EUS followed by EMR for staging of high-grade dysplasia and early cancer in Barrett's esophagus

BACKGROUND: Accurate staging of high-grade dysplasia and of early cancer in Barrett's esophagus is important in the selection of patients for endoscopic therapy. METHODS: Patients with Barrett's esophagus and biopsy specimen proven high-grade dysplasia and adenocarcinoma in focal nodular lesions or in endoscopically unapparent flat lesions in short-segment Barrett's esophagus were initially staged with EUS. In patients with disease limited to the mucosa on EUS, cap-assisted EMR was performed. The depth of tumor invasion on EMR specimens was classified in a similar manner to squamous-cell cancer of the esophagus: m1 (epithelial layer, dysplasia), m2 (lamina propria invasion), m3 (muscularis mucosae invasion), sm (submucosal invasion). RESULTS: EUS was performed in 48 consecutive patients (27 with focal nodular lesions and 21 with microscopic lesions), and submucosal invasion was diagnosed in 8 (confirmed in 7/8 at surgery). EMR was carried out in the remaining 40 patients without significant complications. In the 25 patients with high-grade dysplasia on prior biopsy specimens, EMR confirmed m1 disease in 19; whereas in 6 (24%), invasive adenocarcinoma was detected (to m2 in 4; to m3 in 2). In the 15 patients with invasive cancer on prior biopsy specimens and staged as intramucosal cancer on EUS, intramucosal carcinoma was confirmed in 9 (m2 in 3; m3 in 6); whereas, in 6 patients (40%), submucosal invasion was found. Overall, EUS provided accurate staging in 41/48 patients (85%) with one patient overstaged and 6 patients understaged compared with pathologic staging obtained by surgery or EMR. Of the 34 patients with m1 to m3 staging after EMR, 29 were treated endoscopically and had no evidence of cancer after a mean follow-up of 22.9 months(standard deviation 9.2 months). CONCLUSIONS: EMR provides pathologic staging information that, in addition, may be helpful after EUS if a stage-determined approach is used in the management of high-grade dysplasia and of early cancer in Barrett's esophagus. EMR may be particularly useful for staging of focal nodules or in short-segment Barrett's esophagus with microscopic lesions when endoscopic therapy is an option.     

Dysplasia in Barrett's esophagus--intra- and interobserver variability in histopathological diagnosis

BACKGROUND: Barrett's esophagus is a well-known pre-malignant condition. Pathologic interpretation of biopsy specimens guides endoscopic surveillance as well as the therapeutic approach that will be carried out. However, the predictive value of histopathologic diagnosis can be questioned due to its poor intra- and interobserver reproducibility. AIMS: To assess intra- and interobserver variability in the diagnosis of Barrett's dysplasia. MATERIAL AND METHODS: Three-micrometer thick sections from biopsy specimens from 42 patients with Barrett's esophagus were stained with hematoxylin-eosin and PAS-alcian blue. The reading of the slides was carried out blindly in a light microscope. Intra and interobserver variability in the interpretation of the slides was determined by kappa statistics. RESULTS: The number of tissue specimens was 229, with average of 5.45 (1 to 18) fragments for patient. Low grade dysplasia was diagnosed by pathologists in 21.4% to 52.4% of the cases. The intra-observer agreement for the diagnosis of low grade dysplasia was slight (kappa = 0.30). The interobserver agreement for the diagnosis of low grade dysplasia was poor, with kappa scores between 0.05 and 0.16. The diagnosis of dysplasia, with agreement for all pathologists examining the same set of slides, was 14.3%. CONCLUSIONS: Pathologic interpretation of Barrett's dysplasia may be subject to marked intra- and interobserver variabiliaty. Interpretation of low grade dysplasia, as high grade dysplasia, should also be considered for review by two or more pathologists.     

