- Email: [email protected]
Positron emission tomography and uterine leiomyomas: Authors' response
594
Letters to the Editor
However, malignant-type leiomyosarcomas should often be kept in mind, although the incidence is rare and the majority of leiomyosarcomas are diagnosed after hysterectomy or myomectomy, at the time of the pathologic review [1]. Therefore, how to distinguish between a leiomyoma and a leiomyosarcoma prior to surgery is an interesting issue and worthy of further evaluation. Many imaging studies, including high-resolution ultrasound, computed tomography and magnetic resonance imaging have been tried. However, none of them are adequate in achieving satisfactory sensitivity or specificity partly due to the small sample size. Although the use of positron emission tomography (PET) in oncologic diagnosis has rekindled interest in this technique [3], the application of PET for distinguishing leiomyomas from leiomyosarcomas is doubtful [1] and needs further evaluation [4]. We welcome Chura et al.'s efforts to explore the pathogenesis of PET scanpositive leiomyomas and observed the striking phenomenon that the PET scan-positive leiomyoma has increased vascularity [1]. However, this striking phenomenon may be the result of an accident. In our previous study, although the data was limited by the very small series (a total of 4 women), 2 women with surgery-proved myomas did not show an increased accumulation of (fluorine-18)-2-deoxygelucose (FDG) in either the normal uterine tissue or the uterine myoma preoperatively [5]. By contrast, the other 2 women, who were treated with 4 courses of gonadotropin-releasing hormone agonist (GnRH agonist) preoperatively, and then received a PET evaluation, demonstrated an increased FDG uptake, with a distribution that correlated with the uterine leiomyoma area, which was proved by myomectomy [5]. The application of GnRH agonist in uterine myoma preoperatively is a well-accepted procedure based on advantages that include a significant decrease of blood loss and easy manipulation [6]. If the increased vascularity is correlated with the PET scan-positive leiomyoma, why were the abovementioned benefits found when we performed myomectomy after GnRH agonist treatment? By contrast, if the increased vascularity of the uterine leiomyoma is real, it may contribute to regrowth of GnRH agonist treated uterine myomas after cessation of therapy [5], although the blood flow change in the uterine myoma before and after GnRH agonist treatment was still inconclusive in literature reviews [7,8]. We hope to see further discussion and suggestions on this issue.
[3] Wang PH, Liu RS, Li YF, Ng HT, Yuan CC. Whole-body PET with (fluorine-18)-2-deoxygelucose for detecting recurrent primary serous peritoneal carcinoma. Gynecol Oncol 2000;77:44–7. [4] Umesaki N, Tanaka T, Miyama M, et al. Positron emission tomography with 18F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging. Gynecol Oncol 2000; 80:372–7. [5] Lee WL, Liu RS, Yuan CC, Chao HT, Wang PH. Relationship between gonadotropin-releasing hormone agonist and myoma cellular activity: preliminary findings on positron emission tomography. Fertil Steril 2001; 75:638–9. [6] Palomba S, Zupi E, Zullo F. A prospective study of laparoscopy versus minilaparotomy in the treatment of uterine myomas. J Minim Invasive Gynecol 2006;13:253 [author reply 253–4]. [7] Wang PH, Yang AH, Yuan CC, Ng HT, Chao HT. Uterine myoma after cessation of gonadotropin-releasing hormone agonist: ultrasound and histopathologic findings. J Chin Med Assoc 1998;61:625–9. [8] Chia CC, Huang SC, Chen SS, Kang JY, et al. Ultrasonographic evaluation of the uterine fibroids induced by treatment with a GnRH analog. Taiwan J Obstet Gynecol 2006;45:124–8.
Wen-Ling Lee Division of Endocrinology and Metabolism, Department of Medicine, Cheng Hsin Rehabilitation Center-Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Chiou-Chung Yuan Peng-Hui Wang* Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan *Corresponding author. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan. Fax: +886 2 2873 4101. E-mail address: [email protected] 26 June 2007 doi:10.1016/j.ygyno.2007.08.005
Acknowledgments
Positron emission tomography and uterine leiomyomas: Authors' response
This article was supported in part, by Grants from Taipei Veterans General Hospital and National Science Council.
