Barrett's Mucosa Research Articles

Efficacy and safety of liquid nitrogen cryotherapy for treatment of Barrett's esophagus.

AIMTo evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE, with and without dysplasia, or intramucosal adenocarcinoma (IMC).METHODSThis was a retrospective, single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-naïve or who had persistent intestinal metaplasia (IM), dysplasia, or IMC despite prior therapy. Barrett’s mucosa was resected via EMR when clinically appropriate, then patients underwent cryotherapy until eradication or until deemed to have failed treatment. Surveillance biopsies were taken at standard intervals.RESULTSFrom 2010 through 2014, 33 patients were studied regarding the efficacy of cryotherapy. Overall, 29 patients (88%) responded to cryotherapy, with 84% having complete regression of all dysplasia and cancer. Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy. Following cryotherapy, 15 patients with high-grade dysplasia (HGD) had 30% complete regression, 50% IM, and 7% low-grade dysplasia (LGD); one subject had persistent HGD. Complete eradication of dysplasia occurred in all 5 patients with LGD. In 5 patients with IM, complete regression occurred in 4, and IM persisted in one. In 136 cryotherapy sessions amongst 45 patients, adverse events included chest pain (1%), stricture (4%), and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR.CONCLUSIONCryotherapy is an efficacious and safe treatment modality for Barrett’s esophagus with and without dysplasia or intramucosal adenocarcinoma.

Long term follow-up of non-goblet cell and goblet cell columnar lined lower end esophagus

Background: Significance of non goblet (GC) columnar mucosa (CM) present at lower end esophagus (LEE) remains controversial, and there is limited information of the follow-up data. Aim: to evaluate outcome of Barrett's mucosa (BM) and NGCM in long term follow-up biopsies. Methods: retrospectively evaluated biopsies reported as columnar mucosa (CM) with and without GC and correlated with clinical outcome. Results: There were 178 patients, mean age of 52.1±15.6, 7

TGR5 expression in benign, preneoplastic and neoplastic lesions of Barrett's esophagus: Case series and findings.

AIMTo examined the bile acid receptor TGR5 expression in squamous mucosa, Barrett’s mucosa, dysplasia and esophageal adenocarcinoma (EA).METHODSSlides were stained with TGR5 antibody. The staining intensity was scored as 1+, 2+ and 3+. The extent of staining (percentage of cells staining) was scored as follows: 1+, 1%-10%, 2+, 11%-50%, 3+, 51%-100%. A combined score of intensity and extent was calculated and categorized as negative, weak, moderate and strong staining. TGR5 mRNA was measured by real time PCR.RESULTSWe found that levels of TGR5 mRNA were significantly increased in Barrett’s dysplastic cell line CP-D and EA cell line SK-GT-4, when compared with Barrett’s cell line CP-A. Moderate to strong TGR5 staining was significantly higher in high-grade dysplasia and EA cases than in Barrett’s esophagus (BE) or in low-grade dysplasia. Moderate to strong staining was slightly higher in low-grade dysplasia than in BE mucosa, but there is no statistical significance. TGR5 staining had no significant difference between high-grade dysplasia and EA. In addition, TGR5 staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis.CONCLUSIONWe conclude that TGR5 immunostaining was much stronger in high-grade dysplasia and EA than in BE mucosa or low-grade dysplasia and that its staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis. TGR5 might be a potential marker for the progression from BE to high-grade dysplasia and EA.

Expression profiles of cancer stem cell markers: CD133, CD44, Musashi-1 and EpCAM in the cardiac mucosa—Barrett’s esophagus—early esophageal adenocarcinoma—advanced esophageal adenocarcinoma sequence

IntroductionBarrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE − EAC sequence are not fully elucidated yet. AimsWe used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression. MethodsImmunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies. ResultsAll markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett’s epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett’s metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS). ConclusionOur results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa.

Silencer-of-Death Domain Mediates Acid-Induced Decrease in Cell Apoptosis in Barrett's Associated Esophageal Adenocarcinoma Cells.

