Esophagectomy Specimens Research Articles

Characterization of esophageal inflammation in patients with achalasia. A retrospective immunohistochemical study

Summary Autoimmunologic phenomena triggered by CD8-positive cytotoxic T cells may be involved in the pathogenesis of achalasia, but the pathogenic mechanisms generally remain unknown, and the concomitant histopathologic changes in the esophageal epithelium in achalasia are incompletely described. This study was designed to characterize the inflammation within the esophageal epithelium of these patients. We collected 72 esophageal specimens from 38 consecutive patients with achalasia (16 men, 22 women) representing different disease stages. The inflammatory cells were characterized immunohistochemically. Seven end-stage disease esophagectomy specimens were also included. Our data show a T-cell–rich inflammatory response predominantly composed of CD4-positive T cells with an overall CD4/CD8 ratio of 1.82 and only few CD4-CD25-FoxP3–positive regulatory T cells or CD20-positive B cells. Signs of inflammation were most pronounced in the middle esophagus, followed by upper and lower esophagus. Between different stages of disease, there were statistically significant differences among CD25-positive lymphocytes in the upper esophagus and CD4-, CD8-, and CD25-positive lymphocytes in the middle esophagus. The esophageal epithelial inflammation in achalasia seems to be of reactive and unspecific nature and does not reflect the composition of the CD8-dominant inflammatory infiltrate within the muscular esophageal wall in active disease. The statistically significant differences in unspecific inflammation between different stages of disease are more likely due to effects of the dysmotility and cannot be assumed pathognomic for the disease. In conclusion, we assume that it is not possible to diagnose or confirm achalasia by means of esophageal biopsy alone.

Fat clearance of upper gastrointestinal resection specimens increases lymph node yield and may result in nodal upstaging

IntroductionLymph node retrieval and quantification is an important element in staging upper gastrointestinal cancers. Our department introduced fat clearance for oesophagectomy and gastrectomy specimens in 2014. This study assessed the...

Acidic Bile Salts Induce Epithelial to Mesenchymal Transition via VEGF Signaling in Non-Neoplastic Barrett’s Cells

Metaplastic glands buried under squamous epithelium are frequently detected in patients with Barrett esophagus (BE). This subsquamous intestinal metaplasia might be responsible for cancers that develop despite endoscopic surveillance and for metaplasia recurrences after endoscopic ablation. To determine whether reflux induces BE cells to undergo an epithelial-to-mesenchymal transition (EMT) that produces subsquamous intestinal metaplasia, we assessed EMT in BE cells exposed to acidic bile salts and in rat and human esophageal tissues. We compared markers of EMT and cell motility in trans-well and 3-dimensional organotypic culture systems among dysplastic BE epithelial cell lines, nondysplastic telomerase-immortalized BE cell lines (BAR-T), and BAR-T cells exposed acutely or for 20 weeks to acidic bile salts. Vascular endothelial growth factor (VEGF) A was inhibited with a neutralizing antibody or CRISPR-Cas9n and VEGF receptor 2 was inhibited with SU1498 or shRNA, and cells were analyzed by immunohistochemistry, quantitative polymerase chain reaction, or immunoblotting for markers of VEGF signaling and EMT; cell motility was assessed by trans-well assay. We used immunohistochemistry and quantitative polymerase chain reaction to assess EMT markers in the columnar-lined esophagus of rats with surgically induced reflux esophagitis and in esophagectomy specimens from patients with BE. We detected features of EMT (decreased cadherin 1 [CDH1]; increased fibronectin 1, vimentin, and matrix metalloproteinase 2; and increased motility) in dysplastic BE epithelial cell lines and in BAR-T cells exposed for 20 weeks, but not in unexposed BAR-T cells. Acute acidic bile salt exposure induced expression of zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) in BAR-T cells, which decreased their expression of CDH1 and increased motility; inhibitors of VEGF signaling blocked these effects. Columnar-lined esophagus of rats with reflux esophagitis had increased expression of ZEB1/2 and decreased expression of CDH1 compared with controls. Dysplastic BE tissues also had significantly increased levels of ZEB1 and significantly decreased levels of CDH1 compared with nondysplastic BE tissues. In BE cell lines, acidic bile salts induce EMT by VEGF signaling, which increases expression of ZEB1/2, repressors of CDH1. These observations suggest that reflux induces EMT in metaplastic BE tissues, which promotes development of subsquamous intestinal metaplasia.