To the Editor:
References [1] Chura JC, Truskinovsky AM, Judson PL, Johnson L, Geller MA, Downs LS. Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review. Gynecol Oncol 2007;104:247–52. [2] Liu WM, Wang PH, Chou CS, et al. Efficacy of combined laparoscopic uterine artery occlusion and myomectomy via minilaparotomy in the treatment of recurrent uterine myomas. Fertil Steril 2007;87:356–61.
We appreciate the interest of Dr. Lee and colleagues regarding the issue of PET scans and uterine leiomyomas [1] that we recently presented [2]. This intersection of a widely used diagnostic test and the most common tumor of the female genital tract presents a vexing clinical scenario: How should PET scan positive uterine tumors be managed? Lee et al. introduce another variable into the question above with their use of GnRH agonist therapy in two patients with
Letters to the Editor
PET scan positive myomas [3]. Unfortunately, we do not know whether or not the GnRH treatment influenced the FDG uptake as the PET scans were only obtained after therapy. In their two patients who did not receive GnRH treatment, preoperative PET evaluation was negative for increased uptake in the myomas. The precise molecular mechanism of GnRH agonist treatment on uterine fibroids is not wholly understood, although the clinical benefits are clear with reduced tumor size and blood loss at surgery [4]. In one study, GnRH treatment resulted in decreased blood flow in the leiomyometrial vessels as well as main uterine vessels as assessed by ultrasound [5]. An immunochemistry evaluation of vascular endothelial growth factor (VEGF) expression and other markers of angiogenesis also demonstrated decreased vascularity in myomas after GnRH therapy [6]. This leads to the issue raised by Lee et al.: If increased vascularity accounts for the PET positive uterine myomas we reported [2], and if GnRH treatment decreases myoma vascularity [5,6], then uterine myomas should be PET negative after GnRH therapy. There are problems, however, with this logic. First, data are conflicting with regards to the effect of GnRH therapy and myoma vascularity. Two additional studies failed to detect vascular changes in GnRH treated myomas [7,8]. Second, although Lee et al. observed PET positive myomas after GnRH therapy, we do not know the status of the myomas prior to therapy. It is possible that GnRH treatment resulted in a relative reduction of FDG uptake, but a degree of positivity still persisted. It is also entirely possible the GnRH therapy contributed to PET positivity of the myomas. The common thread among our patients with PET positive myomas and the patients of Lee and colleagues appears to be a menopausal status. Although not stated explicitly in our initial report, all patients were menopausal. Perhaps this menopausal status, whether natural or pharmacologic (as in the patients of Lee et al.), plays a role in the phenomenon of PET positive myomas. Clearly, all arguments above are speculative in nature. As we note in our original manuscript, further investigation of this issue is warranted. We appreciate this interesting question which will hopefully stimulate further research. References [1] Lee W-L, Yuan C-C, Wang P-H. Positron emission tomography and uterine leiomyomas. Gynecol Oncol 2007;107: 593–4. [2] Chura JC, Truskinovsky AM, Judson PL, et al. Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scanpositive leiomyomas and literature review. Gynecol Oncol 2007;104(1): 247–52. [3] Lee WL, Liu RS, Yuan CC, Chao HT, Wang PH. Relationship between gonadotropin-releasing hormone agonist and myoma cellular activity: preliminary findings on positron emission tomography. Fertil Steril 2001;75(3): 638–9. [4] Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001(2):CD000547. [5] Aleem FA, Predanic M. The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity: a prospective study using
595
transvaginal color Doppler sonography. Gynecol Endocrinol Sep 1995;9 (3):253–8. [6] Di Lieto A, De Falco M, Pollio F, et al. Clinical response, vascular change, and angiogenesis in gonadotropin-releasing hormone analogue-treated women with uterine myomas. J Soc Gynecol Investig 2005;12(2):123–8. [7] Wang PH, Yang AH, Yuan CC, et al. Uterine myoma after cessation of gonadotropin-releasing hormone agonist: ultrasound and histopathologic findings. Zhonghua Yi Xue Za Zhi (Taipei) Nov. 1998;61(11):625–9. [8] Chia CC, Huang SC, Chen SS, et al. Ultrasonographic evaluation of the change in uterine fibroids induced by treatment with a GnRH analog. Taiwan J Obstet Gynecol Jun 2006;45(2):124–8.
