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Hysteroscopic resection of endometrial hyperplasia
May 1999, Vol. 6, No. 2
TheJournal of the American Associationof Gynecologic Laparoscopists
Hysteroscopic Resection of Endometrial Hyperplasia Luciano Cianferoni, M.D., Augusto Giannini, M.D., and Mario Franchini, M.D.
Abstract Study Objective. To evaluate the efficacy and safety of hysteroscopic resection of endometrial hyperplasia without atypia. Design. Pilot feasibility study (Canadian Task Force classification II- 1). Setting. Department of gynecology at a general hospital. Patients. Seventy-three women. Intervention. Transcervical hysteroscopic endometrial resection under general or spinal anesthesia. Measurements and Main Results. Efficacy of treatment was based on hysteroscopic and histologic regression of endometrial hyperplasia and subjectively assessed uterine bleeding. Safety was evaluated by adverse events. Fortyfour cycling women experienced complete remission of uterine bleeding and none had persistence of endometrial hyperplasia during follow-up; four underwent hysterectomy. Atrophic endometrium was present in 24 menopausal women, one of whom underwent hysterectomy. Conclusion. Endometrial resection was effective in achieving regression of endometrial hyperplasia and preventing its recurrence. (J Am AssocGynecol Laparosc6(2):151-154, 1999)
Endometrial hyperplasia has been linked to endometrial cancer for many years, but the relationship of the two is not well defined. In recent years attention has been directed to cytologic atypia as an indicator for the development of carcinoma. ~ Less than 2% of hyperplasia without cytologic atypia progresses to
carcinoma, compared with 23% with such findings if left untreated, z One-third of women with endometrial hyperplasia may become asymptomatic after diagnostic curettage? Oral or local progestins and danazol also have been widely used to treat the disorder for many years,
From the Departments of Obstetrics and Gynecology (Drs. Cianferoni and Franchini) and Pathology (Dr. Giannini), Santa Maria Annunziata Hospital, Florence, Italy. Address reprint requests to Luciano Cianferoni, M.D., 7 Costa Scarpuccia, 50125 Florence, Italy; fax 39 055 500 t815. Presented at the 26th annual meeting of the American Association of Gynecologic Laparoscopists, Seattle, Washington, September 23-28, 1997. Accepted for publication March 10, 1999.
151
Hysteroscopic Resection of Endometrial Hyperplasia Cianferoni et al
with failure rates ranging from 13% to 2 0 % . 4-7 In the past decade endometrial resection has become the treatment of choice for benign uterine pathologyS.9; however, its role in managing endometrial hyperplasia is still under investigation. We evaluated the efficacy and safety of endometrial hysteroscopic resection in women with symptomatic, histologically proved endometrial hyperplasia without cytologic atypia. Materials and Methods
Starting in February 1992, 48 premenopausal and 25 postmenopausal women (mean age 52 yrs, range 40-78 yrs) with abnormal uterine bleeding and histologically proved endometrial hyperplasia without atypia gave informed consent and were enrolled in the study. Time since last menses in postmenopausal women ranged from 1 to 35 years. To be eligible, they had to have a normal pelvic examination, and uterine size less than 10 weeks and sound measurement of less than 10 cm. Twenty-one (43.8%) premenopausal patients were given preoperative endometrial preparation, seven with medroxyprogesterone acetate, six with danazol, and eight with tryptorelin, a gonadotropin-releasing hormone analog. None of the postmenopausal women received pretreatment; three were receiving hormone replacement therapy. Three premenopausal and four postmenopausal women were being treated with tamoxifen because of breast cancer. Until December 1995, all participants were routinely given a single dose of preoperative prophylactic cephazolidine 2 g intravenously.
balance was carefully monitored, and the procedure was interrupted if fluid loss exceeded 1000 ml. Endometrial resection was performed with a wire loop electrode set at 100 to 120 W pure cutting current. Endometrial ablation of tubal ostia and a narrow strip of the fundus was carried out with a rollerball set at 50 to 70 W coagulation (Birtcher 4400 Power Plus; Birtcher Medical System Inc., Irvine, CA). Endomyometrial resection was performed to a depth of 4 to 5 mm, including 2 to 3 mm of myometrium. Strips of endometrium were removed from the cavity and sent for histologic examination. In case of intraoperative bleeding, a balloon catheter was placed in the uterine cavity and filled with 15 ml saline solution at the end of surgery and removed after 6 hours. All women were evaluated 6 and 12 months postoperatively and then yearly with transvaginal ultrasound and hysteroscopy. Endometrial biopsies were performed every 12 months, and in case double-layer endometrial thickness was more than 4 mm in menopausal women.
