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Endometrial cancer: predictors and oncological safety of tumor tissue manipulation

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Abstract

Purpose

The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results.

Methods

We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen.

Results

A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99–7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66–3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68–1.19); p = 0.479).

Conclusion

Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used.

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Data availability

All data are encripted in different databases provided by each center. If needed, each author should be contacted for further information.

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.

    Article  PubMed  Google Scholar 

  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  3. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78.

    Article  PubMed  Google Scholar 

  4. Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021;31(1):12–39.

    Article  PubMed  Google Scholar 

  5. Cho KR, Cooper K, Croce S, Djordevic B, Herrington S, Howitt B, et al. International society of gynecological pathologists (ISGyP) endometrial cancer project: guidelines from the special techniques and ancillary studies group. Int J Gynecol Pathol. 2019;38:S114–22.

    Article  PubMed  Google Scholar 

  6. Jorge S, Hou JY, Tergas AI, Burke WM, Huang Y, Hu JC, et al. Magnitude of risk for nodal metastasis associated with lymphvascular space invasion for endometrial cancer. Gynecol Oncol. 2016;140(3):387–93.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hahn HS, Lee IH, Kim TJ, Lee KH, Shim JU, Kim JW, et al. Lymphovascular space invasion is highly associated with lymph node metastasis and recurrence in endometrial cancer. Aust N Z J Obstet Gynaecol. 2013;53(3):293–7.

    Article  PubMed  Google Scholar 

  8. Bosse T, Peters EEM, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Mens JWM, et al. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer—a pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer. 2015;51(13):1742–50.

    Article  PubMed  Google Scholar 

  9. Padilla-Iserte P, Lago V, Tauste C, Díaz-Feijoo B, Gil-Moreno A, Oliver R, et al. Impact of uterine manipulator on oncological outcome in endometrial cancer surgery. Am J Obstet Gynecol. 2021;224(1):65.e1-65.e11.

    Article  PubMed  Google Scholar 

  10. Logani S, Herdman AV, Little JV, Moller KA. Vascular “pseudo invasion” in laparoscopic hysterectomy specimens: a diagnostic pitfall. Am J Surg Pathol. 2008;32(4):560–5.

    Article  PubMed  Google Scholar 

  11. Takac I, Zegura B. Office hysteroscopy and the risk of microscopic extrauterine spread in endometrial cancer. Gynecol Oncol. 2007;107(1):94–8.

    Article  PubMed  Google Scholar 

  12. Dewdney SB, Jiao Z, Roma AA, Gao F, Rimel BJ, Thaker PH, et al. The prognostic significance of lymphovascular space invasion in laparoscopic versus abdominal hysterectomy for endometrioid endometrial cancer. Eur J Gynaecol Oncol. 2014;35(1):7–10.

    CAS  PubMed  Google Scholar 

  13. Radley-Gardner O, Beale H, Zimmermann R. Fundamental texts on European private law. Oxford: Hart Publishing; 2016.

    Book  Google Scholar 

  14. Kim S, Park HK, Jung HY, Lee SY, Min KW, Kim WY, et al. ERG Immunohistochemistry as an endothelial marker for assessing lymphovascular invasion. Korean J Pathol. 2013;47(4):355–64.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009;105(2):103–4.

    Article  PubMed  Google Scholar 

  16. Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33(1):1–22.

    Article  PubMed  PubMed Central  Google Scholar 

  17. R Foundation for Statistical Computing. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing. 2020. Avaiable at: http://www.r-project.org/index.html

  18. Simon N, Friedman J, Hastie T, Tibshirani R. Regularization paths for cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011;39(5):1.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Therneau TM, Grambsch PM. Modeling survival data: extending the Cox model. New York Berlin Heidelberg: Springer; 2000. p. 350.

    Book  Google Scholar 

  20. Gorostidi Pulgar M, Diaz de la Noval B, Gil-Ibañez B, Lago Leal V, Jaunarena Marin I, Padilla IP. Lymphovascular space invasion for endometrial cancer: undertreatment and overtreatment risks. Int J Gynecol Cancer. 2017;27(6):1191–9.

    Article  PubMed  Google Scholar 

  21. Capozzi VA, Rosati A, Uccella S, Riemma G, Tarascio M, Torella M, et al. Role of uterine manipulator during laparoscopic endometrial cancer treatment. Transl Cancer Res. 2020;9(12):7759–66.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gueli Alletti S, Perrone E, Cretì A, Cianci S, Uccella S, Fedele C, et al. Feasibility and perioperative outcomes of percutaneous-assisted laparoscopic hysterectomy: a multicentric Italian experience. Eur J Obstet Gynecol Reprod Biol. 2020;245:181–5.

