Transvaginal ultrasound intrauterine echo flow resistance index as predictor of lymphovascular space invasion in endometrioid adenocarcinoma

Background: Lymphovascular space invasion (LVSI) is an independent factor that affects the survival of patients with endometrioid carcinoma (EEC). However, few preoperative methods that can predict LVSI. Transvaginal ultrasonography (TVS) is a routine examination performed in patients with EEC. Therefore, the authors sought to assess whether there is a correlation between uterine blood flow resistance index (RI), determined by TVS, and LVSI. Materials and Methods: The authors performed a case-control study to examine patients with LVSI-positive (n = 30) and LVSI-negative (n = 148) Stage I-III endometrial cancer (EC) who underwent hysterectomy-based surgical staging. The risk associated with TVS intrauterine echo flow RI was estimated based on LVSI patterns. Results: Among 178 patients, the mean RI of patients without LVSI was 0.486 ± 0.15 and that of patients with LVSI was 0.581 ± 0.18. Univariate analysis showed that RI was a risk factor for LVSI (p = 0.027). Multivariate logistic regression analysis indicated that RI was not related to BMI, endometrial thickness, or uterine length. Hypertension, endometrial thickness, and length of intrauterine echo may increase risk through changes in RI (p < 0.05). Conclusion: Increased RI in EEC can predict the presence of LVSI. History of hypertension, endometrial thickness, and length of intrauterine echo also influence RI. Preoperative RI measurement is a useful tool for guiding clinical and surgical treatment.

Endometrioid carcinoma; Lymphovascular space invasion; Transvaginal ultrasonography

[1] Creutzberg C.L., van Putten W.L., Wárlám-Rodenhuis C.C., van den Bergh A.C., de Winter K.A., Koper P.C., et al.: “Outcome of highrisk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the postoperative radiation therapy in endometrial carcinoma trial” J. Clin. Oncol., 2004, 22, 1234.

[2] Marnitz S.: “Current therapy of patients with endometrial carcinoma. A critical review”. Strahlenther. Onkol., 2012, 188, 12.

[3] Mahdi H, Jernigan A., Nutter B., Michener C., Rose P.G.: “Lymph node metastasis and pattern of recurrence in clinically early stage endometrial cancer with positive lymphovascular space invasion”. Gynecol. Oncol., 2015, 26, 208.

[4] AlHilli M.M., Podratz K.C., Dowdy S.C., Bakkum-Gamez J.N., Weaver A.L., McGree M.E., et al.: “Risk-scoring system for the individualized prediction of lymphatic dissemination inpatients with endometrioid endometrial cancer”. Gynecol. Oncol., 2013, 131, 103.

[5] Weinberg L.E., Kunos C.A., Zanotti K.M.: “Lymphovascular space invasion (LVSI) is an isolated poor prognostic factor for recurrence and survival among women with intermediate-to high-risk early-stage endometrioid endometrial cancer”. Int. J. Gynecol. Cancer, 2013, 23, 1438.

[6] Mannelqvist M., Stefansson I.M., Bredholt G., Hellem Bø T., Oyan A.M., Jonassen I., et al.: “Gene expression patterns related to vascular invasion and aggressive features in endometrial cancer”. Am. J. Pathol., 2011, 178, 861.

[7] Kumar S., Bandyopadhyay S., Semaan A., Shah J.P., Mahdi H., Morris R., et al.: “The role of frozen section in surgical staging of low risk endometrial cancer”. PLoS One, 2011, 6, e21912.

[8] Tsuruchi N., Kaku T., Kamura T., Tsukamoto N., Tsuneyoshi M., Akazawa K., Nakano H.: “The prognostic significance of lymphovascular space invasion in endometrial cancerwhen conventional hemotoylin and eosin staining is compared to immunohistochemicalstaining”. Gynecol. Oncol., 1995, 57, 307.

[9] Ito K., Noro K., Yanagisawa Y., Sakamoto M., Mori S., Shiga K., et al.: “High accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems”. Ultrasound Med. Biol., 2015, 41, 3120.

[10] Uggowitzer M., Kugler C., Machan L., Gröll R., Stauber R., Mischinger H.J., et al.: “Power Doppler imaging and evaluation of the resistive index in focal nodular hyperplasia of the liver”. Abdom. Imaging, 1997, 22, 268.

[11] GaianiS., Casali A., Serra C., Piscaglia F., Gramantieri L., Volpe L., et al.: “Assessment of vascular patterns of smallliver mass lesions: value and limitation of the different Doppler ultrasoundmodalities”. Am. J. Gastroenterol., 2000, 95, 3537.

[12] Mousavi A.S., Borna S., Moeinoddini S.: “Estimation of probability of malignancy using a logistic model combining color Dopplertransvaginal ultrasonography, serum CA125 level in women with a pelvic mass”. Int. J. Gynecol. Cancer, 2006, 16, 92.

[13] Green R.W., Valentin L., Alcazar J.L., Chiappa V., Erdodi B., Franchi D., et al.: “Endometrial cancer off-line staging using two-dimensional transvaginal ultrasound and three-dimensional volume contrast imaging: Intermethod agreement, interrater reliability and diagnostic accuracy”. Gynecol. Oncol., 2018, 150, 438.

[14] Colombo N., Preti E., Landoni F., Carinelli S., Colombo A., Marini C., et al.: “Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”. Ann. Oncol., 2011, 22, vi35.

[15] Wright J.D., BarrenaMedel N.I., Sehouli J., Fujiwara K., Herzog T.J.: “Contemporary managementof endometrial cancer”. Lancet, 2012, 379, 1352.

[16] Amant F., Mirza M.R., Creutzberg C.L.: “Cancer of the corpus uteri”. Int. J. Gynecol. Obstet., 2012, 119, S110.

[17] Creutzberg C.L., van Putten W.L., Koper P.C., Lybeert M.L., Jobsen J.J., Wárlám-Rodenhuis C.C., et al.: “Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: Multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma”. Lancet, 2000, 355, 1404.

[18] Keys H.M., Roberts J.A., Brunetto V.L., Zaino R.J., Spirtos N.M., Bloss J.D., et al.: “A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: A Gynecologic Oncology Group study”. Gynecol. Oncol., 2004, 92, 744.

[19] Todo Y., Kato H., Kaneuchi M., Watari H., Takeda M., Sakuragi N.: “Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis”. Lancet, 2010, 375, 1165.