Detection of Barrett's esophagus after endoscopic healing of erosive esophagitis.

BACKGROUND: The presence of erosive esophagitis (EE) in patients presenting for upper endoscopy may prevent the detection of underlying Barrett's esophagus (BE) in the distal esophagus. AIM: To prospectively determine the proportion of patients detected with BE upon repeat endoscopy after healing of EE. METHODS: Patients with endoscopically confirmed EE without BE were treated with standard doses of acid suppression therapy and a repeat endoscopy was performed to assess the presence of BE. If columnar mucosa was visualized in the distal esophagus, targeted biopsies were obtained and all biopsies were evaluated for the presence of intestinal metaplasia. BE was defined as columnar mucosa in the distal esophagus with intestinal metaplasia on biopsy. RESULTS: A total of 172 patients with reflux symptoms were diagnosed with EE without BE on initial endoscopy. They were treated with standard doses of proton pump inhibitor therapy, and after a mean duration of 11 wk (range 8-16 wk), a repeat endoscopy was performed to confirm healing of EE and to document the presence of BE. On repeat endoscopy, EE was completely healed in 116 patients (67%), and of those, BE was suspected in 32 patients (i.e., columnar-lined distal esophagus) and was confirmed in 16 patients (13.8%). In the 56 patients with persistent EE on repeat endoscopy, columnar mucosa in areas of previously healed esophagitis was visualized in 8 and confirmed in 5 patients (8.9% of nonhealed cases). Overall, 21 (12%) patients were confirmed with BE on repeat endoscopy; all men, mean age 61 yr with a median BE length of 0.5 cm (range 0.5-5 cm, interquartile range 0.5 cm). The majority of these patients (N = 19) had short segment Barrett's esophagus (SSBE) (i.e., length <3 cm). CONCLUSIONS: In patients with EE undergoing treatment with acid suppressive therapy, BE (mainly SSBE) is detected in approximately 12% of patients on repeat endoscopy. Patients with reflux symptoms undergoing endoscopy for the detection of BE (i.e., screening) should be treated with acid suppressive therapy prior to endoscopy to enhance the yield of BE. Alternatively, if the goal is to document BE and if EE is found at the initial endoscopy, then repeat endoscopy may be considered after acid suppressive therapy.

Angiogenic switch in Barrett's adenocarcinoma: the role of vascular endothelial growth factor.

The development of cancerous cells from the normal cells is the consequence of multiple genetic and epigenetic abuses. Activation of "Angiogenic switch" or formation of new blood vessels is one of the upshots of these abuses. Multiple factors are associated with the activation of angiogenic switch. Vascular endothelial growth factor (VEGF) and its down stream signaling molecules is important troupe of this event. In this article, we reviewed the role this troupe in the development of Barrett's adenocarcinoma and also discussed the possible remedies, which have the impact on blocking the function of this troupe.

Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus.

BACKGROUND & AIMS: The exact incidence of adenocarcinoma in patients with Barrett's esophagus (BE) is not known and is reported to vary from 0.2%-2% per year. Published series of patients with BE have included relatively small numbers of patients with limited duration of follow-up. The goal of this study was to define the prevalence and incidence of dysplasia and cancer and evaluate the paths of progression in a large multicenter cohort of BE patients. METHODS: The BE study is a multicenter clinical and endoscopic outcomes project involving a single large database of patients with BE. Data from each of the participating centers were merged into the main study database. Cancers and HGD occurring within 12 months of the index endoscopy were regarded as prevalent cases. RESULTS: One thousand three hundred seventy-six patients met the study criteria (95% white, 14% women); 91 patients had cancer at the initial endoscopy (prevalent cases, 6.7%; 95% confidence interval [CI], 4.8%-8.7%). Six hundred eighteen patients were followed for a total of 2546 patient-years; mean follow-up was 4.12 years. Twelve patients developed cancer during follow-up, a cancer incidence of 1 in 212 patient-years of follow-up (0.5% per year; 95% CI, 0%-1.1%). The combined incidence of HGD and/or cancer was 1 in 75 patient-years of follow-up or 1.3% per year (95% CI, 0%-2.2%). Of the 34 patients developing HGD and/or cancer, 18 patients (53%) had at least 2 initial consecutive endoscopies with biopsies revealing nondysplastic mucosa. The incidence of LGD was 4.3% per year (95% CI, 2.8%-6.0%). In the 156 patients with LGD, regression to no dysplasia occurred in 66%, persistent LGD in 21%, and progression to HGD/cancer in 13%. The incidence of cancer in patients with LGD was 1 in 156 patient-years of follow-up or 0.6% per year (95% CI, 0%-1.3%). CONCLUSIONS: Preliminary results from this trial define the prevalence and incidence of dysplasia and cancer in a multicenter cohort of patients with BE. At least half the patients who developed HGD and/or cancer had 2 consecutive initial endoscopies with biopsies revealing nondysplastic mucosa. The majority of patients with LGD regressed and had a cancer incidence similar to all BE patients.

