UpToDate’ attdatrerint om uptepatet www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. @.Wolters Kluwer Clinical manifestations, diagnosis, and staging of esophageal cancer ‘AUTHORS: John R Saltzman, MD, FACP, FACG, FASGE, AGAF, Michael K Gibson, MD, PhD, FACP SECTION EDITORS: Douglas A Howell, MD, FASGE, FACG, Richard M Goldberg, MD. bePUTY EDITOR: Sonali Shah, MD. All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2023. ‘This topic last updated: May 31, 2023. INTRODUCTION Squamous cell carcinoma (SCC) and adenocarcinoma account for over 95 percent of esophageal malignant tumors. For most of the 20" century, SCC predominated. In the 1960s, SCC accounted for more than 90 percent of esophageal tumors in the United States, and adenocarcinomas were considered so uncommon that some authorities questioned their existence. However, over time, the incidence of esophageal adenocarcinoma (predominantly arising in the distal esophagus and esophagogastric junction [EGJ]) has increased dramatically in Western countries such that adenocarcinoma now accounts for >60 percent of all esophageal cancers in the United States [1]. In contrast, worldwide, SCC still predominates [2]. (See "Epidemiology and pathobiology of esophageal cancer") Esophageal SCCs and adenocarcinomas differ in a number of features, including tumor location and predisposing factors (table 1). Smoking and alcohol are major risk factors for SCC, while Barrett's esophagus (BE) with intestinal metaplasia (a complication of gastroesophageal reflux disease [GERD)), obesity, and smoking are the risk factors for adenocarcinoma [3]. Although there is little doubt that esophageal SCCs and adenocarcinomas represent two different diseases with characteristic pathogenesis, epidemiology, tumor biology, treatment, and outcomes, whether and how histology influence the therapeutic approach remains controversial. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus", section on ‘Squamous cell versus adenocarcinoma’ and "Epidemiology and pathobiology of esophageal cancer".)The clinical manifestations, diagnosis, and staging of esophageal cancer are reviewed here. The epidemiology, risk factors, and pathobiology of SCC and adenocarcinoma are covered elsewhere. (See "Epidemiology and pathobiology of esophageal cancer".) IMPORTANCE OF PRETREATMENT STAGING ASSESSMENT Itis vitally important that newly diagnosed esophageal cancer is accurately staged in order to select appropriate treatment: * For patients with potentially resectable tumors, the choice of initial treatment is highly dependent on clinical stage at diagnosis ( table 2): + Aminority of patients have disease that is limited to the mucosa or submucosa (ie, T1a/bNO), which has a high cure rate from surgical or endoscopic therapy alone. (See "Management of superficial esophageal cancer".) + Surgery is the primary curative modality for both esophageal and esophagogastric junction (EG)) cancers that invade through the esophageal wall or are node positive. Long-term outcomes are not satisfactory with resection alone, even if microscopically complete (RO). This poor long-term outcome prompted evaluation of multimodality approaches, which have evolved in parallel for thoracic esophagus and EG} tumors, respectively. For most patients with T3 or node-positive tumors, combined modality therapy is preferred over surgery alone. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus" and "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas") + The optimal approach to clinical T2NO disease is debated, and guidelines from expert groups differ. Some suggest initial chemoradiotherapy for SCC, and either neoadjuvant chemotherapy or chemoradiotherapy for adenocarcinomas of the distal esophagus or EG) [4]. Others, including the National Comprehensive Cancer Network (NCCN) [5], suggest initial resection for clinical T2NO adenocarcinomas or SCCs as long as they are <3 cm and well differentiated, but initial chemoradiotherapy for others with either histology who have high-risk disease. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus", section on ‘Clinical T2NO disease’ and "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas", section on ‘Patients with clinical T1/2, node-negative disease’.)* Regardless of histology, between 50 and 80 percent of patients with esophageal and EGJ cancers present with incurable, locally advanced unresectable or metastatic disease [6]. Survival is often extended by anticancer therapy, but concurrent supportive care is essential. (See "Management of locally advanced, unresectable and inoperable esophageal cancer" and “Initial systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer") Selection of patients for any of these therapies is first of all dependent upon accurate staging. CLINICAL MANIFESTATIONS Patients with advanced thoracic or cervical esophageal carcinoma present with progressive dysphagia and weight loss. Chronic gastrointestinal blood loss from esophageal and esophagogastric junction (EG)) cancer is common and may result in iron deficiency anemia. Early intramucosal adenocarcinomas of the distal esophagus that are recognized at endoscopy in an area associated with Barrett's esophagus (BE) is usually not symptomatic. Thoracic esophageal tumors — Despite differing histologies, both adenocarcinoma and squamous cell carcinoma (SCO) arising in the thoracic esophagus have similar clinical presentations. In contemporary series, approximately 6 to 10 percent are asymptomatic at the time of diagnosis [7]. Most early (superficial) esophageal cancers in the United States are detected serendipitously or during screening for or surveillance of BE. Early intramucosal cancers are not symptomatic. (See "Management of superficial esophageal cancer") Dysphagia and weight loss — Among patients with locally advanced esophageal cancer, obstruction of the esophagus by the tumor causes progressive dysphagia, often accompanied by weight loss. Dysphagia usually occurs once the esophageal lumen diameter is less than 13 mm (reduction by approximately 70 percent of luminal diameter), which indicates at minimum locally advanced disease. Weight loss is due to changes in diet to accommodate the dysphagia, and tumor-related anorexia may contribute. Approximately 20 percent of patients experience odynophagia (painful swallowing). Early symptoms of esophageal cancer may be subtle and nonspecific, Transient "sticking" of solid food, which may easily be overcome by