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Objective: To evaluate the role of talcum powder use as a risk factor for the development of epithelial ovarian cancer. Methods: In a case-control study, 499 patients with epithelial ovarian cancer were frequency matched for age at diagnosis (±5 years) with a control population of 755 patients. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, education, geographic location, history of tubal ligation, and previous hysterectomy. Results: Two hundred twenty-one of 462 patients (47.8%) in the study population and 311 of 693 patients (44.9%) in the control population had ever used talcum powder (OR 0.92; 95% confidence interval [CI] 0.24, 3.62). A significant association between duration of talc use and development of epithelial ovarian cancer was not demonstrable for 1–9 years (OR 0.9; 95% CI 0.6, 1.5), for 10–19 years (OR 1.4; 95% CI 0.9, 2.2), or for more than 20 years (OR 0.9; 95% CI 0.6, 1.2). To eliminate the possible confounding variable of surgery for the management of ovarian cancer, we omitted 135 patients in the study population who underwent hysterectomy within 5 years of the diagnosis of ovarian cancer. Within this subgroup of patients, tubal ligation or hysterectomy among talc users still failed to demonstrate an increased risk for the development of ovarian cancer (OR 0.9; 95% CI 0.4, 2.2). Conclusion: A significant association between the use of talcum powder and the risk of developing epithelial ovarian cancer is not demonstrable, even with prolonged exposure.

The purpose of this study was to determine if tumor estrogen receptor (ER) or progesterone receptor (PR) status were significant prognostic variables of survival and progression-free survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV epithelial ovarian cancer. Tumor steroid receptor status was evaluated among 67 consecutive patients who underwent primary surgery from June 1983 through September 1990. Characteristics of receptor-negative and receptor-positive populations were compared by chi-square analysis. Univariate and multivariate analyses were used to identify variables prognostic of survival and progression-free survival. Fifty-one of 67 patients (76.1%) had ER-positive tumors and 31 (46.3%) patients had PR-positive tumors. Significant differences between receptor-positive and receptor-negative populations were not observed. Neither univaritate nor multivariate analysis identified ER or PR status as significant prognostic variables of survival (p = 0.93 and p = 0.06. rcspectively). Progesterone receptor-positive status was a significant prognostic variablc of progression-free survival in both univaritate (p = 0.03) and multivariate (p =0.04) analyses even after adjustment for residual disease and patient age. Estrogen receptor status was not a significant prognostic indicator of progression-free survival in either univariate or multivariate analyses. Progesterone receptor-positive tumor status is shown to be an independent prognostic variable of improved progression-free survival among patients with advanced epithelial ovarian cancer.

Objective: To describe the epidemiologic features of women with extraovarian primary peritoneal carcinoma and compare them with those of women with primary epithelial ovarian cancer. Methods: The epidemiologic features of 50 women with extraovarian primary peritoneal carcinoma were compared with those of 503 women with primary epithelial ovarian cancer. We included all women with the respective diagnoses admitted to the Roswell Park Cancer Institute between October 1982 and October 1996 who returned an epidemiologic questionnaire. Epidemiologic features of the study and control groups were extracted from a database compiled from a self-administered questionnaire that has been given to patients as part of the admission process since 1982. Individual variables between the study and control groups were compared using Student t test, χ2 analysis, and Wilcoxon nonparametric test. Two-tailed P < .05 was considered significant. Results: We found few significantly different epidemiologic features between women with extraovarian primary peritoneal carcinoma and those with primary epithelial ovarian cancer. Women with extraovarian primary peritoneal carcinoma were significantly older (mean age 63.8 versus 55.0 years, P < .001), had later menarche (13.3 versus 12.8 years, P = .024), and were less likely to have used perineal talc powder (26.0% versus 48.1%, P = .003). There were no significant differences with respect to reproductive history, contraceptive use, or use of hormone replacement therapy. A larger proportion of ovarian cancer patients reported a family history of breast cancer, but the numbers were too small to reach statistical significance. Conclusion: The epidemiologic features of women with extraovarian primary peritoneal carcinoma compared with women with primary epithelial ovarian cancer show few differences. The observed areas of difference warrant further research to determine whether they suggest the occurrence of distinct disease entities.