Intraoperative frozen section margin evaluation in gastric cancer of the cardia surgery

BACKGROUND/AIMS: The use of intraoperative frozen section to determine the extent of margin resection is a common practice. Our aim was to identify the value of intraoperative frozen section in margin evaluation and to investigate its indication for gastric cancer of the cardia. METHODOLOGY: Intraoperative frozen section examinations of the proximal margins of 66 patients with gastric adenocarcinoma of the cardia were reviewed. The frozen section results were compared with those of the permanent sections. Clinicopathological features that predict a positive frozen section margin were examined by univariate and multivariate analysis. RESULTS: The overall accuracy, sensitivity and specificity of an intraoperative frozen section, was 97%, 77.8%, and 100%, respectively. Infiltration on frozen section occurred in 10.7% (7/66) of the proximal margins, while in 28.6% (2/7) of the entire additional resection margins. The positive margins were associated with more advanced in depth of tumor invasion and disease stage. However, the depth of invasion was the only independent predictor for a positive frozen margin. CONCLUSIONS: Routine evaluation of the proximal resection margin by intraoperative frozen section does not appear to be necessary in gastric cancer surgery of the cardia. However, this technique is advisable for patients with T3 or T4 lesions.     

Significance of neoplastic involvement of margins obtained by endoscopic mucosal resection in Barrett's esophagus

OBJECTIVES: Although EMR has been used for elimination of neoplasia in BE, the significance of positive carcinoma margins and depth of invasion on endoscopic resection pathology has not been assessed using a valid standard. The aim of this study was to assess the accuracy of tumor staging by EMR using esophagectomy as the standard. METHODS: Medical records of patients, who underwent endoscopic resection for esophageal carcinoma or high-grade dysplasia in BE followed by esophagectomy, were reviewed. Data were abstracted from a prospectively maintained EMR database. Endosonography and endoscopic resection were performed by a single experienced endoscopist. Two experienced GI pathologists interpreted all histological results. Standard statistical tests were used to compare continuous and categorical variables. RESULTS: Twenty-five patients were included in the study. Three patients had mucosal carcinoma and 16 had submucosal carcinoma following endoscopic resection. Surgical pathology staging was consistent with preoperative EMR staging in all patients. No patient with negative mucosal resection margins had residual tumor at the resection site at esophagectomy. In patients with submucosal carcinoma, 8 had residual carcinoma at the EMR site at surgery and 5 patients had metastatic lymphadenopathy. CONCLUSIONS: Tumor staging using EMR pathology is accurate when compared with surgical pathology following esophagectomy. Negative margins on EMR pathology correlate with absence of residual disease at the EMR site at esophagectomy. Submucosal carcinoma on EMR specimens was associated with a high prevalence of residual disease at surgery (50%) and metastatic lymphadenopathy (31%).     

Endoscopic mucosal resection for lesions with endoscopic features suggestive of malignancy and high-grade dysplasia within Barrett's esophagus

BACKGROUND: Endoscopic mucosal resection has been used in the treatment of superficial squamous cell cancers and gastric malignancies. Our aim was to determine whether endoscopic mucosal resection can be used in the diagnosis of lesions within Barrett's esophagus whose endoscopic appearances raise suspicion of carcinoma or high-grade dysplasia. METHODS: Twenty-five patients with such lesions within Barrett's esophagus underwent endoscopic mucosal resection for diagnostic and therapeutic purposes. All patients underwent endoscopic ultrasound to determine the feasibility of endoscopic resection. Only lesions found to be uT0 or uT1 underwent EMR. The lift and cut technique was used in 23 patients and a variceal ligating device was used on 2 patients. RESULTS: Endoscopic mucosal resection was performed because of a nodule or polyp within Barrett's esophagus in 11 patients (44%) and suspected superficial cancer or high-grade dysplasia in 14 patients (56%). Endoscopic mucosal resection diagnosed superficial adenocarcinoma in 13 patients (52%) and high-grade dysplasia in 4 (16%); it confirmed lesions in 8 patients (40%) to be of lower neoplastic risk. No complications occurred due to the procedure itself. CONCLUSIONS: Endoscopic mucosal resection is a technique with low morbidity and mortality. It has led to a change in diagnosis in patients with Barrett's esophagus and lesions with endoscopic features that suggest neoplasia. Its major advantages include simplicity and retrieval of the specimen en bloc.     

Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions

There is uncertainty regarding the value of endoscopic biopsy surveillance in Barrett's esophagus because, in retrospective studies, some patients with high-grade dysplasia in endoscopic biopsy specimens have had unexpected advanced adenocarcinoma discovered at the time of esophageal resection. We compared the accuracy of preoperative endoscopic biopsy diagnoses with the final pathologic diagnoses in esophagectomy specimens in 4 patients who had both high-grade dysplasia and intramucosal carcinoma and 4 other patients who had only high-grade dysplasia preoperatively. The histologic lesions in all 8 patients were documented in intact mucosa with no gross evidence of neoplasia by endoscopy. The preoperative diagnoses were defined with an endoscopic biopsy protocol in which specimens were taken with large-channel biopsy forceps at least every 2 cm throughout the length of Barrett's epithelium. Final pathologic diagnoses derived from detailed analysis of the resected specimens confirmed high-grade dysplasia without carcinoma in 4 patients and intramucosal carcinoma in 2 patients. The remaining 2 patients with a preoperative diagnosis of intramucosal carcinoma had focal submucosal invasion by carcinoma in the resected specimens, but no involvement of the muscularis propria or adventitial lymph nodes. Because the natural history of high-grade dysplasia is not known, the decision to operate on patients with this lesion must be carefully weighed and individualized for each patient. Two of our patients who underwent esophageal resection for high-grade dysplasia without cancer died, one immediately postoperatively and the other 9 mo later after a postoperative stroke. Once intramucosal carcinoma is documented, surgery should be considered if the patient is an acceptable operative risk. We conclude that systematic preoperative endoscopic biopsy of intact mucosa in Barrett's esophagus can correctly detect high-grade dysplasia, either alone or in combination with early, treatable adenocarcinoma.     

EMR for Barrett's esophagus-related superficial neoplasms offers better diagnostic reproducibility than mucosal biopsy

BACKGROUND: EMR of Barrett's esophagus (BE)-related superficial neoplasms represents an efficacious staging modality. It also allows for better pathologic grading compared with mucosal biopsy specimens. However, the interobserver variation in the interpretation of EMR specimens has not been tested. OBJECTIVE: To evaluate consistency in the diagnosis of BE-related neoplasia on EMR specimens. DESIGN: Nine pathologists reviewed 25 esophageal EMR specimens and corresponding biopsy specimens independently. Each pathologist classified the cases as either non-neoplastic BE, low-grade dysplasia, high-grade dysplasia, intramucosal adenocarcinoma, or invasive adenocarcinoma. Interobserver concordance for both specimens from EMRs and biopsies was measured by intraclass correlation and Kendall's coefficient of concordance. The proportion of agreement was also calculated for each specimen and compared for EMR and biopsy by using the Wilcoxon signed rank test. SETTING: Teaching hospitals. PATIENTS: Twenty-five patients who underwent EMR for BE-related neoplasia. RESULTS: The intraclass correlation and the Kendall's coefficient for the 25 biopsy specimens was 0.938 (95% CI 0.880-0.965) and 0.677, respectively; for the 25 EMRs, these were significantly improved, at 0.977 (95% CI 0.957-0.987) and 0.831, respectively. In addition, the proportion of agreement for EMR specimens was significantly better compared with biopsy specimens (P = .015). CONCLUSIONS: Interobserver agreement of BE-related neoplasia on EMR specimens is significantly higher compared with biopsy specimens. The results may relate to the larger tissue sampling compared with biopsy specimens and the ability to evaluate mucosal landmarks, such as double muscularis mucosae. Thus, we suggest that EMRs, in addition to being a staging and therapeutic procedure, improve diagnostic consistency.     

Study of the intrahepatic surgical margin of hilar bile duct carcinoma

BACKGROUND/AIMS: The diagnosis and treatment for hilar bile duct carcinoma has greatly improved. Frozen section is one of the modalities used to determine the intrahepatic surgical margin and the surgical approach for tumor resection. But we are sometimes faced with the case where we are perplexed whether to carry out additional surgical resection or not according to the result of frozen section, due to its inaccuracy. We studied herein the relation between the prognosis and the intrahepatic surgical margin according to the result of frozen section. METHODOLOGY: We reviewed 23 cases of hilar bile duct carcinoma whose intrahepatic surgical margin was determined by frozen section and studied the cause of death and surgical procedure. Results of the frozen sections were compared with the permanent paraffin sections. RESULTS: The overall survival rates at 1, 3 and 5 years after operation were 68.1, 41.3, and 33.0%, respectively. The accuracy, sensitivity and specificity of frozen section was 56.5%, 75.0%, and 46.7%, respectively. CONCLUSIONS: We concluded that by evaluating the diagnosis of frozen section during the surgery it was difficult to determine intrahepatic surgical margin. Aggressive hepatic resection sometimes causes a high risk of hepatic failure in which case the histological diagnosis of the frozen section throughout should not be carried out.     