Prognosis of patients with superficial T1esophageal cancer who underwent endoscopic resection before esophagectomy-A propensity score-matched comparison.

The aim of this retrospective study was to compare the prognosis of patients with esophageal cancer after non-curative endoscopic resection (ER) followed by esophagectomy (ER + S) with that of patients after primary surgery (PS). Between 2000 and 2015, 287 patients had esophagectomy for T1 esophageal cancer. 81 of these patients underwent at least one ER in curative intention before surgery (7 squamous cell carcinomas, 74 adenocarcinomas). Indications for esophagectomy were R1-resection, submucosal infiltration, multifocality, long-segment Barrett esophagus, recurrence, postinterventional stenosis or a combination of these factors. Using propensity-score matching with gender, age, year of diagnosis, tumor localization, mucosal/submucosal infiltration and histology, the clinicopathologic and survival data of these patients were compared to those of 81 patients after PS (median follow-up: 5.5years). There were no significant differences between both groups concerning number of resected lymph nodes and percentage of nodal metastasis (9.3% total). 9% of esophagectomy specimens after ER showed pT2/pT3-tumors. The 5-year survival rate was 86% in the PS and 85% in the ER + S group (p = 0.498). The disease-free survival was 85% in patients with ER + S and 98% in PS (p < 0.005). The recurrence rate after esophagectomy was higher after ER + S compared to PS (p = 0.015). More than 3months time delay between ER and surgery was associated with reduced survival, but only within the first postinterventional year. As the disease-free survival was inferior in the ER + S compared to the PS group the indication for ER, especially repeated ERs, should be restricted to cases with high expectation of success.

Perineural invasion through the sheath in posttherapy esophagectomy specimens predicts poor survival in patients with esophageal squamous cell carcinoma

BackgroundThe prognostic impact of perineural invasion (PNI) in patients with esophageal cancer who receive neoadjuvant chemoradiotherapy (nCRT) remains unclear. MethodsA thorough pathological review of PNI was performed on post-nCRT esophagectomy specimens obtained from non-ypT0 patients with esophageal squamous cell carcinoma (ESCC). When PNI was identified, it was classified according to the presence or absence of penetration through the nerve sheath (i.e., PNI surrounding the nerve sheath [PNI-SS] versus PNI penetrating through the nerve sheath [PNI-TS]). The impact of PNI on overall survival (OS) was assessed in combination with clinical and pathological risk factors. ResultsA total of 177 eligible patients were identified between 1998 and 2008. PNI was identified in 43.5% (77/177) of participants. Of them, 33 and 44 had PNI-SS and PNI-TS, respectively. The 5-year OS rate of patients with PNI-TS was significantly lower (6.7%) than that observed in those without PNI (30.6%, P < 0.001). However, the 5-year OS observed in the latter group did not differ significantly from that of patients with PNI-SS (26%, P = 0.68). Multivariate analysis identified PNI-TS (hazard ratio [HR] = 1.965, P = 0.02), LVI (HR = 1.514, P = 0.048), and ypN2 stage (HR = 2.39, P = 0.007) as independent adverse prognostic factors for OS. ConclusionsThe presence of PNI-TS after nCRT is associated with poor survival. A thorough assessment of distinct PNI patterns (i.e., PNI-TS versus PNI-SS) should be part of the routine post-nCRT histopathological work-up of ESCC patients.

Prognostic significance of IgG4+ plasma cell infiltrates following neoadjuvant chemoradiation therapy for esophageal adenocarcinoma