careful chewing and slower eating, may precede frank dysphagia. The dysphagia gradually progresses from solids to liquids. Patients may also notice retrosternal discomfort or a burning sensation. Differential diagnosis — The differential diagnosis of dysphagia is broad and includes nonmalignant strictures, achalasia and other esophageal motility disorders, esophagitis, andesophageal webs and rings. (See "Approach to the evaluation of dysphagia in adults", section on '‘Symptom-based differential diagnosis'.) The differential diagnosis of an esophageal mass includes lesions that typically arise beneath an intact mucosa, including gastrointestinal stromal tumors, leiomyomas and leiomyosarcomas, as well as high-grade neuroendocrine neoplasms (extrapulmonary small cell cancers); all of these are rare. (See "Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors", section on ‘Location’ and "Local treatment for gastrointestinal stromal tumors, leiomyomas, and leiomyosarcomas of the gastrointestinal tract’, section on ‘Esophagus’ and "High-grade gastroenteropancreatic neuroendocrine neoplasms") Other symptoms — Regurgitation of saliva or food uncontaminated by gastric secretions may also occur. Aspiration pneumonia is infrequent. Hoarseness and/or cough may occur if the recurrent laryngeal nerve is invaded by either the primary tumor or associated nodal metastases. Chronic gastrointestinal blood loss from esophageal and EG] cancer is common and may result in iron deficiency anemia [8]. However, patients seldom notice melena, hematemesis, or blood in regurgitated food. Acute upper gastrointestinal bleeding as a result of tumor erosion into the aorta or pulmonary or bronchial arteries is rare. Tracheobronchial fistulas are a late complication. They are caused by direct invasion of tumor through the esophageal wall and into the mainstem bronchus. Such patients often present with intractable coughing or recurrent pneumonias. Stent placement is the treatment of choice. (See "Tracheo- and broncho-esophageal fistulas in adults” and "Endoscopic palliation of esophageal cancer") Signs or symptoms referable to distant metastatic disease often occur. The most common sites of distant metastases are the liver, lungs, bones, and adrenal glands [9]. Adenocarcinomas most frequently metastasize to intraabdominal sites (liver, peritoneum), while metastases from SCCs are usually intrathoracic. However, many other sites are described, including cutaneous, muscle, and brain metastases [10]. Cervical esophageal tumors — Between 5 and 6 percent of esophageal cancers arise in the cervical portion of the esophagus, which is 6 to 8 cm long and extends from the hypopharynx (upper esophageal sphincter) to the sternal notch(table3and__ figure 1) [11]. Most patients have locally advanced disease at the time of diagnosis, sometimes with extension to the hypopharynx. In retrospective series, the most common complaints are weight loss and dysphagia, and 11 to 24 percent have hoarseness as a presenting symptom 112-14].DIAGNOSIS The diagnosis of esophageal cancer requires a histologic examination of tumor tissue. A diagnostic biopsy may be obtained by upper endoscopy or, if metastases are present, by image-guided biopsy of a metastatic site. Endoscopic biopsy — Early esophageal cancers appear endoscopically as superficial plaques, nodules, or ulcerations (__ picture 1). Advanced lesions appear as strictures (picture 2), ulcerated masses (_ picture 3), circumferential masses (_ picture 4), or large ulcerations. (See "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)".) While endoscopic visualization of a large mucosal mass is nearly pathognomonic of esophageal cancer, biopsy must be performed to confirm the diagnosis. The greater the number of biopsies (up to seven), the higher the diagnostic accuracy. As an example, in a series of 202 consecutive patients, 47 of whom had gastric or esophageal carcinoma, the percentages of correct diagnoses of esophageal carcinoma were as follows Us: * First biopsy - 93 percent * Four biopsies - 95 percent * Seven biopsies - 98 percent For small lesions, endoscopic resection of the entire lesion may be feasible. Following histologic analysis, endoscopic resection alone may represent suitable therapy if the tumor is small and superficial (see "Overview of endoscopic resection of gastrointestinal tumors", section on ‘Esophageal cancer’). Assessment and endoscopic management of superficial esophageal cancer are discussed in greater detail elsewhere. (See "Overview of endoscopic resection of gastrointestinal tumors", section on ‘Esophageal cancer’ and "Management of superficial esophageal cancer", section on ‘Initial assessment',) PRETREATMENT STAGING EVALUATION The prognosis of esophageal cancer is strongly associated with disease stage. Accurate clinical staging of both local tumor extent and the presence or absence of distant metastases is critical for estimating prognosis and selecting the appropriate treatment strategy.Overview — Once the diagnosis of esophageal cancer is established, pretreatment staging includes an evaluation for both locoregional disease and distant metastases: * Endoscopic ultrasound (EUS) is the preferred method for locoregional staging. For patients with a thoracic esophageal tumor at or above the carina, bronchoscopy is also indicated. For cervical squamous cell carcinomas (SCCs), flexible laryngoscopy to assess local disease spread and exclude a synchronous malignancy of the head and neck is generally recommended. (See ‘Locoregional staging’ below and ‘Bronchoscopy and laryngoscopy’ below.) * The evaluation for distant metastases includes tomographic testing, including contrast- enhanced computed tomography (CT) of the neck, chest, and abdomen; whole-body integrated fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT; EUS; and sometimes diagnostic laparoscopy. + Integrated FDG-PET/CT scans are more sensitive than contrast-enhanced CT for detecting metastatic disease and are now indicated for the detection of occult metastases; if they are not detected on the initial staging CT. Use of preoperative PET/CT in the pretreatment staging evaluation results in a change in management (usually upstaging and thus avoidance of unnecessary surgery) in up to 20 percent of patients. At some institutions, PET with a diagnostic, contrast-enhanced CT is carried out with intravenous (IV) contrast, which replaces the need for a separate contrast-enhanced CT, but this