- Email: [email protected]
A new technique for laparoscopic prophylactic oophoropexy before craniospinal irradiation in children with medulloblastoma
Adolesc Pediatr Gynecol (1995) 8:77-81
Adolescent and Pediatric Gynecology © 1995 Springer-Verlag New York Inc.
A New Technique for Laparoscopic Prophylactic Oopboropexy Before Craniospinal Irradiation in Children With Medulloblastoma* M.R. Laufer, M.D./,2 A.L. Billett, M.D.,3 L. Diller, M.D.,3 L.M. Chin, D.Sc.,4 and N.J. Tarbell, M.D.4 lDivision of Pediatric/Adolescent Gynecology, Department of Surgery, Division of AdolescentlYoung Adult Medicine, Department of Medicine, Children's Hospital-Boston; 2Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital; 3Division of Pediatric Oncology, Children's Hospital-Boston; 4The Joint Center for Radiation Therapy, and the Department of Radiation Oncology, Children's Hospital-Boston; Harvard Medical School, Boston, Massachusetts
Abstract. The study objective was to develop a laparoscopic technique for oophoropexy with the marking of both ovaries with titanium clips so as to be able to calculate the radiation dosage to each ovary. We propose a laparoscopic approach to oophoropexy for patients with medulloblastoma planning for craniospinal radiation. Therapeutic radiation dose exposure to the pexed and nonpexed ovaries is calculated. A surgical outpatient laparoscopic procedure for oophoropexy is described. It was determined that if the pexed ovary is moved 1 cm outside of a megavoltage radiation beam, then the dosage of radiation to the ovary is reduced to approximately 9% of the prescription dose (300 cOy), whereas if the pexed ovary is moved 2 cm outside of a megavoltage radiation beam, then the dosage of radiation is reduced to less than 5% (180 cOy). This new laparoscopic oophoropexy procedure can be performed as an outpatient before craniospinal irradiation in order to increase the chances for the preservation of gonadal steroid production and fertility in girls.
Key Words. Oophoropexy-Laparoscopy-Medulloblastoma-Carniospinal irradiation Introduction Medulloblastoma is a primitive, undifferentiated malignancy of the cerebellum, most commonly ocAddress reprint requests to: Marc R. Laufer, M.D., Division of Pediatric/Adolescent Gynecology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115. *Presented in part at the Eighth Annual Meeting of the North American Society for Pediatric and Adolescent Gynecology, Atlanta, Georgia, 1994.
curring in young children. I This tumor is known to metastasize via cerebrospinal fluid. I The 5-year overall survival rate for medulloblastoma has improved from approximately 30% in 19692 to 65-72% in more recent studies. 3 Curative treatment for medulloblastoma involves craniospinal irradiation to the level of the base of the dural sac, at least to the level of S2 inferiorly. 7 Oophoropexy, with the repositioning of ovaries out of the radiation field by laparotomy, has been previously described with documentation of resultant decreased exposure to radiation and improved gonadal function in girls with Hodgkin's disease.8-12 However, the need for a laparotomy to accomplish this prophylactic procedure adds morbidity at a time when patients are usually undergoing diagnostic evaluation and therapeutic interventions. We describe our experience with a new procedure, laparoscopic oophoropexy, that should facilitate the ability to preserve reproductive potential in girls with medulloblastoma who are about to undergo spinal irradiation. The purposes of this study were 1) to evaluate the safety of laparoscopic oophoropexy, and 2) to determine the theoretic dosage of radiation exposure to the pexed and nonpexed ovaries. Patients and Methods We report three cases of pelviscopic oophoropexy in three girls (ages 5, 7, and 9 years), with medulloblastoma who were to undergo spinal irradiation. The radiation to the spine was planned at 3,600
