Since its advent in the 1980s endoscopic ultrasound (EUS) has played an important role in the diagnosis, staging, and therapeutic management of various gastrointestinal malignancies. EUS has emerged as a vital tool in the evaluation of esophageal cancer as it provides a detailed view of the layers of the esophageal wall and surrounding tissues. This permits determination of tumor invasion depth and local lymph node metastases. It is the most sensitive and specific method available for locoregional staging of esophageal cancer. The information obtained via EUS is vital in determining the appropriate diagnosis, prognosis, and treatment options. Thus, this article aims to present a review of the accuracy and utilization of EUS in the staging of esophageal cancer.

Endoscopic ultrasound (EUS) is considered a gold standard in the initial staging of esophageal cancer. There is an ongoing debate whether EUS is useful for tumor staging after neoadjuvant chemotherapy (NAC).

Ninety-five patients with esophageal cancer were retrospectively analyzed. In 45 patients, EUS was performed prior to and after NAC, while 50 patients had no induction therapy. Histological correlation through surgery was available. uT/uN classifications were compared to pT/pN stages. Statistical analysis included calculation of sensitivity, specificity, and accuracy rates. Agreement between endosonography and T staging was assessed with Cohen's kappa statistics.

For those patients with prior NAC, overall accuracy of yuT and yuN classification was 29 and 62%, respectively. Sensitivity, specificity, and accuracy rates for local tumor extension after NAC were as follows (%): T1: -/97/84, T2: 13/76/53, T3:86/29/46, T4:20/100/91, T1/2: 27/83/56, T3/4: 89/31/56. Cohen's kappa indicated poor agreement (kappa = 0.129) between yuT classification and ypT stage. Relative to positive lymph node detection, sensitivity and specificity were 100 and 6%, respectively (kappa = 0.06). T stage was overstaged in 23 (51%) and understaged in seven (16%) patients.

EUS is an unreliable tool for staging esophageal cancer after NAC. Overstaging of the T stage is common after NAC.

Despite recent advances in imaging techniques, adequate classification of esophageal lesions is still challenging. Accurate staging of tumors of the esophagus is a precondition for targeted therapy. In this retrospective, multicenter study, we report the role of high-frequency endoscopic ultrasound (EUS) catheter probes in pretherapeutic staging of esophageal neoplasms and thus guiding treatment decisions.

A total of 143 patients (mean age of 63.8 ± 10.7 years) with esophageal carcinoma were recruited from five German centers (Münster, Oldenburg, Hannover, Wiesbaden, and Lüneburg). Tumor type was adenocarcinoma in 112 (78 %) cases and squamous cell carcinoma in 31 (22 %). Tumor localization was as follows: proximal 3, mid esophagus 7, and distal third 133. Histological correlation either through EMR or surgery was available. In all patients, pretherapeutic uT and uN classifications were compared to pT/pN classification obtained from surgically (esophagectomy, n = 93) or endoscopically (EMR, n = 50) resected tissue.

Overall, accuracy of uT classification was 60 % and of uN classification was 74 %. Sensitivity, specificity, and accuracy rates for local tumor extension were as follows (%): T1: 68/97/83; T2: 39/84/75; T3: 72/81/79; T4: 13/97/93; T1/2: 73/81/75; T3/4: 78/82/81. Relating to positive lymph node detection, sensitivity and specificity were 76 and 71 %, respectively.

Miniprobe EUS is an established method for the staging of esophageal tumors. Our large multicenter cohort shows a solid accuracy of miniprobe EUS with respect to differentiating locally advanced from limited cancer and assisting to determine the treatment regimen in the era of neoadjuvant therapy; consequently, 78 % of patients would have been assigned to the adequate therapeutic regimen, whereas 11 % of patients would have been overtreated and 11 % undertreated.

Various studies have demonstrated that 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET), measuring altered tissue glucose metabolism, is a promising non-invasive method for detecting both distant nodal and haematogenous metastases in patients with oesophageal carcinoma (OC) and might thus prevent futile esophagectomy. Moreover, FDG-PET is a promising tool in assessing response to non-surgical treatment, and might therefore be used for an early decision on whether treatment should be stopped or continued.

Review of the recent literature regarding the diagnostic performance of FDG-PET in the preoperative staging of patients with OC and regarding diagnostic accuracy of FDG-PET in assessing response to neoadjuvant therapy in patients with OC compared to conventional techniques (especially computed tomography (CT) and endoscopic ultrasonography (EUS)).