practice is not widespread. (See 'CT, PET, and integrated PET/CT' below.) + EUS can visualize liver metastases <1 cm in the left lobe of the liver and malignant ascites; EUS-guided fine-needle aspiration (FNA) or fine needle biopsy (FNB) can get tissue from either of these sites. + Invasive staging (laparoscopy, thoracoscopy) may be used to enhance or replace EUS or imaging; however, no study has compared these approaches with EUS plus PET/CT, which are superior to conventional imaging for detecting distant metastases. Some clinicians advocate diagnostic laparoscopy for patients with potentially resectable clinical T3/T4 adenocarcinomas arising at the EG] or cardia or if there is suspicion for intraperitoneal metastatic disease that cannot otherwise be confirmed. We do not utilize thoracoscopy for patients who have access to integrated PET/CT. (See 'Laparoscopy and thoracoscopy’ below.) + Routine brain imaging is not a cost-effective or necessary evaluation unless symptoms or signs raise suspicion for brain metastases. (See ‘Other tests’ below.)TNM staging criteria — The tumor, node, metastasis (TNM) staging system of the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) for esophageal cancer is used universally. In the most recent (2017, eighth edition) revision [11,16], tumors involving the EGj with the tumor epicenter no more than 2 cm into the proximal stomach are staged as esophageal cancer. In contrast, EG) tumors with their epicenter located more than 2 cm into the proximal stomach are staged as stomach cancers, as are all cardia cancers not involving the EG), even if they are within 2 cm of the EG). Thus, regardless of histology, all esophageal tumors arising in the cervical, thoracic, or abdominal esophagus and those involving the EG) that have an epicenter within 2 cm of the EG)(__ table 3) share the same criteria for T, N, and M stage designation (table 2). However, there are separate stage groupings for SCC and adenocarcinoma regardless of site. Pathologic staging is indicated by a p designation, and pathologic staging after preoperative therapy is indicated by a yp prefix. Histology-specific stage groupings, initially introduced in 2010, were based on an analysis of worldwide data from 4627 patients with cancer of the esophagus or EGJ who underwent surgery alone. Among patients with node-negative tumors, prognosis was dependent on not only T stage but also on histology and grade of differentiation, and for SCs, tumor location [17]. Subsequently, investigators used updated data from the Worldwide Esophageal Cancer Collaboration to develop the following figures to illustrate risk-adjusted survival according to clinical, pathologic, and posttreatment pathologic stage for adenocarcinomas( figure 2) and SCCs(_ figure 3) [18-23]. Regional lymph nodes — Prior to 2010, the specific lymph node groups that were considered regional for esophageal cancer varied according to the anatomic compartment and location within the esophagus. Data suggesting the prognostic importance of the number of involved lymph nodes rather than the location (particularly in the surgical specimen after chemoradiotherapy [24-32]) led to a change in the N stage classification in the 2010 (and subsequent 2017) revision of the AJCC/UICC staging system, with an emphasis on the number of involved nodes rather than location. Regional lymph nodes for all locations in the esophagus extend from periesophageal lymph nodes to celiac nodes and are illustrated in the figure( figure 4). Locoregional staging EUS — EUS uses a high-frequency ultrasound transducer to provide detailed images of esophageal masses and their relationship with the five-layered structure of the esophageal wall. (See "Endoscopic ultrasound: Examination of the upper gastrointestinal tract".) EUS is the most accurate technique for locoregional staging of invasive esophageal cancer.T stage — The sensitivity and specificity rates of EUS for the correct evaluation of T stage are 81 to 92, and 94 to 97 percent, respectively; in general, EUS performs better with advanced (eg, T4) than with early (ie, T1) disease [33]. Briefly: * If the EUS identifies only mucosal (T1a) disease, endoscopic mucosal resection (EMR) is usually the next step to endoscopic resection of the tumor and precisely define the depth of invasion, The pathology result from the EMR or endoscopic submucosal dissection (particularly the presence or absence of lymphovascular invasion) is used to guide therapeutic decisions. (See "Management of superficial esophageal cancer" and “Endoscopic ultrasound in esophageal cancer", section on 'EUS for T staging of superficial tumors'.) * By EUS, T2, T3, and T4 tumors appear as strictures, ulcerations, or exophytic masses (picture 2and picture 3). 72 tumors involve the muscularis propria but do not have transmural invasion through the esophageal wall. By EUS, they appear as. irregular hypoechoic masses involving the esophageal wall, leaving the muscularis intact, as evidenced by a smooth contour of the mass and muscularis propria. T3 and T4 tumors are both intra- and extraesophageal. Masses that extend into the adventitia are stage T3. T4 masses have invaded through the muscularis propria and adventitia to involve locoregional structures such as pericardium, atrium aorta, vena cava, bronchus, diaphragm, peritoneum, or pleura. The finding of an irregular outer border with invasion through the wall of the esophagus may or may not indicate local unresectability. In the eighth edition TNM classification (__ table 2), tumors classified as T4 are divided into those that are potentially resectable (T4a: tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum) and those that are categorically unresectable (T4b: invasion of other adjacent structures, such as the aorta, vertebral body, or airway). (See “Endoscopic ultrasound in esophageal cancer”, section on 'EUS for staging locally advanced tumors’ and "Endoscopic ultrasound in esophageal cancer", section on ‘Accuracy of EUS for determining unresectability’.) * A caveat for EUS staging of esophageal wall penetration (T staging) is that the instrument cannot traverse a tumor-induced stenosis (which occurs in approximately 30 percent of cases). In these settings, EUS may under-stage the tumor because the entire lesion and the celiac axis as well as liver are not seen. It is controversial as to whether to dilate the esophagus for the purpose of a staging examination, since perforations may occur. This