Metaplastic Areas Research Articles

Abstract A076: Somatic deletion of Tert inhibits clonal expansion of pancreatic acinar cell stem cells

Abstract Tert-expressing cells have been identified within the acinar cell compartment of the pancreas in mice. Lineage tracing experiments indicate that these cells can maintain the exocrine compartment during homeostasis and repopulate the tissue during regeneration. Additional expression of mutant Kras in Tert-expressing acinar cells accelerates acinar clone formation and causes transdifferentiation to pre-invasive pancreatic intraepithelial neoplasms after injury. Here, using a genetic approach, we generated mice where tamoxifen injection leads to simultaneous deletion of TERT in Tert-expressing cells and activation of a reporter allele. We performed lineage tracing experiments to investigate the role of TERT in those cells. We studied the effect of acute deletion of TERT during homeostasis, regeneration and tumorigenesis. Acute deletion of TERT significantly inhibited the clone forming capability of Tert-expressing cells during homeostasis in pancreas after one year. To explore the requirement for TERT in an injury setting, we treated mice with cerulein to induce pancreatitis. Somatic inactivagion of TERT in Tert-expressing acinar stem cells impaired clone formation in mice treated with cerulein. To understand if loss of TERT affected transformation, we deleted TERT in acinar stem cells while specifically expressing activated Kras in these cells. Acute deletion of TERT in the presence of a mutant KrasG12D allele decreased the formation of metaplastic areas and PanIN lesions post-injury. These data suggest that a functional allele of Tert is necessary for the clone forming ability of Tert-expressing cells during homeostasis and regeneration as well as acinar to ductal metaplasia and PanIN formation in tumorigenesis. Citation Format: Patrick Neuhöfer, Stewart J. Kim, Gregory W. Charville, Steven E. Artandi. Somatic deletion of Tert inhibits clonal expansion of pancreatic acinar cell stem cells [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A076.

Cellulose Sponge, the Detector of Esophageal Cancer: Innovation for Early Detection of Esophageal Cancer without Biopsy?: A Mini Review

Patients with esophageal cancer each year can reach 400,000 people. Inefficient screening methods and worsening symptoms, patients often come late. Squamous cell carcinoma, which is the cause of esophageal cancer, has percentage of 84% of all cancer incidences. So far, the current screening strategy is endoscopy with biopsy. This screening has the main side effect of bleeding in metaplastic area. Cellulose Sponge, the Detector of Esophageal Cancer (CaSPER), can be used for screening without a biopsy using a cellulose sponge. The method used in this mini review is an evidence-based method that focuses on evaluating pre-existing journals. The result is that CaSPER is able to provide strong cellular results of 98%, specificity of 100%, and sensitivity of 97%. Capsules made of glucose and cytosponge of cellulose will bring the metaplastic cells to the sponge. This screening is feasible, safe, comfortable, and without side effects. Using trefoil factor 3 as biomarker is able to distinguish between goblet and pseudogoblet cells. CaSPER is minimally invasive, cheaper, and easily accepted, so that in the future it is hoped that it can be mass produced, especially for areas with high esophageal cancer.

Masquelet-Induced Membrane Characteristics in Chicken Radii Bone Defects.

This study evaluated the formation of a Masquelet-induced membrane created through the formation of segmental bone defects in the radii of 15 healthy domestic chickens. When the chickens were in a surgical plane of anesthesia, a 1.5-cm segmental bone defect was produced in the left radius, which was subsequently filled with a bone cement spacer during its pasty polymerization phase. The bone defects were evaluated through radiographic imaging immediately after surgery and at 7, 15, 21, and 30 days after the creation of the bone defect. Five birds were euthanatized at 15, 21, and 30 days postoperatively for histological evaluation of the bone defect site. Immediate postoperative radiographic examination of the radii showed the presence of bone cement, which occupied the segmental bone defect. Thirty days after the surgical procedure, the presence of new bone formation at the fractured extremities was evident in the 5 remaining chickens. Histologically, the induced-membrane had 3 distinct zones at 15 days postoperatively, including 1 cell layer in contact with the bone cement spacer, 1 layer with collagen fibers, and 1 layer in contact with muscle, which was composed of disorganized connective tissue, active fibroblasts, and blood vessels. Twenty-one days after surgery, the zones were less defined, and there were metaplastic areas comprising cartilage and bone. Postoperative, diffuse mineralization of the membrane was observed 30 days after the surgical procedure. Formation of the induced membrane was observed during all periods of evaluation. The best histological characteristics for the Masquelet-induced membrane were detected 15 days after the formation of the bone defect, suggesting this would be the optimal time for second-stage surgery for bone reconstruction.