78
Laufer et al.:
New Technique for Laparoscopic Oophoropexy
cGy, to a field extending from C5 to the inferior border of S2 (S2-S4, depending on the inferior extent of the dural sac as determined by magnetic resonance imaging). Before the start of radiation, patients underwent a laparoscopy with standard video operating equipment under general anesthesia. For the first patient, a lO-mm laparoscope with a camera positioned in the to-mm umbilical port and three additional ports placed suprapubically (one 12 mm and two 5 mm) were used. For the subsequent patients, a 12-mm umbilical port and three 5-mm suprapubic ports were used. The 12-mm port was used for the lO-mm laparoscope, followed by the l2-mm clip appliers with visualization via a 5-mm suprapubic laparoscope. This modification improved cosmetic results. The pelvis was inspected and noted to be normal in each case. The normal prepubertal location of the ovary was observed to be higher in the pelvis compared with the relative final location in an adult, and the ovary was also noted to have a longer uteroovarian ligament, as compared with the relative adult size. It was elected to relocate the left ovary to avoid a confusing differential diagnosis between ovarian pain and appendicitis if subsequent pain was to occur in the right lower quadrant. Titanium clips 9 mm medium-large (Endoclip, United States Surgical Corporation, Norwalk, CT) were used to reduce reactive adhesion formation and to avoid interfering with magnetic resonance imaging. The superior border of the right ovary was tagged with a titanium clip in order to mark its location. The left ovary and the utero-ovarian ligament were identified, and the utero-ovarian ligament was cut with hooked scissors and electrocautery. The left infundibular pelvic ligament was identified, and its associated peritoneum was dissected in order to gain additional mobility of the ovary. (It should be noted that if the peritoneum is not mobilized, many surgeons have observed that a severe adynamic ileus may result.) The superior border of this ovary was also tagged for future identification with titanium clips. The left ovary was then relocated and attached to the anterior peritoneum as inferior and caudad as possible. The ovary was positioned with a 4.8 mm titanium staple (Endohernia Stapler, United States Surgical Corporation, Norwalk, CT) incorporating the remnant of the utero-ovarian ligament and the peritoneum. Results
The patients had no operative complications and were discharged to their homes after a short stay in the recovery room. The patients had no postopera-
,
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.
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.1' ' ". .:~ .}~~ ' ~ '. ••
.".
./'~ ~_,
'l'~ ' ~.
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....
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. .Sil;.. (.
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._~_ ~
..
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-
Fig. 1. Postoophoropexy showing the location of the right ovary and the pexed left (L) ovary.
Fig. 2. Postoperative KUB showing the location of the right ovary and the pexed left (L) ovary with demonstration of the radiation beam edge.
tive left lower quadrant pain, and each proceeded with her spinal radiation therapy. Figure 1 is postoophoropexy showing the relative locations of the ovaries. The left pexed ovary is labeled "L." Figure 2 is a representation of the geometric positions of the ovaries in reference to the edge of the radiation beam. The right ovary is tagged at its inferior aspect along the utero-ovarian ligament. The left ovary is positioned obliquely, thus appearing smaller than the right ovary in this radiograph.
Laufer et aL:
New Technique for Laparoscopic Oophoropexy
Lateral Brain Fields
Fig. 3. Lateral brain fields and spinal field for craniospinal irradiation.