Disease Classification Endometrial hyperplasia was classified as typical or atypical. These were subdivided into simple and complex according to the classification of the International Society of Gynecological Pathologists. 10The lesion was considered as having regressed, persisted, or recurred according to the following criteria: Regression--hysteroscopy and biopsy indicated that the lesion reverted to a normal phase or became atrophic. Persistence--hysteroscopy and subsequent endometrial samples showed a hyperplastic process. Recurrence--hysteroscopy and endometrial samples showed a proliferative lesion after a disease-free period.
Operative Procedure The procedures were scheduled as same day surgery. Most (87%) were performed under general anesthesia with propofol 2 mg/kg and spontaneous ventilation with a mixture of 60% nitrous oxide and 40% oxygen isofluothane. The rest (13%) had spinal anesthesia with hyperbaric bupivacaine hydrochloride 0.5%. After the cervix was dilated to 9 mm, hysteroscopic resection was performed with a standard dualchannel, 26F irrigating resectoscope (Karl Storz, Tuttlingen, Germany). The distention medium was 1.5% glycine and 1.5% mannitol solution, and a suction-irrigating unit (Endomat; Karl Storz) provided positive pressure and continuous flow control. Fluid
Results
The overall complication rate was 8.2%. One menopausal patient (1.36%) had a uterine perforation during removal of endometrial chips. She was kept overnight for observation and discharged the next day. No further investigation or treatment were required. In two premenopausal women (2.74%) postoperative hemorrhage was controlled with an intrauterine balloon catheter that was inserted for 6 hours at the end of endometrial resection.
152
May 1999, Vol. 6, No. 2
Thejournal of the American Association of Gynecologic Laparoscopists
Histologic diagnoses at enrollment were complex hyperplasia in six (12.5%) premenopausal and three (12%) postmenopausal women, and simple hyperplasia in all the others. In 11 (20.8%) and 18 (72%) participants, respectively, the disease was associated with single or multiple polyps that in some cases filled the entire endometrial cavity. All 73 patients were followed for mean 34 months (range 9-83 mo) and answered a questionnaire at every 6-month follow-up visit. Of 48 cycling women, 44 (91.6%) experienced complete remission of abnormal uterine bleeding and none had persistence of endometrial hyperplasia. Eighteen (40.9%) of 44 premenopausal women became amenorrheic 5 to 6 weeks after the initial treatment, 16 (36.3%) hypomenorrheic, and 10 (22.7%) eumenorrheic. Four (8.4%) underwent hysterectomy, three for persistence of menorrhagia after 6 months, and one for development of large fibroid after 14 months. Histologic reports showed evidence of residual hyperplasia only in one patient. Two premenopausal women became amenorrheic and after 6 months developed cyclic pain controlled with medical treatment. One case of tubal syndrome was treated by laparoscopic right salpingectomy. Of 25 postmenopausal women, 21 were amenorrheic and 3 (12.5 %) had persistent light spotting without need of further treatment. Endometrial hyperplasia with cytologic atypia was detected in endometrial chips in a postmenopausal woman and hysterectomy was performed within 2 weeks. Sixty-eight women were satisfied with the procedure. At 12-month follow-up visit, endometrial biopsies showed regression of hyperplasia and presence of functional or atrophic endometrium. No infections were reported in these patients, and for that reason prophylactic antibiotic therapy was discontinued in 1995.
