Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society.

Japanese Classification of Esophageal Cancer, 12th Edition: Part I.

This is the first half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Japanese Classification of Esophageal Cancer, 12th Edition: Part II.

This is the second half of English edition of Japanese Classification of Esophageal Cancer, 12th Edition that was published by the Japan Esophageal Society in 2022.

Integrated genomic characterization of oesophageal carcinoma.

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

Mapping of Lymph Node Metastasis From Esophagogastric Junction Tumors: A Prospective Nationwide Multicenter Study.

OBJECTIVE: The aim of the study was to determine the optimal extent of lymph node dissection for the 2 histological types of esophagogastric junction (EGJ) tumors based on the incidence of metastasis in a prospective nationwide multicenter study. BACKGROUND: Because most previous studies were retrospective, the optimal surgical procedure for EGJ tumors has not been standardized. METHODS: Patients with cT2-T4 adenocarcinoma or squamous cell carcinoma located within 2.0 cm of the EGJ were enrolled before surgery. Surgeons dissected all lymph nodes prespecified in the protocol, using either the abdominal transhiatal or right transthoracic approach. The primary endpoint was the metastasis rate of each lymph node. Lymph nodes were classified according to metastasis rate, as follows: category-1 (strongly recommended for dissection), rate more than 10%; category-2 (weakly recommended for dissection), rate from 5% to 10%; and category-3 (not recommended for dissection), rate less than 5%. RESULTS: Between 2014 and 2017, 1065 patients with EGJ tumor were screened, and 371 were enrolled. Among 358 patients who underwent surgical resection, category-1 nodes included abdominal stations 1, 2, 3, 7, 9, and 11p, whereas category-2 nodes included abdominal stations 8a, 19, and lower mediastinal station 110. If esophageal involvement exceeded 2.0 cm, station 110 was assigned to category-1. Among 98 patients who had either adenocarcinoma with esophageal involvement over 3.0 cm or squamous cell carcinoma, there were no category-1 nodes in the upper/middle mediastinal field, whereas category-2 nodes included upper mediastinal station 106recR and middle mediastinal station 108. When esophageal involvement exceeded 4.0 cm, station 106recR was assigned to category-1. CONCLUSION: The study accurately identified the distribution of lymph node metastases from EGJ tumors and the optimal extent of subsequent lymph node dissection.

Identification of the distinct genomic features in gastroesophageal junction adenocarcinoma and its Siewert subtypes.

Rates of gastroesophageal junction adenocarcinomas (GEJAs) have shown an alarming increase; however, the genetic background of GEJA and its Siewert classification have yet to be uncovered. Here, 60 paired tumor and normal DNA samples from GEJA patients were analyzed by whole-exome sequencing. Among them, 13 were Siewert type I, 14 were type II, and 33 were type III. A predominance of C/G>T/A substitutions was discovered in GEJA, followed by C/G>A/T substitutions. Notably, Siewert type I and type II/III display distinct sets of driver genes, mutational spectrum, and recurrently disrupted pathways. Siewert type I showed similarity to esophageal adenocarcinomas (EACs) and the chromosomal instability subtype of stomach adenocarcinomas, while Siewert type II/III showed similarity to the genomic stable subtype of stomach adenocarcinoma. We also found that mutation of FBXW7, a driver gene of GEJA, was enriched in Siewert type I. Our data identify differences between GEJA and stomach/EACs at the genomic level and provide evidence for differential treatment based on Siewert classification of GEJA. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5-25 kg/m2 : HR = 1.94, 95% CI: 1.25-3.03) and women (HR = 2.66, 95% CI: 1.15-6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99-6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52-4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35-14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76-18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14-0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32-0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04-3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

Development and validation of the international Blue Light Imaging for Barrett's Neoplasia Classification.