Objective To evaluate the role of hormone replacement therapy (HRT) as a risk factor for the development of epithelial ovarian cancer. Methods A case-control study was performed that used 491 patients with epithelial ovarian cancer frequency matched for age at diagnosis (±5 years) with a control population of 741 patients with malignancies of nonestrogen-dependent tissues. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, and education. Results One hundred of 491 patients (20.4%) in the study population had ever used HRT, and 160 of 741 patients (21.6%) in the control population had ever used HRT (OR 0.85; 95% confidence interval [CI] 0.62, 1.2). A significant association between HRT and specific histologic subtypes of epithelial ovarian cancer was not demonstrable for serous cystadenocarcinoma (OR 1.2, 95% CI 0.8, 1.7), clear cell carcinoma (OR 1.1, 95% CI 0.4, 3.4), or endometrioid carcinoma (OR 0.4; 95% CI 0.2, 1.2). A significant association between duration of use of HRT and the risk of developing epithelial ovarian cancer was not demonstrable for under 5 years (OR 0.8; 95% CI 0.5,1.2), 5-9 years (OR 0.6; 95% CI 0.3, 1.1), or 10 or more years (OR 0.6; 95% CI 0.3, 1.4). Conclusion A significant association between the use of HRT and the risk of developing epithelial ovarian cancer, even with prolonged exposure, is not demonstrable.

Twenty patients with advanced or recurrent cervical cancer were treated with bleomycin 30 U, ifosfamide 5 g/m2, and cisplatin 50 mg/m2 (BIP) every 28 days in a phase II trial. The primary purpose of this study was to compare response rate, survival, and toxicity of this regimen with results obtained in a similar group of patients treated with cisplatin 1 mg/kg per week for six courses followed by cisplatin, 20 mg/m2, plus ifosfamide 1.2 g/m2 daily for 3 days every 28 days. Four of 17 evaluable patients (23.5%) treated with BIP demonstrated a response to therapy (complete response 11.7%; partial response 11.7%). The median duration of response was 8.5+ months (range, 6+ to 24 months). These data do not differ significantly (P = 0.76) from a response rate of 27.5% among patients treated with cisplatin plus ifosfamide (PI). A significant (P = 0.003) increase in myelotoxicity was observed among patients treated with BIP versus those treated with PI. The median survival of patients treated with BIP of 13.5+ months (range, 8+ to 24 months) does not differ significantly from the median survival of 9+ months (3 to 26+ months) among patients treated with PI. The addition of bleomycin and dose-escalated ifosfamide did not significantly improve response rate or survival among patients with advanced or recurrent cervical cancer and resulted in a significant increase in myelotoxicity.

The outcome of 55 patients with primary vaginal carcinoma treated with radiation therapy at Roswell Park Cancer Institute was retrospectively reviewed. Forty-four (80%) had a squamous cell carcinoma and 11 (20%) had an adenocarcinoma. The median age was 61 years and the median dose of radiation administered, external beam and brachytherapy, was 7,040 cGy. Fifteen percent of patients developed severe radiation-induced complications, and 36% developed recurrence of disease. The overall 5-year survival and 5-year disease-free survival for the entire group was 49 and 58%, respectively. Variables positively influencing survival included younger age, early stage, involvement of the upper vagina, total radiation dosage > 7,500 cGy, and the use of combination external beam and brachytherapy. However, only age acted as an independent prognostic factor affecting survival. The pelvis was the site of disease in the majority of patients who suffered recurrence.