All three patients underwent daily craniospinal irradiation after recovery from oophoropexy, as shown in Figure 3. We noted that the unpexed ovary was exposed to varying radiation dosage depending on the treatment energy, geometry, the size of the ovary, and the distance the ovary was from the edge of the beam. It was also noted that there was significant day-to-day variability in the location of the unpexed ovary, resulting in significant variability in the daily exposure of that ovary to radiation. As daily radiographs were not obtained, it can theoretically be shown that if the unpexed ovary is approximately 1 cm from the beam edge, then the dose is approximately 10% of the total prescription dose at the center of the ovary. The dose to this ovary could reach 70% if it moves 0.5 em closer to the radiation beam edge. We calculated that if the pexed ovary is moved 1 cm from the edge of the radiation beam, then the average dose is approximately 8-9% (288-324 cGy). If the pexed ovary is moved 2 em away from the lower edge of the radiation field, then that ovary receives less than 5% of the radiation dosage « 180 cGy). The beam profile for a 6 MY linear accelerator for a spinal field of 8 x 30 cm2 at a depth of 5 cm is shown in Figure 4. The first patient to undergo this new technique had been diagnosed and treated at age 9 and became pubertal at age 10. She has normal serum-luteinizing hormone and follicle-stimulating hormone levels. In addition, she has had bilateral ovarian function documented by ultrasound. It is too early to determine ovarian function in the remaining two patients. Discussion The deleterious effects of radiation on gonadal function are well known, and with improvements in the
79
survival rates of patients with childhood malignancies, methods for reducing the risks of long-term side effects need investigation. Radiation-induced gonadal dysfunction is known to be dose dependent. 13 The gonadal state at the time of the insult is also felt to affect outcome, with prepubescent individuals having a better prognosis for gonadal function than sexually mature individuals. 14 ,15 Sha1et and colleagues 16 reported that ovarian failure occurred in girls between 1 and 13 receiving abdominal irradiation in a dosage of 2,000-3,000 cGy. In another study, Stillman et al. l ? reported that there was no incidence of ovarian failure in girls between the ages of 1 and 17 receiving approximately 54 cGy (range 5-150) of abdominal irradiation and that the failure rate rose to 14% with dosages of approximately 290 cGy (range 90-1,(00) and to 68% with dosages of approximately 3,200 cGy (range 1,200-5,(00). In patients treated for medulloblastoma, there have been differing opinions as to the cause of the gonadal dysfunction, with some authors attributing gonadal damage to scatter from spinal irradiation, 18,19 whereas others have concluded that adjuvant chemotherapy was the causative insult. 2o In one study involving 42 girls with intracranial tumors, it was found that 0 (0%) of 14 had ovarian dysfunction with cranial irradiation alone and 2 (67%) of 3 had ovarian dysfunction with cranial irradiation in addition to chemotherapy, giving a total of 2 (12%) of 17 having gonadal dysfunction after cranial irradiation with or without chemotherapy. For those individuals who received craniospinal irradiation alone, 7 (64%) of 11 had ovarian dysfunction, whereas 9 (64%) of 14 had ovarian dysfunction with both craniospinal irradiation and chemotherapy, giving a total of 16 (64%) of 25 having gonadal dysfunction after craniospinal irradiation with or without chemotherapy. 21 The incidence of ovarian failure from spinal irradiation is not exactly known but is usually estimated to be in the range of 40-60% induction of menstrual irregularities andlor complete gonadal failure with subsequent infertility.15,18,22 We investigated a method of unilateral 00phoropexy via laparoscopy in order to relocate an ovary out of the radiation field in young girls undergoing spinal irradiation. The ovary that is moved is relocated inferiorly and laterally out of the radiation field. Only one ovary is moved so as not to eliminate the possibility of normal means of conception should the unmoved ovary maintain ovulatory function. The amounts of radiation to both ovaries can be determined once the locations of the ovaries relative to the radiation field are known. These locations can be identified by searching for the titanium clips, which have been placed at the ovarian bor-
