstrating improved outcomes in scheduled unsedated colonoscopy by the water method

BACKGROUND An observational study in veterans showed that a novel water method (water infusion in lieu of air insufflation) enhanced cecal intubation and willingness to undergo a repeat scheduled unsedated colonoscopy. OBJECTIVE To confirm these beneficial effects and significant attenuation of discomfort in a randomized, controlled trial (RCT). DESIGN Prospective RCT, intent-to-treat analysis. SETTING Veterans Affairs ambulatory care facility. PATIENTS Veterans undergoing scheduled unsedated colonoscopy. INTERVENTIONS During insertion, the water and traditional air methods were compared. MAIN OUTCOME MEASUREMENTS Discomfort and procedure-related outcomes. RESULTS Eighty-two veterans were randomized to the air (n = 40) or water (n = 42) method. Cecal intubation (78% vs 98%) and willingness to repeat (78% vs 93%) were significantly better with the water method (P < .05; Fisher exact test). The mean (standard deviation) of maximum discomfort (0 = none, 10 = most severe) during colonoscopy was 5.5 (3.0) versus 3.6 (2.1) P = .002 (Student t test), and the median overall discomfort after colonoscopy was 3 versus 2, P = .052 (Mann-Whitney U test), respectively. The method, but not patient characteristics, was a predictor of discomfort (t = -1.998, P = .049, R(2) = 0.074). The odds ratio for failed cecal intubation was 2.09 (95% CI, 1.49-2.93) for the air group. Fair/poor previous experience increased the risk of failed cecal intubation in the air group only. The water method numerically increased adenoma yield. LIMITATIONS Single site, small number of elderly men, unblinded examiner, possibility of unblinded subjects, restricted generalizability. CONCLUSIONS The RCT data confirmed that the water method significantly enhanced cecal intubation and willingness to undergo a repeat colonoscopy. The decrease in maximum discomfort was significant; the decrease in overall discomfort approached significance. The method, but not patient characteristics, was a predictor of discomfort. (Clinical trial registration number NCT00747084).

Water-aided colonoscopy: a systematic review

BACKGROUND Water-aided methods for colonoscopy are distinguished by the timing of removal of infused water, predominantly during withdrawal (water immersion) or during insertion (water exchange). OBJECTIVE To discuss the impact of these approaches on colonoscopy pain and adenoma detection rate (ADR). DESIGN Systematic review. SETTING Randomized, controlled trial (RCT) that compared water-aided methods and air insufflation during colonoscope insertion. PATIENTS Patients undergoing colonoscopy. INTERVENTION Medline, PubMed, and Google searches (January 2008-December 2011) and personal communications of manuscripts in press were considered to identify appropriate RCTs. MAIN OUTCOME MEASUREMENTS Pain during colonoscopy and ADR. RCTs were grouped according to whether water immersion or water exchange was used. Reported pain scores and ADR were tabulated based on group assignment. RESULTS Pain during colonoscopy is significantly reduced by both water immersion and water exchange compared with traditional air insufflation. The reduction in pain scores was qualitatively greater with water exchange as compared with water immersion. A mixed pattern of increases and decreases in ADR was observed with water immersion. A higher ADR, especially proximal to the splenic flexure, was obtained when water exchange was implemented. LIMITATIONS Differences in the reports limit application of meta-analysis. The inability to blind the colonoscopists exposed the observations to uncertain bias. CONCLUSION Compared with air insufflation, both water immersion and water exchange significantly reduce colonoscopy pain. Water exchange may be superior to water immersion in minimizing colonoscopy discomfort and in increasing ADR. A head-to-head comparison of these 3 approaches is required.

Gastric mucosal blood flow in rats after administration of 16,16-dimethyl prostaglandin E2 at a cytoprotective dose

