Adenocarcinoma In Barrett's Esophagus Research Articles

Endoscopic therapy for Barrett's esophagus and early esophageal cancer: Where do we go from here?

Since Barrett’s esophagus is a precancerous condition, efforts have been made for its eradication by various ablative techniques. Initially, laser ablation was attempted in non-dysplastic Barrett’s esophagus and subsequently, endoscopic ablation using photodynamic therapy was used in Barrett’s patients with high-grade dysplasia who were poor surgical candidates. Since then, various ablative therapies have been developed with radiofrequency ablation having the best quality of evidence. Resection of dysplastic areas only without complete removal of entire Barrett’s segment is associated with high risk of developing metachronous neoplasia. Hence, the current standard of management for Barrett’s esophagus includes endoscopic mucosal resection of visible abnormalities followed by ablation to eradicate remaining Barrett’s epithelium. Although endoscopic therapy cannot address regional lymph node metastases, such nodal involvement is present in only 1% to 2% of patients with intramucosal adenocarcinoma in Barrett esophagus and therefore is useful in intramucosal cancers. Post ablation surveillance is recommended as recurrence of intestinal metaplasia and dysplasia have been reported. This review includes a discussion of the technique, efficacy and complication rate of currently available ablation techniques such as radiofrequency ablation, cryotherapy, argon plasma coagulation and photodynamic therapy as well as endoscopic mucosal resection. A brief discussion of the emerging technique, endoscopic submucosal dissection is also included.

Volumetric Laser Endomicroscopy for Barrett's Esophagus - Looking at the Fine Print.

Barrett's esophagus (BE) is a premalignant condition. The incidence of adenocarcinoma in BE has been reported to be between 0.1-3%. Dysplasia in BE is patchy and extensive biopsy sampling is labor intensive, low yield and does not eliminate the sampling error completely. Volumetric laser endomicroscopy (VLE) is expected to enable endoscopists to do targeted biopsy of dysplastic/cancerous lesions (not visible on white light endoscopy) among patients with BE. We reviewed 7 studies with a total of 62 subjects who had undergone VLE. Of 34 patients with available data, VLE correlated with histology in 17 subjects (50%). It missed the underlying diagnosis in one subject (2.9%). VLE led to inadvertent biopsy in 16 patients (47.1%), and led or would have led to upstaging of disease in 11 subjects (32.4%). In the entire cohort, the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of VLE for diagnosis of dysplasia, buried Barrett's or intramucosal carcinoma was 92.3%, 23.8%, 42.9% and 83.3%, respectively. High sensitivity and NPV can potentially help space out the surveillance intervals. Low specificity does lead to a high number of biopsies, which are likely less than non targeted biopsies. Volumetric laser endomicroscopy is a safe and sensitive test to identify mucosal lesions in patients with BE which are invisible under standard white light endoscopy.

IMP3 Immunoreactivity is More Sensitive Than AMACR in Detecting Dysplastic Epithelium and Early Adenocarcinoma in Barrett Esophagus.