Lymphoplasmacytic infiltrates in esophageal adenocarcinoma (EAC) tissue following chemoradiotherapy (CRT) reflect alterations in the tumor immunoenvironment. The presence and role of plasma cells in this process are poorly understood. Our aim was to characterize the IgG4+ plasma cell population in EAC following CRT. Seventy-one esophagectomy specimens post-CRT were compared with a surgery-only group of 31 EACs. The distribution, density, and ratio of IgG4+ and IgG+ plasma cells were evaluated by immunohistochemistry and correlated with clinicopathologic features, treatment response, and survival. In the CRT group, the presence of higher numbers of IgG4+ (≥ median of 94/high-power field) and IgG+ (≥ median of 225/high-power field) plasma cells and increased IgG4+/IgG+ ratio (≥ median of 41%) within ulcers was associated with complete or near-complete treatment response (P = .0077, P = .0503, and P = .0063, respectively). Lower tumor grade, smaller tumor size, and higher levels of IgG4+ plasma cells in posttherapy ulcers significantly correlated with better overall survival, whereas pretherapy clinical stage, posttherapy pathologic stage, smaller tumor size, and lower tumor grade were associated with longer recurrence-free survival. Multivariate analysis revealed that both posttherapy pathologic stage and high IgG4+ plasma cells in ulcers were independent predictors of overall survival (P = .05 and P = .01), whereas only posttherapy pathologic stage was associated with recurrence-free survival (P < .01). This is the first study describing a dense IgG4+ plasma cell infiltrate in EAC following CRT. The presence of increased IgG4+ plasma cells may be a novel reliable factor to predict prognosis of EAC patients following CRT.

5-Fluorouracil upregulates cell surface B7-H1 (PD-L1) expression in gastrointestinal cancers

BackgroundResistance to chemotherapy is a major obstacle in the effective treatment of cancer patients. B7-homolog 1, also known as programmed death ligand-1 (PD-L1), is an immunoregulatory protein that is overexpressed...

OC-051 Outcomes of SM Invasive Barrett’s Cancers Following Endoscopic Resection: Radical Intervention is not Always Required?: Abstract OC-051 Table 1

Introduction Endoscopic resection (ER) of Barrett’s cancer with curative intent is extremely effective for lesions limited to the mucosal layer of the oesophagus. Lesions extending beyond the muscularis mucosae into the submucosa are considered for radical therapy due to risk of lymph node metastases. Radical treatment is not without risk, reported mortality of oesophagectomy is 2–5%. Methods All patients referred for ER of Barrett’s cancer had data collected prospectively between 2006 and 2015. The database was interrogated by independent researchers blinded to the endoscopic procedures for patients with SM invasive cancers. Results 261 endoscopic resections were performed in 182 patients during the study period. 26 (14%) patients had SM invasion following ER. 12 had undergone endoscopic submucosal dissection (ESD) and 14 endoscopic mucosal resection (EMR). 22 (85%) lesions were superficially submucosally invasive (SM1), 4 were >SM1 (15%). Table 1 shows outcomes after ER. Mean disease free survival was 4.31 years (Range 0.7 to 10.8) in this cohort. 3 patients died of recurrent cancer, 3 patients died of co-morbid conditions. All 9 patients in the endoscopy group were clear of cancer at follow up. There was 1 recurrence treated with further ER. Of the 6 patients undergoing surgery 5 had no residual neoplasia in the oesophagectomy specimen (pTxN0M0). 1 patient had a pT1N0M0 cancer with LVI and signet ring cells and died 2 years after surgery. 1 patient was considered for surgery but was turned down due to comorbidities and subsequently died of cancer 6 years following ER. 3 patients have been discharged to their referring centres for consideration of surgery. 7 patients underwent chemoradiotherapy. 6 of 7 patients treated with chemoradiotherapy were clear of recurrence on follow up. 1 patient developed recurrence of cancer and died 2 years after ER. Conclusion This data challenges the current paradigm of radical therapy following ER of SM1 Barrett’s cancers. Outcomes for patients managed endoscopically are excellent. 5 patients undergoing surgery in our cohort had no residual disease in the oesophagectomy specimen and potentially could have undergone endoscopic follow up alone. Patients found to have SM1 lesions without poor prognostic features can effectively be managed without radical intervention. SM invasive cancers require an individualised management plan tailored to histology and co-morbidities. There does not appear to be a demonstrable difference between chemoradiotherapy and surgery. Disclosure of Interest None Declared

Immunoexpression of p53 as an indicator of invasiveness in esophageal carcinoma: -a tertiary care hospital study from Punjab, India