The purpose of the present study was to determine whether the gastric cytoprotective effect of a prostaglandin such as 16,16-dimethyl prostaglandin (dmPGE2) is mediated by an increase in mucosal blood flow. Gastric mucosal blood flow was measured in urethane-anesthetized rats by the hydrogen gas clearance technique. In control rats given no ethanol, intragastric administration of dmPGE2 (10 micrograms/kg body wt) produced a significant reduction (15.3%) in gastric mucosal blood flow 30 min after treatment. This dose of dmPGE2 significantly reduced the formation of the gross gastric lesions produced by absolute ethanol in anesthetized rats. In vehicle-pretreated animals, blood flow was invariably absent in the ethanol-induced mucosal lesion areas. In the nonlesion areas, gastric mucosal blood flow was the same in prostaglandin-pretreated and vehicle-pretreated animals as in control (no ethanol) rats. Thus, although dmPGE2 pretreatment protected against ethanol-induced gastric mucosal injury and prevented the accompanying blood flow stasis, it did not do this by an increase in gastric mucosal blood flow. The protection also is not due to a decrease in flow because, in separate groups of anesthetized rats, a 15% reduction in gastric mucosal blood flow induced by either hemorrhage or intravenous vasopressin did not protect the gastric mucosa against absolute ethanol-induced injury. Whether the maintenance of gastric mucosal blood flow is a primary or secondary effect of prostaglandin cytoprotection remains to be determined.

Options for screening colonoscopy without sedation: a pilot study in United States veterans

Background  The direct and indirect costs of sedation limit access to screening colonoscopy amongst United States veterans.

Effects of Smoking and Nicotine on the Gastric Mucosa: A Review of Clinical and Experimental Evidence

Epidemiological and experimental evidence have shown that nicotine has harmful effects on the gastric mucosa. The mechanisms by which cigarette smoking or nicotine adversely affect the gastric mucosa have not been fully elucidated. In this report, clinical and experimental data are reviewed. The effects of nicotine from smoking on gastric aggressive or defensive factors are discussed. Nicotine potentiates gastric aggressive factors and attenuates defensive factors; it also increases acid and pepsin secretions, gastric motility, duodenogastric reflux of bile salts, the risk of Helicobacter pylori infection, levels of free radicals, and platelet-activating factor, endothelin generation, and vasopressin secretion. Additionally, nicotine impairs the therapeutic effect of H2-receptor antagonists and decreases prostaglandin synthesis, gastric mucosal blood flow, mucus secretion, and epidermal growth factor secretion. Although many of the studies provide conflicting results, the bulk of the evidence supports the hypothesis that nicotine is harmful to the gastric mucosa.

Impact of a novel water method on scheduled unsedated colonoscopy in U.S. veterans

BACKGROUND Intermittent warm-water infusion in lieu of air insufflation permitted 52% of patients who accepted sedation on demand to complete colonoscopy without sedation. OBJECTIVE To test the hypothesis that the water method enhances cecal intubation and increases the proportion of patients who report willingness to repeat a scheduled unsedated colonoscopy. DESIGN Observational study. PATIENTS Two consecutive groups of veterans. INTERVENTIONS From June 2005 to May 2006, the usual air insufflation method was used to aid colonoscope insertion. From June 2006 to October 2007, the water method was used. MAIN OUTCOME MEASUREMENTS Cecal intubation; report of willingness to repeat unsedated colonoscopy. RESULTS Sixty-two and 63 veterans were examined by the air method and the water method, respectively. Intention-to-treat analysis revealed that the cecal intubation rate with the water method (97% [61/63]) was significantly higher than that with the air method (76% [47/62]). The proportion of patients who reported willingness to repeat unsedated colonoscopy was significantly higher with the water method (90% [57/63]) compared with the air method (69% [43/62]). LIMITATIONS Single site, nonrandomized, unblinded, small number of elderly male veterans. CONCLUSION The effects of the water method in the group for scheduled unsedated colonoscopy were sufficiently provocative to warrant calling for their confirmation by a randomized controlled trial.

Gastric Mucosal Blood Flow Response to Stimulation and Inhibition of Gastric Acid Secretion

The effect of stimulation (with graded doses of intravenous pentagastrin) and inhibition (with an H2-blocker or a proton pump inhibitor) of acid secretion on corpus mucosal blood flow was investigated. Hydrogen gas clearance was used to measure blood flow in the basal portion of the mucosa of anesthetized rats. A dose-related increase in acid output increments above resting level was observed with the doses of pentagastrin from 0 (saline infusion) to 40 micrograms/kg.h. With the doses of pentagastrin from 0 to 80 micrograms/kg.h there was a dose-related increase in mucosal blood flow increments above resting levels. A linear correlation (r = 0.7) was observed between increments in acid output and increments in mucosal blood flow with increasing doses of pentagastrin from 0 to that producing maximal acid secretion (40 micrograms/kg.h). Inhibition of pentagastrin-stimulated acid secretion by cimetidine or omeprazole returned stimulated gastric mucosal blood flow to baseline levels.