Peroxiredoxin-I Sustains Inflammation During Pancreatitis.

Peroxiredoxin-I Sustains Inflammation During Pancreatitis.

Mucinous Cystadenoma Arising From Renal Pelvis

Primary mucinous cystic tumors occurring in the renal pelvis or the entire pelvicaliceal system are uncommon. Most are mucinous cystadenoma and less frequently mucinous cystadenocarcinomas. In fact, the publications on these neoplasms are limited to a few cases. Because mucinous cystadenomas of kidney are exceedingly rare, little is known about their natural history, pathogenesis and clinicopathologic features. Herein, we describe a case of mucinous cystadenoma arising from the renal pelvis, which resembled hydronephrosis. The patient presented with a history of intermittent dull pain on the left loin for 6 months. He had no history of removing urinary calculus or long- standing chronic infection in urinary system. The histopathology was unique since the inner surface of the cyst was covered by a mucinous epithelium connected to a urothelium, a transition from non- neoplastic urothelium to mucinous epithelium. This suggests that mucinous cystadenoma of renal pelvis, like its malignant counterpart, may arise in foci of metaplastic mucinous areas. Faridpur Med. Coll. J. Jul 2019;14(2): 104-106

Immunohistochemical diagnosis of necrotizing sialometaplasia

The article presents a clinical case of an immunohistochemical study of a rare disease: necrotizing sialometaplasia in the hard palate. Due to the complexity of the differential diagnosis between necrotizing sialometaplasia and squamous cell carcinoma, an immunohistochemical method was used with antibodies to proteins Ki-67, P53, P63 and cytokeratins-7 and Immunohistochemical study established low proliferative activity of glandular cells in excretory ducts and metaplastic squamous epithelium for Ki-67 protein, significant expression of protein P63 was detected both in the ductal epithelium nuclei and in metaplastic areas and expression of the mutant protein P53 was approximately absent. Marked expression of cytokeratin-7 in the ducts cells and weak expression in necrotic acini of the glands and metaplastic epithelium was noted. It was shown that cytokeratin-15 homogeneously stains the peripheral zone of metaplastic epithelium, which is characteristic of a benign lesion. Thus, the panel of antibodies to proteins Ki-67, P53 and cytokeratins-7 and 15 allows to verify necrotizing sialometaplasia.

Clinical associations of mucin 1 in human lung cancer and precancerous lesions.

Mucin 1 (MUC1) is a cell membrane glycoprotein overexpressed in non-small cell lung cancer (NSCLC) and has been implicated in carcinogenesis of premalignant lung lesions. Thus, MUC1 has been a target of interest for vaccine strategies for lung cancer treatment and prevention. Here, we assessed MUC1 expression by immunohistochemistry using tumor samples from patients with biopsy-proven NSCLC. Levels of expression in areas of dysplasia, metaplasia, adenocarcinoma in situ, and carcinoma within the same tissue sample were characterized independently on a scale of 0–3 for paired comparison. We also assessed clinical data for correlations with MUC1 expression. Our analysis included 16 samples from patients with squamous lesions and 19 from patients with adenocarcinoma lesions. Among squamous lesions, MUC1 expression score was significantly increased in dysplastic compared with metaplastic areas (mean difference = 0.83, 95% confidence interval [CI], 0.21-infinity; P = 0.021). MUC1 expression was also increased among areas of squamous cell carcinoma versus dysplastic areas (mean difference = 0.44, 95% CI, −0.006-infinity; P = 0.052). In the adenocarcinoma lesions, MUC1 expression was increased in adenocarcinoma versus adenocarcinoma in situ, although not significantly (mean difference = 0.20, 95% CI, −0.055-infinity; P = 0.094). The increase in MUC1 expression with the progression of premalignant lung lesions to invasive carcinoma in patients with NSCLC supports MUC1 as a possible therapeutic target for the prevention and treatment of lung cancer.

