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Reply to “Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical Hyperplasia and Endometrial Cancer: How Important are Intrauterine Adhesions?”
Letters to the Editor
Reply to ‘‘Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical Hyperplasia and Endometrial Cancer: How Important are Intrauterine Adhesions?’’ To the Editor: In response to the letter to the editor submitted by Dr. T. Shokeir related to our article, we appreciate the time spent in writing his comments and hope to cover all the issues raised by Dr. T. Shokeir. Intrauterine adhesions (IUAs) are one of the main longterm complications of hysteroscopic surgery and are advocated by many as a possible limiting factor for the safety of conservative hysteroscopic treatment of endometrial carcinoma in women desiring to preserve their fertility. Our aim was that of supporting this approach by reporting a singlecenter experience, which shows a satisfactory oncologic outcome without any fertility impairment. The prevalence of IUAs was not expected to be low in our population, therefore representing a clinical concern, because the hysteroscopic resection was performed according to the ‘‘3 steps’’ technique first described by Mazzon et al [1]. This technique includes the resection of the tumor and/or hyperplastic areas and of the underlying myometrium. In cases of multiple and diffuse lesions, this procedure was done on the fundus and on all uterine walls. To note, the possible development of IUAs is described even in those procedures limited to the basilar layer of the endometrium, without involving the myometrium [2]. We agree with Dr. Shokeir that the experience of the operator is a critical issue that may affect the rate of IUA development. In our population all procedures were performed by the same experienced hysteroscopic surgeons and homogenously treated following the same resection protocol. Considering the results reported in our study and in the previous series, this approach combining hysteroscopic resection with high-dosage progestin therapy seems to be more advisable in the treatment of endometrial cancer/atypical complex hyperplasia when compared with progestin therapy alone for several reasons. As already explained in our discussion, hysteroscopic resection is useful for an accurate pathologic evaluation and staging, because it helps both in excluding an occult adenocarcinoma that could be present in 43% of atypical complex hyperplasias and in the evaluation of endometrial margins near the lesion/underlying myometrium in cases of endometrial cancer. Moreover, hysteroscopic resection of
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the pathologic endometrium seems to improve response to progestin therapy. Remarkably, endometrial curettage, often routinely performed for the diagnosis of endometrial cancer instead of hysteroscopy, is one of the main procedures associated with IUA development [2]. Even if surely requiring further investigation and longer follow-up, the effectiveness of such a procedure is supported by literature: The rate of initial response to high-dose progestin therapy alone was 76% with an average response time of 18 months, as reported in the most recent metaanalysis available [3], with a relapse rate of 40% and a live birth rate of 28%. In the few series describing the combination of hysteroscopic resection and progestin therapy, the response rate seems to be higher and the recurrence rate lower [1,4]. This does not seem to impair fertility. Our study further confirms these findings, with a live birth rate of 28.5% comparable with that reported by Gallos et al [3]. Certainly, all the questions raised by Dr. Shokeir in the final part of his letter are of great interest. However, they do not meet the purpose of our investigation and might better be addressed in a new research. Patrizia De Marzi, MD Alice Bergamini, MD Stefania Luchini, MD Micaela Petrone, MD Gianluca Taccagni, MD Giorgia Mangili, MD Gabriella Colombo, MD Massimo Candiani, MD Department of Obstetrics and Gynecology San Raffaele Hospital Milan, Italy References 1. Mazzon G, COrrado G, Morricone D, et al. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: hysteroscopic resection. Int J Gynaecol Cancer 2005;15:974–978. 2. Deans R, Abbott J. Review of intrauterine adhesions. J Minim Invasive Gynecol 2010;17:555–569. 3. Gallos ID, Shehmar M, Thangaratinam S, et al. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:547.e1–547.e10. 4. Laurelli G, Di Vagno G, Scaffa C, et al. Conservative treatment of early endometrial cancer: preliminary results of a pilot study. Gynecol Oncol 2011;120:43–46. http://dx.doi.org/10.1016/j.jmig.2015.07.010
