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Richard E Sampliner

Publications and source records attributed to Richard E Sampliner.

At least 19 recordsLinked to original sources
PubMed2006

Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is a premalignant condition associated with an increased risk for the development of oesophageal adenocarcinoma (ADCA). Previous studies indicated that oxidative damage contributes to the development of ADCA. OBJECTIVE: To test the hypothesis that bile acids and gastric acid, two components of refluxate, can induce oxidative stress and oxidative DNA damage. METHODS: Oxidative stress was evaluated by staining Barrett's oesophagus tissues with different degrees of dysplasia with 8-hydroxy-deoxyguanosine (8-OH-dG) antibody. The levels of 8-OH-dG were also evaluated ex vivo in Barrett's oesophagus tissues incubated for 10 min with control medium and medium acidified to pH 4 and supplemented with 0.5 mM bile acid cocktail. Furthermore, three oesophageal cell lines (Seg-1 cells, Barrett's oesophagus cells and HET-1A cells) were exposed to control media, media containing 0.1 mM bile acid cocktail, media acidified to pH 4, and media at pH 4 supplemented with 0.1 mM bile acid cocktail, and evaluated for induction of reactive oxygen species (ROS). RESULTS: Immunohistochemical analysis showed that 8-OH-dG is formed mainly in the epithelial cells in dysplastic Barrett's oesophagus. Importantly, incubation of Barrett's oesophagus tissues with the combination of bile acid cocktail and acid leads to increased formation of 8-OH-dG. An increase in ROS in oesophageal cells was detected after exposure to pH 4 and bile acid cocktail. CONCLUSIONS: Oxidative stress and oxidative DNA damage can be induced in oesophageal tissues and cells by short exposures to bile acids and low pH. These alterations may underlie the development of Barrett's oesophagus and tumour progression.

8-Hydroxy-2'-Deoxyguanosine↗
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↗
PubMed2005

Epidemiology, pathophysiology, and treatment of Barrett's esophagus: reducing mortality from esophageal adenocarcinoma.

The definition of BE has evolved over time. BE is the key premalignant lesion for developing EAC. The epidemiology and pathophysiology of BE is outlined, and risk factors for BE and EAC are reviewed. GERD plays a crucial role in the pathophysiology and the clinical identification of BE. Endoscopy with biopsy is the best tool for diagnosing and surveying patients with BE. Detection of early neoplasia is the present approach to reduce EAC mortality. Novel technology should assist in the early detection of dysplasia to enable targeted therapy. Effective chemopreventive strategies may reduce the risk of progression to EAC.

Adenocarcinoma↗
PubMed2005

The better burn.

Explore the source record for details and available documents.

Barrett Esophagus↗
PubMed2005

Endoscopic antireflux procedures: a good wrap?

BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD) is prevalent worldwide. Until recently patients and physicians have had a choice between long-term medical therapy, usually in the form of proton pump inhibitors (PPIs), or surgical fundoplication. During the past several years, endoscopic antireflux therapies have been approved for GERD patients to potentially obviate the risks of surgery and avoid long-term medication use. The objective of this review was to critically evaluate existing literature on endoscopic antireflux therapies with regards to efficacy and safety. METHODS: A review of human studies by using Pub Med was performed. RESULTS: Injectable LES implants, endoscopically placed gastric plications, and radio frequency energy application to the LES comprise the 3 modes of antireflux therapies. These techniques received approval by the Food and Drug Administration on the basis of symptomatic evidence supplied by numerous uncontrolled trials. As a group, these techniques have demonstrated efficacy less than medical and surgical options, and yet they carry a rare but significant risk of serious complications and even death. CONCLUSIONS: The field is still evolving at this stage, and there is a need for more randomized sham and placebo-controlled trials to better define the subjective and objective outcomes of these endoscopic procedures. At this time endoscopic antireflux procedures should be used with caution after discussing risks and benefits with the patient.

Catheter Ablation↗
PubMed2005

Apoptosis resistance in Barrett's esophagus: ex vivo bioassay of live stressed tissues.

