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Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Gastric signet ring cell carcinoma (SRC) has shown a favorable outcome in early stages but has a worse prognosis than non-SRC in advanced stages. However, the cause for this stage-dependent prognostic impact has not been determined. This study aimed to compare clinicopathologic features and recurrence patterns between gastric SRC and non-SRC in a cohort of Eastern patients.

Methods

This study reviewed the prospectively collected data of 764 patients undergoing curative resection for gastric cancer from 2005 to 2008. The demographics, clinicopathologic characteristics, disease-specific survival (DSS) rate, and recurrence-free survival (RFS) rate of the patients were analyzed.

Results

The SRC patients (n = 176) had a worse prognosis than the non-SRC patients (n = 588), especially in stages T3 and T4. Peritoneal recurrence and the incidence of neural invasion (NI) were significantly increased in the SRC patients, albeit only in stages T3 and T4. In the T3 and T4 patients with NI, peritoneal recurrence occurred more frequently in SRC than in non-SRC (28.7% vs. 13.7%; p = 0.001), but not in the T3 and T4 patients without NI. Only in the patients with NI, SRC led to a significantly shorter DSS (67.6 vs. 90.7 months; p = 0.008) and RFS (67.1 vs. 80.3 months; p = 0.036) than non-SRC.

Conclusions

This report is the first to present the relationship between NI and peritoneal recurrence as the cause of stage-dependent prognoses for SRC. A better understanding of NI may lend insight into cancer spread and recurrence, especially in gastric SRC.

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References

  1. Piessen G, Messager M, Leteurtre E, Jean-Pierre T, Mariette C. Signet ring cell histology is an independent predictor of poor prognosis in gastric adenocarcinoma regardless of tumoral clinical presentation. Ann Surg. 2009;250:878–87.

    Article  PubMed  Google Scholar 

  2. Ribeiro MM, Sarmento JA, Sobrinho Simoes MA, Bastos J. Prognostic significance of Lauren and Ming classifications and other pathologic parameters in gastric carcinoma. Cancer. 1981;47:780–4.

    Article  CAS  PubMed  Google Scholar 

  3. Hyung WJ, Noh SH, Lee JH, et al. Early gastric carcinoma with signet ring cell histology. Cancer. 2002;94:78–83.

    Article  PubMed  Google Scholar 

  4. Kunisaki C, Shimada H, Nomura M, Matsuda G, Otsuka Y, Akiyama H. Therapeutic strategy for signet ring cell carcinoma of the stomach. Br J Surg. 2004;91:1319–24.

    Article  CAS  PubMed  Google Scholar 

  5. Chon HJ, Hyung WJ, Kim C, et al. Differential prognostic implications of gastric signet ring cell carcinoma: stage-adjusted analysis from a single high-volume center in Asia. Ann Surg. 2017;265:946–53.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol. 2010;17:3077–9.

    Article  PubMed  Google Scholar 

  7. Japanese gastric cancer A. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer. 2011;14:113–23.

    Article  Google Scholar 

  8. Nagakawa T, Mori K, Nakano T, et al. Perineural invasion of carcinoma of the pancreas and biliary tract. Br J Surg. 1993;80:619–21.

    Article  CAS  PubMed  Google Scholar 

  9. Beard CJ, Chen MH, Cote K, et al. Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer. Int J Radiat Oncol Biol Phys. 2004;58:19–24.

    Article  CAS  PubMed  Google Scholar 

  10. Fordice J, Kershaw C, El-Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg. 1999;125:149–52.

    Article  CAS  PubMed  Google Scholar 

  11. Jiang N, Deng JY, Liu Y, Ke B, Liu HG, Liang H. Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis staging system. Tumour Biol. 2014;35:9429–36.

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka A, Watanabe T, Okuno K, Yasutomi M. Perineural invasion as a predictor of recurrence of gastric cancer. Cancer. 1994;73:550–5.

    Article  CAS  PubMed  Google Scholar 

  13. Kong P, Wu R, Yang C, et al. Prognostic impact of the signet ring cell type in node-negative gastric cancer. Sci Rep. 2016;6:26313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bilici A, Seker M, Ustaalioglu BB, et al. Prognostic significance of perineural invasion in patients with gastric cancer who underwent curative resection. Ann Surg Oncol. 2010;17:2037–44.

    Article  PubMed  Google Scholar 

  15. Tianhang L, Guoen F, Jianwei B, Liye M. The effect of perineural invasion on overall survival in patients with gastric carcinoma. J Gastrointest Surg. 2008;12:1263–7.

    Article  PubMed  Google Scholar 

  16. Yoshida M, Sugino T, Kusafuka K, et al. Peritoneal dissemination in early gastric cancer: importance of the lymphatic route. Virchows Arch. 2016;469:155–61.

    Article  PubMed  Google Scholar 

  17. Tanaka A, Yoshikawa H, Okuno K, et al. The importance of neural invasion (NI) as a prognostic factor in diffuse invasive gastric cancer. Surg Today. 1997;27:692–5.

    Article  CAS  PubMed  Google Scholar 

  18. Kim YB, Han SU, Lee D. Prominent neural invasion of mucosal gastric cancer into the muscularis propria. Histopathology. 2017. https://doi.org/10.1111/his.13259.

    Google Scholar 

  19. Hassan MO, Maksem J. The prostatic perineural space and its relation to tumor spread: an ultrastructural study. Am J Surg Pathol. 1980;4:143–8.

    Article  CAS  PubMed  Google Scholar 

  20. Rodin AE, Larson DL, Roberts DK. Nature of the perineural space invaded by prostatic carcinoma. Cancer. 1967;20:1772–9.

    Article  CAS  PubMed  Google Scholar 

  21. Liebl F, Demir IE, Mayer K, et al. The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study. Ann Surg. 2014;260:900–7. (discussion 7–8).

    Article  PubMed  Google Scholar 

  22. Yamada H, Kojima K, Inokuchi M, Kawano T, Sugihara K. Efficacy of celiac branch preservation in Roux-en-y reconstruction after laparoscopy-assisted distal gastrectomy. Surgery. 2011;149:22–8.

    Article  PubMed  Google Scholar 

  23. Uyama I, Sakurai Y, Komori Y, et al. Laparoscopic gastrectomy with preservation of the vagus nerve accompanied by lymph node dissection for early gastric carcinoma. J Am Coll Surg. 2005;200:140–5.

    Article  PubMed  Google Scholar 

  24. Weerasuriya A, Mizisin AP. The blood–nerve barrier: structure and functional significance. Methods Mol Biol. 2011;686:149–73.

    Article  CAS  PubMed  Google Scholar 

  25. Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1C1B2003970), by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0364), and by the New Faculty Research Fund of Ajou University School of Medicine.

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Correspondence to Hoon Hur MD, PhD.

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Lee, D., Son, SY., Kim, YB. et al. Neural Invasion is a Significant Contributor to Peritoneal Recurrence in Signet Ring Cell Gastric Carcinoma. Ann Surg Oncol 25, 1167–1175 (2018). https://doi.org/10.1245/s10434-018-6371-3

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  • DOI: https://doi.org/10.1245/s10434-018-6371-3

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