Biomedical subjects
Publications and source records attributed to L A Walton.
Tumor tissue specimens obtained at the time of disease diagnosis from patients with ovarian carcinoma were analyzed for cellular DNA content and CA-125 antigen expression. The presence or absence of aneuploidy did not influence the expression of the CA-125 antigen. In addition, both intra- and interlesional heterogeneity of cellular DNA content and CA-125 antigen expression were noted.
Aneuploidy is commonly associated with malignancy and certain premalignant conditions. Recent studies have demonstrated an association between prognosis and the presence of aneuploidy. In this study, flow cytometry was used to determine the deoxyribonucleic acid (DNA) content of tissues with cervical intraepithelial neoplasia or invasive cervical carcinoma. Of 41 evaluable patients with cervical intraepithelial neoplasia, aneuploidy was demonstrated in the specimens of three of ten patients with cervical intraepithelial neoplasia II and six of 13 with cervical intraepithelial neoplasia III. No specimens with cervical intraepithelial neoplasia I, with condylomata, or without pathologic diagnosis contained aneuploid populations. Of the 22 evaluable specimens with invasive cervical carcinoma, 13 contained aneuploid populations. In stage I cervical lesions, aneuploidy appeared to be a poor prognostic factor with an overall survival of two of five patients with aneuploid tumors versus five of five patients with diploid tumors.
From April 1969 through December 1980, 203 patients with Stage III epidermoid carcinoma of the cervix were treated with radiation therapy with curative intent. The disease-free survival at 2, 5, and 10 years was 50%, 33%, and 27%, respectively. The survival was better for patients with Stage IIIB disease than for those with Stage IIIA disease. Eighty-eight patients were treated with external beam therapy only, and 115 received external beam and brachytherapy. The disease-free survival was better for the combination therapy group initially, but this difference was not sustained beyond 5 years. One hundred eight patients experienced recurrence within the irradiated field, for a locoregional recurrence rate of 53%. Twenty-seven patients had complications (13%). The complications were mild in 13 patients, moderate in 4 patients, and severe in 10 patients. A study was made of the relationship of the dose to Point A and the occurrence of complications. Similar analyses were made of the bladder and rectal doses and the subsequent occurrence of urinary and intestinal complications. In these analyses, the mean dose to Point A and the critical organs was higher for the groups of patients with complications than for those patients without complications. This relationship was also observed when the patients were stratified for treatment with either external beam plus brachytherapy or external beam therapy alone.
The genesis of uterine sarcomas in vivo has been difficult to elucidate. The reasons are multifactorial and are compounded by the rarity of these tumors. In an effort to understand the biologic activity of this disease, normal endometrial tissue was subjected to tissue culture, histochemical study, and hormonal manipulation. Protein markers were used to differentiate endometrial epithelium from endometrial stromal cells in culture. The endometrial stromal cells grew rapidly following subculturing and were responsive to hormonal manipulation. When the stromal cells in culture were treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the resultant morphologic changes mimicked uterine sarcomas grown in culture. These changes appeared to occur in a sequential manner, somewhat analogous to changes occurring in the endometrial epithelium as it undergoes transformation to endometrial adenocarcinoma. These studies, therefore, may serve as a model system in understanding the genesis and biologic activity of uterine sarcomas.
Between January 1980 and the present, 42 patients with symptomatic, incurable gynecologic malignancies were treated at the University of North Carolina with 1000 cGy in a single fraction to the pelvis, repeated once or twice at monthly intervals as necessary. Of patients with adequate follow-up, total cessation of bleeding was seen in 18 of 30 (60%), complete pain relief in 2/9 (22%), and complete tumor eradication in 7/28 (25%). These palliative benefits were permanent in approximately half of the patients. Five serious treatment complications have been documented, four occurred more than 10 months after treatment. We conclude that 1000 cGy single-fraction whole pelvis treatment can be an effective means of palliating advanced gynecologic cancer provided the patient has a life expectancy of less than 1 year. Patients with a longer life expectancy are at risk for both recurrence of symptoms and for treatment related complications.