Background: Esophageal carcinoma (EC) is an upcoming major health challenge with 4,07,000 deaths related to it reported globally in the year 2008 alone. Its risk factors apart from tobacco and alcohol vary according to various geographical areas which include ethnicity, dietary and other socio-economic factors. This can have a bearing on its various prognostic factors in which Immunohistochemistry (IHC) has emerged as a major tool for predicting the same. p53 has proved to be a particular important molecule in development of many tumors including esophageal carcinoma as it has a role in both tumor immunity and cell cycle. The present study was conducted in Punjabi population where tobacco usage is low because of the societal and religious taboos and where life style and developmental indicators are high in comparison to rest of India. The aim was to analyze epidemiologically the cases suffering from esophageal carcinoma, to study p53 expression in histologically proven cases of esophageal carcinoma and also to correlate p53 positive expression with the type and grade of the tumor along with other clinico-pathological parameters. Material and Methods: The study was conducted on 50 cases of EC diagnosed in the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India. The 50 cases (either endoscopic biopsies or esophagectomy specimen) were independently verified for sub classification and histopathological grading. In all the cases patient’s complains, age, gender and other important clinical parameters were recorded. All the cases were taken up for IHC study for p53 expression. The results obtained were tabulated and statistically analyzed. A p value less than 0.05 was considered statistically significant. Result: In the present study, maximum cases (60%) were observed in the age group of 41-60 years where female patients outnumbered male patients in a ratio of (1.3:1). Lower segment (56%) was the most common segm

Examination of Surgical Specimens of the Esophagus.

Esophageal cancer continues to be one of the most lethal of all gastrointestinal malignancies. Its prognostic parameters are based on the gross and histopathologic examination of resected specimens by pathologists. To describe the implications of appropriate handling and examination of endomucosal resection and esophagectomy specimens from patients with esophageal carcinoma while considering the implications of the surgical techniques used to obtain such specimens. Parameters include histopathologic findings necessary for accurate staging, differences in the assessment of margins, residual malignancy, and criteria to evaluate for tumor regression after chemoradiation therapy as well as the role of immunohistochemistry and the judicious use of frozen sections. Sources were a review of the literature and the authors' experience handling these types of specimens. Examining surgical specimens of the esophagus is critical in the management of patients with esophageal carcinoma, and it requires careful consideration of the diagnostic pitfalls, staging-related parameters, and results of molecular tests.

Can the Risk of Lymph Node Metastases Be Gauged in Endoscopically Resected Submucosal Esophageal Adenocarcinomas? A Multi-Center Study

Endoscopic resection (ER) allows for local therapy of superficial esophageal cancers. Factors reported to be associated with an increased risk of lymph node metastases in patients with adenocarcinoma are poor differentiation, lymphovascular invasion (LVI), and submucosal invasion >500 μ. The aim of this study was to determine whether depth of invasion and tumor characteristics in an ER specimen can be used to gauge the risk of lymph node metastases in patients with superficial esophageal adenocarcinoma. Patients from seven US centers that had ER of an adenocarcinoma followed by an esophagectomy were identified. The ER pathology slides were rereviewed by three experienced GI pathologists for depth of invasion, presence of LVI, and tumor differentiation. The findings from the ER specimen were correlated with the presence and number of lymph node metastases in the final esophagectomy specimen. There were 19 T1a and 23 T1b tumors. A median of 24 nodes were resected per patient. None of the T1a tumors had involved lymph nodes despite the presence of LVI in 5 % and poor differentiation in 21 % of patients. In contrast, 26 % of T1b tumors had involved nodes. None of the four patients with submucosal invasion ≤500 μ, no LVI, and no poor differentiation had involved nodes. However, with an increasing number of risk factors, the likelihood of involved lymph nodes increased, reaching 50 % when all three factors were present. Endoscopic therapy appears appropriate for intramucosal tumors and may be an option for low-risk T1b tumors. Esophagectomy is preferred for patients with submucosal invasion and one or more risk factors.

Predictors of Disease Recurrence and Survival in Esophageal Adenocarcinomas With Complete Response to Neoadjuvant Therapy.