Phenotypical changes in a differentiating immortalized bronchial epithelial cell line after exposure to mainstream cigarette smoke and e-cigarette vapor

3D constructs composed of differentiated immortalized primary normal human bronchial epithelial (NHBE) cells (CL-1548) were repeatedly exposed at the air-liquid interface to non-lethal concentrations of mainstream cigarette smoke (4 cigarettes a day, 5days/week, 8 repetitions in total) and e-cigarette vapor (50 puffs a day, 5 days/week, 8 repetitions in total) to build up a permanent burden on the cells. Samples were taken after 4, 6 and 8 times of repeated smoke exposure and the cultures were investigated using histopathological methods Compared to the clean air-exposed cultures (process control) and incubator control, the aerosol-exposed cultures showed a reduction of ciliated, mucus-producing and club cells. At the end of the exposure phase, we even found metaplastic areas positive for CK13 antibody in the cultures exposed to mainstream cigarette smoke and e-liquid vapor, commonly seen in squamous cells as a marker for non-cornified squamous epithelium. The control cultures (incubator cells) showed no comparable phenotypical changes. In conclusion, our in vitro model presents a valuable tool to study the induction of phenotypical changes after exposure to hazardous airborne material.

Gut Mesenchymal Stromal Cells in Immunity.

Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal). In Crohn's disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC). The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFNγ) is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn's disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer.

Barrett's oesophagus and associated dysplasia are not equally distributed within the esophageal circumference

BackgroundA careful endoscopic surveillance of Barrett's oesophagus is warranted to prevent esophageal cancer. AimTo identify the preferred location of non-circumferential Barrett's oesophagus and associated dysplasia within the esophageal circumference. MethodsWe retrospectively reviewed a prospectively maintained database of patients with non-circumferential lesions. The location of metaplastic lesions and dysplastic lesions within the esophageal circumference was identified as on a clock face, and their distribution in the 4 quadrants was compared. ResultsOf overall 443 patients with Barrett's oesophagus, 192 (43%) were eligible for our study. Multiple lesions were diagnosed in 110 (57%) of them, for a total amount of 352 metaplastic areas. Barrett's oesophagus lesions were located significantly more in the posterior wall of the oesophagus (38.4%), rather than in the right wall (28.8%), the anterior wall (22.6%), or the left wall (10.2%) (P<0.0001). Among all metaplastic lesions, 28 were associated with dysplasia (7.9%), and one with adenocarcinoma (0.3%). Dysplastic lesions were significantly more common in the posterior wall (39.3%) than, respectively, in the anterior wall (35.8%), the right wall (21.4%) or the left wall (3.5%) (P=0.03). ConclusionOur results show that the posterior wall of the oesophagus is the preferential location of both Barrett's oesophagus and associated dysplasia.

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

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

GLUT-1 Expression in Cutaneous Basal and Squamous Cell Carcinomas.

Glucose uptake is a key regulating step in glucose metabolism and is mediated by facilitative glucose transporters (GLUTs), and GLUT-1 is the predominant glucose transporter in many types of human cells. Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent the most common skin cancer in Egypt. The present study aimed at evaluation of the pattern and distribution of GLUT-1 in cutaneous BCC (16 cases) and SCC (16 cases) by means of immunohistochemistry. GLUT-1 was expressed in all SCC (100%) and in 62.5% of BCC. Membranous pattern of GLUT-1 was seen in 62.5% of SCC and 31.25% of BCC. Positivity (P = .02) and percentage (P = .000) of GLUT-1 expression were in favor of SCC in comparison to BCC. The high percentage of GLUT-1 expression was associated with high grade in SCC (P = .03). The immunoreactivity for GLUT-1 was more in the periphery of malignant nests of SCC while it was more in the center of BCC nests. GLUT-1 is overexpressed in cutaneous non-melanoma skin cancer. Its expression in SCC is related to differentiation status, and its expression in BCC is intimately associated with squamous metaplastic areas.

NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar–Ductal Transdifferentiation in the Pancreas

Oncogenic mutations in KRAS contribute to the development of pancreatic ductal adenocarcinoma, but are not sufficient to initiate carcinogenesis. Secondary events, such as inflammation-induced signaling via the epidermal growth factor receptor (EGFR) and expression of theSOX9 gene, are required for tumor formation. Herein we sought to identify the mechanisms that link EGFR signaling withactivation of SOX9 during acinar-ductal metaplasia, a transdifferentiation process that precedes pancreatic carcinogenesis. We analyzed pancreatic tissues from Kras(G12D);pdx1-Cre and Kras(G12D);NFATc1(Δ/Δ);pdx1-Cre mice after intraperitoneal administration of caerulein, vs cyclosporin A or dimethyl sulfoxide (controls). Induction of EGFR signaling and its effects on the expression of Nuclear factor of activated T cells c1 (NFATc1) or SOX9 were investigated by quantitative reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemical analyses of mouse and human tissues and acinar cell explants. Interactions between NFATc1 and partner proteins and effects on DNA binding or chromatin modifications were studied using co-immunoprecipitation and chromatin immunoprecipitation assays in acinar cell explants and mouse tissue. EGFR activation induced expression of NFATc1 in metaplastic areas from patients with chronic pancreatitis and in pancreatic tissue from Kras(G12D) mice. EGFR signaling also promoted formation of a complex between NFATc1 andC-JUN in dedifferentiating mouse acinar cells, leading toactivation of Sox9 transcription and induction of acinar-ductal metaplasia. Pharmacologic inhibition of NFATc1 or disruption of the Nfatc1 gene inhibited EGFR-mediated induction of Sox9 transcription and blocked acinar-ductal transdifferentiation and pancreatic cancer initiation in mice. EGFR signaling induces expression of NFATc1 and Sox9, leading to acinar cell transdifferentiation and initiation of pancreatic cancer. Strategies designed to disrupt this pathway might be developed to prevent pancreatic cancer initiation in high-risk patients with chronic pancreatitis.

Reactivation of CDX2 in Gastric Cancer as Mark for Gene Silencing Memory.

To explore the epigenetic mechanism that reactivates CDX2 (a homeobox transcription factor that serves as a tumor-suppressor gene) in intestinal-type gastric cancer during cancer progression, we examined the methylation status of the CDX2 gene promoter and the expression pattern of methyl-CpG binding protein-2 (MeCP2). From archives of the pathology records of surgically excised advanced stomach cancer cases in the Department of Molecular Pathology, Ehime University in a past decate (n=265), 10 cases of intestinal-type tubular adenocarcinoma, well-differentiated type (wel) with minor poorly-differentiated adenocarcinoma (por) components were selected. The expression pattern of CDX2, MUC2 and MeCP2 in these 10 cases was analyzed by immunohistochemistry. The cancerous and non-cancerous areas were selectively obtained by microdissection, and the methylation status of the CDX2 promoter of each area was assessed by methylation-specific polymerase chain reaction (MSP). In all 10 cases, CDX2 expression was clearly observed in the nucleus of the non-cancerous background of the intestinal metaplasic area, where the unmethylation pattern of the CDX2 gene promoter prevailed with reduced MeCP2 expression. In this metaplastic area, CDX2 expression was co-localized with its target gene, MUC2. CDX2 expression then disappeared from the deep invasive wel area. Reflecting the reduced CDX2 expression, microdissected samples from all the wel areas showed hypermethylation of the CDX2 gene promoter by MSP, with prominent MeCP2 expression. Interestingly, while hypermethylation of the CDX2 gene promoter was maintained in the por area in 8 of the 10 cases, CDX2 expression was restored in por areas where MeCP2 expression was markedly and selectively reduced. The other two cases, however, showed a constant MeCP2 expression level comparable to the surrounding deep invasive wel area with negative CDX2 expression. Therefore, gene silencing by hypermethylation may be overcome by the reduction of methyl-CpG binding proteins, resulting in apparent but non-functional reactivation of CDX2 as a mere molecular mark for gene silencing memory.

