Skip to main content
Top
Published in: Annals of Surgical Oncology 1/2020

01-01-2020 | Hemicolectomy | Peritoneal Surface Malignancy

Outcomes After Adjuvant Hyperthermic Intraperitoneal Chemotherapy for High-Risk Primary Appendiceal Neoplasms After Complete Resection

Authors: Laura M. Enomoto, MSc, MD, M. Haroon Choudry, MD, David L. Bartlett, MD, Linsay Totin, BS, Gary N. Mann, MD, Joseph J. Skitzki, MD, Kathleen C. Perry, BS, Konstantinos I. Votanopoulos, MD, PhD, Edward A. Levine, MD, Perry Shen, MD

Published in: Annals of Surgical Oncology | Issue 1/2020

Login to get access

Abstract

Introduction

Appendiceal neoplasms are uncommon tumors. Optimal treatment for patients with perforation or high-grade pathology after initial resection is unknown. This study evaluated patients with increased risk for peritoneal dissemination after primary resection, but no evidence of peritoneal disease, who underwent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

This multi-institutional cohort study evaluated 56 patients with high-risk (HR) appendiceal neoplasms with a peritoneal carcinomatosis index of 0 who underwent HIPEC. The patients were divided into two groups: perforated low-grade appendiceal (LGA) carcinoma and HR neoplasms, which included perforated high-grade appendiceal carcinoma, positive margins after initial resection, minimal macroscopic peritoneal disease that was previously resected or completely responded to systemic chemotherapy prior to HIPEC, goblet cell carcinoma, and adenocarcinoma with signet ring cell features. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan–Meier analysis.

Results

Thirty-eight percent of patients had perforated LGA and 68% had HR features. Five-year OS probability was 82.1% for the entire cohort, and 100% and 70.1% for patients with perforated LGA and HR features, respectively (p = 0.024). Five-year RFS probability was 79.3% for the entire cohort, and 90.0% and 72.4% for patients with perforated LGA and HR features, respectively (p = 0.025). Eight patients recurred after HIPEC and their OS was significantly worse (p < 0.001).