Complete response to neoadjuvant therapy, determined by pathologic examination of the resection specimen (pCR), is associated with a favorable outcome in esophageal adenocarcinomas (EAC), but there is significant heterogeneity in survival reported within this group. Our aim was to determine predictors of disease recurrence (DR) and survival in EAC patients with pCR to neoadjuvant therapy. A total of 93 EAC patients with pCR to neoadjuvant therapy were identified, and a predetermined set of clinicopathologic variables was examined, including patient age, sex, tumor location, pretreatment tumor size, endoscopic ultrasound T and N stage, histologic tumor type, and grade in pretreatment biopsies. The esophagectomy specimens were evaluated for the extent of sampling of the tumor bed, depth of treatment-related changes, presence of treatment effect in lymph nodes, and the total number of lymph nodes examined. Complete histologic examination of the tumor bed was the most significant predictor of favorable outcome for both DR (hazard ratio [HR]=0.42; 95% confidence interval [CI]: 0.21-0.82; P=0.011) and disease-specific mortality (HR=0.40; 95% CI: 0.22-0.70; P<0.01). The presence of a high-grade adenocarcinoma component in pretreatment biopsies (HR=2.19; 95% CI: 1.22-3.94; P<0.01) was associated with a higher disease-specific mortality, and involvement of the gastroesophageal junction (HR=2.37; 95% CI: 1.11-5.06; P=0.026) was associated with a higher rate of DR. Heterogeneity in outcomes for EAC patients with pCR to therapy can be explained by adequacy of histologic examination of the tumor bed, high tumor grade, and involvement of the gastroesophageal junction.

Thoracolaparoscopic dissection of esophageal lymph nodes without esophagectomy is feasible in human cadavers and safe in a porcine survival study.

High-risk early esophageal adenocarcinoma (i.e. submucosal invasion >500 nm, poor differentiation, and/or presence of lymphovascular invasion) is currently treated with esophagectomy with lymph node (LN) dissection given the high rates of LN metastases. However, esophagectomy is associated with substantial morbidity and mortality. Endoscopic radical resection followed by thoracolaparoscopic LN dissection without concomitant esophagectomy could be an alternative. The study aim was to evaluate the feasibility and safety of thoracolaparoscopic dissection of esophageal LNs in a preclinical setting. (i) In human cadavers, thoracolaparoscopic dissection of LNs involved in drainage of the esophagus was performed. Subsequently, esophagectomy was performed to be able to detect retained LNs. Outcome parameters included the number of dissected LNs, the number of retained LNs in the esophagectomy specimen (ES), and technical success. (ii) In swine, thoracolaparoscopic LN dissection was also performed. After the procedure, the swine survived for 28 days. Thereafter, the swine were sacrificed and esophagectomy was performed. Outcome parameters included the presence of ischemia and/or stenosis in the ES and other complications. (i) In five human cadavers, a median of 26 LNs (interquartile range 22-46) were dissected. In two ES, one retained LN was found: one high paraesophageal, one low paraesophageal. Technical success rate was 100%. (ii) None of the seven porcine ES showed signs of ischemia or stenosis. One swine died because of ventricular fibrillation during surgery; during follow up no complications were observed. Thoracolaparoscopic dissection of LNs involved in the drainage of the esophagus is feasible in human cadavers and swine. The porcine survival study suggests that the esophageal vascularity is not severely compromised by the procedure. As anatomy differs between swine and humans, safety of the procedure will have to be investigated thoroughly before applying this new technique as the treatment of choice.

223 Survival After Resection of Gastrointestinal Stromal Tumor and Sarcoma Liver Metastases: A Single-Center Experience of 146 Patients