Justin C. Chura Levi S. Downs Jr.* University of Minnesota, Department of Obstetrics, Gynecology and Women’s Health, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USA E-mail address: [email protected]. ⁎Corresponding author. 2 August 2007 doi:10.1016/j.ygyno.2007.08.006
Letter to the Editor concerning Petignat et al.'s “Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis.” Gynecol Oncol 2007;105(2): 530–5
To the Editor: Though we agree with Petignat et al.'s conclusion [1] that the self-test for high-risk human papillomavirus (HR-HPV) is correlated with the physician-collected test for HR-HPV, we disagree with their conclusion that the two tests are equivalent and that the self-test may simplify conduction of epidemiologic studies and monitoring efficacy of HPV vaccines. Petignat et al. use a meta-analysis of two-by-two tables comparing self- and physician-collected HR-HPV, and, as kappa is 0.66, concludes that the two tests are correlated. Petignat et al. cites our second China study (ref #15), but does not include it in the metaanalysis because the data needed to create the two-by-two tables were not presented. In Petignat et al.'s reference #15, in Table 5, we correlated selfand physician-collected specimens for 1932 women from our first cervical cancer screening study. In Table 3 from this citation, we Table 5 Correlation of self-test and physician-collected test for HR-HPV in 1932 women participating in the first Shanxi Province Cervical Cancer Screening Program
Self HR-HPV pos Self HR-HPV neg
Physician-collected HR-HPV pos (number ≥CIN 2)
Physician-collected HR-HPV neg (number ≥ CIN 2)
274 (69) 89 (12) 363
55 (0) 1514 (2) 1569
329 1603 1932
Numbers in parenthesis are the number of women diagnosed with cervical intraepithelial neoplasia (CIN) 2 or worse.
Letters to the Editor
However, malignant-type leiomyosarcomas should often be kept in mind, although the incidence is rare and the majority of leiomyosarcomas are diagnosed after hysterectomy or myomectomy, at the time of the pathologic review [1]. Therefore, how to distinguish between a leiomyoma and a leiomyosarcoma prior to surgery is an interesting issue and worthy of further evaluation. Many imaging studies, including high-resolution ultrasound, computed tomography and magnetic resonance imaging have been tried. However, none of them are adequate in achieving satisfactory sensitivity or specificity partly due to the small sample size. Although the use of positron emission tomography (PET) in oncologic diagnosis has rekindled interest in this technique [3], the application of PET for distinguishing leiomyomas from leiomyosarcomas is doubtful [1] and needs further evaluation [4]. We welcome Chura et al.'s efforts to explore the pathogenesis of PET scanpositive leiomyomas and observed the striking phenomenon that the PET scan-positive leiomyoma has increased vascularity [1]. However, this striking phenomenon may be the result of an accident. In our previous study, although the data was limited by the very small series (a total of 4 women), 2 women with surgery-proved myomas did not show an increased accumulation of (fluorine-18)-2-deoxygelucose (FDG) in either the normal uterine tissue or the uterine myoma preoperatively [5]. By contrast, the other 2 women, who were treated with 4 courses of gonadotropin-releasing hormone agonist (GnRH agonist) preoperatively, and then received a PET evaluation, demonstrated an increased FDG uptake, with a distribution that correlated with the uterine leiomyoma area, which was proved by myomectomy [5]. The application of GnRH agonist in uterine myoma preoperatively is a well-accepted procedure based on advantages that include a significant decrease of blood loss and easy manipulation [6]. If the increased vascularity is correlated with the PET scan-positive leiomyoma, why were the abovementioned benefits found when we performed myomectomy after GnRH agonist treatment? By contrast, if the increased vascularity of the uterine leiomyoma is real, it may contribute to regrowth of GnRH agonist treated uterine myomas after cessation of therapy [5], although the blood flow change in the uterine myoma before and after GnRH agonist treatment was still inconclusive in literature reviews [7,8]. We hope to see further discussion and suggestions on this issue.
