Diagnostic Efficacy of Type B Vessels in the Japan Esophageal Society Classification for the Depth of Invasion of Superficial Esophageal Squamous Cell Carcinoma.

AIM: The preoperative diagnostic method for superficial esophageal squamous cell carcinoma (SESCC) invasion depth based on the Japan Esophageal Society (JES) classification has been promoted. However, there have been a few investigations into its diagnostic performance in clinical settings. Therefore, we aimed to elucidate the actual diagnostic performance of the JES classification using a single-center retrospective study design. METHODS: We retrospectively analyzed the clinical data of 315 newly diagnosed SESCC patients who underwent narrow-band imaging magnifying endoscopy (NBI-ME) examination and received endoscopic submucosal dissection (ESD) or esophagectomy in our center during the past 5 years. To evaluate the diagnostic performance of JES classification in assessing the depth of invasion of SESCC, clinical data of these patients were collected, and the concordance between NBI-ME findings and postoperative pathology reports was analyzed. RESULTS: This study included a total of 338 lesions. The diagnostic accuracy of vascular morphology was 76.0%. The sensitivity (87.0%) and positive predictive value (PPV, 85.4%) of B1 vessels were high, but the specificity (42.0%) and negative predictive value (NPV, 45.3%) were low. The specificity (86.9% and 98.8%) and NPVs (87.5% and 96.8%) of B2 and B3 vessels were high, but the sensitivity (36.4% and 21.4%) and PPVs (35.1% and 42.9%) ware low. Furthermore, only a few lesions (n = 57) described avascular area, but the overall diagnostic accuracy was not ideal (21.1%). However, if lesions invading the superficial submucosa or shallower were included in the category of "suitable for ESD", the overall accuracy of the JES classification was found to be 95.6%. CONCLUSIONS: In actual clinical settings, the overall accuracy of the JES classification system decreases, but the diagnostic performance of each subtype retains its original characteristics. Additionally, this classification is appropriate for determining whether type 0-II SESCC lesions are suitable for ESD.

Review of the Japanese Classification of Esophageal Cancer 12th Edition, and Proposals for the 13th Edition.

In this review, we summarize the modifications made in the Japanese Classification of Esophageal Cancer 12th edition, identify several issues, and discuss the prospects for the next 13th edition.

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.

Integrative analysis of genomic, epigenomic and transcriptomic data identified molecular subtypes of esophageal carcinoma.

Esophageal cancer (EC) involves many genomic, epigenetic and transcriptomic disorders, which play key roles in the heterogeneous progression of cancer. However, the study of EC with multi-omics has not been conducted. This study identified a high consistency between DNA copy number variations and abnormal methylations in EC by analyzing genomics, epigenetics and transcriptomics data and investigating mutual correlations of DNA copy number variation, methylation and gene expressions, and stratified copy number variation genes (CNV-Gs) and methylation genes (MET-Gs). The methylation, CNVs and expression profiles of CNV-Gs and MET-Gs were analyzed by consistent clustering using iCluster integration, here, we determined three subtypes (iC1, iC2, iC3) with different molecular traits, prognostic characteristics and tumor immune microenvironment features. We also identified 4 prognostic genes (CLDN3, FAM221A, GDF15 and YBX2) differentially expressed in the three subtypes, and could therefore be used as representative biomarkers for the three subtypes of EC. In conclusion, by performing comprehensive analysis on genomic, epigenetic and transcriptomic regulations, the current study provided new insights into the multilayer molecular and pathological traits of EC, and contributed to the precision medication for EC patients.

Two updates on oesophagogastric junction adenocarcinoma from the fifth WHO classification: Alteration of definition and emphasis on HER2 test.

