Esophageal Squamous Dysplasia Research Articles

American Gastroenterological Association (AGA) Institute Technology Assessment on Image-Enhanced Endoscopy

This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute Technology Assessment on "Image-Enhanced Endoscopy." It was approved by the Clinical Practice and Economics Committee on August 3, 2007, and by the AGA Institute Governing Board September 27, 2007.

Gene Expression Differences in Normal Esophageal Mucosa Associated with Regression and Progression of Mild and Moderate Squamous Dysplasia in a High-Risk Chinese Population

A randomized, double-blinded, placebo-controlled 2 x 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia. Results from this study indicated that asymptomatic adults with mild dysplasia were more likely to show an improvement when treated with selenomethionine compared with placebo (P = 0.02). Prompted by this finding, we examined the molecular profiles associated with regression and progression of dysplastic lesions in normal mucosa from 29 individuals, a subset of the Linxian cohort, using the Affymetrix U133A chip. Twenty differentially expressed genes were associated with regression and 129 were associated with progression when we compared the change in gene expression over time. Genes associated with immune response (n = 15), cell cycle (n = 15), metabolism (n = 15), calcium transport or calcium ion activity (n = 10), regulation of transcription (n = 9), signal transduction (n = 7), cytoskeleton and microtubules (n = 5), nucleotide processing and biosynthesis (n = 4), G-coupled signaling (n = 4), and apoptosis (n = 3) were present in the list of 149 genes. Using the Expression Analysis Systematic Explorer pathway analysis program, only the immune response pathway was significantly overrepresented among these 149 genes. Individuals whose lesions regressed seemed to have higher expression of genes associated with immune stimulation, such as antigen presentation, survival of T cells, and T-cell activation (HLA-DRA, HLA-DPA1, HLA-DBQ1, CD58, and FCER1A). In contrast, individuals whose lesions progressed had higher expression of genes involved in immune suppression and inflammation (CNR2, NFATC4, NFRKB, MBP, INHBB, CMKLR1, CRP, ORMS, SERPINA7, and SERPINA1). These data suggest that local and systemic immune responses may influence the natural history of esophageal squamous dysplasia.

Histological and biological characteristics of esophageal dysplasia

Dysplasia is an important problem in esophageal carcinogenesis, and there are controversial opinions concerning whether esophageal squamous dysplasia is a cancerous lesion. In the present study, it was histopathologically and biologically confirmed that dysplasia has a close correlation with cancer. Dysplasia was frequently observed with early stages of carcinoma. Although continuity of dysplastic lesions into the carcinoma area is not frequently observed, this continuity is observed in severe dysplasia more often than in mild or moderate dysplasia. The proliferating cell nuclear antigen labeling index (PCNA LI) showed no substantial difference in the cell proliferative activities of dysplasia and intraepithelial carcinoma. In addition, p53 immunohistochemical analysis revealed that p53 positivities in carcinomas and dysplasias were contiguous to each other. These findings indicate that the relationship between the severity of dysplasia and carcinoma has high potential for leading to malignancy. Therefore, dysplasias can be treated as early cancerous lesions of the esophagus to prevent serious results.

Randomized, Placebo-Controlled, Esophageal Squamous Cell Cancer Chemoprevention Trial of Selenomethionine and Celecoxib

Esophageal squamous cell carcinoma remains a leading cause of cancer death worldwide. Squamous dysplasia, the accepted histological precursor for esophageal squamous cell carcinoma, represents a potentially modifiable intermediate end point for chemoprevention trials in high-risk populations. We conducted a randomized, controlled trial of selenomethionine 200 microg daily and/or celecoxib 200 mg twice daily (2 x 2 factorial design) among residents of Linxian, People's Republic of China. Subjects had histologically confirmed mild or moderate esophageal squamous dysplasia at baseline. Esophagogastroduodenoscopy was performed before and after a 10-month intervention. Per-subject change (regression, stable, or progression) in the worst dysplasia grade was defined as the primary end point. Results were compared by agent group (selenomethionine vs placebo; celecoxib vs placebo). Two hundred sixty-seven subjects fulfilled all eligibility criteria, and 238 (89%) completed the trial. Overall, selenomethionine resulted in a trend toward increased dysplasia regression (43% vs 32%) and decreased dysplasia progression (14% vs 19%) compared with no selenomethionine (P = .08). In unplanned stratified analyses, selenomethionine favorably affected a change in dysplasia grade among 115 subjects with mild esophageal squamous dysplasia at baseline (P = .02), but not among 123 subjects with moderate esophageal squamous dysplasia at baseline (P = 1.00). Celecoxib status did not influence changes in dysplasia grade overall (P = .78) or by baseline histology subgroup. After a 10-month intervention, neither selenomethionine nor celecoxib inhibited esophageal squamous carcinogenesis for all high-risk subjects. However, among subjects with mild esophageal squamous dysplasia at baseline, selenomethionine did have a protective effect. Although it is based on unplanned stratified analyses, this finding is the first report of a possible beneficial effect for any candidate esophageal squamous cell carcinoma chemopreventive agent in a randomized controlled trial.