    Article  PubMed  Google Scholar 

  23. van den Haak L, Alleblas C, Nieboer TE, Rhemrev JP, Jansen FW. Efficacy and safety of uterine manipulators in laparoscopic surgery: a review. Arch Gynecol Obstet. 2015;292(5):1003–11.

    Article  PubMed  Google Scholar 

  24. Abdel Khalek Y, Bitar R, Christoforou C, Garzon S, Tropea A, Biondi A, et al. Uterine manipulator in total laparoscopic hysterectomy: safety and usefulness. Updat Surg. 2020;72(4):1247–54.

    Article  Google Scholar 

  25. Krizova A, Clarke BA, Bernardini MQ, James S, Kalloger SE, Boerner SL, et al. Histologic artifacts in abdominal, vaginal, laparoscopic, and robotic hysterectomy specimens: a blinded retrospective review. Am J Surg Pathol. 2011;35(1):115–26.

    Article  PubMed  Google Scholar 

  26. Kitahara S, Walsh C, Frumovitz M, Malpica A, Silva EG. Vascular pseudoinvasion in laparoscopic hysterectomy specimens for endometrial carcinoma: a grossing artifact? Am J Surg Pathol. 2009;33(2):298–303.

    Article  PubMed  Google Scholar 

  27. Machida H, Hom MS, Adams CL, Eckhardt SE, Garcia-Sayre J, Mikami M, et al. Intrauterine manipulator use during minimally invasive hysterectomy and risk of lymphovascular space invasion in endometrial cancer. Int J Gynecol Cancer. 2018;28(2):208–19.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Seifi F, Parkash V, Clark M, Menderes G, Tierney C, Silasi DA, et al. Pseudovascular invasion: minimally invasive surgery for endometrial cancer. JSLS. 2019;23(2):e2019.00021.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mariani A, Dowdy SC, Podratz KC. New surgical staging of endometrial cancer: 20 years later. Int J Gynecol Obstet. 2009;105(2):110–1.

    Article  Google Scholar 

  30. Sáinz de la Cuesta R, Espinosa JA, Crespo E, Granizo JJ, Rivas F. Does fluid hysteroscopy increase the stage or worsen the prognosis in patients with endometrial cancer? A randomized controlled trial. Eur J Obstet Gynecol Reprod Biol. 2004;115(2):211–5.

    Article  PubMed  Google Scholar 

  31. Quintana-Bertó R, Padilla-Iserte P, Gil-Moreno A, Oliver-Pérez R, Coronado PJ, Martín-Salamanca MB, et al. Oncological safety of hysteroscopy in endometrial cancer. Int J Gynecol Cancer. 2022. https://doi.org/10.1136/ijgc-2022-003586.

    Article  PubMed  Google Scholar 

  32. Cicinelli E, Tinelli R, Colafiglio G, Fortunato F, Fusco A, Mastrolia S, et al. Risk of long-term pelvic recurrences after fluid minihysteroscopy in women with endometrial carcinoma: a controlled randomized study. Menopause N Y N. 2010;17(3):511–5.

    Article  Google Scholar 

  33. Namazov A, Gemer O, Helpman L, Hag-Yahia N, Eitan R, Raban O, et al. The oncological safety of hysteroscopy in the diagnosis of early-stage endometrial cancer: an Israel gynecologic oncology group study. Eur J Obstet Gynecol Reprod Biol. 2019;243:120–4.

    Article  PubMed  Google Scholar 

  34. Chang YN, Zhang Y, Wang YJ, Wang LP, Duan H. Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer cells: a meta-analysis. Fertil Steril. 2011;96(4):957-961.e2.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We want to thank the Spanish Society of Gynecology and Obstetrics Spain-GOG for endorsing this entire project. In addition, we also want to acknowledge A. Torné (University Hospital Clínic of Barcelona), A. Gil-Moreno (Vall d'Hebron University Hospital), C. Aghabayan (General University Hospital of Valencia) T. Marina and L. Matute (La Fe University and Polytechnic Hospital), L. Sánchez (University General Hospital of Ciudad Real) for their contribution and support.

Funding

There is no financial support, commercial association or another type of funding sources.