INTRODUCTION: The incidence of oesophagogastric junction adenocarcinoma has increased rapidly but remains controversial over the last decades. There are two crucial updates of the fifth World Health Organization (WHO) classification, including the alteration of its definition and the emphasis on the human epidermal growth factor receptor 2 (HER2) test. METHODS: A total of 566 clinicopathological samples from patients who were diagnosed with gastric adenocarcinoma were retrospectively analyzed. We comprehensively compared the clinicopathological features of oesophagogastric junction adenocarcinoma between the fourth (V4.0) and fifth (V5.0) WHO versions. The clinicalpathological features among oesophagogastric junction, proximal and distal gastric tumors with fourth and fifth edition were also compared, respectively. Also, we discuss the correlation of HER2-expression with clinicopathological features according to the V5.0. RESULTS: The results showed that the difference was mainly between oesophagogastric junction and distal adenocarcinoma in V4.0, while some were found between proximal and distal adenocarcinoma in V5.0. Tumors invading the oesophagus more than 3cm were still mainly oesophagogastric junction tumors. The expression of HER2 in oesophagogastric junction and proximal gastric adenocarcinoma was still higher than that in gastric body and distal sites. CONCLUSIONS: The clinicopathological parameters of the oesophagogastric junction tumors changed to some extent in the updated WHO version. The proximal gastric tumors tended to be more invasive, more than those located in oesophagogastric junction. But the latter with oesophageal invasion required additional management. The HER2-expression of oesophagogastric junction adenocarcinoma is the highest. The classification of V5.0 is reasonable and worth recommendation.

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.

Updates on World Health Organization classification and staging of esophageal tumors: implications for future clinical practice.

The Fifth edition of the World Health Organization classification of digestive system and American Joint Committee on Cancer staging manual contain substantial refinements of information for esophageal tumors. The epithelial tumors of esophagus are classified as benign, dysplasia, and malignant groups. Dysplasia is divided into Barrett dysplasia and squamous dysplasia and graded into either low-grade or high-grade. Malignant esophageal tumors are often adenocarcinoma or squamous cell carcinoma. The main update in cancer staging in esophageal tumors is the subdivision of the prognostic staging into 3 groups; squamous cell carcinoma, adenocarcinoma, and carcinoma after adjuvant therapy. HER-2 amplification is recognized as a molecular target for therapy of esophagogastric adenocarcinoma. The other esophageal tumors are adenoid cystic carcinoma, mucoepidermoid/adenosquamous carcinoma, undifferentiated carcinoma and neuroendocrine neoplasms. Overall, the incorporation of new data and definitions on histopathology, prognostic factors, and genetics are important for personalized management of patients with esophageal tumors.

Clinicopathologic factors associated with pathologic upstaging in patients clinically diagnosed stage T2N0M0 squamous cell esophageal carcinoma.

BACKGROUND: Even with the use of contrast-enhanced thin-layer chest computed tomography (CT) and endoscopic ultrasonography (EUS), the likelihood of cT2N0M0 squamous cell esophageal cancer correlating with the final pathologic outcome is exceedingly low. We therefore sought to investigate the associations between different risk factors and pathologic upstaging in stage T2N0M0 esophageal cancer patients who underwent esophagectomy. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological characteristics of 224 stage T2N0M0 squamous cell esophageal cancer patients who underwent complete resection over a 2-year period (October 2016-September 2018). The tumor volume (TV) was automatically measured from thin-layer chest CT scans using imaging software. Univariate and multivariate analyses were performed to identify the risk factors associated with upstaging. A receiver operating characteristic (ROC) curve was plotted, and its ability to identify pathological upstaging was assessed. RESULTS: A total of 224 patients with clinical stage T2N0M0 squamous cell esophageal carcinoma (SCEC) underwent esophagectomy; of these patients, 96 (42.86%) had a more advanced stage during the final pathologic review than during the initial diagnosis. The risk factors for pathologic upstaging included a large TV, high total cholesterol (TC), high triglycerides (TGs), high platelet-to-lymphocyte ratio (PLR), and high number of lymph nodes examined. The ROC analysis demonstrated an area under the curve of 0.845 (95% confidence interval 0.794-0.895). CONCLUSIONS: In SECC diagnosed as stage T2N0M0 by CT and EUS, the incidence of postoperative pathologic upstaging increases with a large TV, high TC, high TGs, high PLR, and high number of lymph nodes examined.

Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort.

