John O. Clarke

Classifying Esophageal Motility by Pressure Topography Characteristics: A Study of 400 Patients and 75 Controls

AIM:This study aimed to devise a scheme for the systematic analysis of esophageal high-resolution manometry (HRM) studies displayed using topographic plotting.METHODS:A total of 400 patients and 75 control subjects were studied with a 36-channel HRM assembly. Studies were analyzed in a stepwise fashion for: (a) the adequacy of deglutitive esophagogastric junction (EGJ) relaxation, (b) the presence and propagation characteristics of distal esophageal persitalsis, and (c) an integral of the magnitude and span of the distal esophageal contraction.RESULTS:Two strengths of pressure topography plots compared to conventional manometric recordings were: (a) the ability to delineate the spatial limits, vigor, and integrity of individual contractile segments along the esophagus, and (b) the ability to distinguish between loci of compartmentalized intraesophageal pressurization and rapidly propagated contractions. Making these distinctions objectified the identification of distal esophageal spasm (DES), vigorous achalasia, functional obstruction, and nutcracker esophagus subtypes. Applying these distinctions made the diagnosis of spastic disorders quite rare: (a) DES in 1.5% patients, (b) vigorous achalasia in 1.5%, and (c) a newly defined entity, spastic nutcracker, in 1.5%.CONCLUSIONS:We developed a systematic approach to analyzing esophageal motility using HRM and pressure topography plots. The resultant scheme is consistent with conventional classifications with the caveats that: (a) hypercontractile conditions are more specifically defined, (b) distinctions are made between rapidly propagated contractions and compartmentalized esophageal pressurization, and (c) there is no “nonspecific esophageal motor disorder” classification. We expect that pressure topography analysis, with its well-defined functional implications, will prove valuable in the clinical management of esophageal motility disorders.

A Review of Complementary and Alternative Approaches to Immunomodulation.

Current Western therapies for inflammatory diseases are suboptimal; increasingly, patients are turning to complementary and alternative medicine for symptom relief and improved quality of life. There is emerging evidence that many of these therapies have the ability to modulate the immune system and disrupt the proinflammatory cascade through a variety of mechanisms, including antioxidant effects, alterations in cell signaling (in particular the nuclear factor (NF)-κB pathway), cytokines, proinflammatory mediators, and disruption of bacterial flora. Using inflammatory bowel disease (IBD) as a model of inflammation, we explore the principal complementary and alternative medicine treatments that show promise in this regard, namely, resveratrol, green tea, curcumin, boswellia, fish oil, vitamin D, and probiotics. With each agent, we detail the mechanisms that have been described with regard to immune modulation, discuss the medical conditions for which it has been evaluated, and explore the data to date for the prevention or treatment of IBD.

EUS-guided portal vein catheterization: a promising novel approach for portal angiography and portal vein pressure measurements

BACKGROUND Portal vein (PV) pressure measurements can provide valuable information for the management of patients with liver disease and portal hypertension. OBJECTIVE To evaluate the feasibility and the safety of EUS-guided PV catheterization and pressure measurements in a porcine model. SETTING Acute and survival experiments on five 50-kg pigs. DESIGN AND INTERVENTIONS Intrahepatic PV was punctured under EUS guidance by using a 19-gauge FNA needle. A 0.035-inch guidewire was advanced through the needle into the PV. The needle was withdrawn. A 5.5F ERCP catheter was advanced over the guidewire into the PV and then connected to a pressure monitor. Continuous PV measurements were obtained for an hour. Afterward, the catheter was removed, and the animals were observed for 30 minutes. Three animals were then immediately euthanized for a necropsy. The other two animals were observed for two weeks and then were euthanized. MAIN OUTCOME MEASUREMENTS The ability to perform EUS-guided PV catheterization and pressure measurement without complications. RESULTS PV catheterization, angiography, and pressure measurements were performed without any problems or complications. There were no changes in vital signs and hemodynamic parameters during PV catheterizations, angiography, pressure measurements, and catheter removal. Survival experiments did not demonstrate any change in animal condition, behavior, or eating habits after the procedure. A necropsy in all animals revealed no active bleeding, and no damage to the liver, other intra-abdominal organs, or blood vessels. LIMITATIONS No validation of measured PV pressure was made. CONCLUSIONS EUS-guided PV catheterization is feasible, safe, and can be used for portal angiography and pressure measurements.

