[Show abstract][Hide abstract] ABSTRACT: Barrett's esophagus (BE) develops as a consequence of chronic esophageal acid exposure, and is the major risk factor for esophageal adenocarcinoma (EAC). The practices of endoscopic screening for-and surveillance of-BE, while widespread, have failed to reduce the incidence of EAC. The majority of EACs are diagnosed in patients without a known history of BE, and current diagnostic tools are lacking in their ability to stratify patients with BE into those at low risk and those at high risk for progression to malignancy. Nonetheless, advances in endoscopic imaging and mucosal therapeutics have provided unprecedented opportunities for intervention for BE, and have vastly altered the approach to management of BE-associated mucosal neoplasia.
[Show abstract][Hide abstract] ABSTRACT: Background
& Aims: Endoscopic intervention or pharmacologic inhibition of cyclooxygenase might be used to prevent progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC). We investigated whether patients with BE prefer endoscopic therapy or chemoprevention of EAC.
Eighty-one subjects with nondysplastic BE were given a survey that described 2 scenarios. The survey explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by 50%, with a 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased the risk for ulcer by 75%. Subjects indicated their willingness to undergo either treatment A and/or treatment B if endoscopic surveillance was required every 3–5 years, every 10 years, or was not required. Visual aids were included to represent risk and benefit percentages.
When surveillance was required every 3–5 years, more subjects were willing to undergo treatment A than treatment B (78% [63/81] vs 53% [43/81], P<.01). There were no differences in age, sex, education level, or history of cancer, heart disease, or ulcer between patients willing to undergo treatment A and those willing to undergo treatment B. Altering the frequency of surveillance did not affect patients’ willingness to undergo either treatment.
In a simulated scenario, patients with BE preferred endoscopic intervention over chemoprevention for EAC. Further investigation may be warranted of the shared decision making process regarding preventive strategies for patients with BE.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2014; · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the prevalence of Subsquamous intestinal metaplasia (SSIM) in patients undergoing endoscopic mucosal resection (EMR) for staging of Barrett's esophagus (BE).
Thirty-three patients with BE associated neoplasia underwent EMR at our institution between September 2009 and September 2011; 22 of these patients met study inclusion criteria. EMR was targeted at focal abnormalities within the BE segment. EMR was performed in standardized fashion using a cap-assisted band ligation technique, and resection specimens were assessed for the presence of SSIM. Demographic and clinical data were analyzed to determine predictors of SSIM.
SSIM was detected in 59% of patients. SSIM was detected in 73% of patients with short segment (< 3 cm) BE, and in 45% of patients with long-segment (≥ 3 cm) BE (P = NS). There was no association between presence/absence of SSIM and age, gender, or stage of BE-associated neoplasia.
EMR detects SSIM in a majority of patients with BE-associated neoplasia. While the long-term clinical significance of SSIM remains uncertain, these results highlight the importance of EMR as an optimal diagnostic tool for staging of BE and detection of SSIM, and should further limit concerns that SSIM is purely a post-ablation phenomenon.
World journal of gastrointestinal endoscopy. 12/2013; 5(12):590-4.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Accurate endoscopic detection and staging are critical for appropriate management of Barrett's esophagus (BE)-associated neoplasia. Prior investigation has demonstrated that the distribution of endoscopically detectable early neoplasia is not uniform but instead favors specific directional distributions within a short BE segment; however, it is unknown whether the directional distribution of neoplasia differs with increasing distance from the gastroesophageal junction, including in patients with long-segment BE. OBJECTIVE: To identify whether directional distribution of BE-associated neoplasia is influenced by distance from the gastroesophageal junction. DESIGN: Retrospective cohort study. SETTING: Tertiary-care referral center. PATIENTS: Patients with either short-segment or long-segment BE undergoing EMR. INTERVENTION: EMR. MAIN OUTCOME MEASUREMENTS: Directional distribution of BE-associated neoplasia stratified by