BACKGROUND: Obesity has been positively associated with upper gastrointestinal cancers, but prospective data by subtype/subsite are limited. Obesity influences hormonal factors, which may play a role in these cancers. We examined anthropometry, body fat and reproductive factors in relation to oesophageal and gastric cancer by subtype/subsite in the UK Biobank cohort. METHODS: Among 458,713 UK Biobank participants, 339 oesophageal adenocarcinomas, 124 oesophageal squamous cell carcinomas, 137 gastric cardia and 92 gastric non-cardia cancers were diagnosed during a mean of 6.5 years follow-up. Cox models estimated multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Body mass index (BMI), hip circumference, waist circumference, waist-to-hip ratio, waist-to-height ratio, total body fat and trunk fat were positively associated with oesophageal adenocarcinoma (highest vs lowest category: HR = 2.33, 95%-CI:1.65-3.28; HR = 1.56, 95%-CI:1.15-2.13; HR = 2.30, 95%-CI:1.47-3.57; HR = 1.71, 95%-CI:1.01-2.90; HR = 2.87, 95%-CI:1.88-4.38; HR = 1.96, 95%-CI:1.30-2.96; HR = 2.34, 95%-CI:1.70-3.22, respectively). Although there were no statistically significant associations in combined sex analyses, BMI (HR = 1.83, 95%-CI:1.00-3.37), waist circumference (HR = 2.21, 95%-CI:1.27-3.84) and waist-to-hip ratio (HR = 1.92, 95%-CI:1.11-3.29) were associated with gastric cardia cancer in men; however, mutual adjustment attenuated the associations for BMI and waist-to-hip ratio. For oesophageal squamous cell carcinoma, statistically significant inverse associations were observed among women for BMI, hip circumference, waist circumference, waist-to-height ratio, total body fat and trunk fat, although they were based on small numbers. In addition, older age at first (HR = 0.44, 95%-CI:0.22-0.88) and last live birth (HR = 0.44, 95%-CI:0.22-0.87) were inversely associated with oesophageal squamous cell carcinoma and having a stillbirth/miscarriage/termination was positively associated (HR = 1.84, 95%-CI:1.10-3.07). CONCLUSIONS: Obesity and abdominal obesity specifically may be a risk factor for oesophageal adenocarcinoma and gastric cardia cancer in men. Some reproductive factors may be associated with oesophageal squamous cell carcinoma in women.

Multidisciplinary Evaluation and Management of Early Stage Esophageal Cancer.

Early esophageal cancer involves the mucosal and submucosal layers of the esophagus. Early esophageal cancer is a heterogeneous group, and achieving optimal outcomes requires a multidisciplinary approach to align patients to their optimal treatment. Although organ-sparing endoscopic resection has become the preferred management option for superficial esophageal cancer, it is not adequate in all tumors, such as high-risk lesions with poorly differentiated pathology, lymphovascular invasion, or deep submucosal invasion. In such high-risk lesions, surgery, chemotherapy, and/or radiation may be required. In this article, we present our multidisciplinary approach to early esophageal cancer.

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.

Ways and tradition of Japan in esophageal surgery for cancer.

OBJECTIVE: This report presents the essence in practice of Japanese methods and tradition in surgery for esophageal cancer. METHODS: The etiology of esophageal cancer and the concepts of lymphadenectomy in esophagectomy, in neoadjuvant treatments, and in stage classifications are compared between Western countries and Japan. RESULTS: With respect to the type and relative incidence of esophageal cancer, in Western countries, adenocarcinoma in the lower thoracic esophagus and in the cardia is common, and among esophageal surgeons, there remains some controversy over the extent of lymphadenectomy. On the other hand, in Japan, squamous cell carcinoma in the middle thoracic esophagus is common, and concerning lymphadenectomy, Japanese esophageal surgeons consider that three-field lymphadenectomy is superior to other types of lymphadenectomy. In Japan, surgeons believe that most patients with esophageal cancer even those having lymph node metastasis can be best treated using esophagectomy and lymphadenectomy. CONCLUSIONS: In Japan, the tradition in esophageal surgery places great significance on lymphadenectomy. The ways and procedures for esophageal cancer surgery, the neoadjuvant and adjuvant treatments, the Japanese Classification of Esophageal Cancer, the Esophageal Cancer Practice Guidelines, and other scientific reports are all based on a close combination of esophagectomy with lymphadenectomy.

A Novel Three-miRNA Signature Identified Using Bioinformatics Predicts Survival in Esophageal Carcinoma.

