Chemotherapy for malignant mixed Müllerian tumors of the ovary.

OBJECTIVE: The aim of this study was to review the chemotherapy experience at Magee-Womens Hospital for malignant mixed müllerian tumor (MMMT) of the ovary. Patients were treated with either paclitaxel/carboplatin (PC) outpatient chemotherapy or platinum/ifosfamide (PI) inpatient chemotherapy as first- or second-line therapy. METHODS: Thirteen patients diagnosed with MMMT of the ovary after complete surgical staging from 1990 to 1999 were studied retrospectively. Six patients received PC combination chemotherapy, of which 3 patients received PC as first-line treatment. The other 3 patients received PC as second-line therapy. Eight patients were treated with PI. Demographic data, pathology, cytoreductive surgery, treatment, and survival rates were reviewed. Complete clinical response (CR) was defined as the disappearance of all measurable disease or normalization of elevated CA 125 level after chemotherapy. Kaplan-Meier analysis was used for survival analysis. RESULTS: The median survival time of patients receiving PC was 19 months. One patient, after receiving PC as first-line treatment, demonstrated a CR and is free of disease beyond 33 months. The median survival time of patients managed with PI was 23 months. Three patients with suboptimal disease demonstrated CR after receiving PI. CONCLUSIONS: Optimal chemotherapy regimen for MMMT of ovary remains to be determined. Platinum-based chemotherapy in combination with ifosfamide or paclitaxel may be active against this rare malignancy.

Use of preoperative MR imaging in the management of endometrial carcinoma: cost analysis.

PURPOSE: To compare the cost of magnetic resonance (MR) imaging and its ability to direct the use of lymph node dissection with the cost and ability of conventional surgery for the staging of endometrial carcinoma. MATERIALS AND METHODS: Preoperative MR images of 25 patients who underwent hysterectomy for endometrial carcinoma were retrospectively evaluated. MR imaging results were compared with those of intraoperative gross dissection of the uterus and final histopathologic examination. Medicare reimbursements for two scenarios were compared in each patient. In the MR imaging scenario, the necessity for lymph node dissection was based on MR imaging results and histologic findings at biopsy. In the actual scenario, lymph node dissection was performed at the surgeon's discretion on the basis of findings at gross dissection of the uterus and histologic examination at biopsy. RESULTS: The cost of the MR imaging scenario, as defined by Medicare reimbursements, was 1% ($1, 265/$148,500) less than that of the actual scenario. In the MR imaging scenario, all patients who required lymph node dissection received it, and 86% of the lymph node dissections performed were necessary. In the actual scenario, one necessary lymph node dissection was not performed, and only 31% of the lymph node dissections performed were necessary. CONCLUSION: Staging with MR imaging has costs and accuracy similar to those of the current method of staging with intraoperative gross dissection of the uterus. In addition, MR imaging decreases the number of unnecessary lymph node dissections.

Complete clinical responses to neoadjuvant chemotherapy for uterine serous carcinoma.

Three cases of serous carcinoma of the uterus with radiographically documented widespread metastases are presented. Following confirmation of histopathology, all were treated with a standard regimen of carboplatin and paclitaxel for eight courses with complete resolution of distant metastases on CT scan prior to postchemotherapy surgical exploration. Two patients had gross disease at laparotomy, and one had only microscopic tumor found in the uterine specimen. This experience offers rationale for treatment of patients with widely metastatic uterine serous carcinoma or other relative contraindications to surgery with primary carboplatin and paclitaxel. In addition, we believe this experience supports the hypothesis that this regimen may result in prolonged disease-free survival when employed as postsurgical adjuvant therapy.

Metastatic complete hydatidiform mole with a surviving coexistent twin. A case report.

BACKGROUND: Complete hydatidiform molar pregnancy with a coexistent live fetus is a rare clinical entity with poor fetal survival and an uncertain maternal risk. CASE: A twin gestation consisting of a complete molar pregnancy as one twin and a normal second "twin" was identified in the second trimester. The patient was managed expectantly until 28 weeks' gestation, at which time evidence of metastatic trophoblastic disease was identified. She delivered a healthy infant by cesarean section and received postoperative single-agent chemotherapy. She was disease free six months after treatment. CONCLUSION: Patients with documented complete molar pregnancies and coexistent live fetuses present several complex clinical issues. Though successful in some instances, expectant management should be used with caution in these patients.

CA 125 may not reflect disease status in patients with uterine serous carcinoma.

