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Prognostic factors in Krukenberg tumor

  • Ruggero Lionetti
  • Marcello De Luca
  • Antonio TravaglinoEmail author
  • Antonio Raffone
  • Gabriele Saccone
  • Antonietta Di Cicco
  • Luigi Insabato
  • Massimo Mascolo
  • Maria D’Armiento
  • Fulvio Zullo
  • Francesco Corcione
Review

Abstract

Background

Krukenberg tumor (KT) is a rare secondary ovarian tumor. Little is known about clinicopathologic factors affecting prognosis in KT.

Objective

To assess the prognostic value of clinicopathologic factors in KT through a systematic review and meta-analysis.

Methods

Electronic databases were searched from their inception to February 2019 for studies assessing the association of clinicopathologic factors with overall survival in KT. Pooled hazard ratio (HR) was calculated for each factor; a p value < 0.05 was considered significant.

Results

Twenty-three studies with 1743 patients were included. A decreased overall survival was significantly associated with peritoneal involvement (HR 1.944; p = 0.003), ascites (HR 2.055; p = 0.034), synchronous presentation (HR 1.679; p = 0.034) and increased serum CEA levels (HR 1.380; p = 0.010), but not with age > 50 (HR 0.946; p = 0.743), menopausal status (HR 1.565; p = 0.204), gastric origin (HR 1.600; p = 0.201), size > 5 cm (HR 1.292; p = 0.119), size > 10 cm (HR 0.925; p = 0.714), bilateral ovarian involvement (HR 1.113; p = 0.347), non-peritoneal extaovarian metastases (HR 1.648; p = 0.237), liver metastases (HR 1.118, p = 0.555), predominant signet ring cell morphology (HR 1.322; p = 0.208) and levels of CA125 (HR 0.933; p = 0.828) and CA19.9 (HR 0.996; p = 0.992).

Conclusion

Peritoneal involvement, synchronous presentation, ascites and increased serum CEA levels appear as unfavorable prognostic factors in KT and might affect the patient management.

Keywords

Cancer Metastasis Prognosis Management Oncology Hazard ratio Therapy 

Notes

Author contributions

RL, MDL: study conception, electronic search, eligibility of the studies, inclusion criteria, risk of bias, data extraction and data analysis. AR, AT: study conception, disagreement resolution, manuscript preparation, data extraction and data analysis. GS, ADC: electronic search, eligibility of the studies, inclusion criteria, risk of bias, data extraction and data analysis. MM: methods supervision, manuscript preparation. MDA, LI: study design, methods supervision, manuscript preparation. FZ: study design, manuscript preparation, whole study supervision. FC: study design, methods supervision, whole study supervision.

Funding

No financial support was received for this study.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

Given the study design (systematic review and meta-analysis), Institutional Review Board approval was not requested, since no new patients’ data were handled.

Supplementary material

404_2019_5301_MOESM1_ESM.png (16 kb)
Supplementary material 1 Supplementary Figure 1. Flow diagram of studies identified in the systematic review (Prisma template [Preferred Reporting Item for Systematic Reviews and Meta-analyses]). (PNG 17 kb)
404_2019_5301_MOESM2_ESM.png (24 kb)
Supplementary material 1 Supplementary Figure 2. Assessment of risk of bias. Summary of risk of bias for each study; Plus sign: low risk of bias; minus sign: high risk of bias; question mark: unclear risk of bias. (PNG 25 kb)