BACKGROUND AND AIMS: Barrett's esophagus (BE) is a premalignant lesion of the distal esophagus in which squamous epithelial cells are replaced by metaplastic intestinal-like columnar epithelium that contains goblet cells. The factors that contribute to the progression from normal squamous mucosa to BE, Barrett's dysplasia, and adenocarcinoma are not well understood at the molecular level. Since reflux of bile acids is associated with BE development, we speculate that cells with an apoptosis-resistant phenotype are selected after long-term repeated exposure to pulses of bile acids. This will result in the survival of cells with unrepaired DNA damage, and a consequent increase in genomic instability leading to cancer progression. The major goal of this study is to compare sensitivity to apoptosis induced by the bile acid, deoxycholate (DOC), a known inducer of apoptosis, in normal esophageal squamous epithelium, normal colon epithelium, and BE. METHODS: Thirteen patients with a confirmed diagnosis of BE and four patients who had undergone clinically indicated colectomy were included in the present study. Freshly obtained biopsies were incubated with control medium or medium supplemented with 1 mM DOC for 3 h and then evaluated for apoptotic changes using transmission electron microscopy and immunohistochemical staining for two apoptotic markers, cleaved caspase 3 and cleaved cytokeratin 18. RESULTS: Our results indicate that BE is resistant to apoptosis induced by DOC compared to esophageal squamous epithelium and normal colon epithelium. In addition, electron micrographs revealed mitochondrial swelling in squamous epithelial cells treated ex vivo with DOC, which was absent in epithelial cells of BE. Formation of swollen mitochondria is an early marker of apoptotic cell death. Altogether, the data indicate that reduced apoptosis capability in BE tissue may contribute to progression to esophageal adenocarcinoma.

Adult↗
PubMed2004

Is the length of newly diagnosed Barrett's esophagus decreasing? The experience of a VA Health Care System.

BACKGROUND & AIMS: Secular trends in the length of newly diagnosed Barrett's esophagus (BE) are unknown. We have anecdotally noticed less frequent new diagnoses of long segments of BE. METHODS: This is a retrospective analysis of prospectively collected information on a well-characterized large cohort of patients with documented BE that was diagnosed between 1981 and 2000 at Southern Arizona Department of Veterans Affairs Health Care System. We examined temporal changes in the length of BE at the time of diagnosis (frequency and proportions). We conducted correlation analyses, as well as multivariate linear regression analyses, to examine the association between year of diagnosis and BE length while adjusting for temporal differences in age, sex, ethnicity, previous use of antisecretory therapy, and the presence of intestinal metaplasia (IM) of the gastric cardia. RESULTS: There were 340 patients with BE first diagnosed between 1981 and 2000. All cases were defined by the presence of areas of salmon-colored mucosa in the lower end of the tubular esophagus and IM in biopsy specimens obtained from these areas on at least 2 endoscopic examinations. There were no significant changes over time in mean age of patients with BE (61 yr) or proportion of white patients (84%). The mean length of BE at the time of first diagnosis declined progressively over time. In the earliest period (1981-1985), mean BE length was 6 +/- 3.8 cm, whereas mean BE length in 1996-2000 was 3.6 +/- 2.9 cm. This observation was explained not only by more frequent diagnoses of short BE, but also by less frequent diagnoses of long BE (> or =3 cm). There was a strong inverse correlation between BE length at the time of diagnosis and year of diagnosis (Pearson's correlation coefficient, -0.29; P <0.0001). In the multivariate linear regression model, a more recent year of BE diagnosis was an independent predictor of shorter BE length (P <0.0001). Similar results were obtained in analyses restricted to veteran patients or those with BE > or = 3 cm. CONCLUSIONS: There has been a progressive decline in the length of newly diagnosed BE as a result of an increase in short-segment BE, but, curiously, also because of a decline in long-segment BE (> or =3 cm). These changes cannot be explained fully by changes in demographic features of patients, previous therapy, or the increasing emphasis on IM of the gastric cardia. The role of referral bias and/or temporal changes in the definitions cannot be excluded.

Age Distribution↗
PubMed2004

Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett's esophagus.