BACKGROUND AND AIMS: Detecting subtle Barrett's neoplasia during surveillance endoscopy can be challenging. Blue-light imaging (BLI) is a novel advanced endoscopic technology with high-intensity contrast imaging that may improve the identification of Barrett's neoplasia. The aim of this study was to develop and validate the first classification to enable characterization of neoplastic and non-neoplastic Barrett's esophagus using BLI. METHODS: In phase 1, descriptors pertaining to neoplastic and non-neoplastic Barrett's esophagus were identified to form the classification, named the Blue Light Imaging for Barrett's Neoplasia Classification (BLINC). Phase 2 involved validation of these component criteria by 10 expert endoscopists assessing 50 BLI images. In phase 3, a web-based training module was developed to enable 15 general (nonexpert) endoscopists to use BLINC. They then validated the classification with an image assessment exercise in phase 4, and their pre- and post-training results were compared. RESULTS: In phase 1 the descriptors were grouped into color, pit, and vessel pattern categories to form the classification. In phase 2 the sensitivity of neoplasia identification was 96.0% with a very good level of agreement among the experts (κ = .83). In phase 3, 15 general endoscopists completed the training module. In phase 4 their pretraining sensitivity (85.3%) improved significantly to 95.7% post-training with a good level of agreement (κ = .67). CONCLUSIONS: We developed and validated a new classification system (BLINC) for the optical diagnosis of Barrett's neoplasia using BLI. Despite the limitations of this image-based study with a high prevalence of neoplasia, we believe it has the potential to improve the optical diagnosis of Barrett's neoplasia given the high degree of sensitivity (96%) noted. It is also a promising tool for training in Barrett's esophagus optical diagnosis using BLI.

True esophagogastric junction adenocarcinoma: background of its definition and current surgical trends.

The definition of true esophagogastric junction (EGJ) adenocarcinoma and its surgical treatment are debatable. We review the basis for the current definition and the Japanese surgical strategy in managing true EGJ adenocarcinoma. The Siewert classification is a well-known anatomical classification system for EGJ adenocarcinomas: type II tumors in the region 1 cm above and 2 cm below the EGJ are described as "true carcinoma of the cardia". Coincidentally, this range matches gastric cardiac gland distribution. Conversely, Nishi's classification is generally used to describe EGJ carcinomas, defined as tumors with the center located within 2 cm above and 2 cm below the EGJ, regardless of their histological subtype. This range coincides with the extent of the lower esophageal sphincter combined with gastric cardiac gland distribution. The current Japanese surgical strategy focuses on the tumor range from the EGJ to the esophagus and stomach. According to previous studies, the strategy can be roughly classified into three types. The optimal surgical procedure for true EGJ adenocarcinoma is controversial. However, an ongoing Japanese nationwide prospective trial will help confirm the appropriate standard surgery, including the optimal extent of lymph node dissection.

The sub-classification of type B2 vessels according to the magnifying endoscopic classification of the Japan Esophageal Society.

OBJECTIVES: Guidelines for magnified endoscopic diagnosis of esophageal squamous cell carcinoma (SCC) have been proposed by the Japan Esophageal Society. Type B1, B2, and B3 reflect increasing tumor invasion depths (within mucosal epithelium or into lamina propria mucosa [T1a-EP/LPM], into muscularis mucosa or superficial invasion into submucosa [T1a-MM/T1b-SM1], and into submucosa [T1b-SM2], respectively). The diagnostic accuracy of type B1 and B3 is high, but accuracy of type B2 is low. We aimed to improve the diagnostic accuracy of type B2. METHODS: We retrospectively reviewed 248 SCC lesions treated with endoscopic submucosal dissection between January 2012 and July 2018 and identified the B2 lesions. The maximum diameter of the area presenting B2 was measured and evaluated in relation to tumor invasion, for which receiver-operating characteristic (ROC) curves were generated. The optimal area size for distinguishing T1a-EP/LPM from T1a-MM or deeper invasion was determined. RESULTS: There were 78 lesions with B2, of which 26 (33%) were T1a-MM or T1b-SM1 SCCs. ROC curve analysis indicated that the optimal cut-off for the target area showing B2 was 4 mm. The invasion depth (EP/LPM: MM/SM1: SM2) of B2 observed in an area with a diameter <4 mm (B2-Narrow) and those with diameter ≥4 mm (B2-Broad) was 46:11:1 and 1:15:4, respectively. To predict T1a-MM or deeper invasion, B2-Broad had a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 98%, 95%, and 79%, respectively. CONCLUSION: The diagnostic accuracy of type B2 was improved by evaluating the area of type B2.

Preoperative indicators of misdiagnosis in invasion depth staging of esophageal cancer: Pitfalls of magnifying endoscopy with narrow-band imaging.

