- Email: [email protected]
Authors’ response to comment on “Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study” Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–128.
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Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 133 (2007) 119–122
Comment on ‘‘Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study’’ Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–128. Dear Editor, We read with interest the article by Mathelin et al. titled ‘Endometrial brush cytology in the surveillance of postmenopausal patients under tamoxifen: A prospective longitudinal study’ [1]. We believe that the abbreviation ‘H&C’ used throughout the text refers to dilatation and curettage (D&C) rather than hysteroscopy and curettage. Otherwise two methods (endometrial brush cytology and hysteroscopy oriented biopsy) would not be comparable especially in terms of diagnosing endometrial polyps. In fact, in patients with thickened endometrium measured by transvaginal ultrasonography (TVU), a D&C is not sufficient, as TVU has not the ability to differentiate between endometrial polyps and myometrial changes. A hysteroscopy and directed biopsy could be performed for this purpose [2]. On the other hand one of the main obstacles with TVU accuracy in identifying endometrial pathologies in postmenopausal tamoxifen treated patients is due to the difficulty in establishing an accurate ultrasonographic cutoff value. Cutoff values of 5 mm, 6 mm, 8 mm and 10 mm have been used in such patients [3]. Actually endometrial cancer can be detected in tamoxifen treated patients with endometrial thickness 5 mm. Hence, there is no general agreement on this issue. Reference number 16 provided by the authors in the text refers to the year 1994. Stromal edema caused by tamoxifen, abnormal adenomyomatous-like changes in the proximal endometrium, existence of subendometrial sonolucencies in adjacent myometrium, or a thick mid-uterine structure resembling a thickened endometrium with no histologic evidence of endometrial neoplasm are all claimed to be the reasons for the false-positive ultrasonographic appearance of thick endometrium seen in these patients [3]. Thus, it is difficult to determine a reliable cutoff value for ultrasonographic evaluation. Recent studies imply that diagnosis and treatment of baseline endometrial atypical lesions before the start of tamoxifen therapy decrease the incidence of serious endometrial lesions [4,5]. Keeping all this in mind, we assent to the difficulties of performing such a study and appreciate the authors’ effort. We believe that studies with patients who had undergone pretreatment evaluation for endometrial pathologies would help us to understand the effectiveness of enometrial brush cytology which is a quick, painless and cheap method.
DOI of original article: 10.1016/j.ejogrb.2006.10.040.
References [1] Mathelin C, Youssef C, Annane K, et al. Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study. Eur J Obstet Gynecol Reprod Biol 2007; 132(1):126–8. [2] Liedman R, Lindahl B, Andolf E, et al. Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Res 2000;20(6C): 4889–91. [3] Markovitch O, Tepper R, Fishman A, et al. The value of transvaginal ultrasonography in the prediction of endometrial pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated patients. Gynecol Oncol 2004;95(3):456–62. [4] Garuti G, Grossi F, Centinaio G, et al. Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer. Eur J Obstet Gynecol Reprod Biol May 2006. [5] McGonigle KF, Smith DD, Marx HF, et al. Uterine effects of tamoxifen: a prospective study. Int J Gynecol Cancer 2006;16(2):814–20.
Ozer Oztekin* Department of Obstetrics and Gynecology, Faculty of Medicine, Pamukkale Univerity, Denizli, Turkey *Correspondence to: Erenler mah. 406 sok. Gokkusagi apt. No: 2/2, Servergazi, Denizli, Turkey. Tel.: +90 532 436 14 99 E-mail address: [email protected] 16 August 2006 doi:10.1016/j.ejogrb.2006.10.041
Authors’ response to comment on ‘‘Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study’’ Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–128. Dear Editor, We read with interest Oztekin’s comments concerning our article entitled ‘‘Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: a prospective longitudinal study’’ [1]. The abbreviation ‘‘H&C’’ used throughout the text refers to hysteroscopy and curettage. Indeed, as explained in ‘‘material and method’’, patients having an endometrial double layer thickness of more than 8 mm at transvaginal ultrasonography (TVUS) were prospectively recruited in a clinical trial, including a cytological sampling of the endometrium using a standard Endobrush1, followed by H&C which was performed under general anesthesia. We demonstrated that cytological endometrial sampling, analyzed by a well trained cytologist, was a reliable and well accepted diagnostic test to discriminate benign from atypical or malignant endometrial lesions. DOI of original article: 10.1016/j.ejogrb.2006.10.041.
