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Gary W Falk

Publications and source records attributed to Gary W Falk.

At least 19 recordsLinked to original sources
PubMed2006

Gastric and esophageal pH in patients with Barrett's esophagus treated with three esomeprazole dosages: a randomized, double-blind, crossover trial.

BACKGROUND: It has been suggested that patients with Barrett's esophagus (BE) are unusually resistant to the antisecretory effects of proton pump inhibitors (PPIs). OBJECTIVES: To compare intragastric and intraesophageal acidity in patients with BE receiving esomeprazole 40 mg three times daily (t.i.d.), esomeprazole 40 mg twice daily (b.i.d.), and esomeprazole 20 mg t.i.d. METHODS: In this randomized, double-blind, three-way crossover study, patients with long-segment BE received each of the three esomeprazole dosages for 5 days separated by 10-14-day washout periods. Intragastric and intraesophageal pHs were measured for 24 h on day 5. RESULTS: Among 31 patients with evaluable pH data, intragastric pH was >4.0 for 88.4%, 81.4%, and 80.4% of day 5 after treatment with esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. Esomeprazole 40 mg t.i.d. was significantly more effective than the other dosages (p < 0.01). Intraesophageal pH was <4.0 for mean values of <5% of the monitoring period with all the three dosing regimens, but esophageal pH remained <4.0 for >5% of the time in 16%, 23%, and 19% of patients receiving esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. All dosages were well tolerated. CONCLUSIONS: All the three esomeprazole dosages significantly decreased intragastric acidity and reduced esophageal acid exposure to mean normal values in the total group of patients with BE. However, abnormal esophageal acid exposure continued in 16-23% of patients despite the significant decrease in gastric acidity. These results suggest that the apparent "PPI resistance" described in patients with BE may be caused by their profound reflux diathesis rather than by gastric resistance to the antisecretory effects of PPIs.

Aged↗
PubMed2006

Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus.

BACKGROUND & AIMS: The exact incidence of adenocarcinoma in patients with Barrett's esophagus (BE) is not known and is reported to vary from 0.2%-2% per year. Published series of patients with BE have included relatively small numbers of patients with limited duration of follow-up. The goal of this study was to define the prevalence and incidence of dysplasia and cancer and evaluate the paths of progression in a large multicenter cohort of BE patients. METHODS: The BE study is a multicenter clinical and endoscopic outcomes project involving a single large database of patients with BE. Data from each of the participating centers were merged into the main study database. Cancers and HGD occurring within 12 months of the index endoscopy were regarded as prevalent cases. RESULTS: One thousand three hundred seventy-six patients met the study criteria (95% white, 14% women); 91 patients had cancer at the initial endoscopy (prevalent cases, 6.7%; 95% confidence interval [CI], 4.8%-8.7%). Six hundred eighteen patients were followed for a total of 2546 patient-years; mean follow-up was 4.12 years. Twelve patients developed cancer during follow-up, a cancer incidence of 1 in 212 patient-years of follow-up (0.5% per year; 95% CI, 0%-1.1%). The combined incidence of HGD and/or cancer was 1 in 75 patient-years of follow-up or 1.3% per year (95% CI, 0%-2.2%). Of the 34 patients developing HGD and/or cancer, 18 patients (53%) had at least 2 initial consecutive endoscopies with biopsies revealing nondysplastic mucosa. The incidence of LGD was 4.3% per year (95% CI, 2.8%-6.0%). In the 156 patients with LGD, regression to no dysplasia occurred in 66%, persistent LGD in 21%, and progression to HGD/cancer in 13%. The incidence of cancer in patients with LGD was 1 in 156 patient-years of follow-up or 0.6% per year (95% CI, 0%-1.3%). CONCLUSIONS: Preliminary results from this trial define the prevalence and incidence of dysplasia and cancer in a multicenter cohort of patients with BE. At least half the patients who developed HGD and/or cancer had 2 consecutive initial endoscopies with biopsies revealing nondysplastic mucosa. The majority of patients with LGD regressed and had a cancer incidence similar to all BE patients.

