Improving Adenoma Detection Rates: The Role of the Fecal Immunochemical Test.

Background There is limited knowledge about adenoma detection rates (ADRs) in patients with a positive fecal immunochemical test (FIT). We hypothesized that colonoscopy performed after FIT would result in higher ADRs. Methods We reviewed ADRs for colonoscopies performed after a positive FIT test and compared them to ADR rates for routine colonoscopy performed without an initial FIT test between November 2014 and March 2017 at multiple endoscopy sites. Results A total of 979 patients underwent a FIT testing in the Texas panhandle, of whom 12.1% (n=119) tested positive. Also, 32.8% (n=39) were found to have one or more tubular adenomatous polyps on final pathological examination. Among these patients, the majority were female (64.1%; n=25). Of the patients, 15.9% (n=19) had a hyperplastic polyp, 1.7% (n=2) had findings consistent with ulcerative colitis, and 0.8% (n=1) were positive for an adenocarcinoma. In the control group of 2,603 patients in whom routine colonoscopy was performed as the initial tool for screening, 719 were found to have one or more tubular adenomas, with an ADR rate of 27.5%. In this group, the cancer rate was found to be 1%. Conclusions There was a significant increase in the ADR when colonoscopy is conducted after a positive FIT test. Recommending colonoscopies after a positive FIT test will not only improve ADRs significantly but also lower the overall healthcare cost for screening colon cancer in this era of escalating healthcare costs.

Post-sphincterotomy transampullary balloon dilation is a safe and effective technique.

PURPOSE: To evaluate the safety and efficacy of performing ampullary balloon dilation (ABD) following endoscopic sphincterotomy (ES). METHODS: Retrospective review of patients that underwent ABD at Thomas Jefferson University from 2000 to 2007. In all cases, dilation was performed with Hurricane RX hydrostatic balloons (Boston Scientific, Natick MA) or CRE esophageal dilating balloons (Boston Scientific, Natick MA). RESULTS: ABD following ES was performed in 69 patients. The procedure was performed for choledocholithiasis in 58%, abnormal imaging in 26%, and abnormal liver enzymes in 23% of patients. ABD following ES was 86% successful in achieving the intended therapeutic goal of the procedure. Pancreatitis (2.9%) post endoscopic retrograde cholangiopancreatography (ERCP) occurred in two individuals, with one case of hemorrhage (1.5%) and one perforation (1.5%). CONCLUSION: ABD following ES is a safe and effective alternative to ES alone, particularly for the extraction of large common bile duct (CBD) stones.

Is There a Role for Sonde Enteroscopy in Patients with Obscure Gastrointestinal Bleeding? A Comparison with Capsule Endoscopy.

BACKGROUND: In the 1980's and 1990's combined Push and Sonde Enteroscopy was the primary endoscopic tool used to evaluate the small intestine in patients with obscure gastrointestinal bleeding (OGIB). It was available in only a few centers due to the technical difficulties associated with its use. The introduction of wireless capsule endoscopy in 2001 revolutionalized small bowel endoscopic imaging making Sonde enteroscopy a rarely used procedure despite the lack of studies comparing the efficacy of the two modalities. The aim of this study was to restrospectively compare the findings of Sonde enteroscopy with capsule endoscopy in patients with OGIB. METHODS: Design: One hundred patients who underwent Sonde enteroscopy and 101 patients who underwent capsule endoscopy were retrospectively studied. Setting: All patients had their procedures completed by physicians within the same gastroenterology practice. Patients: All patients who underwent either Sonde enteroscopy or capsule endoscopy were enrolled. Interventions: None. Main outcome measurements: Outcome was defined as the number of patients in which a distinct bleeding site could be identified. RESULTS: A total of 100 patients underwent Push and Sonde enteroscopy and a potential bleeding site was identified in 55 (55%) patients. A total of 101 patients underwent capsule endoscopy and a potential bleeding site was identified in 60 (59%) patients. A one-tailed P value showed no statistically significant difference in the diagnostic yield between the procedures. CONCLUSIONS: Capsule endoscopy is at least as efficacious as Push/Sonde enteroscopy in evaluating patients with OGIB. We can comfortably retire Sonde enteroscopy as a diagnostic tool.

