Clinics in obstetrics and gynaecology最新文献

Endometrial glandular proliferations form a morphological and biologic continuum. The new definition of stromal invasion provides a means of identifying lesions with a relatively high probability of myometrial invasion and malignant behavior. With more standardized terminology and classification, the natural history of preinvasive lesions is better understood. Caution must be exercised because confusion is hard to avoid completely. It is now apparent that the presence of cytological atypia in a preinvasive lesion identifies a lesion at high risk to develop carcinoma. Glandular hyperplasia without cytological atypia identifies a patient likely to have an abnormal endocrine milieu, but it is not a significant preinvasive lesion and has little tendency to develop into one. The presence of cytological atypia provides the basis for selection of therapy.

Screening and initial diagnosis of endometrial cancer can be accomplished by cytologic or histologic sampling techniques when these are positive for malignant cells. When they are negative, the evaluation of the symptomatic patient requires further diagnostic procedures. Fractional dilatation and curettage remains the most reliable method and can begin to establish extent of disease. When dilatation and curettage results are negative in the symptomatic patient, hysterography or hysteroscopy can help identify lesions missed by curettage. Once the diagnosis has been established, a careful search for metastatic disease begins with careful pelvic examination and chest X-ray. When the endocervical curettage contains tumor cells, tracheloscopy and contact hysteroscopy can identify those patients with true endocervical involvement. Preoperative computed axial tomography (CT) or magnetic resonance imaging can direct a thin needle biopsy to prove metastatic disease when enlarged nodes are seen. These imaging techniques can also identify and localize highly suspicious nodes to be biopsied at surgery. Because of a high rate of false negativity, neither of these imaging techniques can exclude the presence of metastatic disease. If CT scanning is done, liver-spleen scan and intravenous pyelography may not be necessary as additional studies. In the absence of CT scanning, intravenous pyelography should be done as a routine, and liver-spleen scanning if liver function tests or physical examination indicate abnormalities. Magnetic resonance imaging and isotope scanning may be useful in the future but are not readily available yet. Surgical evaluation must include removal of the uterus, tubes and ovaries, sampling of the pelvic and para-aortic lymph nodes, and cytology on washings of the pelvic cavity for determination of the extent of disease and of factors placing the patient at high risk for disseminated metastases. Histopathologic evaluation of depth of myometrial invasion, presence of occult cervical involvement and lymph node metastasis and grade of tumor complete the identification of high-risk disease. Speedy and accurate evaluation and diagnosis of endometrial carcinoma and extent of disease can direct timely treatment and offer the patient the best chance for survival.

With the arrival of progestin therapy for advanced, metastatic and recurrent endometrial cancer a quarter of a century ago, came the discovery that approximately one-third of all these tumors would show a clinical response. Probably no more than half of this group will survive more than 5 years. Identification of the type of patient who is most likely to respond has proven difficult. Both clinical and histopathological characteristics act only as an unreliable guide. The site of metastasis and the time for a recurrence to appear are the most constant of these factors. It is hoped that the steroid receptor content of the tumor will prove to be as valuable as it has been in the case of breast cancer. At the moment this is under investigation with numerous ongoing studies. Type, dosage and mode of administration of progestin do not appear to be critical factors in tumor response, nor does the type of synthetic agent used. However, medroxyprogesterone has been the subject of numerous symposia and is the best researched. It also offers the opportunity of being administered orally and in large doses. All agents are virtually free of toxic effects and cessation on this basis is unusual. For patients with tumors that either do not respond to progestin, or else have a temporary response, other agents--antiestrogens and cytotoxic--may well prove to be of value either simultaneously or sequentially. These possibilities are under current investigation. The definitive therapy of primary 'nonadvanced' disease is not established and is at this point unproven in any significant published randomized study. Orthodox proven methods of treatment, i.e. surgery and irradiation, must form the initial component in every patient's therapy, whatever the stage of the disease. It is hoped that prospective studies will elucidate the place of progestins in an adjunctive primary setting. However, it must be emphasized that such studies must concentrate on 'high-risk' patients. The probability of proof in any group of 'good prognosis' patients--whatever the numbers entered--appears to be very low.

In evaluating these trends in the East-West comparison, one notes that the epidemiologic features connoting high risk are similar in both cultures; while they are more common in the West, they are more strongly associated in the East. Clearly, a prospective interview method of obtaining reproductive data will be more informative for such a crosscultural study with greater numbers lending better support. In summary, there exists a grouping of reproductive phenomena fairly common in Western societies that are related to higher risk for endometrial cancer, and we have noted similar characteristics in Eastern women who have developed this disease, while control groups in Eastern societies where this disease is uncommon have a low profile for such attributes in comparison to the West.

Unopposed estrogens, both exogenous and endogenous, increase the risk of endometrial cancer although the magnitude of the association between estrogen replacement therapy and adenocarcinoma has been exaggerated by the epidemiologic case-control studies. Not all postmenopausal women need estrogen replacement therapy since some produce sufficient endogenous estrogens to remain asymptomatic and prevent atrophic vaginitis, osteoporosis and atherosclerosis. However, within this group may be those at risk for endometrial cancer, so they need to be identified and treated with cyclic progestogens. Sequential oral contraceptives did not protect young women from adenocarcinoma of the endometrium because of too little progestogen for too short a duration in view of the relatively high dosage of estrogen. However, combination birth control pills significantly decrease the risk for endometrial carcinoma. Endometrial hyperplasia is a precancerous lesion in some women and can be effectively reversed with 10-13 days of progestogen monthly in at least 98% of patients. The progestogen challenge test has been devised to identify postmenopausal women at greatest risk for adenocarcinoma. It should be administered to all postmenopausal women with an intact uterus. This includes asymptomatic women, patients receiving estrogen replacement therapy and women being evaluated for hormone therapy. If there is a positive response to the progestogen challenge, as manifested by withdrawal bleeding, then the progestogen should be continued for 13 days each month for as long as withdrawal bleeding results. If there is no response then the progestogen challenge test should be repeated at each annual examination. Universal use of the progestogen challenge test should prevent nearly all endometrial cancers.

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.

The central issues of the immunology of the placenta are poorly defined. As an allograft its success almost certainly depends on the absence of transplantation antigens from syncytiotrophoblast. The placenta is an imperfect immune barrier between mother and fetus. Rhesus isoimmunization is one well-known consequence but maternal graft-versus-host disease is another, although much rarer. The placenta performs an important function by transferring maternal IgG to the fetus and filters out potentially harmful cytotoxic antibodies. However, autoantibodies may, in rare circumstances, cause passively acquired fetal autoimmune disease. Direct maternal immune attack on the placenta is not a clear pathological entity but may occur with placental villitis and pemphigoid gestationis; and may contribute to recurrent abortion of unknown aetiology or to pre-eclampsia.

Chorion villus biopsy answers the pressing need for early prenatal diagnosis. The technique is carried out at about 10 weeks gestation and in most instances this tissue is amenable to direct analysis without culture. This technique is particularly suitable for gene probe diagnosis. However, it is now widely offered for cytogenetic diagnosis on the basis of maternal age and some 10 000 patients have been reported to a Central Registry. The procedure-related abortion rate in skilled hands would seem to be about 2-3%, although this is probably lower with the new transabdominal route. Despite the great deal of attention which is focused on this technique, it is still too early to tell whether chorion villus biopsy will replace amniocentesis as the standard method of prenatal diagnosis.