We have shown that NADPH oxidase (NOX)5-S may mediate the acid-induced decrease in cell apoptosis. However, mechanisms of NOX5-S-dependent decrease in cell apoptosis are not fully understood. In this study, we found that silencer-of-death domain (SODD) was significantly increased in esophageal adenocarcinoma (EA) tissues, EA cell lines FLO and OE33, and a dysplastic cell line CP-B. Strong SODD immunostaining was significantly higher in low-grade dysplasia (66.7%), high-grade dysplasia (81.2%), and EA (71.2%) than in Barrett's mucosa (10.5%). Acid treatment significantly increased SODD protein and mRNA expression and promoter activity in FLO cells, an increase that was significantly decreased by the knockdown of NOX5-S and nuclear factor κB (NF-κB)1 p50 with their small interfering RNAs. Similarly, acid-induced increase of SODD mRNA was blocked by knockdown of NOX5-S and p50 in a BE cell line CP-A. Overexpression of NOX5-S significantly increased SODD protein expression in FLO cells. Moreover, overexpression of NOX5-S or p50 significantly increased the SODD promoter activity and decreased the caspase 9 activity or apoptosis. NOX5-S overexpression-induced increase in SODD promoter activity was significantly decreased by knockdown of p50. In addition, acid treatment significantly decreased the caspase 9 activity, a decrease that was significantly inhibited by knockdown of SODD. Furthermore, chromatin immunoprecipitation assay showed that NF-κB1 p50 bound to SODD genomic DNA containing a NF-κB-binding element GGGGACACCCT. This binding element was further confirmed by a gel mobility shift assay. We conclude that acid-induced increase in SODD expression and decrease in cell apoptosis may depend on the activation of NOX5-S and NF-κB1 p50 in FLO cells.

Association of medications for lifestyle-related diseases with reflux esophagitis

BackgroundBecause of a change in lifestyle, especially adoption of westernized eating habits, lifestyle-related diseases have become increasingly prevalent. The aim of this study was to investigate the association of medications for lifestyle-related diseases with reflux esophagitis (RE).MethodsWe conducted a hospital-based, cross-sectional retrospective study of consecutive outpatients who received an upper gastrointestinal endoscopy in our department from February 2008 to November 2014, which was performed by one specialist who was a member of the Japan Gastroenterological Endoscopy Society. We investigated the patient profile, Helicobacter pylori (H. pylori) infection status, medications for lifestyle-related diseases (including calcium channel blockers, statins, and bisphosphonates), and upper gastrointestinal endoscopic findings (RE, hiatal hernia, Barrett’s mucosa, and endoscopic gastric mucosal atrophy [EGA]). Patients with gastrectomy, peptic ulcer disease, gastric or esophageal malignant disease, and those who used proton pump inhibitors or histamine-2 receptor antagonists were excluded. We divided the subjects into a group without RE (RE(−)) and a RE (RE(+)) group as judged by endoscopy, and investigated the risk factors for RE.ResultsOf 1,744 consecutive cases, 590 cases (300 males and 290 females; mean age 60.5±13.2 years) were eligible. RE(−) and RE(+) cases numbered 507 and 83, respectively. Bivariate analysis showed significant positive associations of RE with male sex, body mass index (BMI), calcium channel blockers, Barrett’s mucosa, hiatal hernia and negative associations of RE with H. pylori positivity, EGA. Multivariate analysis showed significant positive associations of RE with BMI (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.10–1.29), use of calcium channel blockers (OR: 2.12, 95% CI: 1.16–3.87), Barrett’s mucosa (OR: 2.97, 95% CI: 01.64–5.38), hiatal hernia (OR: 3.13, 95% CI: 1.79–5.47) and negative associations of RE with H. pylori positivity (OR: 0.20, 95% CI: 0.07–0.57), use of statins (OR: 0.42, 95% CI: 0.18–0.96), and EGA (OR: 0.83, 95% CI: 0.70–0.98).ConclusionCalcium channel blockers were positively associated with RE and statins were negatively associated with RE, while bisphosphonates were not associated with RE.

