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Hematometra after Radiotherapy for Cervical Carcinoma
GYNECOLOGIC ONCOLOGY ARTICLE NO.
67, 325–327 (1997)
GO974883
CASE REPORT Hematometra after Radiotherapy for Cervical Carcinoma C. B. Vernooij,* R. F. P. M. Kruitwagen,*,†,1 P. Rodrigus,† H. C. L. V. Kock,† and H. W. H. Feyen† *Bosch Medical Center, Department of Obstetrics and Gynecology, P.O. 90153, 5200 ME ’s-Hertogenbosch, The Netherlands; and †Task Force Gynecologic Oncology of the Comprehensive Cancer Centre South (IKZ), Eindhoven, The Netherlands Received April 28, 1997
whole-pelvis irradiation in 4 weeks and two intracavitary cesium applications directed to Manchester point A of 20 Gy each, after which a complete remission occurred. Because of climacteric complaints 2.5 mg tibolone 1 dd (Livial) was prescribed in December 1993. In May 1996 (3.5 years after the primary treatment and 2 years after starting the use of tibolone) she complained of vague abdominal pain. Physical examination did not reveal any abnormalities; however, ultrasonographic examination showed a filled uterine cavity. Dilatation and curettage was not successful because of fibrosis of the cervix with complete obliteration of the cervical canal. It was decided to perform a total hysterectomy and bilateral salpingo-oophorectomy. The cervix was difficult to remove because of extensive fibrosis. During the procedure a rupture at the corporal– cervical junction occurred with efflux of a brown serous fluid. Histology of the removed specimen showed no recurrence of the squamous cell carcinoma. The uterine cavity was lined with atrophic endometrium, although small endometriotic foci were noticed throughout the myometrium. At present, 6 years after primary treatment, the patient is well without recurrence of disease. Patient B, a 46-year-old woman, presented with complaints of postcoital blood loss in December 1994. Colposcopical directed biopsies revealed a squamous cervical cancer. Further investigation confirmed a stage IB cervical squamous cell carcinoma, according to the FIGO classification. A class III extended hysterectomy according to Rutledge [2] was intended; however, during the operation an enlarged lymph node was found in the right fossa obturatoria, which at frozen section showed the presence of the squamous cell carcinoma. It was decided to complete the bilateral lymphadenectomy along the iliacal vessels and not to remove the uterus and its ligaments. Histological examination revealed no further nodal metastases. The patient received radiotherapy (whole-pelvis irradiation of 45 Gy and two intracavitary cesium applications directed to
The development of a hematometra after radiotherapy for cervical carcinoma is often related to recurrent disease. We present two cases in which a hematometra developed during the use of estrogen replacement therapy. This development was related to regained endometrial activity in combination with fibrosis and obliteration of the upper vagina and/or cervix. In one patient a dilatation and curettage could be performed; in the other a hysterectomy was necessary in order to exclude recurrent disease. These two cases show once more that endometrium can regain its proliferative activity after radiotherapy for cervical cancer. Estrogen replacement therapy in these patients should include the use of a progestagen agent in order to avoid continuous unopposed endometrial stimulation. In the absence of progesterone withdrawal bleeding the uterine cavity should be routinely examined for the development of a hematometra. © 1997 Academic Press
INTRODUCTION The occurrence of fluid collection within the uterine cavity after radiotherapy for cervical cancer is often related to recurrence of disease or a second primary tumor which needs further investigation [1]. We report two cases that demonstrate the possibility of regained endometrial activity as the cause of such fluid collection in patients who started hormonal replacement therapy. CASE REPORTS Patient A, a 48-year-old adipose woman, presented in September 1992 with postcoital vaginal blood loss which appeared to be related to a grade III squamous cervical cancer stage III B, according to the FIGO classification. The size of the tumor was estimated at 8 cm in diameter (‘‘barrel shaped’’) with infiltration of the left parametrium extending to the pelvic side wall. Radiation therapy consisted of 40-Gy 1
To whom correspondence should be addressed.
325
0090-8258/97 $25.00 Copyright © 1997 by Academic Press All rights of reproduction in any form reserved.
326
VERNOOIJ ET AL.