β‐Catenin splice variants and downstream targets as markers for neoplastic progression of esophageal cancer

This study characterizes the frequency of exon 3 CTNNB1 mutations and compares the expression of CTNNB1 transcript variants and downstream targets MYC and WAF1 (p21) across the neoplastic progression of esophageal squamous cell carcinomas (ESCCs). Mutational analysis was performed on 56 tumors and corresponding germline DNA, using primers to exon 3 of CTNNB1 and SSCP DNA sequencing gels. Quantitative Real Time RT-PCR was performed on 45 foci representing the histological spectrum from normal to invasive cancer, using specific primer sets for alternative splice variants that differ by the presence (16A) or absence (16B) of a 159-bp noncoding segment of exon 16 of CTNNB1, in conjunction with downstream targets MYC and WAF1. Two unique mutations were identified, S37F in the SxxxS repeat region, and a germline polymorphism, T59A. Thus, mutation of CTNNB1 exon 3 is a rare event in this population. RT-PCR analysis successfully confirmed the presence of both beta-catenin splice variants in histologically normal and preneoplastic squamous epithelium, and invasive tumors of the esophagus, and identified a significant reduction in the 16A/16B ratio (P = 0.014) and an accompanying significant increase in the MYC/WAF1 expression ratio (P = 0.001) with progression from normal mucosa to dysplasia. This represents the first identification of two CTNNB1 transcripts in histologically "normal" esophageal squamous cells, squamous dysplasia, and invasive ESCC. These results show an increase in the minor mRNA (16B) isoform and changes in the expression of downstream markers consistent with increased transcription during the histological progression from normal to squamous dysplasia.

Differential protein expression between esophageal squamous cell carcinoma and dysplasia, and prognostic significance of protein markers

The aim of the current study was to evaluate the protein expression involved in the progression from dysplasia to invasive esophageal squamous cell carcinomas and to analyze the prognostic value of markers. Immunohistochemistry was performed for cell cycle regulators [p53, p21, p27, p16, cyclin D1, Rb], apoptosis-related proteins [Fas, Fas-L, FADD, TRAIL, DR4, DR5, caspase-8, caspase-3, bcl-2, Bax], tumor suppressor proteins [ β-catenin, E-cadherin, FHIT, Smad 4, VHL, PTEN, KAI-1], and oncoproteins [c-myc, COX-2, EGFR]. Caspase-3, TRAIL, Fas-L, Fas, Smad 4, VHL, E-cadherin, and EGFR revealed significant differences between dysplasia and their corresponding invasive cancer portion in 25 cases. In a total of 118 cases of invasive cancer, proteins with frequent (⩾60% of the cases) alterations were p53 (overexpression in 64% of SCCs), p27 (loss in 91%), p16 (loss in 81%), and FHIT (loss in 75%). Early clinical stage and bcl-2 immunopositivity were related to the survival rate of patients. In conclusion, caspase-3, TRAIL, Fas-L, Fas, Smad 4, VHL, E-cadherin, and EGFR may be involved in the progression from dysplasia to invasive esophageal SCCs. Clinical stage and bcl-2 are independent prognostic factors throughout the multivariate analysis.

Expression of cyclooxygenase-2 (COX-2) in human esophageal cancer and in vitro inhibition by a specific COX-2 inhibitor, NS-398.

