Virginia K. Pierce

Treatment of endometrial stromal tumors

We reviewed 31 cases of endometrial stromal tumors treated on the Gynecology Service at Memorial Sloan-Kettering Cancer Center from 1970 to 1984. Twenty-two patients had endolymphatic stromal myosis and 9 patients had endometrial stromal sarcoma. Twenty-six patients initially had disease confined to the uterus. Following hysterectomy, 7 patients received various adjuvant therapies, but no active adjuvant regimen was identified. All 3 patients who presented with advanced endometrial stromal sarcoma died of rapidly progressive disease; only 2 of 6 patients with stage I endometrial stromal sarcoma developed recurrence. Among patients with endolymphatic stromal myosis, a higher recurrence rate was noted in patients with residual ovarian tissue (100%) than in those without residual ovarian tissue (43%). Fifteen patients were treated for recurrent disease (13 with endolymphatic stromal myosis, 2 with endometrial stromal sarcoma). Following attempts to resect disease surgically, objective responses were attained with both chemotherapy (57%) and radiation (40%). The median survival following treatment of recurrent disease was 46 months. Actuarial survival for all patients in this study was 76% at 5 years and 69% at 10 years.

A review of second-look laparotomy for ovarian cancer

One hundred twenty-seven patients underwent second-look laparotomies from July 1969 to June 1982. To be included in this report they must have met the following criteria: a documented ovarian neoplasm; previous surgery; adequate chemotherapy for cessation if no disease was found; and no X-ray, chemical, or clinical evidence of disease including an exam under anesthesia. Forty-one percent had residual disease at second-look laparotomy. The original stage and the percentage of tumor debulked at initial surgery were inversely related to the likelihood of finding residual disease. Age, histologic type and grade, and type of chemotherapy did not show a significant relationship with the likelihood of disease persisting. Recurrent tumor was subsequently detected in 16% of patients who had been found to be free of disease at second-look laparotomy. Of thirty stage III and IV patients treated with combinations containing cis-platinum, 10 (33%) had recurrences. This rate of recurrence was significantly greater than the 17.6% recurrence rate in 17 patients with Stage III and IV disease whose chemotherapy consisted of single alkylating agents or with combinations without cis-platinum. Twenty patients underwent a third-look laparotomy after completion of additional chemotherapy. Nine were found to have no residual disease. Two of the nine (22%) subsequently had recurrence of disease. Three of the eleven patients with persistent disease at the time of a third-look laparotomy underwent a fourth-look laparotomy. All were found free of disease and none have recurred. Six (55%) of those with persistent disease at the third-look laparotomy have died despite continued therapy. The ability to successfully treat some patients with persistent disease continues to be a justification for the use of a second-look laparotomy. However, the high rate of recurrence after cessation of treatment following the finding of no residual disease raises the question of whether it is appropriate to discontinue all therapy at this time.

Pelvic exenteration for recurrent or persistent gynecologic malignancies: A 10-year review of the Memorial Sloan-Kettering Cancer Center experience (1972–1981)

From January 1, 1972 to December 31, 1981, sixty-five patients underwent pelvic exenteration as treatment for recurrent or persistent gynecologic malignancy at Memorial Sloan-Kettering Cancer Center. Cervical carcinoma was the disease most commonly treated by exenteration. The operative mortality of 9.2% represents an improvement over previous reports from this institution. After routine use of prophylactic minidose heparin, no cases of thrombophlebitis or pulmonary embolus occurred postoperatively. A 5-year survival rate of 23% warrants continued use of exenteration in carefully selected patients. The significant mortality and morbidity associated with pelvic exenteration preclude its use as a palliative procedure.

