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Hydatidiform mole in the elderly: Hysterectomy or evacuation?
Int. J. Gymxol. Ohvet., 1989.29: 233-238 I~~ter~tiontal Federation of Gynecology and Obstetrics
233
Hydatidiform mole in the elderley: hysterectomy or evacuation? A.M. BahaP, M.S. El-Ashnehib and A. Senthilselvanc ‘&lnwtmenl of OiMetrics and Gynaecology, Universi@ of Kuwait and Kuwait Ma&rnity Hospiial, P.O. Box 24923, sqfrril3110 Kuwait. ‘Lkpartmenl of O&&ics and Gynaeologv, Matemily Htwpiial, Kuwai& P.O. Box 4080, &far, 13W Kuwait and ‘~rtment of CommuniiyMedicinrandE&avioumlScience, University of Kuwai& P.O. Box24923,13110 Kuwait (Received April 25th. 1988)
(Revised and accepted August 16th, 1988)
Msttact
Ten patients with hydatidiform mole treated by primary hysterectomy were retrospectively compared with 24 patients whose moles were evacuated by suction curettage. AN patients were 35 years old or more and were followed up for 1 year following the evacuation. Duringfollow-up, 10% of the hysterectomized patients needed chemotherapy in comparison with 33.4% of the non-hysterectomized patients. This difference was not statistically significant. There was ako no statistically significant difference when the serial serum beta-subunit of human chorionic gonadotrophin (fl-hCG) regression rates of the two groups were compared. The study shows that primary hysterectomy does not worsen the prognosis of gestational trophoblastic disease, however, it does not negate the need for careful followup. mole; Keywords: Hydatidiform patients; Primary hysterectomy; curettage; Postmolar gestational blastic disease.
Elderly Suction tropho-
Introduction The risk of malignancy complicating molar 0020-7292/89/$03.50 @1989International Federation of Published and Printed in Ireland
pregnancy increases with advanced maternal age [2,6,13]. Suction evacuation of molar pregnancy is nowadays the preferred method of primary surgical treatment; but in elderly patient8 who have completed their families, primary hysterectomy is an alternative. However, concern ha8 been expressed that primary hysterectomy may be associated with a subsequent increased incidence of postmolar gestational trophoblastic disease t1,5,141. This retrospective study evaluate8 the prognosis following primary hysterectomy. This is significant in our community where preservation of fertility to an advanced age is desirable. Materials and methods During the period January, 1983 to December, 1986, 141 patients with gestational trophoblastic disease were treated and followed up at Kuwait Maternity Hospital Trophoblastic Registry Clinic. Forty-three of them were 35 year8 old or more and were of Middle-Eastern origin. Out of these 43 patients, 15 had hysterectomy, 11 a8 primary 3 for persistent uterine hysterectomy, bleeding following molar evacuation and one for failed chemotherapy. The remaining 28 patient8 had molar evacuation by suction curettage. Clinical and Clinical Reseaxh
Gynecology and Obstetrics
234
Bahar et al.