Role of nitric oxide in beta3-adrenoceptor activation on basal tone of internal anal sphincter.

Effects of activation of beta3-adrenoceptor (beta3-AR) have not been determined in the spontaneously tonic smooth muscle of the internal anal sphincter (IAS). The effects of disodium (R,R)-5-[2-[2-3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316243), a selective beta3-AR agonist, on the basal smooth muscle tone and direct release of nitric oxide (NO) by circular smooth muscle strips of the opossum IAS were determined. We also examined the presence of endothelial nitric oxide synthase (eNOS) protein by Western blot studies. CL 316243 produced a concentration-dependent relaxation of the smooth muscle that remained unmodified by different neurohumoral antagonists. The smooth muscle relaxation by CL 316243 was selectively antagonized by L 748337, a beta3-AR antagonist. Such relaxation was several times longer than by isoproterenol. The effect of CL 316243 was significantly attenuated by a nonselective NOS inhibitor N(omega)-nitro-l-arginine (l-NNA) and by putative inhibitor of eNOS l-N5-(1-iminoethyl)-ornithine dihydrochloride (l-NIO). Inhibitors of iNOS [N-(3-aminomethyl)benzyl acetamide 2HCl] and nNOS [1-[2-(trifluoromethylphenyl)imidazole]] had no effect on this relaxation. Relaxation of the IAS smooth muscle induced by CL 316243 was accompanied by an increased release of NO; this was attenuated by l-NNA and l-NIO. In addition, Western blot studies revealed the presence of eNOS in the circular smooth muscle of the IAS. These data demonstrate potent and protracted IAS smooth muscle relaxation by beta3-AR activation, which is partly transduced via NOS, possibly smooth muscle eNOS. Multiple signal-transduction pathways including NOS activation may explain the characteristic IAS relaxation by beta3-AR activation. The studies may have therapeutic implications in anorectal motility disorders.

Functional and molecular characterization of beta-adrenoceptors in the internal anal sphincter.

The purpose of the present study was to characterize different beta-adrenoceptors (beta-ARs) and determine their role in the spontaneously tonic smooth muscle of the internal anal sphincter (IAS). The beta-AR subtypes in the opossum IAS were investigated by functional in vitro, radioligand binding, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR) studies. ZD 7114 [(S)-4-[2-hydroxy-3-phenoxypropylaminoethoxy]-N-(2-methoxyethyl)phenoxyacetamide], a selective beta(3)-AR agonist, caused a potent and concentration-dependent relaxation of the IAS smooth muscle that was antagonized by the beta(3)-AR antagonist SR 59230A [1-(2-ethylphenoxy)-3-[[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]-(2S)-2-propanol hydrochloride]. Conversely, the IAS smooth muscle relaxation caused by beta(1)- and beta(2)-AR agonists (xamoterol and procaterol, respectively) was selectively antagonized by their respective antagonists CGP 20712 [(+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulfonate salt] and ICI 118551. Saturation binding of [(125)I]iodocyanopindolol to beta-AR subtypes revealed the presence of a high-affinity site (K(d1) = 96.4 +/- 8.7 pM; B(max1) = 12.5 +/- 0.6 fmol/mg protein) and a low-affinity site (K(d2) = 1.96 +/- 1.7 nM; B(max2) = 58.7 +/- 4.3 fmol/mg protein). Competition binding with selective beta-AR antagonists revealed that the high-affinity site correspond to beta(1)/beta(2)-AR and the low affinity site to beta(3)-AR. Receptor binding data suggest the predominant presence of beta(3)-AR over beta(1)/beta(2)-AR. Western blot studies identified beta(1)-, beta(2)-, and beta(3)-AR subtypes. The presence of beta(1)-, beta(2)-, and beta(3)-ARs was further demonstrated by mRNA analysis using RT-PCR. The studies demonstrate a comprehensive functional and molecular characterization of beta(1)-, beta(2)-, and beta(3)-ARs in IAS smooth muscle. These studies may have important implications in anorectal and other gastrointestinal motility disorders.

