Skip to main content

Advertisement

SpringerLink
Log in

Risk of metastasis in adenocarcinoma of the esophagus: a multicenter retrospective study in a Japanese population

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 02 April 2018

Abstract

Background

Little is known about the specific risks of metastasis in esophageal adenocarcinoma in relation to invasion depth or other pathologic factors.

Methods

We conducted a multicenter retrospective study in 13 high-volume centers in Japan from January 2000 to October 2014 to elucidate the risk of metastasis of esophageal adenocarcinoma. A total of 458 patients (217 surgically resected and 241 endoscopically resected) with esophageal adenocarcinoma or esophagogastric adenocarcinoma involving the esophagus were included. Metastasis was considered positive if there was histologically confirmed metastasis in the surgical specimen or clinically confirmed metastasis during follow-up. Metastasis was considered negative if no metastasis was identified in resected specimens and during follow-up in patients treated surgically or no metastasis during follow-up for >5 years in patients treated by endoscopic resection.

Results

Metastasis was identified in 72 patients. Multivariate analysis confirmed lymphovascular involvement [odds ratio (OR) 6.20; 95 % confidence interval (CI) 3.12–12.32; p < 0.001], a poorly differentiated component (OR 3.69; 95 % CI 1.92–7.10; p < 0.001), and lesion size >30 mm (OR 3.12; 95 % CI 1.63–5.97; p = 0.001) as independent risk factors for metastasis. No metastasis was detected in patients with mucosal cancer without lymphovascular involvement and a poorly differentiated component (0/186 lesions) or in patients with cancer invading the submucosa (1–500 µm) without lymphovascular involvement, a poorly differentiated component, and ≤30 mm (0/32 lesions).

Conclusions

Mucosal and submucosal cancers (1–500 µm invasion) without risk factors have a low incidence of metastasis and may thus be good candidates for endoscopic resection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. DeMeester SR. Adenocarcinoma of the esophagus and cardia: a review of the disease and its treatment. Ann Surg Oncol. 2006;13:12e30.

    Article  Google Scholar 

  2. Shaheen NJ, Richter JE. Barrett’s oesophagus. Lancet. 2009;373:850–61.

    Article  CAS  PubMed  Google Scholar 

  3. Brown LM, Devesa SS, Chow WH. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 2008;100:1184–7.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wu JC. Gastroesophageal reflux disease: an Asian perspective. J Gastroenterol Hepatol. 2008;23:1785–93.

    Article  PubMed  Google Scholar 

  5. Hongo M, Nagasaki Y, Shoji T. Epidemiology of esophageal cancer: orient to occident. Effects of chronology, geography and ethnicity. J Gastroenterol Hepatol. 2009;24:729–35.

    Article  PubMed  Google Scholar 

  6. Gillison EW, Powell J, Mcconkey CC, et al. Surgical workload and outcome after resection for carcinoma of the oesophagus and cardia. Br J Surg. 2002;89:344–8.

    Article  CAS  PubMed  Google Scholar 

  7. Inadomi JM, Sampliner R, Lagergren J, et al. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med. 2003;138:176–86.

    Article  PubMed  Google Scholar 

  8. Sharma P, Sidorenko EI. Are screening and surveillance for Barrett’s oesophagus really worthwhile? Gut. 2005;54:i27–32.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Abela JE, Going JJ, Mackenzie JF, et al. Systematic four-quadrant biopsy detects Barrett’s dysplasia in more patients than nonsystematic biopsy. Am J Gastroenterol. 2008;103:850–5.

    Article  PubMed  Google Scholar 

  10. Nakagawa K, Koike T, Iijima K, et al. Comparison of the long-term outcomes of endoscopic resection for superficial squamous cell carcinoma and adenocarcinoma of the esophagus in Japan. Am J Gastroenterol. 2014;109:348–56.

    Article  PubMed  Google Scholar 

  11. Pech O, May A, Manner H, et al. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology. 2014;146:652–60.

    Article  PubMed  Google Scholar 

  12. Manner H, Pech O, Heldmann Y, et al. Efficacy, safety, and long-term results of endoscopic treatment for early stage adenocarcinoma of the esophagus with low-risk sm1 invasion. Clin Gastroenterol Hepatol. 2013;11:630–5.

    Article  PubMed  Google Scholar 

  13. Westerterp M, Koppert LB, Buskens CJ, et al. Outcome of surgical treatment for early adenocarcinoma of the esophagus or gastro-esophageal junction. Virchows Arch. 2005;446:497–504.

    Article  PubMed  Google Scholar 

  14. Stein HJ, Feith M, Bruecher BL, et al. Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection. Ann Surg. 2005;242:566–73.

    PubMed  PubMed Central  Google Scholar 

  15. Barbour AP, Jones M, Brown I, et al. Risk stratification for early esophageal adenocarcinoma: analysis of lymphatic spread and prognostic factors. Ann Surg Oncol. 2010;17:2494–502.