α-methylacyl coenzyme A racemase (AMACR) and insulin-like growth factor-II mRNA-binding protein 3 (IMP3) are 2 markers helpful in detecting difficult cases of dysplasia in Barrett esophagus (BE). However, no comparison studies have been performed to assess their performance in the same patient population. The aim of our study was to compare the immunohistochemical expression of IMP3 and AMACR in dysplastic lesions and early adenocarcinoma (EAC) arising in BE and evaluate their sensitivity and specificity. A total of 98 cases [BE negative for dysplasia, n=24; indefinite for dysplasia (BE-IND), n=18; low-grade dysplasia (LGD), n=24; high-grade dysplasia (HGD), n=16; and EAC, n=16] were immunostained for AMACR and IMP3 and evaluated for the degree, the extent, and the intensity of staining. No immunoreactivity for AMACR or IMP3 was observed in all 24 cases of BE negative for dyplasia. One of 18 (5.5%) cases of BE-IND was positive for IMP3, but all were negative for AMACR. AMACR and IMP3 were positive in 16.7% versus 41.7 % of the cases with BE-LGD, 25% versus 62.5% of BE-HGD, and 62.5% versus 93.7% of EAC, respectively. The sensitivity of AMACR and IMP3 for the detection of dysplasia in BE is 16.7% and 41.7% for LGD, 25% and 62.5% for HGD, and 62.5% and 93.7% in EAC, respectively. The specificity is 100% for both markers. In addition, a comparison of the intensity of reactivity shows a better result with IMP3 (36/98, 36.7%) than with AMACR (18/98, 18.4%) (P<0.001). IMP3 has a similar specificity, but a better sensitivity, intensity, and extent of reactivity in comparison with AMACR, and may be used as an alternative to AMACR, in support of the diagnosis of BE-dysplasia and EAC.

Predictors Of Treatment Failure After Radiofrequency Ablation For Intramucosal Adenocarcinoma in Barrett Esophagus: A Multi-institutional Retrospective Cohort Study.

Radiofrequency ablation (RFA), with or without endoscopic mucosal resection (EMR), is a safe, effective, and durable treatment option for Barrett esophagus (BE)-associated dysplasia (DYS), but few studies have identified predictors of treatment failure in BE-associated intramucosal adenocarcinoma (IMC). The aim of this study was to determine the rate of IMC eradication when using RFA±EMR and to identify clinical and pathologic predictors of treatment failure. A retrospective review of medical records and a central review of index histologic parameters were performed for 78 patients who underwent RFA±EMR as the primary treatment for biopsy-proven IMC at 4 academic tertiary medical centers. Complete eradication (CE) (absence of IMC/DYS on first follow-up endoscopy) was achieved in 86% of patients, and durable eradication (DE) (CE with no recurrence of IMC/DYS until last follow-up) was achieved in 78% of patients, with significant variation between the 4 study sites (P=0.03 and 0.09 by analysis of variance for DE and CE, respectively). Use of EMR before RFA significantly reduced the risk for treatment failure for IMC/DYS (hazard ratio, 0.15; 95% confidence interval, 0.05-0.48; P=0.001), whereas IMC involving ≥50% of the columnar metaplastic area on index examination significantly increased the risk for treatment failure (hazard ratio, 4.24; 95% confidence interval, 1.53-11.7; P=0.005). Endoscopic and pathologic factors associated with treatment failure in BE-associated IMC treated with RFA±EMR may help identify the subset of IMC patients for whom a more aggressive initial approach may be justified.

High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett's Esophagus.

PurposeGoblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE). The aim of this study was to determine the relationship between goblet cells (GC) and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients.Experimental DesignBaseline mucosal biopsies (N=2988) from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (#) of GC, mean # of GC/crypt (GC density), # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length.ResultsHigh GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively).ConclusionsThe results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities.

961 Toll-Like Receptor 4 Activation May Promote Development of Esophageal Adenocarcinoma in Barrett's Esophagus Through Induction of COX2