Visible endoscopic and histologic changes in the cardia, before and after complete Barrett's esophagus ablation.

BACKGROUND: Adverse events associated with the thermal ablation of Barrett's esophagus (BE) include the generation of gastric mucosa buried beneath the neosquamous regrowth, and unrecognized development and growth of adenocarcinomas. No reports exist regarding the endoscopic appearance and histology of the cardia before and after BE ablation. The aim of our study was to assess the relative frequency of the occurrence of visible endoscopic and histologic changes in the cardia, before and after complete BE ablation. METHODS: A subset analysis of patients with uncomplicated BE, BE with dysplasia, or early carcinoma, who had been enrolled into one of 4 ongoing prospective studies of mucosal ablation, was examined. Eighty-two patients were identified who entered a BE ablation study, with 75 of these completing BE mucosal ablation. Cardia biopsy specimens were taken in all patients before ablation and serially after BE ablation. Cardia histology was graded by using the modified Sydney System for gastritis. RESULTS: Before ablation, cardia nodules were noted in 3, cardia intestinal metaplasia (IM) in 7 (8.5%), and none harbored cardia dysplasia. Postablation surveillance ranged from 3 to 75 months (mean 31.1 months [19.5]). Six subjects (8%) developed cardia nodules during surveillance; cardia IM was found in 21(28%), with 17 of these being a new finding (incidence of 25%). Cardia low-grade dysplasia incidence was 1.3% and high-grade dysplasia was 4% after BE ablation. CONCLUSIONS: The pathophysiology of the abnormal cardia histology and the endoscopic lesions (nodules) is unclear, but endoscopic surveillance of not only the neosquamous epithelium but also the cardia should be considered after ablation, especially in those high-grade dysplasia and early adenocarcinoma BE patients.

The prevalence of Barrett's esophagus and erosive esophagitis in patients undergoing upper endoscopy for dyspepsia in a VA population.

The purpose of this study was to establish the prevalence of Barrett's esophagus and erosive esophagitis in a group of patients undergoing upper endoscopy for dyspepsia. Computerized endoscopy records were retrospectively evaluated to identify patients who underwent upper endoscopy for dyspepsia. Objective findings were recorded, including the presence of Barrett's esophagus, erosive esophagitis, and peptic ulcer disease. Among 264 patients, Barrett's esophagus was found in 16 (6.1%). The mean length of Barrett's was 2.0 cm, and the majority (81.3%) was short segment. Erosive esophagitis was found in 62 patients (23.%), and peptic ulcer disease was found in 25 patients (9.5%). Approximately 30% of patients undergoing endoscopy for dyspepsia had esophageal lesions. The prevalence of Barrett's in this population was 6%. Based on these results, a trial of acid suppression may benefit a third of patients with dyspepsia. Current screening practices for Barrett's in reflux patients alone may need to be reevaluated.

Risk stratification of Barrett's esophagus: updated prospective multivariate analysis.

OBJECTIVES: Prospective evaluation of Barrett's esophagus (BE) in order to determine what demographic, endoscopic, and histologic features are predictive of the prevalence and incidence of Barrett's high-grade dysplasia (HGD) and adenocarcinoma (Ca). METHODS: Newly diagnosed BE patients were entered into and followed in a standardized surveillance protocol. The following features were examined using either forward, stepwise multiple regression analysis, or Cox proportional hazards to determine their ability to predict the presence of HGD or Ca at index BE diagnosis as well as their ability to predict progression of BE during follow-up: age, race, gender, length of BE in cm, size of a hiatal hernia, severity of dysplasia at index diagnosis as well as during surveillance, gastric Helicobacter pylori infection status, and type of medical acid-reflux treatment. RESULTS: A total of 550 patients were diagnosed with BE over the study period. Stepwise multiple regression analysis showed three factors significantly associated with index diagnosis of HGD or Ca: hiatal hernia (larger size), Barrett's length (longer length), and absence of H. pylori infection. Three hundred and twenty-four BE entered the surveillance protocol. Cox proportional hazards models revealed a significant and independent association for five factors predictive of the time to progression of BE: presence of dysplasia at index diagnosis (p < 0.001), severity of dysplasia during surveillance (p < 0.001), length of Barrett's epithelium (p= 0.012), size of hiatal hernia (p= 0.006), and gastric H. pylori infection status (p= 0.023). CONCLUSIONS: Endoscopic and histologic features of BE at initial diagnosis are predictive of index HGD and cancer as well as with risk of BE progression.

Use of lasers in Barrett's esophagus.

Lasers are used in the management of Barrett's esophagus for specific tasks. First is for the ablation of non-dysplastic and dysplastic Barrett's as part of an aggressive, minimally invasive, yet unproven preventive interventional strategy for both low-risk and high-risk of progression subgroups. Secondly is for potentially curative treatment of early mucosal cancers (Tis and T1mN0M0). Finally, lasers are used for palliation of dysphagia for advanced tumors. The first two laser uses should be considered experimental and undertaken in the setting of an institutionally approved research protocol. Paramount to the success of ablation of dysplastic and early cancerous Barrett's is careful selection of patients by meticulous video endoscopic inspection of the mucosa, use of high frequency and dedicated endosonography (to uncover unsuspected tumors that penetrate the submucosa or involve lymph nodes that cannot be targeted by laser treatment), and experienced GI pathologists. Lasers can also play an important adjuvant role in the management of dysphagia for advanced cancers: however, the specific patients' characteristics for this group of patients is currently not well-defined in this era of easily placed expandable metallic stents.