The purpose of the present paper was to study the expression of cyclooxygenase-2 (COX-2) in normal squamous epithelium, squamous dysplasia and squamous cell carcinoma (SCC) of the esophagus, to elucidate the role of COX-2 in esophageal carcinogenesis, and to evaluate the in vitro effect and mechanism of a COX-2 inhibitor, NS-398, in inducing growth inhibition and apoptosis of human esophageal cancer cells. Biopsy specimens of esophageal dysplasia (n = 21), and surgical resections of SCC (n = 37) were compared with normal esophagus (n = 37) and analyzed by RT-PCR. Human esophageal cells were used for the study. Anti-proliferative effect was measured by MTT, apoptosis was determined by DNA fragmentation assay. Marked COX-2 expression was shown in SCC and esophageal squamous dysplasia, and no marked COX-2 expression was observed in the normal squamous epithelium, respectively. NS-398 could inhibit esophageal cells growth in a dose-dependent manner, induce apoptosis, and elevate caspase-3 activity in vitro. This study provides evidence that COX-2 is upregulated in the majority of cases of squamous dysplasia and SCC of esophagus, and that NS-398 can inhibit growth and induce apoptosis via activating caspase-3 activity in vitro. These results suggest that selective inhibitors of COX-2 may be an effective preventive and therapeutic option for esophageal carcinoma.

Expression of cyclooxygenase-2 in esophageal squamous cell carcinogenesis

To investigate the expression of cyclooxygenase-2 (cox-2) protein in normal squamous epithelium, squamous dysplasia and squamous cell carcinoma of the esophagus, and to elucidate the role of cox-2 in esophageal carcinogenesis. Biopsy specimens of atypical esophageal dysplasia (n = 47) and surgical resection of squamous cell carcinoma (n = 86) were compared with normal esophageal specimens (n = 42) and the expression of cox-2 in those specimens was analyzed by immunohistochemistry and western blotting. A significant elevated cox-2 expression was shown in atypical esophageal squamous dysplasia and squamous cell carcinoma, as compared to that in normal esophageal squamous epithelium, with immunohistochemical stain scores of 2.67 +/- 1.77, 2.19 +/- 1.79 and 0.71 +/- 0.46, respectively. Results of western blotting analysis confirmed those obtained by immunohistochemistry. Cox-2 expression significantly correlated with proliferation activity assessed by proliferating cell nuclear antigen index in dysplastic and carcinomous lesions, respectively, and no such correlation could be found in normal esophageal mucosa. Elevated cox-2 expression was not associated with clinical-pathological features of esophageal squamous carcinoma, including age, gender, tumor size, histological grade, lymph node metastasis and clinical stage. Elevated expression of cox-2 in atypical squamous dysplasia and squamous cell carcinoma of the esophagus, which correlated with cell proliferation activity, indicated that cox-2 may be involved in the early stage of squamous carcinogenesis of the esophagus, and may be a target of prevention and treatment for esophageal squamous cell carcinoma.

Cyclooxygenase-2 expression in squamous dysplasia and squamous cell carcinoma of the esophagus.

Cyclooxygenase-2 (cox-2) overexpression has been observed in several types of human cancers and has been implicated in carcinogenesis. To elucidate the role of cox-2 in esophageal carcinogenesis, we evaluated the expression of cox-2 in normal squamous epithelium squamous epithelial dysplasia (n=47), and squamous cell carcinoma of the esophagus (n=86) by immunohistochemistry, reverse transcription-PCR assay, and western blotting. A significant overexpression of cox-2 was observed in esophageal squamous dysplasia and squamous cell carcinoma compared with normal squamous epithelium. The immunoreactive score of cox-2 expression, an index determined by intensity and positivity of cox-2 staining, was 0.71 +/- 0.46 (mean +/- SD) in normal squamous esophagus, 2.19 +/- 1.79 in squamous epithelial dysplasia, and 2.67 +/- 1.77 in squamous cell carcinoma. The results of immunohistochemistry were confirmed by a reverse transcription-PCR assay and western blotting analysis. Cox-2 expression level was correlated with proliferation activity assessed by proliferating cell nuclear antigen (PCNA) index and MIB-1 index in dysplastic lesion (r=0.55, P<0.01 with PCNA and r=0.72, P<0.01 with MIB-1) and carcinoma (r=0.56, P<0.01 with PCNA and r=0.72, P<0.01 with MIB-1). Elevated cox-2 expression was associated with high p53 expression (p<0.001) but not with clinicopathological features including age, sex, tumor size, histological grade, lymph node metastasis, and TNM stage. The results indicated that cox-2 may be involved in an early stage of squamous carcinogenesis of the esophagus, and that cox-2 overexpression was related to cell proliferation in esophageal squamous dysplasia and squamous cell carcinoma.