Laufer et al.:
80
New Technique for Laparoscopic Oophoropexy
1.0
8 x 30 cnf Field
0.9
+- Geometric beam edge
0.8
at depth of 5 em
0.7 Q)
(/)
0
0.6
C Q)
.~
Cii a; a:
0.5
+- 40% of dose at center
0.4
Ovary 1 em 8IN8y from edge average dose-8-9%
0.3 0.2 0.1 0.0
a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Distance from Center of Field (cm) Fig. 4. Beam profile for 6 MV linear accelerator for spinal field. ders at the time of the laparoscopy. By taking advantage of the sharp declining gradient at the beam edges from modern megavoltage linear accelerators, radiation exposure is predicted on radiographic films to be decreased to a level not associated with gonadal failure if the pexed ovary is moved 1-2 cm away from the edge of the radiation field. If the unmoved ovary should fail and if the relocated ovary remains functional, normal estrogen production should result at puberty. Other reports have shown spontaneous fertility after 00phoropexy.8-10,23 If spontaneous conception does not occur, because of tubal factor infertility from tubal stretching, then the single functioning ovary can be used in controlled hyperstimulation and ovum aspiration for in vitro fertilization. In this study, we have reported a new method of oophoropexy for young girls undergoing craniospinal radiation therapy. The method has been found to be safe and to result in a calculated decrease in radiation exposure to the relocated ovary . We found that if the pexed ovary is moved I cm from the radiation beam, then the dosage of radiation to the ovary is reduced to 288-324 cGy, whereas if the pexed ovary is moved 2 cm from the radiation beam, then the dosage of radiation is reduced to less than 180 cGy. For at least one patient, the onset of puberty after the completion of the therapy has been observed. We plan to institute this form of outpatient preventive therapy for patients before beginning spinal irradiation, with the possibility that
central venous line placement can be carried out during the same anesthetic. With this new technique, we hope to preserve gonadal steroid production and fertility in female long-term survivors of medulloblastoma.
References 1. Bailey P, Cushing H: Medulloblastoma cerebelli: a
common type of midcerebellar glioma of childhood. Arch Neuro Psychiatr 1925; 4:192 2, Bloom HI, Wallace EN, Henk 1M: The treatment and prognosis of medulloblastoma in children: a study of 82 verified cases. Am 1 Roentgenol Radium Ther Nuc1 Med 1969; 105:43 3. Bloom HIG, Bessell EM: Medulloblastoma in adults: a review of 47 patients treated between 1952 and 1981. Int 1 Radiat Oncol Bioi Phys 1990; 18:763 4. Evans AE, lenkin RD, Sposto R, et al: The treatment of medulloblastoma: results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. 1 Neurosurg 1990; 72:572
5. Hughes EN, Shillito 1, Sallan SE, et al: Medulloblastoma at the joint center for radiation therapy between 1968 and 1984. Cancer 1988; 61: 1992 6. Tarbell Nl, Loeffler IS, Silver B, et al: The change in patterns of relapse in medulloblastoma. Cancer 1991; 68: 1600
7. Dunbar SF, Barnes PD, Tarbell Nl: Radiographic determination of the caudal border of the spinal field in cranial spinal irradiation. Int 1 Radiat Oncol Bioi Phys 1993; 26:669
Laufer et al.:
New Technique for Laparoscopic Oophoropexy