Background: Limited studies indicate that VEGF expression is upregulated in colorectal cancer (CRC). Since normal colonic epithelial cells have minimal or no expression of VEGF, increased VEGF in CRC represents its aberrant expression. The mechanisms of this phenomenon are not explained. Importins mediate in some cells (e.g., HeLa) the nuclear transport of transcription factors and signaling proteins that potentially can activate the VEGF gene. We hypothesized that upregulation of importins α and/or β is the underlying mechanism for the aberrant VEGF expression in CRC and cell proliferation by facilitating the nuclear transport of transcription factors (P-STAT3 and P-CREB) and P-MAPK/Erk1/2, respectively. Methods: We used: (1) human colon tissue arrays (CRC and normal specimens, n=60), and (2) human CRC cell lines HCT116 & HT29 and normal colonic epithelial cells NCM356 & NCM460 cultured in nutrient media. Studies: 1) Expressions of VEGF, its receptors (VEGFR1 & VEGFR2), importins, P-CREB, P-STAT3 and P-MAPK/Erk1/2 proteins in CRC cells in tissue array, and in cultured CRC and normal epithelial cells by immunostaining and/or western blotting; 2) In cultured CRC and normal epithelial cells: a) downregulation of importins with specific siRNAs, b) expression of VEGF mRNA by real time RTPCR, c) cell proliferation by BrdU assay, d) apoptosis by TUNEL staining.Results: Expression of VEGF and its receptor was aberrant and was significantly increased by 2-4 fold (P 80% (p<0.001). Conclusions: 1) Expression of VEGF and its receptors is upregulated in CRC cells, 2) Aberrant VEGF expression in CRC cells is dependent on upregulation of importin and is mediated by increased nuclear transport of P-CREB and P-STAT3, which bind to and activate VEGF gene promoter, 3) Increased expression of VEGF and its receptors in CRC cells suggests a direct regulation of their growth by VEGF through an autocrine mechanism.

S1064 Evaluation of Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) in Esophageal Adenocarcinoma in Barrett's Esophagus

Background:Epithelial mesenchymal transition(EMT) is a crucial event in the metastatisis of carcinoma. EMT enables epithelial tumors to invade into the mesenchymal submucosa. The key feature of EMT is E-cadherin down-regulation. Snail, Slug and Twist are well recognized transcriptional factors as repressors of E-cadherin expression. Recently, a direct link has been shown between the EMT and cancer stem cell(CSC). CSC has the ability to self-renew and continually sustain tumorigenesis. Cells undergoing an EMT could be the precursors to metastatic carcinoma, perhaps as CSCs. CD133 is recognized marker for gastrointestinal CSCs. Aim:To characterize expressions of Snail, Slug, Twist and CD133 in the metastatic esophageal adenocarcinoma(EAC) in Barrett's esophagus(BE). Method:Formalin-fixed, paraffin embedded specimens of surgically treated early EAC were used. All slides were first reviewed by a well experienced GI pathologist, then were immunohistochemically stained for primary antibodies to Snail, Slug, Twist and CD133. We assessed if invading edges of tumor in the submucosa were stained for each antibody, and if there were differences of intensity of staining between in intramucosal cancer cells and in submucosal metastatic cells. The slides were scored by (1) intensity of staining (0=negative, 1=weak, 2=moderate, 3= intense);(2) percentage of epithelial cells staining (0=0-5%, 1=6-25%, 2=26-50%, 3=5175%, 4=76-100%);(3) percentage of invading cancer cells staining (same as epithelial cells). Cellular localization (nuclear, cytoplasm, cell surface) and uniformity (focal, general) were also assessed. Result:10 patients were analyzed. All four proteins were expressed in the cancers with uniform staining in both the mucosa and submucosa with Snail being more localized in the nucleus while Slug, Twist and CD133 were exclusively in the cytoplasm. Intensity of staining of metastatic cancer cells in submucosa was similar to those in the mucosa. Semi-quantitative scored analyses of Snail, Slug, Twist and CD133 for overall intensity were 2.5, 2.8, 1.9, and 2.4, respectively. For epithelial tumor cells, the scores were 4.0, 3.8, 3.3, and 3.2, respectively, whereas for invading metastatic cells, 4.0, 3.6, 3.1, and 3.6. Conclusion:This is the first report assessing the expression of known E-cadherin repressors, Snail, Slug, Twist and CSC marker, CD133 in the development of EAC in BE. All invading edges of tumor were found to abundantly express Snail, Slug, Twist and CD133 suggesting that unlike late staged cancers, early staged cancers are predominantly made of cells with metastatic potential which emphasizes the need to completely remove these early cancers.