    Article  PubMed  Google Scholar 

  16. Lee L, Ronellenfitsch U, Hofstetter WL, et al. Predicting lymph node metastases in early esophageal adenocarcinoma using a simple scoring system. J Am Coll Surg. 2013;217:191–9.

    Article  PubMed  Google Scholar 

  17. Altorki NK, Lee PC, Liss Y, et al. Multifocal neoplasia and nodal metastases in T1 esophageal carcinoma: implications for endoscopic treatment. Ann Surg. 2008;247:434–9.

    Article  PubMed  Google Scholar 

  18. Pennathur A, Farkas A, Krasinskas AM, et al. Esophagectomy for T1 esophageal cancer: outcomes in 100 patients and implications for endoscopic therapy. Ann Thorac Surg. 2009;87:1048–54.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Dubecz A, Kern M, Solymosi N, et al. Predictors of lymph node metastasis in surgically resected T1 esophageal cancer. Ann Thorac Surg. 2015;99:1879–86.

    Article  PubMed  Google Scholar 

  20. Prasad GA, Wu TT, Wigle DA, et al. Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett’s esophagus. Gastroenterology. 2009;137:815–23.

    Article  PubMed  Google Scholar 

  21. Alvarez HL, Pouw RE, van Vilsteren FG, et al. Risk of lymph node metastasis associated with deeper invasion by early adenocarcinoma of the esophagus and cardia: study based on endoscopic resection specimens. Endoscopy. 2010;42:1030–6.

    Article  Google Scholar 

  22. Buskens CJ, Westerterp M, Lagarde SM, et al. Prediction of appropriateness of local endoscopic treatment for high-grade dysplasia and early adenocarcinoma by EUS and histopathologic features. Gastrointest Endosc. 2004;60:703–10.

    Article  PubMed  Google Scholar 

  23. Sepesi B, Watson TJ, Zhou D, et al. Are endoscopic therapies appropriate for superficial submucosal esophageal adenocarcinoma? An analysis of esophagectomy specimens. J Am Coll Surg. 2010;210:418–27.

    Article  PubMed  Google Scholar 

  24. Leers JM, DeMeester SR, Oezcelik A, et al. The prevalence of lymph node metastases in patients with T1 esophageal adenocarcinoma a retrospective review of esophagectomy specimens. Ann Surg. 2011;253:271–8.

    Article  PubMed  Google Scholar 

  25. Dunbar KB, Spechler SJ. The risk of lymph-node metastases in patients with high-grade dysplasia or intramucosal carcinoma in Barrett’s esophagus: a systematic review. Am J Gastroenterol. 2012;107:850–62.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Japan Esophageal Society. Japanese Classification of Esophageal Cancer, tenth edition: part I. Esophagus. 2009;6:1–58.

    Article  Google Scholar 

  27. Metz CE. Basic principles of ROC analysis. Semin Nucl Med. 1978;8:283–98.

    Article  CAS  PubMed  Google Scholar 

  28. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer. 2000;3:219–25.

    Article  PubMed  Google Scholar 

  29. Morson BC, Whiteway JE, Jones EA, et al. Histopathology and prognosis of malignant colorectal polyps treated by endoscopic polypectomy. Gut. 1984;25:437–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Goseki N, Koike M, Yoshida M. Histopathologic characteristics of early stage esophageal carcinoma. A comparative study with gastric carcinoma. Cancer. 1992;69:1088–93.

    Article  CAS  PubMed  Google Scholar 

  31. Bogomoletz WV, Molas G, Gayet B, et al. Superficial squamous cell carcinoma of the esophagus. A report of 76 cases and review of the literature. Am J Surg Pathol. 1989;13:535–46.

    Article  CAS  PubMed  Google Scholar 

  32. Sugimachi K, Ikebe M, Kitamura K, et al. Long-term results of esophagectomy for early esophageal carcinoma. Hepatogastroenterology. 1993;40:203–6.

    CAS  PubMed  Google Scholar 

  33. Sabik JF, Rice TW, Goldblum JR, et al. Superficial esophageal carcinoma. Ann Thorac Surg. 1995;60:896–902.

    Article  CAS  PubMed  Google Scholar 

  34. Davison JM, Landau MS, Luketich JD, et al. A model based on pathologic features of superficial esophageal adenocarcinoma complements clinical node staging in determining risk of metastasis to lymph nodes. Clin Gastroenterol Hepatol. 2016;14:369–77.

    Article  PubMed  Google Scholar 

  35. Griffin SM, Burt AD, Jennings NA. Lymph node metastasis in early esophageal adenocarcinoma. Ann Surg. 2011;254:731–6.

    Article  CAS  PubMed  Google Scholar 

  36. Bollschweiler E, Baldus SE, Schroder W, et al. High rate of lymph-node metastasis in submucosal esophageal squamous cell carcinomas and adenocarcinomas. Endoscopy. 2006;38:149–56.