Radiofrequency ablation for low-grade dysplasia in Barrett's esophagus.

The diagnosis and management of low-grade dysplasia (LGD) in Barrett's esophagus continue to evolve and vary in practice. Radiofrequency ablation (RFA) is now an acceptable option for the treatment of LGD. Therefore, the purpose of this review article is to present current literature on the diagnosis and management of LGD, and to explore when to optimally pursue RFA for the treatment of LGD. The challenge of the management of LGD begins with its diagnosis. Because of high interobserver variability among pathologists in the diagnosis of dysplasia, it is recommended that an expert gastrointestinal pathologist confirms the diagnosis of LGD. Endoscopic mucosal resection is indicated to remove visible lesions in the setting of dysplasia to obtain an accurate diagnosis, especially regarding T staging. Management options include intense surveillance and endoscopic eradication therapy. RFA provides a reasonable method to eradicate flat Barrett's mucosa. Endoscopic eradication of confirmed LGD has been demonstrated to reduce the risk of progression to esophageal cancer. Additional data about the risk factors associated with progression, and the benefits and risks of treatment are discussed, and can be incorporated in patient counseling and decision making. Endoscopic eradication therapy with RFA may be an appropriate treatment option for LGD in Barrett's esophagus after the benefits and risks have been discussed in detail with the patient.

Dysregulation of WNT5A/ROR2 Signaling Characterizes the Progression of Barrett-Associated Esophageal Adenocarcinoma.

The mechanism underlying the progression of normal esophageal mucosa to esophageal adenocarcinoma remains elusive. WNT5A is a noncanonical WNT, which mainly functions via the receptor tyrosine kinase-like orphan receptor 2 (ROR2), and has an unclear role in carcinogenesis. In this study, we aimed to determine the role of WNT5A/ROR2 signaling in esophageal adenocarcinoma. Analysis of WNT5A and ROR2 expression patterns in healthy controls, Barrett and esophageal adenocarcinoma patients' esophageal clinical specimens as well as in various esophageal cell lines demonstrated a ROR2 overexpression in esophageal adenocarcinoma tissues compared with Barrett and healthy mucosa, whereas WNT5A expression was found significantly downregulated toward esophageal adenocarcinoma formation. Treatment of esophageal adenocarcinoma OE33 cells with human recombinant WNT5A (rhWNT5A) significantly suppressed proliferation, survival, and migration in a dose-dependent fashion. rhWNT5A was found to inhibit TOPflash activity in ROR2 wild-type cells, whereas increased TOPflash activity in ROR2-knockdown OE33 cells. In addition, ROR2 knockdown alone abolished cell proliferation and weakened the migration properties of OE33 cells. These findings support an early dysregulation of the noncanonical WNT5A/ROR2 pathway in the pathogenesis of esophageal adenocarcinoma, with the loss of WNT5A expression together with the ROR2 overexpression to be consistent with tumor promotion. The dysregulation of WNT5A/ROR2 noncanonical WNT signaling in Barrett-associated esophageal adenocarcinoma introduces possible prognostic markers and novel targets for tailored therapy of this malignancy. Mol Cancer Res; 14(7); 647-59. ©2016 AACR.

Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma

BackgroundToll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma.MethodsTLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99).ResultsWe found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis.ConclusionsTLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma.

Feasibility of optical coherence tomography for the evaluation of Barrett's mucosa buried underneath esophageal squamous epithelium.