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 133 (2007) 119–122
Endometrial cytology does not have the capability to precisely diagnose the type of endometrial benign lesions (glandulocystic atrophy, polyp, fibroma, etc.). Because of the very low risk of malignant degeneration of some of these lesions, H&C can be omitted for most of them. On the contrary, endometrial cytology cannot replace conventional H&C for atypical hyperplasia. Indeed, pathogenetic relation between atypical hyperplasia and malignancy was demonstrated [2] and these lesions should be resected by H&C. Likewise, in the case of malignant pathology, H&C should be used as a second line diagnostic test for confirmation of endometrial cancer and staging. We agree with Oztekin on the fact that there is no established ultrasonographic endometrial cutoff value to diagnose endometrial pathologies in asymptomatic postmenopausal tamoxifen-treated patients. Before beginning our clinical trial [1], we tried to seek for the most accurate cutoff value in tamoxifen-treated patients. Multiple ultrasonographic cutoff points were evaluated on patients who had TVUS examinations followed by H&C. Like other studies [3,4], we observed that there is a gradual increase in specificity and a gradual decrease in sensitivity when ultrasonographic endometrial cutoff value increases. The best cutoff value appeared to be 8–9 mm. The latter was also obtained in numerous other studies [5–7]. If the cutoff value is too high, many endometrial pathologies can be undiagnosed. On the other hand, too small a cutoff value can lead to many needless H&C, which may induce bleeding, uterine perforation and endometritis. Ciatto et al. [4] quantified these data in a consecutive cohort of 1205 breast cancer patients under tamoxifen treatment, undergoing TVUS as follow-up. No endometrial cancer [4] was observed with an endometrial cutoff value below 6 mm. The authors had the following results: for a cutoff value superior or equal to 6, 8, 12 and 18 mm; the specificity was 25.8, 44.5, 76.1 and 91.5%, respectively, and the sensitivity was 100, 91.6, 75.0, 66.6%, respectively. Finally, we agree with Oztekin and other authors on the fact that diagnosis and treatment of baseline endometrial atypical lesions before tamoxifen therapy could decrease the incidence of serious endometrial lesions [2,8]. In our opinion, this does not influence the effectiveness of endometrial brush cytology in the surveillance of postmenopausal women under tamoxifen.
References [1] Mathelin C, Youssef C, Annane K, Brettes JP, Bellocq JP, Walter P. Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: a prospective longitudinal study. Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–8. [2] Garuti G, Grossi F, Centinaio G, Sita G, Nalli G, Luerti M. Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer. Eur J Obstet Gynecol Reprod Biol 2007;132:101–6. [3] Markovitch O, Tepper R, Fishman A, Shapira J, Aviram R, Cohen I. The value of transvaginal ultrasonography in the prediction of endometrial
[4]
[5]
[6]
[7]
[8]
121
pathologies in asymptomatic postmenopausal breast cancer tamoxifentreated patients. Gynecol Oncol 2004;95(3):456–62. Ciatto S, Cecchini S, Gervasi G, Landini A, Zappa M, Crocetti E. Surveillance for endometrial cancer with transvaginal ultrasonography of breast cancer patients under tamoxifen treatment. Br J Cancer 2003;88(8):1175–9. Hann LE, Giess CS, Bach AM, Tao Y, Baum HJ, Barakat RR. Endometrial thickness in tamoxifen-treated patients: correlation with clinical and pathologic findings. Am J Roentgenol 1997;168(3):657–61. Liedman R, Lindahl B, Andolf E, Willen R, Ingvar C, Ranstam J. Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Res 2000;20(6C):4889–91. Franchi M, Ghezzi F, Donadello N, Zanaboni F, Beretta P, Bolis P. Endometrial thickness in tamoxifen-treated patients: an independent predictor of endometrial disease. Obstet Gynecol 1999;93(6):1004–8. McGonigle KF, Smith DD, Marx HF, Morgan RJ, Vasilev SA, Roy S, et al. Uterine effects of tamoxifen: a prospective study. Int J Gynecol Cancer 2006;16(2):814–20.