presence or absence seems to be important in assessing the biologic behavior of the malignancy. ~2 Furthermore, endometrial resection may help to identify immediately patients who require further evaluation or treatment. In all our patients we obtained strips of endometrium for histopathologic examination, and no endometrial carcinoma was found. Techniques that do not provide specimens for histologic study, such as microwave treatment of the endometrium, heated saline endometrial ablation, uterine balloon thermal therapy, and photosensitive dyes to destroy endometrium, should be performed with caution. Our data suggest that endometrial resection was effective in treating endometrial hyperplasia and in preventing recurrence during 34-month follow-up even in women with tamoxifen-induced hyperplasia. The best results were obtained in postmenopausal women, which suggests that the procedure is preferably performed in women close to menopause. Failure in premenopausal women may be due to development of other benign uterine pathology such as flbroids and adenomyosis. Therefore, careful selection of patients is recommended to improve success rates. Because endometrial resection is a safe and effective procedure with minimal morbidity, it may be considered a reasonable strategy for one-time evaluation and treatment of premalignant endometrial pathology. References
1. Ferency A, Gelfand M: The biologic significance of cytologic atypia in progesterone-treated endometrial hyperplasia. Am J Obstet Gynecol 160:126-31, 1989 . Kurman RJ, Kaminski PF, Norris HJ: The behavior of "untreated" hyperplasia in 170 patients. Cancer 56:403-412, 1985 . Di Saja PJ, Creasman WT: Endometrial hyperplasia/ estrogen therapy. In Clinical Gynecologic Oncology, 4th ed. Edited by PJ Di Saja, WT Creasman. St. Louis, Mosby-Year Book, 1993, pp 126-155
Discussion
A one-step procedure that may be diagnostic and therapeutic, allowing treatment while performing selective endometrial sampling under direct visualization of the uterine cavity, results in reduced discomfort, cost, and recuperation for patients at highest risk for endometrial cancer, u Endometrial hyperplasia is often associated with endometrial cancer, and its
4. Gal D, Edman CD, Vellios F, et al: Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Am J Obstet Gynecol 146:316-321, 1983 . Nilsson CG, Luukkainen T, Arko H: Endometrial morphology of women using a d-norgestrel releasing intrauterine device. Fertil Steril 29:396-401, 1978
153
Hysteroscopic Resection of Enclometrial Hyperplasia Cianferoni et al
10. Silverberg SG, Kurman RJ: Endometrial polyps and hyperplasias. In Tumors of the Uterine Corpus and Gestational Trophoblastic Disease, 3rd ed. Edited by J Rosai. Washington, DC, Armed Forces Institute of Pathology, 1992, pp 315-345
6. Podratz KC, O'Brien PC, Malkasian GD, et al: Effects of progestational agents in treatment of endometrial carcinoma. Obstet Gynecol 66:106-110, 1985 7. Sob E, Sato K: Clinical effects of danazol on endometrial hyperplasia in menopausal and postmenopausal women. Cancer 66:983-988, 1990
11. Kaku T, Tsukamoto N, Hachisuga T. et al: Endometrial carcinoma associated with hyperplasia. Gynecol Oncol 60:22-25, 1996
8. Garry R: Good practice with endometrial ablation. Obstet Gynecol 85:144-151, 1995
12, TownsendDE, Fields G, McCauslandA, et al: Diagnostic and operative hysteroscopy in the management of persistent postmenopausal bleeding. Obstet Gynecol 82:419-421, 1993
9. Vilos GA, gilos EC, King JH: Experience with 800 endometrial ablations. J Am Assoc Gynecol Laparosc 4(1):33-38, 1996
154
TheJournal of the American Associationof Gynecologic Laparoscopists
Hysteroscopic Resection of Endometrial Hyperplasia Luciano Cianferoni, M.D., Augusto Giannini, M.D., and Mario Franchini, M.D.
Abstract Study Objective. To evaluate the efficacy and safety of hysteroscopic resection of endometrial hyperplasia without atypia. Design. Pilot feasibility study (Canadian Task Force classification II- 1). Setting. Department of gynecology at a general hospital. Patients. Seventy-three women. Intervention. Transcervical hysteroscopic endometrial resection under general or spinal anesthesia. Measurements and Main Results. Efficacy of treatment was based on hysteroscopic and histologic regression of endometrial hyperplasia and subjectively assessed uterine bleeding. Safety was evaluated by adverse events. Fortyfour cycling women experienced complete remission of uterine bleeding and none had persistence of endometrial hyperplasia during follow-up; four underwent hysterectomy. Atrophic endometrium was present in 24 menopausal women, one of whom underwent hysterectomy. Conclusion. Endometrial resection was effective in achieving regression of endometrial hyperplasia and preventing its recurrence. (J Am AssocGynecol Laparosc6(2):151-154, 1999)
Endometrial hyperplasia has been linked to endometrial cancer for many years, but the relationship of the two is not well defined. In recent years attention has been directed to cytologic atypia as an indicator for the development of carcinoma. ~ Less than 2% of hyperplasia without cytologic atypia progresses to
carcinoma, compared with 23% with such findings if left untreated, z One-third of women with endometrial hyperplasia may become asymptomatic after diagnostic curettage? Oral or local progestins and danazol also have been widely used to treat the disorder for many years,
From the Departments of Obstetrics and Gynecology (Drs. Cianferoni and Franchini) and Pathology (Dr. Giannini), Santa Maria Annunziata Hospital, Florence, Italy. Address reprint requests to Luciano Cianferoni, M.D., 7 Costa Scarpuccia, 50125 Florence, Italy; fax 39 055 500 t815. Presented at the 26th annual meeting of the American Association of Gynecologic Laparoscopists, Seattle, Washington, September 23-28, 1997. Accepted for publication March 10, 1999.