Reply to ‘‘Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical Hyperplasia and Endometrial Cancer: How Important are Intrauterine Adhesions?’’ To the Editor: In response to the letter to the editor submitted by Dr. T. Shokeir related to our article, we appreciate the time spent in writing his comments and hope to cover all the issues raised by Dr. T. Shokeir. Intrauterine adhesions (IUAs) are one of the main longterm complications of hysteroscopic surgery and are advocated by many as a possible limiting factor for the safety of conservative hysteroscopic treatment of endometrial carcinoma in women desiring to preserve their fertility. Our aim was that of supporting this approach by reporting a singlecenter experience, which shows a satisfactory oncologic outcome without any fertility impairment. The prevalence of IUAs was not expected to be low in our population, therefore representing a clinical concern, because the hysteroscopic resection was performed according to the ‘‘3 steps’’ technique first described by Mazzon et al [1]. This technique includes the resection of the tumor and/or hyperplastic areas and of the underlying myometrium. In cases of multiple and diffuse lesions, this procedure was done on the fundus and on all uterine walls. To note, the possible development of IUAs is described even in those procedures limited to the basilar layer of the endometrium, without involving the myometrium [2]. We agree with Dr. Shokeir that the experience of the operator is a critical issue that may affect the rate of IUA development. In our population all procedures were performed by the same experienced hysteroscopic surgeons and homogenously treated following the same resection protocol. Considering the results reported in our study and in the previous series, this approach combining hysteroscopic resection with high-dosage progestin therapy seems to be more advisable in the treatment of endometrial cancer/atypical complex hyperplasia when compared with progestin therapy alone for several reasons. As already explained in our discussion, hysteroscopic resection is useful for an accurate pathologic evaluation and staging, because it helps both in excluding an occult adenocarcinoma that could be present in 43% of atypical complex hyperplasias and in the evaluation of endometrial margins near the lesion/underlying myometrium in cases of endometrial cancer. Moreover, hysteroscopic resection of
1319
the pathologic endometrium seems to improve response to progestin therapy. Remarkably, endometrial curettage, often routinely performed for the diagnosis of endometrial cancer instead of hysteroscopy, is one of the main procedures associated with IUA development [2]. Even if surely requiring further investigation and longer follow-up, the effectiveness of such a procedure is supported by literature: The rate of initial response to high-dose progestin therapy alone was 76% with an average response time of 18 months, as reported in the most recent metaanalysis available [3], with a relapse rate of 40% and a live birth rate of 28%. In the few series describing the combination of hysteroscopic resection and progestin therapy, the response rate seems to be higher and the recurrence rate lower [1,4]. This does not seem to impair fertility. Our study further confirms these findings, with a live birth rate of 28.5% comparable with that reported by Gallos et al [3]. Certainly, all the questions raised by Dr. Shokeir in the final part of his letter are of great interest. However, they do not meet the purpose of our investigation and might better be addressed in a new research. Patrizia De Marzi, MD Alice Bergamini, MD Stefania Luchini, MD Micaela Petrone, MD Gianluca Taccagni, MD Giorgia Mangili, MD Gabriella Colombo, MD Massimo Candiani, MD Department of Obstetrics and Gynecology San Raffaele Hospital Milan, Italy References 1. Mazzon G, COrrado G, Morricone D, et al. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: hysteroscopic resection. Int J Gynaecol Cancer 2005;15:974–978. 2. Deans R, Abbott J. Review of intrauterine adhesions. J Minim Invasive Gynecol 2010;17:555–569. 3. Gallos ID, Shehmar M, Thangaratinam S, et al. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol 2010;203:547.e1–547.e10. 4. Laurelli G, Di Vagno G, Scaffa C, et al. Conservative treatment of early endometrial cancer: preliminary results of a pilot study. Gynecol Oncol 2011;120:43–46. http://dx.doi.org/10.1016/j.jmig.2015.07.010