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Volume: Barrett's Esophagus
Chapter: Adenocarcinomas

What is the accuracy of endosonographic staging of adenocarcinomas of the esophagus and esophagogastric junction?

I. Waxman (Galveston)

Presently, Barrett's esophagus has been identified as the single most important risk factor for adenocarcinoma of the esophagus and gastric cardia [1, 2]. Over the past two decades, the incidence of adenocarcinoma of the esophagus increased at a rate exceeding that for any other cancer to the point that today, 50% of all esophageal cancers in white American men are adenocarcinomas. Patients with Barrett's esophagus develop adenocarcinoma of the esophagus at a rate of 1/125 patient-years, an incidence that is 30-125 times that of the general population. For every 100,000 patients with Barrett's esophagus, 800 will develop an adenocarcinoma each year [3]. The prognosis of adenocarcinoma in Barrett's esophagus is related to the stage at diagnosis [4]. The timely identification and surgical resection of intramucosal adenocarcinoma, or an early submucosal cancer within Barrett's esophagus offers an 80-100% chance of cure [5-7].

Prognosis and staging

Once adenocarcinoma of the esophagus becomes symptomatic, it carries a poor prognosis, with a 5-year survival of approximately 17% after complete resection of tumor, and less than 1% for unresectable lesions [8-11]. Esophageal adenocarcinoma tends to metastasize to the lymph nodes early in the disease process. In patients undergoing en bloc esophagectomy with extended abdominal and mediastinal lymphadenectomy for intramucosal adenocarcinoma for example, 33% had lymph node metastases. The prevalence of nodal metastases rose to 66% for those whose tumor had spread into the muscularis propria and to 89% in those with transmural tumors [12]. Only 50% of patients with lymph node metastases will be alive two years after resection, and about 15% survive more than 5 years [13].

Depth of esophageal wall invasion, in particular the distinction between partial and full thickness penetration, has major prognostic implications regarding lymph node status, long-term survival and local recurrence [14-16].

Therefore accurate staging has important clinical implications. The American Joint Committee on Cancer published their classification for staging esophageal cancer in 1987 and has so far remained unchanged [17]. This classification is based on the TNM staging system, which defines the anatomical extent of the disease. T indicates the depth of primary tumor invasion into the gastrointestinal tract wall; N indicates the spread of cancer to specified regional lymph nodes. In the case of adenocarcinoma of the esophagus, any regional lymph node metastasis is considered N1. M indicates distant metastases to lymph nodes outside specific regional lymph nodes, or to organs not in direct contact with the primary tumor. Metastatic celiac axis nodes are considered M1 for adenocarcinomas located mainly on the esophageal side of the esophagogastric junction (EGJ) and N2 (distant regional lymph nodes) when most of the tumor involves the gastric side of the EGJ [18].

Endosonographic evaluation

Over the last decade, endoscopic ultrasonography (EUS) has become a powerful tool for gastrointestinal cancer staging. EUS provides high resolution imaging of the layered structure of the gastrointestinal wall and surrounding structures [19]. At the conventional echoendoscope frequencies of 7.5 and 12 MHz, the gastrointestinal tract wall is imaged as a five acoustic layered structure, which corresponds with mural histology. In a recent review on esophageal cancer staging by EUS, Rosch reported an average accuracy for EUS of 84% and 77% in preoperative T and N staging, compared to surgical pathology results [20].

For patients with cancer of the esophagus and EGJ, EUS has been shown to be far superior to CT-scan in determining the depth and the presence of regional lymph node involvement [21, 22]. Reported overall EUS accuracy in assessing the depth of invasion in esophageal cancer range from 76% to 92% when compared to 49% to 59% for CT-scan, and for nodal status, 72% to 80% and 46% to 51% for EUS and CT-scan respectively [22-25]. For M staging, EUS is limited due to it's inability to image distant metastases, making this an area where CT-scan should be used in a complementary fashion.

Clinical impact of endosonography

In addition to accurate staging information, preoperative EUS findings have been shown to correlate with survival and predict surgical outcome. Hiele et al. analyzed survival data in 86 patients who underwent EUS staging of tumors of the esophagus and the EGJ. The authors found a median survival of 28 months for patients with tumors staged as T2 compared to a 19 months for those staged as T3. Patients whose tumors where staged as T4 had the worst prognosis with a median survival of 8 months. Regarding lymph node status, patients staged N0 by EUS had a median survival of 28 months as compared with 8 months for patients in whom malignant nodes where suspected. In patients with EGJ cancers in particular, involvement of celiac axis nodes had a significant correlation with survival. Median survival was 30 months and 3 months in the absence and presence of positive celiac axis nodes on EUS. Finally, in patients with stage II (absence of pathological lymph nodes) tumors, over 90% had a curative resection [26].

