Elvis S. Donaldson

The significance of vascular invasion and lymphocytic infiltration in invasive cervical cancer

Surgical specimens from 100 patients with stage I B cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy were reviewed with respect to vascular invasion and lymphoplasmacytic infiltration. Lymph nodes from these patients were classified morphologically according to the criteria proposed by Cottier. Vascular invasion was associated with a significant increase in nodal metastases and tumor recurrence particularly to extrapelvic sites. A marked lymphoplasmacytic infiltrate around tumor cells was associated with decreased nodal metastases and tumor recurrence. There was no significant relationship between the degree of lymphoplasmacytic infiltration of the primary tumor and regional lymph node morphology.

Therapeutic implications of patterns of recurrence in cancer of the uterine cervix

Five hundred twenty‐six patients with invasive cervical cancer, treated at the University of Kentucky from 1964 to 1976, were followed 2–12 years after therapy. One hundred and sixty patients (31%) developed tumor recurrence. Recurrent cancer was noted within 1 year after therapy in 58% of patients and within 2 years of treatment in 76% of patients. Only 6% of patients with recurrent cervical cancer survived 3 or more years. Stage of disease, cell type, lesion size, and the presence of lymph vascular space invasion by tumor cells were all shown to be prognostically significant. The addition of extrafascial hysterectomy to radiation therapy significantly decreased the incidence of recurrence in stage IB cervical tumors 5 cm or more in diameter. Analysis of this data suggests that radical hysterectomy and pelvic lymphadenectomy is as effective as irradiation only in the treatment of large cell squamous carcinomas 2 cm or less in diameter.

Transvaginal sonography as a screening method for ovarian cancer a report of the first 1000 cases screened

From November 1987 to April 1989, 1000 women 40 years or older underwent screening vaginal sonography at the University of Kentucky Medical Center (Lexington, KY). Patients included in this investigation were all asymptomatic and had no known pelvic abnormalities. Each ovary was measured in three planes and ovarian volume was calculated using the prolate ellipsoid formula. The upper limit of normal for ovarian volume was 18 cm3 in premenopausal women and 8 cm3 in postmenopausal women. In patients with normal scans, mean ovarian volumes decreased from 6.8 cm3 to 3.0 cm3 with menopause. Thirtyone patients (3.1%) had abnormal vaginal sonograms and 24 underwent exploratory laparotomy. All patients undergoing surgery had ovarian or fallopian tube tumors with dimensions identical to those predicted by ultrasound. Histologic diagnoses of these tumors included the following: adenocarcinoma, one; serous cystadenoma, eight; endometrioma, six; and cystic teratomas, two. Vaginal sonography was performed easily and without complications, and was well accepted by patients. All patients with normal sonograms have been rescreened annually and none have subsequently developed ovarian cancer. Further clinical trials to determine the efficacy of vaginal sonography as a screening method for ovarian cancer are indicated.

Ovarian cancer screening in asymptomatic postmenopausal women by transvaginal sonography

From November 1987 to January 1991, 1300 postmenopausal women underwent screening with transvaginal sonography (TVS). Women eligible for screening were all asymptomatic with no known ovarian tumors. Ovarian volume was calculated using the prolate ellipsoid formula, and a value in excess of 8.0 cm3 was considered abnormal. Ovarian abnormalities were detected in 33 women (2.5%), and 27 underwent exploratory laparotomy. Ovarian tumors were noted in all 27 patients, including 2 primary carcinomas and 14 serous cystadenomas. The two women with ovarian carcinomas had normal results of pelvic examinations and normal serum CA‐125 levels. Both women had Stage I disease, and are alive and well after conventional therapy. TVS was time efficient, easy to perform, and well‐accepted by patients. Currently, there are more than 3000 patient years of follow‐up in the screened population, and there have been no deaths due to ovarian cancer. A multi‐institutional trial to determine the efficacy of TVS as a screening method for ovarian cancer is indicated.

The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer.

Surgical specimens from 111 patients with Stage I endometrial cancer were reviewed for the presence of lymph‐vascular space invasion by tumor cells. Lymph‐vascular space invasion was noted in 16 cases, and occurred most frequently in poorly differentiated tumors with deep myometrial penetration. Tumor recurrence developed in 44% of patients whose tumors demonstrated lymph‐vascular space invasion as opposed to only 2% of patients without this finding (p < 0.001). Of seven patients with lymph‐vascular space invasion who experienced tumor recurrence, five developed extra‐pelvic metastases. Discriminant function analysis of these data revealed a statistically significant correlation between lymph‐vascular space invasion and tumor recurrence, independent of histologic differentiation of myometrial penetration. These findings suggest that lymph‐vascular space invasion by tumor cells is an important prognostic variable in Stage I endometrial cancer which should be considered in treatment planning.