From April 1969 through December 1980, 251 patients with invasive, epidermoid carcinoma of the cervix received radical radiation therapy consisting of a combination of external beam and intracavitary therapy designed to deliver 7000 to 8000 rad to Point A and 6000 to 6500 rad to the pelvic lymph nodes. The disease-free survival at 2, 5, and 10 years for patients with Stage IIA disease was 90%, 76%, and 76%, respectively, whereas for patients with Stage IIB disease it was 77%, 62%, and 59%, respectively. The survival for the entire group at 2, 5, and 10 years was 80%, 65%, and 62%, respectively. Sixty-eight patients had a recurrence within the irradiated volume, for a locoregional recurrence rate of 27% (68/251). In 49 patients complications developed for an overall complication rate of 19.5% (49/251). An analysis of the complications and their degree of severity revealed a correlation with the dose of intracavitary plus external beam therapy given to Point A and to the rectum. The mean dose to Point A for patients with and without complications were 7877 rad (standard error [SE] +/- 95) and 7593 rad (SE +/- 67), respectively. The mean rectal dose for patients with and without intestinal complications were 6767 rad (SE +/- 157) and 6426 rad (SE +/- 78), respectively. The dose difference between patients with and without complications was statistically significant for Point A (P = to 0.0163) but not for the rectal dose (P = to 0.0887). There was no correlation between the bladder dose and urinary complications. Other treatment methods as well as patient and tumor parameters, are being currently analyzed to identify which factors, singly or in combination, may contribute to the development of treatment failures or complications.
Percutaneous nephrostomy is a useful method of supravesical diversion when ureteral obstruction occurs at initial diagnosis of gynecologic cancer or recurrence of disease. Although survival is prolonged, the attendant quality of life would indicate that percutaneous nephrostomy should be performed only in those cases in which there is a reasonable chance for palliation or a hope for cure or when temporization is needed to define adequately the etiology of ureteral obstruction following therapy.
The management of the patient with advanced gynecologic malignancies presents multiple problems for the gynecologic and radiation oncologists involved in their care. When palliative management only is indicated, conventional treatment protocols occupy a significant portion of the patient's remaining life span, often times with associated morbidity. Single-fraction external radiation therapy, consisting of 1,000 rads to the whole pelvis, was used in 30 patients with advanced gynecologic malignancies to palliate locally advanced pelvic disease. Alleviation of symptoms and maintenance of a reasonable quality of life were obtained in all patients. No untoward acute side effects were observed. Thirteen patients are alive from 2 to 19 months after treatment, with a mean overall survival after treatment of 8.4 months. It is concluded that this regimen should be considered as the palliative therapy of choice for certain patients with advanced gynecologic malignancies.
Endolymphatic stromal myosis is a neoplasm derived from the endometrial stromal cell. As such it should respond to hormonal manipulation. Reported are positive estrogen and progesterone cytosol receptors in three cases of endolymphatic stromal myosis with disease regression following progestational therapy. Estrogen and progesterone receptor studies are recommended in all cases of endolymphatic stromal myosis. When positive, progestational therapy is appropriate.
Both the tissue lactate dehydrogenase (LDH) isoenzyme pattern and total LDH activity were investigated in a series of human uterine sarcomas and cell lines derived from these tumors. Abnormal LDH isoenzyme patterns characterized by shifts toward the muscle isoenzyme forms (LDH4 and 5) were found in some, but not all, of the sarcomas. The tumors containing rhabdomyosarcomatous elements usually had normal or only slightly altered LDH isoenzyme patterns. The LDH isoenzyme patterns expressed by cultured cell lines established from the uterine sarcomas, in general, resembled those found in the primary tumors. These results suggest that the normal or near normal LDH isoenzyme distributions found in uterine sarcomas with rhabdomyosarcomatous differentiation may be a potential characteristic which may be used for distinguishing these tumors from other uterine sarcomas.