In order to evaluate the effect of primary hysterectomy on the prognosis of molar pregnancy, 10 out of the 11 patients who had primary hysterectomy were selected for the study. None of them had evidence of clinical metastases at the time of surgery and histological examination of the removed uteri showed benign molar tissue without any myometrial invasion. The eleventh patient was excluded from the study because histological examination revealed uterine choriocarcinoma. Out of the 28 patients treated by suction curettage, 4 were excluded from the study because histological examination of the evacuated molar tissues choriocarcinoma. Histological revealed examination in the remaining 24 patients revealed benign molar tissue and clinically there was no evidence of me&static lesions at the time of molar evacuation. These 24 patients were compared with the selected 10 patients who were treated by primary hysterectomy. Following the primary treatment, all the studied patients were followed up regularly in the clinic for at least 1 year. Seventeen out of the 24 patients of the non-hysterectomy group received low dose ostrogen-progestogen oral contraceptive pills for 1 year, while the remaining 7 used barrier contraceptives. During the period of follow-up all patients were regularly examined clinically and had check up of liver function tests, complete hemogram and chest X-rays. Liver and brain scans were done when indicated. Serial estimation of serum beta-subunit of human chorionic gonadotrophin @-hCG) by radioimmunoassay were carried out weekly until remission was achieved and then every 4 weeks (Radioassay Systems Laboratories, Inc., RSL QUAN-PREG TM-125 1 KIT, Dominguez Technology Centre, Carson). The lower limit of sensitivity in this system is 0.5 ng/ml (1 ng = 9.8 mIU/ml). Values below 1.0 ng/ml (9.8 mIU/ml) are considered normal non-pregnant levels in this system. The results obtained were plotted against a standard hCG regression curve. No Int J Gynecoi Obstet 29
used. was chemotherapy prophylactic Chemotherapy was indicated when there was a progressive rise in serum hCG level on three consecutive measurements, when a plateau occurred (3 successive stationary levels above the remission value), when remission was not achieved by 10 weeks post evacuation or when there was histological or radiological evidence of malignancy. Remission was diagnosed when 3 successive measurements of serum flhCG, 2 weeks apart, fell below 5 mIU/ml. The two groups of patients were compared regarding the need for chemotherapy. To test the effect of primary hysterectomy on the resolution of /3-hCG, the mode of regression and time taken to remission were compared between the cases who did not need chemotherapy in the two groups (9 in the hysterectomy group and 15 out of 16 in the nonhysterectomy group). The 16th case in the non-hysterectomy group was excluded because three successive values of fl-hCG were not estimated due to poor attendance. For statistical analysis, two sample MannWhitney U-test was used to test the difference in age and uterine size between the hysterectomy and the non-hysterectomy groups, while difference in gravidity was tested by the two sample median test. To facilitate comparison of data, the rate of resolution of P-hCG over time was estimated by fitting linear regression models for the log of /3-hCG levels against time. For every patient the slope was calculated individually and then the means of the slopes in the two groups were compared using the Mann-Whitney U-test. For statistical comparison values below 5 mIU/ml were recorded as 5 mIU/ml (remission value). The same test was used to estimate the difference in time taken to remission. Two sample proportion test was used to test the difference in the need for chemotherapy in the two groups. Results
Table I shows that the two groups were comparable regarding the gravidity and
HydatidVonn mole in the elderly Tsbk I.
235
Comparison by age. gravidity and uterine size between hysterectomy and non-hysterectomy groups. Hysterectomy group (n = 10)
Non-hysterectomy group (n = 24)
statistical signitkance
37-53 41.7 (4.8)
3549 37.9 (3.4)
u = 44.5 P< 0.01 (S)
Age (yeus)
we
Mean (S.D.) GravidiQ Ranse Median
4-11 7.0
Uterine&e (weeks) Ranse Mean (S.D.)
l-11 4.0
12-22 15.4 (3.1)
The remaining five patients had rising P-hCG titers only. Only one patient from the hysterectomy group needed chemotherapy. This patient had persistent high /3-hCG titers after 10 weeks post hysterectomy. This difference in the need for chemotherapy between the two groups was not statistically significant (Table II). When the mean of the log of the weekly serial values of /3-hCG were compared between 9 cases in the hysterectomy group and 15 cases in the non-hysterectomy group in
h&cations for chemotherapy.
Indication
Post molar mctastatic trophoblastic disease (1) M~tolung (2) MctWascs to lung
and vulva (B) Post-molar non-mctastatic trophoblastic disease (1) Persistent high /?-hCGtiter (2) Rising fl-hCG titer
Non-hysterectomy group
Hysterectomy group No.
(A)
u = 117.5 P> 0.9 (NS)
lo-22 15.4 (4.2)
uterine size. However, the mean maternal age in the hysterectomy group was significantly higher than that in the non-hysterectomy group (41.7 f 4.8 years versus 37.9 f 3.4 years), P< 0.01. Eight patients from the non-hysterectomy group needed chemotherapy. Of these, two patients developed me&stases, and one patient with a rising hCG titer was found to have choriocarcinoma diagnosed histologically from uterine curettings following curettage carried out for uterine bleeding. Table II.
x’ = 1.7 P> 0.1 (NS)
%
No.
Vo
0 0
0.0 0.0
1 1
4.2 4.2
1
10.0
0
0.0
0
0.0
6
20.8’
Total
33.4b
Qnc patlent had uterine choriocarcinoma diagnosed histologically from uterine curettings. ‘Signif~cc of difference between the two groups: x’ = 2.0; P > 0.1 (NS). Clinical and Clinical Rtsearch
236
Bahar et al.