subject is discussed in detail elsewhere. (See "Endoscopic ultrasound in esophageal cancer’, section on 'EUS for staging locally advanced tumors'.)Regional nodes — EUS achieves nodal staging of esophageal cancer by ultrasound image characteristics and FNA or FNB tissue acquisition: * Endosonographic criteria that are suggestive of malignant involvement of the visible lymph nodes include width >10 mm, round shape, smooth border, and echo-poor pattern( table4and image 1). Of these, echo-poor pattern and width >10 mm are the most specific for malignancy. When all four features are present, there is an 80 to 100 percent chance of metastatic involvement. However, only 25 percent of malignant nodes will have all of these features. These results demonstrate the limitations of EUS criteria for use in preoperative lymph node staging. (See "Endoscopic ultrasound in esophageal cancer", section on ‘EUS for preoperative lymph node staging’.) * EUS-guided FNA or FNB may improve the accuracy of N staging by providing cytologic confirmation of metastatic disease from accessible nodes, as long as the primary tumor is not in the pathway of the needle. Sensitivity, specificity, and accuracy of EUS- guided FNA for locoregional lymph nodes are all over 85 percent when surgical resection specimen or cytology results are considered the gold standard. (See “Endoscopic ultrasound in esophageal cancer", section on ‘Endoscopic ultrasound- guided fine-needle aspiration biopsy’,) The endoscopic finding of a malignant node in the celiac area remote from the primary tumor (ie, for SCCs or for lesions in the upper or middle thoracic esophagus ( _ figure 1)) was previously an indicator of unresectability and was staged as M1a metastatic disease. However, celiac nodal metastases are scored as regional nodal disease in the newest 2017 TNM revision (__ table 2) regardless of the primary tumor location or histology [11,34]. Nevertheless, prognosis is poor in such cases, even if the primary tumor is located in the distal esophagus or EG] [35]. (See ‘Regional lymph nodes’ above and ‘TNM staging criteria’ above.) Bronchoscopy and laryngoscopy — Preoperative bronchoscopy with biopsy and brush cytology is advocated by some (including the National Cooperative Cancer Network [NCCN]) as the last investigation in the staging workup for patients with locally advanced, nonmetastatic tumors located at or above the carina (ie, upper esophageal and cervical SCCs) [5]. In a study of 116 consecutive patients with potentially operable upper or cervical esophageal carcinoma, bronchoscopy was superior to CT and excluded 10 percent of patients from surgery because of airway invasion [36]. For cervical SCCs, which are often diagnosed by ear, nose and throat (ENT) clinicians, flexible laryngoscopy is used to assess local disease extent and to detect a synchronous malignancy of the head and neck. (See "Overview of the diagnosis and staging of head and neck cancer", section on ‘Incidence of second and multiple primaries! and "Management of locallyadvanced, unresectable and inoperable esophageal cancer", section on 'Cervical esophageal tumors'.) Evaluation for distant metastases — The most common sites of distant metastases in patients with esophageal cancer are the liver, lungs, bones, and adrenal glands [9]. Adenocarcinomas most frequently metastasize to intraabdominal sites (liver, peritoneum), while metastases from SCCs are typically intrathoracic, (See ‘Regional lymph nodes' above.) M staging is carried out with cross-sectional imaging (contrast-enhanced CT, PET/CT scanning), EUS, and for selected patients, diagnostic laparoscopy. EUS — EUS can visualize liver metastases of <1 cm and malignant ascites. EUS-guided FNA or FNB can provide a tissue diagnosis for liver metastases and FNA may be performed to sample malignant ascites. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract", section on ‘Other lesions'.) CT, PET, and integrated PET/CT — FDG-PET and integrated PET/CT scans are useful to detect occult metastatic disease in patients who are otherwise believed to be surgical candidates after routine staging with conventional contrast-enhanced helical CT. Integrated PET/CT imaging is increasingly favored over PET alone due to better spatial resolution. It involves performance of both PET and CT sequentially during a single visit on a hybrid PET/CT scanner. However, the CT component of integrated PET/CT imaging is performed in most institutions without the use of IV contrast, which compromises the detection of small metastases both within and outside the liver. In the absence of IV contrast, an integrated PET/CT cannot substitute for a dedicated IV-contrast-enhanced CT. At some institutions, PET/CT is carried out with IV contrast. This may replace the need for a separate contrast- enhanced CT, but this practice is not widespread. While relatively inexpensive, contrast-enhanced (oral plus IV) helical CT has a limited ability to identify locally advanced (T4( _ table 2)) disease and subclinical distant metastatic disease, particularly in the peritoneal cavity [37,38]. FDG-PET is more sensitive than contrast-enhanced CT or EUS for the detection of distant metastases [37,39-44]. The addition of PET to the preoperative assessment alters management in 5 to 20 percent of cases, mainly by detecting occult metastases (ie, upstaging) that reduces the number of patients who undergo needless surgery [9,39 42,45,46]. The improved sensitivity of PET for the detection of metastatic disease makes it potentially the most cost-effective method of identifying patients with occult metastases for whom curative therapy should not be pursued [38,45,47,48] A major drawback of PET for the evaluation of the primary site and nodal metastases is its poor spatial resolution that makes it difficult to localize the anatomic location of the FDGuptake. This limitation is significantly reduced by the use of integrated PET/CT imaging, a technique in which both PET and CT are performed sequentially during a single visit on a hybrid PET/CT scanner. The PET and CT images are then co-registered using fusion software, enabling the physiologic data obtained on PET to be localized according to the anatomic CT images (_ image 2). Limited data suggest a greater accuracy of integrated PET/CT over PET alone in patients with cancer, including esophageal cancer [49,50], and most institutions are now performing integrated PET/CT rather than PET alone because of the better spatial