Inhibitory effect of beta3-adrenoceptor agonist in lower esophageal sphincter smooth muscle: in vitro studies.

We investigated the effects of (R,R)-5-[2-[2-3-chlorophenyl)-2-hydroxyethyl] - amino]propyl] - 1,3 - benzodioxole - 2, 2 - dicarboxylate (CL 316243) (a typical beta3-agonist) on the spontaneously tonic smooth muscle of the lower esophageal sphincter (LES). Studies were carried out in smooth muscle strips and smooth muscle cells (SMCs) of opossum LES. Isometric tension was recorded in the basal state and after CL 316243, and before and after beta3-antagonist (S)-N-[4-[2-[[3-[-(acetamidomethyl)phenoxy]-2-hydroxypropyl]amino]ethyl]phenyl]benzenesulfonamide (L 748337) and nonselective antagonist propranolol. In some experiments, the effects of nonadrenergic noncholinergic (NANC) nerve activation by electrical field stimulation (EFS) were also examined. The effects of CL 316243 were compared with those of nonselective beta-agonist isoproterenol. CL 316243 caused a concentration-dependent relaxation of the LES smooth muscle. The relaxant action of CL 316243 was determined to be directly at the smooth muscle because it remained unmodified by the neurotoxin tetrodotoxin and other neurohumoral antagonists, and also was observed in the SMCs. L 748337 selectively antagonized the relaxant effect of CL 316243 and, conversely, had no significant effect on the inhibitory actions of isoproterenol. CL 316243 (1 x 10(-8) M) caused an augmentation of NANC relaxation in the LES. Another beta3-agonist, (S)-4-[hydroxy-3-phenoxy-propylamino-ethoxy]-N-(2-methoxyethyl)-phenoxyacetamide (ZD 7114), also caused concentration-dependent full relaxation of the LES that was selectively antagonized by beta3-anatagonist 3-(2-ethylphenoxy)-1-[(1S)1,2,3,4-tetrahydronaphth-1-ylaminol]-(2S)-2-propanol oxalate (SR 59230A). These studies defined the effects of characteristic inhibitory beta3-adrenoceptors in the spontaneously tonic LES smooth muscle and suggested a potential therapeutic role in the esophageal motility disorders characterized by hypertensive LES.

Beta3 adrenergic stimulation inhibits the opossum lower esophageal sphincter.

BACKGROUND & AIMS: Previous studies have identified adrenergic receptor sites in the lower esophageal sphincter (LES) of animals and humans. A beta3 adrenoceptor has been identified and cloned. The binding site for this receptor has been found in the rat LES in vitro. The aim of the study was to assess the role of a specific beta3 agonist (CL316243) on LES pressure (LESP) in vivo. METHODS: Anesthetized adult opossums were given CL316243 and isoproterenol intravenously as boluses before and after continuous infusion of L748337 (a specific beta3 antagonist), propranolol, and bethanechol. Blood pressure, heart rate, and LESP were continuously recorded. RESULTS: CL316243 caused a dose-dependent maximal inhibition of LESP of 88.5% +/- 4.8%. The mean duration of inhibition was 62.2 +/- 9.2 minutes with minimal change in cardiovascular parameters. Isoproterenol caused dose-dependent maximal inhibition of 89.4% +/- 4.7% with mean duration of action of 5.1 +/- 0.9 minutes but was associated with significant hypotension and tachycardia. L748337 and propranolol significantly blocked the effects of CL316243 and isoproterenol, respectively. CL316243 and isoproterenol inhibited the bethanechol-mediated hypertensive LES. CONCLUSIONS: (1) A selective beta3 agonist, CL316243, caused significant, prolonged, and dose-dependent inhibition of LESP and, unlike isoproterenol, had minimal effect on heart rate and mean arterial pressure. (2) The beta3 antagonist, L748337, selectively inhibited CL316243 without altering the isoproterenol response. (3) CL316243 and isoproterenol both caused inhibition of cholinergic-mediated hypertensive LESP.