Table UL
Regression of /%hCG and time taken to remission. Hysterectomy Broup (n = 9)
Non-hysterectomy group (n = 15)
Slope Mean (S.D.)
-0.7775 (0.315)
-0.6367 (0.209)
Time (weeks) Mean (S.D.)
8.78 (1.09)
8.53 (1.68)
There is no significant statistical difference groups.
between both
a linear regression model, it was found that there was no statistically significant difference in the mode of the slope of regression between the two groups. There was also no statistically significant difference in the time taken from primary treatment to remission between the two groups (8.78 f 1.09 weeks versus 8.53 f 1.68 weeks) (Table III and Fig. 1). Discussion Suction evacuation is currently the standard primary treatment of hydatidiform mole. In older patients, particularly those who have completed their families, primary
I... I
1
2
3
4
5
6 Time
7
B
9
10
(Weeks)
Mean (f S.E.M.) of serum levels of /3-hCG in hysterctomy group n = 9 (0 -0) and in non-hysterectomy group R = 15 (0 - - - 0) against time in weeks from primary treatment transformed into a linear regression by plotting in a logarithm scale. Fig.
1.
Int J Gynecol Obstet 29
hysterectomy is recommended by many authors [4,8,11,15] because of the propensity to malignant sequelae in older patients. The possible benefit8 of hysterectomy in these patients are removal of the diseased focus and accurate hence histological diagnosis, shortening the period of chemotherapy and hospital stay, reducing the incidence of malignant and improving the change outcome. However, in most of these studies hysterectomy was combined with prophylactic chemotherapy, calling for caution in interpreting the results. Other authors [1,5,14] have been concerned about the higher incidence of malignancy subsequent to primary hysterectomy. For instance Curry et al. [S] in a study of patients who had been registered and followed up in the Southeastern Regional Trophoblastic Disease Centre, reported a 20% incidence of malignancy following primary hysterectomy. Their data were collected from the patients’ clinical files, related correspondence, hCG assay data and a detailed questionnaire sent to the referring physcians. In their study, age, parity and uterine size were not examined in relation to the mode of evacuation of the hydatidiform moles. Stone and Bagshawe [ 141analyzing the records of 611 patients registered in the Royal College of Obstetricians and Gynaecologists (London) and the Department of Health and Social Security, reported a two to three fold increase in the need for chemotherapy in patients who had undergone a medical induction, hysterectomy or hysterotomy compared with those whose hydatidiform moles had been evacuated by vacuum or surgical curettage or who had aborted spontaneously. They found that 15% of patients treated by primary hysterectomy needed chemotherapy compared with 4.3% of those whose moles were evacuated by vacuum curettage. Their study was lacking information on uterine size and the effect of gravidity was not analyzed. In the present study, gravidity and uterine size were similar between the two groups. Inspite of the higher
Hydatidiform mole in the elderly
patients, age of the hysterectomized numerically the outcome was better, although without statistically significant difference. Since the mainstay of follow-up after trophoblastic disease is the serial measurement of serum /%hCG levels, it is worthy to test the effect of hysterectomy on its mode of regression and the time taken from treatment to remission. The study showed no statistically significant difference between the two groups. This agrees with the findings of Ho Yuen and Cannon [9] who found no difference in the time needed for resolution of hCG between 5 hysterectomy and 120 nonhysterectomy cases (75.8 versus 73.6 days). In the present study, the regression rates of /3hCG were similar in both groups, in spite of the fact that 13 out of the 15 patients in the non-hysterectomy group used the low dose hormonal contraceptive pill, indicating that the low dose pill did not affect the regression rate. This finding is consistent with that reported by Berkowitz et al. [3] and Morrow et al. [12]. Berkowitz et al. reported that the mean time needed for serum /3-hCG resolution was 7 weeks in oral contraceptive users compared with 7.2 weeks in those who used barrier