References

  1. 1.
    Al-Agha OM, Nicastri AD (2006) An in-depth look at Krukenberg tumor: an overview. Arch Pathol Lab Med 130(11):1725–1730Google Scholar
  2. 2.
    Yang C, Sun L, Zhang L et al (2018) Diagnostic utility of SATB2 in metastatic Krukenberg tumors of the ovary: an immunohistochemical study of 70 cases with comparison to CDX2, CK7, CK20, chromogranin, and synaptophysin. Am J Surg Pathol 42(2):160–171CrossRefGoogle Scholar
  3. 3.
    Kubeček O, Laco J, Špaček J et al (2017) The pathogenesis, diagnosis, and management metastatic tumors to the ovary: a comprehensive review. Clin Exp Metastasis 34(5):295–307CrossRefGoogle Scholar
  4. 4.
    Turan T, Aykan B, Koc S et al (2006) Analysis of metastatic ovarian tumors from extragenital primary sites. Tumori 92(6):491–495CrossRefGoogle Scholar
  5. 5.
    Kiyokawa T, Young RH, Scully RE (2006) Krukenberg tumors of the ovary: a clinicopathologic analysis of 120 cases with emphasis on their variable pathologic manifestations. Am J Surg Pathol 30(3):277–299CrossRefGoogle Scholar
  6. 6.
    Novak E, Gray LA (1938) Krukenberg tumors of the ovary: clinical and pathological study of 21 cases. Surg Gynecol Obstet 66:157–167Google Scholar
  7. 7.
    Lionetti R, De Luca M, Travaglino A et al (2019) Treatments and overall survival in patients with Krukenberg tumor. Arch Gynecol Obstet 300(1):15–23CrossRefGoogle Scholar
  8. 8.
    Travaglino A, Raffone A, Saccone G et al (2018) Loss of B-cell lymphoma 2 immunohistochemical expression in endometrial hyperplasia: a specific marker of precancer and novel indication for treatment: A systematic review and meta-analysis. Acta Obstet Gynecol Scand 97(12):1415–1426CrossRefGoogle Scholar
  9. 9.
    Travaglino A, Raffone A, Saccone G et al (2019) Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria. Histopathology 74(5):676–687CrossRefGoogle Scholar
  10. 10.
    Raffone A, Travaglino A, Saccone G et al (2019) PAX2 in endometrial carcinogenesis and in differential diagnosis of endometrial hyperplasia. A systematic review and meta-analysis of diagnostic accuracy. Acta Obstet Gynecol Scand 98(3):287–299CrossRefGoogle Scholar
  11. 11.
    Raffone A, Travaglino A, Saccone G et al (2019) Loss of PTEN expression as diagnostic marker of endometrial precancer: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 98(3):275–286CrossRefGoogle Scholar
  12. 12.
    Moher D, Shamseer L, Clarke M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1CrossRefGoogle Scholar
  13. 13.
    Travaglino A, Raffone A, Saccone G et al (2018) PTEN as a predictive marker of response to conservative treatment in endometrial hyperplasia and early endometrial cancer. A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 231:104–110CrossRefGoogle Scholar
  14. 14.
    Raffone A, Travaglino A, Saccone G et al (2019) Management of women with atypical polypoid adenomyoma of the uterus: a quantitative systematic review. Acta Obstet Gynecol Scand 98(7):842–855CrossRefGoogle Scholar
  15. 15.
    Travaglino A, Raffone A, Saccone G et al (2019) Immunohistochemical predictive markers of response to conservative treatment of endometrial hyperplasia and early endometrial cancer: a systematic review. Acta Obstet Gynecol Scand.  https://doi.org/10.1111/aogs.13587 [Epub ahead of print] Google Scholar
  16. 16.
    Slim K, Nini E, Forestier D et al (2003) Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 73(9):712–716CrossRefGoogle Scholar
  17. 17.
    Travaglino A, Raffone A, Saccone G et al (2019) Immunohistochemical nuclear expression of β-catenin as a surrogate of CTNNB1 exon 3 mutation in endometrial cancer. Am J Clin Pathol 151(5):529–538CrossRefGoogle Scholar
  18. 18.