Carole Mathelin* Cherif Youssef Service de gyne´cologie-obste´trique, Centre Hospitalier Universitaire, 1 place de l’Hoˆpital, 67091 Strasbourg Cedex, France *Corresponding author. Tel.: +33 3 88 11 60 71; fax: +33 3 88 11 53 91 E-mail address: [email protected] (C. Mathelin) 18 September 2006 doi:10.1016/j.ejogrb.2006.10.040
Anoscopy could be beneficial for women with external anogenital condyloma Dear Editor, The percentage of the population regularly performing anogenital sex appears to be increasing. Consequently, sexually transmitted diseases, such as human papiloma virus (HPV) induced intra-anal condyloma, could be expected in sexually active women. Palefsky et al. [1] reported that 76% of HIV-positive and 42% of high risk HIV-negative women had anal HPV infection. Conley et al. [2] showed a higher risk of developing vulvovaginal or anal high grade dysplasia-bearing condylomata in women who are HIV-positive. Despite these facts, as well as in many other studies, we still can read articles [3] which minimise the importance of genital condyloma and call them a cosmetic nuisance. Minimising the importance of external anogenital condyloma, inadequate previous treatment and ignoring the fact that the anorectum could serve as a sexual organ could be responsible for the delay of proctological evaluation in two young women treated at our institution in the last 2 years who developed ‘‘in situ’’ verrucose intraDOIs of original articles: 10.1016/j.ejogrb.2006.12.023., 10.1016/j.ejogrb.2006.12.024.
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 133 (2007) 119–122
Comment on ‘‘Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study’’ Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–128. Dear Editor, We read with interest the article by Mathelin et al. titled ‘Endometrial brush cytology in the surveillance of postmenopausal patients under tamoxifen: A prospective longitudinal study’ [1]. We believe that the abbreviation ‘H&C’ used throughout the text refers to dilatation and curettage (D&C) rather than hysteroscopy and curettage. Otherwise two methods (endometrial brush cytology and hysteroscopy oriented biopsy) would not be comparable especially in terms of diagnosing endometrial polyps. In fact, in patients with thickened endometrium measured by transvaginal ultrasonography (TVU), a D&C is not sufficient, as TVU has not the ability to differentiate between endometrial polyps and myometrial changes. A hysteroscopy and directed biopsy could be performed for this purpose [2]. On the other hand one of the main obstacles with TVU accuracy in identifying endometrial pathologies in postmenopausal tamoxifen treated patients is due to the difficulty in establishing an accurate ultrasonographic cutoff value. Cutoff values of 5 mm, 6 mm, 8 mm and 10 mm have been used in such patients [3]. Actually endometrial cancer can be detected in tamoxifen treated patients with endometrial thickness 5 mm. Hence, there is no general agreement on this issue. Reference number 16 provided by the authors in the text refers to the year 1994. Stromal edema caused by tamoxifen, abnormal adenomyomatous-like changes in the proximal endometrium, existence of subendometrial sonolucencies in adjacent myometrium, or a thick mid-uterine structure resembling a thickened endometrium with no histologic evidence of endometrial neoplasm are all claimed to be the reasons for the false-positive ultrasonographic appearance of thick endometrium seen in these patients [3]. Thus, it is difficult to determine a reliable cutoff value for ultrasonographic evaluation. Recent studies imply that diagnosis and treatment of baseline endometrial atypical lesions before the start of tamoxifen therapy decrease the incidence of serious endometrial lesions [4,5]. Keeping all this in mind, we assent to the difficulties of performing such a study and appreciate the authors’ effort. We believe that studies with patients who had undergone pretreatment evaluation for endometrial pathologies would help us to understand the effectiveness of enometrial brush cytology which is a quick, painless and cheap method.
