Major problems in clinical surgery最新文献

A totally satisfying concept of treatment is not easy to formulate from the complex and often conflicting results of local therapeutic interventions for breast cancer. It seems evident that clinically occult cancer is often beyond the pale of both resection and irradiation at primary treatment, particularly when cancer is found in regional lymph nodes. Despite all combinations of local treatment, the ultimate risk of failure correlates more closely with the stage of the disease at the time of treatment than with the particular form of treatment. Thus the extent of disease must be considered the major, perhaps the ultimate determinant of prognosis. Because, under controlled conditions, several therapeutic alternatives have appeared to provide virtually identical end results in terms of survival and ultimate dissemination of the disease, the adequacy of control within the field of treatment may, in fact, be the most meaningful end result of local treatment. The experience that has accumulated with treatment of breast cancer supports the thesis that removal of the breast accomplishes all that can be achieved in terms of curing the disease, and wider treatment with surgery or irradiation serves only to improve the prospects for local control. Halsted demonstrated this principle with his radical mastectomy and it still seems to be the case. This fact provides further impetus for detecting and treating cancer while it is still localized to the breast. With these generalizations in mind some empirical observations can be added. An anatomic fact is that multiple microscopic foci of cancer that are not evident clinically are often present in the mammary parenchyma. Undisturbed, at least some, and perhaps eventually all, of these foci of cancer progress to become clinical cancers. Thorough removal of the entire breast (the entire mammary parenchyma) eliminates this particular hazard and, one may presume, terminates the disease if it is still limited to the breast. Removal of the underlying pectoralis major muscle provides additional margin around the tissues primarily involved, but sacrific of the muscle is apparently needless unless it is directly invaded by cancer. Microscopic metastases are also often present in regional lymph nodes without being clinically detectable and, left untreated, have the capacity to enlarge and become clinically apparent. Routine wide removal of regional lymph nodes improves the control of cancer at these sites when metastases are present, but whether it improves the chances for cure is doubtful. The fact is that approximately 25 per cent of patients with axillary metastases enjoy prolonged survival free of recurrence, some remaining well even after thirty years (Adair et al., 1974). Whether they would survive as well without removal of the metastases is uncertain. Desease-free survival is highest if metastases are removed while still microscopic, but this phenomenon may simply reflect treatment at an earlier phase in th

Increased demands are made upon the pathologist to work closely with the surgeon and the mammographer in the interest of early detection. The smallest of cancers and the very earliest phases of neoplastic development are being detected, necessitating fine discriminations between cancer and noncancer. Agreement is not always uniform at these new frontiers of diagnosis, and accuracy is paramount. Tumors are populations of heterogeneous cells. Their morphology lends itself poorly to simple categorization, and their biology is not always accurately reflected in their gross and histologic appearances. Clearly evident to the pathologist are the limitations of morphology, of the light microscope and of routine techniques for examining surgical specimens. Paradoxically, "noninvasive" cancers occasionally metastasize, and lymph nodes originally "free" of cancer are found to contain metastases on more meticulous re-examination. Notwithstanding these limitations a prognostic statement can be made with relative confidence with regard to certain morphologic types of carcinoma. Pure intraductal carcinoma and lobular carcinoma in situ entail negligible threat to normal life expectancy if the breast is thoroughly removed. Other types with a favorable prognosis are intracystic papillary carcinomas and pure mucinous carcinomas. Tumors classified as well differentiated or tubular adenocarcinoma infrequently metastasize and have excellent prospects for cure. Unfortunately, these and other favorable histologic types comprise less than one quarter of all mammary carcinomas. Most carcinomas are without such distinctive features. In this category the degree of anaplasia and the nature of the tumor borders, as well as the presence or absence of blood vessel invasion, dermal lymphatic invasion and metastases in regional lymph nodes, are of major importance in arriving at an estimate of prognosis.

Additive hormonal therapy remains the treatment of choice for disseminated breast cancer in postmenopausal women. Patients with hormone-dependent tumors receive excellent and long-lasting palliation from alterations in the hormonal milieu. Now that hormone receptor assays are clinically available, responses can be accuratedly predicted in a large percentage of cases. Tables 11--6 is a summary of additive hormonal therapy in postmenopausal patients. Endocrine ablative therapy remains of primary importance in premenopausal women because of the superior results, but androgens or antiestrogens may be helpful when patients are not surgical candidates. Castration continues to be the initial approach, with adrenalectomy or hypophysectomy reserved for promising candidates. In postmenopausal women the initial choice is estrogens. The exceptions are those patients with metastases limited to bone, when androgens excel because of an equivalent objective response and superior subjective and metabolic effects. Patients who respond to estrogens and then progress are observed for a rebound regression following the discontinuation of estrogen therapy. Whereas some who do not respond to androgens will respond to estrogens, the converse does not appear to be true (Kennedy, 1974). Currently progestins are the secondary hormonal agent of choice in postmenopausal women, but they may be displaced by antiestrogens as more data become available. In general, if a patient's tumor lacks estrogen receptors or the patient fails to respond to an adequate trial of endocrine or hormonal therapy, one should proceed directly to cytotoxic chemotherapy. A suggested plan for the integration of endocrine with hormonal therapy and both with other forms of palliation is diagrammed at the end of Chapter 12.

Though the etioolgy of mammary cancer in humans remains obscure, epidemiologic data, animal models and in-depth studies of patient populations are providing insights. The rapid progress and sophistication of these investigations promise to clarify with increasing precision the genetic and environmental determinants of risk, if not the fundamental cause. The importance of this information cannot be overestimated; inherent in it lies the possibility of prevention.