Endoscopic mucosal resection in the upper gastrointestinal tract

Endoscopic mucosal resection （EMR） is a technique used to locally excise lesions confined to the mucosa. Its main role is the treatment of advanced dysplasia and early gastrointestinal cancers. EMR was originally described as a therapy for early gastric cancer. Recently its use has expanded as a therapeutic option for ampullary masses, colorectal cancer, and large colorectal polyps. In the Western world, the predominant indication for EMR in the upper gastrointestinal tract is the staging and treatment of advance dysplasia and early neoplasia in Barrett＇s esophagus. This review will describe the basis, indications, techniques, and complications of EMR, and its role in the management of Barrett＇s esophagus.     

The diagnosis of low-grade dysplasia in Barrett's esophagus and its implications for disease progression

OBJECTIVE: The reported risk of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or carcinoma (CA) in Barrett's esophagus varies. However, the validity of a diagnosis of LGD may be questioned because of interobserver variability. METHODS: A search of the Cleveland Clinic Foundation surgical pathology files between 1986 and 1997 yielded biopsy specimens from 43 patients with Barrett's esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnoses of HGD or carcinoma were excluded. The LGD cases were randomized and blindly reviewed by three gastrointestinal (GI) pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia (ND; n = 28), indefinite for dysplasia (IND; n = 14), or HGD (n = 15). Each pathologist classified every biopsy specimen as ND, IND, LGD, or HGD, and interobserver agreements were determined by kappa statistics (K). Follow-up data were available on 25 patients originally diagnosed with LGD. Progression was defined as a subsequent diagnosis of HGD or CA on esophageal biopsy or resection specimens. RESULTS: Agreement between two GI pathologists for a diagnosis of LGD was fair (K = 0.28) and poor (K = 0.21 and -0.04). Individual GI pathologists agreed with the original diagnosis of LGD in 70%, 56%, and 16% of cases. The 25 patients with follow-up included 21 men and four women (mean age, 67 yr) with a mean follow-up of 26 months (range: 2-84 months). Seven patients (28%) with follow-up developed HGD (five patients) or CA (two patients), 2-43 months (median: 11 months) after a diagnosis of LGD. The individual GI pathologists' diagnosis did not correlate with progression. However, when at least two GI pathologists agreed on LGD, there was a significant association with progression (seven of 17 patients, 41%, p = 0.04). When all three GI pathologists agreed on a diagnosis of LGD, four of five patients progressed (p = 0.012). In contrast, of the eight patients with follow-up and no agreement among GI pathologists for a diagnosis of LGD, none progressed. CONCLUSIONS: A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus-related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.     

Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus.

BACKGROUND: Endoscopic mucosal resection (EMR) and photodynamic therapy have been proposed as treatments for early stage cancers. EMR is limited by its focal nature whereas photodynamic therapy is dependent on precise staging. The combination of EMR and photodynamic therapy were studied in the treatment of superficial cancer in patients with Barrett's esophagus. METHODS: Seventeen consecutive nonsurgical patients with superficial cancers underwent EMR followed by photodynamic therapy with a porphyrin photosensitizer. Photoradiation was performed at 630 nm for a total dose of 200 J/cm of diffuser. RESULTS: Seventeen patients (15 men; mean age 69 +/- 13 years) underwent EMR. The mean diameter of mucosal resection was 1 cm. The margins were involved by cancer in 3 cases. EMR improved staging in 8 patients (47%). Sixteen (94%) patients remained in remission (median follow-up 13 months). Complications included minor bleeding after EMR in 1 patient (6%), stricture in 5 (30%), cutaneous phototoxicity in 2 (12%), and supraventricular tachycardia in 1 patient (6%). CONCLUSIONS: Combined EMR and photodynamic therapy appears to be an effective and safe therapy for superficial esophageal cancer within Barrett's esophagus. This combination improves cancer staging, removes the superficial cancer, and eliminates remaining mucosa at risk for cancer development.     

