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Impact of extracapsular lymph node involvement on tumor progression in esophageal squamous cell carcinoma after neoadjuvant therapy and effects on lymph nodes induced by chemotherapy and chemoradiotherapy

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Abstract

Background

Neoadjuvant therapy followed by surgery can improve long-term survival and reduce local recurrence in patients with esophageal squamous cell carcinoma (ESCC). Extracapsular lymph node involvement (ECLNI) reflects tumor progression in gastrointestinal malignancies. The aim of this study was to clarify the correlation between ECLNI and clinical outcome in ESCC following neoadjuvant therapy.

Methods

A total of 36 patients with ESCC who underwent neoadjuvant therapy followed by surgery were enrolled in this study (CT: n = 16; CRT: n = 20). The correlation between ECLNI and clinicopathological variables was investigated. In addition, we also evaluated whether differences in pathological response existed between primary tumors and metastatic lymph nodes (LNs), and whether chemotherapy (CT) and chemoradiotherapy (CRT) had different effects on LNs.

Results

Of 36 patients, 22.2 % had detectable ECLNI. ECLNI was significantly correlated with tumor size (>40 mm), LN density (≧20 %), advanced stage, lymphatic invasion, non-R0 resection, and poor pathological response. Patients with ECLNI had a significantly poorer prognosis than those without ECLNI (P = 0.0040). No differences in pathological response were observed between primary tumors and metastatic LNs for each type of therapy. The median number of dissected LNs was 21, 45, and 14 in the surgery alone (n = 22), CT, and CRT groups, respectively (P < 0.05). More severe morphologic changes in LNs appeared to be induced by CRT than by CT.

Conclusion

ECLNI was correlated with poor prognosis in patients with ESCC after neoadjuvant therapy. CT and CRT had different effects on LNs.

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References

  1. Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381:400–12.

    Article  PubMed  Google Scholar 

  2. Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.

    Article  PubMed  Google Scholar 

  3. Wind J, Lagarde SM, Ten Kate FJ, Ubbink DT, Bemelman WA, van Lanschot JJ. A systematic review on the significance of extracapsular lymph node involvement in gastrointestinal malignancies. Eur J Surg Oncol. 2007;33:401–8.

    Article  PubMed  CAS  Google Scholar 

  4. Lerut T, Coosemans W, Decker G, De Leyn P, Ectors N, Fieuws S, et al. Extracapsular lymph node involvement is a negative prognostic factor in T3 adenocarcinoma of the distal esophagus and gastroesophageal junction. J Thorac Cardiovasc Surg. 2003;126:1121–8.

    Article  PubMed  CAS  Google Scholar 

  5. Lagarde SM, ten Kate FJ, de Boer DJ, Busch OR, Obertop H, van Lanschot JJ. Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Am J Surg Pathol. 2006;30:171–6.

    Article  PubMed  Google Scholar 

  6. Metzger R, Drebber U, Baldus SE, Monig SP, Holscher AH, Bollschweiler E. Extracapsular lymph node involvement differs between squamous cell and adenocarcinoma of the esophagus. Ann Surg Oncol. 2009;16:447–53.

    Article  PubMed  Google Scholar 

  7. D’Journo XB, Avaro JP, Michelet P, Trousse D, Tasei AM, Dahan L, et al. Extracapsular lymph node involvement is a negative prognostic factor after neoadjuvant chemoradiotherapy in locally advanced esophageal cancer. J Thorac Oncol. 2009;4:534–9.

    Article  PubMed  Google Scholar 

  8. Metzger R, Bollschweiler E, Drebber U, Monig SP, Schroder W, Alakus H, et al. Neoadjuvant chemoradiotherapy for esophageal cancer: impact on extracapsular lymph node involvement. World J Gastroenterol. 2010;16:1986–92.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Tachikawa D, Inada S, Kotoh T, Futami K, Arima S, Iwashita A. An evaluation of malignancy and prognostic factors based on mode of lymph node metastasis in esophageal carcinoma. Surg Today. 1999;29:1131–5.

    Article  PubMed  CAS  Google Scholar 

  10. Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003;33:49–54.

    Article  PubMed  CAS  Google Scholar 

  11. Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012;19:68–74.

