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Defining “Complete Cytoreduction” After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) for the Histopathologic Spectrum of Appendiceal Carcinomatosis



The completeness of cytoreduction (CC) score, which quantifies residual tumor, is a major prognostic factor when treating appendiceal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Both CC-0 and CC-1 are considered complete cytoreductions (CC-0/1) and associated with the best outcomes. We analyzed if the CC-0/1 definition is reliable across appendiceal histopathologic subtypes.


A prospective database of CRS/HIPEC patients with appendiceal carcinomatosis from 1998 to 2019 was reviewed to identify patients with CC-0/1. Kaplan–Meier overall survival (OS) and progression-free survival (PFS) by CC-score for each histopathology were calculated.


Overall, 297 patients had CC-0/1. Mean age was 54 ± 12 years with 67% females. Histopathologic subtypes were 45% low-grade mucinous carcinoma peritonei (LGMCP), 27% high-grade MCP (HGMCP), 20% HGMCP with signet ring cells (HGMCP-S), and 8% goblet cell adenocarcinoma (GCAC). CC-0 and CC-1 occurred in 57% and 43% of LGMCP, 65% and 35% of HGMCP, 68% and 32% of HGMCP-S, and 79% and 21% of GCAC, respectively. OS and PFS were statistically longer for CC-0 versus CC-1 in HGMCP-S (p = 0.001 and p = 0.005, respectively) and GCAC (p < 0.001 and p < 0.001), but not in LGMCP (p = 0.098 and p = 0.398) or HGMCP (p = 0.167 and p = 0.356).


Survival outcomes for CC-0 and CC-1 after CRS/HIPEC are different for HGMCP-S and GCAC but not for LGMCP and HGMCP. In HGCMP-S and GCAC, only CC-0 should be considered a complete cytoreduction and analyzed separately from CC-1. This distinction is key to understand disease behavior, accurately address patient prognosis, and explore new treatment strategies.

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  1. Bradley RF, Carr NJ. Pseudomyxoma peritonei: pathology, a historical overview, and proposal for unified nomenclature and updated grading. AJSP Rev Rep. 2019;24(3):88–93.

    Google Scholar 

  2. Munoz-Zuluaga C, King MC, Sardi A, et al. Selection and characteristics of patients with peritoneal dissemination from appendiceal cancer with exceptional/poor survival after CRS/HIPEC. Ann Surg Oncol. 2019;26:2268–75.

    Article  Google Scholar 

  3. Zambrano-Vera K, Sardi A, Munoz-Zuluaga C, et al. Outcomes in peritoneal carcinomatosis from appendiceal goblet cell carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Ann Surg Oncol. 2020;27(1):179–87.

    Article  Google Scholar 

  4. Zhang K, Meyerson C, Kassardjian A, Westbrook LM, Zheng W, Wang HL. Goblet cell carcinoid/carcinoma: an update. Adv Anatomic Pathol. 2019;26(2):75–83.

    CAS  Article  Google Scholar 

  5. Sugarbaker PH. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 2006;7(1):69–76.

    Article  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. Baratti D, Kusamura S, Nonaka D, Cabras AD, Laterza B, Deraco M. Pseudomyxoma peritonei: biological features are the dominant prognostic determinants after complete cytoreduction and hyperthermic intraperitoneal chemotherapy. Ann Surg. 2009;249(2):243–9.

    Article  Google Scholar 

  8. Sugarbaker P. Technical handbook for the integration of cytoreductive surgery and perioperative intraperitoneal chemotherapy into the surgical management of gastrointestinal and gynecologic malignancy, 4th edn. Washington: Foundation for Applied Research in Gastrointestinal Oncology; 2005.

    Google Scholar 

  9. Sugarbaker PH. Pseudomyxoma peritonei and peritoneal metastases from appendiceal malignancy. In: Sugarbaker PH, editor. Cytoreductive surgery and perioperative chemotherapy for peritoneal surface malignancy, 2nd edn. Woodbury: Cine-Med, Inc.; 2017. p. 109–32.

    Google Scholar 

  10. Kusamura S, Dominique E, Baratti D, Younan R, Deraco M. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98(4):247–52.