A search of the literature resulted in the inclusion of 16 studies on the diagnostic value of FDG-PET. Sensitivity and specificity for the detection of locoregional metastases were moderate. Sensitivity and specificity were reasonable for distant metastases. The diagnostic accuracy of FDG-PET in assessing response to treatment was similar to the accuracy of EUS, but significantly higher than that of CT.

The staging value of FDG-PET in OC patients is limited in the detection of locoregional metastases; however; its value is higher in the detection of distant lymphatic and haematogenous metastases. Moreover, FDG-PET is a valuable tool for the non-invasive assessment of histopathologic tumour response after neoadjuvant therapy..

Neoadjuvant or adjuvant multimodality therapy in oesophageal cancer is introduced in an effort to improve prognosis. However, in a substantial fraction of patients there is no response to this non-surgical therapy. Non-invasive imaging modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) have been evaluated for assessing patient response to therapy, and these are described in this review. Currently, FDG-PET seems to be the best available tool for neoadjuvant therapy response assessment in oesophageal cancer.

Luminal gastrointestinal (GI) tract cancers are responsible for substantial morbidity and mortality. Since the first pairing of ultrasonography with endoscopy in 1980, technologic advances and the increased availability of trained endosonographers have propelled endoscopic ultrasonography (EUS) to the forefront of luminal GI cancer staging. In this article we discuss the role of EUS for evaluating luminal GI cancers.

Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is the most accurate imaging modality for locoregional staging of esophageal cancer. It remains unclear whether this technology impacts on the outcome of patients with this malignancy. The aim of the present study was to assess the impact of EUS FNA by comparing the clinical outcomes of patients with esophageal cancer before and after the introduction of this staging modality in our institution.

Outcomes of patients with de novo non-metastatic esophageal cancer seen in 1998 without EUS FNA evaluation (non-EUS control group) were compared to patients evaluated in 2000 with EUS FNA (EUS group).

Outcomes of 60 (non-EUS control group) and 107 (EUS group) patients with non-metastatic esophageal cancer were compared. Preoperative neoadjuvant therapy was administered to 35 patients in the EUS group, all of whom had advanced disease. Cox proportional hazards demonstrated EUS FNA to be associated with reduced recurrence risk (hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.43-0.87), P = 0.004, and reduced mortality (HR: 0.66; 95% CI: 0.47-0.90), P = 0.008.

The EUS staging of esophageal cancer leads to appropriate use of preoperative neoadjuvant therapy in patients with advanced disease. Use of EUS is associated with a recurrence-free survival advantage and overall survival advantage in patients, thus supporting its routine use in esophageal cancer staging.

Therapy of esophageal carcinoma is stage dependent. The role of EUS-guided fine-needle aspiration (EUS FNA) in this setting is unclear. The aims of this study were to compare the performance characteristics of CT, EUS, and EUS FNA for preoperative nodal staging of esophageal carcinoma and to measure the impact of each staging test on treatment decisions.

From December 1999 to March 2001, all patients with esophageal carcinoma seen at the Mayo Clinic Rochester were prospectively evaluated with CT, EUS, and EUS FNA. The impact of tumor stage on final therapy was assessed.

A total of 125 patients with esophageal carcinoma were enrolled. EUS FNA was more sensitive (83% vs. 29%; P < 0.001) than CT and more accurate than CT (87% vs. 51%; P < 0.001) or EUS (87% vs. 74%; P = 0.012) for nodal staging. Direct surgical resection was contraindicated in 77% of patients evaluated due to advanced locoregional/metastatic disease. Tumor location, patient age, comorbidities, and tumor stage determined by CT, EUS, and EUS FNA were associated with treatment decisions (P < 0.05). EUS FNA resulting in a higher/worse stage than CT (41 patients) was associated with a greater rate of treatments that were not direct surgeries compared with cases in which the stage was the same or better.

EUS FNA is more accurate for nodal staging and impacts on therapy of patients with esophageal carcinoma. EUS FNA should be included in the preoperative staging algorithm of these patients.

Preoperative identification of lymph node metastases associated with esophageal carcinoma may influence treatment. EUS is the most accurate method for locoregional staging of these tumors. The impact of EUS-guided fine-needle aspiration (EUS-FNA) on lymph node staging in esophageal carcinoma is unclear.

From May 1996 to May 1999, 74 patients with esophageal carcinoma underwent preoperative EUS. After October 1998 EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. The results of EUS with and without FNA were retrospectively reviewed and compared. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Ten of the 74 patients had to be excluded for lack of lymph node stage confirmation. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group).

The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Complications comprised 1 patient who developed self-limited bleeding after dilation that did not preclude completion of the EUS (1%, 95% CI [0%, 7%]).

EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.