OBJECTIVES: The Japan Esophageal Society classification has been widely applied for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCCs). Although Type B2 of the classification clinically corresponds to SESCCs with muscularis mucosa or slight submucosal invasion (MM/SM1), diagnostic yield based on Type B2 is insufficient. This study aimed to investigate risk factors for misdiagnosis in preoperative invasion depth staging. METHODS: We included a total of 104 SESCCs in which Type B2 was observed by magnifying endoscopy. SESCCs were classified as either correct diagnosis (pMM/SM1, 39 lesions), overdiagnosis (epithelium or the lamina propria [pEP/LPM], 34 lesions), or underdiagnosis (deep invasion into the submucosa [pSM2-3], 31 lesions) based on pathological depth of invasion. The association between misdiagnosis and endoscopic features, including distinct features, was evaluated using logistic regression analysis. Distinct features were defined as nodular protrusion, thickness, and/or clearly depressed area. The diameter of type B2 area was endoscopically measured, and the cut-off value was determined using a receiver operating characteristic curve. RESULTS: Type B2 area <6 mm (area under the curve, 0.776) and Type B2 vessels around erosion were significantly associated with overdiagnosis (odds ratio, 16.6 and 11.0, respectively), while distinct features were significantly associated with underdiagnosis (odds ratio, 8.7). Adjusted by these misdiagnosis factors, positive predictive value of Type B2 significantly improved from 38% to 65% (P < 0.01). CONCLUSIONS: Lesions with a small Type B2 area (<6 mm) and/or Type B2 vessels around erosion should be diagnosed as EP/LPM and lesions with distinct features as SM2-3.

Classification for invasion depth of esophageal squamous cell carcinoma using a deep neural network compared with experienced endoscopists.

BACKGROUND AND AIMS: Cancer invasion depth is a critical factor affecting the choice of treatment in patients with superficial squamous cell carcinoma (SCC). However, the diagnosis of invasion depth is currently subjective and liable to interobserver variability. METHODS: We developed a deep learning-based artificial intelligence (AI) system based on Single Shot MultiBox Detector architecture for the assessment of superficial esophageal SCC. We obtained endoscopic images from patients with superficial esophageal SCC at our facility between December 2005 and December 2016. RESULTS: After excluding poor-quality images, 8660 non-magnified endoscopic (non-ME) and 5678 ME images from 804 superficial esophageal SCCs with pathologic proof of cancer invasion depth were used as the training dataset, and 405 non-ME images and 509 ME images from 155 patients were selected for the validation set. Our system showed a sensitivity of 90.1%, specificity of 95.8%, positive predictive value of 99.2%, negative predictive value of 63.9%, and an accuracy of 91.0% for differentiating pathologic mucosal and submucosal microinvasive (SM1) cancers from submucosal deep invasive (SM2/3) cancers. Cancer invasion depth was diagnosed by 16 experienced endoscopists using the same validation set, with an overall sensitivity of 89.8%, specificity of 88.3%, positive predictive value of 97.9%, negative predictive value of 65.5%, and an accuracy of 89.6%. CONCLUSIONS: This newly developed AI system showed favorable performance for diagnosing invasion depth in patients with superficial esophageal SCC, with comparable performance to experienced endoscopists.

Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

Comparison between gastric and esophageal classification system among adenocarcinomas of esophagogastric junction according to AJCC 8th edition: a retrospective observational study from two high-volume institutions in China.