Introduction: Endoscopic resection (ER) has revolutionized the therapy for esophageal adenocarcinoma. Intramucosal tumors rarely have node metastases, but the is 10-30% with submucosal (T1b) invasion. Factors reported to increase this are poor differentiation, lymphovascular invasion (LVI) and invasion >500 microns into the submucosa. Lesions without these factors have been labelled low risk and are potentially suitable for endoscopic therapy. The aim of this study was to evaluate whether it is possible to gauge the of lymph node metastases after endoscopic resection of a T1b adenocarcinoma based on differentiation, LVI and measured depth of submucosal invasion. Methods: Patients with submucosal invasion on ER specimens who subsequently had an esophagectomy were identified at 5 US centers. The ER pathology slides were independently reviewed by 2-3 expert pathologists for differentiation, presence of LVI and depth of invasion. The pathologists collectively measured the depth of submucosal invasion, the width of invasion at the mucosal / submucosal interface, and the depth of uninvolved submucosa below the tumor to the resection margin. The esophagectomy pathology report was reviewed to determine the presence of lymph node metastases. Patients were excluded from analysis for other than T1b lesions, a poorly sectioned ER specimen or neoadjuvant therapy prior to esophagectomy. Results: There were 20 patients with confirmed submucosal invasion. The median depth of invasion into the submucosa was 1360 microns, the median width was 2780 microns and the median depth of uninvolved submucosa below the lesion was 740 microns. Tumor characteristics and lymph node metastases are shown (Table). Overall 7 patients (35%) had lymph node metastases and the of node metastases could not be gauged using tumor differentiation, LVI or depth of submucosal invasion. The frequency of node metastases was similar between patients with low risk lesions and those with higher lesions (p=1). There were 9 patients with ≤ 500 microns of uninvolved submucosa between the tumor and the resection margin and 6 had node metastases. Residual tumor was present in the esophagectomy specimen in 8 patients. Conclusions: Esophagectomy after an ER that showed submucosal invasion confirmed lymph node metastases in 35% of patients. There was no safe depth of submucosal invasion, nor was there a low risk lesion. Poor differentiation and LVI did not impact the risk, but 66% of patients with ≤ 500 microns of uninvolved submucosa below the tumor had node metastases. Endoscopic therapy would frequently be inadequate for T1b esophageal adenocarcinoma. Submucosal adenocarcinoma and the of lymph node metastases.

Neoadjuvant Treatment Response in Negative Nodes Is an Important Prognosticator After Esophagectomy

The current American Joint Committee on Cancer Seventh Edition (AJCC7) pathologic staging for esophageal adenocarcinoma (EAC) is derived from data assessing the outcomes of patients having undergone esophagectomy without neoadjuvant treatment and has unclear significance in patients who have received multimodality therapy. Lymph nodes with evidence of neoadjuvant treatment effect without residual cancer cells may be observed and are not traditionally considered in pathologic reports, but may have prognostic significance. All patients who underwent esophagectomy after completing neoadjuvant therapy for EAC at our institution between 2006 and 2012 were reviewed. Slides of pathologic specimens were reexamined for locoregional treatment-response nodes lacking viable cancer cells but with evidence of acellular mucin pools, central fibrosis, necrosis, or calcifications suggesting prior tumor involvement. Kaplan-Meier survival functions were estimated, and Cox proportional hazards regression models were used to compare staging models. Ninety patients (82 men) underwent esophagectomy after neoadjuvant therapy for EAC (mean age, 61.8 ± 8.9 years). All patients received preoperative chemotherapy, and 50 patients also underwent preoperative radiotherapy. Median Kaplan-Meier survival was 55.6 months, and 5-year survival was 35% (95% confidence interval, 19% to 62%). A total of 100 treatment-response nodes were found in 38 patients. For patients with limited nodal disease (62 ypN0-N1), the presence of treatment-response nodes was associated with significantly worse survival (p = 0.03) compared with patients lacking such nodes. Adjusting for patient age and AJCC7 pathologic stage showed the presence of treatment-response nodes significantly increased the risk of death (hazard ratio, 2.7; 95% confidence interval, 1.1 to 6.9; p = 0.04). When stage-adjusted survival was modeled, counting treatment-response nodes as positive nodes offered a better model fit than ignoring them. Treatment-response lymph nodes detected from esophagectomy specimens in patients having undergone neoadjuvant chemotherapy or combined chemoradiation for EAC provide valuable prognostic information, particularly in patients with limited nodal disease. The current practice of considering lymph nodes lacking viable cancer cells, but with evidence of tumor necrosis, as pathologically negative likely results in understaging. Future efforts at revising the staging system for EAC should consider incorporating treatment-response lymph nodes in the analysis.

PTU-164 Evidence Of Two Aetiologies Of Gastroesophageal Junctional Cancers Based On Gastric Parietal Cell Density

IntroductionSerum pepsinogen I:II ratio, a surrogate marker of atrophic gastritis, suggests that some adenocarcinomas at the gastroesophageal junction (GOJ) develop on a background of atrophic gastritis, similar to non-cardia gastric...

Necrotizing sialometaplasia-like change of the esophageal submucosal glands is associated with Barrett's esophagus.