Present status of photodynamic therapy for high-grade dysplasia in Barrett's esophagus

GOALS: Review recent developments in Barrett's dysplasia including regulatory approval of porfimer sodium photodynamic therapy. BACKGROUND: Barrett's esophagus is thought to be the result of long-standing gastroesophageal reflux disease and is known to be the most important risk factor for the development of esophageal adenocarcinoma. The natural history of Barrett's esophagus is not well known, but the annual incidence of invasive adenocarcinoma is estimated to be 0.5% (reported range, 0.2%-2.0%). This represents an increased risk for esophageal cancer of 30 to 60 times higher than normal subjects. As for colorectal cancer, malignant degeneration is Barrett's esophagus is thought to occur through a continuum of histologic stages: metaplasia, dysplasia and neoplasia. Barrett's high-grade dysplasia (formerly referred to as carcinoma in situ) is the histologic stage of disease that immediately precedes the development of invasive carcinoma. CONCLUSIONS: Previously, Barrett's high-grade dysplasia patients were routinely referred for esophageal resection surgery based upon the assumption of inevitable progression to cancer, the high rate of undiagnosed synchronous cancers, and few treatment alternatives. Important developments in Barrett's high-grade dysplasia include recent publications regarding the natural history of Barrett's high-grade dysplasia and the regulatory approval for endoscopic ablation therapy using porfimer sodium photodynamic therapy (Photofrin PDT).     

In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy.

BACKGROUND & AIMS: Confocal laser endomicroscopy allows subsurface analysis of the intestinal mucosa and in vivo histology during ongoing endoscopy. Here, we have applied this technique to the in vivo diagnosis of Barrett's epithelium and associated neoplasia. METHODS: Fluorescein-aided endomicroscopy was performed by applying the endomicroscope over the whole columnar-lined lower esophagus. Images obtained within 1 cm of the columnar-lined lower esophagus were stored digitally and a targeted biopsy examination or endoscopic mucosal resection of the examined areas was performed. In vivo histology was compared with the histologic specimens. All digitally stored images were re-assessed by a blinded investigator by the confocal Barrett classification system to predict histology. Intraobserver and interobserver variations of the involved endoscopists were evaluated by using kappa statistics. RESULTS: Endomicroscopy allowed distinguishing between different types of epithelial cells and detected cellular and vascular changes in Barrett's epithelium at high resolution during ongoing endoscopy in 63 patients. Barrett's esophagus and associated neoplasia could be predicted with a sensitivity of 98.1% and 92.9% and a specificity of 94.1% and 98.4%, respectively (accuracy, 96.8% and 97.4%). The mean kappa value for interobserver agreement for the prediction of histopathological diagnosis was .843, whereas the intraobserver agreement showed a mean kappa value of .892. CONCLUSIONS: Fluorescence-aided endomicroscopy of Barrett's esophagus allows in vivo histology of the mucosal layer during ongoing endoscopy. Gastric and Barrett's epithelium and Barrett's-associated neoplastic changes can be diagnosed with high accuracy. Thus, endomicroscopy may be helpful in the management of patients with Barrett's esophagus.     

p53 and Ki-67 in Barrett's carcinoma: is there any value to predict recurrence after circumferential endoscopic mucosal resection?

BACKGROUND: There are situations in which the specimens obtained after endoscopic mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus are not adequate for histopathological assessment of the margins. In these cases, immunohistochemistry might be an useful tool for predicting cancer recurrence. AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting the cancer recurrence in patients with Barrett's esophagus-related cancer referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy specimens from 41 patients were analyzed. All endoscopic biopsies prior to endoscopic mucosal resection presented high-grade dysplasia and cancer was detected in 23 of them. Positive reactions were considered the intense coloration in the nuclei of at least 90% of the cells in each high-power magnification field, and immunostaining could be classified as superficial or diffuse according to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal resection samples detected cancer in 21 cases. In these cases, p53 immunohistochemistry revealed a diffuse positivity for the great majority of these cancers (90.5% vs. 20%), and Ki-67 showed a diffuse pattern for all cases (100% vs. 30%); conversely, patients without cancer revealed a superficial or negative pattern for p53 (80% vs. 9.5%) and Ki-67 (70% vs. 0%). During a mean follow-up of 31.6 months, 5 (12.2%) patients developed six episodes of recurrent cancer. Endoscopic mucosal resection specimens did not show any significant difference in the p53 and Ki-67 expression for patients developing cancer after endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful to confirm the cancer; however, they had not value for predicting the recurrent carcinoma after circumferential endoscopic mucosal resection of Barrett's carcinoma.     

