High Rate of Lymph-Node Metastasis in Submucosal Esophageal Squamous-Cell Carcinomas and Adenocarcinomas

 

 Buy Article Permissions and Reprints

Background and study aims: The application of endoscopic mucosectomy in early esophageal cancer is limited by the presence of lymph-node metastasis. The aim of this prospective study was to analyze the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor penetration, comparing squamous-cell carcinomas and adenocarcinomas.
Patients and methods: A total of 60 patients with pT1 esophageal cancer - 24 with squamous-cell carcinomas (SCCs) and 36 with adenocarcinomas - were treated with transthoracic en-bloc esophagectomy with two-field lymphadenectomy (n = 50) or transhiatal esophageal resection (n = 10). An average of 30 lymph nodes were examined, and the following characteristics were evaluated: histology, mucosal infiltration, depth of submucosal wall infiltration in three thirds (sm1, sm2, sm3), grading, resection category, ratio of metastatic to resected lymph nodes, and locations of metastatic nodes.
Results: The rates of lymph-node metastasis were 0 % for the 16 mucosal carcinomas and 45 % for the 44 submucosal carcinomas (P < 0.01). There were no significant differences in the extent of lymph-node involvement between submucosal adenocarcinomas (41 %) and submucosal SCCs (50 %). Sm1 carcinomas were associated with a lower rate of lymph-node metastasis (SCCs 33 %, adenocarcinomas 22 %) than sm3 carcinomas (SCCs 69 %, adenocarcinomas 78 %). Two patients (9 %) with submucosal SCCs and five patients (23 %) with submucosal adenocarcinomas were classified as having stage pM1 lymph. The average lymph-node ratio in patients with pN1 was 0.13 for adenocarcinomas and 0.1 for SCCs (difference not significant). In the multivariate analysis, the parameters mucosal vs. submucosal (P < 0.01) and G1/G2 vs. G3 (P < 0.05) showed a significant impact in relation to metastatic lymph nodes.
Conclusions: The most important factor for predicting lymph-node metastasis in early esophageal cancer is the presence of submucosal infiltration. Early adenocarcinomas and SCCs do not differ with regard to their rate of lymphatic involvement. The rate of lymph-node metastasis increases with the depth of submucosal infiltration, but metastases can already occur in sm1 lesions. Submucosal infiltration is a contraindication for endoscopic mucosectomy. Limited surgical procedures without adequate lymphadenectomy do not appear to be appropriate in the treatment of patients with submucosal esophageal carcinomas.