Manchester point A of 17.5 Gy each) combined with three courses of 5-FU and carboplatin as additive treatment to radiotherapy. In June 1995 estrogen replacement therapy was started on account of climacteric complaints, initially 2.5 mg tibolone 1dd1 (Livial), which after 3 months was changed to 50-mg estradiol plasters twice a week (Menorest). In May 1996 she complained of vague abdominal pain as well as dyspareunia. Physical examination revealed no abnormalities. Vaginal ultrasonography showed a filled uterine cavity. A CT scan showed no other abnormalities besides the enlarged uterus. At dilatation and curettage efflux of bloody fluid occurred. Histological examination revealed proliferating endometrium without evidence of malignancy. After this procedure the complaints disappeared and the ultrasonographic findings remained normal. In order to minimize the vasomotor symptoms 0.025 mg clonidine 2dd1 (Dixarit) was prescribed. In November 1996 (nearly 2 years after primary treatment) the patient developed pain and edema of her left leg. Vaginal examination revealed a mass at the left pelvic side wall. This was confirmed by CT scan, which also identified a hydronephrosis of the left kidney. The uterus showed no abnormalities, especially no fluid within the uterine cavity. A combined operative and radiotherapeutic treatment was performed according to Ho¨ckel et al. [3]. Frozen section of the resected tumor confirmed recurrence of disease. DISCUSSION Treatment of cervical carcinoma by radiotherapy destroys ovarian function unless one or both ovaries are transposed to an extrapelvic site [4], furthermore, it has been thought to ablate the endometrium, both factors resulting in a secondary amenorrhea. It is known, however, that normal endometrium can tolerate a high dose of radiation and has a good ability to recover from radiation injury [5]. Larson et al. described two cases of endometrial response to endogenous hormones after pelvic irradiation in patients who had undergone lateral ovarian transposition, demonstrating the ability of endometrial tissue to resume functional activity after radiation [4]. Barnhill et al. described 16 patients who were evaluated for uterine bleeding after radiotherapy for cervical cancer [6]. All patients used estrogen replacement therapy. Proliferative endometrium was found in 7 patients, demonstrating that proliferative endometrium may persist. One case had cystic hyperplasia, one atypical adenomatous hyperplasia, and one adenocarcinoma. They stated that patients who have had radiation therapy for cervical carcinoma should be treated with both an estrogen and a progestagen agent in order to avoid continuous unopposed endometrial stimulation with an associated increased risk of developing endometrial adenocarcinoma [7]. Mc Kay et al. described 22 patients with persisting cyclical uterine bleeding receiving
hormonal replacement therapy after radiation therapy for carcinoma of the cervix [8]. The cyclical bleeding persisted up to 4 months after radiation. They suggested that this may represent the slow death of endometrial cells subsequent to radiation treatment. The present paper confirms the concept that even after a high radiation dose the endometrium can preserve its proliferative activity, and thus, hormonal treatment should consist of an estrogen in combination with a progestagen agent. Patient A used tibolone (Livial), which has weak estrogenic, androgenic, and progestagenic activity. In general it does not induce endometrial proliferation although uterine bleeding may occur in a small percentage of treated patients [9]. Aartsen reported 16 patients with fluid collection in the uterine cavity after radiotherapy for cervical cancer [1]. In 3 of his patients the fluid collection was related to the start of estrogen replacement therapy. In 75% a malignancy appeared to be responsible for this phenomenon. Therefore, when fluid collection within an irradiated uterus is suspected by ultrasound, further examination is necessary, for which dilatation and curettage is the first method of choice. However, as in patient A, dilatation and curettage may not be successful because of extensive radiation fibrosis and obliteration of the cervical canal after radiotherapy [1]. Kwon et al. described 8 patients who developed an adenocarcinoma of the uterine corpus following radiotherapy for cervical cancer [10]. Only 2 of them presented with abnormal vaginal bleeding, the paucity of this alarming symptom probably being due to postradiation stenosis and obliteration of the upper vagina. Dilatation and curettage was attempted but failed in 3 of 5 patients because of this fibrotic obliteration of the upper vagina and cervix. Since histology of the endometrium in these cases is mandatory, a total abdominal hysterectomy is advisable in case dilatation and curettage fails. In conclusion, the occurrence of a filled uterine cavity after radiotherapy for cervical cancer is not necessarily related to recurrent disease. Especially when estrogen replacement therapy is started, the endometrium can regain its proliferative activity. In patients who begin using estrogen replacement therapy a progestagen agent should be added and the uterine cavity should be routinely examined for the development of a hematometra, especially in the absence of a progestagen withdrawal bleeding.