resolution. At most institutions, the CT component of integrated PET/CT imaging is performed without the use of IV contrast material or in partial/complete expiration, precluding the optimal detection of small lung and liver metastases. Increasingly, PET/CT is carried out with IV contrast, but this practice is not widespread [51]. Measurement of the standardized uptake value (SUV), which reflects the metabolic activity of the tumor, may also be a prognostic factor. In a meta-analysis of seven studies that evaluated the impact of the SUV on overall survival, high SUV predicted worse survival [52] However, in a large retrospective series that was not included in the meta-analysis, an initially high SUV did not correlate with worse survival [53]. In fact, the results suggested a better response to preoperative chemoradiotherapy in the high SUV group. The value of FDG-PET as a predictive marker of response to neoadjuvant therapy remains uncertain, however [54] Suspicious PET findings should be confirmed with biopsy before excluding a patient from surgical consideration, given the high rate of false-positive findings [55]. As with contrast-enhanced CT scanning alone, PET/CT is of limited value for staging the extent of locoregional tumor, particularly nodal status [37]. This may be due, at least in part, to high FDG uptake in the primary esophageal malignancy, which obscures increased FDG uptake in the regional nodes, and/or low sensitivity for small involved lymph nodes. Furthermore, PET/CT is not consistently able to differentiate the depth of primary tumor invasion. EUS is more accurate than either PET/CT or contrast-enhanced CT alone [56], and it is the locoregional tumor staging modality of choice. (See ‘EUS’ above.) PET restaging after induction therapy — Integrated PET/CT may be also be useful for restaging after preoperative therapy. Limited experience suggests that whole-body PET/CT imaging detects distant metastases in approximately 8 percent of patients following induction chemoradiotherapy with or without induction chemotherapy [57]. In many of these cases, the metastases were located in sites (eq, skeletal muscle, subcutaneous soft tissue, brain, thyroid) that are not imaged well by conventional radiographic staging techniques. Some clinicians order a post-induction-therapy PET/CT approximately four weeks after the completion of induction therapy. This is a method to assess for distant metastatic disease and potentially prevent unneeded surgery, an approach that is endorsed in the consensus-based NCCN guidelines [5]. (See "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas", section on 'PET-directed therapy’,) In addition to detecting otherwise occult metastatic disease, post-induction-therapy FDG-PET provides information on metabolic response in the primary tumor that may be clinically useful in the selection of subsequent therapy: * Early data from retrospective series suggest that post-chemoradiotherapy FDG-PET scanning may serve to identify those patients for whom surgery might be avoided. * Other data suggest that responses observed on PET scans during induction chemotherapy have significant predictive and prognostic benefit [58]. These data are discussed in detail elsewhere. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus", section on ‘Utility of postinduction therapy PET scans’ and "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas", section on 'PET-directed therapy’.) Laparoscopy and thoracoscopy — The need for diagnostic laparoscopy for patients who appear to have potentially resectable esophageal or EG} carcinomas is controversial, and there is no consensus on this issue from expert groups. We reserve diagnostic laparoscopy for patients who, after conventional pretreatment staging studies, appear to have potentially resectable, clinical T3 or T4( table 2), Siewert II to III (ie, located between 1 cm proximal and 5 cm distal to the anatomical squamocolumnar junction or Z-line(__ figure 5)) adenocarcinomas of the EG], or if there is suspicion for intraperitoneal metastatic disease that cannot otherwise be confirmed. We do not perform thoracoscopic staging in patients who have access to PET/CT. In order to limit aggressive treatment to patients with locally advanced disease, diagnostic laparoscopy is sometimes performed to detect occult intraperitoneal metastases in patients with distal esophageal and EG} adenocarcinomas [59-61]. Intraperitoneal metastases are notoriously difficult to diagnose noninvasively by either CT or PET. Laparoscopic (and thoracoscopic) staging procedures have also been examined for their potential to more accurately stage regional lymph nodes (particularly celiac and intrathoracic) as compared with EUS [62-64]. As an example, in a multi-institutional study conducted by the Cancer and Leukemia Group B (CALGB), noninvasive imaging (CT, magnetic resonance imaging [MRI], and EUS) incorrectly staged (either false-negative lymph nodes orfalse-positive metastatic disease) 50, 40, and 30 percent of patients, respectively, as assessed by thoracoscopic or laparoscopic staging [62]. An important limitation of this study was that EUS was performed without FNA, thus limiting the accuracy of noninvasive imaging. Although the available data support the view that invasive staging is more accurate than EUS or CT alone; however, no study has compared this approach with EUS plus integrated PET/CT scanning, which is superior to conventional imaging modalities for detecting distant metastases. The need for diagnostic laparoscopy for patients who appear to have potentially resectable distal esophageal and EG) adenocarcinomas is controversial, and there is no consensus on this issue from expert groups; none of these groups provides guidelines for the use of diagnostic thoracoscopy: * Consensus-based guidelines from the NCCN consider diagnostic laparoscopy to be “optional! for patients with EG) tumors and no evidence of metastatic disease [5]. * Guidelines from the European Society for Medical Oncology (ESMO) advocate diagnostic laparoscopy for all patients with locally advanced (T3/T4) adenocarcinomas of the EG infiltrating the gastric cardia [4]. * The — Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) states that patients who are considered to be candidates for curative resection (early stage esophageal cancer with no evidence of distant or lymph node metastases on high- quality preoperative imaging) may benefit from staging laparoscopy (grade B). We reserve diagnostic laparoscopy for patients who, after conventional pretreatment staging studies, appear to have potentially resectable, clinical T3 or T4( table 2), Siewert II to Ill (ie, located between 1 cm proximal and 5 cm distal to the anatomical squamocolumnar junction or Z-line( figure 5)) adenocarcinomas of the EG), or if there is suspicion for intraperitoneal metastatic disease that cannot otherwise be confirmed. The surgical approach, diagnostic accuracy, and yield of diagnostic laparoscopy for esophageal cancer are discussed in greater detail elsewhere. (See "Diagnostic staging laparoscopy for digestive system cancers", section on 'Esophagogastric junction and gastric cancer',) Another approach, laparoscopic ultrasound, may provide the benefits of both locoregional and intraperitoneal staging [65-67]. In a study of 26 patients with gastric or esophageal cancers, T and N staging with laparoscopic ultrasound were comparable with results from EUS [65]. The accuracy of M staging with laparoscopic ultrasound was better than with laparoscopy alone or CT (89 versus 44 and 64 percent, respectively). No randomized trials or large reviews have been performed to determine if laparoscopic ultrasound offers a significant advantage over laparoscopy alone for detecting unresectable disease inesophageal cancer. (See "Diagnostic staging laparoscopy for digestive system cancers", section on ‘Laparoscopic ultrasound’,) Other tests — Consensus-based guidelines for staging, such as those published by the NCCN [5] and ESMO [4], do not recommend routine pretreatment brain imaging for patients with esophageal or EG) cancers. Brain metastases have been considered uncommon in patients with esophageal cancer (published incidence <5 percent [68,69]). However, in more contemporary esophageal cancer cohorts with higher percentages of adenocarcinoma, the incidence of brain metastases may be higher (13 percent in one series [70]). Despite these data, however, routine brain imaging is not considered cost effective or necessary as part of the routine staging evaluation unless symptoms or signs raise suspicion for brain metastases. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Esophageal cancer" INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5" to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10" to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) * Basics topics (see "Patient education: Upper endoscopy (The Basics)" and "Patient education: Esophageal cancer (The Basics)") * Beyond the Basics topics (see "Patient education: Upper endoscopy (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS* Clinical presentation - Patients with advanced thoracic or cervical esophageal carcinoma usually present with progressive dysphagia and weight loss. (See ‘Clinical manifestations! above.) * Establishing the diagnosis - The diagnosis of esophageal or esophagogastric junction (EG)) cancer is usually established by endoscopic biopsy. Early cancers may appear as superficial plaques, nodules, or ulcerations (_ picture 1), Advanced lesions may appear as strictures (picture 2), ulcerated masses (__ picture 3), circumferential masses (picture 4), or large ulcerations. The endoscopic appearance of a large mucosal mass is frequently diagnostic of esophageal cancer, Biopsies confirm the diagnosis in more than 90 percent of cases. (See 'Diagnosis' above.) * Staging and pretreatment assessment + The tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) for esophageal cancer is used universally ( table 2). In the most recent (eighth edition, 2017) version, tumors involving the EG} with the tumor epicenter no more than 2 cm into the proximal stomach are staged as esophageal cancers. In contrast, EG) tumors with their epicenter located more than 2.cm into the proximal stomach are staged as stomach cancers, as are all cardia cancers not involving the EG), even if they are within 2 cm of the EG)(__ table 3). (See 'TNM staging criteria’ above.) + Once the diagnosis of esophageal cancer is established, selection of the appropriate therapeutic approach for an esophageal cancer is highly dependent on the accuracy of pretreatment assessment. The pretreatment staging assessment includes an evaluation for both locoregional disease extent and distant metastases: Endoscopic ultrasound (EUS) is the preferred method for locoregional staging. Preoperative bronchoscopy with biopsy and brush cytology is indicated for patients with locally advanced, nonmetastatic tumors that are located at or above the level of the carina, and flexible laryngoscopy is generally recommended for cervical squamous cell carcinomas (SCCs). (See 'Locoregional staging’ above.) All patients should undergo contrast-enhanced CT of the neck, chest, and abdomen to evaluate for distant metastases. For selected patients, whole-body integrated fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, EUS, and/or diagnostic laparoscopy may be indicated: - FDG-PET/CT is more sensitive than contrast-enhanced CT for detecting metastases and are now widely used to detect occult metastases if metastasesare not seen on the initial staging CT scans. At some institutions, PET/CT is carried out with intravenous contrast, and this might effectively replace the need for a separate contrast-enhanced CT, but this practice is not widespread. Suspicious PET/CT findings should be histologically confirmed before excluding a patient from surgical consideration. (See ‘CT, PET, and integrated PET/CT’ above.) - EUS-guided fine-needle aspiration (FNA) or fine needle biopsy can provide a tissue diagnosis for suspected liver metastases and FNA may be done to diagnose malignant ascites. - The role of staging laparoscopy is controversial. We reserve diagnostic laparoscopy for patients with potentially resectable clinical T3/T4 (table 2) adenocarcinomas arising within the abdominal portion of the esophagus (__ table 3) or if there is suspicion for intraperitoneal metastatic disease that cannot otherwise be confirmed. We do not utilize thoracoscopy for patients who have access to EUS and integrated PET/CT. (See 'Laparoscopy and thoracoscopy’ above.) - Routine brain imaging is not indicated unless symptoms or signs raise suspicion for brain metastases. (See ‘Other tests’ above.) Use of UpToDate is subject to the Terms of Use. Topic 2502 Version 46.0GRAPHICS Epidemiology of esophageal cancer in the United States, 2012 Squamous cell Adenocarcinoma Incidence