Almost 15 years after its introduction endosonography is an important technique in a wide range of gastrointestinal diseases. Two types of dedicated echoendoscopes are commercially available each with their own advantages. Thinner instruments with higher resolutions, that will go through a normal endoscope are currently in development. With these probes differentiation between T1 and T in situ will be possible in the near future. Characterization of 'submucosal' lesions in the upper gastrointestinal tract is a field in which ES is the most reliable technique for determining the origin of these lesions. Also submucosal vessels are easily visualized and ES is acquiring an important role in the investigation of portal hypertension. ES is the most accurate staging technique for oesophageal and gastric carcinoma as well as for gastric lymphoma. T- and N-staging results are superior to CT scanning, although ES is not very reliable in individual lymph nodes. Therefore a lot of effort is put into obtaining cytological samples from lesions outside the gastrointestinal tract. It is now possible to get cytological proof of mediastinal lymph nodes through ES-guided fine needle aspiration biopsy. It seems that low grade malignant gastric lymphomas show a typical picture on ES, which may help in selecting treatment. The future will bring us higher resolution images and three-dimensional reconstruction is already being investigated. This last technique will probably become a standard preoperative investigation in oesophageal carcinoma before the century is over.

Endoscopic ultrasonography (EUS) and computed tomography (CT) should be used as complementary methods for TNM staging of esophageal cancer. EUS is the most accurate modality for staging primary tumor and mediastinal lymph node metastases. CT should be used to detect infiltration of other mediastinal organs and distant metastases. For esophageal cancer staging magnetic resonance imaging (MRI) is not superior to CT. For detection of cervical lymph node metastases percutaneous ultrasonography is appropriate. In patients with advanced distal carcinoma of the esophagus, hepatic and peritoneal metastases and intraabdominal lymph node infiltration should be ruled out by laparoscopy prior to surgery. The results of preoperative staging are relevant if the management of esophageal cancer comprises not only surgery but also endoscopic mucosectomy, primary palliative procedures, and especially neoadjuvant radiochemotherapy. Within therapeutic trials the precise staging prior to treatment is essential for analysis of the results. The value of routine postoperative staging during a follow-up program is yet unproved for esophageal cancer.

Preoperative endoscopic ultrasonography (EUS) was performed in 51 consecutive patients with biopsy-verified esophageal or gastric cancer, to judge resectability. A comparison between preoperative EUS and surgical (and histologic) findings was possible in 39 patients (76%). In 33 of these 39 patients (85%) EUS made a correct preoperative assessment. In three cases misinterpretation was due to metastasis outside the viewing field of the echoendoscope. Although based on preliminary experience, we are convinced that EUS will help us to select patients who will ultimately benefit from surgery. Further prospective studies are necessary to clarify the possible benefits in terms of costs, effects of palliation in selected patients, and long-term survival.

Prognostic factors that may alter the indications for primary surgical resection or that can be influenced by the extent of the procedure were analysed in a homogeneous group of 186 patients with squamous cell carcinoma of the oesophagus. All patients underwent standardized en bloc oesophagectomy and lymph node dissection with prospective documentation of the histopathological findings; follow-up was complete. Multivariate analysis identified the Union Internacional Contra la Cancrum R category (i.e. the presence of residual tumour after resection) as the most important independent prognostic factor (P < 0.001) followed by the ratio of invaded to removed lymph nodes (P < 0.001). These data suggest that only patients in whom R0 resection can be anticipated based on preoperative assessment should undergo primary resection for oesophageal cancer. Extended lymphadenectomy may improve survival in patients with a limited number of invaded mediastinal nodes.

Barrett's esophagus (i.e. columnar epithelial metaplasia in the distal esophagus) is an acquired condition that in most patients results from chronic gastroesophageal reflux. It is a disorder of the white male in the Western world with a prevalence of about 1/400 population. Due to the decreased sensitivity of the columnar epithelium to symptoms, Barrett's esophagus remains undiagnosed in the majority of patients. Gastroesophageal reflux disease in patients with Barrett's esophagus has a more severe character and is more frequently associated with complications as compared with reflux patients without columnar mucosa. This appears to be due to a combination of a mechanically defective lower esophageal sphincter, inefficient esophageal clearance function, and gastric acid hypersecretion. Excessive reflux of alkaline duodenal contents may be responsible for the development of complications (i.e., stricture, ulcer, and dysplasia). Therapy of benign Barrett's esophagus is directed towards treatment of the underlying reflux disease. Barrett's esophagus is associated with a 30- to 125-fold increased risk for adenocarcinoma of the esophagus. The reasons for the dramatic rise in the incidence of esophageal adenocarcinoma, which occurred during the past years, are unknown. High grade dysplasia in a patient with columnar mucosa is an ominous sign for malignant degeneration. Whether an esophagectomy should be performed in patients with high grade dysplasia remains controversial. Complete resection of the tumor and its lymphatic drainage is the procedure of choice in all patients with a resectable carcinoma who are fit for surgery. In patients with tumors located in the distal esophagus, this can be achieved by a transhiatal en-bloc esophagectomy and proximal gastrectomy. Early adenocarcinoma can be cured by this approach. The value of multimodality therapy in patients with advanced tumors needs to be shown in randomized prospective trials.