How good is capsule endoscopy for detection of periampullary lesions? Results of a tertiary-referral center

BACKGROUND Ampullary adenomas are increasingly being recognized, particularly in patients with familial adenomatous polyposis. A capsule endoscopy (CE) is routinely recommended for surveillance of small-intestinal polyposis. Performance characteristics of CE for the detection of periampullary lesions are unclear. OBJECTIVE To evaluate the ability of CE to detect the major duodenal papilla. DESIGN AND PATIENTS A total of 146 consecutive CE studies were reviewed by 2 CE gastroenterologists at 5 frames per second. Primary outcome was visualization of the major duodenal papilla. Discrepancies were reviewed by 5 CE gastroenterologists. SETTING A tertiary-referral center. MAIN OUTCOME MEASUREMENTS The ability of CE to detect the duodenal papilla. RESULTS Among 146 consecutive CE studies, 21 were excluded: capsule retention (3), patient age <18 years (6), duplicate study (8), and prior surgery disrupting duodenal anatomy (4). Of the remaining 125 studies, indications were the following: obscure GI bleeding (45.6%), iron deficiency anemia (19.2%), abdominal pain (17.6%), diarrhea (10.4%), and Crohns disease (4.8%). In total, 13 major duodenal papillae were visualized. The median time of detection was 31 seconds after the first duodenal image. This translates to a CE sensitivity of 10.4% for detection of the major papilla. LIMITATION Papilla position was not verified by an EGD. CONCLUSIONS CE has limited sensitivity to visualize the major papilla and lesions in the periampullary small intestine. Nondiagnostic CE studies must not be relied upon as proof that small-bowel lesions do not exist. Consideration should be given for an enteroscopy or side-viewing duodenoscopy in cases where significant clinical concern exists for unrecognized periampullary lesions. The current recommendations about surveillance for small-bowel polyposis should be revised.

The Added Diagnostic Value of Liquid Gastric Emptying Compared with Solid Emptying Alone

The medical literature states that solid gastric-emptying studies are more sensitive for the detection of gastroparesis than are liquid studies; thus, liquid studies are rarely required. However, we have seen patients with normal solid but delayed liquid emptying. The purpose of this investigation was to determine whether a study of clear liquid gastric empting has added value for the diagnosis of gastroparesis over a study of solid emptying alone. Methods: A total of 101 patients underwent both solid and liquid gastric-emptying studies, acquired sequentially on the same day. A 30-min (1-min frames) liquid study (300 mL of water with 7.4 MBq [0.2 mCi] of 111In-diethylenetriaminepentaacetic acid) was followed by a standardized 4-h solid-meal study (a 99mTc-sulfur colloid–labeled egg-substitute sandwich meal). Emptying was quantified as a best-fit exponential emptying rate (T1/2) for liquids and percentage emptying at 4 h for solid empting. Thirty healthy volunteers underwent a study of clear liquid emptying to establish normal values. The results of the liquid and solid studies were compared. 111In liquid downscatter into the subsequent 99mTc solid meal results was analyzed. Results: The upper range of normal for clear liquid emptying (T1/2) for healthy volunteers was 22 min (mean ± 3 SDs) and 19 min (mean ± 2 SDs). Of 101 patients, delayed emptying was found in 36% of liquid and 16% of solid studies. Of all patients with normal solid emptying, 32% had delayed liquid emptying. 111In downscatter into the 99mTc window was not generally significant. Conclusion: For the detection of gastroparesis, a 30-min study of clear liquid gastric-emptying has considerable added diagnostic value over a study of solid emptying alone.

Refractory gastroparesis can be successfully managed with endoscopic transpyloric stent placement and fixation (with video).