BACKGROUND AND AIMS: Esophageal acid exposure is important in the pathogenesis of Barrett's esophagus (BE), and possibly in the progression of BE to dysplasia and carcinoma. The aim of this study is to compare the development of dysplasia in BE patients treated with or without proton pump inhibitor (PPI) or histamine 2-receptor antagonist (H2RA). METHODS: We analyzed prospectively collected data by a single endoscopist on patients with BE in a VA (Veterans Affairs) setting over a 20-yr time period (1981-2000). A pathologist used standard criteria to diagnose BE/dysplasia. Pharmacy information after 1994 was retrieved from a computerized database, and from research files for the period before that. The receipt and the duration of H2RA and/or PPI use was compared between those with and without dysplasia. The incidence of dysplasia was examined in a Kaplan-Meier survival analysis stratified by PPI treatment status, and the risk of dysplasia was examined in a Cox multiple regression analysis controlling for demographic features, length of BE, and the year of BE diagnosis. RESULTS: We analyzed data for 236 unique veteran patients with a mean age at BE diagnosis of 61.5 yr, 86% Caucasian, and 98% male. During 1,170 patient-yr of follow-up, 56 patients developed dysplasia giving an annual incidence rate of 4.7%. Of those, 14 had high-grade dysplasia. The cumulative incidence of dysplasia was significantly lower among patients who received PPI after BE diagnosis than in those who received no therapy or H2RA; log rank test (p < 0.001). Furthermore, among those on PPIs, a longer duration of use was associated with less frequent occurrence of dysplasia. In multivariate analysis, the use of PPI after BE diagnosis was independently associated with reduced risk of dysplasia, hazards ratio: 0.25 (95% CI 0.13-0.47), p < 0.0001. Longer segments of BE and Caucasian race were other independent risk factors for developing dysplasia. In general, similar findings were observed when only cases with high-grade dysplasia were analyzed. CONCLUSIONS: These results indicate that PPI therapy is associated with a significant reduction in the risk of developing dysplasia in patients with BE. However, more studies are required to confirm this finding.

Barrett Esophagus↗
PubMed2003

Prevention of adenocarcinoma by reversing Barrett's esophagus with mucosal ablation.

The ultimate goal of therapy in patients with Barrett's esophagus (BE) is to reduce the risk of developing adenocarcinoma of the esophagus. Neither pharmacologic nor surgical therapy has been documented to reduce this risk. There is preliminary evidence that many forms of mucosal ablation combined with acid reduction therapy result in restitution of normal squamous epithelium in patients with BE. Acid reduction can be accomplished with high-dose proton pump inhibitor therapy or antireflux surgery. Endoscopic ablation can be accomplished with photodynamic therapy, laser, multipolar electrocoagulation, a heater probe, and argon plasma coagulation. These techniques require further study so the complication rates can be compared. The success of reversing BE must be evaluated in a standard way utilizing large-capacity biopsy forceps through a therapeutic endoscope. Ideally, patients at high risk of developing adenocarcinoma of the esophagus can be treated with ablation therapy and followed to document a reduction in the development of adenocarcinoma of the esophagus. A validated biomarker would help select high risk patients appropriate for reversal therapy. Currently, patients who are at prohibitive risk for surgery or who refuse surgery are candidates for combination therapy including mucosal ablation to reverse their BE. This therapy offers the promise of less morbidity and greater quality of life than resection.

Adenocarcinoma↗
PubMed2003

Multipolar electrocoagulation.

Multipolar electrocoagulation (MPEC) is a readily available technique that can be applied for endoscopic ablation of Barrett's esophagus. MPEC, in combination with high dose proton pump inhibitor therapy or antireflux surgery, results in normal squamous epithelium in most patients without major adverse effects. The ultimate clinical role of MPEC has not been determined but may be adjunctive to other techniques in appropriately selected patients at high risk for neoplastic progression.

Barrett Esophagus↗
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

Progression or regression of Barrett's esophagus--is it all in the eye of the beholder?

