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Annals of Surgical Oncology

, Volume 25, Issue 3, pp 702–708 | Cite as

Histologic Predictors of Recurrence in Mucinous Appendiceal Tumors with Peritoneal Dissemination after HIPEC

  • Meera Reghunathan
  • Kaitlyn J. Kelly
  • Mark A. Valasek
  • Andrew M. Lowy
  • Joel M. Baumgartner
Gastrointestinal Oncology
  • 289 Downloads

Abstract

Background

Mucinous appendiceal tumors (MAT) are rare neoplasms that can metastasize to the peritoneum and often are treated with cytoreductive surgery (CRS) and HIPEC. Pathologic classification and outcomes vary, but standardized histologic definitions are emerging. We sought to evaluate outcomes in this disease after CRS/HIPEC using standardized pathologic criteria.

Method

Outcomes of MAT with peritoneal metastases (PM) after CRS/HIPEC from 2007 to 2015 were reviewed at our institution. Standardized histologic categories per WHO and consensus definitions were used: low-grade appendiceal mucinous neoplasm (LAMN), low-grade adenocarcinoma (LGAC), or high-grade adenocarcinoma (HGAC) primary tumors; and acellular mucin (AM), low-grade mucinous carcinoma peritonei (LGMCP), or high-grade mucinous carcinoma peritonei (HGMCP) peritoneal metastases. Cox proportional hazards model was used identify predictors of progression-free survival (PFS) by univariate and multivariate analyses.

Results

A total of 183 patients undergoing 197 CRS/HIPECs were included. Among 75 patients with primary histology review, there were 33 (44.0%) LAMNs, 28 (37.3%) LGACs, and 14 (18.7%) HGACs. Peritoneal histology was benign in 6 (3.0%), AM in 33 (16.8%), LGMCP in 114 (57.9%), and HGMCP in 44 (22.3%). PFS was not reached for AM, 34.3 months for LGMCP, and 16.8 months for HGMCP (p < 0.001). Peritoneal histology predicted PFS on multivariate analysis (hazard ratio 9.82 and 24.60 for LGMCP and HGMCP, respectively, vs. AM, p < 0.001). Among the LGMCP group, CEA and completeness of cytoreduction (CC score) predicted PFS on multivariate analysis.

Conclusions

Standardized peritoneal histology in patients with PM from MAT predicts PFS and patients with low-grade histology can be further discriminated by CEA and CC score.

Notes

Acknowledgement

This study was supported by a UCSD Clinical and Translational Research Institute Grant (UL1TR001442).

Disclosures

None of the authors of this manuscript have any disclosures or relevant conflicts of interest to declare.

References

  1. 1.
    Shaib WL, Goodman M, Chen Z, et al. Incidence and survival of appendiceal mucinous neoplasms: A SEER analysis. Am J Clin Oncol. 2015;40(6): 569–73.CrossRefGoogle Scholar
  2. 2.
    Connor SJ, Hanna GB, Frizelle FA. Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7970 appendectomies. Dis Colon Rectum. 1998;41(1):75–80.CrossRefPubMedGoogle Scholar
  3. 3.
    Pai RK, Beck AH, Norton JA, Longacre TA. Appendiceal mucinous neoplasms: clinicopathologic study of 116 cases with analysis of factors predicting recurrence. Am J Surg Pathol. 2009;33(10):1425–39.CrossRefPubMedGoogle Scholar
  4. 4.
    Gough DB, Donohue JH, Schutt AJ, et al. Pseudomyxoma peritonei. Long-term patient survival with an aggressive regional approach. Ann Surg. 1994;219(2):112–9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449–56.CrossRefPubMedGoogle Scholar
  6. 6.
    Austin F, Mavanur A, Sathaiah M, et al. Aggressive management of peritoneal carcinomatosis from mucinous appendiceal neoplasms. Ann Surg Oncol. 2012;19(5):1386–93.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pai RK, Longacre TA. Appendiceal mucinous tumors and pseudomyxoma peritonei: histologic features, diagnostic problems, and proposed classification. Adv Anatomic Pathol. 2005;12(6):291–311.CrossRefGoogle Scholar
  8. 8.
    Davison JM, Choudry HA, Pingpank JF, et al. Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. Mod Pathol. 2014;27(11):1521–39.CrossRefPubMedGoogle Scholar
  9. 9.
    Misdraji J. Appendiceal mucinous neoplasms: controversial issues. Arch Pathol Lab Med. 2010;134(6):864–70.PubMedGoogle Scholar
  10. 10.
    Bosman TF, Carniero F, Hruban RH, Theise ND, eds. World health organization classification of tumours of the digestive tract. 4th edn, vol 3. Lyon: IARC Press; 2010.Google Scholar
  11. 11.
    Carr NJ, Cecil TD, Mohamed F, et al. A consensus for classification and pathologic reporting of pseudomyxoma peritonei and associated appendiceal neoplasia: the results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process. Am J Surg Pathol. 2016;40(1):14–26.CrossRefPubMedGoogle Scholar
  12. 12.
    Carr NJ, Bibeau F, Bradley RF, et al. The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei. Histopathology. 2017;71:847–58.CrossRefPubMedGoogle Scholar
  13. 13.
    Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.CrossRefPubMedGoogle Scholar
  14. 14.
    Baumgartner JM, Tobin L, Heavey SF, Kelly KJ, Roeland EJ, Lowy AM. Predictors of progression in high-grade appendiceal or colorectal peritoneal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2015;22(5):1716–21.CrossRefPubMedGoogle Scholar
  15. 15.
    Portilla AG, Shigeki K, Dario B, Marcello D. The intraoperative staging systems in the management of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):228–31.CrossRefPubMedGoogle Scholar
  16. 16.
    Sugarbaker PH. Successful management of microscopic residual disease in large bowel cancer. Cancer Chemother Pharmacol. 1999;43 Suppl:S15–25.CrossRefPubMedGoogle Scholar
  17. 17.
    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer (Oxford, England : 1990). 2009;45(2):228–47.CrossRefGoogle Scholar
  18. 18.
    Enblad M, Birgisson H, Wanders A, Skoldberg F, Ghanipour L, Graf W. Importance of absent neoplastic epithelium in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2015;23:1149–56.CrossRefPubMedGoogle Scholar
  19. 19.
    Huang Y, Alzahrani NA, Chua TC, Morris DL. Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasm with peritoneal dissemination. Dis Colon Rectum. 2017;60(4):360–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Winer J, Zenati M, Ramalingam L, et al. Impact of aggressive histology and location of primary tumor on the efficacy of surgical therapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2014;21(5):1456–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Wagner PL, Austin F, Sathaiah M, et al. Significance of serum tumor marker levels in peritoneal carcinomatosis of appendiceal origin. Ann Surg Oncol. 2013;20(2):506–14.CrossRefPubMedGoogle Scholar
  22. 22.
    Villeneuve L, Isaac S, Glehen O, et al. The RENAPE network: towards a new healthcare organization for the treatment of rare tumors of the peritoneum. Description of the network and role of the pathologists. Ann Pathol. 2014;34(1):4–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Valasek MA, Thung I, Gollapalle E, et al. Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care. PLoS ONE. 2017;12(6):e0179216.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Meera Reghunathan
    • 1
  • Kaitlyn J. Kelly
    • 1
  • Mark A. Valasek
    • 2
  • Andrew M. Lowy
    • 1
  • Joel M. Baumgartner
    • 1
  1. 1.Department of Surgery, Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA
  2. 2.Department of Pathology, Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA

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