REFERENCES 1. Aartsen EJ: Fluid detection in the uterus during and after irradiation for carcinoma of the cervix— clinical implications. Eur J Surg Oncol 16:42– 46, 1990 2. Piver MS, Rutledge FN, Smith PJ: Five classes of extended hysterectomy of women with cervical cancer. Obstet Gynecol 44:265–272, 1974 3. Ho¨ckel M, Schlenger K, Hamm H, Knapstein PG, Hohenfellner R, Ro¨sler HP: Five-year experience with combined operative and radiotherapeutic
CASE REPORT
4.
5. 6.
7.
treatment of recurrent gynecologic tumors infiltrating the pelvic wall. Cancer 77:1918 –1933, 1996 Larson JE, Whitney CW, Zaino R, Kaminski P, Podczaski E, Mortel R: Endometrial response to endogenous hormones after pelvic irradiation for genital malignancies. Gynecol Oncol 36:106 –109, 1990 Disaia PJ, Creasman WT: Clinical gynecological oncology. 4th ed, Mosby–Year Book, 1993 Barnhill D, Heller P, Dames J, Hoskins W, Gallup D, Park R: Persistence of endometrial activity after radiation therapy for cervical carcinoma. Obstet Gynecol 66:805– 808, 1985 Gambrell RD, Massey FM, Castaneda TA, Ugenas AJ, Ricci CA, Wright
327
JM: Use of the progestagen challenge test to reduce the risk of endometrial cancer. Obstet Gynecol 55:732–738, 1980 8. Mc Kay MJ, Bull CA, Houghton CR, Langlands AO: Persisting cyclical uterine bleeding in patients treated with radical radiation therapy and hormonal replacement for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 18:921–925, 1990 9. Ginsburg J, Prelevic G, Butler D, Okolo S: Clinical experience with tibolone (Livial) over 8 years. Maturitas 21:71–76, 1995 10. Kwon Th, Prempree T, Tang C, VillaSanta U, Scott RM: Adenocarcinoma of the uterine corpus following irradiation for cervical cancer. Gynecol Oncol 11:102–113, 1981
67, 325–327 (1997)
GO974883
CASE REPORT Hematometra after Radiotherapy for Cervical Carcinoma C. B. Vernooij,* R. F. P. M. Kruitwagen,*,†,1 P. Rodrigus,† H. C. L. V. Kock,† and H. W. H. Feyen† *Bosch Medical Center, Department of Obstetrics and Gynecology, P.O. 90153, 5200 ME ’s-Hertogenbosch, The Netherlands; and †Task Force Gynecologic Oncology of the Comprehensive Cancer Centre South (IKZ), Eindhoven, The Netherlands Received April 28, 1997
whole-pelvis irradiation in 4 weeks and two intracavitary cesium applications directed to Manchester point A of 20 Gy each, after which a complete remission occurred. Because of climacteric complaints 2.5 mg tibolone 1 dd (Livial) was prescribed in December 1993. In May 1996 (3.5 years after the primary treatment and 2 years after starting the use of tibolone) she complained of vague abdominal pain. Physical examination did not reveal any abnormalities; however, ultrasonographic examination showed a filled uterine cavity. Dilatation and curettage was not successful because of fibrosis of the cervix with complete obliteration of the cervical canal. It was decided to perform a total hysterectomy and bilateral salpingo-oophorectomy. The cervix was difficult to remove because of extensive fibrosis. During the procedure a rupture at the corporal– cervical junction occurred with efflux of a brown serous fluid. Histology of the removed specimen showed no recurrence of the squamous cell carcinoma. The uterine cavity was lined with atrophic endometrium, although small endometriotic foci were noticed throughout the myometrium. At present, 6 years after primary treatment, the patient is well without recurrence of disease. Patient B, a 46-year-old woman, presented with complaints of postcoital blood loss in December 1994. Colposcopical directed biopsies revealed a squamous cervical cancer. Further investigation confirmed a stage IB cervical squamous cell carcinoma, according to the FIGO classification. A class III extended hysterectomy according to Rutledge [2] was intended; however, during the operation an enlarged lymph node was found in the right fossa obturatoria, which at frozen section showed the presence of the squamous cell carcinoma. It was decided to complete the bilateral lymphadenectomy along the iliacal vessels and not to remove the uterus and its ligaments. Histological examination revealed no further nodal metastases. The patient received radiotherapy (whole-pelvis irradiation of 45 Gy and two intracavitary cesium applications directed to