References

• 1 Banki F, Mason R J, De Meester S R. et al . Vagal-sparing esophagectomy: a more physiologic alternative.  Ann Surg. 2002;  236 324-336
  PubMedGoogle Scholar
• 2 Ell C. Early esophageal carcinoma: diagnosis and endoscopic therapy.  Z Gastroenterol. 2002;  40 (Suppl 2) 12-14
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Stein H, Feith M, Mueller J. et al . Limited resection for early adenocarcinoma in Barrett’s esophagus.  Ann Surg. 2000;  232 733-742
  CrossrefPubMedGoogle Scholar
• 4 Gutschow C, Schroder W, Wolfgarten E. et al . Merendino procedure with preservation of the vagus for early carcinoma of the gastroesophageal junction. [In German].  Zentralbl Chir. 2004;  129 276-281
  Article in Thieme ConnectPubMedGoogle Scholar
• 5 May A, Gunter E, Roth F. et al . Accuracy of staging in early oesophageal cancer using high resolution endoscopy and high resolution endosonography: a comparative, prospective, and blinded trial.  Gut. 2004;  53 634-640
  CrossrefPubMedGoogle Scholar
• 6 Mönig S, Baldus S, Zirbes T. et al . Topographical distribution of lymph node metastasis in adenocarcinoma of the gastroesophageal junction.  Hepatogastroenterology. 2002;  49 419-422
  PubMedGoogle Scholar
• 7 Schröder W, Mönig S, Baldus S. et al . Frequency of nodal metastases to the upper mediastinum in Barrett’s cancer.  Ann Surg Oncol. 2002;  9 807-811
  CrossrefPubMedGoogle Scholar
• 8 Gotohda N, Nishimura M, Yoshida J. et al . The pattern of lymphatic metastases in superficial squamous cell carcinoma of the esophagus.  Hepatogastroenterology. 2005;  52 105-107
  PubMedGoogle Scholar
• 9 Araki K, Ohno S, Egashira A. et al . Pathologic features of superficial esophageal squamous cell carcinoma with lymph node and distal metastasis.  Cancer. 2002;  94 570-575
  CrossrefPubMedGoogle Scholar
• 10 Igaki H, Kato H, Tachimori Y. et al . Prognostic evaluation of patients with clinical T1 and T2 squamous cell carcinomas of the thoracic esophagus after 3-field lymph node dissection.  Surgery. 2003;  133 368-374
  CrossrefPubMedGoogle Scholar
• 11 Tajima Y, Nakanishi Y, Ochiai A. et al . Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors.  Cancer. 2000;  88 1285-1293
  CrossrefPubMedGoogle Scholar
• 12 Matsubara T, Ueda M, Abe T. et al . Unique distribution patterns of metastatic lymph nodes in patients with superficial carcinoma of the thoracic oesophagus.  Br J Surg. 1999;  86 669-673
  CrossrefPubMedGoogle Scholar
• 13 Tachibana M, Yoshimura H, Kinugasa S. et al . Clinicopathological features of superficial squamous cell carcinoma of the esophagus.  Am J Surg. 1997;  174 49-53
  CrossrefPubMedGoogle Scholar
• 14 Rice T. Superficial oesophageal carcinoma: is there a need for three-field lymphadenectomy?.  Lancet. 1999;  354 792-794
  PubMedGoogle Scholar
• 15 Liebermann-Meffert D. Anatomical basis for the approach and extent of surgical treatment of esophageal cancer.  Dis Esophagus. 2001;  14 81-84
  CrossrefPubMedGoogle Scholar
• 16 Kudo S. Endoscopic mucosal resection of flat and depressed types of early colorectal cancer.  Endoscopy. 1993;  25 455-461
  Article in Thieme ConnectPubMedGoogle Scholar
• 17 Ono H, Kondo H, Gotoda T. et al . Endoscopic mucosal resection for treatment of early gastric cancer.  Gut. 2001;  48 225-229
  CrossrefPubMedGoogle Scholar
• 18 Vieth M, Ell C, Gossner L. et al . Histological analysis of endoscopic resection specimens from 326 patients with Barrett’s esophagus and early neoplasia.  Endoscopy. 2004;  36 776-781
  Article in Thieme ConnectPubMedGoogle Scholar
• 19 Endo M, Yoshino K, Kawano T. et al . Clinicopathologic analysis of lymph node metastasis in surgically resected superficial cancer of the thoracic esophagus.  Dis Esophagus. 2000;  13 125-129
  CrossrefPubMedGoogle Scholar
• 20 Siewert J R, Hölscher A H, Becker K. et al . Kardiakarzinom. Versuch einer therapeutisch relevanten Klassifikation.  Chirurg. 1987;  58 25-29
  PubMedGoogle Scholar
• 21 Hölscher A H, Bollschweiler E, Bumm R. et al . Prognostic factors of resected adenocarcinoma of the esophagus.  Surgery. 1995;  118 845-855
  CrossrefPubMedGoogle Scholar
• 22 Hölscher A H, Schröder W, Bollschweiler E. et al . How safe is high intrathoracic esophagogastrostomy?.  Chirurg. 2003;  74 726-733
  CrossrefPubMedGoogle Scholar
• 23 Bartels H, Stein H J, Siewert J R. Risk analysis in esophageal surgery.  Recent Results Cancer Res. 2000;  155 89-96
  PubMedGoogle Scholar
• 24 Bollschweiler E, Schröder W, Hölscher A. et al . Preoperative risk analysis in patients with adenocarcinoma or squamous cell carcinoma of the oesophagus.  Br J Surg. 2000;  87 1106-1110
  CrossrefPubMedGoogle Scholar
• 25 Alderson D, Coutnesy S P, Kennedy R H. Radical transhaital oesophagectomy under direct vision.  Br J Surg. 1994;  81 404-407
  PubMedGoogle Scholar
• 26 Japanese Society for Esophageal Diseases . Guidelines for the clinical and pathological studies on carcinoma of the esophagus.  Jpn J Surg. 1976;  6 69-78
