Surgery for the treatment of locally recurrent disease.

BACKGROUND AND METHODS: Total pelvic exenteration is a salvage procedure done in the effort to eliminate completely pelvic cancer. Low colorectal anastomosis and continent urinary diversion are two new procedures that allow complete pelvic evisceration without the need for external appliances. From 1984 through 1994, 67 patients have undergone rectosigmoid colectomy and low-colorectal anastomosis. Sixteen patients underwent surgery as part of a total pelvic exenteration for recurrent cervical cancer, and 51 patients underwent surgery for either primary or recurrent ovarian carcinoma as part of an optimal debulking procedure. Between 1988 and 1995, 55 patients have received continent urinary diversion with the Miami Pouch. Fifty-two patients underwent surgery for recurrent cervical cancer, two patients for advanced vulvar cancer, and one patient for a vesico-vaginal fistula. All of the patients with recurrent cervical cancer had previously received radiation therapy for gynecologic cancer. RESULTS: Of the 16 patients with recurrent cervical cancer who had a low colorectal anastomosis, 14 had a temporary colostomy. Of these 14 patients, eight had a colostomy takedown and have maintained fecal continence. Of the 51 patients with ovarian cancer who had a low colorectal anastomosis, all achieved fecal continence. With the Miami Pouch, a urinary continence rate of 86% was obtained. Twenty-four (44%) patients had early complications, including ureteral obstruction, ureterocolonic anastomotic leak, reservoir cutaneous fistula, small bowel obstruction, and pyelonephritis. Nineteen (35%) patients had late complications, including ureteral reflux, urinary incontinence, difficult catheterizations, and reservoir stones. There was a perioperative mortality rate of 5%. CONCLUSIONS: Low-colorectal anastomosis is an attractive alternative to permanent colostomy, allowing all patients who had the protective colostomies taken down to achieve fecal continence. Continent urinary diversion with the Miami Pouch is also a worthwhile procedure because of its high continence rate. Although survival advantage for either procedure has not been proven, the quality of life of patients undergoing such procedures has been substantially improved because of the avoidance of external appliances. This has been achieved with acceptable morbidity and mortality rates.

Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study.

PURPOSE: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. METHODS AND MATERILAS: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery. RESULTS: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. CONCLUSION: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation.

Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study.

PURPOSE: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma. METHODS AND MATERIALS: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I--14, Stage II--40, Stage III--27, Stage IVA--5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m2/day for 96 hours and cisplatin 50 mg/m2 in weeks 1 and 5. RESULTS: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3-4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I--50%, Stage II--39%, and Stage III/IVA--38%. CONCLUSIONS: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.

Optimization of high dose-rate cervix brachytherapy; Part I: Dose distribution.

Computer controlled high dose-rate (HDR) brachytherapy afterloading machines are equipped with a single, miniaturized, high activity Ir-192 source that can be rapidly moved in fine increments among several channels. Consequently, by appropriate programming of source dwell positions and times, the dose distribution can be optimized as desired. We have explored the optimization potential of this new technology for two applications: (a) cervix brachytherapy, and (b) transvaginal irradiation. Cervix brachytherapy with a gynecologic ring applicator was simulated by 48 sources of relative activities ranging from 0.17 to 1.00 that were equally distributed between the tandem and the ring. The results confirmed that the optimized distribution of physical doses are superior to those achievable with standard brachytherapy sources and applicators. For example, with five-point optimization, the relative dose-rate in the rectum was only 47% of that in point A; for standard application the dose rate was 47% higher. For transvaginal application 27 sources of relative activities between 0.07-0.79 were placed in the ring and a single source of unit strength in the tandem. Using dose distribution homogeneity as an optimization criterion, the results (+/- 2.5%) were again superior to those obtained for commonly used double ovoid (+/- 15%), linear cylinder (+/- 27%), or a "T" source (31%).

Malignant melanoma of the vulva.

During the years 1969 to 1982, 16 patients with primary malignant melanoma of the vulva were entered into the Tumor Registry at the University of Miami Jackson Memorial Medical Center. The mean age was 55, with a range of 18 to 89 years. Treatment was primarily by radial vulvectomy with bilateral groin and pelvic node dissection. Survival was correlated to FIGO staging, Clark and Breslow classifications, and lymph node involvement. Survival correlated best to tumor thickness and Clark levels. Patients with Clark level 2 or less and less than 1.5 mm depth of penetration had the best prognosis. Lymph node involvement was present in 25% of the patients, and there were no survivors in this group. There were no instances of positive pelvic nodes when the groin nodes were negative, and routine pelvic lymphadenectomy is not recommended.