Regeneration from acute pancreatitis requires transcriptional silencing of NFATc1

Introduction: Tissue injury initiates a complex regenerative programme ensuring complete restoration of organ structure and function. Understanding the molecular key events in mediation and regeneration from pancreas injury is critical to develop novel therapeutic strategies. Recent evidence suggests important roles for developmental and inflammatory transcription factors in several steps of the regeneration process. Aims: To analyze whether and how the inflammatory transcription factor NFATc1 is involved in the course of acute pancreatitis. Methods: Caerulein and L-Arginin were used to induce acute pancreatitis in different pancreas specific transgenic mice models with differential expression of NFATc1. Mice were sacrificed at different time points after induction of acute pancreatitis to isolate pancreata for further analysis. Gene expression in mice tissue and acinar cell explants were determined by using RT-PCR, immunoblotting, immunofluorescence and immunohistochemical stainings. Local histone modifications on the NFATc1 promoter were investigated by ChIP analysis. Results: Caerulein mediated acute pancreatitis initiates acinar to ductal metaplasia, which goes along with activation of NFATc1 in metaplastic areas of the pancreas. Regeneration of the pancreas requires inactivation of NFATc1 by H3K27 trimethylation mediated by the Polycomb protein EZH2. While pharmacological or genetic inactivation of NFATc1 in mice accelerates pancreas regeneration, sustained activation of NFATc1 overcomes transcriptional silencing and fully prevents restoration of the organ. Conclusion: Our results provide evidence, that transcriptional silencing of NFATc1 by EZH2 is an inevitable prerequisite for sufficient regeneration from acute pancreatitis.

Dendritic Cells in Barrett's Esophagus Carcinogenesis: An Inadequate Microenvironment for Antitumor Immunity?

Barrett's esophagus corresponds to the replacement of the normal esophageal squamous epithelium by a columnar epithelium through a metaplastic process. This tissue remodeling is associated with chronic gastroesophageal reflux and constitutes a premalignant lesion leading to a 30- to 60-fold increase in the risk to evolve into esophageal adenocarcinoma. The present study aimed to investigate a possible immune evasion in Barrett's esophagus favoring esophageal adenocarcinoma development. We demonstrated that myeloid and plasmacytoid dendritic cells are recruited during the esophageal metaplasia-dysplasia-carcinoma sequence, through the action of their chemoattractants, macrophage inflammatory protein 3α and chemerin. Next, we showed that, in contrast to plasmacytoid dendritic cells, myeloid dendritic cells, co-cultured with Barrett's esophagus and esophageal adenocarcinoma cell lines, display a tolerogenic phenotype. Accordingly, myeloid dendritic cells co-cultured with esophageal adenocarcinoma cell lines stimulated regulatory T cell differentiation from naïve CD4(+) T cells. In agreement with those results, we observed that both metaplastic areas and (pre)malignant lesions of the esophagus are infiltrated by regulatory T cells. In conclusion, soluble factors secreted by epithelial cells during the esophageal metaplasia-dysplasia-carcinoma sequence influence dendritic cell distribution and promote tumor progression by rendering them tolerogenic.