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

BackgroundMucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification.MethodsSpecimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies.ResultsEleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old). The tumor size had a mean of 4.7 ± 2.3 cm, and the extension of BE had a mean of 7.7 ± 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive) and intestinal type in 4/13 (MUC2 positive). Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047.ConclusionBarrett's esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barrett's esophagus may reflect the original cell type involved in the malignant transformation.

Barrett's Esophagus and Esophageal Adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has risen dramatically over the past three decades in western countries. The importance of Barrett's esophagus (BE) derives from its potential to transform to adenocarcinoma. BE is characterized by endoscopically recognized displacement of the squamocolumnar junction proximal to the gastroesophageal junction, with replacement of squamous mucosa with columnar lined mucosa. Adenocarcinomas of the esophagus appear to arise from Barrett's mucosa through progressive degrees of dysplasia, but the pathogenesis and natural history of this process are still unclear. Much of our knowledge regarding BE and the risk of EAC is based on observational and cross-sectional analyses, and recommendations regarding management have traditionally represented "expert opinion." The past few years have seen an explosion in new information and the initiation of longitudinal studies to define the risk of adenocarcinoma in BE, the identification of predictive and prognostic markers of cancer risk, sensitive and cost-effective methods of surveillance, and methods of management of dysplasia and early neoplasia including disease prevention.

M1592 Long-Term Survival Following Endoscopic and Surgical Treatment of Mucosal (T1a) Esophageal Adenocarcinoma in Barrett's Esophagus

M1592 Long-Term Survival Following Endoscopic and Surgical Treatment of Mucosal (T1a) Esophageal Adenocarcinoma in Barrett's Esophagus

Duplication of the Muscularis Mucosae in Barrett Esophagus: An Underrecognized Feature and Its Implication for Staging of Adenocarcinoma

Depth of invasion is one of the most important prognostic indicators in esophageal adenocarcinoma. Unlike other regions of the gastrointestinal tract, the esophagus in Barrett metaplasia frequently develops duplication of the muscularis mucosae (MM), but this feature is underrecognized, and its effect on appropriate staging of superficially invasive adenocarcinoma is unclear. We first randomly selected 50 esophageal resections for high-grade dysplasia or T1 adenocarcinoma in Barrett esophagus (BE) to evaluate the sensitivity and specificity of MM duplication for BE and its histologic characteristics, including percentage of the Barrett segment involved by MM duplication, origin of the duplicated muscle layer, and appearance of the tissue between duplicated MM. Twenty esophageal resections for squamous cell carcinoma served as controls. Next, to study the clinical significance of MM duplication, we evaluated 30 resections for BE that had superficial adenocarcinoma confined to regions of duplicated MM. Each case was classified as: depth of invasion (inner MM, space between duplicated MM, or outer MM), angiolymphatic invasion, and rate of lymph node metastasis. We observed MM duplication in 46 of 50 (92%) BE resections, involving 5% to >90% of the Barrett segment, in contrast to none in 20 (0%) resected squamous cell carcinoma, P<0.0001. In 5 (10%) cases, the MM was focally triplicated. The outer MM was continuous with the single MM beneath squamous epithelium, suggesting that outer MM represents the "original" muscle layer. The space between duplicated MM predominantly consisted of loose fibrovascular tissue similar to submucosa; in 15 (30%) cases, there were also areas of fibrosis or thin muscle strands joining the 2 MM layers. Of 30 adenocarcinomas invading duplicated MM, 10 (33%) invaded only inner MM, 12 (40%) invaded the space between MM, and 8 (27%) invaded the outer MM. Angiolymphatic invasion was present in 5 (17%) cases, and nodal metastases in 3 (10%, 1 case each of invasion into inner MM, between MM, and outer MM). These data show that MM duplication is a characteristic finding in BE, but it can pose difficulty in proper staging of superficial adenocarcinomas. The 17% rate of angiolymphatic invasion and 10% rate of lymph node metastases in our patients with invasion into duplicated MM suggest that these tumors can behave aggressively despite their technically intramucosal location.