distance from gastroesophageal junction. RESULTS: EMR was performed on 60 lesions meeting study criteria during the specified time period. Pathology demonstrated low-grade dysplasia in 22% (13/60), high-grade dysplasia in 38% (23/60), intramucosal (T1a) adenocarcinoma in 23% (14/60), and invasive (≥T1b) adenocarcinoma in 17% (10/60). Directional distribution of lesions was not uniform (P < .001), with 62% of lesions (37/60) located between the 1 o'clock and 5 o'clock positions. When circular statistics methodology was used, there was no difference in the directional distribution of neoplastic lesions located within 3 cm of the gastroesophageal junction compared with ≥3 cm from the gastroesophageal junction. LIMITATIONS: Single-center study may limit external validity. CONCLUSION: The directional distribution of neoplastic foci within a BE segment is not influenced by distance of the lesion from the gastroesophageal junction. Mucosa between the 1 o'clock and 5 o'clock locations merits careful attention and endoscopic inspection both in individuals with short-segment BE and long-segment BE.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Endoscopic therapy has emerged as an alternative to surgical esophagectomy for the management of Barrett's esophagus (BE)-associated neoplasia. Accurate pretreatment staging is essential to ensure an appropriate choice of therapy and optimal long-term outcomes. This study aimed to assess the frequency with which expert histopathologic review of biopsies combined with endoscopic mucosal resection (EMR) would alter the pretreatment diagnosis of BE-associated neoplasia. METHODS: Patients referred to the Vanderbilt Barrett's Esophagus Endoscopic Treatment Program (V-BEET) were retrospectively identified. Demographic, histopathologic, and endoscopic data were extracted from the medical record. RESULTS: For this study, 29 subjects referred for endoscopic staging of BE fulfilled the entry criteria. The referral diagnosis was low-grade dysplasia (LGD) in 3 % (1/29), high-grade dysplasia (HGD) in 62 % (18/29), intramucosal adenocarcinoma (T1a) adenocarcinoma in 17 % (5/29), and invasive adenocarcinoma in 17 % (5/29) of the subjects. Expert histopathologic review of available referral biopsy specimens altered the diagnosis in 33 % (5/15) of the cases. Further diagnostic staging with EMR showed BE without dysplasia in 10 % (3/29), LGD in 14 % (4/29), HGD in 34 % (10/29), T1a adenocarcinoma in 28 % (8/29), and invasive adenocarcinoma in 14 % (4/29) of the patients. The combination of expert histopathologic review and EMR altered the initial diagnosis for 55 % (16/29) of the subjects, with 56 % (9/16) upstaged to more advanced disease and 44 % (7/16) downstaged to less advanced disease. CONCLUSIONS: The practice of combined expert histopathologic review and EMR alters the pretreatment diagnosis for the majority of patients with BE-associated neoplasia. Caution is advised for those embarking on endoscopic or surgical treatment for BE-associated neoplasia in the absence of these staging methods.
[Show abstract][Hide abstract] ABSTRACT: Upper gastrointestinal tract hemorrhage (UGIH) remains a common presentation requiring urgent evaluation and treatment. Accurate assessment, appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge. The advent of pharmacologic acid suppression, endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease (PUD) has revolutionized the treatment of UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and mortality. This review aims to discuss current areas of uncertainty and controversy in the management of UGIH. Neoadjuvant proton pump inhibitor (PPI) therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non-variceal UGIH, and PPIs are extremely effective at promoting ulcer healing. However, neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality. The optimal timing of upper endoscopy in UGIH is often debated. Upon completion of volume resuscitation and hemodynamic stabilization, upper endoscopy should be performed within 24 h in all patients with evidence of UGIH for both diagnostic and therapeutic purposes. With rising healthcare cost paramount in today's medical landscape, the ability to appropriately triage UGIH patients is of increasing value. Upper endoscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low-risk lesions or admission for further monitoring and treatment in higher-risk lesions. Concomitant pharmacotherapy with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents, such as clopidogrel, has a major impact on the etiology, severity, and potential treatment of UGIH. Long-term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review.