Adenocarcinoma↗
PubMed2006

Barrett's esophagus at a tertiary care center: association of age on incidence and prevalence of dysplasia and adenocarcinoma.

OBJECTIVES: Barrett's esophagus (BE) is traditionally thought of as a disease of middle-aged Caucasian men. Little is known about BE in younger patients. We sought to assess the effect of age on features of BE including the prevalence and incidence of dysplasia and carcinoma. METHODS: All patients enrolled into the Cleveland Clinic BE registry from 1979 to 2002 were studied. Age, ethnicity, number of endoscopies, hiatal hernia size, length of Barrett's segment, prevalence and incidence of dysplasia, and cancer were compared between patients > or = 50 yr old and < 50 yr old. RESULTS: There were 837 patients in the registry (638 > or = 50 yr, 199 < 50 yr). Hiatal hernia size was larger in patients > or = 50 yr than in those < 50 yr (median 4.0 cm, interquartile range 2.0-5.0 cm vs 3.0, 2.0-4.0 cm; p < 0.01). Otherwise, there were no significant differences among other features in the patient population. There were 225 patients with dysplasia or cancer (195 > or = 50 yr and 30 < 50 yr; p < 0.01). Of this group, 176 were prevalent cases (159 > or = 50 yr and 17 < 50 yr) and 49 were incident cases (36 > or = 50 yr and 13 < 50 yr). The odds of those > or = 50 yr being a prevalent case of high-grade dysplasia or cancer was five times the odds of those < 50 yr (p < 0.01). The incidence of dysplasia or cancer was similar in both age groups. CONCLUSIONS: Our study supports emerging data that approximately 25% of BE patients are less than 50 yr of age. While older patients had a higher prevalence of dysplasia or adenocarcinoma, the incidence of dysplasia and adenocarcinoma is similar in both age groups. Future screening strategies for BE should recognize these important findings.

Adenocarcinoma↗
PubMed2005

Esophageal manometry: assessment of interpreter consistency.

BACKGROUND AND AIMS: Manometry is used widely in the evaluation of esophageal disorders. Our aim was to assess the intra- and interobserver reliability of esophageal manometry and identify potential causes for diagnostic variability. METHODS: Seventy-two esophageal manometry tracings were selected randomly from archives. Eight interpreters randomly and blindly evaluated tracings. Interpreters were divided into 3 groups: highly experienced (N = 3), moderately experienced (N = 3), and inexperienced (N = 2). Each tracing was examined for abnormalities involving the lower-esophageal sphincter (LES) and esophageal body. Interpreters rendered a single diagnosis from a list of 7 manometric diagnoses: normal, nutcracker, hypertensive LES, hypotensive LES, diffuse esophageal spasm (DES), nonspecific/ineffective esophageal motility (IEM), and achalasia. Intra- and interobserver agreements were determined and reasons for varied diagnoses were investigated. RESULTS: Overall intraobserver agreement was good (kappa = .63, P < .0001). There was no difference ( P = .9) between the highly and midexperienced interpreters (kappa = .61 and .65, respectively). Interobserver agreement for the diagnosis of achalasia and normal motility was good (kappa = .65 and .56, respectively). However, other manometric diagnoses yielded only fair interobserver agreement (kappa = .27). DES, nonspecific/ineffective esophageal motility (IEM), and hypo- and hypertensive LES diagnoses showed the least agreement. Poor adherence to established manometric criteria, misinterpretation of intrabolus pressure, and technical inadequacy were the most common sources of inconsistency in interpretations. CONCLUSIONS: Manometric diagnoses of conditions other than normal or achalasia are variable and have poor interobserver variability. Given their uncertain clinical implications, we must either redefine them or eliminate them from practice.

Adult↗
PubMed2005

Barrett's esophagus in women: demographic features and progression to high-grade dysplasia and cancer.