8. Ray GR, Trueblood HW, Enright LP, et al: 00phoropexy: a means of preserving ovarian function following pelvic megavoltage radiotherapy for Hodgkin's disease. Radiology 1970; 96: 175 9. Le Floch 0, Donaldson SS, Kaplan HS: Pregnancy following oophoropexy and total nodal irradiation in women with Hodgkin's disease. Cancer 1976; 38:2263 10. Thomas PRM, Win stanly D, Peckham MJ, et al: Reproductive and endocrine function in patients with Hodgkin's disease: effects of oophoropexy and irradiation. Br J Cancer 1976; 33:226 11. Damewood MD, Hesla HS, Lowen M, et al: Induction of ovulation and pregnancy following lateral oophoropexy for Hodgkin's disease. Int J Gynaecol Obstet 1990; 33:369 12. Thibaud E, Ramirez M, Brauner R, et al: Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood. J Pediatr 1992; 121 :880 13. Mandl AM: A quantitative study of the sensitivity of oocytes to X-irradiation. Proc R Soc BioI 1958; 150: 53 14. Baker TG: Radiosensitivity of mammalian oocytes with particular reference to the human female. Am J Obstet Gynecol 1971; 110:746 15. Nicholson HS, Byrne J: Fertility and pregnancy after treatment for cancer during childhood or adolescence. Cancer 1993; 71:3392
81
16. Shalet SM, Beardwell CG, Jones PH, et al: Ovarian failure following abdominal irradiation in childhood. Br J Cancer 1976; 33:655 17. Stillman RJ, Schinfeld JS, Schiff I, et al: Ovarian failure in long-term survivors of childhood malignancy. Am J Obstet Gynecol1981; 139:62 18. Rappaport R, Brauner R, Czernichow P, et al: Effect of hypothalamic and pituitary irradiation on pubertal development in children with cranial tumors. J Clin Endocrinol Metab 1982; 54: 1164 19. Brown IH, Lee TJ, Eden OB, et al: Growth and endocrine function after treatment for medulloblastoma. Arch Dis Child 1983; 58:722 20. Ahmed SR, Shalet SM, Campbell RHA, et al: Primary gonadal damage following treatment of brain tumors in childhood. J Pediatr 1983; 103:562 21. Livesey EA, Brook CGD: Gonadal dysfunction after treatment of intracranial tumours. Arch Dis Child 1988; 63:495 22. Hamre MR, Robison LL, Nesbit ME, et al: Effects of radiation on ovarian function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children's Cancer Study Group. J Clin Oncol 1987; 5: 1759 23. Horning SJ, Hoppe RT, Kaplan HS, et al: Female reproductive potential after treatment for Hodgkin's disease. N Engl J Med 1981; 304:1377
Adolescent and Pediatric Gynecology © 1995 Springer-Verlag New York Inc.
A New Technique for Laparoscopic Prophylactic Oopboropexy Before Craniospinal Irradiation in Children With Medulloblastoma* M.R. Laufer, M.D./,2 A.L. Billett, M.D.,3 L. Diller, M.D.,3 L.M. Chin, D.Sc.,4 and N.J. Tarbell, M.D.4 lDivision of Pediatric/Adolescent Gynecology, Department of Surgery, Division of AdolescentlYoung Adult Medicine, Department of Medicine, Children's Hospital-Boston; 2Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital; 3Division of Pediatric Oncology, Children's Hospital-Boston; 4The Joint Center for Radiation Therapy, and the Department of Radiation Oncology, Children's Hospital-Boston; Harvard Medical School, Boston, Massachusetts
Abstract. The study objective was to develop a laparoscopic technique for oophoropexy with the marking of both ovaries with titanium clips so as to be able to calculate the radiation dosage to each ovary. We propose a laparoscopic approach to oophoropexy for patients with medulloblastoma planning for craniospinal radiation. Therapeutic radiation dose exposure to the pexed and nonpexed ovaries is calculated. A surgical outpatient laparoscopic procedure for oophoropexy is described. It was determined that if the pexed ovary is moved 1 cm outside of a megavoltage radiation beam, then the dosage of radiation to the ovary is reduced to approximately 9% of the prescription dose (300 cOy), whereas if the pexed ovary is moved 2 cm outside of a megavoltage radiation beam, then the dosage of radiation is reduced to less than 5% (180 cOy). This new laparoscopic oophoropexy procedure can be performed as an outpatient before craniospinal irradiation in order to increase the chances for the preservation of gonadal steroid production and fertility in girls.
Key Words. Oophoropexy-Laparoscopy-Medulloblastoma-Carniospinal irradiation Introduction Medulloblastoma is a primitive, undifferentiated malignancy of the cerebellum, most commonly ocAddress reprint requests to: Marc R. Laufer, M.D., Division of Pediatric/Adolescent Gynecology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115. *Presented in part at the Eighth Annual Meeting of the North American Society for Pediatric and Adolescent Gynecology, Atlanta, Georgia, 1994.