The evaluation of Barrett's glands buried underneath esophageal squamous epithelium becomes increasingly important to achieve curative treatments. However, clinically available endoscopies have critical limitations in depicting the subsurface structure, resulting in non-curative treatments. Optical coherence tomography (OCT) can acquire a high-resolution cross-sectional image, equivalent to an 'optical biopsy'. We aimed to assess the feasibility of the in vivo use of probe-type OCT imaging to evaluate Barrett's mucosa buried underneath esophageal squamous epithelium METHODS: We conducted a single-center prospective study with 14 consecutive patients with Barrett's adenocarcinoma from 2008 to 2014. The enrolled patients were examined by a probe-type OCT in vivo, followed by en bloc endoscopic submucosal dissection (ESD) with electric marking. Then, the one-to-one correlations between the OCT images of the buried mucosa and their histological assessment were examined. The overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the buried mucosa in the OCT imaging were 85.7% (12/14), 77.8% (7/9), 100% (5/5), 100% (7/7) and 71.4% (5/7), respectively. However, OCT could not easily distinguish non-dysplastic glands from dysplastic glands. Additionally, the linear distance from the histological squamo-columnar junction in correct cases tended to be longer than that in incorrect cases (mm, median [range]: 2.0 [0.7-7.5] vs. 0.5 [0.5-0.5]). We demonstrated, for the first time, that pre-operative OCT imaging might be feasible for detecting the oral side extension of buried Barrett's mucosa to remove the entire area with malignant potential by ESD. This article is protected by copyright. All rights reserved.

Barrett′s mucosa segmentation in endoscopic images using a hybrid method: Spatial fuzzy c-mean and level set

Barrett's mucosa is one of the most important diseases in upper gastrointestinal system that caused by gastro-esophagus reflux. If left untreated, the disease will cause distal esophagus and gastric cardia adenocarcinoma. The malignancy risk is very high in short segment Barrett's mucosa. Therefore, lesion area segmentation can improve specialist decision for treatment. In this paper, we proposed a combined fuzzy method with active models for Barrett's mucosa segmentation. In this study, we applied three methods for special area segmentation and determination. For whole disease area segmentation, we applied the hybrid fuzzy based level set method (LSM). Morphological algorithms were used for gastroesophageal junction determination, and we discriminated Barrett's mucosa from break by applying Chan-Vase method. Fuzzy c-mean and LSMs fail to segment this type of medical image due to weak boundaries. In contrast, the full automatic hybrid method with correlation approach that has used in this paper segmented the metaplasia area in the endoscopy image with desirable accuracy. The presented approach omits the manually desired cluster selection step that needed the operator manipulation. Obtained results convinced us that this approach is suitable for esophagus metaplasia segmentation.

Post-ablation surveillance in Barrett's esophagus: A review of the literature.

Barrett's esophagus (BE) is a pre-malignant condition affecting up to 15% of patients with gastroesophageal reflux disease. Neoplastic Barrett's mucosa is defined as harboring high grade dysplasia or intra-mucosal cancer, and carries a high risk of progression to esophageal adenocarcinoma. The rising incidence of Barrett's lesions along with the high morbidity of surgical approaches has led to the development of numerous validated endoscopic techniques capable of eradicating neoplastic mucosa in a minimally invasive manner. While there has been widespread adoption of these techniques, less is known about optimal surveillance intervals in the post-therapy period. This is due in part to limitations in current surveillance methods, questions about durability of treatment response and the risk of subendothelial progression. As we are now able to achieve organ sparing eradication of superficial neoplasia in BE, we need to also then focus our attention on how best to manage these patients after eradication is achieved. Implementing optimal surveillance practices requires additional understanding of the biology of the disease, appreciation of the limits of current tools and treatments, and exploration of the role of adjunctive technologies. The aim of this article is to provide a comprehensive review of current literature surrounding post-ablation surveillance in neoplastic BE.

Endoscopic Treatment of Early Barrett's Neoplasia: Expanding Indications, New Challenges.

Endoscopic therapy of early Barrett's neoplasia is nowadays the treatment of choice and recommended over surgery in most current guidelines. Recent data suggest radiofrequency ablation of low-grade intraepithelial neoplasia when confirmed by an expert pathologist. Endoscopic therapy of high-grade intraepithelial neoplasia and mucosal Barrett's adenocarcinoma consists of two steps: first endoscopic resection of all visible lesions, and second ablation of the remaining flat Barrett's mucosa to reduce the rate of recurrences and metachronous neoplasia. The preferred ablation method is radiofrequency ablation. In case of Barrett's adenocarcinoma with incipient submucosal invasion, endoscopic treatment can be considered curative when there are no further risk factors present.