To assess the impact on progression-free survival of the use of the multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma: 20 evaluable patients who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for stage I uterine sarcoma received adjuvant multiagent chemotherapy with vincristine sulfate 1 mg/m2 days 1 and 4, doxorubicin (Adriamycin) 40 mg/m2 and cyclophosphamide 400 mg/m2 day 2, and dacarbazine 200 mg/m2 days 1 through 4 for a total of 9 monthly cycles or until recurrence of disease was documented. Patients were followed for a median of 65 months (range: 5-116 months). Myelotoxicity was monitored by weekly complete blood counts, cardiac toxicity by monthly radionuclide angiography, and neurotoxicity by monthly physical examination. Survival and progression-free survival were calculated by the method of Kaplan and Meier (17). The Fisher exact test was employed to determine the significance of recurrence rates between histologic groups (18). These 20 patients received 172 of a planned 180 cycles of chemotherapy. Dose reductions in response to myelotoxicity were necessitated in four cycles among three patients. Mild neurotoxicity was observed in six patients (30%) and moderate neurotoxicity in one patient (5%). A decrease in cardiac ejection fraction of > 10% was observed in two patients (10%). No deaths ascribable to complications arising from chemotherapy were observed. Seven patients (35%) developed recurrence of disease. Recurrence rates for pure sarcomas and mixed mesodermal tumors did not differ significantly (P = .65). Progression-free survival for the population at 2 years was 80% and at 5 years was 65%. This study describes the largest prospective trial of adjuvant combination chemotherapy for patients with stage I uterine sarcoma reported to date. Adjuvant chemotherapy employing the combination of cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) failed to impact significantly on long-term survival in this group of patients with stage I uterine sarcoma.

Pancreatic cancer and jejunal cancer are aggressive diseases with grim prognoses. The long term survival of pancreatic carcinoma is still one of the worst of all cancers. Ninety-five percent of the patients die of their disease within 5 years [Wagener et al : Ann Oncol 5(Suppl 3) : S87-S90, 1994]. Eighty-five percent of patients with jejunal carcinoma die of their disease within 5 years [Lioe, Biggart : J Clin Pathol 43 :533-536, 1990]. To date, there are disappointingly few effective cytotoxic agents in the treatment of these cancers. We present a case of advanced-stage pancreatic carcinoma and a case of advanced stage jejunal carcinoma, each showing marked response to Taxol and platinum chemotherapy. © 1995 Wiley-Liss, Inc.

Twenty patients with metastatic or recurrent endometrial adenocarcinoma not amenable to surgery or radiation were treated with monthly cisplatin (20 mg/m2 x 3), etoposide (75 mg/m2 x 3), Adriamycin (40 mg/m2) (PAV) and Megace. Patient characteristics were as follows: grade 3 differentiation, 55%; papillary subtype, 15%; prior radiotherapy, 70%; prior chemotherapy, 10%; and prior hormonal therapy, 20%. Hematologic toxicity was significant but acceptable: WBC nadirs, 50%; platelet nadirs, 40%. There was no hematologic mortality. There was a 75% objective response rate and a 55% complete response rate with PAV. The median survival was 15+ months, the 2-year survival was 42%, and the 2-year progression-free survival was 20%. PAV appears to be an active combination with acceptable toxicity in the treatment of metastatic or recurrent endometrial cancer, and we believe that phase III evaluation is indicated.

A case of vulvar carcinoma with 0.5 mm of invasion treated by radical wide local excision only, which later developed ipsilateral inguinal lymph node recurrence, is presented. This represents the least amount of invasion reported resulting in inguinal lymph node metastasis. Review of the literature of stage I vulvar carcinoma with less than 1 mm of invasion indicates that this phenomenon occurs in only 1.6% of all patients who have undergone inguinal lymphadenectomy. Although this represents the second report of ipsilateral inguinal nodal metastasis associated with less than 1 mm of invasion, we continue to perform radical wide local excision without ipsilateral inguinal lymphadenectomy until more cases demonstrate a higher incidence of lymph node involvement. © 1993 Wiley-Liss, Inc.