BACKGROUND: The new 8th TNM system attributes AEG Siewert type II to esophageal classification system. However, the gastric and esophageal classification system which was more suitable for type II remains in disputation. This study aimed to illuminate the 8th TNM-EC or TNM-GC system which was more rational for type II, especially for patients underwent transhiatal approaches. METHODS: We collected the database of patients with AEG who underwent radical surgical resection from two high-volume institutions in China: West China Hospital (N = 773) and Xi Jing Hospital of Fourth Military University (N = 637). The cases were randomly matched into 705 training cohort and 705 validation cohort. All the cases were reclassified by the 8th edition of TNM-EC and TNM-GC. The distribution of patients in each stage, the hazard ratio of each stage, and the separation of the survival were compared. Multivariate analysis was performed using the Cox proportional hazard model. Comparisons between the different staging systems for the prognostic prediction were performed with the rcorrp.cens package in Hmisc in R (version 3.4.4. http://www.R-project.org/ ). The validity of these two systems was evaluated by Akaike information criterion (AIC) and concordance index (C-index). RESULTS: By univariate analysis, the HRs from stage IA/IB to stage IV/IVB were monotonously increased according to TNM-GC scheme in both cohorts (training 2.63, 3.91, 5.02, 8.64, 15.51 and 29.64; validation 1.54, 3.55, 4.91, 7.14, 11.67, 18.71 and 48.32) whereas only a fluctuating increased tendency was found when staged by TNM-EC. After the multivariate analysis, TNM-GC (P < 0.001), TNM-EC (P = 0.001) in training cohort and TNM-GC (P < 0.001) TNM-EC (P < 0.001) in the validation cohort were both independent prognostic factors. The C-index value for the TNM-GC scheme was larger than that of TNM-EC system in both training (0.721 vs. 0.690, P < 0.001) and validation (0.721 vs. 0.696, P < 0.001) cohorts. After stratification analysis for Siewert type II, the C-index for TNM-GC scheme was still larger than that of TNM-EC in both training (0.724 vs. 0.694, P = 0.005) and validation (0.723 vs. 0.699, P < 0.001) cohorts. CONCLUSIONS: The 8th TNM-GC scheme is superior to TNM-EC in predicting the prognosis of AEG especially for type II among patients underwent transhiatal approaches.

Digital image analysis of HER2 immunohistochemistry in gastric- and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens.

AIMS: To test the validity of diagnostics incorporating digital image analysis (DIA) for human epidermal growth factor 2 (HER2) immunohistochemistry (IHC) in gastro-oesophageal adenocarcinomas, as an alternative to current standard diagnostics using manual scoring. METHODS AND RESULTS: We included 319 consecutive gastro-oesophageal adenocarcinomas (232 biopsies and 87 surgical specimens). DIA was applied to determine HER2 IHC classification, using both standard breast cancer (BC) and modified gastro-oesophageal cancer (GEC) cut-offs. Consensus manual scores were established by four independent observers. Chromogenic in-situ hybridization (CISH) was performed on all 2+ cases by manual scoring, DIA or both. HER2 status was considered positive in 3+ and CISH-positive 2+ cases. Overall agreement between DIA and consensus manual scores was 76.5% (weighted κ = 0.66, BC cut-offs) and 85.6% (weighted κ = 0.80, GEC cut-offs). Agreement was similar for biopsies and surgical specimens. All disagreement occurred in the manual IHC equivocal cases. DIA resulted in a reduction of 2+ cases: 75.8% with BC cut-offs and 46.5% with GEC cut-offs. HER2 status was positive in 48 cases (15%) with standard diagnostics and DIA using GEC cut-offs, and 46 cases (14.4%) using BC cut-offs (all with CISH in 2+ cases). Considering standard diagnostics as a reference, DIA showed 93.8% sensitivity and 99.6% specificity (BC cut-offs) or 97.9% sensitivity and 99.6% specificity (GEC cut-offs). CONCLUSIONS: DIA is a reliable and feasible alternative to manual HER2 IHC scoring in gastro-oesophageal adenocarcinoma, both in biopsies and surgical specimens, leading to a reduction of 2+ cases for which subsequent ISH testing is required.

A training program of a new simplified classification of magnified narrow band imaging for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS: A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS: The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P < 0.05). CONCLUSIONS: A well-designed training program can improve the diagnostic accuracy in evaluating cancer invasion depth, with substantial agreement.

New classification for the thoracic paraaortic lymph nodes of patients with esophageal squamous cell carcinoma.