Dynamics of SOX2 and CDX2 Expression in Barrett's Mucosa.

Barrett's esophagus (BE) is the replacement of the normal esophageal squamous epithelium by a columnar lining epithelium. It is a premalignant condition for the development of adenocarcinoma of the esophagus and esophagogastric junction. BE is associated with gastroesophageal reflux which might change the expression profile of key transcription factors involved in the establishment of tissue differentiation, namely, SOX2 (associated with esophageal and gastric differentiation) and CDX2 (associated with intestinal differentiation). Here, we sought to characterize the expression profile of SOX2 and CDX2 in the sequential alterations of the esophageal mucosa towards adenocarcinoma and compare it with the well-established gastric and intestinal mucin profiles (MUC5AC, MUC6, and MUC2). We observed that SOX2 and CDX2 expression correlates with gastric and intestinal differentiation in BE, defined by morphological parameters and mucin expression. We show the presence of a complete intestinal profile in BE, without gastric mucins and without SOX2, and we observed an evolutionary modulation of the metaplastic phenotype by SOX2 and CDX2. We observed that adenocarcinomas harbor more frequently a mixed gastric and intestinal phenotype. In conclusion, our study establishes a role for transcription factors SOX2 and CDX2 in the progression from gastric to gastrointestinal differentiation in Barrett's metaplasia.

Acetic acid chromoendoscopy: Improving neoplasia detection in Barrett's esophagus.

Barrett's esophagus (BE) is an important condition given its significant premalignant potential and dismal five-year survival outcomes of advanced esophageal adenocarcinoma. It is therefore suggested that patients with a diagnosis of BE undergo regular surveillance in order to pick up dysplasia at an earlier stage to improve survival. Current "gold-standard" surveillance protocols suggest targeted biopsy of visible lesions followed by four quadrant random biopsies every 2 cm. However, this method of Barrett's surveillance is fraught with poor endoscopist compliance as the procedures are time consuming and poorly tolerated by patients. There are also significant miss-rates with this technique for the detection of neoplasia as only 13% of early neoplastic lesions appear as visible nodules. Despite improvements in endoscope resolution these problems persist. Chromoendoscopy is an extremely useful adjunct to enhance mucosal visualization and characterization of Barrett's mucosa. Acetic acid chromoendoscopy (AAC) is a simple, non-proprietary technique that can significantly improve neoplasia detection rates. This topic highlight summarizes the current evidence base behind AAC for the detection of neoplasia in BE and provides an insight into the direction of travel for further research in this area.

Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus

ObjectiveBarrett's oesophagus commonly presents as a patchwork of columnar metaplasia with and without goblet cells in the distal oesophagus. The presence of metaplastic columnar epithelium with goblet cells on oesophageal...

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Both low-grade dysplasia (LGD) and high-grade dysplasia (HGD) are associated with an increased risk of progression to EAC. However, histological interpretation and grading of dysplasia (particularly LGD) is subjective and poorly reproducible. This study has combined whole slide imaging with DNA image cytometry to provide a novel method for the detection of abnormal DNA content through image analysis of tissue sections. A total of 20 cases were evaluated, including 8 negative for dysplasia (NFD), 6 LGD, and 6 HGD. Feulgen-stained esophageal sections were scanned in their entirety. Barrett's mucosa was interactively chosen for automatic nuclei segmentation where irrelevant cell types were ignored. The combined DNA content histogram for all nuclei within selected image regions was then obtained. In addition, three histogram measurements were computed, including xER-5C, 2cDI, and DNA-MG. Visual evaluation suggested the shape of DNA content histograms from NFD, LGD, and HGD cases exhibiting identifiable differences. The histogram measurements, xER-5C, 2cDI, and DNA-MG, were shown to be effective in differentiating metaplastic from dysplastic cases with statistical significance. Moreover, they also successfully separated NFD, LGD, and HGD patients with statistical significance. Whole slide image cytometry is a novel and effective method for the detection of abnormal DNA content in BE. Compared with histological review, it is more objective. Compared with flow cytometry and cytology-preparation image cytometry, it is low cost, simple to use, only requires a single 1 μm section, and facilitates selection of tissue and topographical correlation. Whole slide image cytometry can detect differences in DNA content between NFD, LGD, and HGD patients in this cross-sectional study. Abnormal DNA content detection by whole slide image cytometry is a promising biomarker of progression that could affect future diagnostics in BE.