BACKGROUND: Although CA 125 level correlates with response to therapy in patients with serous carcinoma of the ovary, the utility of CA 125 in patients with high risk or metastatic endometrial carcinoma has not been established. METHODS: CA 125 was tested as a marker of disease status in patients with endometrial serous carcinoma (SC) undergoing adjuvant chemotherapy. All patients received monthly intravenous chemotherapy with cisplatin, cyclophosphamide, and doxorubicin at standard doses (median number of courses, 6; range, 2-8 courses). Serum CA 125 was measured at diagnosis and before each course. After the completion of chemotherapy, patients were examined every 3 months and the CA 125 level was measured. RESULTS: A total of 220 serum specimens from 15 patients with invasive SC were analyzed. All five patients who died of disease had clinical or radiographic evidence of tumor, which CA 125 elevation did not precede or predict. One patient with advanced disease at staging never had an elevated CA 125 level but died of disseminated disease 14 months after diagnosis. At last follow-up, 3 patients who were without evidence of disease > 36 months from diagnosis had significant false-positive elevations in their CA 125 level (>50 u/mL) lasting 1, 2, and 4 months, respectively, during therapy. The sensitivity for advanced disease was only 57% at presentation. CONCLUSIONS: CA 125 may reflect advanced stage disease and portend a poor prognosis, but may not add information to that gained by history and physical examination, preoperative studies, or surgery that already is mandated by this high risk histology. This circulating marker appears to have limited utility in monitoring the effects of adjuvant therapy for SC, and may not predict recurrence in the absence of other clinical findings.

A phase II study of irinotecan (CPT-11) in patients with advanced squamous cell carcinoma of the cervix.

BACKGROUND: This study was conducted to determine the efficacy and safety of irinotecan (CPT-11) as second-line therapy in patients with advanced cervical carcinoma. METHODS: Sixteen patients with platinum-resistant squamous cell carcinoma were treated with CPT-11 as second-line therapy. CPT-11 was administered in repeated 6-week cycles comprised of the administration of CPT-11 once weekly for 4 weeks, followed by a 2-week rest. The starting dose of CPT-11 was 125 mg/M2 given intravenously over 90 minutes; subsequent doses were adjusted based on individual patient tolerance. RESULTS: The median age of the patients was 43 years (range, 27-69 years). Three patients had a baseline Eastern Cooperative Oncology Group performance score (PS) of 0, 8 had a PS of 1, and 5 had a PS of 2. All patients had received cisplatin-based chemotherapy and 13 of 16 patients (81.3%) had been treated with prior pelvic/abdominal radiation therapy. Fourteen patients were evaluable for response. There were no objective responses although subjective decreases in symptoms were observed in some patients. Grade 3 to 4 toxicities included diarrhea in three patients, nausea and emesis in one patient, leukopenia in six patients, and neutropenia in five patients. Eighteen of 25 cycles required dose reductions leading to a median dose intensity of only 59.4 mg/M2/week, which was 71% of the planned dose of 83.3 mg/M2/week. CONCLUSIONS: The amount of CPT-11 actually delivered to the patients under the conditions of this pilot study failed to result in an antitumor response. However, the marked subjective improvement of symptoms observed in this study and the significant activity reported by other investigators justify future studies of CPT-11 in patients with cervical carcinoma.

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report.

The purpose of this study was to evaluate the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in patients with endometrial cancer known to be resistant to standard therapy. Subjects were taken from three groups: (1) recurrent or persistent disease following surgery and/or radiation, (2) advanced disease at diagnosis, and (3) high-risk histology. The combination of carboplatin (pharmacologically dosed at an area under the concentration-time curve of 5) and paclitaxel (135 to 175 mg/m2 over 3 hours) was given intravenously every 4 weeks for eight courses. Data about response, overall and progression-free survival, and toxicity were collected. Response and toxicity were evaluated by physical examinations, x-ray films, and blood tests. Twenty patients have participated to date, including eight considered evaluable for response. Due to limited follow-up, survival and progression-free intervals are not yet assessable. Of patients with measurable disease, five of eight (63%) have had significant reduction in the size of evaluable tumor masses, constituting a partial response. Although two patients had clinical and radiographic complete responses, occult disease was found at surgery. There were no complete responders. Fifteen patients had grade 3 or 4 hematologic toxicity, but none had neutropenic fever or hospitalization for sepsis. One patient was taken off study for grade 3 neuropathy. There was one possible treatment-related death. In this preliminary report, this combination is active against tumors of the endometrium, with acceptable levels of toxicity. Further follow-up will be required to determine the duration of response and whether progression-free and overall survival are influenced by treatment with these drugs.

A case-matched molecular comparison of extraovarian versus primary ovarian adenocarcinoma.