  PubMedGoogle Scholar
• 27 Japanese Gastric Cancer Association . Japanese classification of gastric carcinoma: 2nd English edition.  Gastric Cancer. 1998;  1 10-24
  CrossrefPubMedGoogle Scholar
• 28 Sobin L, Wittekind C (eds). TNM classification of malignant tumours, 6th edition. New York; Wiley-Liss 2002
  Google Scholar
• 29 Wittekind C, Greene F, Henson D. et al .TNM supplement: a commentary on uniform use. New York; Wiley-Liss 2003
  Google Scholar
• 30 Fitz A, Percy C, Jack A. et al .International classification of diseases for oncology (ICD-O), 3rd ed. Geneva; World Health Organization 2000
  Google Scholar
• 31 Hamilton S, Aaltonen L (eds). Pathology and genetics: tumours of the digestive system. Lyons; IARC Press 2000
  Google Scholar
• 32 Hölscher A H, Bollschweiler E, Schneider P M. et al . Early adenocarcinoma in Barrett’s oesophagus.  Br J Surg. 1997;  84 1470-1473
  CrossrefPubMedGoogle Scholar
• 33 Altorki N. Three-field lymphadenectomy for esophageal cancer.  Chest Surg Clin N Am. 2000;  10 553-560
  PubMedGoogle Scholar
• 34 Van Sandick J, van Lanschot J, ten Kate F. et al . Indicators of prognosis after transhiatal esophageal resection without thoracotomy for cancer.  J Am Coll Surg. 2002;  194 28-36
  CrossrefPubMedGoogle Scholar
• 35 Lerut T, Coosemans W, Decker G. et al . Extended surgery for cancer of the esophagus and gastroesophageal junction.  J Surg Res. 2004;  117 58-63
  CrossrefPubMedGoogle Scholar
• 36 Hagen J, De Meester T R, Peters J. et al . Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc esophagectomies.  Ann Surg. 2001;  234 520-531
  CrossrefPubMedGoogle Scholar
• 37 Wang G, Jiao G, Chang F. et al . Long-term results of operation for 420 patients with early squamous cell esophageal carcinoma discovered by screening.  Ann Thorac Surg. 2004;  77 1740-1744
  CrossrefPubMedGoogle Scholar
• 38 Hölscher A, Bollschweiler E, Schröder W. et al . Prognostic differences between early squamous-cell and adenocarcinoma of the esophagus.  Dis Esophagus. 1997;  10 179-184
  PubMedGoogle Scholar
• 39 Ruol A, Merigliano S, Baldan N. et al . Prevalence, management and outcome of early adenocarcinoma (pT1) of the esophago-gastric junction: comparison between early cancer in Barrett’s esophagus (type I) and early cancer of the cardia (type II).  Dis Esophagus. 1997;  10 190-195
  PubMedGoogle Scholar
• 40 Nigro J, Hagen J, de Meester T R. et al . Prevalence and location of nodal metastases in distal esophageal adenocarcinoma confined to the wall: implications for therapy.  J Thorac Cardiovasc Surg. 1999;  117 16-25
  PubMedGoogle Scholar
• 41 Westerterp M, Koppert L, Buskens C J. et al . Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction.  Virchows Arch. 2005;  446 497-504
  CrossrefPubMedGoogle Scholar
• 42 Yasuda K, Shiraishi N, Suematsu T. et al . Rate of detection of lymph node metastasis is correlated with the depth of submucosal invasion in early stage gastric carcinoma.  Cancer. 1999;  85 2119-2123
  CrossrefPubMedGoogle Scholar
• 43 Rice T, Zuccaro G, Adelstein D. et al . Esophageal carcinoma: depth of tumor invasion is predictive of regional lymph node status.  Ann Thorac Surg. 1998;  65 787-792
  CrossrefPubMedGoogle Scholar
• 44 Pech O, Gossner L, May A. et al . Endoscopic resection of superficial esophageal squamous-cell carcinomas: Western experience.  Am J Gastroenterol. 2004;  99 1226-1232
  CrossrefPubMedGoogle Scholar
• 45 Ishigami S, Yoshinaka H, Sakamoto F. et al . Preoperative assessment of the depth of early gastric cancer invasion by transabdominal ultrasound sonography (TUS): a comparison with endoscopic ultrasound sonography (EUS).  Hepatogastroenterology. 2004;  51 1202-1205
  PubMedGoogle Scholar
• 46 Ohashi S, Segawa K, Okamura S. et al . The utility of endoscopic ultrasonography and endoscopy in the endoscopic mucosal resection of early gastric cancer.  Gut. 1999;  45 599-604
  CrossrefPubMedGoogle Scholar
• 47 Heeren P AM, van Westreenen H L. et al . Influence of tumor characteristics on the accuracy of endoscopic ultrasonography in staging cancer of the esophagus and esophagogastric junction.  Endoscopy. 2004;  36 966-971
  Article in Thieme ConnectPubMedGoogle Scholar
• 48 Mönig S, Schröder W, Baldus S. et al . Preoperative lymph-node staging in gastrointestinal cancer: correlation between size and tumor stage.  Onkologie. 2002;  25 342-344
  CrossrefPubMedGoogle Scholar
• 49 Schröder W, Baldus S, Mönig S. et al . Lymph node staging of esophageal squamous cell carcinoma in patients with and without neoadjuvant radiochemotherapy: histomorphologic analysis.  World J Surg. 2002;  26 584-587
  CrossrefPubMedGoogle Scholar

A. H. Hölscher, M.D.

Dept. of Visceral and Vascular Surgery

University of Cologne Medical Center · Kerpener Strasse 62 · 50937 Cologne · Germany

Fax: +49-221-4784843

Email: Arnulf.Hoelscher@uk-koeln.de