A inter-relação das sialomucinas (antígenos Tn e Stn) com o adenocarcinoma no esôfago de Barrett

Barrett's esophagus (BE) is a consequence of chronic gastroesophageal reflux and is considered a risk factor for adenocarcinoma. The study of the mucus, especially acid mucins, such as the sialomucins in the goblet cells which characterize BE, showed that in intestinal metaplasia, frequent in the digestive tract, the organ's original epithelium could express Tn and Stn antigens. These antigens have already been detected in gastric and colonic tumors, however references in BE were not found. This research aimed to analyze these antigens in patients with BE and in adenocarcinoma associated with BE. Utilizing immunohistochemistry tests, Tn and Stn antigens were studied in the endoscopic biopsies of 29 patients with BE and seven with adenocarcinoma in BE, as well as eight individuals with normal esophageal epithelium at upper digestive endoscopy. The Stn antigen was positive in the goblet cells of patients with BE in 100% of the cases and the Tn was positive in 48%. In the columnar cells, Stn was always negative, while Tn was positive in 100% of the cases. However, in adenocarcinoma in BE, both antigens were 100% positive. In normal individuals, the Tn antigen was positive and the antigen Stn negative in all cases. It is probable that the BE group in which the Tn antigens in the goblet cells are positive, similarly to the same antigen in the adenocarcinoma group, might indicate a higher susceptibility for potential occurrence of cancer. In the future, trials with sialomucins could be used routinely, thereby contributing as a prognostic factor of adenocarcinoma in BE.

Adenocarcinoma in Barrett Esophagus

Gastrointestinal cancer accounts for approximately 25% of all cancers and approximately 9% of all deaths worldwide. Cancer is the cause of death in 25% of cases in the United Kingdom compared with 22% in the United States. Although death rates of most of the top 10 cancers have decreased in the last decade, male esophageal cancers are on the rise (3% increase). Screening the population for Barrett metaplasia is not cost-effective exercise especially if patients are asymptomatic. Moreover, though surveillance is now widely done for Barrett metaplasia both for short-segment and long-segment, the incidence of esophageal cancer is much higher than expected, as most of these do not come to light until late in the elderly. The best therapeutic strategy hence would be chemoprevention. This review paper mainly addresses the issues such as the epidemiology of adenocarcinoma in Barrett esophagus; the rationale for prevention; why chemoprevention would be the best option and will describe the major trial on chemoprevention in Barrett Metaplasia (Aspirin Esomeprazole Chemoprevention Trial).

Endoscopic Follow-Up of Patients with Barrett Esophagus from Metaplastic Mucosa to Adenocarcinoma

Introduction: The detection of pre-malignant and malignant alterations in mataplastic mucosa is very important. Few studies have reported the endoscopic evolution of metaplastic mucosa to adenocarcinoma in Barrett esophagus(BE). We reported a series of 9 patients with BE developing the sequence metaplastic mucosa to adenocarcinoma. Aims and Methods:Between 1993 and 2004 we followed up endoscopically 9 patientes with BE without displasia or minimal displasic findings up to the appearence of adenocarcinoma (7 male, 2 female with median age of 64 years, range 50-81). The procedures were performed at 12 months intervals by 3 experienced endoscopists and the histopathology was analyzed by 4 pathologists using the same criteria. Results: The median time between the identification of BE to the diagnosis of cancer was 7 years. The extention of BE varied between 1.5 cm and 7 cm (median 4.5 cm). 2 patients presented with short BE. 6 patients revealed slightlyelevated lesions(0-IIa), 5 early and 1 advanced adenocarcinoma, 1 patient with depressed type(0-IIc) and 2 with polypoid type lesion(0-Is early cancer). 2 patiens underwent open surgery(1 with polypoid lesion and the patient with advanced cancer, who died in the post-operative period). 7 patients underwent endoscopic mucosal ressection(EMR). 2 patients were treated by EMR plus argon plasma coagulation of the remaining BE. 8 patients are alive without evidence of cancer recurrence, assimptomatic. Conclusion: BE adenocarcinoma can develop in patients without previous diagnosis of dysplasia and surveillance is strongly recommended. As it occurs in other forms of early gastrointestinal cancers, EMR can become the treatment of choice for BE adenocarcinoma.

