Stop confusing us with EUS prior to endoscopic resection

Endoscopic ultrasound (EUS) plays an important role in the staging of esophageal cancer and is the most accurate method for locoregional staging of esophageal carcinomas, if done by an experienced endosonographer [1] [2] [3]. Standard EUS operates with frequencies of 7.5 and 12 MHz. These lower frequencies provide higher penetration, which is important for lymph node staging, but also means a lower resolution. Therefore the visualization of superficial cancers and the determination of the extent of the cancer into the mucosal and/or submucosal layer can be difficult. However, the dramatic increase in the diagnosis of early esophageal cancers, particularly of early adenocarcinomas in Barrett’s esophagus in the Western world, together with the increasing acceptance of endoscopic resection as a curative therapy for early (mucosal) esophageal tumors, at least in Asia and Europe, mean better pretherapeutic staging is desirable [4] [5] [6] [7] [8] [9] [10] [11].

Technological advancement has led to the development of miniprobes with higher frequencies (15 - 30 MHz) and therefore higher resolution, which permits an improved accuracy of T-staging of T1 esophageal tumors [12] [13]. Due to the lower penetration of these miniprobes, a combination of miniprobe EUS and standard EUS seemed to be the optimal method for pretherapeutic T- and N-staging of early esophageal cancers - together with high-resolution video endoscopy [5] [6].

After the first optimistic and promising results achieved in two small trials [12] [13], which showed an accuracy of about 80 % - 90 % in T staging of T1 esophageal cancers, facts had to be faced. Larger studies on EUS with miniprobes had been done mainly by Asian research groups, and they focussed on early gastric cancer or neoplasias of the large bowel. But the situation in the esophagus, especially at the esophagogastric junction is different and more problematic. In this issue of Endoscopy, Chemaly et al. demonstrated with their trial (91 patients with superficial Barrett’s adenocarcinomas or squamous cell cancers, 106 lesions), that the miniprobes only have a limited accuracy in the detection of submucosal invasion of early esophageal cancers. The overall accuracy was 73.5 %. In 26.5 % of the tumors the assessment was incorrect (overstaging 18.6 %, understaging 7.8 %). In nearly 70 % of the tumors assessed as submucosal lesions by the miniprobe EUS, histology of the endoscopically or surgically resected specimen revealed only a mucosal cancer. These results are similar to our results of a prospective study published 3 years ago [14], where the overall accuracy was 79.6 %. However, the sensitivity for submucosal cancers was only 48 %, but combined with a specificity of 91 %. The main problem concerned lesions that were starting to infiltrate the submucosa (sm1 types), whereas the majority of sm2- and sm3-type cancers could be detected correctly.

Another independent risk factor for misinterpretation in the retrospective trial of Chemaly et al. was the localization of the cancer in the distal part of the esophagus. Whereas nearly 90 % of the lesions in the proximal and mid-part of the esophagus had been staged correctly, less than half of the lesions (47.6 %) in the distal esophagus had been assessed correctly. Again, these data confirm our own experiences [14]. The main problem is adequate water filling in the region of the esophagogastric junction, particularly in the presence of an axial hiatus hernia, which is very common in patients with Barrett’s adenocarcinoma. Hopes were placed on the use of balloon-sheathed catheters, but Chemaly et al. demonstrated that this technique cannot overcome the problems. Quite the reverse: the water-filled lumen was superior to the balloon-sheathed catheters. Therefore, new techniques have still to be evaluated to prove their value in this problematic situation.

These disappointing results question the role of miniprobe EUS in the pretherapeutic staging of early esophageal cancers, and underline the value of high-resolution video endoscopy and endoscopic resection as the first choice for endoscopic therapy of all detectable lesions. By using high-resolution video endoscopy (in combination with chromoendoscopy) done by an endoscopist with experience in early esophageal cancers, an accuracy in T1-staging of nearly 85 % can be achieved [14]. But even performed in experienced centers, the pretherapeutic staging cannot achieve 100 % accuracy. This level of accuracy, together with the problematic situation of sm-type tumors and tumors localized in the region of the esophagogastric junction, and the fact that histology is still the gold standard for the exact assessment of a carcinoma, endoscopic resection plays a very important role. Nowadays, there is no doubt that endoscopic resection is the preferred method for local endoscopic therapy, as it allows - in contrast to photodynamic therapy or thermal ablation - precise pathological staging of the resected specimen. This assessment includes the degree of differentiation (grading), of invasion of lymphatic vessels (L status) and veins (V status), the freedom from tumor on the lateral and basal margins of the specimen (R status), and provides reliable differentiation between mucosal and submucosal tumor infiltration as well as the exact depth of invasion (mucosal level m1 - 4 for Barrett’s adenocarcinoma, m1 - 3 for squamous cell carcinoma, and sm1 - 3 for both cancers). The importance of endoscopic resection is proved by the data of Chemaly et al., because 70 % of their patients who were sm-staged using the EUS miniprobes revealed only a mucosal cancer by histology. This means that the majority of these patients would have been referred to surgery, which is associated with a substantial risk of morbidity and mortality, when curative endoscopic therapy could have been performed. Therefore, histology of the endoscopic resected specimen has become a central component in the management of patients with early esophageal cancer. If the pretherapeutic assessment of a low-risk situation of the neoplasia is confirmed or even ”down-staged“ by histology, endoscopic therapy and surveillance after complete endoscopic resection of the lesion can be continued [10] [11]. A strict follow-up program including high-resolution video endoscopy and standard EUS is absolutely mandatory for patients who have undergone curative endoscopic therapy in early esophageal cancer, due to the risk of developing metachronous lesions [5] [6] [11] [15] or lymph node metastases under certain conditions (e. g. high-risk patients such as those with sm-infiltration).

In contrast to EUS miniprobes, standard EUS done by an experienced endosonographer plays a central role in the pretherapeutic T- (T1 vs. T2) and N-staging of early esophageal cancers, in order to differentiate between patients in whom endoscopic therapy is suitable and those who need surgical treatment. EUS miniprobes might still be used for T1 staging of lesions in the tubular esophagus, when under certain conditions a combination of endoscopic resection and photodynamic therapy/thermal ablation is considered, but nowadays they have no place in the T1 staging of lesions in the esophagogastric junction. High-resolution video endoscopy and histological assessment of the endoscopically resected specimen play central roles in the management of patients with early esophageal cancer without signs of lymph node metastases on standard EUS.

Competing interests: None

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