contraceptive methods. Morrow et al. in a controlled study showed that the incidence of abnormal serum /3-hCG regression patterns in patients using 22.6% contraception was hormonal compared with 34.5% in those on non-hormonal contraception, however the difference was not statistically significant. Therefore, in the numerically increased this study, incidence of postmolar trophoblastic disease in the non-hysterectomy group was unlikely to be due to the low dose pill. Ho Yuen and Burch [lo] found no increase in the requirements of chemotherapy for patients who used the low dose oral contraceptive pills, but they found that the demand for chemotherapy was higher in those who used high dose oral contraceptive pills. Goldberg et al. [7] found no increase in the incidence of postmolar trophoblastic disease in patients using oral contraceptive pills containing less
231
than 50 pg of estrogen and in patients using medroxyprogesterone acetate (Depo-provera, Upjohn) injections. We conclude that primary hysterectomy at least does not worsen the prognosis of the disease. Due to the small number of patients in this study, a definite answer to the question is difficult. More controlled studies on larger samples are needed to settle this matter. This is comforting in areas like ours where patients wish to continue on reproduction to an advanced and tend to refuse age hysterectomy. Although the diseased focus was eliminated by hysterectomy, the fi-hCG regression pattern and time taken to remission were not affected. Therefore careful follow-up of such patients is mandatory. References Baja-Panlilio H, Sanchez FS: A better incidence of chorionic malignancy following hydatidiform mole. A longitudinal study of 868 cases admitted in a Maternity Hospital in Manila. In Proceedings of the First InterCongress of Asian Federation of Obstetrics and Gynaecology 2: 89, 1976. Bandy LC, Clarke-Pearson DL, Hammond CB: Malignant potential of gestational trophoblastic disease at the extreme ages of reproductive life. Obstet Gynecol64: 395, 1984. Berkowitz RS, Goldstein DP, Marean AR, Bernstein M: Oral contraceptives and post molar trophoblastic disease. Obstet Gynecol58: 474,198 1. Chun D, Braga C, Chew C, Lok L: Clinical observations on some aspects of hydatidiform mole. J Obstet Gynaecol Br Commonw 71: 180,1964. Curry SL, Hammond CB, Tyrey L, Creasman WT, Parker RT: Hydatidiform mole: diagnosis, management and long term follow-up of 347 patients. Obstet Gynecol 45: 1,1975. Fasoli M, Ratti E, Franceschi S, Vecchia C, Pecorelli S, Mangioni C: Management of gestational trophoblastic disease: results of a cooperative study. Obstet Gynecol60: 205, 1982. Goldberg GL, Cloete K, Bloch B, Wiswedel K, Altaras M: Medroxy progesterone acetate in non-metastatic gestational trophoblastic disease. Br J Obstet Gynaecol 94: 22, 1987. Hammond CB, Weed JC, Currie JL: The role of operation in the current therapy of gestational trophoblastic disease. Am J Obstd GynecolZ36:844, 1980. Ho Yuen B. Cannon W: Molar pregnancy in British Columbia: Estimated incidence and postevacuation
Clinical and Clinical Research
238
10
11
12
13
Bahar et al.
regression patterns of the beta subunit of human chorionic gonadotrophin. Am J Obstet Gynecol 139: 316, 1981. Ho Yuen B, Burch P: Relationship of oral contraceptives and the intrauterine devices to the regression of concentrations of the beta subunit of human chorionic gonadotrophin and invasive complications after molar pregnancy. Am J Obstet Gynecol145: 214.1983. Ilancheran A, Ratnam SS: The Role of Surgery in the treatment of trophoblastic disease. Int J Gynaecol Obstet 18: 231,198O. Morrow P, Nakamura R, Schlaerth J, Gaddis 0 Jr, Eddy G: The influence of oral contraceptives on the postmolar human chorionic gonadotrophin regression curve. Am J Obstet GynecolI51: 906.1985. Soma H, Takayama Saito T, Isaka K: Management of hydatidiform mole in women over 45 years old. AsiaOceania J Obstet Gynaecol9: 393.1983.
Int J Gynecoi Obstet 29
14
Stone M, Bag&we KD: An analysis of the influences of maternal age, gestational age, contraceptive method and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy. Br J Obstet Gynaecol86: 782,1979. 15 Tsukamoto N, Iwasaka T, Kashimura Y, Uchino H. Kashimura M, Matsyama T: Gestational trophoblastic disease in women aged 50 or more. Gynaecol Oncol20: 53,1985.