DOI of original article: 10.1016/j.ejogrb.2006.10.040.
References [1] Mathelin C, Youssef C, Annane K, et al. Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study. Eur J Obstet Gynecol Reprod Biol 2007; 132(1):126–8. [2] Liedman R, Lindahl B, Andolf E, et al. Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Res 2000;20(6C): 4889–91. [3] Markovitch O, Tepper R, Fishman A, et al. The value of transvaginal ultrasonography in the prediction of endometrial pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated patients. Gynecol Oncol 2004;95(3):456–62. [4] Garuti G, Grossi F, Centinaio G, et al. Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer. Eur J Obstet Gynecol Reprod Biol May 2006. [5] McGonigle KF, Smith DD, Marx HF, et al. Uterine effects of tamoxifen: a prospective study. Int J Gynecol Cancer 2006;16(2):814–20.
Ozer Oztekin* Department of Obstetrics and Gynecology, Faculty of Medicine, Pamukkale Univerity, Denizli, Turkey *Correspondence to: Erenler mah. 406 sok. Gokkusagi apt. No: 2/2, Servergazi, Denizli, Turkey. Tel.: +90 532 436 14 99 E-mail address: [email protected] 16 August 2006 doi:10.1016/j.ejogrb.2006.10.041
Authors’ response to comment on ‘‘Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: A prospective longitudinal study’’ Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–128. Dear Editor, We read with interest Oztekin’s comments concerning our article entitled ‘‘Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: a prospective longitudinal study’’ [1]. The abbreviation ‘‘H&C’’ used throughout the text refers to hysteroscopy and curettage. Indeed, as explained in ‘‘material and method’’, patients having an endometrial double layer thickness of more than 8 mm at transvaginal ultrasonography (TVUS) were prospectively recruited in a clinical trial, including a cytological sampling of the endometrium using a standard Endobrush1, followed by H&C which was performed under general anesthesia. We demonstrated that cytological endometrial sampling, analyzed by a well trained cytologist, was a reliable and well accepted diagnostic test to discriminate benign from atypical or malignant endometrial lesions. DOI of original article: 10.1016/j.ejogrb.2006.10.041.
Letters to the Editor / European Journal of Obstetrics & Gynecology and Reproductive Biology 133 (2007) 119–122
Endometrial cytology does not have the capability to precisely diagnose the type of endometrial benign lesions (glandulocystic atrophy, polyp, fibroma, etc.). Because of the very low risk of malignant degeneration of some of these lesions, H&C can be omitted for most of them. On the contrary, endometrial cytology cannot replace conventional H&C for atypical hyperplasia. Indeed, pathogenetic relation between atypical hyperplasia and malignancy was demonstrated [2] and these lesions should be resected by H&C. Likewise, in the case of malignant pathology, H&C should be used as a second line diagnostic test for confirmation of endometrial cancer and staging. We agree with Oztekin on the fact that there is no established ultrasonographic endometrial cutoff value to diagnose endometrial pathologies in asymptomatic postmenopausal tamoxifen-treated patients. Before beginning our clinical trial [1], we tried to seek for the most accurate cutoff value in tamoxifen-treated patients. Multiple ultrasonographic cutoff points were evaluated on patients who had TVUS examinations followed by H&C. Like other studies [3,4], we observed that there is a gradual increase in specificity and a gradual decrease in sensitivity when ultrasonographic endometrial cutoff value increases. The best cutoff value appeared to be 8–9 mm. The latter was also obtained in numerous other studies [5–7]. If the cutoff value is too high, many endometrial pathologies can be undiagnosed. On the other hand, too small a cutoff value can lead to many needless H&C, which may induce bleeding, uterine perforation and endometritis. Ciatto et al. [4] quantified these data in a consecutive cohort of 1205 breast cancer patients under tamoxifen treatment, undergoing TVUS as follow-up. No endometrial cancer [4] was observed with an endometrial cutoff value below 6 mm. The authors had the following results: for a cutoff value superior or equal to 6, 8, 12 and 18 mm; the specificity was 25.8, 44.5, 76.1 and 91.5%, respectively, and the sensitivity was 100, 91.6, 75.0, 66.6%, respectively. Finally, we agree with Oztekin and other authors on the fact that diagnosis and treatment of baseline endometrial atypical lesions before tamoxifen therapy could decrease the incidence of serious endometrial lesions [2,8]. In our opinion, this does not influence the effectiveness of endometrial brush cytology in the surveillance of postmenopausal women under tamoxifen.