The efficacy and toxicity of gemcitabine salvage chemotherapy was evaluated in 27 heavily pretreated patients with recurrent and progressive ovarian, fallopian tube, or peritoneal cancer. At least one platinum-based chemotherapeutic regimen had failed in each patient. The median number of previous chemotherapy regimens and cycles of chemotherapy was 4 and 23, respectively. A total of 124 cycles of gemcitabine were delivered (median, 3 cycles). Hematologic toxicity included four patients with grade 3/4 thrombocytopenia and two patients with grade 3/4 neutropenia. Thrombocytopenia and neutropenia resulted in eight dose reductions and a single 1-week treatment delay. Nonhematologic side effects were well tolerated and largely self-limiting. No complete responses were observed. Three patients (11%) demonstrated partial responses to therapy. The duration of response was 7 months for two of the responders and 5 months for the third responder. Stable disease was observed in 14 patients (52%), in whom the median progression-free interval was 5 months. In conclusion, among heavily pretreated patients, gemcitabine has limited antitumor activity in platinum-resistant carcinomas of the ovary, fallopian tube, and peritoneum. The role of gemcitabine in the treatment of gynecologic malignancies of the ovary, fallopian tube, and peritoneum will be determined by studies that define the efficacy of multiagent regimens of chemotherapy that include gemcitabine and by studies that include patients who have been less heavily pretreated.

Since pelvic exenteration for the treatment of recurrent gynecologic malignancy first was described, reported rates of morbidity and mortality have declined steadily. However, the factors responsible for this decline have never been clearly delineated.We reviewed the charts of 154 patients who underwent pelvic exenteration for gynecologic malignancy between 1954 and 1994. Charts were abstracted for details of the surgical procedure, pathologic findings, postoperative management, short- and long-term complications, time to recurrence, and overall survival.Seventy-two patients (47%) experienced 95 identifiable postoperative complications, resulting in death in 22 patients (14%). The rate of infectious complications declined to a statistically significant degree between the first two decades and latter two decades of the study (odds ratio [OR] 0.28. 95% CI 0.11-0.69). The use of routine prophylactic antibiotics was associated with this decline in infectious complications (OR 0.25, 95% CI 0.07-0.83). The use of preoperative subcutaneous heparin was associated with a reduction in thrombotic complications from 5 of 100 patients to 0 of 54 patients (P = .11), as well as a significant reduction in overall risk of complications (OR 0.53, 95% CI 0.33-0.85) and risk of postoperative mortality (OR 0.19, 95% CI 0.05-0.80). There was a significant reduction in overall risk of postoperative complications with both intensive care unit monitoring postoperatively (OR 0.65, 95% CI 0.43-0.99) and routine postoperative monitoring with a pulmonary artery catheter (OR 0.61, 95% CI 0.38-0.98).Routine use of prophylactic antibiotics, prophylactic subcutaneous heparin, and intensive postoperative monitoring appear to have reduced morbidity from pelvic exenteration.

A prospective pilot study was performed in order to determine the efficacy of 111InCyt103 (ONCOScintr CR/OV) in the detection of the presence and location, or absence of disease among patients with epithelial ovarian cancer who demonstrated no clinical or biochemical (Ca 125: < 35 mu/ml) evidence of disease at the end of first-line therapy. Among 15 patients who underwent second-look laparotomy, the overall accuracy of the test was 60%. The test demonstrated a sensitivity of 62.5% and a specificity of 57.1%. The predictive value of a positive test was 62.5% and of a negative test was 57.1%. The correct location of disease was predicted in 57% of patients with macroscopically appreciable tumors. ONCOScintr CR/OV offers little appreciable advantage over current modalities in discriminating between the presence or absence of disease among patients with epithelial ovarian cancer who demonstrate no clinical evidence of disease at the end of first-line therapy.

A Phase I/II study was initiated to evaluate complications of orthovoltage intraoperative radiation therapy utilized in the treatment of patients with incompletely resected recurrent gynecologic malignancies. There were no osseous, vascular, neurologic, or ureteral complications. Of the 23 treated patients, 2 patients (8.7%) had complications outside the treated area. Survival of patients treated with intraoperative radiation therapy was highest among patients treated to a field of < or = 3 cm in greatest diameter and a tumor thickness of < or = 1 mm. A subgroup of patients (5) with microscopically positive margins following total pelvic exenteration demonstrated an absence of recurrence in the treated field. The role of intraoperative radiation therapy (IORT) in the treatment of recurrent and incompletely resectable gynecologic malignancies remains investigational.