Addresa for reprints:
A.M. B&u
Departmentof Ohsdetrles and Gynhcology Unlvemlty of Kuwait P.O. Box 24923, s&t 13110 Knwalt
233
Hydatidiform mole in the elderley: hysterectomy or evacuation? A.M. BahaP, M.S. El-Ashnehib and A. Senthilselvanc ‘&lnwtmenl of OiMetrics and Gynaecology, Universi@ of Kuwait and Kuwait Ma&rnity Hospiial, P.O. Box 24923, sqfrril3110 Kuwait. ‘Lkpartmenl of O&&ics and Gynaeologv, Matemily Htwpiial, Kuwai& P.O. Box 4080, &far, 13W Kuwait and ‘~rtment of CommuniiyMedicinrandE&avioumlScience, University of Kuwai& P.O. Box24923,13110 Kuwait (Received April 25th. 1988)
(Revised and accepted August 16th, 1988)
Msttact
Ten patients with hydatidiform mole treated by primary hysterectomy were retrospectively compared with 24 patients whose moles were evacuated by suction curettage. AN patients were 35 years old or more and were followed up for 1 year following the evacuation. Duringfollow-up, 10% of the hysterectomized patients needed chemotherapy in comparison with 33.4% of the non-hysterectomized patients. This difference was not statistically significant. There was ako no statistically significant difference when the serial serum beta-subunit of human chorionic gonadotrophin (fl-hCG) regression rates of the two groups were compared. The study shows that primary hysterectomy does not worsen the prognosis of gestational trophoblastic disease, however, it does not negate the need for careful followup. mole; Keywords: Hydatidiform patients; Primary hysterectomy; curettage; Postmolar gestational blastic disease.
Elderly Suction tropho-
Introduction The risk of malignancy complicating molar 0020-7292/89/$03.50 @1989International Federation of Published and Printed in Ireland
pregnancy increases with advanced maternal age [2,6,13]. Suction evacuation of molar pregnancy is nowadays the preferred method of primary surgical treatment; but in elderly patient8 who have completed their families, primary hysterectomy is an alternative. However, concern ha8 been expressed that primary hysterectomy may be associated with a subsequent increased incidence of postmolar gestational trophoblastic disease t1,5,141. This retrospective study evaluate8 the prognosis following primary hysterectomy. This is significant in our community where preservation of fertility to an advanced age is desirable. Materials and methods During the period January, 1983 to December, 1986, 141 patients with gestational trophoblastic disease were treated and followed up at Kuwait Maternity Hospital Trophoblastic Registry Clinic. Forty-three of them were 35 year8 old or more and were of Middle-Eastern origin. Out of these 43 patients, 15 had hysterectomy, 11 a8 primary 3 for persistent uterine hysterectomy, bleeding following molar evacuation and one for failed chemotherapy. The remaining 28 patient8 had molar evacuation by suction curettage. Clinical and Clinical Reseaxh
Gynecology and Obstetrics
234
Bahar et al.
In order to evaluate the effect of primary hysterectomy on the prognosis of molar pregnancy, 10 out of the 11 patients who had primary hysterectomy were selected for the study. None of them had evidence of clinical metastases at the time of surgery and histological examination of the removed uteri showed benign molar tissue without any myometrial invasion. The eleventh patient was excluded from the study because histological examination revealed uterine choriocarcinoma. Out of the 28 patients treated by suction curettage, 4 were excluded from the study because histological examination of the evacuated molar tissues choriocarcinoma. Histological revealed examination in the remaining 24 patients revealed benign molar tissue and clinically there was no evidence of me&static lesions at the time of molar evacuation. These 24 patients were compared with the selected 10 patients who were treated by primary hysterectomy. Following the primary treatment, all the studied patients were followed up regularly in the clinic for at least 1 year. Seventeen out of the 24 patients of the non-hysterectomy group received low dose ostrogen-progestogen oral contraceptive pills for 1 year, while the remaining 7 used barrier contraceptives. During the period of follow-up all patients were regularly examined clinically and had check up of liver function tests, complete hemogram and chest X-rays. Liver and brain scans were done when indicated. Serial estimation of serum beta-subunit of human chorionic gonadotrophin @-hCG) by radioimmunoassay were carried out weekly until remission was achieved and then every 4 weeks (Radioassay Systems Laboratories, Inc., RSL QUAN-PREG TM-125 1 KIT, Dominguez Technology Centre, Carson). The lower limit of sensitivity in this system is 0.5 ng/ml (1 ng = 9.8 mIU/ml). Values below 1.0 ng/ml (9.8 mIU/ml) are considered normal non-pregnant levels in this system. The results obtained were plotted against a standard hCG regression curve. No Int J Gynecoi Obstet 29