    Article  PubMed  Google Scholar 

  12. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.

    Article  PubMed  CAS  Google Scholar 

  13. Kassouf W, Agarwal PK, Herr HW, Munsell MF, Spiess PE, Brown GA, et al. Lymph node density is superior to TNM nodal status in predicting disease-specific survival after radical cystectomy for bladder cancer: analysis of pooled data from MDACC and MSKCC. J Clin Oncol. 2008;26:121–6.

    Article  PubMed  Google Scholar 

  14. Steinkamp HJ, van der Hoeck E, Bock JC, Felix R. The extracapsular spread of cervical lymph node metastases: the diagnostic value of computed tomography. Rofo. 1999;170:457–62.

    Article  PubMed  CAS  Google Scholar 

  15. Steinkamp HJ, Beck A, Werk M, Felix R. Extracapsular spread of cervical lymph node metastases: diagnostic value of magnetic resonance imaging. Rofo. 2002;174:50–5.

    Article  PubMed  CAS  Google Scholar 

  16. Steinkamp HJ, Beck A, Werk M, Rademaker J, Felix R. Extracapsular spread of cervical lymph node metastases: diagnostic relevance of ultrasound examinations. Ultraschall Med. 2003;24:323–30.

    Article  PubMed  CAS  Google Scholar 

  17. Akita H, Doki Y, Yano M, Miyata H, Miyashiro I, Ohigashi H, et al. Effects of neoadjuvant chemotherapy on primary tumor and lymph node metastasis in esophageal squamous cell carcinoma: additive association with prognosis. Dis Esophagus. 2009;22:291–7.

    Article  PubMed  Google Scholar 

  18. Amajoyi R, Lee Y, Recio PJ, Kondylis PD. Neoadjuvant therapy for rectal cancer decreases the number of lymph nodes harvested in operative specimens. Am J Surg. 2013;205:289–92 (discussion 92).

    Article  PubMed  Google Scholar 

  19. Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi. 1984;85:1001–5.

    PubMed  CAS  Google Scholar 

  20. Tsuchikawa T, Md MM, Yamamura Y, Shichinohe T, Hirano S, Kondo S. The immunological impact of neoadjuvant chemotherapy on the tumor microenvironment of esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:1713–9.

    Article  PubMed  Google Scholar 

  21. Suzuki Y, Mimura K, Yoshimoto Y, Watanabe M, Ohkubo Y, Izawa S, et al. Immunogenic tumor cell death induced by chemoradiotherapy in patients with esophageal squamous cell carcinoma. Cancer Res. 2012;72:3967–76.

    Article  PubMed  CAS  Google Scholar 

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Ethical Statement

The study design was approved by the Mie University hospital’s ethics review board. Informed consent was obtained from all patients for being included in the study.

Conflict of interest

There are no financial or relations that could lead to conflict interest.

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Authors and Affiliations

  1. Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Susumu Saigusa, Yasuhiko Mohri, Koji Tanaka, Masaki Ohi, Tadanobu Shimura, Takahito Kitajima, Yoshito Ishino, Hiromi Yasuda, Yoshinaga Okugawa, Yuji Toiyama, Yasuhiro Inoue, Keiichi Uchida & Masato Kusunoki

Authors
  1. Susumu Saigusa
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  2. Yasuhiko Mohri
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  3. Koji Tanaka
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  4. Masaki Ohi
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  5. Tadanobu Shimura
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  6. Takahito Kitajima
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  7. Yoshito Ishino
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  8. Hiromi Yasuda
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  9. Yoshinaga Okugawa
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  11. Yasuhiro Inoue
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  12. Keiichi Uchida
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  13. Masato Kusunoki
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Corresponding author

Correspondence to Susumu Saigusa.

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Saigusa, S., Mohri, Y., Tanaka, K. et al. Impact of extracapsular lymph node involvement on tumor progression in esophageal squamous cell carcinoma after neoadjuvant therapy and effects on lymph nodes induced by chemotherapy and chemoradiotherapy. Esophagus 11, 108–116 (2014). https://doi.org/10.1007/s10388-014-0418-8

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  • DOI: https://doi.org/10.1007/s10388-014-0418-8

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