Book Review

GERD: Reflux to Esophageal Adenocarcinoma provides a descriptive and detailed analysis on the pathogenesis of gastroesophageal reflux disease (GERD), its relationship to Barrett’s esophagus (BE) and the development of esophageal adenocarcinoma. Controversial at times, the text is authored by a pathologist and a surgeon, and comes from the Keck School of Medicine at the University of Southern California (USA). Divided into 17 chapters, all relevant topics are covered. Chapters 1 and 2 provide an overview of GERD, and places BE into a historical perspective. Chapters 3 through 7 summarize the embryology, anatomy and histology of the upper gastrointestinal tract, with a focus on the gastroesophageal junction. Chapters 8 through 11 review the pathology of GERD at both a cellular and an anatomical level. Chapters 12 and 13 define nonerosive reflux disease and GERD. Chapter 14 describes the diagnosis of GERD, BE and dysplasia. The final three chapters, 15 through 17, describe the GERD to adenocarcinoma pathogenesis, the rationale for treating GERD and BE, and strategies aimed at preventing adenocarcinoma. Within each chapter, the book is well-organized and very readable. Subtitles divide the text into concise sections. A literature review within each chapter summarizes and references key papers relevant to the topics covered in that chapter. Numerous tables and figures, as well as histological and gross anatomical photographs, enhance the information found within the text. Although the text and figures are in black and white, there is a superb colour photograph section depicting typical examples of gastroesophageal pathology. The most controversial topic is the role of acid-suppressive medications in the pathogenesis of esophageal adenocarcinoma. This topic is alluded to in the preface, with the statement, “This book provides a theoretical basis of how acid-suppressive drugs promote reflux-induced adenocarcinoma” (page xv). Chapter 16, “Rationale for Treatment of Reflux Disease and Barrett Esophagus” discusses this point further. Initially a review of the effectiveness of acid-suppressive therapy in the treatment of symptomatic reflux disease is given, followed by a discussion on the effect on the development of BE. Statements made at the American Gastroenterological Association Consensus Workshop in Chicago (USA) (Sharma et al, Gastroenterology 2004;127:310–30) are quoted, and at times, questioned. It is pointed out that the utility of acid-suppressive drugs in patients with BE is uncertain, and may actually be harmful. Data are presented suggesting that the use of acid-suppressive drugs is an independent risk factor for the development of esophageal adenocarcinoma. A discussion on the role of surgery in the treatment of patients with GERD is then presented, and compared with medical therapy. Data suggesting that antireflux surgery can prevent BE, thus preventing adenocarcinoma are also presented, along with a pathophysiological explanation for this phenomenon. A comparison is made between gastroenterologists and surgeons in the way they treat GERD patients, and it is suggested that gastroenterologists may not be best suited for this purpose (“The attitude among gastroenterologists is that the problem of adenocarcinoma in Barrett esophagus can be ignored because cancer is a very uncommon event” [page 386]). The authors also state that “If it is ever shown that antireflux surgery decreases the risk of adenocarcinoma when used to treat reflux disease, the basic control of treating patients with reflux disease will shift from gastroenterologists to surgeons” (page 403). Another statement “Most gastroenterologists are not qualified to make the assessment of whether antireflux surgery decreases the risk of adenocarcinomas” (page 404) suggests that, although a pathologist and a surgeon can critically review the literature surrounding acid-suppressive medications, it is well beyond the scope of expertise for a gastroenterologist to be able to appraise similar surgical literature. Although the authors do present some controversial ideas and make some potentially inflammatory statements, the book is an excellent up-to-date review of the pathogenesis of GERD as it relates to the development of BE and adenocarcinoma. Gastroenterologists reading the book may want to take some statements with a grain of salt, but this should not dissuade them from carefully examining the information presented to them. This topic is still not fully understood and the importance and management of complicated GERD patients remain a question at times. This text provides insight into what the future may hold in this important clinical area.