Small cell carcinoma of the uterine cervix

From 1962 to 1985, 2201 patients with invasive cervical cancer were staged, evaluated, and treated at the University of Kentucky Medical Center. After a thorough evaluation, 25 cases (1.1%) fulfilled the histologic criteria for small cell cancer defined by Reagan and coworkers. These patients were computermatched for age, disease stage, and lesion size to 25 patients with large cell nonkeratinizing cancer and 25 patients with keratinizing squamous cell cancer. Morphometric analyses of nuclear size and maximum nuclear diameter were performed on all cases without knowledge of cell type. Small cell cancers were characterized by a nuclear area of 160 μ2 or less and a maximum nuclear diameter of 16.2 μ, which was significantly lower than that for large cell tumors. Thirty‐three percent of the small cell carcinomas stained positively for the neuroendocrine markers (neuron‐specific enolase [NSE] and chromogranin [CGR]), whereas the remainder contained only epithelial markers such as cytokeratin (CYK) and epithelial membrane antigen (EMA). Small cell cancers were associated with a high frequency of lymph‐vascular space invasion and a diminished lymphoplasmacytic response. Patients with small cell cancer had a significantly higher recurrence rate, particularly to extrapelvic sites, than the matched patients with large cell cancers, and their survival was lower. Clinical trials to determine the efficacy of adjuvant chemotherapy in the treatment of small cell cervical cancer are needed.

The prognostic significance of cell type and lesion size in patients with cervical cancer treated by radical surgery

Abstract Tumor cell type and lesion size were evaluated as prognostic factors in 82 patients with invasive cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy. Tumors were classified as large-cell nonkeratinizing cancer, keratinizing squamous-cell cancer, small-cell cancer, and adenocarcinoma according to the histologic criteria proposed by Reagen and colleagues [Reagen, J. W., Hamonic, M. S., and Wentz, W. B., Lab. Invest . 6 , 241–250 (1957)]. The incidence of lymph nodal metastases and tumor recurrence was more directly related to lesion size than to tumor-cell type. The incidence of metastatic disease was significantly increased and survival was reduced in those patients whose tumors were greater than 2 cm in diameter.

Microinvasive carcinoma of the cervix.

One hundred seventy-seven patients with squamous cell carcinoma that invaded the cervical stroma to a depth of 5.0 mm or less were the subjects of this investigation. Fifty-one patients were treated primarily by vaginal hysterectomy, 42 by total abdominal hysterectomy, and 84 by radical hysterectomy with pelvic lymphadenectomy. In 52 patients with lesions that invaded the cervical stroma to a depth of 3.0 mm or less, 984 lymph nodes were examined and none contained metastatic tumor. Conversely, lymph node metastases were present in three of 32 patients with lesions that had stromal invasion of 3.1 to 5.0 mm. After therapy, all patients were followed up from 2 to 14 years, and none was lost to follow-up. Among 145 patients with lesions that invaded the stroma to a depth of 3.0 mm or less, only two developed recurrences, both of which were intraepithelial. Among the 32 cases of carcinoma that invaded the stroma 3.1 to 5.0 mm, there were three invasive recurrences, and two deaths.

Combined radiation therapy and extrafascial hysterectomy in the treatment of stage IB barrel‐shaped cervical cancer

Seventy‐five patients with bulky barrel‐shaped Stage IB cervical cancers, treated at the University of Kentucky from 1965 to 1981, were the subjects of this investigation. Thirty‐two of these patients were treated with radiation therapy alone and 43 were treated with radiation followed by extrafascial hysterectomy. There were no significant differences in age, gravidity, or tumor cell type between the two treatment groups. Patients were seen at regular intervals from 2 to 11 years after treatment and none were lost to follow‐up. Recurrent cancer was noted in 47% of patients treated by radiation alone as compared to 16% of those treated with combined therapy (P < 0.01). The incidence of pelvic recurrence was reduced from 19% to 2% and extrapelvic recurrence from 16% to 7% in patients treated by combination therapy. No rectal or urinary tract fistulae were noted after extrafascial hysterectomy. The findings of this study suggest that the use of extrafascial hysterectomy following radiation therapy in patients with bulky Stage IB cervical cancer causes a significant reduction in tumor recurrence without producing an increase in treatment‐related complications.

Stage I serous papillary carcinoma of the endometrium.

From 1973 to 1987, 16 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I serous papillary endometrial carcinoma were evaluated and treated at the University of Kentucky Medical Center (Lexington, KY). All patients were 60 years of age or older, and all were postmenopausal. Patients were treated with total abdominal hysterectomy, bilateral salpingo‐oophorectomy, and paraaortic lymph node sampling, and 38% were noted to have more extensive disease than appreciated clinically. Nine patients were given adjuvant postoperative radiation. Seven patients (44%) developed recurrent cancer with liver, lung, and upper abdomen being the most common sites of spread. Prognosis was most directly related to the presence of lymph vascular space invasion and the depth of myometrial penetration. No patient with serous papillary carcinoma confined to the endometriunt developed recurrent cancer. In contrast, the recurrence rate of patients having myometrial invasion was 70% (P < 0.03). Hormonal therapy was of limited value in the treatment of recurrent disease. This data suggests the need for adjuvant systemic therapy in the treatment of patients with Stage I serous papillary carcinoma of the endometrium who have myometrial invasion.