BACKGROUND & AIMS: Barrett's esophagus is traditionally considered a disease of older white men. The aims of this study were to compare the demographic features of Barrett's esophagus in men and women and to determine the prevalence and incidence of high-grade dysplasia and cancer in these patients. METHODS: All patients enrolled in the Cleveland Clinic Barrett's Esophagus Registry from 1979-2002 were studied. Age, ethnicity, number of endoscopies, hiatal hernia size, length of Barrett's segment, and prevalence and incidence of high-grade dysplasia and cancer were compared between men and women. RESULTS: There were 839 patients in the registry (628 men and 211 women). Barrett's segment length was greater in men than in women (mean, 5.06 +/- 4.2 vs 4.05 +/- 3.27 cm, respectively; P = .003). There were no significant differences for other parameters. There were 114 prevalence cases of high-grade dysplasia or cancer (96 men, 18 women). Women were less likely to have prevalent high-grade dysplasia or cancer than men (odds ratio, 0.52; 95% confidence interval, 0.31-0.88; P = .015). There were 13 incidence cases of high-grade dysplasia or cancer (11 men, 2 women) during a mean follow-up of 4.72 years, which was similar in both genders with an incidence rate of 1 in 179 patient-years of follow-up for women and 1 in 91 patient-years of follow-up in men. CONCLUSIONS: Twenty-five percent of patients in our registry are women. The length of Barrett's esophagus is greater in men than in women, but other features are similar. The prevalence of high-grade dysplasia/cancer in women is approximately half that of men. Incidence rates for high-grade dysplasia/cancer are similar in men and women, although the number of cases is small.

Adenocarcinoma↗
PubMed2005

Barrett's esophagus-is it bad for your health?

Barrett's esophagus is a clearly recognized risk factor for the development of esophageal adenocarcinoma. Despite the rapidly increasing incidence rate of esophageal adenocarcinoma, the vast majority of patients with Barrett's esophagus will never go on to develop this cancer. Furthermore, esophageal adenocarcinoma is a rare cause of death in Barrett's esophagus patients, and most of these patients die from other causes. While some studies demonstrate that the overall survival of patients with Barrett's esophagus is no different than that of the general population, others have suggested that Barrett's esophagus may be associated with increased mortality. Work by Solaymani-Dodran et al., in the current issue of the American Journal of Gastroenterology, found that all cause mortality was increased by 37% and mortality from causes other than esophageal cancer was increased by 23% compared to the general population, differences that were eliminated when adjusted for ischemic heart disease. Findings such as these point out the need for large, well-done epidemiologic studies of Barrett's esophagus cohorts in order to develop a better understanding of the natural history of this disease.

Adenocarcinoma↗
PubMed2004

Fluorescence in situ hybridization of cytologic specimens from Barrett's esophagus: a pilot feasibility study.

BACKGROUND: Endoscopic brush cytology is a promising surveillance technique for Barrett's esophagus. However, there is a need for ancillary biomarkers to increase the sensitivity of cytology and to allow identification of patients at increased risk for disease progression. The aims of this study were to evaluate the feasibility of fluorescence in situ hybridization of endoscopic brush cytology specimens and to determine if there are specific chromosomal changes in cytologic specimens from patients with cancer that are not present in patients without dysplasia. METHODS: Archival cytology slides from 16 patients with Barrett's esophagus were studied: 8 negative for dysplasia and 8 positive for adenocarcinoma. Fluorescence in situ hybridization was used to detect two alterations: HER-2 gene (17q11.2-q12) and 20q13.2 region amplification. OBSERVATIONS: For 7 of 8 adenocarcinoma cases, there was amplification/aneusomy of at least one of the two analyzed regions by fluorescence in situ hybridization. None of the samples negative for dysplasia were abnormal for either of the two genomic regions studied. CONCLUSIONS: Fluorescence in situ hybridization is feasible by using routine Barrett's esophagus cytologic specimens. Differences in genomic makeup can be detected in cells from patients negative for dysplasia and in those with adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens.