used. was chemotherapy prophylactic Chemotherapy was indicated when there was a progressive rise in serum hCG level on three consecutive measurements, when a plateau occurred (3 successive stationary levels above the remission value), when remission was not achieved by 10 weeks post evacuation or when there was histological or radiological evidence of malignancy. Remission was diagnosed when 3 successive measurements of serum flhCG, 2 weeks apart, fell below 5 mIU/ml. The two groups of patients were compared regarding the need for chemotherapy. To test the effect of primary hysterectomy on the resolution of /3-hCG, the mode of regression and time taken to remission were compared between the cases who did not need chemotherapy in the two groups (9 in the hysterectomy group and 15 out of 16 in the nonhysterectomy group). The 16th case in the non-hysterectomy group was excluded because three successive values of fl-hCG were not estimated due to poor attendance. For statistical analysis, two sample MannWhitney U-test was used to test the difference in age and uterine size between the hysterectomy and the non-hysterectomy groups, while difference in gravidity was tested by the two sample median test. To facilitate comparison of data, the rate of resolution of P-hCG over time was estimated by fitting linear regression models for the log of /3-hCG levels against time. For every patient the slope was calculated individually and then the means of the slopes in the two groups were compared using the Mann-Whitney U-test. For statistical comparison values below 5 mIU/ml were recorded as 5 mIU/ml (remission value). The same test was used to estimate the difference in time taken to remission. Two sample proportion test was used to test the difference in the need for chemotherapy in the two groups. Results
Table I shows that the two groups were comparable regarding the gravidity and
HydatidVonn mole in the elderly Tsbk I.
235
Comparison by age. gravidity and uterine size between hysterectomy and non-hysterectomy groups. Hysterectomy group (n = 10)
Non-hysterectomy group (n = 24)
statistical signitkance
37-53 41.7 (4.8)
3549 37.9 (3.4)
u = 44.5 P< 0.01 (S)
Age (yeus)
we
Mean (S.D.) GravidiQ Ranse Median
4-11 7.0
Uterine&e (weeks) Ranse Mean (S.D.)
l-11 4.0
12-22 15.4 (3.1)
The remaining five patients had rising P-hCG titers only. Only one patient from the hysterectomy group needed chemotherapy. This patient had persistent high /3-hCG titers after 10 weeks post hysterectomy. This difference in the need for chemotherapy between the two groups was not statistically significant (Table II). When the mean of the log of the weekly serial values of /3-hCG were compared between 9 cases in the hysterectomy group and 15 cases in the non-hysterectomy group in
h&cations for chemotherapy.
Indication
Post molar mctastatic trophoblastic disease (1) M~tolung (2) MctWascs to lung
and vulva (B) Post-molar non-mctastatic trophoblastic disease (1) Persistent high /?-hCGtiter (2) Rising fl-hCG titer
Non-hysterectomy group
Hysterectomy group No.
(A)
u = 117.5 P> 0.9 (NS)
lo-22 15.4 (4.2)
uterine size. However, the mean maternal age in the hysterectomy group was significantly higher than that in the non-hysterectomy group (41.7 f 4.8 years versus 37.9 f 3.4 years), P< 0.01. Eight patients from the non-hysterectomy group needed chemotherapy. Of these, two patients developed me&stases, and one patient with a rising hCG titer was found to have choriocarcinoma diagnosed histologically from uterine curettings following curettage carried out for uterine bleeding. Table II.
x’ = 1.7 P> 0.1 (NS)
%
No.
Vo
0 0
0.0 0.0
1 1
4.2 4.2
1
10.0
0
0.0
0
0.0
6
20.8’
Total
33.4b
Qnc patlent had uterine choriocarcinoma diagnosed histologically from uterine curettings. ‘Signif~cc of difference between the two groups: x’ = 2.0; P > 0.1 (NS). Clinical and Clinical Rtsearch
236
Bahar et al.