The esophageal submucosal glands (SMG) protect the squamous epithelium from insults such as gastroesophageal reflux disease by secreting mucins and bicarbonate. We have observed metaplastic changes within the SMG acini that we have termed oncocytic glandular metaplasia (OGM), and necrotizing sialometaplasia-like change (NSMLC). The aim of this study is to evaluate the associated clinicopathological parameters of, and to phenotypically characterize the SMG metaplasias. Esophagectomy specimens were retrospectively assessed on hematoxylin and eosin sections and assigned to either a Barrett's esophagus (BE) or non-BE control group. Clinicopathologic data was collected, and univariate analysis and multivariate logistic regression models were performed to assess the adjusted associations with NSMLC and OGM. Selected cases of SMG metaplasia were characterized. SMG were present in 82 esophagi that met inclusion criteria. On univariate analysis, NSMLC was associated with BE (p = 0.002). There was no relationship between NSMLC and patient age, sex, tumor size, or treatment history. OGM was associated with BE (p = 0.031). No relationship was found between OGM and patient age, sex, or tumor size. On multivariate analysis, BE was independently associated with NSMLC (odds ratio [OR] 4.95, p = 0.003). Treatment history was also independently associated with OGM (p = 0.029), but not NSMLC. Both NSMLC and OGM were non-mucinous ductal type epithelia retaining a p63-smooth muscle actin co-positive myoepithelial cell layer. NSMLC and OGM were present in endoscopic mucosal resection specimens. Our study suggests that SMG metaplasia is primarily a reflux-induced pathology. NSMLC may pose diagnostic dilemmas in resection specimens or when only partially represented in mucosal biopsies or endoscopic resection specimens.

Sa1867 Evidence of Two Aetiologies of Gastroesophageal Junctional Cancers Based on Gastric Parietal Cell Density

Introduction Serum pepsinogen I:II ratio, a surrogate marker of atrophic gastritis, suggests that some adenocarcinomas at the gastroesophageal junction (GOJ) develop on a background of atrophic gastritis, similar to non-cardia gastric cancer, while others arise on a backgrounds of healthy, non-atrophic gastric mucosa similar to oesophageal adenocarcinoma. In this current study, we have directly the background gastric body mucosa in patients with junctional adenocarcinomas compared to oesophageal adenocarcinomas and non-cardia gastric cancers. Methods 127 gastrectomy and oesophagectomy specimens for adenocarcinoma were identified for which clear topographic description allowed assignment to oesophageal, junctional (including cardia) and gastric non-cardia locations. In these gastric body mucosa specimens, well clear of the tumour margin, parietal cells were immunostained using anti- H + /K + ATPase. Parietal cell density was counted in 3 to 5 well-oriented fields (1 mm 2 each) and expressed as mean parietal cell number per 1 mm 2 area. Total mucosal thickness, glandular thickness, intestinal metaplasia, inflammation indicated by polymorphonuclear (PMN) and mononuclear (MN) cells and reactive atypia (RA) were also scored. Non-parametric statistics were used to compare distributions. Results Ten (8%) cases lacked well-orientated blocks of body mucosa. The remaining 117 patients included 34 oesophageal, 52 GOJ and 31 non-cardia gastric adenocarcinomas. Median (IQR) parietal cell densities were 836 (173), 602 (389) and 411 (334) per mm 2 in gastric mucosa of oesophageal, GOJ and gastric cancers, respectively (all differences P 2 , 85% of oesophageal adenocarcinomas had a higher and 84% of non-cardia gastric cancers had a lower values. With the same cut-off, 50% of GOJ adenocarcinomas were gastric and remaining was oesophageal in origin. Glandular mucosa was thicker in patients with GOJ cancer compared to gastric (0.735 vs. 0.600, p = 0.005) and thinner than oesophageal cancer (0.735 vs. 0.900, p Conclusion This study provides direct evidence for marked differences in the gastric mucosal phenotype in the patients with oesophageal versus gastric non-cardia cancer, with the former being healthy and uninflamed, but the latter atrophic and inflamed. The background gastric mucosa of GOJ cancer supported them being two distinct aetiologies, one group resembling oesophageal adenocarcinoma and other gastric non-cardia cancer. Disclosure of Interest None Declared.

Sa1868 Is Endoscopic Submucosal Dissection Safe for Papillary Adenocarcinoma of Stomach?