curring in young children. I This tumor is known to metastasize via cerebrospinal fluid. I The 5-year overall survival rate for medulloblastoma has improved from approximately 30% in 19692 to 65-72% in more recent studies. 3 Curative treatment for medulloblastoma involves craniospinal irradiation to the level of the base of the dural sac, at least to the level of S2 inferiorly. 7 Oophoropexy, with the repositioning of ovaries out of the radiation field by laparotomy, has been previously described with documentation of resultant decreased exposure to radiation and improved gonadal function in girls with Hodgkin's disease.8-12 However, the need for a laparotomy to accomplish this prophylactic procedure adds morbidity at a time when patients are usually undergoing diagnostic evaluation and therapeutic interventions. We describe our experience with a new procedure, laparoscopic oophoropexy, that should facilitate the ability to preserve reproductive potential in girls with medulloblastoma who are about to undergo spinal irradiation. The purposes of this study were 1) to evaluate the safety of laparoscopic oophoropexy, and 2) to determine the theoretic dosage of radiation exposure to the pexed and nonpexed ovaries. Patients and Methods We report three cases of pelviscopic oophoropexy in three girls (ages 5, 7, and 9 years), with medulloblastoma who were to undergo spinal irradiation. The radiation to the spine was planned at 3,600
78
Laufer et al.:
New Technique for Laparoscopic Oophoropexy
cGy, to a field extending from C5 to the inferior border of S2 (S2-S4, depending on the inferior extent of the dural sac as determined by magnetic resonance imaging). Before the start of radiation, patients underwent a laparoscopy with standard video operating equipment under general anesthesia. For the first patient, a lO-mm laparoscope with a camera positioned in the to-mm umbilical port and three additional ports placed suprapubically (one 12 mm and two 5 mm) were used. For the subsequent patients, a 12-mm umbilical port and three 5-mm suprapubic ports were used. The 12-mm port was used for the lO-mm laparoscope, followed by the l2-mm clip appliers with visualization via a 5-mm suprapubic laparoscope. This modification improved cosmetic results. The pelvis was inspected and noted to be normal in each case. The normal prepubertal location of the ovary was observed to be higher in the pelvis compared with the relative final location in an adult, and the ovary was also noted to have a longer uteroovarian ligament, as compared with the relative adult size. It was elected to relocate the left ovary to avoid a confusing differential diagnosis between ovarian pain and appendicitis if subsequent pain was to occur in the right lower quadrant. Titanium clips 9 mm medium-large (Endoclip, United States Surgical Corporation, Norwalk, CT) were used to reduce reactive adhesion formation and to avoid interfering with magnetic resonance imaging. The superior border of the right ovary was tagged with a titanium clip in order to mark its location. The left ovary and the utero-ovarian ligament were identified, and the utero-ovarian ligament was cut with hooked scissors and electrocautery. The left infundibular pelvic ligament was identified, and its associated peritoneum was dissected in order to gain additional mobility of the ovary. (It should be noted that if the peritoneum is not mobilized, many surgeons have observed that a severe adynamic ileus may result.) The superior border of this ovary was also tagged for future identification with titanium clips. The left ovary was then relocated and attached to the anterior peritoneum as inferior and caudad as possible. The ovary was positioned with a 4.8 mm titanium staple (Endohernia Stapler, United States Surgical Corporation, Norwalk, CT) incorporating the remnant of the utero-ovarian ligament and the peritoneum. Results
The patients had no operative complications and were discharged to their homes after a short stay in the recovery room. The patients had no postopera-
,
:~jf
~~". "
.
t'.
.1' ' ". .:~ .}~~ ' ~ '. ••
.".
./'~ ~_,
'l'~ ' ~.
..
,
• '. ':""; l' ~, "
....
-"
.
. .Sil;.. (.
'
•.,
._~_ ~
..
T"...
-
Fig. 1. Postoophoropexy showing the location of the right ovary and the pexed left (L) ovary.
Fig. 2. Postoperative KUB showing the location of the right ovary and the pexed left (L) ovary with demonstration of the radiation beam edge.
tive left lower quadrant pain, and each proceeded with her spinal radiation therapy. Figure 1 is postoophoropexy showing the relative locations of the ovaries. The left pexed ovary is labeled "L." Figure 2 is a representation of the geometric positions of the ovaries in reference to the edge of the radiation beam. The right ovary is tagged at its inferior aspect along the utero-ovarian ligament. The left ovary is positioned obliquely, thus appearing smaller than the right ovary in this radiograph.