BACKGROUND: Extraovarian müllerian adenocarcinoma (EOM) resembles primary ovarian carcinoma (POC) both histologically and clinically, yet little is known regarding the molecular genetic characteristics of this entity. The objective of this study was to compare the expression of three molecular markers of tumor behavior in EOMs and POCs. METHODS: Forty-four patients meeting strict criteria for EOM were identified and matched to POC controls for age, stage, tumor histology and grade, cytoreductive surgery, and survival. Immunohistochemistry was used to determine overexpression of p53 and HER-2/neu. DNA content was evaluated by flow cytometry. Direct DNA sequencing of exons 5-8 of the p53 gene was performed in nine EOM tumors. Statistical comparisons were made using chi-square, Kaplan-Meier, and Mantel-Cox log rank methods. RESULTS: Overexpression of HER-2/neu was demonstrated in 59% (26 of 44) of the EOM group versus 36% overexpression (16 of 44) in the POC controls (P = 0.05). Overexpression of p53 was noted in 48% of the EOM cases, similar to the 59% incidence observed in the control group (P = 0.29). Missense mutations were found in 9 of 9 EOM tumors showing strong p53 nuclear immunostaining. No significant difference in the incidence of aneuploidy was observed when EOM cases were compared with POC controls (65% vs. 63%). High tumor grade was strongly associated with HER-2/neu overexpression in the EOM group (P = 0.002). None of the parameters studied were predictive of prognosis within the EOM and POC groups. CONCLUSIONS: Although overexpression of p53 protein, p53 gene mutations, and abnormal DNA content were similar between EOMs and POCs, EOMs demonstrated almost twice the rate of HER-2/neu overexpression. This result suggests that distinct genetic events may be responsible for malignant transformation in EOMs versus POCs.

Lymphoproliferative disorder involving the cervix in a patient being treated with FK-506.

FK-506 is an immunosuppressive agent used mainly to prevent allograft rejection in organ transplant patients. Recently, it has been applied as a treatment for patients with autoimmune disorders. An entity called posttransplant lymphoproliferative disorder (PTLD) is a well-recognized result of immunosuppression in transplant patients receiving long-term immunosuppression. This disorder is a complication of treatment with FK-506 in 0.7 to 1.6% of transplant patients and is usually of B-cell origin. A majority of patients have serologic evidence of EBV infection. We report a case of a patient receiving long-term FK-506 therapy for multiple sclerosis who developed lymphoproliferative disorder involving the cervix. We will discuss the possible role of FK-506 initiation of this tumor.

A survey of blood transfusion practices of gynecologic oncologists.

OBJECTIVE: To survey the attitudes of gynecologic oncologists about indications for blood transfusion, and compare them to current recommendations about transfusion practice. METHODS: With the permission of the Society of Gynecologic Oncologists (SGO), a study questionnaire was mailed to 548 members and candidates in their directory. The questions asked about transfusion threshold before chemotherapy, following ovarian debulking, and after endometriosis surgery. Indications for transfusion were assessed using a qualitative/quantitative scale. Responses were analyzed with respect to years of SGO membership and practice setting using the chi 2 test and analysis of variance. Results were compared to the 1992 guidelines for transfusion of the American College of Physicians (ACP). RESULTS: Two hundred eighty-five forms were returned (52% of total). Fifty-one percent of respondents were in full-time academic positions; 36% were in private practice. Sixty-one percent were full SGO members, and 35% were candidates. The average prechemotherapy transfusion threshold (TT) was a hemoglobin concentration (hgb) of 7.9 +/- 0.7 g/dl (g). At that level the mean transfusion was 1.9 +/- 0.5 units of packed red blood cells (U). For the ovarian debulking scenario, the mean postoperative TT was 8.1 +/- 0.8 g with a mean transfusion of 1.9 +/- 0.4 U. For the endometriosis case, the mean TT was 7.0 +/- 0.8 g, with a mean transfusion of 1.9 +/- 0.5 U. Analysis showed no difference in practice based on years of SGO membership or practice setting. CONCLUSION: A majority of the gynecologic oncologists surveyed offers transfusion at levels of anemia similar to ACP recommendations, but frequently transfuse more units than recommended. A substantial minority does not follow the guidelines at all.

Nonsurgical management of placenta percreta: a case report.

BACKGROUND: Although placenta percreta is rare, its sequelae include potentially lethal hemorrhage and loss of reproductive function. Therapy directed toward control of life-threatening hemorrhage frequently includes emergency hysterectomy. CASE: A woman with placenta percreta, suspected clinically and documented radiographically, was treated nonsurgically. Following delivery, the placenta was left in situ and methotrexate chemotherapy was initiated to aid destruction of the trophoblastic tissue. Eight months later, hysteroscopy showed a normal uterine cavity with only a small area of calcification at the presumed implantation site. Two years later, the patient had a normal pregnancy and vaginal delivery. CONCLUSION: Placenta percreta can be managed with preservation of the uterus, but careful follow-up may be required until the entire placenta has resorbed.