Table UL
Regression of /%hCG and time taken to remission. Hysterectomy Broup (n = 9)
Non-hysterectomy group (n = 15)
Slope Mean (S.D.)
-0.7775 (0.315)
-0.6367 (0.209)
Time (weeks) Mean (S.D.)
8.78 (1.09)
8.53 (1.68)
There is no significant statistical difference groups.
between both
a linear regression model, it was found that there was no statistically significant difference in the mode of the slope of regression between the two groups. There was also no statistically significant difference in the time taken from primary treatment to remission between the two groups (8.78 f 1.09 weeks versus 8.53 f 1.68 weeks) (Table III and Fig. 1). Discussion Suction evacuation is currently the standard primary treatment of hydatidiform mole. In older patients, particularly those who have completed their families, primary
I... I
1
2
3
4
5
6 Time
7
B
9
10
(Weeks)
Mean (f S.E.M.) of serum levels of /3-hCG in hysterctomy group n = 9 (0 -0) and in non-hysterectomy group R = 15 (0 - - - 0) against time in weeks from primary treatment transformed into a linear regression by plotting in a logarithm scale. Fig.
1.
Int J Gynecol Obstet 29
hysterectomy is recommended by many authors [4,8,11,15] because of the propensity to malignant sequelae in older patients. The possible benefit8 of hysterectomy in these patients are removal of the diseased focus and accurate hence histological diagnosis, shortening the period of chemotherapy and hospital stay, reducing the incidence of malignant and improving the change outcome. However, in most of these studies hysterectomy was combined with prophylactic chemotherapy, calling for caution in interpreting the results. Other authors [1,5,14] have been concerned about the higher incidence of malignancy subsequent to primary hysterectomy. For instance Curry et al. [S] in a study of patients who had been registered and followed up in the Southeastern Regional Trophoblastic Disease Centre, reported a 20% incidence of malignancy following primary hysterectomy. Their data were collected from the patients’ clinical files, related correspondence, hCG assay data and a detailed questionnaire sent to the referring physcians. In their study, age, parity and uterine size were not examined in relation to the mode of evacuation of the hydatidiform moles. Stone and Bagshawe [ 141analyzing the records of 611 patients registered in the Royal College of Obstetricians and Gynaecologists (London) and the Department of Health and Social Security, reported a two to three fold increase in the need for chemotherapy in patients who had undergone a medical induction, hysterectomy or hysterotomy compared with those whose hydatidiform moles had been evacuated by vacuum or surgical curettage or who had aborted spontaneously. They found that 15% of patients treated by primary hysterectomy needed chemotherapy compared with 4.3% of those whose moles were evacuated by vacuum curettage. Their study was lacking information on uterine size and the effect of gravidity was not analyzed. In the present study, gravidity and uterine size were similar between the two groups. Inspite of the higher
Hydatidiform mole in the elderly
patients, age of the hysterectomized numerically the outcome was better, although without statistically significant difference. Since the mainstay of follow-up after trophoblastic disease is the serial measurement of serum /%hCG levels, it is worthy to test the effect of hysterectomy on its mode of regression and the time taken from treatment to remission. The study showed no statistically significant difference between the two groups. This agrees with the findings of Ho Yuen and Cannon [9] who found no difference in the time needed for resolution of hCG between 5 hysterectomy and 120 nonhysterectomy cases (75.8 versus 73.6 days). In the present study, the regression rates of /3hCG were similar in both groups, in spite of the fact that 13 out of the 15 patients in the non-hysterectomy group used the low dose hormonal contraceptive pill, indicating that the low dose pill did not affect the regression rate. This finding is consistent with that reported by Berkowitz et al. [3] and Morrow et al. [12]. Berkowitz et al. reported that the mean time needed for serum /3-hCG resolution was 7 weeks in oral contraceptive users compared with 7.2 weeks in those who used barrier contraceptive methods. Morrow et al. in a controlled study showed that the