Evidence for the efficacy of adjuvant therapy in epithelial ovarian tumors of low malignant potential

During the 10-year period from January 1975 through December 1985, 48 patients with low malignant potential epithelial ovarian tumors were treated on the Gynecology Service at Memorial Sloan-Kettering Cancer Center. No patients were lost to follow-up and the mean duration of follow-up was 42 months. Twenty-nine patients were Stage I, 5 patients were Stage II, 11 patients were Stage III, 1 patient was Stage IV, and 2 patients were unstaged. Patients were divided into those with no residual disease after initial surgical treatment (29), microscopic residual disease (7), and gross residual disease (12). No patient without residual disease died from cancer. Of the 19 patients with residual disease, all received adjunctive chemotherapy alone, radiation therapy alone, or a combination of both. Three of 19 patients died from cancer. Twelve patients with residual disease were found to be free of disease at second-look surgical reassessment following adjunctive therapy. This review indicates that adjunctive therapy can eradicate residual disease in patients with epithelial ovarian tumors of low malignant potential.

Structural similarity of molybdate-stabilized steroid receptors in human breast tumors, uteri and leukocytes

Abstract Hydrodynamic parameters of receptors for three classes of steroids from several benign and malignant human tissues have been evaluated in buffers of similar conductivity containing Na 2 MoO 4 and/or KCl. Estrogen receptors in breast tumor cytosols were labeled with [ 3 H]-estradiol, progcstin receptors in cytosols from breast tumors and benign or carcinomatous uterine endometrium with [ 3 H]-promegestone (R5020) and glucocorticoid receptors in normal lymphocytes and cells from patients with acute lymphoblastic and nonlymphocytic leukemias with [ 3 H]-triamcinolone acetonide. Receptor-bound steroid was resolved from free or loosely bound steroid by charcoal-dextran treatment or chromatography on 9-ml columns of Sephadex LH-20 (Pharmacia) prior to analysis by glycerol gradient centrifugation or filtration on 120-ml columns of Agarose A-1.5 m (BioRad). Ultracentrifugal and Chromatographic patterns obtained in control buffers were heterodisperse, and the recovery and predominant receptor form(s) detected depended on numerous experimental variables: time and temperature of incubation, protein concentration of the cytosol and concentration of salt in the fractionation buffers (30, 50 or 150 mM KCl). In contrast, analyses in hypotonic buffers containing 20 mM Na 2 MoO 4 revealed highly consistent results for both the sedimentation coefficient (s 20 ,w) and Stokes radius ( R s ) of all of the receptors studied. In view of this similarity among the corresponding parameters, the data from 47 gradients and 26 chromatograms were pooled to obtain the following values for the “average” molybdate-stabilized receptor in human tissues: s 20 w = 9.6 ± 0.3 S and R s = 77 ± 4 A (mean ± SD). In a protein of normal density and solvalion, these parameters indicate a molecular weight of ~310,000 and an axial ratio of 11, for a prolate ellipsoid. The observation of similarly large, asymmetric forms of these receptors in buffers containing both 20 mM Na 2 MoO 4 and 120 mM KCl implies that they are not artifactual aggregates formed during extraction and analysis in hypotonic buffers. The remarkable conservation of this structure among receptors for three classes of steroids in both benign and malignant specimens of human breast, uterus and leukocytes suggests that most of this structure is essential to receptor function. Purification and detailed characterization of the molybdate-stabilized complexes should facilitate the elucidation of the common pathways of receptor action in benign and steroid-responsive malignant tissues and the detection of any structural defects in receptors in steroid-resistant cancers.

Pretreatment laparotomy in carcinoma of the cervix.

Abstract In cases of advanced carcinoma of the uterine cervix, control of regional pelvic disease is not always equated with survival. While early disease often does remain localized within the pelvis, more advanced cervical cancers are observed to metastasize to paraaortic nodes and to distant sites. This study reports a surgical protocol designed to define extent of disease in patients having invasive cervical carcinoma prior to administering primary radiation therapy. Three questions have been raised: (1) Which individual patients have disease outside the pelvis? (2) Is it possible to modify therapy to control disease outside the pelvis and thereby influence survival? (3) Are positive paraaortic nodes found at pretreatment laparotomy indicative of systemic spread of disease? This pretreatment laparotomy was done on 127 patients, 31 of whom were found to have positive paraaortic nodes (24.4%). Sixteen patients had metastatic disease within the peritoneal cavity. Standard pelvic radiotherapy was subsequently given, supplemented with a paraaortic field in those cases with positive paraaortic nodes. Survival was not significantly different in patients with or without paraaortic nodal disease. It was further noted that 17 of the 31 patients (54.8%) who had positive paraaortic nodes later had distant metastases (median time 8 months), compared to 2496 (25.0%) with negative nodes having a median time to metastases of 10 months.