BACKGROUND AND AIMS Medical treatment options for gastroparesis are limited. Data from studies of botulinum toxin and surgical pyloroplasty suggest that disruption of the pylorus can result in symptomatic improvement in some patients with refractory gastroparetic symptoms. The aim of this study was to determine the clinical response to transpyloric stent (TPS) placement in patients with gastroparetic symptoms refractory to standard therapy. METHODS Patients with gastroparesis refractory to medical treatment were referred for TPS placement for salvage therapy. Self-reported symptom improvement, stent migration rate, and pre- and post-stent gastric-emptying study results were collected. RESULTS A total of 30 patients with refractory gastroparesis underwent 48 TPS procedures. Of these, 25 of 48 (52.1%) were performed in patients admitted to the hospital with intractable gastroparetic symptoms. Successful stent placement in the desired location across the pylorus (technical success) was achieved during 47 procedures (98%). Most (n = 24) stents were anchored to the gastric wall by using endoscopic suturing with a mean number of sutures of 2 (range 1-3) per procedure. Clinical response was observed in 75% of patients, and all inpatients were successfully discharged. Clinical success in patients with the predominant symptoms of nausea and vomiting was higher than in those patients with a predominant symptom of pain (79% vs 21%, P = .12). A repeat gastric-emptying study was performed in 16 patients, and the mean 4-hour gastric emptying normalized in 6 patients and significantly improved in 5 patients. Stent migration was least common (48%) when stents were sutured. CONCLUSION TPS placement is a feasible novel endoscopic treatment modality for gastroparesis and improves both symptoms and gastric emptying in patients who are refractory to medical treatment, especially those with nausea and vomiting. TPS placement may be considered as salvage therapy for inpatients with intractable symptoms or potentially as a method to select patients who may respond to more permanent therapies directed at the pylorus.

Outcomes and Factors Associated With Reduced Symptoms in Patients With Gastroparesis

BACKGROUND & AIMS Gastroparesis is a chronic clinical syndrome characterized by delayed gastric emptying. However, little is known about patient outcomes or factors associated with reduction of symptoms. METHODS We studied adult patients with gastroparesis (of diabetic or idiopathic type) enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Gastroparesis Registry, seen every 16 weeks and treated according to the standard of care with prescribed medications or other therapies at 7 tertiary care centers. Characteristics associated with reduced symptoms, based on a decrease of 1 or more in the gastroparesis cardinal symptom index (GCSI) score after 48 weeks of care, were determined from logistic regression models. Data were collected from patients for up to 4 years (median, 2.1 y). RESULTS Of 262 patients, 28% had reductions in GCSI scores of 1 or more at 48 weeks. However, there were no significant reductions in GCSI score from weeks 48 through 192. Factors independently associated with reduced symptoms at 48 weeks included male sex, age 50 years and older, initial infectious prodrome, antidepressant use, and 4-hour gastric retention greater than 20%. Factors associated with no reduction in symptoms included overweight or obesity, a history of smoking, use of pain modulators, moderate to severe abdominal pain, a severe gastroesophageal reflex, and moderate to severe depression. CONCLUSIONS Over a median follow-up period of 2.1 years, 28% of patients treated for gastroparesis at centers of expertise had reductions in GCSI scores of 1 or greater, regardless of diabetes. These findings indicate the chronic nature of gastroparesis. We identified factors associated with reduced symptoms that might be used to guide treatment. ClinicalTrials.gov no: NCT00398801.

Small Intestinal Transit Time Is Delayed in Small Intestinal Bacterial Overgrowth

Background: Altered small intestinal motility is thought to contribute to the development of small intestinal bacterial overgrowth (SIBO). The clinical manifestations of SIBO and consequent malabsorption are wide ranging and include abdominal pain, bloating, diarrhea, weight loss, and nutritional deficiencies. However, due to the nonspecific nature of symptoms, the diagnosis may often be overlooked. To date, few studies have illustrated a direct relationship between impaired small intestinal motility and SIBO. In addition, further study has been limited by the technical challenges and lack of widespread availability of antroduodenal manometry. The development of a wireless motility capsule (WMC) (SmartPill) that evaluates pressure, pH, and temperature throughout the GI tract offers the potential to identify patients with small bowel transit delays who may be at risk for bacterial overgrowth. Aims: The primary aims of this study were to: (1) characterize the relationship of prolonged small bowel transit time (SBTT) in patients undergoing WMC with SIBO as based on a positive lactulose breath testing (LBT); and (2) to assess the relationship of prolonged gastric, colonic, and whole gut transit times (WGTT) and additional motility parameters with SIBO (positive LBT). We also sought to evaluate the relationship of small bowel motility parameters (SB motility index, contractions per minute, and SB peak amplitudes) with LBT results. Methods: We performed a retrospective study of consecutive patients who were referred for wireless motility testing at a single, tertiary care institution from April 2009 to December 2012. Of the 72 total patients identified, 34 underwent both WMC and LBT. Gastric, small bowel, colonic, WGTT, and SB motility parameters were measured and correlated with LBT results. Statistical methods utilized for data analysis include ANOVA, 2-sample t tests, nonparametric Kruskal Wallis test, Wilcoxon rank-sum test, and the Fisher exact test. Results: Of the 37 patients who underwent both WMC and LBT, 24 (65%) were LBT positive. The mean SBTT among those who were LBT positive was 6.6 hours as compared with 4.2 hours in those who were LBT negative (P=0.04). Among patients who were LBT positive, 47.6% had prolonged SBTT (≥6 h), whereas only 7.7% of those who were LBT negative had a delay in their SBTT (P=0.01). In addition, patients who were LBT positive were more likely to have prolongation of both colonic and WGTT versus those who were LBT negative (CTT: positive LBT=64.4 h vs. negative LBT=35.5 h, P=0.02; WGTT: positive LBT=70.5 h vs. negative LBT=44.1 h, P=0.02). However, there were no statistical differences observed between the groups for gastric emptying times or other small intestinal motility parameters (SB motility index, contractions per minute, and peak amplitudes) between the 2 groups. Conclusions: Patients with underlying SIBO have significant delays in SBTT as compared with those without. The association between prolonged SBTT and positive LBT may be useful in identifying those patients with SIBO diagnosed by LBT and potentially target therapeutic options for those refractory to standard therapy. Interestingly, patients with positive LBT did not necessarily have a generalized gastrointestinal motility (similar GETs among groups), suggesting that small bowel transit specifically predisposes to the development of SIBO. Future, prospective studies are needed to further characterize intestinal dysmotility and other contributing pathophysiological mechanisms in SIBO and to investigate the potential benefits of prokinetics in this challenging patient population.