World Journal of Gastroenterology 03/2012; 18(11):1159-65. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Buried Barrett's, or subsquamous intestinal metaplasia (SSIM), is defined as the presence of metaplastic, columnar tissue beneath overlying squamous epithelium. Therefore, SSIM cannot be detected by endoscopic visual examination alone; it is detectable only by tissue biopsy. SSIM can develop in patients with Barrett's esophagus (BE) after chronic pharmacologic suppression of gastric acid; it has been identified before and after endoscopic ablative therapies in cohort studies. It is important to determine the malignant potential of SSIM and the effects of endoscopic therapy for BE on development of SSIM; answers to these questions could affect long-term endoscopic surveillance and ablation strategies for patients with BE.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2012; 10(3):220-4. · 5.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cyclooxygenase-2 expression is upregulated in Barrett's esophagus and esophageal adenocarcinoma. Photodynamic therapy using porfimer sodium can result in ablation of dysplasia and intramucosal carcinoma, eradication of Barrett's esophagus, and restitution of squamous epithelium. The aim of this study was to determine the effect of photodynamic therapy on cyclooxygenase-2 expression in esophageal epithelium. Paired pre- and post-photodynamic therapy biopsy samples from the same anatomical levels of 20 individuals who had undergone photodynamic therapy for Barrett's esophagus with high-grade dysplasia and/or intramucosal carcinoma were immunostained using a cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was graded in squamous epithelium, Barrett's esophagus, and neoplasia (if present) as follows: grade 0 (no staining), grade 1 (staining in 1-10% of cells), grade 2 (staining in 11-90% of cells), and grade 3 (staining in >90% of cells). Pre-photodynamic therapy median cyclooxygenase-2 expression was grade 2 (range 1-3) in neoplastic foci and grade 1 (range 1-3) in nondysplastic Barrett's esophagus (P=0.0009 for pairwise comparison). With the exception of a few cells staining in the basal epithelial layers, median cyclooxygenase-2 expression was graded as 0 (similar to controls) in both pre-photodynamic therapy squamous epithelium and post-photodynamic therapy neosquamous epithelium. This was significantly lower when compared to either neoplastic foci (P<0.0001) or nondysplastic Barrett's esophagus (P<0.0001) pre-photodynamic therapy. Notably, in four patients with post-photodynamic therapy recurrent neoplasia, cyclooxygenase-2 expression returned to elevated levels. Cyclooxygenase-2 expression is elevated in Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma prior to photodynamic therapy. Following successful photodynamic therapy, cyclooxygenase-2 expression in neosquamous epithelium returns to a low baseline level similar to that observed in native esophageal squamous epithelium. Post-photodynamic therapy neoplastic recurrence is associated with elevated cyclooxygenase-2 expression. Prospective studies should determine whether cyclooxygenase inhibitors have a role as adjuvant therapy to prevent recurrence of Barrett's esophagus following endoscopic therapy.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 11/2011; 459(6):581-6. · 2.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Barrett's esophagus (BE) is the principal risk factor for esophageal adenocarcinoma. BE patients currently undergo periodic endoscopic surveillance with tissue sampling and histopathologic assessment for dysplasia. They frequently are prescribed proton pump inhibitors to pharmacologically suppress gastric acid that is the cause of BE. These standard endoscopic and pharmacologic approaches for managing BE are crude at best. Identification of novel tissue biomarkers within BE may allow for more accurate endoscopic risk stratification and provide potential targets for chemoprevention.
Cancer Prevention Research 06/2011; 4(6):783-6. · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Spectrally encoded confocal microscopy and optical frequency domain imaging are two non-contact optical imaging technologies that provide images of tissue cellular and architectural morphology, which are both used for histopathological diagnosis. Although spectrally encoded confocal microscopy has better transverse resolution than optical frequency domain imaging, optical frequency domain imaging can penetrate deeper into tissues, which potentially enables the visualization of different morphologic features. We have developed a co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system and have obtained preliminary images from human oesophageal biopsy samples to compare the capabilities of these imaging techniques for diagnosing oesophageal pathology.
Journal of Microscopy 08/2010; 239(2):87-91. · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proton pump inhibitors (PPIs) are frequently prescribed for prophylaxis of nosocomial upper gastrointestinal tract bleeding. Some inpatients receiving PPIs may have no risk factors for nosocomial upper gastrointestinal tract bleeding, and PPIs may be continued unnecessarily at hospital discharge. We aimed to assess the effect of standardized guidelines on PPI prescribing practices.
Guidelines for PPI use were implemented on the medical service at a tertiary center. We reviewed PPI use among inpatient admissions during the month before implementation of guidelines and then prospectively evaluated PPI use among admissions during the month after implementation of guidelines.
Among an overall cohort of 942 patients, 48% were prescribed PPIs while inpatients, and 41% were prescribed PPIs at hospital discharge. Univariate predictors of inpatient PPI use included age, length of hospital stay, history of gastroesophageal reflux disease or upper gastrointestinal tract bleeding, and outpatient PPI, aspirin, or glucocorticoid use. Among patients not on an outpatient regimen of PPIs at admission, implementation of guidelines resulted in lower rates of inpatient PPI use (27% before vs 16% after, P = .001) and PPI prescription at discharge (16% before vs 10% after, P = .03).