OBJECTIVE: We identified differentially expressed microRNAs (DEMs) between esophageal carcinoma (ESCA) tissues and normal esophageal tissues. We then constructed a novel three-miRNA signature to predict the prognosis of ESCA patients using bioinformatics analysis. Materials and Methods. We combined two microarray profiling datasets from the Gene Expression Omnibus (GEO) database and RNA-seq datasets from the Cancer Genome Atlas (TCGA) database to analyze DEMs in ESCA. The clinical data from 168 ESCA patients were selected from the TCGA database to assess the prognostic role of the DEMs. The TargetScan, miRDB, miRWalk, and DIANA websites were used to predict the miRNA target genes. Functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (David), and protein-protein interaction (PPI) networks were obtained using the Search Tool for the Retrieval of Interacting Genes database (STRING). RESULTS: With cut-off criteria of P < 0.05 and |log2FC| > 1.0, 33 overlapping DEMs, including 27 upregulated and 6 downregulated miRNAs, were identified from GEO microarray datasets and TCGA RNA-seq count datasets. The Kaplan-Meier survival analysis indicated that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) was significantly associated with the overall survival of ESCA patients. The results of univariate and multivariate Cox regression analysis showed that the three-miRNA signature was a potential prognostic factor in ESCA. Furthermore, the gene functional enrichment analysis revealed that the target genes of the three miRNAs participate in various cancer-related pathways, including viral carcinogenesis, forkhead box O (FoxO), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (ErbB2), and mammalian target of rapamycin (mTOR) signaling pathways. In the PPI network, three target genes (MAPK1, RB1, and CLTC) with a high degree of connectivity were selected as hub genes. CONCLUSIONS: Our results revealed that a three-miRNA signature (miR-1301-3p, miR-431-5p, and miR-769-5p) is a potential novel prognostic biomarker for ESCA.

[Retrospect of 2019: focus on the surgical treatment for adenocarcinoma of esophagogastric junction].

Adenocarcinoma of esophagogastric junction (AEG) has a special anatomical position. In clinical practice, there are many overplays among thoracic surgeons, gastrointestinal surgeons, gastroenterologists and oncologists. In recent years, AEG has attracted more and more clinical attention with its increasing incidence. It has a tendency to be gradually separated from esophageal cancer and gastric cancer and be defined as a new special type of tumor. At present, there are still many controversies in the definition, classification, TNM staging, surgical approach, extent of resection, lymph node dissection, digestive tract reconstruction and neoadjuvant therapy of AEG. Meanwhile many problems still need to be solved, which is in a stage of gradual improvement and standardization. This article mainly reviews the important research progress in the field of AEG in 2019, summarizes the current clinical hotspots of AEG, especially the surgical treatment hotspots and the current application status of related new technologies, and aims the future development. We suggest that communication and cooperation among multiple disciplines should be strengthened. Through more clinical researches, basic experimental researches, and innovation and application of new technologies, personalized and accurate diagnosis and treatment will be carried out for patients with different conditions to ultimately achieve the common goal of maximizing the benefits of patients.

Accuracy of the revised Vienna Classification for predicting postendoscopic resection outcomes for gastric and oesophageal neoplasms: a retrospective cohort study of patients from a UK tertiary referral centre.

AIMS: To review the effectiveness of the revised Vienna classification (rVC) at predicting histological outcome and defining the postendoscopic resection (ER) clinical management plan of gastro-oesophageal dysplasia and early neoplasia in a UK tertiary-centre population. METHODS: This was a retrospective cohort study between November 2011 and May 2018. 157 patients from Salford Royal NHS Foundation Trust in the UK were included. The primary outcome was the histological results of postsurgical resection (SR) specimens compared with their post-ER rVC. The secondary outcome was overall survival rates of patients with category 4.4 and 5 of the rVC. RESULTS: One-hundred and thirteen patients were diagnosed with category ≥4 of the rVC. 23 patients (20.4%) were referred for additional surgery, whereas 69 patients (61.1%) were on endoscopic surveillance only. 60.9% of post-SR specimens (14/23) revealed no residual neoplasia. 78.6% of these cancer-free specimens were classed as category 5 rVC. The overall 7-year survival rate of 25 patients with category ≥4.4 was 68% with causes of mortality not linked to upper gastrointestinal neoplasia. The overall 7-year and 3-year survival rates of category 4.4 and 5 were 73.6% and 50%, respectively, although age and comorbid state played a role. CONCLUSIONS: This study provides evidence of outcomes comparable to other reported cohorts for cases after ER in a single-centre UK population even at rVC 4.4/5. It suggests surgery may not be necessary in all cases due to the lack of residual disease and further refinement of the rVC category 5 may help guide management.

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.

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.

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.

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.