A randomized, controlled trial to confirm the beneficial effects of the water method on U.S. veterans undergoing colonoscopy with the option of on-demand sedation

BACKGROUND Sedation for colonoscopy discomfort imposes a recovery-time burden on patients. The water method permitted 52% of patients accepting on-demand sedation to complete colonoscopy without sedation. On-site and at-home recovery times were not reported. OBJECTIVE To confirm the beneficial effect of the water method and document the patient recovery-time burden. DESIGN Randomized, controlled trial, with single-blinded, intent-to-treat analysis. SETTING Veterans Affairs outpatient endoscopy unit. PATIENTS This study involved veterans accepting on-demand sedation for screening and surveillance colonoscopy. INTERVENTION Air versus water method for colonoscope insertion. MAIN OUTCOME MEASUREMENTS Proportion of patients completing colonoscopy without sedation, cecal intubation rate, medication requirement, maximum discomfort (0 = none, 10 = severe), procedure-related and patient-related outcomes. RESULTS One hundred veterans were randomized to the air (n = 50) or water (n = 50) method. The proportions of patients who could complete colonoscopy without sedation in the water group (78%) and the air group (54%) were significantly different (P = .011, Fisher exact test), but the cecal intubation rate was similar (100% in both groups). Secondary analysis (data as Mean [SD]) shows that the water method produced a reduction in medication requirement: fentanyl, 12.5 (26.8) μg versus 24.0 (30.7) μg; midazolam, 0.5 (1.1) mg versus 0.94 (1.20) mg; maximum discomfort, 2.3 (1.7) versus 4.9 (2.0); recovery time on site, 8.4 (6.8) versus 12.3 (9.4) minutes; and recovery time at home, 4.5 (9.2) versus 10.9 (14.0) hours (P = .049; P = .06; P = .0012; P = .0199; and P = .0048, respectively, t test). LIMITATIONS Single Veterans Affairs site, predominantly male population, unblinded examiners. CONCLUSION This randomized, controlled trial confirms the reported beneficial effects of the water method. The combination of the water method with on-demand sedation minimizes the patient recovery-time burden. ( CLINICAL TRIAL REGISTRATION NUMBER NCT00920751.).

Water immersion versus standard colonoscopy insertion technique: randomized trial shows promise for minimal sedation.

BACKGROUND AND STUDY AIMS Water immersion is an alternative colonoscopy technique that may reduce discomfort and facilitate insertion of the instrument. This was a prospective study to compare the success of colonoscopy with minimal sedation using water immersion and conventional air insufflation. PATIENTS AND METHODS A total of 229 patients were randomized to either water immersion or the standard air insertion technique. The primary outcome was success of minimal sedation colonoscopy, which was defined as reaching the cecum without additional sedation, exchange of the adult colonoscope or hands-on assistance for trainees. Patient comfort and satisfaction were also assessed. RESULTS Successful minimal-sedation colonoscopy was achieved in 51 % of the water immersion group compared with 28 % in the standard air group (OR, 2.66; 95 % CI 1.48 - 4.79; P = 0.0004). Attending physicians had 79 % success with water immersion compared with 47 % with air insufflation (OR, 4.19; 95 % CI 1.5 - 12.17; P = 0.002), whereas trainees had 34 % success with water compared with 16 % using air (OR, 2.75; 95 % CI 1.15 - 6.86; P = 0.01). Using the water method, endoscopists intubated the cecum faster and this was particularly notable for trainees (13.0 +/- 7.5 minutes with water vs. 20.5 +/- 13.9 minutes with air; P = 0.0001). Total procedure time was significantly shorter with water for both experienced and trainee endoscopists ( P < 0.05). Patients reported less intraprocedural pain with water compared with air (4.1 +/- 2.7 vs. 5.3 +/- 2.7; P = 0.001), with a similar level of satisfaction. There was no difference in the neoplasm detection rates between the groups. CONCLUSION Colonoscopy insertion using water immersion increases the success rate of minimal sedation colonoscopy. Use of the technique leads to a decrease in discomfort, time to reach the cecum, and the amount of sedative and analgesic used, without compromising patient satisfaction.