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We investigated the prevalence of depression in a sample of 9-year-old children from the general population being studied longitudinally. Current point prevalences of major and minor depressive disorder were estimated at 1.8% and 2.5%, respectively. A comparison of children with depression and a nondepressed group disclosed no significant differences by sex, nor any significant association between depression and socioeconomic status, teacher reports of behavior problems, and cognitive or motor development. The children with current depression were reported by a parent to have had a history of more behavioral problems, had been referred more often for assessment or treatment of behavioral or emotional problems, and had more negative self-perceptions of their academic ability. The results suggested that parents may be more sensitive than teachers to the behavior problems exhibited by depressed children.
An analysis has been made of 101 patients treated with radiation therapy for epidermoid carcinoma of the cervix Stage IB (FIGO) from January 1970 through December 1976. The patients were treated with a combination of intracavitary therapy and external beam therapy delivering a total combined dose of 8000 rad to the paracervical areas (Points AR and AL) and 5500 rad to the pelvic lymph nodes (Points IR and IL). The cumulative, disease-free survival at 2, 3 and 5 years was 89%, 87% and 84%. Sixteen failures were recorded in this group of patients, of which 3 were a result of loco-regional disease, 5 loco-regional disease plus distant metastasis and 8 distant metastasis only. The failure rate was greater among the patients who had lesions 4 or more cm in diameter and in patients who received doses of external beam therapy to the whole pelvis of 4000 rad or more. Eighteen patients developed complications; however, one patient had a recto-vaginal and a vesico-vaginal fistula; thus 19 complications were recorded. The complications were divided according to their severity into three groups: Grade I (mild), Grade II (moderate) and Grade III (severe). There were 10 Grade I, 4 Grade II and 5 Grade III complications.
A case of a pure heterologous sarcoma of the uterine corpus composed exclusively of rhabdomyosarcomatous elements has been studied by multiple morphologic and biochemical techniques. The neoplasm filled the endometrial cavity and protruded out the cervical os, but the myometrium was only superficially invaded. The tumor did not extend outside the corpus. The pathologic features are discussed in detail. Evidence of striated muscle differentiation could be identified on light microscopic and ultrastructural examination. Immunoperoxidase staining of tumor cells with antibodies to myoglobin were positive. Histochemical preparations for lactate dehydrogenase, succinic dehydrogenase, and acid phosphatase were also positive in neoplastic cells. Other stains gave equivocal or negative results. These findings are discussed in comparison with previous reports.
Two hundred forty patients, ages 12 to 54 years, with biopsy-confirmed early cervical intraepithelial neoplasia (CIN I) treated by cryosurgery were reviewed. CIN I has been viewed historically as having high rates of remission or stabilization. The initial cure rate was 89%, with a 97% cure rate after retreatment of failures. All failures were confirmed histologically. The initial cure rates are no better than those for higher grades of CIN. Thus, CIN I should be viewed with the same seriousness as CIN II or CIN III.
A patient with recurrent Sertoli-Leydig cell tumor is described. The light and ultrastructural findings are illustrated. The tumor recurred first as a poorly differentiated tumor with rhabdomyoblastic differentiation. Following chemotherapy the next recurrence exhibited well differentiated Sertoli-Leydig cell elements. These findings may reflect the capability of this tumor type to undergo chemotherapeutic transformation similar to the transformation which has been described in germ cell tumors of the ovary and testis. This observation may be of importance in the clinical management of patients with poorly differentiated Sertoli-Leydig cell tumors.
Monolayer cultures can be established from human endometrial tissue after enzymatic dispersal into isolated glands or single cells. Three cell types that have distinct morphology by light and electron microscopy are observed in the resulting primary cultures. One cell type, an elongated spindle cell, is similar in appearance to fibroblasts derived from other tissues. A second cell type forms colonies of tightly cohesive cells, ranging in shape from oval to polygonal. These cells have typical organelles and junctional complexes characteristic of epithelial cells from the endometrium. The third cell type assumes a pavement-like appearance composed of polygonal cells when viewed by phase contrast microscopy, but lacks distinctive ultrastructural features of epithelial cells. These cells in culture resemble the endometrial stromal cell, the predominant cell type of the human endometrium in vivo. The epithelial cell does not survive subculturing but the other two cell types can be passaged through several generations and can be stored in liquid nitrogen and subsequently returned to culture.
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