Recurrent ascites and pleural effusions after surgery for early-stage endometrial adenocarcinoma.

A case of massive postoperative ascites in a woman treated for endometrial cancer is reported. A workup for typical causes of ascites yielded negative results, prompting a more detailed analysis of the patient's condition. Hypothyroidism was discovered. After correction of the hypothyroidism, the ascites slowly resolved. Since myxedema is an uncommon cause of ascites, this is usually a diagnosis of exclusion. However, hypothyroidism must be ruled out to prevent unnecessary and possibly inappropriate treatments for ascites.

Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group.

PURPOSE: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy. METHODS AND MATERIALS: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. RESULTS: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects. CONCLUSION: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.

Management of the adnexal mass in the 1990s.

BACKGROUND: Ovarian carcinoma is the leading cause of deaths from female genital cancers in the United States. During the last three decades, advances in diagnostic techniques, surgical techniques, and adjuvant chemotherapy have led to improved survival in some patients who have an adnexal mass that is later diagnosed as malignant. METHODS: A review of the current technique, compiled with our changing management, was done to help identify possible pitfalls in the initial management of the adnexal mass in specific age groups. The expensive and controversial issues such as screening, management of patients with a genetic history, and management with laparoscopy were reviewed. RESULTS: Appropriate initial surgery improves survival in patients with adnexal masses, later determined to be malignant, particularly when adjuvant, modern combination chemotherapy is used. Laparoscopy for suspicious adnexal masses cannot be condoned, unless immediate appropriate surgical staging can be done. CONCLUSIONS: Awareness and implementation of current diagnostic and treatment modalities can improve survival in the patient with an adnexal mass that is later found to be malignant.

An update on the diagnosis and treatment of common malignant ovarian tumors.

Malignant ovarian tumors are the second most common female type of genital tract cancers, and they are the leading cause of death of women with such malignancies. Over the last 2 decades, advances in epidemiology, diagnostic techniques, and treatment have led to earlier diagnoses and to improved survival, particularly for patients with germ cell tumors. The purpose of this review is to acquaint practicing physicians with the advantages and pitfalls of 1990's diagnostic techniques and to guide them on when to refer. Emphasis will be given to performing the appropriate operation the first time. Adjuvant chemotherapy with newer combined regimens may improve survival in some patients with epithelial ovarian cancer and has been shown to improve survival in patients with germ cell tumors.

Characteristics of patients with rapidly growing cervical cancer.

Between April 1983 and December 1990, 387 newly diagnosed cervical cancer cases were managed at our institution. We retrospectively reviewed 59 of those cases, which were identified as having developed within 3 years of the patients' last normal Pap smear. Squamous cell carcinoma was found in 45 patients, and 33 had poorly differentiated lesions. Six cases had typical histology. However, 27 cases (82%) had distinctive histologic features that have not been previously described in rapidly progressive cervical cancer. Thirty-seven patients had surgical treatment; 7 (19%) died of disease. Twenty-two patients had radiation; 10 (45%) died of disease. Patients who have invasive cervical cancer after a recent normal Pap smear may have unusual histologic types, and some with early-stage disease may have better outcome if treated with radical surgery.

Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG production.

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.

A phase II trial of 5-fluorouracil and high-dose leucovorin in patients with recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

The addition of leucovorin to 5-fluorouracil (5-FU) has been shown to improve the response rate in recurrent colon cancer. The combination of low-dose leucovorin and 5-FU was previously tested by the Gynecologic Oncology Group (GOG) and did not produce response rates greater than rates using 5-FU alone. From June 1990 to April 1992, 55 patients with unresectable recurrent squamous cervical cancer received high-dose leucovorin at 200 mg/m2 i.v. bolus, followed by 5-FU at 370 mg/m2 i.v. bolus daily for 5 days every 4 weeks for the first two courses. Subsequent courses were given every 5 weeks. The median number of courses delivered was two (range 1-15). Fifty patients were evaluable for toxicity and 45 for response. Prior radiotherapy had been given to 43 patients and prior chemotherapy to 38. The overall response rate was 8.8% (95% confidence interval, 2.5-21.2%). There were two complete responses (4.4%) and two partial responses (4.4%). One response was in the pelvis and three were outside the pelvis. None of the extrapelvic responses had received irradiation at the site of measurable disease. The major adverse effect was granulocytopenia, with 15/50 (30%) experiencing GOG grade 3 or 4 granulocytopenia. The median white blood count for patients experiencing leukopenia was 2,000 (range 400-3,800). Grade 3 or 4 gastrointestinal toxicity was seen in 12 patients (24%). In this pretreated population, patients receiving high-dose leucovorin with 5-FU had moderate toxicity but only minimal activity.

Use of a subcutaneous closed drainage system and antibiotics in obese gynecologic patients.

OBJECTIVE: The purpose of this study was to evaluate the effect of subcutaneous closed drainage systems and prophylactic antibiotics on the wound breakdown rate in obese patients undergoing gynecologic surgery. STUDY DESIGN: A prospective study was performed on 197 obese patients who were randomly selected to have a subcutaneous drain. Incision closure technique was standardized. Antibiotic usage was not randomized. Demographic data, perioperative data, and postoperative complications were noted and analyzed by X2 test and 2 x 2 contingency tables. RESULTS: The overall complication rate was 25%, with 20% (22/109) among the group receiving a drain versus 31% (27/88) without a drain. Seventeen patients (8.6%) had wound breakdowns: 7 of 109 (6.4%) with drains and 10 of 88 (11.4%) without drains. Prophylactic antibiotics were given to 46% (50/109) in the drain group and 51% (45/88) without a drain. Fewer patients (2%) with a drain receiving antibiotics had wound breakdowns. The group with the most breakdowns had neither a drain nor antibiotics (14%). CONCLUSION: We suggest the use of subcutaneous drains plus prophylactic antibiotics may decrease morbidity when operating on obese gynecologic patients.

Mitotic count, nuclear atypia, and immunohistochemical determination of Ki-67, c-myc, p21-ras, c-erbB2, and p53 expression in granulosa cell tumors of the ovary: mitotic count and Ki-67 are indicators of poor prognosis.

In spite of extensive research, the behavior of granulosa cell ovarian tumors remains unpredictable and is complicated by the lack of prognostic factors in early-stage disease. Forty patients with granulosa cell tumors were identified from tumor registries and data were analyzed for patient outcome. Mitotic count and nuclear atypia were determined at time of histological review. Paraffin-embedded archival tumor tissues from 32 of 40 patients were available, and immunohistochemical testing for Ki-67, c-myc, p21-ras, c-erbB2, and p53 was performed on archival tissues. Results were correlated with patients' outcome. Mitotic count and Ki-67 were found to be negatively associated with survival in granulosa cell tumors. Nuclear atypia, c-myc, p21-ras, c-erbB2, and p53 were not found to be of prognostic significance.

Carcinoma of the vulva in young women.

OBJECTIVE: To determine if young women with carcinoma of the vulva have a different risk factor history and outcome compared with older women. METHODS: We conducted a retrospective review of the medical records of 78 women treated at the Medical College of Georgia for squamous carcinoma of the vulva during 1979-1993. Women younger than 45 years were compared with those 45 and over for historic risk factors, treatment modality, and outcome. RESULTS: Over the study interval, the average presenting age of these patients decreased from 69 to 55 years. Women under 45 were found to have a stronger history of condyloma (P < .001, 95% confidence interval [CI] 3.69-87.96). There was no significant difference by age in the duration of symptoms before presentation, smoking history, or tumor size. Women 45 and over were more likely to have advanced-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV) (P = .03, 95% CI 0.43-0.91). Treatment did not differ significantly with age. In a univariate analysis, advanced FIGO stage, presence of metastases, and tumor size were associated with shorter survival. There was no detected difference in survival for women in either age group. CONCLUSION: There appears to be a trend in our patient population toward younger women presenting with squamous carcinoma of the vulva. Human papillomavirus infection appears to be more common in younger women with vulvar carcinoma. There may be a difference in the etiologies producing squamous carcinomas of the vulva. Education encouraging the early detection and prevention of sexually transmitted diseases might alter the rising incidence of this disease in younger women.

Phase II trial of mitomycin-C in squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

Fifty-six patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix not previously exposed to cytotoxic drugs, other than as radiosensitizers, were entered into a study of single-agent 20 mg/m2 mitomycin-C every 6 weeks. The overall response rate among the 52 patients evaluable for response was 12% (three complete and three partial responses). Median response duration was 7.3 months. For the entire population, median progression-free interval was 3.0 months, and median survival was 4.9 months. Among 27 patients with pelvic disease only in previously radiated fields, two responses were observed (7%), whereas four responses were observed among 25 patients with extrapelvic disease in nonradiated fields (16%). The most frequent and severe adverse effects were the result of myelosuppression. Based on the modest level of activity observed, no further study of mitomycin-C in squamous cell carcinoma of the cervix is planned.

Long-term remission of previously resistant choriocarcinoma with a combination of etoposide, ifosfamide, and cisplatin.

A 30-year-old white female was diagnosed with gestational trophoblastic disease in 1981. Despite an original World Health Organization score of 4 and initial aggressive combination chemotherapy, she was treated over a 9-year period with multiple chemotherapy agents and had undergone several operative procedures to remove metastatic lesions for persistent disease. Long-term remission has now been obtained after four courses of etoposide, ifosfamide, and cisplatin.

Retroperitoneal dissemination of cervix cancer following surgical staging.