References [1] Mathelin C, Youssef C, Annane K, Brettes JP, Bellocq JP, Walter P. Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: a prospective longitudinal study. Eur J Obstet Gynecol Reprod Biol 2007;132(1):126–8. [2] Garuti G, Grossi F, Centinaio G, Sita G, Nalli G, Luerti M. Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer. Eur J Obstet Gynecol Reprod Biol 2007;132:101–6. [3] Markovitch O, Tepper R, Fishman A, Shapira J, Aviram R, Cohen I. The value of transvaginal ultrasonography in the prediction of endometrial
[4]
[5]
[6]
[7]
[8]
121
pathologies in asymptomatic postmenopausal breast cancer tamoxifentreated patients. Gynecol Oncol 2004;95(3):456–62. Ciatto S, Cecchini S, Gervasi G, Landini A, Zappa M, Crocetti E. Surveillance for endometrial cancer with transvaginal ultrasonography of breast cancer patients under tamoxifen treatment. Br J Cancer 2003;88(8):1175–9. Hann LE, Giess CS, Bach AM, Tao Y, Baum HJ, Barakat RR. Endometrial thickness in tamoxifen-treated patients: correlation with clinical and pathologic findings. Am J Roentgenol 1997;168(3):657–61. Liedman R, Lindahl B, Andolf E, Willen R, Ingvar C, Ranstam J. Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Res 2000;20(6C):4889–91. Franchi M, Ghezzi F, Donadello N, Zanaboni F, Beretta P, Bolis P. Endometrial thickness in tamoxifen-treated patients: an independent predictor of endometrial disease. Obstet Gynecol 1999;93(6):1004–8. McGonigle KF, Smith DD, Marx HF, Morgan RJ, Vasilev SA, Roy S, et al. Uterine effects of tamoxifen: a prospective study. Int J Gynecol Cancer 2006;16(2):814–20.
Carole Mathelin* Cherif Youssef Service de gyne´cologie-obste´trique, Centre Hospitalier Universitaire, 1 place de l’Hoˆpital, 67091 Strasbourg Cedex, France *Corresponding author. Tel.: +33 3 88 11 60 71; fax: +33 3 88 11 53 91 E-mail address: [email protected] (C. Mathelin) 18 September 2006 doi:10.1016/j.ejogrb.2006.10.040
Anoscopy could be beneficial for women with external anogenital condyloma Dear Editor, The percentage of the population regularly performing anogenital sex appears to be increasing. Consequently, sexually transmitted diseases, such as human papiloma virus (HPV) induced intra-anal condyloma, could be expected in sexually active women. Palefsky et al. [1] reported that 76% of HIV-positive and 42% of high risk HIV-negative women had anal HPV infection. Conley et al. [2] showed a higher risk of developing vulvovaginal or anal high grade dysplasia-bearing condylomata in women who are HIV-positive. Despite these facts, as well as in many other studies, we still can read articles [3] which minimise the importance of genital condyloma and call them a cosmetic nuisance. Minimising the importance of external anogenital condyloma, inadequate previous treatment and ignoring the fact that the anorectum could serve as a sexual organ could be responsible for the delay of proctological evaluation in two young women treated at our institution in the last 2 years who developed ‘‘in situ’’ verrucose intraDOIs of original articles: 10.1016/j.ejogrb.2006.12.023., 10.1016/j.ejogrb.2006.12.024.