What is the role of conservative primary surgical management of epithelial ovarian cancer: the United States experience and debate.

Certification in Gynecologic Oncology and creation of the Society of Gynecologic Oncologists in the United States have led to the development of a specialty with individuals capable of performing complex abdominal and pelvic operations in the management of epithelial ovarian carcinoma. These operations can be divided into two types. 1) A staging operation to assess the extent of disease through careful palpation, histologic and cytologic assessment of all peritoneal surfaces along with removal of the uterus, ovaries and fallopian tubes, omentum, together with a bilateral pelvic and aortic lymphadenectomy. Such information allows the clinician to determine prognosis and if postoperative adjuvant therapy is indicated. 2) A debulking operation designed to resect or reduce the size of metastatic lesions as well as to remove the primary tumor including a bilateral salpingo-oophorectomy. This operation is designed to improve survival and cure. In spite of this apparently clear paradigm, there has been a steady debate as to the apparent justification of these operations, especially when the former is performed in a women who has not completed her childbearing and especially when the latter requires "ultraradical" procedures. Many feel that the pendulum is now swinging toward fertility-sparing surgery among young women with early invasive cancers and toward either neoadjuvant chemotherapy or less than ultraradical debulking among women with advanced ovarian cancer. The purpose of this study is not to provide an exhaustive review but rather to outline this debate and focus on the American experience with conservative surgery in the management of epithelial ovarian carcinoma.

Chemoradiation: A new approach for the treatment of cervical cancer.

Despite advances in screening, cervical cancer remains a major health problem worldwide. In an effort to improve loco-regional control, both neoadjuvant and chemoradiation have been trialed. Recently, five randomized clinical trials performed by the Gynecologic Oncology Group, the Radiation Therapy Oncology Group and the Southwest Oncology Group have demonstrated a significant advantage both in progression-free and overall survival when cisplatin-based chemotherapy was administered during radiation for advanced stages of cervical cancer. Based on the results of these trials, the US National Cancer Institute released a Clinical Announcement supporting the concurrent use of cisplatin-based chemotherapy with radiation therapy for high-risk early stage and locally advanced stage cervical cancer. Subsequently, an additional prospective randomized trial performed by the National Cancer Institute of Canada was not able to show benefit with the use of chemoradiation compared with radiation alone for patients with locally advanced stage cervical cancer. This article will analyze these six clinical trials in order to determine the role of chemoradiation in the management of patients with cervical cancer. Furthermore, as anemia is one of the most powerful prognostic factors in patients with cervical cancer, we propose to evaluate the relationship between a decreased level of hemoglobin and treatment outcome.

Recent advancements in the treatment of epithelial ovarian cancer.

Important advances in the management of advanced epithelial ovarian cancer have been made in recent years, with much of the knowledge emanating from clinical trials conducted by the Gynecological Oncology Group (GOG). This monograph reviews the trials that have defined current clinical practice and summarizes some innovative techniques and promising new drugs for the future

Bilateral pheochromocytoma in pregnancy heralding multiple endocrine neoplasia syndrome IIA. A case report.

BACKGROUND: Multiple endocrine neoplasia syndrome type IIA (MEN IIA) has rarely been encountered in pregnancy. CASE: A 22-year-old, nulliparous woman developed bilateral pheochromocytomas during pregnancy. This finding aroused suspicion for MEN IIA, and close endocrinologic follow-up was arranged. Four years later, hyperparathyroidism developed, and the diagnosis was established. The patient underwent prophylactic total thyroidectomy with parathyroid exploration. CONCLUSION: This was the first case of MEN IIA in pregnancy in which the diagnosis was established prior to the development of medullary thyroid cancer, thereby allowing prophylactic thyroidectomy. The presence of bilateral neoplastic disease in young patients may be indicative of a hereditary predisposition to malignancy.

Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring.

OBJECTIVE: The aim of this study was to determine whether 2 photosensitizers, benzoporphyrin-derivative monoacid ring and 5-aminolevulinic acid, are selectively absorbed by dysplastic cervical cells after topical administration. STUDY DESIGN: This phase I clinical trial involved 18 women with biopsy-proven cervical intraepithelial neoplasia at the Beckman Laser Institute, Irvine, Calif. Colposcopically directed cervical biopsy specimens obtained after 1.5, 3, or 6 hours of exposure to a randomly assigned photosensitizer were evaluated for selective drug absorption with hematoxylin and eosin staining and fluorescence microscopy. RESULTS: After exposure to 5-aminolevulinic acid, cervical tissue showed maximal fluorescence in dysplastic cells relative to normal cells, with negligible stromal fluorescence. According to our detection methods benzoporphyrin-derivative monoacid ring demonstrated nonselective, diffusion-driven uptake, with fluorescence appearing in the superficial cells, followed by nonselective drug absorption in the remaining cells and stroma of the epithelium. CONCLUSION: Our data demonstrated selective absorption of 5-aminolevulinic acid by dysplastic cervical cells. This agent therefore represents a promising photosensitizing prodrug for the treatment of cervical intraepithelial neoplasia with photodynamic therapy.

Primary invasive carcinoma of the vagina: treatment with interstitial brachytherapy.