Cryoablation of Dysplasia in Barrett's Esophagus (BE) and Early Stage Esophageal Cancer

Background: To determine the efficacy and safety of endoscopic spray cryoablation in the eradication of BE with dysplasia and early stage esophageal cancer. Methods: Ten patients with low grade dysplasia (LGD), high grade dysplasia (HGD) or esophageal cancer were offered endoscopic cryoablation using low pressure liquid nitrogen spray on their esophageal lesions. All histology was confirmed at the Armed Forces Institute of Pathology (AFIP). Distribution was as follows: LGD: 5, HGD: 3, adenocarcinoma (AC): 1, squamous cell carcinoma (SCCA): 1. LGD was treated with two 20 second cryo applications. HGD and cancer were treated with three 20 second cryo applications. The first 5 patients were treated hemi-circumferentially (H) and the last 5 were treated circumferentially (C). Four quadrant surveillance biopsies were taken every 2 cm in the LGD group and every 1 cm in the HGD and cancer groups. Results: The mean age of the treatment group was 66. The mean length of follow-up for all patients was 16 months. Dysplasia was eliminated in all patients with BE. In the patient with adenocarcinoma in BE (T2N0M0), the adenocarcinoma was downgraded to LGD and the patient is undergoing further treatment. The SCCA patient (T2N0M0) is cancer-free 13 months after treatment. There were no major complications with the exception of an esophageal stricture in the SCCA patient which was successfully dilated. Conclusions: Preliminary results using endoscopic cryoablation with low pressure, liquid nitrogen spray has demonstrated efficacy and safety in the elimination of dysplasia in BE, and in the treatment of early stage adenocarcinoma and SCCA of the esophagus warranting further investigation. Tabled 1Cryoablation Table Pt# Age Pre-BE Length (cm) Post-BE Length (cm) Type of Cryo (H/C) Length of Follow-up (mo) # Rxs Dysplasia pre-cryo Dysplasia post-cryo 1 51 1 0 H 32 6 LGD NEG 2 72 8 2 H 32 8 LGD NEG 3 74 5 0 H 27 5 LGD NEG 4 57 4 0 H 21 6 LGD NEG 5 64 6 0 C 16 1 HGD NEG 6 60 3 2 C 10 4 HGD NEG 7 73 6 0 C 6 3 HGD NEG 8 63 4 p C 2 1 AC LGD 9 74 11 p C 3 1 LGD NEG 10 74 na na H 14 2 SCCA NEG Mean 66 5.3 0.6 16.3 3.7 p: pending; na: non-applicable; H: hemi-circumferential; C: circumferential. Open table in a new tab p: pending; na: non-applicable; H: hemi-circumferential; C: circumferential.

The incidence of adenocarcinoma in Barrett's esophagus in an institutionalized population.