rate, per 100,000 population 12 28 Male-to-female ratio 25:1 6.5:1 White-to-Black ratio 14 41 Most common locations Middle esophagus Distal esophagus Major risk factors Smoking, alcohol Barrett's esophagus Data from: Thrift AP. The epidemic of oesophageal carcinoma: Where are we now? Cancer Epidemiol 2016; 41:88. Graphic 78167 Version 4.0Esophagus and esophagogastric junction cancers TNM staging AJCC UICC 8th edition Primary tumor (T), squamous cell carcinoma and adenocarcinoma Tcategory criteria 1K ‘Tumor cannot be assessed To No evidence of primary tumor Tis High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane 1 Tumor invades the lamina propria, muscularis mucosae, or submucosa Ta Tumor invades the lamina propria or muscularis mucosae Tib ‘Tumor invades the submucosa 12 Tumor invades the muscularis propria 3 Tumor invades adventitia 14 Tumor invades adjacent structures Ta ‘Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum Tab ‘Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway Regional lymph nodes (N), squamous cell carcinoma and adenocarcinoma Neategory Neriteria NX Regional lymph nodes cannot be assessed No No regional lymph node metastasis Ni Metastases in 1 or 2 regional lymph nodes N2 Metastases in 3 to 6 regional lymph nodes NB Metastases in 7 or more regional lymph nodes Distant metastasis (M), squamous cell carcinoma and adenocarcinoma Mcategory Mcriteria mo No distant metastasis, Mt Distant metastasis Histologic grade (G), squamous cell carcinoma and adenocarcinoma G G definition x Grade cannot be assessed Gi Well differentiated G2 Moderately differentiatedGa Poorly differentiated, undifferentiated Location, squamous cell carcinoma Location plays a role in the stage grouping of esophageal squamous cancers. Location Location criteria category x Location unknown Upper Cervical esophagus to lower border of azygos vein Middle Lower border of azygos vein to lower border of inferior pulmonary vein Lower Lower border of inferior pulmonary vein to stomach, including gastroesophageal junction NOTE: Location is defined by the position of the epicenter of the tumor in the esophagus. Prognostic stage groups, squamous cell carcinoma Clinical (cTNM) WhencT = AndcNis... And Mis... Then the stage group is... is... Tis No Mo 0 a No-1 Mo I T2 No-1 Mo a 3 No Mo I 3 M Mo m 13 NZ Mo m1 14 NO-2 Mo IVA AnyT NB Mo IVA AnyT | AnyN M1 vB Pathological (pTNM) When pT And pNis.. And M And location Then the stage group is. Tis No Mo N/A Any 0 Ta No Mo a Any IA Tia No Mo G23 Any IB Tia No mo of Any IA Tb No Mo G13 Any 1B Tib No Mo ox Any 1B 2 No Mo a Any IB2 No Mo G23 Any 1A T2 No Mo x Any IIA 3 No Mo Any Lower 1A 3 No Mo a Upper/middle IIA B No Mo G23 Upper/middle 118 3 No Mo ox Any 1B 3 No Mo Any Location x TB a M Mo Any Any 1B af N2 Mo Any Any 1A 2 M1 Mo Any Any MIA 12 N2 Mo Any Any mB 3 N12 Mo Any Any mB Taa NO-1 Mo Any Any mB Taa N2 Mo Any Any IVA Tab No-2 Mo Any Any IVA AnyT NB Mo Any Any IVA AnyT | AnyN M1 Any Any ve Post-neoadjuvant therapy (ypTNM) When ypT And ypN And M Then the stage group T0-2 = NO Mo 1 3 No Mo I T0200 Nt Mo 1A B M Mo 118 103 NZ mo 1B Taa No mo 1B Taa N12 Mo IVA Taa NX Mo IVA Tab NOo-2 Mo IVA AnyT NB Mo VA AnyT | AnyN M1 vB Prognostic stage groups, adenocarcinoma Clinical (cTNM)WhencT AndcNis... | And Mis. Then the stage group is. Tis No Mo 0 1 No Mo I 1 MI Mo TA 2 No Mo 118 12 M Mo ml 3 No-1 Mo ml Taa No-1 Mo m Ti4a—N2 Mo IVA Tab No-2 Mo IVA AnyT NB Mo IVA AnyT | AnyN M1 1vB Pathological (pTNM) When pT AndpNis.. And Mis. And Gis. Then the stage group is. Tis No Mo N/A 0 Ta No Mo a IA Ta No Mo ox IA Tia No Mo G2 1B Tib No Mo G12 1B Tb No Mo Gx 1B 1 No Mo @ Ic T2 No Mo G2 Ic 2 No Mo GB IA 2 No Mo ox IIA 1 Mt Mo Any mB 3 NO Mo Any uB 1 N2 Mo Any mA 12 MI Mo Any 1A 2 N2 Mo Any 1B 3 N12 Mo ‘Any 1B Taa NO-1 Mo Any mB Ta N2 mo Any IVATab NO-2 Mo Any IVA AnyT NB Mo Any VA AnyT | AnyN M1 Any vB Post-neoadjuvant therapy (ypTNM) When ypT And yp! And Mis... Then the stage group i is. 10-2 = NO Mo 1 3 No Mo ri T0209 Nt Mo MA 3 M Mo mB T03 NZ Mo m8 Ta No Mo mB Téa N12 Mo VA Taa NX Mo IVA Tab No-2 Mo IVA AnyT NB mo IVA AnyT | AnyN M1 VB ‘TNM: tumor, node, metastasis; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control; N/A: not applicable, Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Graphic 111221 Version 9.0,Anatomy of esophageal cancer primary site by ICD-O-3 topography codes Esophageal location Anatomic Compartment name ICD-0-3 Icb- 03 Cervical 15.0 153 Name Upper Anatomic boundaries Hypopharynx to sternal notch Typical esophagectomy (cm) 15 to <20 Thoracic 151 15.3 15.4 15.8 Upper Middle Lower Sternal notch to azygos vein Lower border of azygos vein to inferior pulmonary vein Lower border of inferior pulmonary vein to esophagogastric junction 20 to <25 25 to <30 30 to <40 Abdominal C15.2 C155 16.0 Lower Esophagogastri junction/cardia Esophagogastric junction to 2. cm. below esophagogastric junction Esophagogastric junction to 2m below esophagogastric junction ICD-0-3: International Classification of Diseases for Oncology, 3rd Edition. 40 to 45 40 to 45 Used with permission of the American College of Surgeons, Chicago, lilinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Corrected at 4th printing, 2018. Graphic 111351 Version 7.0,AJCC 8th edition regions of the esophagus Lenoth in centimeters o7 Upper central 10 -| Upper exophagea! as} - Thorade sternal 20-| - Middle thoracic esophagus 30 | -- 35-| puimecsny Lower thoracic esophagus/ esophagogastric junction (EG) a0} - aat- Anatomy of esophageal cancer primary site, including typical endoscopic measurements of each region measured from the incisors. Exact measurements depend on body size and height. For tumors of the EG) and cardia, location of cancer primary site (ie, esophagus, stomach) is defined by cancer epicenter. AJCC: American Joint Committee on Cancer; v: vein. Modified from: Rice TW, Kelsen 0, Blackstone EH, et a. Esophagus and esophagogastric junction. In: AJCC Cancer Staging Manual, 8h Ed, Amin MB (ed), Springer Science+Business Media, LLC, New York, 2017.Graphic 111260 Version 8.0Early, superficial esophageal cancer Early, superficial esophageal cancer seen on endoscopy. Courtesy of William Brugge, MD. Graphic $5091 Version 1.0,Malignant stricture of the esophagus ‘The tumor mass is not readily evident because it is predominantly infiltrating the esophageal wall. Courtesy of william Brugge, MD. Graphic 55542 Version 1.0Ulcerating malignant esophageal mass in distal esophagus