    Raffone A, Travaglino A, Saccone G et al (2019) Should progesterone and estrogens receptors be assessed for predicting the response to conservative treatment of endometrial hyperplasia and cancer? A systematic review and meta-analysis. Acta Obstet Gynecol Scand 98(8):976–987CrossRefGoogle Scholar
  19. 19.
    Travaglino A, Raffone A, Saccone G et al (2019) Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia. APMIS 127(6):427–434CrossRefGoogle Scholar
  20. 20.
    Travaglino A, Raffone A, Saccone G et al (2019) PTEN immunohistochemistry in endometrial hyperplasia: which are the optimal criteria for the diagnosis of precancer? APMIS 127(4):161–169CrossRefGoogle Scholar
  21. 21.
    Raffone A, Travaglino A, Saccone G et al (2019) Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis. Arch Gynecol Obstet 299(5):1233–1242CrossRefGoogle Scholar
  22. 22.
    Raffone A, Travaglino A, Saccone G et al (2019) PTEN expression in endometrial hyperplasia and risk of cancer: a systematic review and meta-analysis. Arch Gynecol Obstet 299(6):1511–1524CrossRefGoogle Scholar
  23. 23.
    Travaglino A, Raffone A, Saccone G et al (2019) Nuclear expression of β-catenin in endometrial hyperplasia as marker of premalignancy. APMIS.  https://doi.org/10.1111/apm.12988 [Epub ahead of print] Google Scholar
  24. 24.
    Raffone A, Travaglino A, Saccone G et al (2019) Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer. APMIS 127(9):597–606CrossRefGoogle Scholar
  25. 25.
    Raffone A, Travaglino A, Saccone G et al (2019) Diabetes mellitus is associated with occult cancer in endometrial hyperplasia. Pathol Oncol Res.  https://doi.org/10.1007/s12253-019-00684-3 [Epub ahead of print] Google Scholar
  26. 26.
    Raffone A, Travaglino A, Saccone G et al (2019) Diabetes mellitus and responsiveness of endometrial hyperplasia and early endometrial cancer to conservative treatment. Gynecol Endocrinol.  https://doi.org/10.1080/09513590.2019.1624716 [Epub ahead of print] Google Scholar
  27. 27.
    Rayson D, Bouttell E, Whiston F, Stitt L (2000) Outcome after ovarian/adnexal metastectomy in metastatic colorectal carcinoma. J Surg Oncol 75(3):186–192CrossRefGoogle Scholar
  28. 28.
    Kim HK, Heo DS, Bang YJ, Kim NK (2001) Prognostic factors of Krukenberg's tumor. Gynecol Oncol 82(1):105–109CrossRefGoogle Scholar
  29. 29.
    Cheong JH, Hyung WJ, Chen J, Kim J, Choi SH, Noh SH (2004) Surgical management and outcome of metachronous Krukenberg tumors from gastric cancer. J Surg Oncol 87(1):39–45CrossRefGoogle Scholar
  30. 30.
    McCormick CC, Giuntoli RL 2nd, Gardner GJ et al (2007) The role of cytoreductive surgery for colon cancer metastatic to the ovary. Gynecol Oncol 105(3):791–795CrossRefGoogle Scholar
  31. 31.
    Yook JH, Oh ST, Kim BS (2007) Clinical prognostic factors for ovarian metastasis in women with gastric cancer. Hepatogastroenterology 54(75):955–959Google Scholar
  32. 32.
    Jiang R, Tang J, Cheng X, Zang RY (2009) Surgical treatment for patients with different origins of Krukenberg tumors: outcomes and prognostic factors. Eur J Surg Oncol 35(1):92–97CrossRefGoogle Scholar
  33. 33.
    Kim WY, Kim TJ, Kim SE et al (2010) The role of cytoreductive surgery for non-genital tract metastatic tumors to the ovaries. Eur J Obstet Gynecol Reprod Biol 149(1):97–101CrossRefGoogle Scholar
  34. 34.
    Jun SY, Park JK (2011) Metachronous ovarian metastases following resection of the primary gastric cancer. J Gastric Cancer 11(1):31–37CrossRefGoogle Scholar
  35. 35.
    Ojo J, De Silva S, Han E et al (2011) Krukenberg tumors from colorectal cancer: presentation, treatment and outcomes. Am Surg 77(10):1381–1385Google Scholar
  36. 36.