Conclusion

While adjuvant HIPEC is both safe and feasible, there appears to be little benefit over close surveillance when outcomes are compared with historical and prospective studies, especially for perforated LGA carcinoma.
Literature
1.
go back to reference 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):3307–3312.CrossRef 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):3307–3312.CrossRef
2.
go back to reference Marmor S, Portschy PR, Tuttle TM, Virnig BA. The rise in appendiceal cancer incidence: 2000–2009. J Gastrointest Surg. 2015;19(4):743–750.CrossRef Marmor S, Portschy PR, Tuttle TM, Virnig BA. The rise in appendiceal cancer incidence: 2000–2009. J Gastrointest Surg. 2015;19(4):743–750.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference Madani A, van der Bilt JD, Consten EC, Vriens MR, Borel Rinkes IH. Perforation in appendiceal well-differentiated carcinoid and goblet cell tumors: impact on prognosis? A systematic review. Ann Surg Oncol. 2015;22(3):959–965.CrossRef Madani A, van der Bilt JD, Consten EC, Vriens MR, Borel Rinkes IH. Perforation in appendiceal well-differentiated carcinoid and goblet cell tumors: impact on prognosis? A systematic review. Ann Surg Oncol. 2015;22(3):959–965.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference Mehta A, Mittal R, Chandrakumaran K, et al. Peritoneal involvement is more common than nodal involvement in patients with high-grade appendix tumors who are undergoing prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Dis Colon Rectum. 2017;60(11):1155–1161.CrossRef Mehta A, Mittal R, Chandrakumaran K, et al. Peritoneal involvement is more common than nodal involvement in patients with high-grade appendix tumors who are undergoing prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Dis Colon Rectum. 2017;60(11):1155–1161.CrossRef
7.
go back to reference 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):2449–2456.CrossRef 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):2449–2456.CrossRef
8.
go back to reference Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22(16):3284–3292.CrossRef Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22(16):3284–3292.CrossRef
9.
go back to reference Glehen O, Gilly FN, Boutitie F, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608–5618.CrossRef Glehen O, Gilly FN, Boutitie F, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608–5618.CrossRef
10.
go back to reference Yan TD, Deraco M, Elias D, et al. A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database. Cancer. 2011;117(9):1855–1863.CrossRef Yan TD, Deraco M, Elias D, et al. A novel tumor-node-metastasis (TNM) staging system of diffuse malignant peritoneal mesothelioma using outcome analysis of a multi-institutional database. Cancer. 2011;117(9):1855–1863.CrossRef
11.
go back to reference Tuvin D, Berger Y, Aycart SN, et al. Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms. Int J Hyperth. 2016;32(3):311–315.CrossRef Tuvin D, Berger Y, Aycart SN, et al. Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms. Int J Hyperth. 2016;32(3):311–315.CrossRef
12.
go back to reference Baratti D, Kusamura S, Iusco D, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of primary curative surgery in patients with colorectal cancer at high risk for metachronous peritoneal metastases. Ann Surg Oncol. 2017;24(1):167–175.CrossRef Baratti D, Kusamura S, Iusco D, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of primary curative surgery in patients with colorectal cancer at high risk for metachronous peritoneal metastases. Ann Surg Oncol. 2017;24(1):167–175.CrossRef
13.
go back to reference Sammartino P, Sibio S, Biacchi D, et al. Prevention of peritoneal metastases from colon cancer in high-risk patients: preliminary results of surgery plus prophylactic HIPEC. Gastroenterol. Res. Pract. 2012;2012:141585.CrossRef Sammartino P, Sibio S, Biacchi D, et al. Prevention of peritoneal metastases from colon cancer in high-risk patients: preliminary results of surgery plus prophylactic HIPEC. Gastroenterol. Res. Pract. 2012;2012:141585.CrossRef
14.
go back to reference Goere D, Glehen O, Quenet F, et al. Results of a randomized phase 3 study evaluating the potential benefit of a second-look surgery plus HIPEC in patients at high risk of developing colorectal peritoneal metastases. J Clin Oncol. 2018;36(15 Suppl):3531.CrossRef Goere D, Glehen O, Quenet F, et al. Results of a randomized phase 3 study evaluating the potential benefit of a second-look surgery plus HIPEC in patients at high risk of developing colorectal peritoneal metastases. J Clin Oncol. 2018;36(15 Suppl):3531.CrossRef
15.
go back to reference Klaver CE, Wisselink DD, Punt CJ, et al. Adjuvant HIPEC in patients with colon cancer at high risk of peritoneal metastases: primary outcome of the COLOPEC multicenter randomized trial. J Clin Oncol. 2019;37(4 Suppl):482.CrossRef Klaver CE, Wisselink DD, Punt CJ, et al. Adjuvant HIPEC in patients with colon cancer at high risk of peritoneal metastases: primary outcome of the COLOPEC multicenter randomized trial. J Clin Oncol. 2019;37(4 Suppl):482.CrossRef
16.
