Phase I-II study of combined 5-fluorouracil and cisplatin chemotherapy and altered fractionation radiotherapy for advanced squamous cell carcinoma of the cervix.

Forty patients with advanced carcinoma of the cervix were prospectively treated by an intermodality approach using chemotherapy combination concomitant with split-course hyperfractionated radiation therapy (RT). Cisplatin (CDDP) (60 mg/m2) was administered before radiotherapy initiation followed by 5-fluorouracil (5-FU) (750 mg/m2) for 5 days during the first week of irradiation. The same schedule was repeated in the last week of the RT, with 5-FU administration (1,000 mg/m2) for only 3 days. RT consisted of 5,020 cGy to the pelvis, followed by two intracavitary applications for a total of 5,000-5,500 mg/h radium equivalent when possible: 140 cGy/fraction was administered in the morning and evening, with a 6-h interval. The remainder of the external beam radiation was delivered at a standard daily fractionation of 180 cGy/fraction to a total dose of 5,020 cGy. This regimen of RT with concomitant chemotherapy had minimal toxicity and did not cause significant prolongation of the treatment program. However, a high rate of late complications was noted in patients who had extended-field RT due to paraaortic lymph node involvement. Thirty-two patients had complete response (CR) (80%). 24 (75%) of whom have no evidence disease (NED), with a median follow-up of 24 months. Our study suggests that this regimen of combined chemotherapy and RT in this group of patients with poor prognosis is effective and well tolerated, with acceptable acute toxicity and late morbidity.

Leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor.

OBJECTIVE: To evaluate leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor (GCT). STUDY DESIGN: We treated six patients who had recurrent or persistent ovarian GCT with monthly intramuscular injections of a depot formulation of leuprolide acetate, 7.5 mg. Four patients had received prior cisplatin-based chemotherapy. Initially these patients' tumors had responded to the cisplatin, but then the disease had progressed in all cases. One of these four patients also had received prior therapy with tamoxifen that had resulted in three months of stable disease. Two patients had received no prior chemotherapy. RESULTS: Responses could be evaluated in five of the six patients; in the sixth patient, only survival was evaluable. Among the five evaluable patients, two achieved partial responses lasting 3 and 11 months, with disease progression-free intervals of 4 and 12 months. The other three patients (60%; 95% confidence interval [CI], 20-95%), including two whose disease had progressed on chemotherapy, had stable disease with disease progression-free intervals of 3+, 3+ and 13+ months. The objective response rate was 40% (two of five patients; 95% CI, 10-90%). Cessation of disease progression was noted in all five of the evaluable patients (100%; 95% CI, 40-100%). The sixth patient, whose disease could not be evaluated, was treated with leuprolide acetate for 24 months and at this writing had no clinical evidence of disease. The therapy was convenient to administer, and no major side effects were noted. Leuprolide acetate thus appears to have activity in patients with refractory GCT, and it may prolong the disease progression-free interval. Further trials of this relatively nontoxic and convenient therapy are warranted.

Aggressive fibromatosis of the female pelvis. A case report and review of the literature.

Aggressive fibromatoses (desmoid tumors) are rare tumors of fibroblastic origin that may arise in any musculoaponeurotic structure with a propensity of infiltrate adjacent tissues, but not to metastasize. Tumors of musculoaponeurotic origin are seldom encountered by the gynecologist. A case of pelvic fibromatosis is reported together with a discussion of theories of etiology and management options.

Aggressive angiomyxoma of the pelvis and perineum. A case report.

BACKGROUND: Aggressive angiomyxoma of the female perineum and pelvis is a slowly growing neoplasm occurring almost exclusively in women of reproductive age. The tumor is characterized by its locally infiltrative behavior. The high recurrence rate has been attributed to incomplete surgical excision. CASE: A case of a huge, recurrent, aggressive angiomyxoma of the perineum and pelvis was treated. CONCLUSION: Correct preoperative diagnosis and assessment of simultaneous perineal and pelvic involvement indicate a combined abdominoperineal surgical approach to achieve wide, tumor-free margins.

Solitary breast metastasis as first manifestation of ovarian carcinoid tumor.

Carcinoid tumor metastatic to the breast is very uncommon. The rarity of this finding may be the reason for its common misinterpretation as primary breast carcinoma. A patient with primary ovarian carcinoid that presented initially with a solitary breast mass is reported. A review of the literature discloses only 12 reported cases of carcinoid tumor metastatic to the breast, with none of the primaries found to be the ovary.

Second primary cancer arising from the neovulva following reconstruction with myocutaneous flaps.

Myocutaneous flaps have been used for vulvar reconstruction following radical vulvectomy. For over 15 years the most common complications related to these flaps are sloughing of the skin and donor site wound infection. A new malignancy arising from the skin of the neovulva is an unusual occurrence. Two cases are presented. The skin of the neovulva may be exposed to the same neoplastic carcinogens that caused the initial lesion. In both patients, the polymerase chain reaction method failed to detect the presence of human papillomavirus DNA in either the initial lesion or the recurrent cancer.

Fallopian tube cancer metastatic to the breast.

The breast is an infrequent site of metastatic disease from a primary genital tract malignancy. A case of fallopian tube carcinoma metastasizing to the breast is presented. A solitary metastasis must be distinguished from the primary breast cancer as the treatment and prognosis are quite different. The pathologic diagnosis of metastatic carcinoma to the breast may be difficult if the tumor is poorly differentiated type.

Malacoplakia of the vagina presenting as a pelvic mass.

Malacoplakia is an unusual type of chronic inflammation that rarely involves the female genital tract. A case of malacoplakia involving the vaginal cuff of a patient previously treated by radical hysterectomy for cervical carcinoma is presented.

Vulvar malignancy.

Treatment of invasive vulvar malignancy has become more individualized during the past decade. In the past, radical vulvectomy with bilateral inguinofemoral lymphadenectomy was the standard therapy for invasive squamous cell carcinoma and melanoma of the vulva. This is no longer always the case. The treatment of stage I and stage II invasive squamous cell carcinoma of the vulva has become more individualized. Less radical surgery appears to produce the same results as ultraradical surgery. Wide local excision of early lesions associated with ipsilateral lymph node dissection appears to be adequate therapy in many cases. Likewise, treatment of early melanoma (0.75 mm in thickness) can be managed by wide local excision with or without groin dissection of the ipsilateral side. This more conservative approach has resulted in significantly fewer postoperative complications and has improved the self-image of many women undergoing treatment for vulvar malignancy.

Reconstructive techniques in gynecologic oncology: the use of human dura mater allografts.

Human dura mater has been utilized in various reconstructive procedures following radical pelvic surgery at the Division of Gynecologic Oncology, University of Miami School of Medicine. Our preliminary results indicate that this allograft is strong, durable, and acts as a good biological barrier. However, it does not seem to prevent the development of enteropelvic fistulae in patients who undergo total pelvic exenteration following radiotherapy. Dura mater has also been employed in abdominal hernia repairs, repair of wound dehiscenses, and in the coverage of the femoral vessels after groin dissection. Provisional results with these reconstructive techniques appear promising. These results are discussed, and suggestions regarding the use of this allograft are delineated.

Gastrointestinal surgery in gynecologic oncology: evaluation of surgical techniques.

In recent years, the use of surgical staples has become popular in all subspecialties of surgery. The advantages proposed have been a decrease in operative time and morbidity. This paper reviews the University of Miami/Jackson Memorial Medical Center, Division of Gynecologic Oncology experience with the use of surgical staples in gastrointestinal surgery on patients with a diagnosis of a gynecologic malignancy. Between January 1, 1979 and July 1, 1985, a total of 152 procedures were done, 81 by stapler and 71 by suture anastomosis. Ninety-one patients had received previous radiation or chemotherapy. The average age of the patients was 52 years. The results show a decrease in operating time, blood loss, and postoperative hospital stay in those patients where the stapler anastomosis was used. The postoperative morbidity and mortality were not increased. Twenty-seven total pelvic exenterations were performed during the period of study and they were evaluated separately. The hospital stay and blood loss as well as the operative time were significantly less using staplers. This report includes a detailed evaluation of the results. From this study, we concluded that surgical staples are a safe alternative in gastrointestinal surgery in patients with a gynecologic malignancy.

Human dura mater allografts in repair of pelvic floor and abdominal wall defects.

Freeze-dried human dura mater has been used as an allograft for reconstructive gynecologic surgery since 1980. So far, 33 grafts have been placed. This versatile and immunologically inert material has been used to reconstruct the pelvic floor after exenterative procedures, replace rectus fascia in the repair of wound dehiscence and ventral or parastomal hernias, and cover the femoral vessels after nodal dissection. In seven patients, dura mater was grafted into infected sites without subsequent rejection. Biopsy of an allograft one year after implantation confirmed the natural tendency of the body to convert the dura mater to a viable and neovascularized tissue. This reconstructive material is a safe and versatile allograft for gynecologic oncologists.

Small bowel complications after supravesical urinary diversion in pelvic exenteration.

Between June, 1966, and June, 1984, 102 pelvic exenterations were performed at Jackson Memorial Hospital/University of Miami Medical Center and all patients had some type of supravesical urinary diversion. Of these patients, 23 were reexplored for a gastrointestinal complication and 15 of those had a small bowel complication. Small bowel fistula occurred in 15 instances and 9 patients were reexplored. The fistula associated mortality was 53.3%. All the fistulas occurred in previously radiated patients who had undergone an enteroenteroanastomosis. The recent use of enterocolostomies after the construction of an ileal conduit in 21 patients has not produced any postoperative small bowel fistula, while in 43 patients who underwent enteroenterostomies, 13 fistulas occurred (P less than 0.01). Patients who did not undergo pelvic floor closure had a higher incidence of fistula and small bowel obstruction, while there were no fistulas in patients with previous enterocolostomies, regardless of the pelvic closure.

Antibiotic prevention of infections complicating radical abdominal hysterectomy.

In this randomized, double-blind study, the effectiveness of a single-agent prophylactic antibiotic in reducing infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy was compared with a placebo. A total of 12 doses of cefoxitin (2g) or placebo were given to 70 patients, starting the evening before surgery. Because of tumor spread beyond the cervix, radical hysterectomy was not performed in 17 patients who were, therefore, excluded from the study. Analysis of 53 patients who completed the study revealed that 15% of cefoxitin patients had surgical site-related infections compared with 52% of placebo patients (P = .005). Significant differences between the groups were also observed in nonsurgical site-related infections (23 versus 48%), overall morbidity (58 versus 89%), and the need for additional antibiotic therapy (38 versus 67%). Socioeconomic status was a significant risk factor with 57% of staff patients demonstrating increased site-related infections as compared with 17% of private patients (P = .002). No clinically significant side effects were observed. The authors recommend the use of antibiotic prophylaxis in patients undergoing radical abdominal hysterectomy for gynecologic malignancies.

Pelvic exenteration: a 15-year experience in a general metropolitan hospital.

Between June, 1966, and June, 1981, 92 pelvic exenterations were performed by gynecologic oncologists at Jackson Memorial Hospital/University of Miami Medical Center. The decrease in postoperative morbidity and mortality and the improved 5-year survival rate probably were related to improvement in hospital facilities and more refined surgical techniques. Urinary and gastrointestinal complications occurred with equal frequency during the period of study and were more common in patients who had received previous radiation therapy. On the basis of our experience, recommendations to decrease gastrointestinal and urinary complications further are presented.

Treatment of advanced or recurrent endometrial adenocarcinoma with cyclophosphamide, doxorubicin, cis-Platinum, and megestrol acetate.

A prospective clinical trial using combination chemotherapy consisting of cyclophosphamide, doxorubicin, cis-Platinum and megestrol acetate (CAP-M) was initiated to study its effect on advanced or recurrent endometrial adenocarcinoma. Fifteen patients were clinically evaluable. Nine patients (60%) demonstrated an overall objective clinical response resulting in either complete regression of disease (33%) or a reduction in tumor size. For all responders the mean progression free interval was eight months, with a range of five to 11 months. Similarly, a mean survival time of 12 months with a range of five to 21 months was observed. An additional four patients showed no progressive disease for a mean of seven months duration. Reversible cis-Platinum-induced nephrotoxicity occurred in two patients. This is the first reported series of endometrial cancer patients using nonhormonal cytotoxic agents, including cis-Platinum, in conjunction with a progestin. This preliminary experience is encouraging and appears worthy of further clinical evaluation.

Paget's disease of the skin. A unifying concept of histogenesis.

Utilizing the peroxidase antiperoxidase technique we explored the presence and the distribution of carcinoembryonic antigen (CEA) in seven cases of mammary and sixteen of extramammary Paget's disease of skin. In every case positive immunostaining was observed in all the Paget's cells and the underlying tumor (where one was present), whereas intervening keratinocytes and melanocytes did not stain. CEA was also present in the cells and secretions of normal eccrine and apocrine glands. Our observations confirm that Paget's cells are of glandular origin.

The Swan-Ganz catheter and its application in the gynecologic patient.

Swan-Ganz catheters were used in the pre- and postoperative management of 22 gynecologic patients admitted to the Surgical Intensive Care Unit, University of Miami School of Medicine. Primary indications include preoperative assessment of fluid and volume status, evaluation of patients with severe heart disease, and management of multisystem organ failure. Seventeen patients required ventilatory assistance and 15 patients required vasoactive drugs as determined by Swan-Ganz measurements. With a low complication rate and highly reliable cardiopulmonary data, the Swan-Ganz catheter should be considered routinely in the optimal management of the critically ill or high-risk gynecologic patient.