Utility of Chromoendoscopy with Lugol Solution Spraying in Early Detection of Esophageal Squamous Cell Carcinoma and Dysplasia

Utility of Chromoendoscopy with Lugol Solution Spraying in Early Detection of Esophageal Squamous Cell Carcinoma and Dysplasia

Expression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders

p63 is a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells. Its expression has never been evaluated in the human gastrointestinal tract. The aim of this study was to evaluate the expression of p63 in the esophagus and related metaplastic and neoplastic disorders to gain insight into the pathogenesis of these processes. Of particular interest was the expression of p63 in Barrett esophagus (BE) and in BE-associated multilayered epithelium. Multilayered epithelium has been postulated to represent an early precursor to the development of BE primarily because it shares morphologic and immunophenotypic features of both squamous and columnar epithelium, and has been shown prospectively to be highly associated with BE. Routinely processed mucosal biopsy or resection specimens that contained normal esophageal squamous epithelium (n = 20), squamous dysplasia (n = 4), squamous cell carcinoma (n = 7), BE (n = 10), BE-associated multilayered epithelium (n = 13), esophageal mucosal gland ducts (n = 10), BE-associated dysplasia (n = 12), and BE-associated adenocarcinoma (n = 7) were immunostained for p63 to determine the extent and location of staining. p63 staining was compared with the staining patterns observed for p53, Ki 67 (proliferation marker), and cytokeratins (CKs) 13 (squamous marker), 14 (basal squamous marker), 8/18 (columnar marker), and 19 (basal/columnar marker). Expression of p63 messenger RNA (mRNA) isoforms was also analyzed by reverse-transcription polymerase chain reaction of freshly isolated tissues. In the normal esophagus, p63 was expressed in the basal and suprabasal layers of the squamous epithelium and in basal cells that line the mucosal gland ducts but was negative in all other epithelia of the gastrointestinal tract, including the stomach, small intestine, and colon. Similarly, p63 was not expressed in BE, but it, was present in the basal layer of multilayered epithelium in 9 of 13 cases (69%). p63-positive cells in multilayered epithelium and in the mucosal gland duct epithelium were positive for CK8/18 (100%) and CK13 (67% and 30%, respectively) and negative for CK14 (0%), in contrast to p63-positive cells in squamous epithelium, which were positive for CK14 and CK13 (100%) but negative for CK8/18. In neoplastic tissues, p63 was diffusely expressed in all cases of esophageal squamous cell dysplasia and carcinoma but was negative in all cases of esophageal and colorectal adenocarcinoma. The ΔN isoform of p63 mRNA predominated in all benign and neoplastic squamous tissues examined. p63 may represent a marker of 2 distinct epithelial progenitor cells (basal squamous epithelium and gland duct epithelium) in the esophagus. P63 is upregulated in squamous neoplastic conditions and in this manner may play a role in squamous carcinogenesis. These data also indicate that multilayered epithelium is phenotypically similar to, and may share a lineage relationship with, mucosal gland duct epithelium. HUM PATHOL 32:1157-1165. Copyright © 2001 by W.B. Saunders Company

Sodium thiosulfate solution spray for relief of irritation caused by Lugol's stain in chromoendoscopy

Background: Mucosal iodine staining is known to improve the endoscopic visualization of esophageal squamous dysplasia and cancer. However, it often causes mucosal irritation leading to retrosternal discomfort. The clinical usefulness of sodium thiosulfate solution (STS) for easing symptoms induced by mucosal staining with Lugol's solution was evaluated in this study. Methods: One hundred twenty healthy men over 50 years of age were enrolled in the study. They each underwent esophagogastroscopy including the spraying of Lugol's iodine solution (10 mL) on the mid and distal esophagus and were subsequently randomized into three groups: (I) no treatment (n = 40), (II) spraying of 20 mL of aluminum-magnesium hydroxide gel (Maalox) by means of endoscopic catheter (n = 40), and (III) spraying of 20 mL of 5% sodium thiosulfate solution by means of endoscopic catheter (n = 40). An hour after the endoscopic examination the subjects were asked to complete a questionnaire that addressed adverse symptoms induced by Lugol's iodine staining. Results: Sodium thiosulfate solution spray substantially reduced adverse symptoms that lasted more than 30 minutes after chromoendoscopy, compared with the no-treatment group. There was no significant difference in the proportion of subjects with symptoms between the Maalox and no-treatment groups. Cost of sodium thiosulfate solution spray per use was $0.15 (15 yen). Conclusions: Sodium thiosulfate solution is recommended for routine use after Lugol's staining. (Gastrointest Endosc 2001;53:199-202).