Accuracy of EUS in the evaluation of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma

BACKGROUND: Nonoperative therapy with intent to cure may be considered for patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma. However, a more advanced stage of disease must be precluded before such treatment. The potential of EUS for this purpose was evaluated. METHODS: EUS was performed in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma based on endoscopy, endoscopic biopsies, and CT before esophagectomy. EUS findings were compared with surgical/pathologic evaluation. RESULTS: EUS suggested submucosal invasion in 6 patients and lymph node involvement in 5 patients. By surgical/pathologic evaluation, 5 of 22 patients (23%) had unsuspected submucosal invasion and 1 had lymph node involvement. EUS detected all 5 instances of submucosal invasion and the single instance of lymph node involvement. EUS was falsely positive for submucosal invasion in 1 patient and for lymph node involvement in 4 patients. Sensitivity, specificity, and negative predictive values of preoperative EUS for submucosal invasion were 100%, 94%, and 100%, and for lymph node involvement were 100%, 81%, and 100%, respectively. A nodule or stricture noted by endoscopy was associated with an increased likelihood of submucosal invasion. CONCLUSIONS: In patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma, EUS detected otherwise unsuspected submucosal invasion and lymph node involvement. Patients should be evaluated with EUS when nonoperative therapy is contemplated.     

Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases

BACKGROUND: Endoscopic mucosal resection (EMR) is an alternative to surgery for removal of superficial neoplastic lesions of the GI tract. The aim of this study was to assess the safety, efficacy, and clinical outcomes of EMR. METHODS: Data from consecutive EMR procedures performed by using suction cap-assisted and/or saline solution-assisted snare resection techniques over a 45-month period were reviewed retrospectively. EUS was performed before EMR in the majority of cases. Immediate and delayed complications were recorded. Survival was assessed in patients with carcinoma or high-grade dysplasia on final histopathology in whom EMR achieved complete resection. RESULTS: One hundred one lesions were removed by EMR in 92 patients. Indications were adenoma (67%), high-grade dysplasia (13%), intramucosal carcinoma (11%), and lesions of uncertain histopathology (10%). Locations were esophagus 19%, stomach 14%, duodenum 27%, rectum 12%, and colon 29%. Suction cap-assisted technique was used in 26% and saline solution-assisted polypectomy in 74% of cases. Complete resection was achieved in 89%. For complete resection, 17% required more than 1 session. Post-EMR histopathology was adenoma 47%, high-grade dysplasia 13%, carcinoma 16%, carcinoid 3%, benign 19%, and low-grade dysplasia 3%. EMR resulted in upgrading of histopathologic staging to carcinoma or high-grade dysplasia in 44%. Bleeding was the only complication (early 16, delayed 6). The median cancer-free survival in patients with adenocarcinoma who underwent complete resection by EMR was 27 months (interquartile range: 17-28 months). CONCLUSION: EMR achieves complete resection in a majority of patients but is associated with a higher risk of bleeding compared with standard polypectomy. EMR changes pathologic stage in a significant number of patients. Survival data are encouraging, but long-term follow-up studies are needed.     

Endoscopic therapy of Barrett esophagus--a supplement to drug and surgical options?

Within the last few years intestinal metaplasia at the gastroesophageal junction (Barrett's esophagus) has turned out to be a "shooting star" in the field of gastrointestinal diseases. The detection rate of Barrett's epithelium by the endoscopists and pathologists has raised dramatically as well as the incidence of the carcinoma at the gastroesophageal junction. Furthermore the "short Barrett" was discovered as a relevant risk factor for cancer development. To date ablation techniques with thermal devices, photodynamic techniques (PDT) and the mucosal resection (EMR) compete as local endoscopic treatment methods. However to date it is still in discussion whether in case of nondysplastic Barrett's esophagus endoscopic therapy is an "overtreatment" and an "undertreatment" in case of Barrett's with high-grade dysplasia or early cancer. The currently available data are discussed.     

Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma

The value of endoscopic surveillance biopsy for dysplasia and carcinoma in patients with Barrett's esophagus is controversial. One reason is that the available histologic criteria are not adequate to separate patients with lesser degrees of dysplasia or predysplastic changes who are at increased risk for carcinoma and therefore require more frequent surveillance from those patients who are not at increased risk. We used flow cytometry and histology to evaluate 317 biopsy specimens from 64 consecutive patients who were in a cancer surveillance program for Barrett's esophagus and 3 additional patients with adenocarcinoma in Barrett's esophagus. Specimens from 10 patients had aneuploid cells; 9 of these had dysplasia or carcinoma, or both, but 1 patient had only specialized metaplastic epithelium. Twenty specimens ahd G2/tetraploid fractions greater than 6%; all 20 came from patients who had cancer or dysplasia, or were indefinite for dysplasia. All patients with dysplasia or adenocarcinoma had evidence of genomic instability (aneuploidy) or abnormalities of mucosal proliferation by flow cytometry, even when the dysplasia was focal or difficult to recognize histologically. In a small subset of patients with specialized metaplastic epithelium whose specimens were histologically negative or indefinite for dysplasia, the mucosa had aneuploid cell populations or proliferative abnormalities that were otherwise found only in dysplasia or carcinoma. Additional study may prove that this subset of patients merits more frequent endoscopic biopsy surveillance because of an increased risk for developing carcinoma. Because the abnormalities we have detected by flow cytometry correlate well with the conventional histologic diagnoses of dysplasia and carcinoma, they may prove to be a valuable objective adjunct in the diagnosis of dysplasia and carcinoma in Barrett's esophagus.     

Does the criterium of positivity for the immunohistochemical analysis of p53 in the confirmation of Barrett's dysplasia make any difference?

BACKGROUND: Barrett's esophagus is the most serious complication of the gastroesophageal reflux disease and presents a malignant potential. The expression of the tumoral marker p53 increases with the dysplasia-adenocarcinoma sequence. AIMS: To evaluate the p53 expression in Barrett's esophagus with or without dysplasia according to the two positive immunostaining criteria. MATERIALS AND METHODS: The material was constituted by endoscopic biopsy specimens from 42 patients with Barrett's esophagus. Section of formalin-fixed and paraffin-embedded biopsies were stained with hematoxylin-eosin, PAS-alcian blue and evaluated the p53 immunohistochemical expression. Two p53 immunostaining criteria were utilized: 1. The staining of, at least, half of the nuclei, and 2. The staining of any nucleus. The diagnosis of dysplasia was confirmed by the agreement between three pathologists. RESULTS: The total number of tissue specimens was 229, with an average of 5.4 specimens per patient. Dysplasia, with agreement for all pathologists examining the same set of slides, was detected in six (14.3%) cases. According to the two different p53 immunostaining criteria, the protein was detected in non-dysplastic Barrett's metaplasia, respectively, in 5 (13.9%) and 14 (38.9%) patients. Specifically in the six dysplastic cases, p53 was detected, according to the immunostaining criteria, in one (16.7%) and four (66.7%) cases, respectively. CONCLUSIONS: In this group, p53 immunohistochemical expression, regardless of positive criteria take into account, was not useful for detecting dysplasia in Barrett's esophagus.     

Autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus

BACKGROUND: The occurrence of precancerous lesions, such as high-grade dysplasia, in patients with short-segment Barrett's esophagus is controversial. This study assessed the efficacy of autofluorescence endoscopy for detection of high-grade dysplasia in short-segment Barrett's esophagus. METHODS: A total of 34 patients (28 men, 6 women; age range 40-77 years) with histopathologically proven short-segment Barrett's esophagus were studied. Autofluorescence endoscopy was performed by using monochromatized blue light (425-455 nm) filtered from a conventional xenon light source. A total of 136 and 109 biopsy specimens were taken from Barrett's mucosa under control, respectively, white light endoscopy and autofluorescence endoscopy. RESULTS: High-grade dysplasia was found in 9 (8.3%) autofluorescence-guided biopsy specimens, which was significantly greater than the number of white light endoscopy-guided biopsy specimens with this finding (one positive biopsy specimen, 0.7% of total biopsy specimens obtained). Autofluorescence endoscopy detected high-grade dysplasia in 7 patients, 6 more than were identified with white light endoscopy. In the one patient with high-grade dysplasia detected by white light endoscopy-guided biopsy specimens, autofluorescence-guided biopsy specimens revealed only low-grade dysplasia. CONCLUSION: Autofluorescence endoscopy in patients with short-segment Barrett's esophagus increases the detection rate of high-grade dysplasia.