Introduction of standardized guidelines resulted in lower rates of PPI use among a subset of inpatients and reduced the rate of PPI prescriptions at discharge.
Archives of internal medicine 05/2010; 170(9):779-83. · 11.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies.
To assess the safety and efficacy of cryotherapy in esophageal carcinoma.
Multicenter, retrospective cohort study.
Ten academic and community medical centers between 2006 and 2009.
Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy.
Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition.
Complete eradication of luminal cancer and adverse events.
Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects.
Retrospective study design, short follow-up.
Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.
[Show abstract][Hide abstract] ABSTRACT: Management options for Barrett’s esophagus with high-grade dysplasia include intensive endoscopic surveillance, surgical esophagectomy,
or endoscopic ablation therapy. Controlled, prospective trials comparing these treatment strategies have not been performed.
In addition, clinical uncertainty may exist with respect to the accuracy of diagnosis of Barrett’s high-grade dysplasia, risk
of cancer progression, and likelihood of durable treatment outcome. Disease models can simulate risk over time in an attempt
to account for these uncertainties. Cost-effectiveness analyses, based on these models, can be used to compare the relative
costs and outcomes of endoscopic therapy for Barrett’s esophagus with high-grade dysplasia, compared to surgery or surveillance
Key WordsBarrett’s esophagus–Cost-effectiveness–Photodynamic therapy–Esophagectomy
[Show abstract][Hide abstract] ABSTRACT: Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution.
The goal of this study was to demonstrate large-area SECM in upper GI tissues and to determine whether the images contain microstructural information that is useful for pathologic diagnosis.
A feasibility study.
Gastrointestinal Unit, Massachusetts General Hospital.
Fifty biopsy samples from 36 patients undergoing routine EGD were imaged by SECM, in their entirety, immediately after their removal.
The microstructure seen in the SECM images was similar to that seen by histopathology. Gastric cardia mucosa was clearly differentiated from squamous mucosa. Gastric fundic/body type mucosa showed more tightly packed glands than gastric cardia mucosa. Fundic gland polyps showed cystically dilated glands lined with cuboidal epithelium. The presence of intraepithelial eosinophils was detected with the cells demonstrating a characteristic bilobed nucleus. Specialized intestinal metaplasia was identified by columnar epithelium and the presence of goblet cells. Barrett's esophagus (BE) with dysplasia was differentiated from specialized intestinal metaplasia by the loss of nuclear polarity and disorganized glandular architecture.
Ex vivo, descriptive study.
Large-area SECM images of gastroesophageal biopsy samples enabled the visualization of both subcellular and architectural features of various upper GI mucosal types and were similar to the corresponding histopathologic slides. These results suggest that the development of an endoscopic SECM probe is merited.
[Show abstract][Hide abstract] ABSTRACT: It is not known whether there have been recent changes in demographic or clinical characteristics among patients newly diagnosed with Barrett's esophagus (BE), which could be a result of changes in disease epidemiology or of screening or surveillance effects, and could have clinical implications.
The aim of this study was to determine whether there has been a shift in age at diagnosis of BE over the past decade. Secondary aims were to determine whether there has been a shift in patient body mass index (BMI) or BE segment length.
An endoscopic database at a tertiary medical center was used to identify all esophagogastroduodenoscopies (EGDs) performed between 1997 and 2007. The cohort was restricted to patients newly diagnosed with BE. Pathology records were reviewed to confirm biopsy findings of intestinal metaplasia (IM).
BE was diagnosed in 378 subjects between 1997 and 2007. Mean age at diagnosis of BE was 60.7 +/- 14.1 years, with mean BMI of 27.4 +/- 5.2 kg/m(2) and mean BE segment length of 4.7 +/- 3.7 cm. Between 1997 and 2007 there was no significant change in mean age at diagnosis, BMI, BE segment length or in proportion of men versus women newly diagnosed.
Despite an increase in volume of EGDs performed in an open-access endoscopy unit between 1997 and 2007, there was no appreciable shift in age at diagnosis of BE. BMI and BE segment length among newly diagnosed patients also remained stable over this time period.
Digestive Diseases and Sciences 10/2009; 55(4):960-6. · 2.26 Impact Factor