Uterus after irradiation

Today, the good prognosis of girl's cancers raises the question of her future fertility. Several studies have focused on preservation of ovarian function, but the uterus, irradiated in childhood, is a crucial component to bear in mind because the somatic damages, in terms of endometrial and myometrial atrophy, scar fibrosis and hypovascularization, are negative factors for the establishment and maintenance of a pregnancy and for a convenient labour. Consequences for procreation are related to the morphologic uterine sequelae and its altered function: early miscarriages, abnormal placentation etc. In addition to some spontaneous pregnancies reported in literature, a few pregnancies, for women experiencing a premature iatrogenic ovarian failure due to mild irradiation, have been obtained after in vitro fertilization and oocyte donation with increased estrogen treatment. Recently, a real hope has surged in relation to the opportunity to reverse the radio-induced fibrosis and thus to obtain a better trophic uterus, using the antioxidant pathway. So, a treatment combining pentoxifylline 800 mg/d and tocopherol 1000 IU/d for 12 months allowed improvement of local uterine conditions such as endometrial thickness (x2), myometrial dimensions (x1.5) and uterine vascularization in all six sterile women studied, who have received high irradiation in childhood (>or=45 Gy). Moreover, two women mildly irradiated (#20 Gy) with endometrium resisting to physiological estrogen status, became spontaneously pregnant after using this combined treatment, and gave birth to healthy children. Further studies are in progress to assess, among other questions, the interest of this therapeutic direction.     

Guidelines for conservative hysterectomy after irradiation

From September 1, 1954, through December 31, 1969, 155 patients with barrel-shaped endocervical carcinoma were treated with radiation followed by conservative extrafascial hysterectomy 6 weeks later. Thirteen patients developed fistulas involving the vagina and 5 patients developed bowel obstruction with an overall complication rate of a 11.6%. From January 1, 1970 through October 31, 1976, 102 patients were treated in a similar fashion. Only 4 patients developed severe complications. A critical review of the treatment features of the 15 patients who developed vaginal fistulas in both series identified pelvic inflammatory disease, blunt dissection, and excessive vaginal apex doses as contributing factors. The prerequisites for successful therapy without significant complications are absence of pelvic inflammatory changes before initiation of therapy, a conservative external radiation dose with cautious application and loading of the intracavitary system, meticulous surgical technique utilizing sharp dissection, and precautionary measures to avoid infection in the irradiated-operated pelvis during recuperation. Conservative extrafascial hysterectomy is adequate to encompass the disease if the patient has a true expanding endocervical barrel-shaped lesion, providing good protection against central failure.     

Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer

From 1 September 1981 to 1 January 1987, 118 patients with FIGO Stage IB, IC, IIA, IIB, and IIC epithelial ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. There was no difference between the regimens with respect to recurrence-free survival (55%) and 4-year overall survival (63%). At routine second-look laparotomy, 16% of patients without clinical detectable tumor showed recurrence. Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery.     

Radical hysterectomy preceded by pelvic irradiation.

A total of 124 patients, who had prior pelvic irradiation, had radical hysterectomy performed at the University of Minnesota Hospitals from 1939 to 1977. The patients fall into two groups: those who had pelvic radiation and radical hysterectomy as primary therapy and those who had radical hysterectomy for postradiation persistent or recurrent cancer of the cervix. A major objective of this report is to describe the incidence, management, and long-term follow-up of patients with complications. Pelvic irradiation followed by radical hysterectomy as primary therapy for cancer of the cervix cannot be justified because of the high risk of urinary tract complications, some of which eventually result in demise of the patient. Radical hysterectomy for postradiation persistent or recurrent cancer is an acceptable procedure for early disease. It would appear from this experience that many patients with small cervical or vaginal postradiation neoplasms can be successfully managed with more conservative procedures such as simple hysterectomy and partial vaginectomy. The value of pelvic lymphadenectomy was not demonstrated. Exenterative procedures are becoming more frequently indicated for eradication of malignancies, with a reduction of long-term urinary tract complications.     

Pituitary-ovarian hormones after low-dose endometrial afterloading irradiation

Low-dose endometrial after loading irradiation was used in 19 mentally retarded women for the induction of therapeutic amenorrhea. They were divided into two subgroups on the basis of age: 13 young patients (mean age 17 years, range 13–26 years) and six patients of middle age (mean age 42 years, range 34–44 years).In the young patients, during the 10-month month follow-up period, the plasma E₂ levels did not decrease. HOwever, the FSH concentration increased. Later on, 2–9 years after treatment, the E₂ levels were significantly higher than those of healthy postmenopausal women and did not differ from the values of healthy women in the sixth to seventh days of the menstrual cycle. At that time the FSH and LH levels were similar to reference values in reproductive age. The E₂/E₁ ratio was significantly higher than that of healthy women in the sixth to seventh days of the cycle and that of postmenopausal women. Most of the menstrual cycles were anovulatory but some ovulatory also occurred. The testosterone concentrations did not differ from reference values. The ovaries of the middle age patients were more sensitive to irradiation than those of the younger patients.     

Pelvic irradiation for stage II ovarian carcinoma

Over a 20-year period, 34 patients with FIGO stage II ovarian carcinoma were treated with postoperative pelvic irradiation at the University of Michigan. Complications of radiation treatment were minimal. The overall actuarial disease-free 5-year survival was 53%. This was not significantly different for substages IIA, IIB, or IIC. Patients with well-differentiated tumors had a significantly better survival than patients with moderate or poorly differentiated tumors (P less than 0.05). The implications for managing stage II ovarian carcinoma are discussed.     

Endometrial carcinoma: the role of irradiation

The role of irradiation in endometrial carcinoma has been discussed. Patients with well-differentiated carcinomas in small uteri with clinical and pathological minimal disease do not require irradiation. For those patients who do benefit from irradiation, the pros and cons of preoperative vs postoperative administration and intracavitary vs external irradiation has been discussed. Techniques and dosages have been suggested. At the present time there exist two schools of thought about the treatment of endometrial carcinoma. Both appear equally effective. It is predicted that, with time and prospective studies, the two schools of therapy will be brought closer together.     

Ovarian carcinoma: Abdominopelvic irradiation following reexploration

Twenty patients with ovarian cancer, who following reexploration were left with residual disease nodules of less than 2 cm diameter, received abdominopelvic irradiation. Of these patients 18 had previous chemotherapy. Fifteen patients completed treatment, 13 of whom had prior chemotherapy. Six of the 18 patients with invasive tumors were alive and disease free 18-53 months postradiotherapy, while only 4 patients had died at the time of follow-up. No patient with residual nodules greater than 1 cm remained disease free. There was no difference in outcome between patients with microscopic or macroscopic less than 1 cm residuum. Complications were acceptable with 3/20 (15%) developing treatment-related intestinal obstruction.