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Outcomes in Peritoneal Dissemination from Signet Ring Cell Carcinoma of the Appendix Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

  • Carlos Munoz-Zuluaga
  • Armando Sardi
  • Mary Caitlin King
  • Carol Nieroda
  • Michelle Sittig
  • Ryan MacDonald
  • Vadim Gushchin
Gastrointestinal Oncology
  • 12 Downloads

Abstract

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard treatment for peritoneal dissemination from appendiceal cancer (AC); however, its role in high-grade histopathologic subtypes (high-grade mucinous carcinoma peritonei [HGMCP] and HGMCP with signet ring cells [HGMCP-S]) is controversial due to their aggressive behavior. This study analyzed clinical outcomes of high-grade AC after CRS/HIPEC.

Methods

A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998–2017 was reviewed. Perioperative variables and survival were analyzed.

Results

Eighty-six HGMCP and 65 HGMCP-S were identified. HGMCP had more positive tumor markers (TM) (CEA/CA-125/CA-19-9) than HGMCP-S (63% vs 40%, p = 0.005). HGMCP had higher Peritoneal Cancer Index (32 vs 26, p = 0.097) and was less likely to have positive lymph nodes (LN) than HGMCP-S (28% vs 69%, p = < 0.001). Complete cytoreduction was achieved in 84% and 83%, respectively. PFS at 3- and 5-years was 59% and 48% for HGMCP vs 31% and 14% for HGMCP-S. Median PFS was 4.3 and 1.6 years, respectively (p < 0.001). OS at 3- and 5-years was 84% and 64% in HGMCP vs 38% and 25% in HGMCP-S. Median OS was 7.5 and 2.2 years, respectively (p < 0.001). LN negative HGMCP-S had longer median PFS and OS than LN positive HGMCP-S (PFS: 3.4 vs 1.5 years, p = 0.03; OS: 5.6 vs 2.1 months, p = 0.021).

Conclusions

The aggressive histology of HGMCP-S is associated with poor OS, has fewer abnormal TM, and is more likely to have positive LN. However, CRS/HIPEC can achieve a 5-year survival of 25%, which may improve to 51% with negative LN.

Notes

Disclosure

Carlos Munoz-Zuluaga, Armando Sardi, Mary Caitlin King, Carol Nieroda, Michelle Sittig, Ryan MacDonald, and Vadim Gushchin declare that there are no conflicts of interest regarding the publication of this paper.

References

  1. 1.
    McCusker ME, Cote TR, Clegg LX, Sobin LH. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973–1998. Cancer. 2002;94(12):3307–12.CrossRefPubMedGoogle Scholar
  2. 2.
    Smeenk RM, van Velthuysen ML, Verwaal VJ, Zoetmulder FA. Appendiceal neoplasms and pseudomyxoma peritonei: a population based study. Eur J Surg Oncol. 2008;34(2):196–201.CrossRefPubMedGoogle Scholar
  3. 3.
    Amin MB, Edge S, Greene F, et al. (eds.) AJCC Cancer Staging Manual. 8th ed, American Joint Commission on Cancer: Springer International Publishing; 2017.Google Scholar
  4. 4.
    Jimenez W, Sardi A, Nieroda C, et al. Predictive and prognostic survival factors in peritoneal carcinomatosis from appendiceal cancer after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2014;21(13):4218–25.CrossRefPubMedGoogle Scholar
  5. 5.
    Reghunathan M, Kelly KJ, Valasek MA, Lowy AM, Baumgartner JM. Histologic predictors of recurrence in mucinous appendiceal tumors with peritoneal dissemination after HIPEC. Ann Surg Oncol. 2018;25(3):702–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Ihemelandu C, Sugarbaker PH. Clinicopathologic and prognostic features in patients with peritoneal metastasis from mucinous adenocarcinoma, adenocarcinoma with signet ring cells, and adenocarcinoid of the appendix treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2016;23(5):1474–80.CrossRefPubMedGoogle Scholar
  7. 7.
    Kelly KJ. Management of appendix cancer. Clinics Colon Rectal Surg. 2015;28(4):247–55.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol. 1995;19(12):1390–408.CrossRefPubMedGoogle Scholar
  9. 9.
    Ronnett BM, Yan H, Kurman RJ, Shmookler BM, Wu L, Sugarbaker PH. Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis. Cancer. 2001;92(1):85–91.CrossRefPubMedGoogle Scholar
  10. 10.
    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(6):847–58.CrossRefPubMedGoogle Scholar
  11. 11.
    Misdraji J. Mucinous epithelial neoplasms of the appendix and pseudomyxoma peritonei. Mod Pathol. 2015;28 Suppl 1:S67–79.CrossRefPubMedGoogle Scholar
  12. 12.
    Chua TC, Pelz JO, Kerscher A, Morris DL, Esquivel J. Critical analysis of 33 patients with peritoneal carcinomatosis secondary to colorectal and appendiceal signet ring cell carcinoma. Ann Surg Oncol. 2009;16(10):2765–70.CrossRefPubMedGoogle Scholar
  13. 13.
    Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995;221(2):124–32.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Alakus H, Babicky ML, Ghosh P, et al. Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin. Genome Med. 2014;6(5):43.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Sugarbaker PH. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 2006;7(1):69–76.CrossRefPubMedGoogle Scholar
  16. 16.
    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
  17. 17.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefPubMedGoogle Scholar
  18. 18.
    Sugarbaker PH. Peritonectomy procedures. Surg Oncol Clin N Am. 2003;12(3):703–27, xiii.CrossRefPubMedGoogle Scholar
  19. 19.
    Shankar S, Ledakis P, El Halabi H, Gushchin V, Sardi A. Neoplasms of the appendix: current treatment guidelines. Hematol Oncol Clin North Am. 2012;26(6):1261–90.CrossRefGoogle Scholar
  20. 20.
    Dindo D, Demartines N, Clavien P-A. Classification of surgical complications. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.CrossRefPubMedGoogle Scholar
  22. 22.
    Shetty S, Natarajan B, Thomas P, Govindarajan V, Sharma P, Loggie B. Proposed classification of pseudomyxoma peritonei: influence of signet ring cells on survival. Am Surg. 2013;79(11):1171–6.PubMedGoogle Scholar
  23. 23.
    Ogino S, Brahmandam M, Cantor M, et al. Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component. Mod Pathol. 2006;19(1):59–68.CrossRefPubMedGoogle Scholar
  24. 24.
    Sirintrapun SJ, Blackham AU, Russell G, et al. Significance of signet ring cells in high-grade mucinous adenocarcinoma of the peritoneum from appendiceal origin. Hum Pathol. 2014;45(8):1597–604.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    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
  26. 26.
    Farquharson AL, Pranesh N, Witham G, et al. A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei. Br J Cancer. 2008;99(4):591–6.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Shapiro JF, Chase JL, Wolff RA, et al. Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin: a single-institution experience. Cancer. 2010;116(2):316–22.CrossRefPubMedGoogle Scholar
  28. 28.
    Lieu CH, Lambert LA, Wolff RA, et al. Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix. Ann Oncol. 2012;23(3):652–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Glehen O, Mohamed F, Sugarbaker PH. Incomplete cytoreduction in 174 patients with peritoneal carcinomatosis from appendiceal malignancy. Ann Surg. 2004;240(2):278–85.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Smeenk RM, Verwaal VJ, Antonini N, Zoetmulder FA. Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg. 2007;245(1):104–9.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Baratti D, Kusamura S, Nonaka D, et al. Pseudomyxoma peritonei: clinical pathological and biological prognostic factors in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Ann Surg Oncol. 2008;15(2):526–34.CrossRefPubMedGoogle Scholar
  32. 32.
    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
  33. 33.
    Sardi A, Jimenez WA, Nieroda C, Sittig M, Macdonald R, Gushchin V. Repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: analysis of survival outcomes. Eur J Surg Oncol. 2013;39(11):1207–13.CrossRefPubMedGoogle Scholar
  34. 34.
    Esquivel J, Sugarbaker PH. Second-look surgery in patients with peritoneal dissemination from appendiceal malignancy: analysis of prognostic factors in 98 patients. Ann Surg. 2001;234(2):198–205.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Votanopoulos KI, Ihemelandu C, Shen P, Stewart JH, Russell GB, Levine EA. Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy. J Am Coll Surg. 2012;215(3):412–7.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Taflampas P, Dayal S, Chandrakumaran K, Mohamed F, Cecil TD, Moran BJ. Pre-operative tumour marker status predicts recurrence and survival after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal Pseudomyxoma Peritonei: analysis of 519 patients. Eur J Surg Oncol. 2014;40(5):515–20.CrossRefPubMedGoogle Scholar
  37. 37.
    Kusamura S, Baratti D, Hutanu I, et al. The role of baseline inflammatory-based scores and serum tumor markers to risk stratify pseudomyxoma peritonei patients treated with cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Surg Oncol. 2015;41(8):1097–105.CrossRefPubMedGoogle Scholar
  38. 38.
    Baratti D, Kusamura S, Martinetti A, et al. Prognostic value of circulating tumor markers in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2007;14(8):2300–8.CrossRefPubMedGoogle Scholar
  39. 39.
    van Ruth S, Hart AA, Bonfrer JM, Verwaal VJ, Zoetmulder FA. Prognostic value of baseline and serial carcinoembryonic antigen and carbohydrate antigen 19.9 measurements in patients with pseudomyxoma peritonei treated with cytoreduction and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2002;9(10):961–7.CrossRefPubMedGoogle Scholar
  40. 40.
    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
  41. 41.
    van Oudheusden TR, Braam HJ, Nienhuijs SW, et al. Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology. J Surg Oncol. 2015;111(2):237–42.CrossRefPubMedGoogle Scholar
  42. 42.
    Quenet F, Elias D, Roca L, et al. A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. J Clin Oncol. 2018;36(18 Suppl):LBA3503.CrossRefGoogle Scholar
  43. 43.
    Prada-Villaverde A, Esquivel J, Lowy AM, et al. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014;110(7):779–85.CrossRefPubMedGoogle Scholar
  44. 44.
    Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21(20):3737–43.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  1. 1.The Institute for Cancer CareMercy Medical CenterBaltimoreUSA
  2. 2.Center for Clinical ExcellenceMercy Medical CenterBaltimoreUSA

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