[3] Wang PH, Liu RS, Li YF, Ng HT, Yuan CC. Whole-body PET with (fluorine-18)-2-deoxygelucose for detecting recurrent primary serous peritoneal carcinoma. Gynecol Oncol 2000;77:44–7. [4] Umesaki N, Tanaka T, Miyama M, et al. Positron emission tomography with 18F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging. Gynecol Oncol 2000; 80:372–7. [5] Lee WL, Liu RS, Yuan CC, Chao HT, Wang PH. Relationship between gonadotropin-releasing hormone agonist and myoma cellular activity: preliminary findings on positron emission tomography. Fertil Steril 2001; 75:638–9. [6] Palomba S, Zupi E, Zullo F. A prospective study of laparoscopy versus minilaparotomy in the treatment of uterine myomas. J Minim Invasive Gynecol 2006;13:253 [author reply 253–4]. [7] Wang PH, Yang AH, Yuan CC, Ng HT, Chao HT. Uterine myoma after cessation of gonadotropin-releasing hormone agonist: ultrasound and histopathologic findings. J Chin Med Assoc 1998;61:625–9. [8] Chia CC, Huang SC, Chen SS, Kang JY, et al. Ultrasonographic evaluation of the uterine fibroids induced by treatment with a GnRH analog. Taiwan J Obstet Gynecol 2006;45:124–8.
Wen-Ling Lee Division of Endocrinology and Metabolism, Department of Medicine, Cheng Hsin Rehabilitation Center-Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Chiou-Chung Yuan Peng-Hui Wang* Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan *Corresponding author. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan. Fax: +886 2 2873 4101. E-mail address: [email protected] 26 June 2007 doi:10.1016/j.ygyno.2007.08.005
Acknowledgments
Positron emission tomography and uterine leiomyomas: Authors' response
This article was supported in part, by Grants from Taipei Veterans General Hospital and National Science Council.
To the Editor:
References [1] Chura JC, Truskinovsky AM, Judson PL, Johnson L, Geller MA, Downs LS. Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review. Gynecol Oncol 2007;104:247–52. [2] Liu WM, Wang PH, Chou CS, et al. Efficacy of combined laparoscopic uterine artery occlusion and myomectomy via minilaparotomy in the treatment of recurrent uterine myomas. Fertil Steril 2007;87:356–61.
We appreciate the interest of Dr. Lee and colleagues regarding the issue of PET scans and uterine leiomyomas [1] that we recently presented [2]. This intersection of a widely used diagnostic test and the most common tumor of the female genital tract presents a vexing clinical scenario: How should PET scan positive uterine tumors be managed? Lee et al. introduce another variable into the question above with their use of GnRH agonist therapy in two patients with
Letters to the Editor
PET scan positive myomas [3]. Unfortunately, we do not know whether or not the GnRH treatment influenced the FDG uptake as the PET scans were only obtained after therapy. In their two patients who did not receive GnRH treatment, preoperative PET evaluation was negative for increased uptake in the myomas. The precise molecular mechanism of GnRH agonist treatment on uterine fibroids is not wholly understood, although the clinical benefits are clear with reduced tumor size and blood loss at surgery [4]. In one study, GnRH treatment resulted in decreased blood flow in the leiomyometrial vessels as well as main uterine vessels as assessed by ultrasound [5]. An immunochemistry evaluation of vascular endothelial growth factor (VEGF) expression and other markers of angiogenesis also demonstrated decreased vascularity in myomas after GnRH therapy [6]. This leads to the issue raised by Lee et al.: If increased vascularity accounts for the PET positive uterine myomas we reported [2], and if GnRH treatment decreases myoma vascularity [5,6], then uterine myomas should be PET negative after GnRH therapy. There are problems, however, with this logic. First, data are conflicting with regards to the effect of GnRH therapy and myoma vascularity. Two additional studies failed to detect vascular changes in GnRH treated myomas [7,8]. Second, although Lee et al. observed PET positive myomas after GnRH therapy, we do not know the status of the myomas prior to therapy. It is