Ovarian cancer in women with prior hysterectomy: a 14-year experience at the University of Miami.

Between 1977-1990, 755 women were evaluated and treated for ovarian cancer at the University of Miami/Jackson Memorial Medical Center. Ninety-five of them (12.6%) had previously undergone hysterectomy with preservation of one or both ovaries. Sixty women (7.9%) had undergone hysterectomies after the age of 40. Review of the literature reveals a 4.5-14.1% incidence of prior hysterectomy in women developing ovarian cancer. Prophylactic oophorectomy in women undergoing hysterectomy at age 40 or older would have prevented 138 of 2632 cases (5.2%) of ovarian cancer in a combined literature series. Applied nationally, such an approach could be expected to prevent over 1000 cases of ovarian cancer annually. We recommend routine prophylactic oophorectomy in all women undergoing hysterectomy after the age of 40. This strategy would have prevented 60 cases of ovarian cancer treated at the University of Miami during the past 14 years.

Comparative efficacy of short-term versus long-term cefoxitin prophylaxis against postoperative infection after radical hysterectomy: a prospective study.

We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy.

Normal endometrial cells in Papanicolaou smears: prevalence in women with and without endometrial disease.

OBJECTIVE: To determine whether the prevalence of normal endometrial cells in Papanicolaou smears of women with and those without endometrial carcinoma or hyperplasia differs significantly. METHODS: Papanicolaou smears of women with biopsy-proved endometrial hyperplasia or carcinoma diagnosed between 1990 and 1998 were reviewed for the presence of normal endometrial cells. Chi-square and a power analysis were used to compare these smears with results of smears from women older than 35 years of age with tissue diagnoses other than hyperplasia or carcinoma. All Papanicolaou smears obtained within the 5 years before endometrial sampling were reviewed. Each patient had at least one smear done within the previous 12 months. Clinical information was available for all patients. RESULTS: Of the 201 women in whom endometrial hyperplasia (n = 103) or carcinoma (n = 98) was diagnosed, 4 (2%) had normal endometrial cells in otherwise negative Papanicolaou smears. Of the 289 women in the comparison group, 15 (5%) had normal endometrial cells in their Papanicolaou smears. The prevalence of normal endometrial cells did not differ significantly between the two groups (P =.071). The study had 80% power to detect a 5% or greater difference between groups. CONCLUSION: The prevalence of normal endometrial cells in Papanicolaou smears of women with endometrial carcinoma or hyperplasia does not significantly differ from that in women without these conditions. Reporting normal endometrial cells in Papanicolaou smears according to the recommendations of the Bethesda System may lead to unnecessary procedures and patient anxiety.

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.

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.

Recurrent cancer of the cervix following radical hysterectomy and pelvic node dissection.

Forty patients with recurrence following radical surgery for early invasive cancer of the cervix were studied. Fifty-eight percent of the recurrences were observed within the first 12 months after surgery and 83% within the first 2 years. The site of recurrence was found to influence diagnosis, symptomatology, clinical findings, prognosis, cause of death, and therapy. The prognosis for patients with recurrent cervical cancer was poor, with only 5 patients (13%) surviving free of disease after 5 years. One patient is presently alive and without disease for more than 2 years. Patients who did not receive a potentially curative course of radiation therapy at the time of diagnosis of the recurrence had a poor prognosis. None of the patients managed by exenterative procedures or chemotherapy survived. Guidelines are suggested for follow-up after primary radical hysterectomy and pelvic node dissection.

Invasive cancer of the cervix after cryosurgery. Pitfalls of conservative management.

Eight cases of invasive cervical carcinoma detected after cryotherapy for presumably noninvasive cervical lesions are reported. Three of these patients died from their disease less than 2 years following definitive therapy. The potential dangers of a less-than-optimal work-up of patients prior to freezing are analyzed and discussed in detail. Possible explanations for failures of cryotherapy are discussed, and guidelines for prevention of failures 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.

Gynecologic malignancies in older women.

The aging of the population is a social phenomenon that will present a challenge to clinical practice in the 21st century. Women constitute a majority of the elderly population as they outlive males by 5 to 7 years. Ovarian, endometrial, and vulvar cancers are diseases seen more commonly in postmenopausal and elderly women. Cervical cancer continues to be a significant problem in the elderly and is usually detected at a later stage in that population than in younger patients. Accordingly, primary care clinicians ought to possess a thorough knowledge of gynecologic malignancies and should refer women who present with these disorders to a gynecologic oncologist. Ovarian cancer patients treated by a gynecologic oncologist are more likely to undergo proper surgical staging, leading to optimal debulking surgery and improved survival. Age, by itself, should not alter the diagnostic and therapeutic approach to gynecologic malignancy. Elderly patients can safely undergo radical pelvic surgery. Multiagent chemotherapy is also possible in the elderly without excess morbidity, and without compromise of response rates. Radiation therapy for cervical cancer appears to be as effective and is generally well tolerated. The Papanicolaou (Pap) test continues to be the primary screening tool for cervical cancer. Although transvaginal ultrasound seems to be useful in detecting early-stage ovarian cancer, its cost effectiveness for screening the general population remains to be demonstrated. The main considerations in the treatment of ovarian, endometrial, cervical, and vulvar cancer are discussed.

History of gynecologic oncology subspecialty.

During the past quarter-century, progress has occurred in the area of coordinated care of the patient with gynecologic cancer. This progress is the result of the refined surgical techniques and perioperative management of patients requiring intensive care after radical pelvic surgery. Furthermore, the addition of radiation therapy and chemotherapy has made major contributions to the improvement and quality of life for patients with gynecologic cancer. All formal training programs in gynecologic oncology now include appropriate rotations and experience with these newer techniques and treatment modalities. The gynecologic oncologist should be fully equipped to manage primary treatment and most of the complications related to the care of patients with gynecologic neoplasms. Formal training programs in gynecologic oncology have been fundamental in the attainment of this goal and provide the infrastructure for future developments. It is anticipated that continued worldwide surgical studies in the area of gynecologic oncology will improve the well-being of women who may have cancer.

Neoplastic pericarditis and gynecologic malignancies--a review of the literature.

Neoplastic involvement of the heart/pericardium is not a common complication of gynecologic malignancies. However, as its occurrence can represent a substantial risk for the patient, it is important for the clinician to understand the pathophysiology, diagnosis, and treatment of this complication. An attempt, therefore, is made to review the pertinent clinical aspects of this condition with emphasis on the treatment options available.

Management of stage I-B, II-A, and II-B carcinoma of the cervix with high-dose-rate brachytherapy: initial results of an institutional clinical trial.

In 1989, the University of Miami began a program incorporating high-dose-rate (HDR) brachytherapy into the definitive treatment of patients with invasive carcinoma of the cervix. Patients received an average total dose to point A of 5,511 cGy (range 4,280-6,360 cGy) in an average of 57 days (range 39-84 days). An analysis of the first 24 cases found 11 FIGO Stage I-B, four Stage II-A, and nine Stage II-B tumors. At the end of all radiation therapy, 19/24 patients' tumors (79.2%) had undergone a clinical complete response (CR). With median follow-up of 26 months (range 14-63 months), three have relapsed locally, two regionally, and six in extrapelvic sites. Almost two-thirds of all failures occurred in patients with tumors >4 cm, who also took more than 8 weeks to complete their treatment. Overall 2-year actuarial survival for the entire study group is approximately 74%. A univariate analysis determined that clinical stage (P = 0.02), overall treatment time (P = 0.03), tumor size (P = 0.05), and response at the end of therapy (P = 0.005) were significant prognostic factors. Multivariate analysis showed that tumor response to therapy was the most important prognosticator of outcome (P = 0.001). Besides five cases of apical vaginal stenosis, there have been no reported chronic complications in this cohort of patients. A prospectively randomized trial is recommended to compare the efficacy of HDR vs. low-dose-rate brachytherapy in cervical carcinoma.

Fine needle aspiration cytology in gynecologic oncology. II. Morphologic aspects.

This study was based on the evaluation of 140 fine-needle spirations from gynecologic lesion. Cytologic criteria for the diagnosis of benign and malignant lesions and cellular changes due to irradiation and chemotherapy are presented. For accurate evaluation of fine-needle aspiration specimens from the pelvis, the exact location of the sampling must be known, clinical data must be available, and the patholgist must have an intimate knowledge of anatomy, histology and pathology of benign and malignant lesions in this area. Fine-needle aspiration cytology provided a high degree of accuracy in the diagnosis of gynecologic lesions.

Fine needle aspiration cytology in gynecologic oncology. I. Clinical aspects.

One hundred forty fine needle aspirations were performed on 124 patients with a variety of gynecologic conditions. The primary goal of this study was to investigate the adequacy of this technique in the primary diagnosis of pelvic masses and in the detection of persistent or recurrent gynecologic malignancies following irradiation or chemotherapy. In this, the first of two articles, the clinical aspects of the procedure, including clinical indications and the different approaches and pelvic sites of fine needle aspiration, are discussed. The simplicity and lack of complications of the method, combined with a high degree of accuracy in predicting the histologic picture of various lesions, merit wider application of this technique as a reliable diagnostic tool in gynecologic oncology.