Laufer et aL:
New Technique for Laparoscopic Oophoropexy
Lateral Brain Fields
Fig. 3. Lateral brain fields and spinal field for craniospinal irradiation.
All three patients underwent daily craniospinal irradiation after recovery from oophoropexy, as shown in Figure 3. We noted that the unpexed ovary was exposed to varying radiation dosage depending on the treatment energy, geometry, the size of the ovary, and the distance the ovary was from the edge of the beam. It was also noted that there was significant day-to-day variability in the location of the unpexed ovary, resulting in significant variability in the daily exposure of that ovary to radiation. As daily radiographs were not obtained, it can theoretically be shown that if the unpexed ovary is approximately 1 cm from the beam edge, then the dose is approximately 10% of the total prescription dose at the center of the ovary. The dose to this ovary could reach 70% if it moves 0.5 em closer to the radiation beam edge. We calculated that if the pexed ovary is moved 1 cm from the edge of the radiation beam, then the average dose is approximately 8-9% (288-324 cGy). If the pexed ovary is moved 2 em away from the lower edge of the radiation field, then that ovary receives less than 5% of the radiation dosage « 180 cGy). The beam profile for a 6 MY linear accelerator for a spinal field of 8 x 30 cm2 at a depth of 5 cm is shown in Figure 4. The first patient to undergo this new technique had been diagnosed and treated at age 9 and became pubertal at age 10. She has normal serum-luteinizing hormone and follicle-stimulating hormone levels. In addition, she has had bilateral ovarian function documented by ultrasound. It is too early to determine ovarian function in the remaining two patients. Discussion The deleterious effects of radiation on gonadal function are well known, and with improvements in the
79
survival rates of patients with childhood malignancies, methods for reducing the risks of long-term side effects need investigation. Radiation-induced gonadal dysfunction is known to be dose dependent. 13 The gonadal state at the time of the insult is also felt to affect outcome, with prepubescent individuals having a better prognosis for gonadal function than sexually mature individuals. 14 ,15 Sha1et and colleagues 16 reported that ovarian failure occurred in girls between 1 and 13 receiving abdominal irradiation in a dosage of 2,000-3,000 cGy. In another study, Stillman et al. l ? reported that there was no incidence of ovarian failure in girls between the ages of 1 and 17 receiving approximately 54 cGy (range 5-150) of abdominal irradiation and that the failure rate rose to 14% with dosages of approximately 290 cGy (range 90-1,(00) and to 68% with dosages of approximately 3,200 cGy (range 1,200-5,(00). In patients treated for medulloblastoma, there have been differing opinions as to the cause of the gonadal dysfunction, with some authors attributing gonadal damage to scatter from spinal irradiation, 18,19 whereas others have concluded that adjuvant chemotherapy was the causative insult. 2o In one study involving 42 girls with intracranial tumors, it was found that 0 (0%) of 14 had ovarian dysfunction with cranial irradiation alone and 2 (67%) of 3 had ovarian dysfunction with cranial irradiation in addition to chemotherapy, giving a total of 2 (12%) of 17 having gonadal dysfunction after cranial irradiation with or without chemotherapy. For those individuals who received craniospinal irradiation alone, 7 (64%) of 11 had ovarian dysfunction, whereas 9 (64%) of 14 had ovarian dysfunction with both craniospinal irradiation and chemotherapy, giving a total of 16 (64%) of 25 having gonadal dysfunction after craniospinal irradiation with or without chemotherapy. 