Jerome H. Rudolph

Uterine sarcomas: natural history, treatment and prognosis.

Seventy‐three documented cases of uterine sarcoma were treated at the University of Rochester Strong Memorial Hospital from 1955 to 1975. Thirty‐three patients (45%) were treated with surgery only [S], 31 (43%) with surgery and radiation [S + R], and 9 (12%) with radiation alone [R]. A review of the literature with over 900 cases was also performed. Several important issues regarding these rare tumors are addressed, such as the prognosis of the several histologic variants, the role of radiation therapy in their management and what perhaps may constitute a comprehensive therapeutic approach. These tumors are characterized by local aggressiveness and early widespread dissemination. There are three main histologic varieties: mixed mesodermal sarcoma (MMS), leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS). Of the three, MMS was the most common, seen in 60% of the cases; LMS occurred in younger patients and tended to be localized to the uterine corpus (Stage I) in 80% of the instances. Tumor extent at diagnosis was the main prognosticator for survival in uterine sarcomas; patients with Stage I tumors had a significantly lower incidence of recurrences, as well as a better survival than patients with more advanced tumors. Stage‐by‐stage, there were no significant differences in survival among the pathologic variants. To ensure adequate staging, a surgical procedure is recommended first whenever possible. Adjuvant radiation therapy significantly improved disease controlability in the pelvis, although it may not have dramatically affected the final outcome. In addition to pelvic irradiation, some form of systemic therapy should be administered to decrease distant metastases.

Uterine sarcomas. Analysis of failures with special emphasis on the use of adjuvant radiation therapy

There were 47 failures among 73 verified cases of uterine sarcoma reported at the University of Rochester Tumor Registry from 1955 to 1975; they constitute the subject of this report. Of 33 patients initially treated with surgery only [S], 19 patients (58%) failed; 20 of 31 patients (65%) treated with surgery and radiation [S + R] failed; 8 of 9 patients (89%) treated by radiation alone [R] failed. According to pathology, failures occurred in 33 of 44 patients (75%) with mixed mesodermal sarcomas (MMS), 7 of 20 patients (35%) with leiomyosarcoma (LMS), 4 of 6 patients with endometrial stromal sarcomas (ESS), and 3 of 3 patients with other types of sarcoma. Once corrected by stage, there were no significant differences in failure rates, spread patterns or survival among these main histologic variants. Twenty of 41 patients (56%) with Stage I tumors failed with an average failure time of 32 months. Twenty‐seven of 32 patients (84%) with Stages II, III, and IV tumor failed; their average failure time was only 9 months. The mean failure time for both the patients treated with [S] and [S + R] was 22 months; for patients treated by [R] it was 3 months. Isolated pelvic failures constituted only 4% of all failures, failures both in the pelvis and in distant sites, 49%, and distant metastases, 47%. There was a marked decrease in pelvic failures in patients treated with [S + R] when compared to those who received [S]. Adjuvant radiation proved to increase tumor control in the pelvis but did not influence the final outcome because over 90% of all failures developed distant spread outside the pelvis. The most common distant failures were in the upper abdomen (mainly omentum and peritoneum) and in the lungs. Lung metastases alone was the only site of failure in 16% of the instances. A comprehensive treatment approach based on the spread and failure patterns will be proposed.

THE MANAGEMENT OF CLINICAL STAGE I ENDOMETRIAL CARCINOMA

A retrospective analyses of 307 cases with clinical Stage I endometrial carcinoma was done in an attempt to determine the role of radiation therapy in the optimal treatment of this disease. A review of the modern literature with over 9000 cases served as a useful tool to corroborate inferences and conclusions. The present series has 155 patients (51%) treated with preoperative megavoltage external pelvic radiation with a variation in doses of less than 6%. Five‐year survival estimates (79%‐83%) in clinical Stage I endometrial carcinoma are similar among the several main treatment combination that are employed; they become a useless parameter for any comparison. The pelvic failure rate constitutes a more useful guideline in assessing the most adequate therapy. The pathologic grade of the tumor is the main prognosticator in endometrial carcinoma. Intimately related to the tumor grade is the depth of myometrial invasion of the carcinoma. The size of the uterus and/or its cavity carry less prognostic significance than traditionally thought. For grade I lesions, there is little error in diagnosis, few pelvic failures and excellent survival (96%); they could be approached with initial surgery and postoperative radiation reserved for selected patients. For grade 2 tumors, the error in diagnosis and the failure rate increases with an overall survival of 87%. For grade 3 tumors, the error in diagnosis and failure rates are quite high with a 5 year survival of only 70%. Preoperative radiation, especially external beam therapy, is suggested for grades 2 and 3 Stage I tumors. The use of this treatment modality yields only 3% pelvic failure and an overall 5 year survival of almost 90%.