Intravenous cisplatin, doxorubicin, and cyclophosphamide in the treatment of uterine papillary serous carcinoma (UPSC).

Thirty patients with uterine papillary serous carcinoma were treated with intravenous cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy, a combination with proven efficacy against ovarian carcinoma. Nineteen patients were given CAP as an adjuvant soon after surgery. Eleven patients were treated after recurrence or failure of other first-line therapy. Of the patients treated adjuvantly, 11 (58%) were alive without evidence of disease with a median follow-up of 24 months. Eight patients (42%), all with metastatic disease at diagnosis, were dead of disease (DOD) with a median survival of 14 months. In the salvage group, all patients were DOD with a median survival of 21 months from diagnosis and a median survival from initiation of CAP of 7 months. Toxicity was observed in all patients, and there was one treatment-related death from cardiotoxicity. In the salvage group there were two partial responses and one complete response (response rate = 27%). We conclude that intravenous CAP was ineffective in the treatment of metastatic or recurrent uterine papillary serious carcinoma, but deserves study as an adjuvant in patients without metastatic or with only microscopic extrauterine disease.

Epithelioid angiosarcoma arising in uterine leiomyomas.

Primary angiosarcomas of the uterus are exceedingly rare. The authors report a unique case of this entity arising in connection with uterine leiomyomas. The malignant tumor cells showed focally epithelioid features and were immunoreactive for keratin. Electron microscopy and immunohistochemistry confirmed their endothelial nature.

Colony-stimulating factor-1 in primary ascites of ovarian cancer is a significant predictor of survival.

OBJECTIVE: Our purpose was to determine whether the concentration of colony-stimulating factor in ascites of ovarian carcinoma is a prognostic factor for survival. STUDY DESIGN: Forty-four ascites samples from patients undergoing primary surgery for ovarian carcinoma were measured for colony-stimulating factor-1 by radioimmunoassay. Retrospective analysis of clinical data allowed comparison of accepted prognostic factors to ascites colony-stimulating factor-1 concentration for impact on survival by means of life-table analysis (Kaplan-Meier) by the Wilcoxon test and the Cox regression methods. RESULTS: In patients with advanced disease (International Federation of Gynecology and Obstetrics stages III and IV, n = 37) ascites colony-stimulating factor-1 concentration levels below a critical cutoff of 8.59 ng/ml were associated with longer overall survival (p < 0.05) and were a better predictor of survival than any other prognostic factor except zero residual disease after cytoreduction. International Federation of Gynecology and Obstetrics stage, tumor histologic type, malignant cells in fluid, grade of tumor, age, and performance status at presentation were not predictive of outcome. CONCLUSION: Colony-stimulating factor-1 in ascites may be an independent indicator of prognosis in patients with epithelial ovarian cancer.

Chediak-Higashi syndrome in pregnancy.

We report the first known case of Chediak-Higashi syndrome in human pregnancy. This rare autosomal recessive disorder is characterized by partial oculocutaneous albinism, decreased leukocyte chemotaxis, susceptibility to infection, and death in childhood. Pathognomonic giant cytoplasmic granules are postulated to be dysfunctional fused lysosomes, which influence a wide range of physiologic processes. Pregnancy did not seem to exert any influence on the course of the disease. The pregnancy, labor, and delivery were not affected and the infant and placenta were normal.

Placenta previa percreta involving the urinary bladder: a report of two cases and review of the literature.

The incidences of both placenta previa and placenta accreta are increased in patients with scarred uteri, and patients with uterine scars and placenta previa are at increased risk for also having placenta accreta. Two cases are presented of placenta previa percreta with involvement of the urinary bladder necessitating cesarean hysterectomy, partial cystectomy, and, in one case, bilateral ureteral reimplantation. Both patients had two previous cesarean deliveries. Serious hemorrhage is common in patients with placenta percreta. The primary goal of surgical management must be to control bleeding, which usually requires resection of all tissue involved by the infiltrating placenta. After hemorrhage is controlled, the surgeon must reestablish the integrity of the urinary system and reconstruct the pelvis as necessary.

Ovarian remnant syndrome: difficulties in diagnosis and management.

Ovarian remnant syndrome should be considered in the differential diagnosis of pelvic pain with a mass in a patient who has had extirpative surgery. Although rarely reported in the literature, it is probably much more prevalent than is suspected. Most commonly, the initial surgery was performed for endometriosis or pelvic inflammatory disease, with incomplete excision of the ovaries. Surgical excision of the ovarian remnant, the definitive treatment, is itself difficult, and is often attended by serious complications. Medical therapy is empiric, and hormonal manipulation may help prevent recrudescence. Three cases are reported, their pathology and the literature is reviewed.