Peri-esophageal Pseudoaneurysms: Unique Cause of Refractory Arterial Bleeding Treated With Novel Technique

A 43 year old female with SLE and dysplastic Barrett's esophagus (Prague class C8 M9) treated with radiofrequency ablation presented with hematemesis. An EGD showed esophageal ulcers without any active bleeding. After 2 days of conservative treatment, the patient had an episode of hematochezia and syncope. Colonoscopy showed fresh blood throughout the colon as well as terminal ileum without any source. EGD showed a large esophageal ulcer with active bleeding. Endoscopic clips did not stop the bleeding. A Sengstaken Blakemore tube was placed. Patient was taken to Interventional radiology suite where brisk active bleeding into the distal esophagus from esophageal branches of the left gastric artery was seen. The arteriogram showed saccular dilation/pseudo-aneurysms that were the source of bleeding (arrow, Figure 1). Gel-foam embolization of the left gastric and esophageal branches, coil embolization of the gastrohepatic trunk and particle embolization of the pseudo-aneurysms stopped the bleeding. Esophageal brushings showed active cytomegalovirus infection along with low complement levels consistent with active vasculitis from SLE and mixed connective tissue disease. The patient eventually underwent exploratory laparotomy with resection of a necrotic esophago-gastric junction as well as thoracic esophagectomy. Pathological evaluation showed submucosal hemorrhage, esophagitis with dysplastic Barrett's mucosa and an ulcer containing cytomegaloviral inclusions. It is probable that the ulcer from cytomegalovirus eroded into the pseudo-aneurysm formed by the persistent SLE mediated vasculitis and lead to the refractory bleeding.Figure 1We report the first case of arterial bleeding from peri-esophageal pseudo-aneurysms present in the aortoesophageal branches in the left gastric arcade. We also report the use of gel-foam and particle embolization for arterial bleeding in the esophagus.

Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett's esophageal adenocarcinoma.

For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett’s esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a “real time” and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett’s esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment.

Significance of i-Scan in the diagnosis of Barrett's esophagus

Objective To evaluate the value of i-Scan in the diagnosis of Barrett's esophagus. Methods 52 patients diagnosed with Barrett's esophagus by gastroscopies and pathological examinations were observed under the ordinary edoscopy and i-Scan respectively.Besides,the Barrett's esophageal mucosa were classified by Endo with i -scan mode, the target lesions was taken to be biopsied and pathologically examined. Results (1)In the 52 patients,mucosal lesions were found in 46 cases(88.5%) under i-Scan and 35 cases(67.3%) under ordinary edoscopy respectively,mucosal lesion detection rate in i-Scan was significantly higher than normal white mode(P< 0.01).In the 33 patients which found mucosal lesions in the two modes,the definition of lesion margins,morphology of lesion cryptaeand mucosa capillaries revealed by i-Scan were superior to that by white lighted endoscopy(P< 0.05);(2)Under i-scan mode,the detection of specific intestinal metaplasia(SIM) of typeⅣ,type V in sensitivity, accuracy,specificity were respectively 90.0%,93.5%,94.4%. Conclusion i-Scan is very easy to operate and has a clear lesion of Barrett's esophagus,which helps to target the lesion at pathological biopsy. Key words: Gastroscopy; Barrett Esophagus; Coloring Agents; Diagnosis