151
Hysteroscopic Resection of Endometrial Hyperplasia Cianferoni et al
with failure rates ranging from 13% to 2 0 % . 4-7 In the past decade endometrial resection has become the treatment of choice for benign uterine pathologyS.9; however, its role in managing endometrial hyperplasia is still under investigation. We evaluated the efficacy and safety of endometrial hysteroscopic resection in women with symptomatic, histologically proved endometrial hyperplasia without cytologic atypia. Materials and Methods
Starting in February 1992, 48 premenopausal and 25 postmenopausal women (mean age 52 yrs, range 40-78 yrs) with abnormal uterine bleeding and histologically proved endometrial hyperplasia without atypia gave informed consent and were enrolled in the study. Time since last menses in postmenopausal women ranged from 1 to 35 years. To be eligible, they had to have a normal pelvic examination, and uterine size less than 10 weeks and sound measurement of less than 10 cm. Twenty-one (43.8%) premenopausal patients were given preoperative endometrial preparation, seven with medroxyprogesterone acetate, six with danazol, and eight with tryptorelin, a gonadotropin-releasing hormone analog. None of the postmenopausal women received pretreatment; three were receiving hormone replacement therapy. Three premenopausal and four postmenopausal women were being treated with tamoxifen because of breast cancer. Until December 1995, all participants were routinely given a single dose of preoperative prophylactic cephazolidine 2 g intravenously.
balance was carefully monitored, and the procedure was interrupted if fluid loss exceeded 1000 ml. Endometrial resection was performed with a wire loop electrode set at 100 to 120 W pure cutting current. Endometrial ablation of tubal ostia and a narrow strip of the fundus was carried out with a rollerball set at 50 to 70 W coagulation (Birtcher 4400 Power Plus; Birtcher Medical System Inc., Irvine, CA). Endomyometrial resection was performed to a depth of 4 to 5 mm, including 2 to 3 mm of myometrium. Strips of endometrium were removed from the cavity and sent for histologic examination. In case of intraoperative bleeding, a balloon catheter was placed in the uterine cavity and filled with 15 ml saline solution at the end of surgery and removed after 6 hours. All women were evaluated 6 and 12 months postoperatively and then yearly with transvaginal ultrasound and hysteroscopy. Endometrial biopsies were performed every 12 months, and in case double-layer endometrial thickness was more than 4 mm in menopausal women.
Disease Classification Endometrial hyperplasia was classified as typical or atypical. These were subdivided into simple and complex according to the classification of the International Society of Gynecological Pathologists. 10The lesion was considered as having regressed, persisted, or recurred according to the following criteria: Regression--hysteroscopy and biopsy indicated that the lesion reverted to a normal phase or became atrophic. Persistence--hysteroscopy and subsequent endometrial samples showed a hyperplastic process. Recurrence--hysteroscopy and endometrial samples showed a proliferative lesion after a disease-free period.
Operative Procedure The procedures were scheduled as same day surgery. Most (87%) were performed under general anesthesia with propofol 2 mg/kg and spontaneous ventilation with a mixture of 60% nitrous oxide and 40% oxygen isofluothane. The rest (13%) had spinal anesthesia with hyperbaric bupivacaine hydrochloride 0.5%. After the cervix was dilated to 9 mm, hysteroscopic resection was performed with a standard dualchannel, 26F irrigating resectoscope (Karl Storz, Tuttlingen, Germany). The distention medium was 1.5% glycine and 1.5% mannitol solution, and a suction-irrigating unit (Endomat; Karl Storz) provided positive pressure and continuous flow control. Fluid
Results
The overall complication rate was 8.2%. One menopausal patient (1.36%) had a uterine perforation during removal of endometrial chips. She was kept overnight for observation and discharged the next day. No further investigation or treatment were required. In two premenopausal women (2.74%) postoperative hemorrhage was controlled with an intrauterine balloon catheter that was inserted for 6 hours at the end of endometrial resection.