possible that GnRH treatment resulted in a relative reduction of FDG uptake, but a degree of positivity still persisted. It is also entirely possible the GnRH therapy contributed to PET positivity of the myomas. The common thread among our patients with PET positive myomas and the patients of Lee and colleagues appears to be a menopausal status. Although not stated explicitly in our initial report, all patients were menopausal. Perhaps this menopausal status, whether natural or pharmacologic (as in the patients of Lee et al.), plays a role in the phenomenon of PET positive myomas. Clearly, all arguments above are speculative in nature. As we note in our original manuscript, further investigation of this issue is warranted. We appreciate this interesting question which will hopefully stimulate further research. References [1] Lee W-L, Yuan C-C, Wang P-H. Positron emission tomography and uterine leiomyomas. Gynecol Oncol 2007;107: 593–4. [2] Chura JC, Truskinovsky AM, Judson PL, et al. Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scanpositive leiomyomas and literature review. Gynecol Oncol 2007;104(1): 247–52. [3] Lee WL, Liu RS, Yuan CC, Chao HT, Wang PH. Relationship between gonadotropin-releasing hormone agonist and myoma cellular activity: preliminary findings on positron emission tomography. Fertil Steril 2001;75(3): 638–9. [4] Lethaby A, Vollenhoven B, Sowter M. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids. Cochrane Database Syst Rev 2001(2):CD000547. [5] Aleem FA, Predanic M. The hemodynamic effect of GnRH agonist therapy on uterine leiomyoma vascularity: a prospective study using
595
transvaginal color Doppler sonography. Gynecol Endocrinol Sep 1995;9 (3):253–8. [6] Di Lieto A, De Falco M, Pollio F, et al. Clinical response, vascular change, and angiogenesis in gonadotropin-releasing hormone analogue-treated women with uterine myomas. J Soc Gynecol Investig 2005;12(2):123–8. [7] Wang PH, Yang AH, Yuan CC, et al. Uterine myoma after cessation of gonadotropin-releasing hormone agonist: ultrasound and histopathologic findings. Zhonghua Yi Xue Za Zhi (Taipei) Nov. 1998;61(11):625–9. [8] Chia CC, Huang SC, Chen SS, et al. Ultrasonographic evaluation of the change in uterine fibroids induced by treatment with a GnRH analog. Taiwan J Obstet Gynecol Jun 2006;45(2):124–8.
Justin C. Chura Levi S. Downs Jr.* University of Minnesota, Department of Obstetrics, Gynecology and Women’s Health, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USA E-mail address: [email protected]. ⁎Corresponding author. 2 August 2007 doi:10.1016/j.ygyno.2007.08.006
Letter to the Editor concerning Petignat et al.'s “Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis.” Gynecol Oncol 2007;105(2): 530–5
To the Editor: Though we agree with Petignat et al.'s conclusion [1] that the self-test for high-risk human papillomavirus (HR-HPV) is correlated with the physician-collected test for HR-HPV, we disagree with their conclusion that the two tests are equivalent and that the self-test may simplify conduction of epidemiologic studies and monitoring efficacy of HPV vaccines. Petignat et al. use a meta-analysis of two-by-two tables comparing self- and physician-collected HR-HPV, and, as kappa is 0.66, concludes that the two tests are correlated. Petignat et al. cites our second China study (ref #15), but does not include it in the metaanalysis because the data needed to create the two-by-two tables were not presented. In Petignat et al.'s reference #15, in Table 5, we correlated selfand physician-collected specimens for 1932 women from our first cervical cancer screening study. In Table 3 from this citation, we Table 5 Correlation of self-test and physician-collected test for HR-HPV in 1932 women participating in the first Shanxi Province Cervical Cancer Screening Program
Self HR-HPV pos Self HR-HPV neg
Physician-collected HR-HPV pos (number ≥CIN 2)
Physician-collected HR-HPV neg (number ≥ CIN 2)
274 (69) 89 (12) 363
55 (0) 1514 (2) 1569
329 1603 1932
Numbers in parenthesis are the number of women diagnosed with cervical intraepithelial neoplasia (CIN) 2 or worse.