To ascertain the incidence rate of adenocarcinoma in Barrett's esophagus (ACE) in a stable population of 28,000 institutionalized intellectually disabled individuals (IDI) in whom the prevalence rate of Barrett's esophagus (BE) was previously estimated in a representative sample by 24 h pH monitoring and endoscopy, and in which all cases of ACE were ascertained over a 6-year period. These IDI do not smoke or drink alcohol and are known to have exceptionally high prevalence rates of gastro-esophageal reflux disease, and consequently of BE. A population comprising 52,038 person-years was observed and all cases of ACE were ascertained. On the basis of the representative sample, the percentage of this population with BE was estimated to be 10.8%. ACE incidence rates could then be estimated and compared with those found in a free-living BE cohort after correction for age and gender differences. In IDI an incidence rate of ACE of 2.5/1000 person-years was found against 6.3/1000 person-years in the free-living BE cohort. However, the age distributions of the IDI and of the free-living BE cohort were very different, and after correction for this factor there was no significantly lower incidence rate of ACE in the IDI (relative risk, 0.79; P = 0.61). This is the first reported incidence study of ACE in a stable, well-defined population. In contrast to squamous cell carcinoma, our findings suggest only a minor role for smoking and alcohol in the etiology of ACE.

Incidence of adenocarcinoma in Barrett's esophagus: Results of a multicenter prospective study

Incidence of adenocarcinoma in Barrett's esophagus: Results of a multicenter prospective study

Long-term endoscopic surveillance of patients with Barrett's esophagus. incidence of dysplasia and adenocarcinoma: a prospective study

Objective Barrett's esophagus (BE) is a premalignant condition for which regular endoscopic follow-up is usually advised. We evaluated the incidence of esophageal adenocarcinoma (AC) in patients with BE and the impact of endoscopic surveillance on mortality from AC. Methods A cohort of newly diagnosed BE patients was studied prospectively. Endoscopic and histological surveillance was recommended every 2 yr. Follow-up status was determined from hospital and registry office records and telephone calls to the patients. Results From 1987 to 1997, BE was diagnosed in 177 patients. We excluded three with high-grade dysplasia (HGD) at the time of enrollment. Follow-up was complete in 166 patients (135 male, 31 female). The mean length of endoscopic follow-up was 5.5 yr (range 0.5–13.3). Low-grade dysplasia (LGD) was present initially in 16 patients (9.6%) and found during follow-up in another 24 patients. However, in 75% of cases, LGD was not confirmed on later biopsies. HGD was found during surveillance in three patients (1.8%), one with simultaneous AC; two with HGD developed AC later. AC was detected in five male patients during surveillance. The incidence of AC was 1/220 (5/1100) patient-years of total follow-up, or 1/183.6 (5/918) patient-years in subjects undergoing endoscopy. Four AC patients died, and one was alive with advanced-stage tumor. The mean number of endoscopies performed for surveillance, rather than for symptoms, was 2.4 (range 1–10) per patient. During the follow-up years the cohort had a total of 528 examinations and more than 4000 biopsies. Conclusions The incidence of AC in BE is low, confirming recent data from the literature reporting an overestimation of cancer risk in these patients. In our patient cohort, surveillance involved a large expenditure of effort but did not prevent any cancer deaths. The benefit of surveillance remains uncertain.

Beta-catenin expression and its association with prognostic factors in adenocarcinoma developed in Barrett esophagus.

The majority of the adenocarcinomas arising in Barrett esophagus manifest clinically at an advanced stage and have a poor prognosis. As a result of this poor prognosis, much attention has been directed toward the exploration of markers for neoplastic progression in Barrett esophagus. The objective of the present study was to determine the expression of beta-catenin by immunohistochemical analysis in 70 adenocarcinomas developed in Barrett esophagus and to examine its relationship to various prognostic factors currently in use. Abnormal beta-catenin expression, consisting of the loss of membranous staining and the appearance of the nuclear staining, was found in 43 cases (61%). Of patients with the 43 tumors showing abnormal beta-catenin expression, 25 (58%) survived more than 1 year. In contrast, only 7 (26%) of 27 patients with tumors showing normal beta-catenin expression survived longer than 1 year. Most of the superficial (Tis-T1) tumors (83% [10/12]) exhibited abnormal beta-catenin expression compared with only 53% (31/58) in the T2-T3 group. These results suggest a possible correlation among beta-catenin expression, tumor stage, and length of survival as prognostic factors in patients with adenocarcinoma in Barrett esophagus.