Metastatic renal cell carcinoma of spleen diagnosed by fine-needle aspiration.

Splenic metastases are infrequent, and determination of the primary site by fine-needle aspiration (FNA) can be complex. We report the case of a 65-year-old man who was found to have a large heterogeneously enhancing 8 x 7-inch splenic mass by abdominal computed tomography (CT). FNA by transesophageal endoscopic ultrasonography demonstrated atypical cells conclusive for malignancy and consistent with metastatic renal cell carcinoma based on cytomorphology, histochemical lipid positivity, and immunohistochemical positivity for cytokeratin, vimentin, and renal cell carcinoma marker. Repeat CT with and without arteriovenous contrast demonstrated bilateral renal cysts, including a 0.9 x 0.8-cm lesion on the left with significant enhancement. Splenectomy confirmed the radiological and cytological findings, and left kidney exploration and nephrectomy demonstrated a small (1.5 cm) lower pole renal cell carcinoma of chromophil (papillary) type, histologically similar to the splenic metastasis. This case demonstrates the diagnostic importance of interdisciplinary involvement (oncology, radiology, gastroenterology, pathology, and general and urologic surgery); cytomorphology; histochemistry, including fat stain on frozen cell block; and immunohistochemistry, including the recently developed renal cell carcinoma marker.

Neodymium:yttrium-aluminum garnet contact laser ablation of Barrett's high grade dysplasia and early adenocarcinoma.

OBJECTIVES: We describe the efficacy and safety of neodymium:yttrium-aluminum garnet (Nd:YAG) contact laser ablation of Barrett's high grade dysplasia (HGD) and/or early adenocarcinoma. METHODS: Consecutive Barrett's patients in whom HGD or adenocarcinoma was detected were eligible. Radial array echoendosonography and high frequency catheter probe ultrasonography were performed. Patients were excluded if ultrasound revealed the presence of Barrett's cancer with regional lymph nodes or celiac trunk metastases or extension of the tumor into superficial submucosa (T1sm1) or greater. Nd:YAG laser used quartz contact probes, with all Barrett's epithelium targeted at each session. Complete ablation was confirmed with Lugol's iodine chromoendoscopy followed by surveillance biopsies of the neosquamous epithelium. Adverse events were ascertained by scheduled telephone contact interviews. RESULTS: A total of 36 patients with HGD/adenocarcinoma were evaluated at our center, 17 of whom met all inclusion criteria. Of the patients, 14 have remained in the study, and all have had successful elimination of HGD and cancer. In addition, 11 patients (78.6%) achieved complete endoscopic and histological ablation of all Barrett's tissue. Two patients (14.3%) achieved 95% destruction of Barrett's with residual metaplastic columnar epithelium containing goblet cells without dysplasia. The remaining patient has obtained 75% ablation of Barrett's, with residual metaplastic columnar epithelium harboring Barrett's with low grade dysplasia. Major complications included two esophageal strictures (11.8%) and one mild upper GI bleed (5.9%). CONCLUSIONS: This preliminary experience with Nd:YAG contact laser for the treatment of Barrett's HGD and early superficial cancers seems promising. The need for additional controlled trials with larger numbers of patients with longer follow-up, as well as consideration of a head-to-head trial with Photofrin photodynamic therapy, is warranted.

Yield of intestinal metaplasia in patients with suspected short-segment Barrett's esophagus (SSBE) on repeat endoscopy.

Biopsies from short segments of columnar appearing mucosa in the distal esophagus often fail to reveal intestinal metaplasia (IM). The yield of IM on repeat upper endoscopy (EGD) and biopsy in these patients is not known. Our aim was to prospectively evaluate the yield of IM on repeat EGD in patients with suspected SSBE (negative for IM on first EGD). Forty-three patients with suspected SSBE underwent repeat EGD with biopsy. This included 42 men and 1 woman, mean age 53 years (range: 45-90) with a mean columnar mucosa length of 1.26 cm (range: 0.5-2.5). On repeat EGD, 10 of 43 patients (23.2%) had evidence of IM. There was no statistically significant difference between the patients with proven SSBE on repeat EGD compared to those with persistent negative IM with regards to age, ethnicity, length of columnar mucosa, GERD symptoms, and hiatal hernia size. In conclusion, more than 20% of patients with suspected SSBE have evidence of IM (ie, proven SSBE) on repeat EGD. Thus repeat EGD with biopsy may be warranted in patients with tongues of columnar mucosa in the distal esophagus but no IM on the first biopsy to confirm the diagnosis of SSBE.