Author information

Authors and Affiliations

  1. Department of Gynecologic Oncology, La Fe University and Polytechnic Hospital, València, Spain

    Raquel Quintana-Bertó, Pablo Padilla-Iserte, Víctor Lago & Santiago Domingo

  2. Department of Gynecologic Oncology, Complejo Hospitalario de Navarra, Navarra, Spain

    Carmen Tauste & Juan Carlos Muruzábal

  3. Institute Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Berta Díaz-Feijoo

  4. Gynecologic Oncology Unit, Gynecology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

    Silvia Cabrera

  5. Gynecologic Oncology-Unit, Department of Obstetrics and Gynecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute, Complutense University of Madrid, Madrid, Spain

    Reyes Oliver-Pérez

  6. Women’s Health Institute of the Hospital Clínico San Carlos, IdISSC, University Complutense, Madrid, Spain

    Pluvio J. Coronado

  7. Gynecology Department, Hospital Universitario de Getafe, Madrid, Spain

    María Belén Martín-Salamanca

  8. Department of Gynecology and Obstetrics, University Hospital Virgen Macarena, Sevilla, Spain

    Manuel Pantoja-Garrido

  9. Department of Obstetrics and Gynecology, Dr. Balmis General University Hospital, Alicante, Spain

    Josefa Marcos-Sanmartin

  10. Department of Public Health, Miguel Hernández University, Sant Joan d‘Alacant, Alicante, Spain

    Josefa Marcos-Sanmartin

  11. Department of Obstetrics and Gynecology, Hospital Universitario de Torrevieja, Alicante, Spain

    Eduardo Cazorla

  12. Department of Obstetrics and Gynecology, Hospital Nuestra Señora de La Calendaria, Santa Cruz de Tenerife, Spain

    Cristina Lorenzo

  13. Gynaecology and Obstetrics Department, University Hospital Virgen de La Arrixaca, El Palmar, Murcia, Spain

    José Ramón Rodríguez-Hernández

  14. Department of Obstetrics and Gynaecology, Clinico Lozano Blesa Hospital, Zaragoza, Spain

    Fernando Roldán-Rivas

  15. Department of Obstetrics and Gynecology, University General Hospital of València, València, Spain

    Juan Gilabert-Estellés

  16. Department of Biostatistics, Health Research Institute La Fe, València, Spain

    Antonio Cañada

  17. Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain

    Josefa Marcos-Sanmartin

Authors
  1. Raquel Quintana-Bertó
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  2. Pablo Padilla-Iserte
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  6. Silvia Cabrera
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  7. Reyes Oliver-Pérez
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  9. María Belén Martín-Salamanca
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  10. Manuel Pantoja-Garrido
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  12. Eduardo Cazorla
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  13. Cristina Lorenzo
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  14. José Ramón Rodríguez-Hernández
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  15. Fernando Roldán-Rivas
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  16. Juan Gilabert-Estellés
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  17. Juan Carlos Muruzábal
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  18. Antonio Cañada
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  19. Santiago Domingo
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Consortia

SEGO Spain-GOG Group

Contributions

Conceptualization: RQ-B, PP-I and AC. methodology: RQ-B, PP-I and AC. validation: PP-I, VL, SD y AC. Formal analysis: PP-I and AC. Investigation: RQ-B and PP-I. Resources: RQ-B, PP-I, VL, CT, BD-F, SC, RO-P, P JC, MBM-S, MP-G, JM-S, EC, CL, JRR-H, FR-R, JG-E, JCM, AC and SD. Data curation: RQ-B, PP-I, VL, CT, BD-F, SC, RO-P, PJC, MBM-S, MP-G, JM-S, EC, CL, JRR-H, FR-R, JG-E, JCM, AC and SD. writing—original draft: RQ-B, PP-I and AC. writing—review & editing: RQ-B, PP-I, AC and SD. visualisation: RQ-B, PP-I, VL, CT, BD-F, SC, RO-P, PJC, MBM-S, MP-G, JM-S, EC, CL, JRR-H, FR-R, J G-E, JCM, AC and SD. supervision: PP-I, SD, VL and AC. project administration: RQ-B and PP-I.

Corresponding author

Correspondence to Raquel Quintana-Bertó.

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Conflict of interests

The authors report no conflict of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee. This study was approved by the Hospital Universitari i Politècnic La Fe de València Research Ethics Committee (registration no. 2019/0075).

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Written informed consent was obtained from the patients included in the study prior to its publication.

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Quintana-Bertó, R., Padilla-Iserte, P., Lago, V. et al. Endometrial cancer: predictors and oncological safety of tumor tissue manipulation. Clin Transl Oncol 26, 1098–1105 (2024). https://doi.org/10.1007/s12094-023-03310-6

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