Association between GSTM1*0 and squamous dysplasia of the esophagus in the high risk region of Linxian, China

Individuals with specific phase I and phase II enzyme polymorphisms may be at increased risk for squamous cell carcinoma of the esophagus. However, to our knowledge there has been only one previous report that evaluates a potential role for these polymorphisms in increasing risk for preneoplastic squamous lesions of the esophagus. To explore this further, we examined polymorphisms in CYP1A1, CYP2E1, GSTM1 and GSTT1, both independently and in combination, for potential associations with the risk of biopsy-proven squamous dysplasia of the esophagus in asymptomatic adults from Linxian, a high risk region in China. Cases consisted of 56 individuals from an esophageal cancer screening study with an endoscopic biopsy diagnosis of mild or moderate squamous dysplasia. Each case was matched on age (± 1 year) and gender to a control. Controls were defined as screening study participants with an endoscopic biopsy diagnosis of normal mucosa or esophagitis. DNA was extracted from frozen cell samples obtained by cytologic balloon examination and genotyped using standard methods. Individuals who were GSTM1 null (homozygous for GSTM1*0) were found to have a tendency for an increased risk of esophageal squamous dysplasia (odds ratio=2.6, 95% CI, 0.9–7.4). No excess risks were observed for inheritance of other putative at risk genotypes CYP1A1*2B, CYP2E1*6 or GSTT1*0. The risk associated with the inheritance of combined genotypes was not significantly different than the risk estimates from the univariate analysis. These results are consistent with the notion that exposure to environmental carcinogens that are detoxified by GSTM1, such as polycyclic aromatic hydrocarbons, may contribute to the etiology of esophageal cancer in Linxian.

Up-regulation of cyclooxygenase-2 in squamous carcinogenesis of the esophagus.

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies including squamous cell carcinomas (SCCs) of the esophagus, but little is known about COX-2 expression in premalignant esophageal squamous dysplasia. To elucidate the role of COX-2 in esophageal carcinogenesis, we examined the expression of this enzyme in normal squamous epithelium (n = 42), squamous dysplasia [high-grade dysplasia (HGD, n = 41; low-grade dysplasia (LGD, n = 33)]; carcinoma in situ (n = 16), mucosal invasive carcinoma (n = 18), and advanced SCC (n = 45). Immunohistochemistry showed a significantly high COX-2 expression in HGD compared with other lesions. The COX-2 score, an index determined by intensity and positivity of COX-2 staining (maximum 3.0), was 0.29 +/- 0.04 in normal esophagus, 1.75 +/- 0.11 in LGD, 2.89 +/- 0.05 in HGD, 2.17 +/-0.18 in CIS, 1.95 +/- 0.22 in mucosal invasive carcinoma, and 1.81 +/- 0.08 in advanced SCC. Results of reverse transcription-PCR assays confirmed those obtained by immunohistochemistry. COX-2 expression correlated with proliferation activity assessed by the proliferating cell nuclear antigen index in dysplastic lesions (P = 0.001) but not in SCCs. COX-2 expression in SCC did not correlate with various clinicopathological parameters including prognosis. Our results indicate that COX-2 is a sensitive marker for HGD and suggest that COX-2 may be involved in early stages of squamous carcinogenesis of the esophagus.

Cyclin D1 overexpression in esophageal dysplasia: a possible biomarker for carcinogenesis of esophageal squamous cell carcinoma.

There is controversy as to whether esophageal squamous dysplasia is a pre-cancerous lesion or a non-cancerous lesion. In this study, we conducted an immunohistochemical investigation of cyclin D1, retinoblastoma (Rb), p16INK4 and p27KIP1 expression in 36 squamous dysplasias and 34 early squamous cell carcinomas of the esophagus. The frequency of cyclin D1 overexpression was similar in dysplasias and early cancers (30% vs. 35%). Loss of p16INK4 and p27KIP1 expression was less frequent in dysplasias than in early cancers (p=0.005 and 0.001, respectively). Loss of Rb protein expression was not detected in dysplasia and rarely observed in early cancer (7%). The proliferation cell nuclear antigen index increased from moderate dysplasia to mucosal invasive carcinoma and was correlated significantly with the expression of cyclin D1, p16INK4 and p27KIP1 (p=0.0001, 0.003, and 0.007, respectively). Thus, this study found that cyclin D1 overexpression starts early in dysplasia and could be a useful marker for its malignant potentiality while reduction of p16INK4 and p27KIP1 occurs during the transformation from dysplasia to cancer. These findings suggest that esophageal dysplasia should be treated as a precancerous lesion.

HLA-DR antigen expression in squamous epithelial dysplasia and squamous cell carcinoma of the esophagus: an immunohistochemical study.