Dysgerminoma of the ovary.

From 1938 to 1977, 21 patients with pure dysgerminoma were treated at Memorial and James Ewing Hospitals, now Memorial Sloan‐Kettering Cancer Center. Twelve patients were considered to have their initial therapy begun or completed at our institution. Eleven (91.7%) of 12 patients were found free of disease from 2 to 38 years (median 6 years). Nine patients were referred with recurrent disease. Only 4 (45%) could be salvaged 2 to 21 years (median 9 years). Because of the lower survival rate in the treatment of recurrent disease in this series, it is difficult to advocate overly conservative therapy initially in all early lesions. The survival rate depends on the original size of the tumor, initial adequate staging and appropriate therapy based on the extent of disease. Recommendations for a treatment protocol are proposed. Cancer 43:798–805, 1979.

Primary chemotherapy and the role of second-look laparotomy in non-dysgerminomatous germ cell malignancies of the ovary

In view of the rarity of germ cell tumors of the ovary, it is not surprising that little information exists about the indications for and significance of findings at second-look laparotomy in patients with these tumors. For this reason, we have reviewed 16 patients who received primary chemotherapy for malignant germ cell tumors of the ovary at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1976 and 1983. Eleven of them underwent a second-look laparotomy after completion of their therapy. Primary therapy consisted of surgery, usually unilateral oophorectomy, and cis-platinum-based VAB chemotherapy. The histologic diagnoses were six immature teratomas, five endodermal sinus tumors, four mixed germ cell tumors, and one nongestational choriocarcinoma. Stage distribution was as follows: Stage IA, eight patients; Stage IC, one patient; Stage IIA, one patient; Stage III, four patients, and unstaged, two patients. The ages ranged from 15 to 56 years, with the mean of 29 years. All of the 11 patients undergoing second-look laparotomy were found to be free of disease. They are alive and have been continuously free of disease from 9 to 77 months (mean 39 months). This paper discusses primary chemotherapy and the role of the second-look laparotomy and suggests its value in modifying treatment, predicting cure, and safely stopping therapy in patients with germ cell malignancies of the ovary.

Intestinal surgery in gynecologic oncology

Intestinal surgery is frequently required in the management of patients with gynecologic malignancies. During a recent 3-year period 10.4% of all laparotomies performed on the Gynecology Service at Memorial Sloan-Kettering Cancer Center included major intestinal surgery. A total of 215 separate intestinal procedures were performed during 171 operations on 158 patients. The majority of operations were performed in patients with ovarian (42.7%), cervical (24%), and endometrial (12.3%) malignancies. Seventy-nine of 171 (46.2%) of operations were performed on previously irradiated patients. The most frequent indications for intestinal surgery were intestinal obstruction (43.2%) and intestinal fistula (21%). Procedures performed included 87 intestinal resections, 26 intestinal bypasses, 82 colostomies, and 20 intestinal conduit urinary diversions. Hand suturing was used in 71% of anastomoses; automatic stapling instruments were used in 29%. There was a single surgical mortality. Complications including infections, obstruction, and fistula formation were infrequent. These difficult intestinal procedures can be performed safely in the context of a fellowship training program. Since a significant proportion of all laparotomies done in gynecologic cancer patients will include major intestinal surgery, physicians managing patients with these diseases should have both the technical skills necessary to perform these procedures, as well as a thorough understanding of the diseases themselves.