Reply to the letter of von Rahden and Stein

“I have learned that R1 is not always the same as R1.” These were the words used by Professor Siewert, former head of the Department of Surgery in Munich, to explain to his fellow surgeons the difference between an endoscopic R1 resection and a surgical R1 resection, when he spoke in September 2007 at the annual meeting of the German Society for Digestive and Metabolic Diseases (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, DGVS). Von Rahden and Stein, who studied with Siewert for many years, do not appear to have learned similarly that a surgical R1 resection is fundamentally different from an endoscopic resection with an R1 character at the lateral margins.

In piecemeal resections, as used in our study, residual neoplasia at the lateral resection margins can be removed endoscopically without problems [1]. The long-term results that have now been presented by several groups, in studies including patients both with early squamous-cell carcinoma and with early Barrett’s carcinoma, have confirmed the safety and oncological radicality of endoscopic resection [2]. The lateral R1 situation only appears to influence the neoplasia recurrence rate - although the published data on this topic are contradictory. No influence on other end points, such as tumor-related survival or long-term complete remission, has yet been observed [2].

The well-informed readers of Endoscopy are of course aware that in contrast to surgical R1 resection - in which residual tumor remains in situ, and which is usually associated with a fatal outcome - residual neoplastic areas following an endoscopic lateral R1 resection can usually be removed without problems during subsequent additional endoscopic resections. The decisive element in endoscopic treatment is not the lateral R1 resection, but rather freedom from tumor at the basal resection margin. If it is not possible to carry out an endoscopic resection with a healthy basal margin, then surgical therapy is indicated, as it is not possible to ensure curative treatment in this situation.

Stein and von Rahden also criticize what appeared to them to be the unclear selection of patients in the study, although this is described in detail in the “Patients and methods” section. The intention-to-treat analysis, which they claim is absent, will also not have escaped the attentive reader. As is explained precisely in our study, a tumor limited to the mucosa was suspected in 74 patients during preoperative staging. Following the first endoscopic resection, however, it was found that infiltration of the submucosa had already taken place in nine patients, who therefore received further treatment with surgery or chemoradiotherapy. As is explained in the paper, “The rate of complete long-term remission achieved at the first attempt can be calculated on an intention-to-treat basis as 62.2 % (46/74 patients).” In contrast to what Stein and von Rahden assert, the results with regard to the recurrence rate, the rate of lymph-node metastasis (3 %), and the tumor-related mortality rate (3 %), which are described in detail in our study, do indeed allow a “judgment of oncologic adequacy” [1].

The sentence in our paper which is criticized, that is, “These tumors have only a very low risk of lymph-node metastasis,” refers to mucosal carcinomas. The rate of lymph-node metastasis observed in our study was two in 65 patients (3 %). Summing up the results in all of the articles published in the January issue of Endoscopy, the rate of positive lymph nodes in the 181 patients who received endoscopic treatment for early squamous-cell carcinoma was 2.7 % (five of 181) [1] [3] [4] [5]. In their own study, cited by von Rahden and Stein in their letter, the metastasis rate for mucosal carcinomas was 8 %; the 36.4 % rate mentioned refers to the rate for all T1 tumors, including submucosal carcinomas. As is mentioned in our study several times, submucosal infiltration is associated with a much higher rate of positive lymph nodes. For this reason, these patients are no longer suitable for endoscopic treatment with curative intent.

In addition to cure, precise differentiation of the depth of penetration is another of the strengths of endoscopic resection. The specimens obtained with this method are processed in minute detail (with serial sections every 1 mm in our study), so that even the tiniest foci of submucosal infiltration can be identified. Endoscopic resection therefore currently represents the most precise method of preoperative - and probably also of postoperative - staging. Following esophageal resection, the specimens are not processed with the same degree of precision, so that here in particular it is possible for foci of tumor infiltration into deeper layers to be overlooked. The surgical data for depth of infiltration and lymph-node metastases in T1 esophageal carcinoma therefore generally need to be regarded with caution.

All of the patients attending our center are informed in detail about the fact that regular follow-up examinations are vital after endoscopic treatment. In view of the mortality and morbidity associated with radical esophageal resection, however, nearly all of the patients are willing to accept the regular endoscopic examinations needed.

The results reported in the other three papers by different research groups from France and Japan, which were published in the same issue of Endoscopy, are by no means the only findings confirming that endoscopic resection for early mucosal squamous-cell carcinoma represents a safe and effective procedure that must not be withheld from patients with mucosal squamous-cell carcinoma.

Competing interests: None

References

• 1 Pech O, May A, Gossner L. et al . Curative endoscopic therapy in patients with early esophageal squamous-cell carcinoma or high-grade intraepithelial neoplasia.  Endoscopy. 2007;  39 30-35
• 2 Pech O, May A, Rabenstein T, Ell C. Endoscopic resection of early oesophageal cancer.  Gut. 2007;  56 1625-1634
• 3 Ciocirlan M, Lapalus M G, Hervieu V. et al . Endoscopic mucosal resection for squamous premalignant and early malignant lesions of the esophagus.  Endoscopy. 2007;  39 24-29
• 4 Higuchi K, Tanabe S, Koizumi W. et al . Expansion of the indications for endoscopic mucosal resection in patients with superficial esophageal carcinoma.  Endoscopy. 2007;  39 36-40
• 5 Esaki M, Matsumoto T, Hirakawa K. et al . Risk factors for local recurrence of superficial esophageal cancer after treatment by endoscopic mucosal resection.  Endoscopy. 2007;  39 41-45