Outcomes in Peritoneal Dissemination from Signet Ring Cell Carcinoma of the Appendix Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
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.
A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998–2017 was reviewed. Perioperative variables and survival were analyzed.
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).
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.
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.
- 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
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.Google Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar