Preliminary analysis of the behavior of stage I ovarian serous tumors of low malignant potential: a Gynecologic Oncology Group study.

PURPOSE: From December 1983 through February 1992, a prospective study designed to determine the clinical course of patients with ovarian tumors of low malignant potential (LMP) was conducted by the Gynecologic Oncology Group (GOG). MATERIALS AND METHODS: This protocol was developed to evaluate the following (1) the biologic behavior of ovarian LMP tumors, (2) the effectiveness of melphalan chemotherapy in patients with clinically detectable residual disease after surgical staging and in patients whose tumors progress or recur after surgical therapy, and (3) the response rate to cisplatin in those who failed to respond to melphalan therapy. The study group consisted of 146 assessable patients with stage I serous LMP tumors. All of these women had the affected ovary (or ovaries) removed, and a complete staging operation was performed in each case. While 123 patients had a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO), 21 retained the uterus and one normal-appearing ovary and fallopian tube. No adjuvant chemotherapy or radiation therapy was administered to any patients in the stage I study group. RESULTS: The median follow-up time was 42.4 months (range, 1.6 to 108). Thus far, no patient with a stage I ovarian serous LMP tumor has developed recurrent disease. CONCLUSION: Stage I ovarian serous LMP tumors rarely, if ever, recur. Limited resection, after meticulous surgical exploration, is adequate therapy for women of reproductive age.

Preferential pericentric lesions and aneuploidy induced in mouse oocytes by the topoisomerase II inhibitor etoposide.

Etoposide (VP-16) is used as an antineoplastic drug in humans. It inhibits topoisomerase II(topoII) activity by forming a ternary complex (DNA-etoposide-topoII). This complex prevents the DNA-strand rejoining activity of topo II, which results in DNA-strand breaks and the formation of structural chromosome aberrations. Topo II activity is also required for removing regions of DNA catenation prior to chromosome segregation. The possibility exists that patients undergoing etoposide chemotherapy may incur genetic damage and, consequently, may be at a greater risk for developing secondary tumors and having genetically abnormal offspring. We studied the ability of etoposide for inducing both structural chromosome aberrations and aneuploidy in mouse oocytes. Different dosages of etoposide were given to female mice at various times before and after human chronic gonadotrophin injection, and ovulated oocytes were collected 17 h later. The proportions of chromatid acentric fragments and of hyperploid metaphase II oocytes were significantly higher (P < 0.01) in the etoposide groups than in concurrent controls. These results indicate that both structural and numerical aberrations can be induced without direct interaction with DNA or with the various organelles associated with chromosome segregation. Additionally, unlike other compounds (vinblastine, colchicine, benomyl, and griseofulvin) that induce both meiotic delay (ovulated metaphase I oocytes and polyploidy) and aneuploidy, etoposide did not cause meiotic delay in oocyte maturation.

Ifosfamide alone and in combination in the treatment of refractory malignant gestational trophoblastic disease.

OBJECTIVE: We attempted to evaluate the use of ifosfamide either alone or in combination in patients with refractory malignant gestational trophoblastic disease. STUDY DESIGN: Our study comprised, in part, a phase II multiinstitutional trial of ifosfamide in refractory gynecologic malignancies and, in part, a review of institutional experience with ifosfamide in combination chemotherapy. RESULTS: Single-agent ifosfamide produced a significant response in titer in one of two patients with refractory choriocarcinoma. Ifosfamide with etoposide and cisplatin (also known as VIP) resulted in significant response in human chorionic gonadotropin titers in three patients with highly refractory metastatic gestational trophoblastic disease and one cure in this group of patients. CONCLUSION: Ifosfamide has activity in refractory choriocarcinoma and, when combined with etoposide and cisplatin (VIP), may be curative.

Management of ovarian neoplasms of low malignant potential.

Ovarian epithelial carcinomas of low malignant potential occur at an earlier age and in an earlier stage than invasive ovarian carcinomas. A thorough knowledge of the histologic characteristics and adequate sampling are vital to making a correct diagnosis. Surgical resection alone is the treatment for Stage I disease, which accounts for 66% of all patients with this disease. Treatment of later stages is controversial, but surgical resection alone may also be adequate therapy for most patients with a more advanced stage. There is a small subpopulation of patients who die with a tumor of low malignant potential that, for poorly understood reasons, progresses.

Clinical-pathologic study of stage IIB, III, and IVA carcinoma of the cervix: extended diagnostic evaluation for paraaortic node metastasis--a Gynecologic Oncology Group study.

Three hundred twenty patients were entered into GOG Protocol 63, a clinical-pathologic study of stage IIB, III, and IVA cervical carcinoma. Following the completion of FIGO staging prerequisites, patients had computerized tomography (CT), a lymph-angiogram (LAG), and an ultrasound (US) of the aortic area. If any study was positive, a cytologic or histologic evaluation by fine-needle aspiration or selective paraaortic lymphadenectomy was performed. Paraaortic node dissection was mandated for patients with negative extended staging studies. Results of extended staging evaluations were compared with histologic or cytologic results. Two hundred sixty-four patients were eligible and evaluable. One hundred sixty-seven patients (63%) were stage IIB, 89 (34%) were stage III, and 8 (3%) were stage IVA. Positive paraaortic nodes occurred in 21% of stage IIB, 31% of stage III, and 13% of stage IVA. LAG sensitivity was 79% with a specificity of 73%. Sensitivity of CT and US was 34 and 19%, respectively, with specificities of 96 and 99%, respectively. The frequency of false-negative results with LAG for patients with stage IIB disease was 6%. This decrease is consistent with a stable sensitivity and specificity. These findings suggest that a negative LAG may be adequate to eliminate surgical staging in subgroups with low risk of metastasis to the aortic nodes. Until new noninvasive testing methods are developed, LAG appears to be the most reliable noninvasive examination to evaluate spread of cervical cancer to aortic nodes.

Echinomycin (NSC 526417) in advanced ovarian cancer. A phase II trial of the Gynecologic Oncology Group.

Twenty-two patients with recurrent carcinoma of the ovary progressive after initial chemotherapy (21 with cisplatin-based treatment) were entered on a phase II trial utilizing Echinomycin at a dosage of 1,500 micrograms/m2 every 4 weeks. There were two complete responders and no partial responders (9% response, 95% confidence intervals for complete and partial responses of 1-29%). Major toxicity was modest and consisted mainly of nausea and vomiting. Echinomycin displays minimal activity as salvage therapy in women with advanced ovarian cancer at this dose and schedule.

Intraoperative evaluation of depth of myometrial invasion in stage I endometrial adenocarcinoma.

In patients with stage I endometrial adenocarcinoma, the incidence of pelvic and para-aortic lymph node metastasis is related to the grade of the tumor and the depth of myometrial invasion. Although the grade of the tumor may be predicted preoperatively by endometrial sampling, the depth of myometrial invasion cannot be determined until after the uterus has been removed. Although complications have been attributed to lymph node sampling, failure to perform the procedure in patients at risk for nodal metastasis may result in underdiagnosis of extrauterine disease, leading to inadequate therapy. Gross visual examination of the cut surface of the tumor at the time of hysterectomy accurately determined the depth of myometrial invasion in 135 of 148 prospectively studied patients (91%) (P less than .001). The sensitivity of the test was 0.71, the specificity was 0.96, and the positive predictive value was 0.80. Intraoperative assessment of the depth of myometrial invasion is a simple, inexpensive, and useful technique for selecting those patients with stage I endometrial adenocarcinoma who might benefit from selective para-aortic lymphadenectomy.

Methotrexate-induced erythema multiforme.

The folic acid antagonist, methotrexate, has many applications in the treatment of neoplastic disease. While methotrexate produces several well-recognized toxic effects, cutaneous reactions are rare. A patient who developed classical erythema multiforme while receiving low-dose methotrexate as treatment of nonmetastatic gestational trophoblastic neoplasia is presented. Erythema multiforme has been associated with a variety of pharmacologic agents. It typically presents as a pruritic papular dermatitis of the extensor surfaces of the extremities and may require multiple skin biopsies to establish the diagnosis. Spontaneous reversal usually occurs with discontinuation of therapy. Patients developing erythema multiforme related to antineoplastic agents should be switched to an alternate regimen.

Vulvar dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans of the vulva is an extremely rare neoplasm. This low-grade sarcoma of the dermis clinically appears to be encapsulated but microscopically has tumor projections well away from the central nodules. Wide local excision is the recommended treatment for dermatofibrosarcoma protuberans; however, a more radical surgical approach may be needed to obtain clear surgical margins. The following case study present the fifth reported patient with this unusual neoplasm on the vulva.

Radical hysterectomy and pelvic lymphadenectomy for stage IB carcinoma of the cervix: 21 years experience.

From September 1971 through December 1982, 153 patients with Stage IB carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy at two of the teaching hospitals of the Uniformed Services University of the Health Sciences. Records were retrospectively analyzed and independent pathologic review was performed. All surgical procedures were performed by fellows or senior residents under the direct supervision of the gynecologic oncology staff of the Walter Reed Army Medical Center or the Naval Hospital, Bethesda, Maryland. In this series, IB carcinoma was defined as squamous carcinoma clinically confined to the cervix with invasion greater than 5 mm from the basement membrane or any adenocarcinoma confined to the cervix. The average age of the patients was 38.3 years. The histologic types were squamous in 72%, adenocarcinoma in 16%, and adenosquamous in 10.5%. The mean operating time was 5 hr and 40 min with an average blood loss of 1800 cc. There were two ureterovaginal and two vesicovaginal fistulae for an overall fistula rate of 2.6%. Actuarial survival for these 153 patients is 84%. This extends the previous series of R. C. Park, W. E. Patow, R. E. Rogers, and E. A. Zimmerman, Obstet. Gynecol. 41, 117-122 (1973) of 122 cases collected from 1961 to September 1971 to 275 cases. In comparing the two time periods, no significant differences were found in operative technique or complications, but there was a change in the incidence of adenocarcinoma and mixed cell types and a difference in survival. A relatively higher incidence of more aggressive tumors may indicate the need for different therapeutic approaches in the future.

Cervical carcinoma found incidentally in a uterus removed for benign indications.

Thirty-five patients with invasive cervical carcinoma discovered in a uterus removed for benign indications were evaluated and treated from 1961 through 1983. Although formal staging was not possible, patients with presumed stage IA disease had a 100% five-year survival rate regardless of the addition of adjuvant therapy. All patients with more advanced disease received radiation therapy. Patients with presumed stage IB disease had a corrected five-year survival rate of 78%, and those with presumed stage IIB disease had a corrected five-year survival rate of 67%. No patient in this series was thought to have disease more advanced than a stage IIB equivalent. The hysterectomy alone may have been adequate therapy for patients with presumed stage IA disease. Adjuvant radiation therapy appears to be effective treatment for patients with presumed stage IB or IIB disease.

The second-look surgical reassessment for epithelial ovarian carcinoma.

The second-look surgical reassessment is currently being performed on most patients with epithelial ovarian carcinoma after first-line chemotherapy if they are clinically free of disease. Ninety-six patients who underwent such procedures at Walter Reed Army Medical Center and the Naval Hospital, Bethesda, from January 1974 through May 1982 are reviewed. The grade of tumor, stage of disease, and amount of residual tumor remaining after initial surgery are predictive of the findings of the surgical reassessment. While a surgical reassessment is beneficial in evaluating response to therapeutic modalities under protocol investigation, its use should be individualized.

Use of the rhomboid flap after partial vulvectomy.

Primary closure of vulvar excisions is usually satisfactory in the anterior vulva, where the skin is mobile. In the posterior and posterolateral areas, however, closure often must be accomplished under tension with resulting wound breakdown and scar formation that can be disfiguring and cause dyspareunia. The rhomboid skin flap was described as early as 1946. Initially described for closure of facial defects, the technique has found application in the closure of a variety of traumatic and surgical defects. The authors present eight patients who underwent closure of vulvar defects using single or multiple rhomboid flaps. The applicability of the procedure to vulvar surgery is discussed and the technique is described.