incidence of abnormal serum /3-hCG regression patterns in patients using 22.6% contraception was hormonal compared with 34.5% in those on non-hormonal contraception, however the difference was not statistically significant. Therefore, in the numerically increased this study, incidence of postmolar trophoblastic disease in the non-hysterectomy group was unlikely to be due to the low dose pill. Ho Yuen and Burch [lo] found no increase in the requirements of chemotherapy for patients who used the low dose oral contraceptive pills, but they found that the demand for chemotherapy was higher in those who used high dose oral contraceptive pills. Goldberg et al. [7] found no increase in the incidence of postmolar trophoblastic disease in patients using oral contraceptive pills containing less
231
than 50 pg of estrogen and in patients using medroxyprogesterone acetate (Depo-provera, Upjohn) injections. We conclude that primary hysterectomy at least does not worsen the prognosis of the disease. Due to the small number of patients in this study, a definite answer to the question is difficult. More controlled studies on larger samples are needed to settle this matter. This is comforting in areas like ours where patients wish to continue on reproduction to an advanced and tend to refuse age hysterectomy. Although the diseased focus was eliminated by hysterectomy, the fi-hCG regression pattern and time taken to remission were not affected. Therefore careful follow-up of such patients is mandatory. References Baja-Panlilio H, Sanchez FS: A better incidence of chorionic malignancy following hydatidiform mole. A longitudinal study of 868 cases admitted in a Maternity Hospital in Manila. In Proceedings of the First InterCongress of Asian Federation of Obstetrics and Gynaecology 2: 89, 1976. Bandy LC, Clarke-Pearson DL, Hammond CB: Malignant potential of gestational trophoblastic disease at the extreme ages of reproductive life. Obstet Gynecol64: 395, 1984. Berkowitz RS, Goldstein DP, Marean AR, Bernstein M: Oral contraceptives and post molar trophoblastic disease. Obstet Gynecol58: 474,198 1. Chun D, Braga C, Chew C, Lok L: Clinical observations on some aspects of hydatidiform mole. J Obstet Gynaecol Br Commonw 71: 180,1964. Curry SL, Hammond CB, Tyrey L, Creasman WT, Parker RT: Hydatidiform mole: diagnosis, management and long term follow-up of 347 patients. Obstet Gynecol 45: 1,1975. Fasoli M, Ratti E, Franceschi S, Vecchia C, Pecorelli S, Mangioni C: Management of gestational trophoblastic disease: results of a cooperative study. Obstet Gynecol60: 205, 1982. Goldberg GL, Cloete K, Bloch B, Wiswedel K, Altaras M: Medroxy progesterone acetate in non-metastatic gestational trophoblastic disease. Br J Obstet Gynaecol 94: 22, 1987. Hammond CB, Weed JC, Currie JL: The role of operation in the current therapy of gestational trophoblastic disease. Am J Obstd GynecolZ36:844, 1980. Ho Yuen B. Cannon W: Molar pregnancy in British Columbia: Estimated incidence and postevacuation
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regression patterns of the beta subunit of human chorionic gonadotrophin. Am J Obstet Gynecol 139: 316, 1981. Ho Yuen B, Burch P: Relationship of oral contraceptives and the intrauterine devices to the regression of concentrations of the beta subunit of human chorionic gonadotrophin and invasive complications after molar pregnancy. Am J Obstet Gynecol145: 214.1983. Ilancheran A, Ratnam SS: The Role of Surgery in the treatment of trophoblastic disease. Int J Gynaecol Obstet 18: 231,198O. Morrow P, Nakamura R, Schlaerth J, Gaddis 0 Jr, Eddy G: The influence of oral contraceptives on the postmolar human chorionic gonadotrophin regression curve. Am J Obstet GynecolI51: 906.1985. Soma H, Takayama Saito T, Isaka K: Management of hydatidiform mole in women over 45 years old. AsiaOceania J Obstet Gynaecol9: 393.1983.
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Stone M, Bag&we KD: An analysis of the influences of maternal age, gestational age, contraceptive method and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy. Br J Obstet Gynaecol86: 782,1979. 15 Tsukamoto N, Iwasaka T, Kashimura Y, Uchino H. Kashimura M, Matsyama T: Gestational trophoblastic disease in women aged 50 or more. Gynaecol Oncol20: 53,1985.
Addresa for reprints:
A.M. B&u
Departmentof Ohsdetrles and Gynhcology Unlvemlty of Kuwait P.O. Box 24923, s&t 13110 Knwalt