Discussion

Endoscopic ultrasonography is probably the most significant advance in endoscopy over the past decade. Housed in the tip of a regular endoscope, the high-frequency ultrasound transducer produces detailed images of the various anatomic layers of the esophagus which appear as alternating hyperechoic and hypoechoic regions. The technique allows the identification of various degrees of involvement of these layers by hypoechoic lesions, benign or malignant, and the presence or absence of nodal metastases. However, the criteria for predicting nodal involvement are not strictly defined, making that assessment operator-dependent to some extent. Several investigators worldwide have substantiated the efficacy of EUS in accurately predicting the T and N stages for esophageal carcinoma. ^3-9

Mural invasion is generally predicted with 85% accuracy while the N stage is diagnosed with 80% accuracy.

The data reported herein confirm those reported by others insofar as T₁ and T₃ lesions are concerned, with a positive predictive value of 100% and 92% respectively. However, ability to positively predict T₂ lesions was quite poor: 31 %. The small number of T₂ lesions may be a possible, though unlikely, explanation of this interpretive error. Others have observed a similar inadequacy of EUS to predict T₂ lesions.¹⁰ Catalano reported a significant discrepancy between experienced endosonographers in diagnosing T₂ tumors.¹⁰ Whether the problem relates to the experience of the observer or to machine-dependent factors is unknown at this time. Tumors invading other mediastinal structures, i.e. T₄ lesions, were also associated, in our experience, with a low positive predictive value of 50%. However, the sensitivity and specificity of EUS for T₄lesions was 100% and 96% respectively. Among four patients in whom EUS predicted T₄ status, only two were pathologically confirmed. We therefore continue to require corroboration of the EUS finding of a T₄ tumor by other staging methods (usually computerized tomography) before deeming the patient inoperable. Occasionally, EUS may delineate the intact fat plane between the aorta and the esophagus not otherwise discernable by computerized tomography.

For staging of the N status, our data suggest that despite the significant advantage of EUS over computerized tomography, several problematic areas remain unresolved. The positive predictive value of N₀ stage was only 44% with a sensitivity and specificity of 66% and 50% respectively. The presence of metastatic disease in lymph nodes less than 1 cm in diameter is a frequent even in patients with esophageal cancer. To date, no precise correlation has been established between the presence or absence of nodal metastases and the size, shape or echogenicity of lymph nodes. Although the sizes of all positive lymph nodes were not documented in this retrospective analysis, it is probable that metastatic disease was present in nodes less than 1 cm. An alternative explanation is our routine use of extended lymphadenectomy, thus excising nodal stations throughout the mediastinum and upper abdomen that are beyond the resolution of current EUS probes. When nodal metastases were present (N₁) the positive predictive value EUS was 79% overall, and up to 93%. This is a definite improvement over our reported 50% accuracy in assessing metastatic nodal disease by computerized tomography.¹¹ A 20% false positive rate is disturbing, since patients may be denied the benefit of a possible curative resection. In our own experience and that of other investigators, the five-year survival for node-negative patients is about 60%.^12,13 The recent introduction of linear-array echoendoscopes equipped with a biopsy channel may allow fine needle aspiration under EUS guidance and decrease the frequency of false positive results.¹⁴ Furthermore, as noted in our data, the increase in incidence of nodal metastasis with increasing mural penetration by the primary tumor may permit an indirect evaluation of the significance of identified nodes. The ability of EUS to correctly predict TNM stage is 62% primarily due to inadequate staging of patients with IIA or IIB. The reasons for this have already been described. A troublesome observation is the overstaging (11-35%) of patients without nodal metastases; with a possible adverse impact on treatment strategy which should be primary curative surgery for such patients.

The role of EUS in treatment planning for patients with carcinoma of the esophagus and cardia remains unclear. The use of preoperative chemotherapy or chemoradiotherapy for patients with N₁disease remains largely investigational. Despite the reported survival advantage of preoperative therapy in most phase II trials,^15-17no such benefit has been borne out in random assignment studies.^18-20 In fact, Roth reported on a randomized trial of 36 patients randomized to receive preoperative cisplatin, bleomycin and vindisine versus surgery alone.¹⁸ No difference was noted in the outcome of both arms of the trial except in a small subgroup of patients who were partial responders. Similar results were reported by Nygaard and Schlag. ^19,20 A national intergroup trial currently in progress continues to evaluate the merit of preoperative chemotherapy. The use of preoperative chemoradiotherapy has also not been shown to confer a survival advantage compared to surgery alone.²¹ However, when chemoradiotherapy was evaluated against primary radiation therapy, a significant survival benefit was noted for the chemoradiation group. ²² Unfortunately, the local failure rate was at least 35%. Our local recurrence rate (defined as mediastinal or anastomotic) following esophagectomy is 12% and only 6% after en bloc resection. We therefore continue to believe that primary radical surgical resection is the standard form of therapy. Although the presence of positive nodes by EUS portends a poor prognosis, it is unclear what impact it might have on treatment plans but EUS is invaluable for benefit/risk and prognosis discussions with patients without distant metastasis. With the introduction of more effective chemotherapeutic agents, EUS may assume a more critical role in determining the preoperative management of patients with carcinoma of the esophagus and cardia.