    Article  Google Scholar 

  11. Gonzalez-Moreno S, Kusamura S, Baratti D, Deraco M. Postoperative residual disease evaluation in the locoregional treatment of peritoneal surface malignancy. J Surg Oncol. 2008;98(4):237–41.

    Article  Google Scholar 

  12. van Velthuysen M-LF, van Eeden S, Carr NJ. The enigma of goblet cell tumors of the appendix. AJSP Rev Rep 2019;24(3):98–104.

    Google Scholar 

  13. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.

    CAS  Article  Google Scholar 

  14. Sugarbaker PH, Chang D. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol. 1999;6(8):727–31.

    CAS  Article  Google Scholar 

  15. Sugarbaker PH, Bakrin N, Deraco M, Glehen O, Morris DL, van der Speeten K. Cytoreductive surgery and perioperative chemotherapy for peritoneal surface malignancy. Textbook and video atlas, 2nd edn. Woodbury: Cine-Med, Inc; 2017.

    Google Scholar 

  16. El Halabi H, Gushchin V, Francis J, et al. The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with high-grade appendiceal carcinoma and extensive peritoneal carcinomatosis. Ann Surg Oncol. 2012;19(1):110–4.

    Article  Google Scholar 

  17. Los G, Mutsaers PH, Lenglet WJ, Baldew GS, McVie JG. Platinum distribution in intraperitoneal tumors after intraperitoneal cisplatin treatment. Cancer Chemother Pharmacol. 1990;25(6):389–94.

    CAS  Article  Google Scholar 

  18. Goodman MD, McPartland S, Detelich D, Saif MW. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. J Gastrointest Oncol. 2016;7(1):45–57.

    PubMed  PubMed Central  Google Scholar 

  19. 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.

    Article  Google Scholar 

  20. Yan TD, Bijelic L, Sugarbaker PH. Critical analysis of treatment failure after complete cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal dissemination from appendiceal mucinous neoplasms. Ann Surg Oncol. 2007;14(8):2289–99.

    Article  Google Scholar 

  21. 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.

    CAS  Article  Google Scholar 

  22. 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.

    CAS  Article  Google Scholar 

  23. 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.

    Article  Google Scholar 

  24. Misdraji J. Mucinous epithelial neoplasms of the appendix and pseudomyxoma peritonei. Mod Pathol. 2015;28 Suppl 1:S67–79.

    Article  Google Scholar 

  25. Sugarbaker PH, Sardi A, Brown G, Dromain C, Rousset P, Jelinek JS. Concerning CT features used to select patients for treatment of peritoneal metastases, a pictoral essay. Int J Hyperthermia. 2017;33(5):497–504.

    Article  Google Scholar 

  26. Heaney RM, Shields C, Mulsow J. Outcome following incomplete surgical cytoreduction combined with intraperitoneal chemotherapy for colorectal peritoneal metastases. World J Gastrointest Oncol. 2015;7(12):445–54.

    Article  Google Scholar 

  27. Spiliotis J, Kalles V, Kyriazanos I, et al. CRS and HIPEC in patients with peritoneal metastasis secondary to colorectal cancer: the small-bowel PCI score as a predictor of survival. Pleura Peritoneum. 2019;4(4):20190018.

    Article  Google Scholar 

  28. Yonemura Y, Canbay E, Ishibashi H. Prognostic factors of peritoneal metastases from colorectal cancer following cytoreductive surgery and perioperative chemotherapy. Sci World J. 2013;2013:978394.

    Article  Google Scholar 

  29. Benizri EI, Bernard JL, Rahili A, Benchimol D, Bereder JM. Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. World J Surg Oncol. 2012;10:56.

    Article  Google Scholar 

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Correspondence to Armando Sardi MD, FACS.

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Munoz-Zuluaga, C.A., King, M.C., Diaz-Sarmiento, V.S. et al. Defining “Complete Cytoreduction” After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) for the Histopathologic Spectrum of Appendiceal Carcinomatosis. Ann Surg Oncol 27, 5026–5036 (2020).

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