    Guzel AB, Kucukgoz G, Paydas S et al (2012) Preoperative evaluation, clinical characteristics and prognostic factors of nongenital metastatic ovarian tumors: review of 48 patients. Eur J Gynaec Oncol 33(5):493–497Google Scholar
  37. 37.
    Lu LC, Shao YY, Hsu CH et al (2012) Metastasectomy of Krukenberg tumors may be associated with survival benefits in patients with metastatic gastric cancer. Anticancer Res 32(8):3397–3401Google Scholar
  38. 38.
    Peng W, Hua RX, Jiang R, Ren C, Jia YN, Li J, Guo WJ (2013) Surgical treatment for patients with Krukenberg tumor of stomach origin: clinical outcome and prognostic factors analysis. PLoS ONE 8(7):e68227CrossRefGoogle Scholar
  39. 39.
    Wu XJ, Yuan P, Li ZY et al (2013) Cytoreductive surgery and hypertermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination. Tumour Biol 34(1):463–469CrossRefGoogle Scholar
  40. 40.
    Cho JH, Lim JY, Choi AR et al (2015) Comparison of surgery plus chemotherapy and palliative chemotherapy alone for advanced gastric cancer with krukenberg tumor. Cancer Res Treat 47(4):697–705CrossRefGoogle Scholar
  41. 41.
    Jeung YJ, Ok HJ, Kim WG, Kim SH, Lee TH (2015) Krukenberg tumors of gastric origin versus colorectal origin. Obstet Gynecol Sci 58(1):32–39CrossRefGoogle Scholar
  42. 42.
    Wu F, Zhao X, Mi B et al (2015) Clinical characteristics and prognostic analysis of Krukenberg tumor. Mol Clin Oncol 3(6):1323–1328CrossRefGoogle Scholar
  43. 43.
    Rosa F, Marrelli D, Morgagni P et al (2016) Krukenberg tumors of gastric origin: the rationale of surgical resection and perioperative treatments in a multicenter western experience. World J Surg 40(4):921–928CrossRefGoogle Scholar
  44. 44.
    Ganesh K, Shah RH, Vakiani E et al (2017) Clinical and genetic determinants of ovarian metastases from colorectal cancer. 123(7):1134–1143CrossRefGoogle Scholar
  45. 45.
    Kammar PS, Engineer R, Patil PS, Ostwal V, Shylasree TS, Saklani AP (2017) Ovarian metastases of colorectal origin: treatment patterns and factors affecting outcomes. Indian J Surg Oncol 8(4):519–526CrossRefGoogle Scholar
  46. 46.
    Xu KY, Gao H, Lian ZJ, Ding L, Li M, Gu J (2017) Clinical analysis of Krukenberg tumours in patients with colorectal cancer—a review of 57 cases. World J Surg Oncol 15(1):25CrossRefGoogle Scholar
  47. 47.
    Yu P, Huang L, Cheng G et al (2017) Treatment strategy and prognostic factors for Krukenberg tumors of gastric origin: report of a 10-year single-center experience from China. Oncotarget 8(47):82558–82570Google Scholar
  48. 48.
    Seow-En I, Hwarng G, Tan GHC, Ho LML, Teo MCC (2018) Palliative surgery for Krukenberg tumors—12-year experience and review of the literature. World J Clin Oncol 9(1):13–19CrossRefGoogle Scholar
  49. 49.
    Tai H, Yang Q, Wu Z et al (2018) PD-L1 expression predicts a distinct prognosis in Krukenberg tumor with corresponding origins. J Immunol Res 2018:9485285Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ruggero Lionetti
    • 1
  • Marcello De Luca
    • 1
  • Antonio Travaglino
    • 2
    Email author
  • Antonio Raffone
    • 3
  • Gabriele Saccone
    • 2
  • Antonietta Di Cicco
    • 2
  • Luigi Insabato
    • 2
  • Massimo Mascolo
    • 2
  • Maria D’Armiento
    • 1
  • Fulvio Zullo
    • 3
  • Francesco Corcione
    • 1
  1. 1.Department of Public Health, School of MedicineUniversity of Naples Federico IINaplesItaly
  2. 2.Department of Advanced Biomedical Sciences, School of MedicineUniversity of Naples Federico IINaplesItaly
  3. 3.Department of Reproductive Sciences and Dentistry, School of MedicineUniversity of Naples Federico IINaplesItaly

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