Endoscopic brush cytology is a promising surveillance technique for Barrett's esophagus. Ancillary markers are sought to increase the sensitivity of cytology and allow identification of patients at increased risk for disease progression. To determine if there are specific genetic changes in Barrett's esophagus with associated high-grade dysplasia/intramucosal adenocarcinoma compared to those without dysplasia, we performed fluorescence in situ hybridization (FISH) on cytologic specimens using probes to chromosomes and genomic regions previously described as altered in this disease. We studied archival brush cytology slides from 40 Barrett's esophagus patients: 21 with biopsy-proven high-grade dysplasia/carcinoma and 19 with no dysplasia and a minimum 5 years of negative follow-up. Centromeric enumeration probes (CEP) for chromosomes 6, 7, 11, and 12, and locus-specific probes (LSI) for 9p21 (p16 gene), and 17p13.1 (p53 gene) loci along with their corresponding CEP (9 and 17, respectively) were used in this study. A positive FISH result was defined as the presence of cells with >2 CEP signals or with a loss of the LSI signals relative to their corresponding CEP. p53 locus loss and/or aneusomy of chromosomes 6, 7, 11, and 12 abnormalities could be detected by FISH in routinely processed endoscopic brush cytology specimens from 95% of biopsy-positive cases with a specificity of 100%. Interestingly, all five cases with cytologic changes classified as indefinite for dysplasia from patients with a positive biopsy showed changes by FISH. Loss of the p16 locus was seen commonly in patients both with and without dysplasia/carcinoma. Selected biomarkers from this study merit further investigation to determine their potential to detect genetic changes in patients with Barrett's esophagus prior to the development of high-grade dysplasia.

Barrett Esophagus↗
PubMed2003

Cytology in Barrett's esophagus.

Brush cytology is complementary to endoscopic biopsy and is recommended by some to be part of the routine endoscopic surveillance of patients with BE. Advantages of cytology include the ability to sample a greater area of involved epithelium, preferential exfoliation of the less cohesive dysplastic cells, simplicity, and lower cost. There are clear cytologic criteria for dysplasia, and biomarker studies can be performed on cytologic specimens. Despite these advantages, cytology is used by only 17% of gastroenterologists in the United States today. Limited data are available on the usefulness of cytology in the diagnosis and surveillance of BE. Cytology has good sensitivity for the detection of adenocarcinoma and HGD and good specificity for the detection of IM without dysplasia. Furthermore, cytology may detect abnormalities missed by biopsy. Cytology has problems in the detection of LGD, however. For cytology to become a useful surveillance option, its sensitivity for low-grade lesions must be improved. One potential way to accomplish this is to add biomarkers to routine cytologic specimens to define patients at increased risk of progression to cancer. If simple prognostic biomarkers could be developed and validated in histology and cytologic specimens, this would provide additional support for the utility of cytologic brushings in the surveillance of BE. Cytology could then conceivably accomplish the goals of improved efficiency, risk stratification, and decreased costs in BE surveillance programs.

Adenocarcinoma↗
PubMed2003

Risk factors for dysplasia in patients with Barrett's esophagus (BE): results from a multicenter consortium.

Studies show Barrett's esophagus prevalence increases with age, while mean length of Barrett's esophagus is unchanged. Few data are available about the relationship between age and length on the development of dysplasia. Our aim was to assess age and length as risk factors for dysplasia. Consecutive patients with Barrett's esophagus were enrolled in a multicenter study establishing a tissue bank of Barrett's esophagus patients 1994 and 1998. Demographics, length of Barrett's esophagus (centimeters), and histology were recorded. Risk factors for dysplasia were assessed, including patient age, gender, and length of Barrett's esophagus. Statistical analysis was performed comparing prevalence of dysplasia (which included the presence of any carcinoma and high- or low-grade dysplasia) to age and length. In all, 309 patients were studied [278 (90%) male and 31 (10%) female]: 5 had adenocarcinoma of the esophagus, 11 had high-grade dysplasia, and 29 had low-grade dysplasia. Patients with Barrett's esophagus without dysplasia were younger than those with dysplasia [62 +/- 0.8 years vs 67 +/- 1.7 years (mean +/- SEM, P = 0.02)]. The risk of dysplasia increased by 3.3%/yr of age. Mean length of Barrett's esophagus in patients with Barrett's alone vs dysplasia was 4.0 +/- 0.2 cm vs 5.4 +/- 0.4 cm (P = 0.003). Patients with Barrett's esophagus length > or = 3 cm had a significantly greater prevalence of dysplasia compared to length < 3 cm (23% vs 9%, P = 0.0001). The risk of dysplasia increased by 14%/cm of increased length. Multivariate analysis showed age and length to be independent risk factors. In conclusions: prevalence of dysplasia is strongly associated with age and length of Barrett's esophagus. These preliminary results can be used to develop a strategy for screening/surveillance based on age and length of Barrett's epithelium.