Ulcerating malignant esophageal mass in distal esophagus seen on endoscopy. Courtesy of william Brugge, MD. Graphic 78958 Version 1.0Circumferential ulcerated esophageal cancer Circumferential ulcerated esophageal cancer seen on endoscopy. Courtesy of William Brugge, MD. Graphic 67522 Version 1.0Risk-adjusted survival after treatment decision for clinically staged (c), path (p), and posttreatment pathologically staged (yp) adenocarcinoma of the esi esophagogastric junction Bl 10 100 = 0 a) z £ 3 3 zo z 6 z = z 3 - ——se_| 3 * : : : 3 = an 3 = a IVA =z 2 ° 10 Years Years é = 2 3 B 3 (A) Risk-adjusted survival after treatment decision for clinically staged (c) adenocarcinoma of the esopha WECC data, (8) Risk-adjusted survival after treatment decision for pathologically staged (p) adenocarcinoma of the e on WECC data. () Risk-adjusted survival after treatment decision for postneoadjuvant pathologically staged (yp) adeno esophagus based on WECC data.WECC: Worldwide Esophageal Cancer Collaboration. Used with permission of the American College of Surgeons, Chicago, Ilinols. The original source for this information is the AJCC ( Eighth Edition (2017) published by Springer International Publishing. Graphic 111241 Version 6.0Risk-adjusted survival after treatment decision for clinically staged (c), path staged (p), and posttreatment pathologically staged (yp) esophageal squam cancer Bl 100 100 a ey 80 8 cu aA ve a Risk-adjusted survi Risk-adjusted survi & 40-| 20-4 20 a T T T T T a ° 2 4 6 8 10 Years 00 so z 60 Risk-adjusted survi & L zo | vane 0 of 4) 6 Bl Years (A) Risk-adjusted survival after treatment decision for clinically staged (c) squamous cell carcinoma of thi esophagus based on Worldwide Esophageal Cancer Collaboration (WECC) data, (8) Risk-adjusted survival after treatment decision for pathologically staged (p) squamous cell carcinoma esophagus based on WECC data (© Risk-adjusted survival after treatment decision for postneoadjuvant pathologically staged (yp) squarr carcinoma of the esophagus based on WECC data.Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information Is the AJCC ¢ Staging Manual, Eighth Edition (2017) published by Springer International Publishing. Graphic 111244 Version 6.0Regional lymph node stations for staging esophageal cancer @ (A-C) Lymph node maps for esophageal cancer. Regional lymph node stations for staging esophageal ca left (A), right (B), and anterior (C) 4R: Right lower cervical paratracheal nodes, between the supraclavicular paratracheal space and apex o 4L: Left lower cervical paratracheal nodes, between the supraclavicular paratracheal space and apex of t 2R: Right upper paratracheal nodes, between the intersection of the caudal margin of the brachiocepha with the trachea and the apex of the lung. 2L: Left upper paratracheal nodes, between the top of the ao! and the apex of the lung. 4R: Right lower paratracheal nodes, between the intersection of the caudal mz the brachiocephalic artery with the trachea and cephalic border of the azygos vein. 4L: Left lower paratri nodes, between the top of the aortic arch and the carina. 7: Subcarinal nodes, caudal to the carina of the 8U: Upper thoracic paraesophageal lymph nodes, from the apex of the lung to the tracheal bifurcation. t Middle thoracic paraesophageal lymph nodes, from the tracheal bifurcation to the caudal margin of the pulmonary vein. 8Lo: Lower thoracic paraesophageal lymph nodes, from the caudal margin of the inferi pulmonary vein to the EG). 9R: Pulmonary ligament nodes, within the right inferior pulmonary ligament. Pulmonary ligament nodes, within the left inferior pulmonary ligament. 15: Diaphragmatic nodes, lying dome of the diaphragm and adjacent to or behind its crura. 16: Paracardial nodes, immediately adjacent gastroesophageal junction. 17: Left gastric nodes, along the course of the left gastric artery. 18: Commo nodes, immediately on the proximal common hepatic artery. 19: Splenic nodes, immediately on the pro» splenic artery. 20: Celiac nodes, at the base of the celiac artery. EG): esophagogastric junction. Used with permission of the American College of Surgeons, Chicago, Ilinols. The original source for this information Is the AJCC ¢ Staging Manuol, Eighth Edition (2017) published by Springer International Publishing.Graphic 111319 Version 8.0Endoscopic ultrasound (EUS) criteria for assessment of lymph nodes Benign Malignant Size (width) <10 mm >10mm Shape Elongated Round Border Irregular Smooth Echogenicity Echorich Echopoor Data from: Catalano, MF; Sivak, MVJr, Rice, T, et al, Gastrointest Endosc 1994; 40:442 and Bhutani, MS, Hawes, RH, Hoffman, Bj, Gastrointest Endosc 1997; 45:474. Graphic 66591 Version 5.0Benign and malignant periesophageal lymph nodes Endoscopic ultrasound images showing a benign (left panel) and malignant (right panel) appearing periesophageal lymph node in a patient with histologically proven esophageal adenocarcinoma, Characteristics of the benign lymph node are its mixed echogenicity, irregular border, elongated shape, and <10 mm width. In contrast, the malignant lymph node is echopoor, has a smooth border, has a round shape, and is >10 mm in width. Courtesy of Enrique Vazquez-Sequeiros, MD, and Maurits J Wiersema, MD. Graphic 57813 Version 3.0Imaging metastatic esophageal carcinoma with CT and PET CT An axial CT image through the mid chest shows a large esophageal mass (arrow). Image 8 is a PET CT ar shows a hypermetabolic mass (arrow). Image C is an axial CT image through the thoracic inlet and show large lymph nodes alongside the brachiocephalic arteries (arrows). Image D is a PET CT showing hypermetabolic activity in the nodes indicating metastatic disease. CT: computed tomography; PET: positron emission tomography. Graphic 97798 Version 1.0Anatomic landmarks for the diagnosis of Barrett's esophagus Zeline (SCI) Columner-tined esophagus Gastroesophageal “junction (GET) ‘The squamocolumnar junction (SCJ or Z-line) is the visible line formed by the juxtaposition of squamous and columnar epithelia, The gastroesophageal junction (GE}) is the imaginary line at which the esophagus ends and the stomach begins. The GEJ corresponds to the most proximal extent of the gastric folds. When the SC] is located proximal to the GE], there is a columnar- lined segment of esophagus. Modified from: Spechier S). The role of gastric carditis in metoplasia and neoplasia ot the gastroesophageal junction. Gastroenterology 1999; 117:218. Graphic 76055 Version 8.0