Evaluation of the oncogenic risk of diffuse gastric polyposis: A case report

Benign polyps of the stomach undergo malignant transformation at a rate correlating to the histological type and size of the proliferative lesion. We report a case of a 50-year-old Caucasian woman, affected by a diffuse gastric polyposis of both hyperplastic and adenomatous type. At endoscopy polyps were more than 1,000, scattered over the entire gastric cavity. The patient underwent total gastrectomy. The perilesional gastric mucosa was characterized by the presence of either atrophic or metaplastic areas and by a mild dysplasia. A single tubulo-villous adenomatous polyp was also present in the ascending tract of the colon. The absence of both high-grade dysplastic lesions and outbreaks of neoplastic transformation well correlated with the histochemical and molecular features, confirming the highly proliferative pattern of the polyps in the lack of signs of malignant progression.

Tumor amorfo calcificado do coração

Calcified amorphous tumor of the heart consists of a cardiac mass of rare nonneoplastic nature that mimics malignancy and causes symptoms due to obstruction or embolization of calcific fragments. We present a case of tumor 17-year-old young, male, in tricuspid valve, with classic pathological findings. It was preferred to approach for classic median esternotomy, installation of the circuit of extracorporal circulation and right atriotomy, exereses of tumor, DeVega's plasty in tricuspid valve and bicuspidization. The amatomopathological study demonstrated presence of extensive calcification and metaplastic bone areas. The patient had an uneventful hospitalization.

L’hyperplasie complexe atypique (HCA) de l’endomètre avec métaplasie malpighienne (MM) extensive. À propos de deux observations

We report two cases of endometrial atypical complex hyperplasia with an extensive squamous hyperplasia occurring in two women aged 48 and 31 years old. The histological study showed an increase in the gland to stroma ratio with a false crowding aspect due to an extensive area of squamous metaplasia; some metaplastic areas were centered by necrosis. There was glandular cytologic atypia. Histologic examination is necessary to confirm the diagnosis and to definitively rule out adenocarcinoma.

A New Method for Barrett's Mucosal Excision

Background: Endoscopic mucosal resection (EMR) is a commonly used therapeutic procedure for Barrett's esophagus. We have developed a new technique for EMR that utilizes a cold blade. The absence of cautery allows an exact and accurate histological analysis of the resection margins. Methods: The mucosal resection technique used was based on a new flexible device (SafeStitch Medical Inc.). The instrument consists of a flexible tube with an integrated distal excision capsule. A standard small calibre transnasal endoscope is introduced into the device for visual orientation. The excision capsule is 5 cm long and is rigid. The resection window is 2.8 cm long, 1.3 cm wide and 0.4 cm deep. A guillotine blade resects the mucosa. After visual endoscopic identification of the metaplastic area, two suction channels pull the mucosa into the capsule and vertical anchor needles help fix the tissue position. To assure the correct cutting depth and under endoscopic surveillance we inject a 1:200,000 Adrenaline solution using a longitudinal injection needle placed above the bottom of the trough. The injectate further separates the muscularis mucosa from the muscularis propria thus increasing the “target space”. Mucosal excision is performed with a single proximal-to-distal pushing movement of the blade. After the mucosectomy is complete, the device is removed from the esophagus with the specimen remaining within the capsule. The specimen can be easily orientated for the pathologist and sent for histological analysis. Using fresh ex-vivo non-fixed human esophagi, the device was studied for completeness of mucosal resection, uniformity of depth, and safety characteristics of the procedure. Excised mucosal strips were fixed in 5% formalin, incorporated in paraffin blocks and stained with haematoxylin-eosin. The excision depth was microscopically determined in 5 mm incremental areas throughout the specimen. Results: A total of 10 excisions were performed on ex-vivo fresh cadaveric human esophagi. The specimens ranged in size from 3 × 2.5 cm to 2.5 × 2.2 cm. Three areas in 150 areas of microscopic examination did not include the muscularis mucosa. In some excisions deep submucosal gland units were included. The average depth of submucosa excision was .297 mm. Conclusion/Expectations: This new device demonstrated reliability and reproducibility of satisfactory excision depth for use in mucosal resection for Barrett's esophagus. Further preclinical study is underway to refine the device for clinical application and study.