Twenty-four patients with advanced or recurrent uterine (13) and ovarian (11) mixed mesodermal sarcomas received a combination of cisplatin. Adriamycin and dacarbazine (PAD) as initial therapy after surgical debulking. Of the 13 patients with metastatic uterine sarcoma, six (46.1%) remained without evidence of disease (NED) from 8 to 36 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 68%, 68%, and 51%, respectively. Of the 11 ovarian sarcoma patients, five (45.4%) were NED at 5, 7, 32, 56, and 59 months from the start of PAD. The estimated 1-, 2-, and 3-year survivals for these patients were 70%, 35%, and 35%, respectively. The PAD regimen is an active regimen in patients with metastatic uterine and ovarian mixed mesodermal sarcomas and progression-free survival may be improved by maximum debulking surgery prior to the initiation of PAD chemotherapy.

From 1975 to 1982, 25 evaluable patients with FIGO Stage I ovarian cancer were treated with intraperitoneal chromic phosphate (32P). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy with (28%) or without (72%) omentectomy, with no other surgical staging procedures prior to referral. Patients were restaged by laparoscopy (inspection of diaphragms, abdomen, and pelvis), biopsy of suspicious lesions, and peritoneal cytologic washings prior to intraperitoneal chromic phosphate therapy. For the 25 patients, the estimated 5- and 10-year recurrence-free rates and the 5- and 10-year survival rates are 84% and 75%, respectively. Excellent 10-year recurrence-free rates were achieved for Stages IA and IC, nonruptured cysts, and Grade I and II tumors. In contrast, very low 10-year survival rates were achieved for patients with Stage IB, ruptured cysts, or Grade III tumors.

A decade ago the five-year survival rate in patients with stage I ovarian carcinoma was only 60% to 70%. Significant advances in staging and treatment, however, promise an improvement. Initially, improvement will be seen because some patients with clinically localized ovarian cancer will be discovered to have subclinical or occult metastasis at initial surgical staging and thus will be upstaged and treated appropriately for more advanced disease. More encouraging are results of recent studies on adjuvant therapy, which indicate that in some patients the need for postoperative adjuvant therapy may be obviated. A major advance in diagnosis would be development of a serum test specific for ovarian cancer--a discovery that may be forthcoming.

A vaginal rhabdomyosarcoma which occurred in an 11-month-old infant was treated with conservative surgical excision, radiation therapy and chemotherapy. The long-term sequelae of this therapy included rectal stenosis, which required surgical correction, and urinary incontinence. The patient may have had fewer long-term complications if a more aggressive surgical procedure had been performed at the time of diagnosis because a gross and microscopically complete excision would have obviated the need of postoperative pelvic irradiation. Strong consideration of total surgical excision should be given to infants with pelvic rhabdomyosarcoma.

One hundred and three women with FIGO stage IB cervical carcinoma were treated either by radical hysterectomy and bilateral pelvic lymphadenectomy, or external pelvic radiation and intracavitary brachytherapy to deliver >6000 rads to point A. Surgical therapy was to be limited to stage IB tumors mea

Fifty-one patients with FIGO stage III and IV ovarian adenocarcinoma underwent six-month interval laparoscopy for assessment of chemotherapy response. Thirty-nine of these patients were followed by a second-look procedure at 12 months or to disease progression if it occurred earlier. A positive interval laparoscopy was predictive of disease in 91% of patients, whereas a negative interval laparoscopy showed absence of disease at second look in only 70.5% of patients. A positive laparoscopic biopsy at six months showed presence of disease at second look procedure in 100% (11 of 11) of patients. It is concluded that either an intensive initial chemotherapy or change in therapy such as intraperitoneal chemotherapy after positive interval laparoscopy is indicated in future studies.

A case is presented of a patient with microinvasive carcinoma of the vulva which was treated by conservative surgery. Six years later, the patient developed inguinal and pelvic lymph node recurrence of carcinoma. A review of the literature on similar cases is also presented.

One hundred and eleven consecutive women with FIGO Stages III and IV ovarian adenocarcinoma were treated with melphalan as their initial chemotherapy. The response rate was 19.8% with 10.8% having a complete response. There was a statistically significant improvement in response in those women with no prior radiation therapy. Moreover, there was a statistically significant improvement in median survival in those patients achieving a complete response to melphalan as compared to those with a partial response, with no change or progression of their malignancy. A review of the results of maximal surgery and combination chemotherapy is presented as a plan of therapy to improve upon the results of melphalan chemotherapy in women with advanced ovarian carcinoma.