go back to reference Glehen O, Passot G, Villeneuve L, et al. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study. BMC Cancer. 2014;14:183.CrossRef Glehen O, Passot G, Villeneuve L, et al. GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study. BMC Cancer. 2014;14:183.CrossRef
17.
go back to reference Coccolini F, Celotti A, Ceresoli M, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) and neoadjuvant chemotherapy as prophylaxis of peritoneal carcinosis from advanced gastric cancer-effects on overall and disease free survival. J Gastrointest Oncol. 2016;7(4):523–529.CrossRef Coccolini F, Celotti A, Ceresoli M, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) and neoadjuvant chemotherapy as prophylaxis of peritoneal carcinosis from advanced gastric cancer-effects on overall and disease free survival. J Gastrointest Oncol. 2016;7(4):523–529.CrossRef
18.
go back to reference Honore C, Caruso F, Dartigues P, et al. Strategies for preventing pseudomyxoma peritonei after resection of a mucinous neoplasm of the appendix. Anticancer Res. 2015;35(9):4943–4947.PubMed Honore C, Caruso F, Dartigues P, et al. Strategies for preventing pseudomyxoma peritonei after resection of a mucinous neoplasm of the appendix. Anticancer Res. 2015;35(9):4943–4947.PubMed
19.
go back to reference Zih FS, Wong-Chong N, Hummel C, et al. Mucinous tumor of the appendix with limited peritoneal spread: is there a role for expectant observation? Ann Surg Oncol. 2014;21(1):225–231.CrossRef Zih FS, Wong-Chong N, Hummel C, et al. Mucinous tumor of the appendix with limited peritoneal spread: is there a role for expectant observation? Ann Surg Oncol. 2014;21(1):225–231.CrossRef
20.
go back to reference McDonald JR, O’Dwyer ST, Rout S, et al. Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms. Br J Surg. 2012;99(7):987–992.CrossRef McDonald JR, O’Dwyer ST, Rout S, et al. Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms. Br J Surg. 2012;99(7):987–992.CrossRef
21.
go back to reference Madsen AH, Ladekarl M, Villadsen GE, et al. Effects of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of goblet cell carcinoma: a prospective cohort study. Ann Surg Oncol. 2018;25(2):422–430.CrossRef Madsen AH, Ladekarl M, Villadsen GE, et al. Effects of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of goblet cell carcinoma: a prospective cohort study. Ann Surg Oncol. 2018;25(2):422–430.CrossRef
22.
go back to reference Votanopoulos KI, Bartlett D, Moran B, et al. PCI is not predictive of survival after complete CRS/HIPEC in peritoneal dissemination from high-grade appendiceal primaries. Ann Surg Oncol. 2018;25(3):674–678.CrossRef Votanopoulos KI, Bartlett D, Moran B, et al. PCI is not predictive of survival after complete CRS/HIPEC in peritoneal dissemination from high-grade appendiceal primaries. Ann Surg Oncol. 2018;25(3):674–678.CrossRef
23.
go back to reference Levine EA, Votanopoulos KI, Qasem SA, et al. Prognostic molecular subtypes of low-grade cancer of the appendix. J Am Coll Surg. 2016;222(4):493–503.CrossRef Levine EA, Votanopoulos KI, Qasem SA, et al. Prognostic molecular subtypes of low-grade cancer of the appendix. J Am Coll Surg. 2016;222(4):493–503.CrossRef
24.
go back to reference Levine EA, Votanopoulos KI, Shen P, et al. A multicenter randomized trial to evaluate hematologic toxicities after hyperthermic intraperitoneal chemotherapy with oxaliplatin or mitomycin in patients with appendiceal tumors. J Am Coll Surg. 2018;226(4):434–443.CrossRef Levine EA, Votanopoulos KI, Shen P, et al. A multicenter randomized trial to evaluate hematologic toxicities after hyperthermic intraperitoneal chemotherapy with oxaliplatin or mitomycin in patients with appendiceal tumors. J Am Coll Surg. 2018;226(4):434–443.CrossRef
25.
go back to reference 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):1425–1439.CrossRef 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):1425–1439.CrossRef
26.
go back to reference Carr NJ, McCarthy WF, Sobin LH. Epithelial noncarcinoid tumors and tumor-like lesions of the appendix. A clinicopathologic study of 184 patients with a multivariate analysis of prognostic factors. Cancer. 1995;75(3):757–768.CrossRef Carr NJ, McCarthy WF, Sobin LH. Epithelial noncarcinoid tumors and tumor-like lesions of the appendix. A clinicopathologic study of 184 patients with a multivariate analysis of prognostic factors. Cancer. 1995;75(3):757–768.CrossRef
27.
go back to reference Misdraji J, Yantiss RK, Graeme-Cook FM, Balis UJ, Young RH. Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases. Am J Surg Pathol. 2003;27(8):1089–1103.CrossRef Misdraji J, Yantiss RK, Graeme-Cook FM, Balis UJ, Young RH. Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases. Am J Surg Pathol. 2003;27(8):1089–1103.CrossRef
28.
go back to reference Dhage-Ivatury S, Sugarbaker PH. Update on the surgical approach to mucocele of the appendix. J Am Coll Surg. 2006;202(4):680–684.CrossRef Dhage-Ivatury S, Sugarbaker PH. Update on the surgical approach to mucocele of the appendix. J Am Coll Surg. 2006;202(4):680–684.CrossRef
29.