21 The incidence of ovarian failure from spinal irradiation is not exactly known but is usually estimated to be in the range of 40-60% induction of menstrual irregularities andlor complete gonadal failure with subsequent infertility.15,18,22 We investigated a method of unilateral 00phoropexy via laparoscopy in order to relocate an ovary out of the radiation field in young girls undergoing spinal irradiation. The ovary that is moved is relocated inferiorly and laterally out of the radiation field. Only one ovary is moved so as not to eliminate the possibility of normal means of conception should the unmoved ovary maintain ovulatory function. The amounts of radiation to both ovaries can be determined once the locations of the ovaries relative to the radiation field are known. These locations can be identified by searching for the titanium clips, which have been placed at the ovarian bor-
Laufer et al.:
80
New Technique for Laparoscopic Oophoropexy
1.0
8 x 30 cnf Field
0.9
+- Geometric beam edge
0.8
at depth of 5 em
0.7 Q)
(/)
0
0.6
C Q)
.~
Cii a; a:
0.5
+- 40% of dose at center
0.4
Ovary 1 em 8IN8y from edge average dose-8-9%
0.3 0.2 0.1 0.0
a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Distance from Center of Field (cm) Fig. 4. Beam profile for 6 MV linear accelerator for spinal field. ders at the time of the laparoscopy. By taking advantage of the sharp declining gradient at the beam edges from modern megavoltage linear accelerators, radiation exposure is predicted on radiographic films to be decreased to a level not associated with gonadal failure if the pexed ovary is moved 1-2 cm away from the edge of the radiation field. If the unmoved ovary should fail and if the relocated ovary remains functional, normal estrogen production should result at puberty. Other reports have shown spontaneous fertility after 00phoropexy.8-10,23 If spontaneous conception does not occur, because of tubal factor infertility from tubal stretching, then the single functioning ovary can be used in controlled hyperstimulation and ovum aspiration for in vitro fertilization. In this study, we have reported a new method of oophoropexy for young girls undergoing craniospinal radiation therapy. The method has been found to be safe and to result in a calculated decrease in radiation exposure to the relocated ovary . We found that if the pexed ovary is moved I cm from the radiation beam, then the dosage of radiation to the ovary is reduced to 288-324 cGy, whereas if the pexed ovary is moved 2 cm from the radiation beam, then the dosage of radiation is reduced to less than 180 cGy. For at least one patient, the onset of puberty after the completion of the therapy has been observed. We plan to institute this form of outpatient preventive therapy for patients before beginning spinal irradiation, with the possibility that
central venous line placement can be carried out during the same anesthetic. With this new technique, we hope to preserve gonadal steroid production and fertility in female long-term survivors of medulloblastoma.
References 1. Bailey P, Cushing H: Medulloblastoma cerebelli: a
common type of midcerebellar glioma of childhood. Arch Neuro Psychiatr 1925; 4:192 2, Bloom HI, Wallace EN, Henk 1M: The treatment and prognosis of medulloblastoma in children: a study of 82 verified cases. Am 1 Roentgenol Radium Ther Nuc1 Med 1969; 105:43 3. Bloom HIG, Bessell EM: Medulloblastoma in adults: a review of 47 patients treated between 1952 and 1981. Int 1 Radiat Oncol Bioi Phys 1990; 18:763 4. Evans AE, lenkin RD, Sposto R, et al: The treatment of medulloblastoma: results of a prospective randomized trial of radiation therapy with and without CCNU, vincristine, and prednisone. 1 Neurosurg 1990; 72:572
5. Hughes EN, Shillito 1, Sallan SE, et al: Medulloblastoma at the joint center for radiation therapy between 1968 and 1984. Cancer 1988; 61: 1992 6. Tarbell Nl, Loeffler IS, Silver B, et al: The change in patterns of relapse in medulloblastoma. Cancer 1991; 68: 1600
7. Dunbar SF, Barnes PD, Tarbell Nl: Radiographic determination of the caudal border of the spinal field in cranial spinal irradiation. Int 1 Radiat Oncol Bioi Phys 1993; 26:669
Laufer et al.:
New Technique for Laparoscopic Oophoropexy
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