Background & Aim: Serum pepsinogen I:II ratio, a surrogate marker of atrophic gastritis, suggests that some adenocarcinomas at the gastroesophageal junction (GOJ) develop on a background of atrophic gastritis, similar to non-cardia gastric cancer, while others arise on a background of healthy, non-atrophic gastric mucosa similar to oesophageal adenocarcinoma. In this current study, we have directly examined the background gastric body mucosa in patients with junctional adenocarcinomas compared to oesophageal adenocarcinomas and non-cardia gastric cancers. Methods: 127 gastrectomy and oesophagectomy specimens for adenocarcinoma were identified for which clear topographic description allowed assignment to oesophageal, junctional (including cardia) and gastric non-cardia locations. In these gastric body mucosa specimens, well clear of the tumour margin, parietal cells were immunostained using antiH+/K+ ATPase. Parietal cell density was counted in 3 to 5 well-oriented fields (1 square mm each) and expressed as mean parietal cell number per 1 square mm area. Inflammation indicated by polymorphonuclear (PMN) and mononuclear (MN) cells were also scored. Non-parametric statistics were used to compare distributions. Results: Ten (8%) cases lacked well-orientated blocks of body mucosa. The remaining 117 patients included 34 oesophageal, 52 GOJ and 31 non-cardia gastric adenocarcinomas. Median (IQR) parietal cell densities were 836 (173), 602 (389) and 411 (334) per square mm in gastric mucosa of oesophageal, GOJ and non-cardia gastric cancers, respectively (all differences P <0.001) (Figure). Using a parietal cell density of 630/square mm, 85% of oesophageal adenocarcinomas had higher and 84% of non-cardia gastric cancers had lower values. In contrast, 50% of the GOJ adenocarcinomas had values greater than and 50% less than this parietal cell density of 630 square mm. Frequency distribution curves of gastric mucosal parietal cell density indicated monophasic patterns for both oesophageal adenocarcinomas and noncardia gastric adenocarcinomas but a biphasic distribution for junctional adenocarcinomas. The chronic inflammatory cell infiltrate [median, (IQR)] was significantly greater in the gastric body mucosa of the non-cardia gastric adenocarcinomas [3(2)] than the oesophageal adenocarcinomas [0(1)]. The junctional adenocarcinoma again had an intermediate score [1(21)], all p values were <0.01. Conclusion: This study provides direct evidence for marked differences in the gastric mucosal phenotype in patients with oesophageal versus gastric non-cardia cancer, with the former being healthy and uninflamed, but the latter atrophic and inflamed. The background gastric mucosa of GOJ cancer supports them being of two distinct aetiologies, one group resembling oesophageal adenocarcinoma and the other gastric non-cardia cancer.

Leptin and adiponectin receptor expression in oesophageal cancer

Oesophageal adenocarcinoma is an exemplar model of an obesity-associated adenocarcinoma. Altered secretion of adipokines by visceral fat is believed to play a key role in tumorigenesis. This study examined leptin receptor (ObR) and adiponectin receptor (AdipoR1 and AdipoR2) expression in oesophageal cancer, and its relationship with patient obesity status, clinicopathological data and patient survival. Tissue microarrays were constructed from paraffin-embedded oesophagectomy specimens. ObR, AdipoR1 and AdipoR2 expression was quantified by immunohistochemistry. Anthropometric data were measured at the time of diagnosis, and obesity status was assessed using visceral fat area determined by computed tomography and body mass index. Receptor expression was correlated with various clinicopathological and anthropometric variables. Patient survival was estimated using the Kaplan-Meier method, and results compared between those with low versus high receptor expression. A Cox multivariable regression model was used to assess the relationship between survival and a number of co-variables. All 125 tumours analysed expressed AdipoR1 and AdipoR2, whereas 96·8 per cent expressed ObR. There was no significant difference in tumour pathological features or patient obesity status between tumours with low versus high ObR expression. A high level of AdipoR1 expression was significantly associated with increased patient age, obesity and less advanced tumour (T) category. Expression of AdipoR2 was inversely associated with T category (P = 0.043). Low AdipoR1 expression was an independent predictor of improved overall survival (hazard ratio 0.56, 95 per cent confidence interval 0.35 to 0.90; P = 0.017). The association between adiponectin receptor expression, obesity status and tumour category and survival suggests a potential mechanism linking obesity and oesophageal cancer.