The value of endoscopy in dysphagia is limited in the diagnosis of motility disorders and small structures, webs, and hiatal hernias. Endoscopy is of special use for the clarification of an organic cause of dysphagia. Intraluminal tumors can be seen and in a high percentage of cases be definitely diagnosed by taking biopsies; a malignant degeneration in Barrett's esophagus is detectable by endoscopy in 89.1% of cases. Gastroesophageal reflux disease can be diagnosed on endoscopy as it leads to an endoscopically visible inflammatory reaction; however, normal findings on endoscopy cannot exclude reflux disease. Endoscopy is the method of choice in the diagnosis of nonreflux esophagitis, especially Candida and viral esophagitis. A further advantage of endoscopy is the fact that a microscopic diagnosis can be obtained and endoscopic treatment can be performed simultaneously. Submucosal or extramural lesions can be missed by endoscopy. Endosonography, the combination of endoscopy and ultrasonography (EUS) yields additional information in diagnosing submucosal and extramural lesions of the esophagus which is missed by other imaging procedures. One of the main advantages of EUS is the detection of small and submucosal lesions. The most important indication is the local staging of esophageal carcinomas; the accuracy of endosonography in determining the depth of infiltration ranges between 79% and 92%. The detection of paraesophageal lymph nodes is successful in 60%-82%, although EUS cannot differentiate benign from malignant lymph nodes. Submucosal tumors can be visualized by endosonography and their size, echopattern, and the layers of origin can be determined with high accuracy. Further indications for EUS are the exclusion of focal lesions in achalasia or peptic strictures.

Staging of esophageal squamous cell carcinoma is a prerequisite to assessing prognosis and deciding on appropriate treatment. Endoscopy provides one means of predicting the extent of tumor growth. Using the classification of the Japanese Society for Esophageal Diseases, which differentiates superficial (type 0) from more advanced stages of esophageal carcinoma, we studied 273 patients with squamous cell cancer of the esophagus. Histopathologic examination of resected specimens (N = 81) or endosonography (N = 128) served to correlate the endoscopically defined categories with the otherwise determined T stages. Not classifiable by endoscopy were 64 patients (23.4%), 42 of whom were pre-treated by means of chemo- or radiation therapy. In the remaining 209 patients, it could be shown that endoscopic assessment was both sensitive (78%) and specific (93%) in predicting the local extent of tumor (overall accuracy, 89%). Detailed analysis showed good sensitivity for stage 0 (83%) which corresponds to T-1 carcinoma and for stages 3 and 4 (82% and 83%) which represent T-3 and T-4 tumors. Only in endoscopic stages 1 and 2 was the concordance with the T stage (T-2) weaker, with a sensitivity of 52%. We conclude that prediction of local tumor extent by endoscopic observation is a generally reliable means of pre-operative staging esophageal cancer.

Eighty-eight patients with carcinoma of the esophagus (N = 44), stomach (N = 41), and duodenum (N = 3) who underwent surgery were pre-operatively examined by endoscopic ultrasonography (EUS). The ability of EUS to accurately predict the T stage and the N stage was 82% and 70% for esophageal carcinoma, 71% and 75% for gastric cancer, and 100% and 66% for duodenal malignancy. In esophageal carcinoma, the accuracy of T staging was only slightly lower in cases with non-traversable tumor stenoses (77%) compared with traversable carcinomas (84%). This was probably due to the fact that all non-traversable tumors were either in stage T3 or T4. The accuracy of EUS in predicting the stages T1 to T3, which correspond to R0 resectability (no macroscopic or microscopic tumor remains), was 92% for adenocarcinoma of the distal esophagus and 85% for gastric cancer. However, in squamous cell carcinoma of the esophagus, R0 resection was possible in only 66% of all cases, whereas EUS predicted an 84% R0 resection rate. In adenocarcinoma of the distal esophagus and stomach, EUS prediction of stages T1 to T3 correlated well with the actual rate of R0 resection. These results show that EUS is a reliable diagnostic method for the local staging of upper gastrointestinal cancer. Its impact on treatment and hence on prognosis of patients with these malignancies has yet to be determined.