Retroperitoneal and cutaneous dissemination of cervical carcinoma occurred following an extraperitoneal surgical staging procedure. This type of event may be rare or merely underreported in surgical staging literature. Extraperitoneal and laparoscopic staging procedures that result in piecemeal removal of tissue should be studied for the incidence of this type of recurrence.

Large loop excision of the transformation zone (LLETZ): a pathologic evaluation.

Forty-six LLETZ cone biopsies were performed at the Medical College of Georgia from January 1991 through December 1991. All LLETZ cones were performed for diagnostic reasons following colposcopic biopsies. The majority of procedures were done by residents in obstetrics and gynecology with direct faculty supervision. All specimens were critically evaluated by one pathologist with regard to specimen orientation, thermal artifact, margins, histologic diagnosis, and overall specimen adequacy. The median number of specimens obtained per patient was two, with a maximum of eight. Sixteen patients had a separate endocervical specimen obtained. Thermal artifact was graded as slight in 16 cases, moderate in 18 cases, and severe in 12 cases. The transformation zone was identified in 33 cases. Margins were positive in 17 cases, negative in 21 cases, and nonevaluable in 8 cases. Only 13 LLETZ specimens were believed to compare in quality to a cold-knife cone biopsy. The main criticism about the specimens was the effect of thermal artifact on critical histologic evaluation. In three cases, the thermal artifact precluded an accurate enough evaluation to rule out microinvasion. Mucosa missing at the margins or inadequate representation of the transformation zone were major reasons to call a specimen inadequate. Endocervical specimens suffered the most thermal injury. Orientation of fragmented cone specimens present a problem in histologic evaluation. A major emphasis needs to be placed on the proper indications for LLETZ cone biopsy as well as education of practitioners and pathologists in proper specimen handling.

Phase II trial of menogaril in patients with squamous carcinoma of the cervix: a Gynecologic Oncology Group study.

A phase II trial of 200 mg/m2 menogaril was conducted by the Gynecologic Oncology Group (GOG) in women with advanced or recurrent squamous carcinoma of the cervix who had received no previous chemotherapy. Twenty-three patients were placed on the study; 22 are evaluable for toxicity and for response. One patient had incomplete data and was inevaluable. Nine patients (40.9%) had previously undergone surgery, and 21 (95.5%) had received radiotherapy before this trial. GOG grade 3 granulocytopenia occurred in 1 patient (4.5%) but none developed grade 3 or 4 thrombocytopenia. One patient (4.5%) had grade 3 gastrointestinal toxicity. Neither complete nor partial responses were observed in this trial, although 9 patients (40.9%) had stable disease lasting 2 months or more. Menogaril at this dose and schedule is inactive in advanced or recurrent squamous carcinoma of the cervix.

Paraaortic lymph node sampling by means of an extraperitoneal approach with a supraumbilical transverse "sunrise" incision.

OBJECTIVES: Extraperitoneal approaches to removal of lymph nodes for staging in cervical cancer patients are numerous, and each has disadvantages. We developed a supraumbilical transverse incision to initiate irradiation within days of cervical cancer staging. STUDY DESIGN: Twenty patients with advanced stage IIB or IIIB cervical cancer underwent surgical staging with a supraumbilical incision during the time period Jan. 1, 1988, to Aug. 1, 1992. The incisions were made 6 cm above the umbilicus and carried laterally in a caudad manner to the iliac crests. All nodes were removed in an extraperitoneal fashion. RESULTS: In the 20 patients who were operated on, the mean number of nodes removed was 9.8. Estimated blood loss ranged from 50 to 300 ml. The procedure time ranged from 50 to 150 minutes. All patients but two had irradiation initiated within 2 weeks of the procedure. Complications included an identified and repaired ureteral injury, a prolonged ileus, and a small bowel obstruction. CONCLUSIONS: An extraperitoneal approach with the "sunrise" incision allows irradiation to begin within days of surgery. The operating time is relatively short. The incision can be extended caudally and extraperitoneally if needed for removal of bulky pelvic nodes.

The gynecologist and multiple organ failure syndrome (MOFS).

Multiple organ failure syndrome (MOFS) has been alluded to since the early 1940s. It was recognized as a progressive failure to organs in the mid 1970s. Mortality from this syndrome increases proportionally, as the number of failed organs increases. Therapies to prevent MOFS and current concepts about treating failures of individual organs will be presented. Data sources were retrieved from critical care and surgical literature using MEDLINE from 1966 to the present. Searches were confined to English. Several promoters of MOFS are related to the care of gynecologic patients, especially sepsis and hemorrhage. Treatment strategies, especially those related to pulmonary, gastrointestinal, renal, cardiovascular, and nutritional aspects are discussed. Outcome and prognosis may be affected if recognition and therapeutic intervention are initiated early in the clinical course. The ability to prognosticate outcome is related to the number of organs involved. Gynecologists should have clear knowledge of the prognosis of progressive organ failure in order to appropriately counsel the patient and her family.