    Article  CAS  PubMed  Google Scholar 

  37. Manner H, Pech O, Heldmann Y, et al. The frequency of lymph node metastasis in early-stage adenocarcinoma of the esophagus with incipient submucosal invasion (pT1b sm1) depending on histological risk patterns. Surg Endosc. 2015;29:1888–96.

    Article  PubMed  Google Scholar 

  38. Greene CL, Worrell SG, Attwood SE, et al. Emerging concepts for the endoscopic management of superficial esophageal adenocarcinoma. J Gastrointest Surg. 2016;20:851–60.

    Article  PubMed  Google Scholar 

  39. Mohiuddin K, Dorer R, El Lakis MA, et al. Outcomes of surgical resection of T1bN0 esophageal cancer and assessment of endoscopic mucosal resection for identifying low-risk cancers appropriate for endoscopic therapy. Ann Surg Oncol. 2016;23:2673–8.

    Article  PubMed  Google Scholar 

  40. Dresner SM, Griffin SM. Pattern of recurrence following radical oesophagectomy with two-field lymphadenectomy. Br J Surg. 2000;87:1426–33.

    Article  CAS  PubMed  Google Scholar 

  41. Sgourakis G, Gockel I, Lang H. Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: a systematic review. World J Gastroenterol. 2013;19:1424–37.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Schlemper RJ, Itabashi M, Kato Y, et al. Differences in diagnostic criteria for gastric carcinoma between Japanese and Western pathologists. Lancet. 1997;349:1725–9.

    Article  CAS  PubMed  Google Scholar 

  43. Stolte M, Kirtil T, Oellig F, et al. The pattern of invasion of early carcinomas in Barrett’s esophagus is dependent on the depth of infiltration. Pathol Res Pract. 2010;206:300–4.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Tomoki Shimizu, Yasutaka Kuribayashi, Yuko Hara, Hiroki Kikuchi, Yuichi Sato, Mitsuhiro Fujishiro, and Taku Yamagata for help with data collection, Yasuo Ohkura, Tomio Arai and Atsusi Ochiai for help with pathologic examination, and Junya Oguma, Takayuki Nishi for general advice.

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3 Nakamichi 1-chome, Higashinari-ku, Osaka, 537-8511, Japan

    Ryu Ishihara & Takashi Kanesaka

  2. Department of Endoscopy, Saku Central Hospital Advanced Care Center, Saku, Japan

    Tsuneo Oyama & Akiko Takahashi

  3. Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan

    Seiichiro Abe, Masayoshi Yamada & Ichiro Oda

  4. Department of Gastroenterology, Keiyukai Daini Hospital, Sapporo, Japan

    Hiroaki Takahashi & Junichi Kodaira

  5. Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan

    Hiroyuki Ono & Masaki Tanaka

  6. Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Junko Fujisaki & Masami Omae

  7. Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan

    Mitsuru Kaise & Akira Matsui

  8. Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan

    Kenichi Goda

  9. Department of Esophageal and General Surgery, Tokyo Medical and Dental University, Tokyo, Japan

    Kenro Kawada & Tatsuyuki Kawano

  10. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Tomoyuki Koike & Masahiro Saito

  11. Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan

    Manabu Takeuchi & Shuji Terai

  12. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Rie Matsuda & Yosuke Tsuji

  13. Department of Gastroenterology, Sendai City Medical Center, Sendai, Japan

    Dai Hirasawa & Yuki Maeda

  14. Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan

    Shinichi Hirooka

  15. Department of Gastrointestinal Surgery, The University of Tokyo Hospital, Tokyo, Japan

    Hiroharu Yamashita & Yasuyuki Seto

  16. Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Yasuhiko Tomita

  17. Department of Medical Informatics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Takashi Matsunaga

  18. Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Japan

    Soji Ozawa

Authors
  1. Ryu Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tsuneo Oyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seiichiro Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroaki Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyuki Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junko Fujisaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mitsuru Kaise
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kenichi Goda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kenro Kawada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tomoyuki Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Manabu Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rie Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Dai Hirasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Masayoshi Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Junichi Kodaira
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Masaki Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Masami Omae
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Akira Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Takashi Kanesaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Akiko Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Shinichi Hirooka
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Masahiro Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Yosuke Tsuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Yuki Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Hiroharu Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Ichiro Oda
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Yasuhiko Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Takashi Matsunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Shuji Terai
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Soji Ozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Tatsuyuki Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Yasuyuki Seto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryu Ishihara.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Saku Central Hospital Ethics Committee.

Funding

Supported by a grant from the Japanese Gastroenterological Association.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ishihara, R., Oyama, T., Abe, S. et al. Risk of metastasis in adenocarcinoma of the esophagus: a multicenter retrospective study in a Japanese population. J Gastroenterol 52, 800–808 (2017). https://doi.org/10.1007/s00535-016-1275-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-016-1275-0

Keywords

Search

Navigation