BACKGROUND: Because primary carcinoma of the vagina comprises less than 2% of all gynecologic malignancies, the reported experience in the treatment of large numbers of patients is available only from a few major centers and most often encompasses a variety of differences in treatment selection and technique. The objective of this study was to assess the long term results of an interstitial iridium-192 afterloading implant technique using the Syed-Neblett dedicated vaginal plastic template. METHODS: Patients who were treated from 1976 to 1997 were examined retrospectively. RESULTS: Seventy-one patients underwent interstitial implantation with (n = 61 patients) or without external beam radiotherapy. The median age was 59 years (range, 16-86 years). Patients were staged according to the International Federation of Gynecology and Obstetrics system and included Stage I (n = 10 patients), Perez modification Stage IIA (n = 14 patients), Perez modification Stage IIB (n = 25 patients), Stage III (n = 15 patients), and Stage IV (n = 7 patients). Each implant delivered an approximately 20-gray (Gy) minimum tumor dose, with the total tumor dose reaching 80 Gy with integrated external beam radiotherapy. Local control was achieved in 53 patients (75%). The median follow-up was 66 months (range, 15-163 months), and the 2-year, 5-year, and 10-year actuarial disease free survival rates are 73%, 58%, and 58%, respectively. By stage, 5-year disease free survival rates included Stage I, 100% of patients; Stage IIA, 60% of patients; Stage IIB, 61% of patients; Stage III, 30% of patients; and Stage IV, 0% of patients. The factors disease stage and primary lesion size independently influenced the survival rates. Significant complications occurred in 9 patients (13%) and included necrosis (n = 4 patients), fistulae (n = 4 patients), and small bowel obstruction (n = 1 patient). CONCLUSIONS: Interstitial irradiation can effect local control in the majority of patients with primary carcinoma of the vagina with acceptable morbidity. Long term cure is demonstrable in patients with Stage I-III disease.

Estrogen replacement therapy in endometrial cancer patients: a matched control study.

OBJECTIVE: To determine if estrogen replacement therapy, in women with a history of endometrial cancer, increases the risk of recurrence or death from that disease. METHODS: Two hundred forty-nine women with surgical stage I, II, and III endometrial cancer were treated between 1984 and 1998; 130 received estrogen replacement after their primary cancer treatments and 49% received progesterone in addition to estrogen. Among this cohort, 75 matched treatment-control pairs were identified. The two groups were matched by using decade of age at diagnosis and stage of disease. Both groups were comparable in terms of parity, grade of tumor, depth of invasion, histology, surgical treatment, lymph node status, postoperative radiation, and concurrent diseases. The outcome events included the number of recurrences and deaths from disease. RESULTS: The hormone users were followed for a mean interval of 83 months (95% confidence interval [CI] 71.0, 91.4) and the nonhormone users were followed for a comparable mean interval of 69 months (CI 59.1, 78.7). There were two recurrences (1%) among the 75 estrogen users compared with 11 (14%) recurrences in the 75 nonhormone users. Hormone users had a statistically significant longer disease-free interval than nonestrogen users (P =.006). CONCLUSION: Estrogen replacement therapy with or without progestins does not appear to increase the rate of recurrence and death among endometrial cancer survivors.

Bowel resection at the time of primary cytoreduction for epithelial ovarian cancer.

BACKGROUND: The purpose of this study was to determine the morbidity and survival associated with bowel resection at the time of primary cytoreductive surgery for ovarian cancer. STUDY DESIGN: We reviewed all patients undergoing bowel resection by gynecologic oncology faculty at the time of primary cytoreduction for advanced epithelial ovarian cancer diagnosed between 1983 and 1995. RESULTS: There were 105 patients meeting the above criteria. The median age was 65 years (range 34 to 85 years). There were 76 stage III and 25 stage IV cancers. The primary indication for bowel resection was tumor debulking in 92% of the patients. Seventy patients had segmental resection of the colon only, and 22 patients underwent resections that included the large and small bowels. Mean operating time was 260 minutes and mean estimated blood loss was 1,447 mL. Thirty-three (31%) patients were optimally cytoreduced to less than 1 cm residual disease. Ten patients experienced major complications directly related to bowel resection, including bowel fistula (4 patients), early postoperative bowel obstruction (5 patients), and stomal hernia (1 patient). Other morbidity included ileus for more than 10 days (18 patients), cardiac complications (17 patients), pneumonia (8 patients), sepsis (5 patients), and thromboembolism (4 patients). Six patients died and five patients required reexploration within 30 days of operation. Patients with preoperative bowel obstruction and suboptimal residual disease were more likely to have postoperative morbidity. Median survival in the optimally debulked patients was 35 months compared with 18 months in patients suboptimally cytoreduced (p = 0.006). Multivariate analysis demonstrated that optimal debulking (p = 0.009) and platinum chemotherapy (p = 0.00006) were independently associated with improved survival. Age, International Federation of Gynecologia Oncologists stage, American Society of Anesthesiologists class, and paclitaxel chemotherapy did not influence survival. CONCLUSIONS: In patients undergoing bowel resection at the time of primary cytoreduction for ovarian cancer, optimal cytoreduction to less than 1 cm residual disease results in improved survival. Morbidity is common but is comparable to other published series of ovarian cancer patients undergoing primary cytoreductive surgery without bowel resection. Additionally, patients with preoperative bowel obstruction and suboptimal residual disease are more likely to have serious morbidity.