EUS has also been shown in a retrospective study to predict poor outcome in patients staged as T4 (invasion of adjacent structures). The study also suggested no difference in survival between patients who underwent surgical and non-surgical palliation, providing important information that could impact management by avoiding surgical interventions in this subset of patients [27].

As preoperative treatment decisions get influenced by the presence or absence of lymphadenopathy, adjuvant therapy (N1) and/or surgical resection (M1 a: celiac lymph node), EUS-guided FNA may play an important role in preoperative staging of patients with esophageal carcinoma. Preliminary studies suggest that EUS FNA is more accurate and sensitive than EUS alone in assessing nodal disease, improving the sensitivity from 63% to 93% and the accuracy from 70% to 93% [28].

Endosonography in Barrett's esophagus with high-grade dysplasia

For patients with cancer in Barrett's esophagus, EUS appears to have a role in staging the tumor, and some authors have suggested that the technique may be useful in determining when to operate on patients with high-grade dysplasia (HGD) who have no endoscopic evidence of carcinoma [29]. Srivastava et al. reported their preliminary experience with EUS in the evaluation of Barrett's esophagus [30]. Esophageal wall thickening was found by endosonography in patients with Barrett's esophagus (n = 15, six with dysplasia) when compared to a control group (n = 10) without esophageal disease. No significant difference in thickness was noted in the patients with dysplasia as compared to those with nondysplastic Barrett's esophagus. Two of the patients had thickening of the submucosal layer, which proved to be submucosal cancer after surgical resection. Falk et al. looked specifically at the role of endosonography in patients with Barrett's esophagus and HGD [31]. Nine patients who were candidates for esophagectomy and who had HGD in the absence of carcinoma were studied. Endosonography was able to identify only one out of three cancers found at surgery and overstaged it as invasive carcinoma (T2, N1 versus T1s). In two patients without intramucosal carcinoma furthermore, endosonography predicted invasive carcinoma (T2, N0). In all cases of overstaging, mucosal nodularity was noted. The authors concluded that current endosonography techniques cannot consistently predict the presence of intramucosal carcinoma and that the finding of mucosal nodularity should be interpreted with caution.

High frequency ultrasound probe sonography (HFUPS) with a 20 MHz ultrasound catheter probe provides finer resolution of the esophageal wall and is able to define up to nine layers of the gastrointestinal wall in contrast to the five layers detected by the conventional endoscope. Waxman et al. studied prospectively the utility of HFUPS in predicting the presence of carcinoma in patients with Barrett's esophagus and HGD [32]. A total of nine patients with Barrett's esophagus and HGD who were candidates for esophagectomy were enrolled. In all patients, HFUPS found diffuse thickening of the superficial hyperechoic and deep hypoechoic sonographic layers of the Barrett's esophagus mucosa. Four of the nine patients were suspected to have invasive carcinoma. Of the four, one was over-staged, one was under-staged, one was pathologically negative for carcinoma and one was correctly staged. Two patients with carcinoma went undiagnosed. The authors concluded that even high frequency ultrasonography was inaccurate at detecting or monitoring HGD, carcinoma in situ or early adenocarcinoma in patients with Barrett's esophagus.

Similar experience was reported by Parent et al. [33] in 13 patients with HGD. Thickening of layer two was noted in all patients studied but HFUPS could not detect adenocarcinomas in patients with HGD in the absence of endoscopically visible lesions. Furthermore, in patients with biopsy proven intramucosal carcinoma where studied, a normal sonographic examination could not exclude the presence of submucosal carcinoma [33].

To date, the data addressing the role of endosonography in patients with dysplasia in Barrett's epithelium are few, and suggests that the technique is not sufficiently accurate in predicting tumor at an early stage [35].

Limitations of endosonography

Limitations of EUS accuracy in staging involve overstaging (especially T1 and T2) due to peritumoral fibrotic or inflammatory changes and understaging, due to microscopic tumor invasion below the resolution of the scanning device with the majority of cases in T3 lesions. High-grade malignant strictures prevent adequate tumor evaluation by preventing passage of the endoscope in 20 to 38% of patients with esophageal carcinoma. This finding has been associated with an advanced carcinoma usually stage III or IV in up to 91% of patients. Attempts at EUS staging of these tumors from the region proximal to the stenosis have a poor accuracy [36]. At the present time, most endosonographers agree that esophageal dilatation solely for the purpose of passing the echoendoscope for staging does not outweigh the 24% risk of perforation reported [36]. The role of through the endoscope catheter probes is still being studied at the present time [25, 37]. The accuracy for detection of lymph node metastases is increasing due to the introduction of the curved linear array echoendoscope, which permits ultrasound scanning parallel to the long axis of the endoscope, allowing us-guided tissue sampling [38]. In spite of these technological advances, nodal micrometastases below the resolution of current EUS devices will continue to present a challenge in the staging of this disease [39].


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Publication date: August 2003 OESO©2015