To clarify the biologic significance of esophageal squamous epithelial dysplasia, especially the similarity to carcinoma in situ, immunohistochemical investigation of HLA-DR antigen expression and lymphocyte infiltration was performed. HLA-DR antigen was expressed in 12 of the 35 invasive carcinomas (34.4%), 23 of the 38 intraepithelial carcinomas (60.5%), 21 of the 50 areas of dysplasia (42.0%) and only 2 of the 625 specimens of non-cancerous squamous epithelium (0.3%). The HLA-DR-positive rate of dysplasia localized continuous to HLA-DR-positive carcinoma was 68.4%, which was significantly higher than that for HLA-DR positive dysplasia localized continuous to HLA-DR negative cancer (11.1%) (p<0.05). In areas of dysplasia and intraepithelial carcinoma, T cell infiltration was significantly increased at the sites of HLA-DR antigen expression (P<0.01). B cell infiltration was also more common in areas of positive expression. These results suggest that HLA-DR antigen is associated with the local immune response to squamous epithelial dysplasia, and that HLA-DR antigen expression may prevent tumor invasion similarly to its role in intraepithelial carcinoma.

Cyclin D1 overexpression combined with N-nitrosomethylbenzylamine increases dysplasia and cellular proliferation in murine esophageal squamous epithelium.

We previously described the oral-esophageal tissue-specific expression of cyclin D1 with the Epstein-Barr virus ED-L2 promoter in transgenic mice, and resulting dysplasia. Given the evidence for an interplay between environmental and genetic factors in esophageal squamous carcinogenesis, the aim of this study was to determine the potential cooperation of the nitrosamine compound N-nitrosomethylbenzylamine (NMBA), an esophageal specific carcinogen, in the cyclin D1 transgenic mice. NMBA was first demonstrated to induce dysplasia in two strains of inbred mice, C57BL/6 and FVB/N. Subcutaneous NMBA was then administrated to wild type and transgenic mice beginning at 4 weeks of age. Mice were monitored for the duration of the study for general appearance, activity and weight, and were euthanized at 12 and 15 months. Histopathologic analysis revealed increased severity of dysplasia in cyclin D1 mice treated with NMBA compared with treated age-matched wild-type mice and untreated mice. There was also increased proliferating cell nuclear antigen (PCNA) expression in the esophagi of NMBA treated cyclin D1 mice. Taken together, these findings suggest that a genetic alteration, specifically cyclin D1 overexpression and a chemical carinogen, NMBA, may cooperate to increase the severity of esophageal squamous dysplasia, a prominent precursor to carcinoma.

Lugol's staining improves endoscopic detection of esophageal squamous dysplasia and cancer in highrisk chinese patients

Lugol's staining improves endoscopic detection of esophageal squamous dysplasia and cancer in highrisk chinese patients

Cytologic detection of esophageal squamous dysplasia and cancer using esophageal balloon and sponge samplers in Linxian, China

Cytologic detection of esophageal squamous dysplasia and cancer using esophageal balloon and sponge samplers in Linxian, China

Natural history and significance of esophageal squamous cell dysplasia

Balloon-mesh cytologic screening for esophageal cancer done in 255 asymptomatic high-risk United States veterans (age greater than 40 years, ethanol abuse for greater than 20 years, and cigarette smoking greater than 20 pack years) identified 37 patients with squamous cell dysplasia. Of the 37 patients with dysplasia, 28 were re-evaluated prospectively at 6-month intervals for up to 36 months by balloon-mesh cytology, esophagoscopy with vital staining and biopsies, chest radiographs, oropharyngeal examination, and indirect laryngoscopy. During prospective follow-up evaluation, cytology specimens were repetitively normal in 16 patients (57%), showed inflammatory changes in eight patients (29%), persisted as dysplasia in two patients (7%) (both had endoscopic and histologic evidence of esophagitis), and progressed to carcinoma in two patients (7%) (one esophageal, one laryngeal). Although histologic findings concurred with the resolution of dysplasia, biopsy specimens were characterized by a similar difficulty in distinguishing dysplasia from inflammation. Erroneous histologic diagnoses of carcinoma in situ were made in two patients with reflux esophagitis evident endoscopically and confirmed during the course of a 24-36 month follow-up period. The authors conclude that squamous cell dysplasia detected by balloon-mesh cytology is seldom a precursor of esophageal cancer in the high-risk U.S. population but, rather, is often related to esophagitis. Thus, balloon-mesh cytology has limited use as a screening method for the early detection of esophageal cancer in the United States.