152
May 1999, Vol. 6, No. 2
Thejournal of the American Association of Gynecologic Laparoscopists
Histologic diagnoses at enrollment were complex hyperplasia in six (12.5%) premenopausal and three (12%) postmenopausal women, and simple hyperplasia in all the others. In 11 (20.8%) and 18 (72%) participants, respectively, the disease was associated with single or multiple polyps that in some cases filled the entire endometrial cavity. All 73 patients were followed for mean 34 months (range 9-83 mo) and answered a questionnaire at every 6-month follow-up visit. Of 48 cycling women, 44 (91.6%) experienced complete remission of abnormal uterine bleeding and none had persistence of endometrial hyperplasia. Eighteen (40.9%) of 44 premenopausal women became amenorrheic 5 to 6 weeks after the initial treatment, 16 (36.3%) hypomenorrheic, and 10 (22.7%) eumenorrheic. Four (8.4%) underwent hysterectomy, three for persistence of menorrhagia after 6 months, and one for development of large fibroid after 14 months. Histologic reports showed evidence of residual hyperplasia only in one patient. Two premenopausal women became amenorrheic and after 6 months developed cyclic pain controlled with medical treatment. One case of tubal syndrome was treated by laparoscopic right salpingectomy. Of 25 postmenopausal women, 21 were amenorrheic and 3 (12.5 %) had persistent light spotting without need of further treatment. Endometrial hyperplasia with cytologic atypia was detected in endometrial chips in a postmenopausal woman and hysterectomy was performed within 2 weeks. Sixty-eight women were satisfied with the procedure. At 12-month follow-up visit, endometrial biopsies showed regression of hyperplasia and presence of functional or atrophic endometrium. No infections were reported in these patients, and for that reason prophylactic antibiotic therapy was discontinued in 1995.
presence or absence seems to be important in assessing the biologic behavior of the malignancy. ~2 Furthermore, endometrial resection may help to identify immediately patients who require further evaluation or treatment. In all our patients we obtained strips of endometrium for histopathologic examination, and no endometrial carcinoma was found. Techniques that do not provide specimens for histologic study, such as microwave treatment of the endometrium, heated saline endometrial ablation, uterine balloon thermal therapy, and photosensitive dyes to destroy endometrium, should be performed with caution. Our data suggest that endometrial resection was effective in treating endometrial hyperplasia and in preventing recurrence during 34-month follow-up even in women with tamoxifen-induced hyperplasia. The best results were obtained in postmenopausal women, which suggests that the procedure is preferably performed in women close to menopause. Failure in premenopausal women may be due to development of other benign uterine pathology such as flbroids and adenomyosis. Therefore, careful selection of patients is recommended to improve success rates. Because endometrial resection is a safe and effective procedure with minimal morbidity, it may be considered a reasonable strategy for one-time evaluation and treatment of premalignant endometrial pathology. References
1. Ferency A, Gelfand M: The biologic significance of cytologic atypia in progesterone-treated endometrial hyperplasia. Am J Obstet Gynecol 160:126-31, 1989 . Kurman RJ, Kaminski PF, Norris HJ: The behavior of "untreated" hyperplasia in 170 patients. Cancer 56:403-412, 1985 . Di Saja PJ, Creasman WT: Endometrial hyperplasia/ estrogen therapy. In Clinical Gynecologic Oncology, 4th ed. Edited by PJ Di Saja, WT Creasman. St. Louis, Mosby-Year Book, 1993, pp 126-155
Discussion
A one-step procedure that may be diagnostic and therapeutic, allowing treatment while performing selective endometrial sampling under direct visualization of the uterine cavity, results in reduced discomfort, cost, and recuperation for patients at highest risk for endometrial cancer, u Endometrial hyperplasia is often associated with endometrial cancer, and its
4. Gal D, Edman CD, Vellios F, et al: Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Am J Obstet Gynecol 146:316-321, 1983 . Nilsson CG, Luukkainen T, Arko H: Endometrial morphology of women using a d-norgestrel releasing intrauterine device. Fertil Steril 29:396-401, 1978
153
Hysteroscopic Resection of Enclometrial Hyperplasia Cianferoni et al
10. Silverberg SG, Kurman RJ: Endometrial polyps and hyperplasias. In Tumors of the Uterine Corpus and Gestational Trophoblastic Disease, 3rd ed. Edited by J Rosai. Washington, DC, Armed Forces Institute of Pathology, 1992, pp 315-345
6. Podratz KC, O'Brien PC, Malkasian GD, et al: Effects of progestational agents in treatment of endometrial carcinoma. Obstet Gynecol 66:106-110, 1985 7. Sob E, Sato K: Clinical effects of danazol on endometrial hyperplasia in menopausal and postmenopausal women. Cancer 66:983-988, 1990
11. Kaku T, Tsukamoto N, Hachisuga T. et al: Endometrial carcinoma associated with hyperplasia. Gynecol Oncol 60:22-25, 1996
8. Garry R: Good practice with endometrial ablation. Obstet Gynecol 85:144-151, 1995
12, TownsendDE, Fields G, McCauslandA, et al: Diagnostic and operative hysteroscopy in the management of persistent postmenopausal bleeding. Obstet Gynecol 82:419-421, 1993
9. Vilos GA, gilos EC, King JH: Experience with 800 endometrial ablations. J Am Assoc Gynecol Laparosc 4(1):33-38, 1996
154