go back to reference Yantiss RK, Shia J, Klimstra DS, Hahn HP, Odze RD, Misdraji J. Prognostic significance of localized extra-appendiceal mucin deposition in appendiceal mucinous neoplasms. Am J Surg Pathol. 2009;33(2):248–255.CrossRef Yantiss RK, Shia J, Klimstra DS, Hahn HP, Odze RD, Misdraji J. Prognostic significance of localized extra-appendiceal mucin deposition in appendiceal mucinous neoplasms. Am J Surg Pathol. 2009;33(2):248–255.CrossRef
30.
go back to reference Roxburgh CS, Fenig YM, Cercek A, et al. Outcomes of low-grade appendiceal mucinous neoplasms with remote acellular mucinous peritoneal deposits. Ann Surg Oncol. 2019;26(1):118–124.CrossRef Roxburgh CS, Fenig YM, Cercek A, et al. Outcomes of low-grade appendiceal mucinous neoplasms with remote acellular mucinous peritoneal deposits. Ann Surg Oncol. 2019;26(1):118–124.CrossRef
31.
go back to reference Haslinger M, Francescutti V, Attwood K, et al. A contemporary analysis of morbidity and outcomes in cytoreduction/hyperthermic intraperitoneal chemoperfusion. Cancer Med. 2013;2(3):334–342.CrossRef Haslinger M, Francescutti V, Attwood K, et al. A contemporary analysis of morbidity and outcomes in cytoreduction/hyperthermic intraperitoneal chemoperfusion. Cancer Med. 2013;2(3):334–342.CrossRef
32.
go back to reference Bao P, Bartlett D. Surgical techniques in visceral resection and peritonectomy procedures. Cancer J. 2009;15(3):204–211.CrossRef Bao P, Bartlett D. Surgical techniques in visceral resection and peritonectomy procedures. Cancer J. 2009;15(3):204–211.CrossRef
33.
go back to reference Levine EA, Stewart JH 4th, Shen P, Russell GB, Loggie BL, Votanopoulos KI. Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients. J Am Coll Surg. 2014;218(4):573–585.CrossRef Levine EA, Stewart JH 4th, Shen P, Russell GB, Loggie BL, Votanopoulos KI. Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients. J Am Coll Surg. 2014;218(4):573–585.CrossRef
34.
go back to reference Bradley RF, Stewart JH 4th, Russell GB, Levine EA, Geisinger KR. Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic analysis of 101 patients uniformly treated at a single institution, with literature review. Am J Surg Pathol. 2006;30(5):551–559.CrossRef Bradley RF, Stewart JH 4th, Russell GB, Levine EA, Geisinger KR. Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic analysis of 101 patients uniformly treated at a single institution, with literature review. Am J Surg Pathol. 2006;30(5):551–559.CrossRef
35.
go back to reference Radomski M, Pai RK, Shuai Y, et al. Curative surgical resection as a component of multimodality therapy for peritoneal metastases from goblet cell carcinoids. Ann Surg Oncol. 2016;23(13):4338–4343.CrossRef Radomski M, Pai RK, Shuai Y, et al. Curative surgical resection as a component of multimodality therapy for peritoneal metastases from goblet cell carcinoids. Ann Surg Oncol. 2016;23(13):4338–4343.CrossRef
36.
go back to reference Blackham AU, Swett K, Eng C, et al. Perioperative systemic chemotherapy for appendiceal mucinous carcinoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2014;109(7):740–745.CrossRef Blackham AU, Swett K, Eng C, et al. Perioperative systemic chemotherapy for appendiceal mucinous carcinoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2014;109(7):740–745.CrossRef
37.
go back to reference Bijelic L, Kumar AS, Stuart OA, Sugarbaker PH. Systemic chemotherapy prior to cytoreductive surgery and HIPEC for carcinomatosis from appendix cancer: impact on perioperative outcomes and short-term survival. Gastroenterol Res Pract. 2012;2012:163284.PubMedPubMedCentral Bijelic L, Kumar AS, Stuart OA, Sugarbaker PH. Systemic chemotherapy prior to cytoreductive surgery and HIPEC for carcinomatosis from appendix cancer: impact on perioperative outcomes and short-term survival. Gastroenterol Res Pract. 2012;2012:163284.PubMedPubMedCentral
38.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–213.CrossRef Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–213.CrossRef
39.
go back to reference Yan TD, Black D, Sugarbaker PH, et al. A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer. Ann Surg Oncol. 2007;14(10):2702–2713.CrossRef Yan TD, Black D, Sugarbaker PH, et al. A systematic review and meta-analysis of the randomized controlled trials on adjuvant intraperitoneal chemotherapy for resectable gastric cancer. Ann Surg Oncol. 2007;14(10):2702–2713.CrossRef
40.
go back to reference Coccolini F, Cotte E, Glehen O, et al. Intraperitoneal chemotherapy in advanced gastric cancer Meta-analysis of randomized trials. Eur J Surg Oncol. 2014;40(1):12–26.CrossRef Coccolini F, Cotte E, Glehen O, et al. Intraperitoneal chemotherapy in advanced gastric cancer Meta-analysis of randomized trials. Eur J Surg Oncol. 2014;40(1):12–26.CrossRef
Metadata
Title
Outcomes After Adjuvant Hyperthermic Intraperitoneal Chemotherapy for High-Risk Primary Appendiceal Neoplasms After Complete Resection
Authors
Laura M. Enomoto, MSc, MD
M. Haroon Choudry, MD
David L. Bartlett, MD
Linsay Totin, BS
Gary N. Mann, MD
Joseph J. Skitzki, MD
Kathleen C. Perry, BS
Konstantinos I. Votanopoulos, MD, PhD
Edward A. Levine, MD
Perry Shen, MD
Publication date
01-01-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 1/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-019-07634-y

Other articles of this Issue 1/2020

Annals of Surgical Oncology 1/2020 Go to the issue