The development of a hematometra after radiotherapy for cervical carcinoma is often related to recurrent disease. We present two cases in which a hematometra developed during the use of estrogen replacement therapy. This development was related to regained endometrial activity in combination with fibrosis and obliteration of the upper vagina and/or cervix. In one patient a dilatation and curettage could be performed; in the other a hysterectomy was necessary in order to exclude recurrent disease. These two cases show once more that endometrium can regain its proliferative activity after radiotherapy for cervical cancer. Estrogen replacement therapy in these patients should include the use of a progestagen agent in order to avoid continuous unopposed endometrial stimulation. In the absence of progesterone withdrawal bleeding the uterine cavity should be routinely examined for the development of a hematometra. © 1997 Academic Press
INTRODUCTION The occurrence of fluid collection within the uterine cavity after radiotherapy for cervical cancer is often related to recurrence of disease or a second primary tumor which needs further investigation [1]. We report two cases that demonstrate the possibility of regained endometrial activity as the cause of such fluid collection in patients who started hormonal replacement therapy. CASE REPORTS Patient A, a 48-year-old adipose woman, presented in September 1992 with postcoital vaginal blood loss which appeared to be related to a grade III squamous cervical cancer stage III B, according to the FIGO classification. The size of the tumor was estimated at 8 cm in diameter (‘‘barrel shaped’’) with infiltration of the left parametrium extending to the pelvic side wall. Radiation therapy consisted of 40-Gy 1
To whom correspondence should be addressed.
325
0090-8258/97 $25.00 Copyright © 1997 by Academic Press All rights of reproduction in any form reserved.
326
VERNOOIJ ET AL.
Manchester point A of 17.5 Gy each) combined with three courses of 5-FU and carboplatin as additive treatment to radiotherapy. In June 1995 estrogen replacement therapy was started on account of climacteric complaints, initially 2.5 mg tibolone 1dd1 (Livial), which after 3 months was changed to 50-mg estradiol plasters twice a week (Menorest). In May 1996 she complained of vague abdominal pain as well as dyspareunia. Physical examination revealed no abnormalities. Vaginal ultrasonography showed a filled uterine cavity. A CT scan showed no other abnormalities besides the enlarged uterus. At dilatation and curettage efflux of bloody fluid occurred. Histological examination revealed proliferating endometrium without evidence of malignancy. After this procedure the complaints disappeared and the ultrasonographic findings remained normal. In order to minimize the vasomotor symptoms 0.025 mg clonidine 2dd1 (Dixarit) was prescribed. In November 1996 (nearly 2 years after primary treatment) the patient developed pain and edema of her left leg. Vaginal examination revealed a mass at the left pelvic side wall. This was confirmed by CT scan, which also identified a hydronephrosis of the left kidney. The uterus showed no abnormalities, especially no fluid within the uterine cavity. A combined operative and radiotherapeutic treatment was performed according to Ho¨ckel et al. [3]. Frozen section of the resected tumor confirmed recurrence of disease. DISCUSSION Treatment of cervical carcinoma by radiotherapy destroys ovarian function unless one or both ovaries are transposed to an extrapelvic site [4], furthermore, it has been thought to ablate the endometrium, both factors resulting in a secondary amenorrhea. It is known, however, that normal endometrium can tolerate a high dose of radiation and has a good ability to recover from radiation injury [5]. Larson et al. described two cases of endometrial response to endogenous hormones after pelvic irradiation in patients who had undergone lateral ovarian transposition, demonstrating the ability of endometrial tissue to resume functional activity after radiation [4]. Barnhill et al. described 16 patients who were evaluated for uterine bleeding after radiotherapy for cervical cancer [6]. All patients used estrogen replacement therapy. Proliferative endometrium was found in 7 patients, demonstrating that proliferative endometrium may persist. One case had cystic hyperplasia, one atypical adenomatous hyperplasia, and one adenocarcinoma. They stated that patients who have had radiation therapy for cervical carcinoma should be treated with both an estrogen and a progestagen agent in order to avoid continuous unopposed endometrial stimulation with an associated increased risk of developing endometrial adenocarcinoma [7]. Mc Kay et al. described 22 patients with persisting cyclical uterine bleeding receiving