Biofeedback therapy for defecatory dysfunction: "real life" experience.

Background: Biofeedback therapy (BF) is a well-established treatment modality for patients with dyssynergic defecation and fecal incontinence (FI). Randomized controlled trials from highly specialized tertiary care centers report response rates of 70% to 80% for dyssynergic defecation and 55% to 75% for FI. Whether this therapy is as successful outside of clinical trials or specialized biofeedback referral centers remains unclear. Aim: Our primary aim was to determine what percentage of patients referred for BF actually complete therapy and identify barriers to treatment. Our secondary aim was to determine the clinical response rate in a heterogenous population of patients undergoing BF at our institution and a variety of regional locations. Methods: We retrospectively reviewed patients who underwent high resolution anorectal manometry between 2007 and 2010 for symptoms of defecatory dysfunction. BF was recommended at the time of manometry analysis based on findings of dyssynergy, impaired or heightened rectal sensation, or poor augmentation of sphincter on squeeze maneuvers. Clinical response was recorded after a course of BF (≥5 sessions). Results: Two hundred three patients (78% female, 72% white; median age 52) underwent anorectal manometry for symptoms of constipation (130), FI (54), combination (12), and rectal pain (7). BF was recommended in 119 cases (58.6%): constipation (80), FI (27), combination (9), and rectal pain (3). Only 39 out of 80 (48%) patients with constipation ultimately underwent BF. Of the 27 FI cases, only 12 (44%) patients underwent BF. Barriers to BF included lack of insurance coverage, distance to local treatment facilities, and acute medical issues taking precedence. Of those who underwent at least 5 BF sessions, subjective short-term response rates based on patient opinion were 17/28 (60%) in the constipation group and 8/10 (80%) in the FI group. Age, sex, and race had no effect on whether the patients attended biofeedback or whether they responded to treatment. The location of BF also did not predict response to therapy. Conclusions: In a heterogenous patient population, less than half of patients recommended for BF ultimately underwent therapy. Despite this, the response rates in this small population undergoing BF in the “real world” are only slightly less than published randomized control trials. Prospective studies are warranted to further elucidate and eliminate barriers to BF, especially given that “real world” BF response rates may be comparable with those seen in clinical trials.

Pyloric sphincter therapy: botulinum toxin, stents, and pyloromyotomy.

Gastroparesis is a syndrome characterized by delayed gastric emptying with associated symptoms. Gastric emptying is a complex process and pyloric dysfunction may play a key role in select subsets of patients with gastroparesis. Diagnostic tests to measure pyloric physiology are now available and have the potential to be more widely used in clinical practice. Targeted therapies including botulinum toxin, transpyloric stent placement, surgical pyloroplasty and endoscopic pyloromyotomy have been developed. Data are emerging regarding efficacy and durability, but these therapies may play a prominent role in select patients with gastroparesis and pyloric dysfunction.