Alternating 5-day chemotherapy with methotrexate and dactinomycin as primary therapy for nonmetastatic gestational trophoblastic disease was studied in nine patients. The complete response rate was 100% with follow-up of a median of 80 months. Stomatitis was universal but rarely prevented oral alimentation or delayed therapy. Overall, 94% of toxicity was mild or moderate in severity and all toxicity was reversible. This alternating non-cross resistant regimen, reported in a total of 40 patients in the literature, is the only regimen to result in a 100% response rate. This response rate is statistically improved when compared to historical controls receiving methotrexate/folinic acid or pulse dactinomycin. No patients required hysterectomy for disease control. Cooperative prospective phase III studies are needed to determine the efficacy and toxicity of current regimens.

We have evaluated the effect of adjuvant chemotherapy on time to recurrence and survival in two prospective trials of women with stage I uterine sarcomas. The first trial compared surgery only to surgery plus Adriamycin. The 5-year estimated survival rate was 36% for surgery alone and 63% for surgery plus Adriamycin. The 5-year recurrence free rate for surgery alone was 46% as compared to 75% for surgery plus Adriamycin. The second trial, without a concurrent control group, included patients with stage I uterine sarcoma and adjuvant cyclaphosphamide, vincristine, Adriamycin, and dacarbazine (CYVADIC) chemotherapy. The 5-year survival rate was 89% and the recurrence-free rate was 80%. In all of these trials, as well as in the report of Van Nagell et al (Cancer 57:1451-1454, 1986) of adjuvant vincristine, actinomycin-D, and cyclophosphamide (VAC) chemotherapy, there are too few patients to make any formal statistical comparison of the groups, although the surgery plus CYVADIC group appears to be the most promising.

From 1958 to 1967, a prospective randomized trial was conducted in 189 women with stage I, group I endometrial adenocarcinoma, comparing treatment by hysterectomy alone, preoperative uterine radium followed by hysterectomy, and hysterectomy and postoperative vaginal radium. All women have been followed for a minimum of 10 years. The actual survival rate at 5 years for all patients was 94.5% and at 10 years, 92.6%, with no statistical significance among the 3 treatment groups. Ther was also no statistical significance in survival rate in relation to size of uterine or myometrial invasion. There was a statistically significant difference in survival between grade I and grade III lesions (P less than 0.01) and between grade II and grade III lesions (P less than 0.05).

Lymphography was employed as an initial staging procedure in 93 patients with carcinoma of the uterine cervix. The lymphangiograms were positive in 25% of the Stage IIB, in 48% of the Stage IIIA, and in 75% of the Stage IIIB cases. In Stage III disease the incidence of common iliac node metastasis was 44% and of para-aortic node metastasis 17%. Lymphangiography in cervical carcinoma may be useful in diagnosing metastatic nodes, in designing optimum irradiation portals, and in discovering recurrence.

Twenty-five patients with FIGO stage III and IV ovarian carcinoma were treated with cisplatin plus VP16-213 chemotherapy as the second, third, or fourth line of therapy. There were two (8%) partial responses, 18 with stable disease and five with progression of disease. Neurotoxicity was observed in all patients, with two patients developing severe paresthesias and difficulty in walking.

Thirty-three women with carcinoma of the clitoris underwent surgical therapy, and 12% subsequently developed pelvic recurrence. However, none of the 18 patients without initial evidence of inguinal node metastases developed a pelvic recurrence. Of the 15 women with initial evidence of inguinal node metastases, 26.6% developed pelvic recurrence. It is, therefore, concluded that the addition of the routine use of pelvic lymphadenectomy to radical vulvectomy and bilateral inguinal lymphadenectomy in women with carcinoma of the clitoris is not warranted and that only those patients with histologically proven inguinal node metastases should undergo pelvic lymphadenectomy. If pelvic node metastases are documented, it is suggested that such patients receive postoperative pelvic irradiation.