OBJECTIVES: Accurate measurements of Barrett's esophagus length are important in clinical follow-up as well as in studies of therapeutic intervention in Barrett's esophagus. Our aim was to evaluate both the inter- and intraobserver reliability in measuring Barrett's length during two consecutive endoscopies by either the same or different experienced endoscopists. The relationship between Barrett's mucosa length and the absolute change in Barrett's length measurements on a follow-up endoscopy was also evaluated. METHODS: A total of 96 Barrett's patients underwent two consecutive endoscopies. The diagnosis of Barrett's esophagus was confirmed by the presence of intestinal metaplasia on biopsy. The Barrett's esophagus length was carefully measured and recorded during the two endoscopies. Procedures were performed by only two experienced endoscopists, who were not aware of previous endoscopic measurements. Only patients with long-segment (> or =3 cm) Barrett's esophagus were included in this study. RESULTS: The 55 patients who had their consecutive endoscopies performed by the same endoscopist had a mean 1.6-cm difference between the two measurements as compared to 1.4 cm in the 41 patients who had their endoscopies performed by different endoscopists (p = 0.3). The agreement between the two Barrett's length measurements was high in both groups, although it was slightly higher for endoscopies performed by the same endoscopist (r = 0.79 vs r = 0.67). Linear regression analysis of the absolute change in Barrett's length between the two endoscopic measurements and Barrett's mucosa length demonstrated a significant relationship (r = 0.28, p = 0.005). For every 1-cm increase in the mean length of Barrett's mucosa, a 0.15-cm increase in the absolute difference between two consecutive endoscopic measurements of Barrett's length was observed. CONCLUSIONS: Consecutive measurements of Barrett's length performed by different experienced endoscopists or by the same experienced endoscopist demonstrated a high degree of agreement. A range of variability in Barrett's length measurement was determined (+/-1.4-1.6 cm). True regression or progression of Barrett's mucosa should be considered only if the change is greater than the range of variability. In addition, endoscopists should be well aware that the longer the Barrett's mucosa the greater the absolute difference in Barrett's length measurement on follow-up endoscopy.

Barrett Esophagus↗
PubMed2003

Barrett's oesophagus: optimal strategies for prevention and treatment.

Barrett's oesophagus is a change in the lining of the distal oesophagus recognised at endoscopy and documented to have intestinal metaplasia by biopsy. It is thought that it is an acquired condition resulting from chronic gastro-oesophageal reflux disease (GORD). Barrett's oesophagus has the potential to progress to adenocarcinoma of the oesophagus. Evidence to support the association between Barrett's oesophagus and GORD appears to be strong but circumstantial. The intermediate steps that lead from GORD to Barrett's oesophagus are speculative and the timeline for the development of this condition remains obscure. It has yet to be demonstrated that erosive oesophagitis is a necessary intermediate step for the development of Barrett's oesophagus. In spite of effective therapy, documentation that medical or surgical therapy prevents Barrett's oesophagus is lacking. The goal of screening for Barrett's oesophagus is ultimately to improve the survival of patients with adenocarcinoma of the oesophagus. This goal has not been achieved and the evidence-based criteria for screening remain to be defined. Medical and surgical therapy of Barrett's oesophagus is effective in controlling reflux, although not proven to prevent neoplastic progression of the at risk mucosa. Endoscopic techniques of mucosal injury have been applied as alternatives to oesophagectomy in efforts to prevent progression to cancer. Surveillance endoscopy and biopsy is the currently accepted method aimed at early intervention and improved survival for oesophageal adenocarcinoma. A working surveillance protocol to accomplish this is proposed based on dysplasia grade. If no dysplasia is found and confirmed with subsequent endoscopy and biopsy, a 3-year interval is recommended. If only low grade dysplasia is confirmed, then annual endoscopy until no dysplasia is recognised is recommended. On the basis of defined risk factors, high grade dysplasia can lead to intense surveillance every 3 months or an intervention. Future developments in understanding the biology of Barrett's oesophagus and in therapeutic interventions will provide an opportunity for more effective screening, surveillance and prevention of neoplastic progression.

Adenocarcinoma↗