hormonal replacement therapy after radiation therapy for carcinoma of the cervix [8]. The cyclical bleeding persisted up to 4 months after radiation. They suggested that this may represent the slow death of endometrial cells subsequent to radiation treatment. The present paper confirms the concept that even after a high radiation dose the endometrium can preserve its proliferative activity, and thus, hormonal treatment should consist of an estrogen in combination with a progestagen agent. Patient A used tibolone (Livial), which has weak estrogenic, androgenic, and progestagenic activity. In general it does not induce endometrial proliferation although uterine bleeding may occur in a small percentage of treated patients [9]. Aartsen reported 16 patients with fluid collection in the uterine cavity after radiotherapy for cervical cancer [1]. In 3 of his patients the fluid collection was related to the start of estrogen replacement therapy. In 75% a malignancy appeared to be responsible for this phenomenon. Therefore, when fluid collection within an irradiated uterus is suspected by ultrasound, further examination is necessary, for which dilatation and curettage is the first method of choice. However, as in patient A, dilatation and curettage may not be successful because of extensive radiation fibrosis and obliteration of the cervical canal after radiotherapy [1]. Kwon et al. described 8 patients who developed an adenocarcinoma of the uterine corpus following radiotherapy for cervical cancer [10]. Only 2 of them presented with abnormal vaginal bleeding, the paucity of this alarming symptom probably being due to postradiation stenosis and obliteration of the upper vagina. Dilatation and curettage was attempted but failed in 3 of 5 patients because of this fibrotic obliteration of the upper vagina and cervix. Since histology of the endometrium in these cases is mandatory, a total abdominal hysterectomy is advisable in case dilatation and curettage fails. In conclusion, the occurrence of a filled uterine cavity after radiotherapy for cervical cancer is not necessarily related to recurrent disease. Especially when estrogen replacement therapy is started, the endometrium can regain its proliferative activity. In patients who begin using estrogen replacement therapy a progestagen agent should be added and the uterine cavity should be routinely examined for the development of a hematometra, especially in the absence of a progestagen withdrawal bleeding.
REFERENCES 1. Aartsen EJ: Fluid detection in the uterus during and after irradiation for carcinoma of the cervix— clinical implications. Eur J Surg Oncol 16:42– 46, 1990 2. Piver MS, Rutledge FN, Smith PJ: Five classes of extended hysterectomy of women with cervical cancer. Obstet Gynecol 44:265–272, 1974 3. Ho¨ckel M, Schlenger K, Hamm H, Knapstein PG, Hohenfellner R, Ro¨sler HP: Five-year experience with combined operative and radiotherapeutic
CASE REPORT
4.
5. 6.
7.
treatment of recurrent gynecologic tumors infiltrating the pelvic wall. Cancer 77:1918 –1933, 1996 Larson JE, Whitney CW, Zaino R, Kaminski P, Podczaski E, Mortel R: Endometrial response to endogenous hormones after pelvic irradiation for genital malignancies. Gynecol Oncol 36:106 –109, 1990 Disaia PJ, Creasman WT: Clinical gynecological oncology. 4th ed, Mosby–Year Book, 1993 Barnhill D, Heller P, Dames J, Hoskins W, Gallup D, Park R: Persistence of endometrial activity after radiation therapy for cervical carcinoma. Obstet Gynecol 66:805– 808, 1985 Gambrell RD, Massey FM, Castaneda TA, Ugenas AJ, Ricci CA, Wright
327
JM: Use of the progestagen challenge test to reduce the risk of endometrial cancer. Obstet Gynecol 55:732–738, 1980 8. Mc Kay MJ, Bull CA, Houghton CR, Langlands AO: Persisting cyclical uterine bleeding in patients treated with radical radiation therapy and hormonal replacement for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 18:921–925, 1990 9. Ginsburg J, Prelevic G, Butler D, Okolo S: Clinical experience with tibolone (Livial) over 8 years. Maturitas 21:71–76, 1995 10. Kwon Th, Prempree T, Tang C, VillaSanta U, Scott RM: Adenocarcinoma of the uterine corpus following irradiation for cervical cancer. Gynecol Oncol 11:102–113, 1981