PURPOSE: To create a new classification for the thoracic paraaortic lymph nodes (No. 112ao) of patients with esophageal squamous cell carcinoma (ESCC). Classification of these nodes in ESCC patients has been the focus of very few reports. METHODS: The subjects of this study were 27 patients with positive No. 112ao nodes on computed tomography (CT) images before treatment. We divided the No. 112ao nodes into No. 112aoA, located on the esophageal side as anterior No. 112ao nodes, and No. 112aoP, located on the opposite side of the esophagus as posterior No. 112ao nodes. We examined the association between No. 112aoA and No. 112aoP and clinicopathological factors. Recurrence-free survival (RFS) was compared between the No. 112aoA- and No. 112aoP-positive groups. RESULTS: There were 12 patients in the No. 112aoA-positive group and 15 patients in the No. 112aoP-positive group. The No. 112aoP-positive group had significantly worse RFS than the No. 112aoA-positive group (p = 0.004). Cox multivariate analysis of RFS revealed that No. 112aoP positivity was an independent prognostic factor (p = 0.043). CONCLUSIONS: Our new classification of No. 112ao nodes into No. 112aoA and No. 112aoP is useful clinically. No. 112aoP could correspond to the clinical N4 category of patients with ESCC.

[Esophagogastric junction and its tumours - comments to definition and classification]. / Ezofagogastrická junkce a její nádory - poznámky k definici a klasifikaci.

In spite of the worldwide decreasing incidence of gastric cancer the number of esophagogastric junction and proximal third of stomach carcinomas has been gradually growing up. The reason of that is an increasing incidence of reflux esophagitis with Barrett´s metaplasia and a successful eradication of Helicobacter pylori infection. The aim of this work is to provide various views on definition of the esophagogastric junction and to give an overview of tumours classification schemes being used.

Development and Validation of a Classification System to Identify High-Grade Dysplasia and Esophageal Adenocarcinoma in Barrett's Esophagus Using Narrow-Band Imaging.

BACKGROUND & AIMS: Although several classification systems have been proposed for characterization of Barrett's esophagus (BE) surface patterns based on narrow-band imaging (NBI), none have been widely accepted. The Barrett's International NBI Group (BING) aimed to develop and validate an NBI classification system for identification of dysplasia and cancer in patients with BE. METHODS: The BING working group, composed of NBI experts from the United States, Europe, and Japan, met to develop a validated, consensus-driven NBI classification system for identifying dysplasia and cancer in BE. The group reviewed 60 NBI images of nondysplastic BE, high-grade dysplasia, and esophageal adenocarcinoma to characterize mucosal and vascular patterns visible by NBI; these features were used to develop the BING criteria. We then recruited adult patients undergoing surveillance or endoscopic treatment for BE at 4 institutions in the United States and Europe, obtaining high-quality NBI images and performing histologic analysis of biopsies. Experts individually reviewed 50 NBI images to validate the BING criteria, and then evaluated 120 additional NBI images (not previously viewed) to determine whether the criteria accurately predicted the histology results. RESULTS: The BING criteria identified patients with dysplasia with 85% overall accuracy, 80% sensitivity, 88% specificity, 81% positive predictive value, and 88% negative predictive value. When dysplasia was identified with a high level of confidence, these values were 92%, 91%, 93%, 89%, and 95%, respectively. The overall strength of inter-observer agreement was substantial (κ = 0.681). CONCLUSIONS: The BING working group developed a simple, internally validated system to identify dysplasia and EAC in patients with BE based on NBI results. When images are assessed with a high degree of confidence, the system can classify BE with >90% accuracy and a high level of inter-observer agreement.

Delineation of disease phenotypes associated with esophageal adenocarcinoma by MALDI-IMS-MS analysis of serum N-linked glycans.

N-Linked glycans, extracted from patient sera and healthy control individuals, are analyzed by Matrix-assisted laser desorption ionization (MALDI) in combination with ion mobility spectrometry (IMS), mass spectrometry (MS) and pattern recognition methods. MALDI-IMS-MS data were collected in duplicate for 58 serum samples obtained from individuals diagnosed with Barrett's esophagus (BE, 14 patients), high-grade dysplasia (HGD, 7 patients), esophageal adenocarcinoma (EAC, 20 patients) and disease-free control (NC, 17 individuals). A combined mobility distribution of 9 N-linked glycans is established for 90 MALDI-IMS-MS spectra (training set) and analyzed using a genetic algorithm for feature selection and classification. Two models for phenotype delineation are subsequently developed and as a result, the four phenotypes (BE, HGD, EAC and NC) are unequivocally differentiated. Next, the two models are tested against 26 blind measurements. Interestingly, these models allowed for the correct phenotype prediction of as many as 20 blinds. Although applied to a limited number of blind samples, this methodology appears promising as a means of discovering molecules from serum that may have capabilities as markers of disease.