Endometrial carcinoma: Analysis of failures with special emphasis on the use of initial preoperative external pelvic radiation

Abstract This paper analyzes in detail a total of 75 failures occurring among 364 patients with endometrial carcinoma. Approximately one half of all patients received preoperative external pelvic radiation for initial treatment. One-half of all failures occurred in the pelvis, the other half in distant sites. Failures in endometrial carcinoma are associated with a higher pathologic grade and clinical stage. An increase in grade and/or stage is associated with a higher incidence and depth of myometrial invasion and pelvic nodal involvement. The use of preoperative external pelvic radiation has eliminated vaginal recurrences in clinical Stages I and If and has reduced the overall incidence of pelvic failures to only 3%. Approximately one-third of patients with failures localized to the pelvis after initial surgery can be salvaged by the use of external pelvic radiation. Patients with distant metastases benefit significantly from therapy other than supportive measures.

Estrogen-binding proteins of the human uterus☆

Abstract 1. 1. Sucrose gradient centrifugation analysis and agarose gel chromatography of the human uterine cytosols, equilibrated with [3H]estradiol, have demonstrated the presence of two specific estrogen-binding proteins. The endometrial cytosol contained estrogen-binding proteins which sediment in sucrose gradients at 8 S, with a secondary estrogen-binding protein sedimenting at 3 S, while the myometrial cytosol contained almost exclusively a 3-S (3.1 ± 0.1 S) estrogen-binding protein. A non-specific [3H]-estradiol-binding protein with a sedimentation coefficient of 4.6 S was shown to be serum albumin. 2. 2. The addition of diisopropylfluorophosphate (DFP) to the homogenization buffer resulted in the appearance of the 8-S and no 3-S estrogen-binding protein in the myometrial cytosol, suggesting that the 3-S species may be obtained from the 8-S estrogen-binding protein by limited proteolysis, but without loss of the estradiol-binding capacity. 3. 3. The myometrial 3-S estrogen-binding protein has a molecular Stokes radius of 26.7 (+ 0.4) A, with a frictional ratio ( ƒ ƒ 0 ) of 1.20–1.25, and a molecular weight of 35 000–38 000 as approximated by agarose gel chromatography and sucrose gradient analysis. 4. 4. The apparent dissociation constant of the myometrial estrogen-binding protein was 1·10−9 M and the binding capacity was 67 (± 10)·10−15 mole of [3H]-estradiol bound per mg protein, with large variation among patients, 25·10−15 140·10−15 mole of estradiol bound per protein. Test compounds competed with the [3H]estradiol for binding by the myometrial estrogen-binding protein in the following sequence: 17β-estradiol > estrone > ethynylestradiol ≥ diethylstilbestrol > 17α-estradiol > estriol > CI-628 > U11, 100A >cis-clomiphene > 5-androsten-3β,17β-diol > 4-androsten-3β,17β-diol. Dihydrotestosterone, testosterone, androstenedione, progesterone or cortisol were not effective competitors of [3H]estradiol for the myometrial estrogen-binding protein.

Adenosquamous carcinoma of the endometrium. An entity with an inherent poor prognosis

Mixed adenosquamous carcinomas of the endometrium have been reported in recent years to have a steady increase in incidence, extreme aggressiveness, poor responses to radiation therapy, and a low five‐year survival (less than 20%). In the present report, 87 mixed carcinomas (MC) are compared with 260 pure adenocarcinomas (AC) and 29 adenoacanthomas (AA). There were no basic differences in incidence, clinical history, responses to radiation therapy, and prognosis for any of these three entities. Adenocarcinomas of the endometrium with and without squamous elements should be regarded and approached as any pure AC. There is an overall tendency for endometrial carcinomas to be at an early stage at diagnosis and the five‐year survival regardless of pathologic type, stage, grade, myometrial invasion, and therapy is 80%. Cancer 40:119–130, 1977.

A Method for Obtaining Monolayer Cultures of Human Fetal Cells from Term Placentas.

Summary Technics are presented for obtaining monolayer cultures of human fetal cells from the chorionic villi of mature placentas. Mixed cultures of epithelioid and spindle cells are obtained with these methods. The fetal origin of the cells in culture is confirmed with studies of the sex chromatin pattern of the nuclei and by examination of histological sections of the trypsinized tissue for the presence of decidua. Detection of chorionic gonadotrophin in the medium of 2 cultures of cells from mature placentas is reported. The investigators are indebted to Dr. Herbert R. Morgan for consultation and advice during these studies and to Virginia Eldridge and Eleanor Dudley for technical assistance.

Cryotherapy of a heterografted human bladder tumor: Long-term observations

Summary The effect of freezing (0° to −3°C), as compared to simple cooling (10° to 15°C), of a heterografted human bladder tumor was studied. The cortisonized hamster check pouch was used for the host site. The heterografted tissue was a sterile metastatic lymph node obtained from a patient with a biopsy-proven epidermoid carcinoma of the urinary bladder. The studies showed that the tumor implant was sensitive to freezing but not to cooling. The surrounding check pouch maintained its integrity with freezing. It was concluded that the tumor studied was more sensitive to freezing than the surrounding normal tissues.