Adenocarcinoma↗
PubMed2003

Motility and GI function studies billing and coding guidelines: a position paper of the American Motility Society.

Tests that measure gastrointestinal function, such as esophageal motility testing, ambulatory twenty-four hour pH, electrogastrography, gastroduodenal, sphincter of Oddi, and anorectal manometry, as well as hydrogen breath testing are now an essential part in the evaluation of patients with functional gastrointestinal disorders. They are widely performed in a variety of clinical settings. In this paper we outline the position of the American Motility Society on billing and coding for these studies, and review the issues for these studies under the current United States Relative Value Scale system. We have also provided an outline for standardization of reports for these procedures, and propose changes and modifications of current medical necessity diagnoses.

Diagnostic Techniques, Digestive System↗
PubMed2002

Barrett's esophagus.

Barrett's esophagus is an acquired condition resulting from severe esophageal mucosal injury. It still remains unclear why some patients with gastroesophageal reflux disease develop Barrett's esophagus whereas others do not. The diagnosis of Barrett's esophagus is established if the squamocolumnar junction is displaced proximal to the gastroesophageal junction and if intestinal metaplasia is detected by biopsy. Despite this seemingly simple definition, diagnostic inconsistencies remain a problem, especially in distinguishing short segment Barrett's esophagus from intestinal metaplasia of the gastric cardia. Barrett's esophagus would be of little importance were it not for its well-recognized association with adenocarcinoma of the esophagus. The incidence of esophageal adenocarcinoma continues to increase and the 5-year survival rate for this cancer remains dismal. However, cancer risk for a given patient with Barrett's esophagus is lower than previously estimated. Current strategies for improved survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This can be accomplished either by screening more patients for Barrett's esophagus or with endoscopic surveillance of patients with known Barrett's esophagus. Current screening and surveillance strategies are inherently expensive and inefficient. New techniques to improve the efficiency of cancer surveillance are evolving rapidly and hold the promise to change clinical practice in the future. Treatment options include aggressive acid suppression, antireflux surgery, chemoprevention, and ablation therapy, but there is still no clear consensus on the optimal treatment for these patients.

Adenocarcinoma↗
PubMed2002

Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa.

OBJECTIVE: The etiology of inflammation below the normal Z-line is an area of intense debate. Some suggest this is the earliest change of chronic gastroesophageal reflux disease (GERD), whereas others indict Helicobacter pylori (H. pylori) as the main cause. The aim of this study was to evaluate the relationship among inflammation of gastric cardiac mucosa (carditis), H. pylori infection, and intestinal metaplasia in patients with GERD and Barrett's esophagus compared with age-matched controls. METHODS: Patients with GERD and Barrett's esophagus were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the gastric cardia (obtained on retroflexed view), fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: The prevalence of H. pylori infection did not significantly differ among the study populations: controls (42%), GERD (33%), and Barrett's esophagus (27%) (p = 0.20). However, the prevalence of carditis significantly decreased from the control group (30%) to those with GERD (23%) and Barrett's esophagus (11%) (p = 0.03). Overall, 42 of 51 (82%) patients with carditis had H. pylori; all had pangastritis. The prevalence of cardia intestinal metaplasia also significantly decreased from the control group (15%) to those with GERD (4%) and Barrett's esophagus (0%) (p = 0.003). Of 13 patients with cardia intestinal metaplasia, 12 had carditis, 10 had H. pylori infection, and seven had intestinal metaplasia elsewhere in the stomach. CONCLUSIONS: Inflammation of gastric cardiac mucosa decreases in prevalence from controls to patients with GERD and Barrett's esophagus and correlates strongly with H. pylori infection. Cardia intestinal metaplasia is associated with H. pylori-related cardiac inflammation and intestinal metaplasia elsewhere in the stomach.

Adult↗