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From 1978 until 1988, 116 patients with epithelial ovarian cancer were entered onto one of three consecutive prospective clinical trials involving cisplatin-based combination chemotherapy. They had the following characteristics: (1) stage III or IV disease, (2) grade 2 or 3 tumors, and (3) optimally debulked tumors (residual disease < or = 2 cm). The purpose of the study was to investigate the influence of duration of chemotherapy on survival. The treatment plans were as follows: Trial 1, 12 cycles of cisplatin/melphalan (43 patients); Trial 2, 12 cycles of cisplatin/cyclophosphamide (24 patients); and Trial 3, 6 cycles of cisplatin/cyclophosphamide (49 patients). The total dose of cisplatin was 60 mg/m2 in the first trial and 50 mg/m2 in the second and third trials. Median survival times for the three groups were 58, 29, and 35 months, respectively (NS). Median progression-free survival (PFS) times were 37, 23, and 15 months, respectively (P = 0.0008). Combining patients from the first two trials, the median PFS for patients receiving 12 planned cycles of chemotherapy was 30 months versus 15 months for patients receiving 6 planned cycles (P = 0.0004). Using a forward stepwise Cox proportional hazard model, the use of 12 cycles of therapy and melphalan predicted increased PFS (P = 0.0001 and P = 0.0002, respectively). In view of these results, the lack of published data supporting the superiority of 6 over 12 cycles of chemotherapy, and the rather recent availability of less toxic maintenance therapy (i.e., carboplatin), we believe that a multiinstitutional trial comparing the 6-cycle regimen with more prolonged chemotherapy is justifiable.

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.

Primary carcinoma of the fallopian tube is uncommon and is often treated using regimens active in ovarian carcinoma. Evidence is scant that such therapies benefit patients with fallopian tube carcinoma. Between December 1979 and July 1988, we treated 18 patients who had adenocarcinoma of the fallopian tube with the combination of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) administered intravenously on 1 day every 28 days. Histologic confirmation of fallopian tube carcinoma was obtained before entry in the study. Three patients had stage I disease, five had stage II, nine had stage III, and one had stage IV. Sixteen patients received the combination therapy as first-line treatment after cytoreductive surgery, and two patients received it for recurrent carcinoma. Seven patients had clinically measurable disease at the start of therapy. Two of these patients had a complete clinical response, two had stable disease, and three had progressive disease. Eight of the 15 patients with stages II-IV disease underwent second-look laparotomy; four had a complete response to therapy and four had a partial response, making the overall response rate 53%. The toxicity of the regimen was moderate. The median survival was 81 months. Patients with stages II-IV disease had a median survival of 43.9 months and a progression-free survival of 22.5 months. This regimen appears to be active in fallopian tube carcinoma and can result in response rates comparable to those reported for epithelial ovarian cancer.

Lymph node metastasis is uncommon in patients with microinvasive squamous cell carcinoma of the cervix and is particularly unusual in tumors with early stromal invasion. We describe a patient with maximum stromal invasion of 0.8 mm who had extensive pelvic and para-aortic nodal metastases discovered at laparotomy. Despite combined modality therapy, she died with progressive disease. New clinical staging definitions for Stage IA cervical carcinoma incorporate measurement of both depth of invasion and lateral tumor spread and have resolved many of the descriptive controversies surrounding this entity. Our case illustrates that any degree of stromal invasion carries some risk of nodal metastasis. The management of patients with microinvasive carcinoma should be individualized. An abdominal approach should be considered for patients being treated by extrafascial hysterectomy to allow assessment of the regional lymph nodes. Whether more aggressive therapy will influence the outcome for the rare patient with lymph node metastasis is unknown.

Gastrointestinal stapling instruments have achieved wide-spread application in intestinal surgery. Reported advantages of stapled bowel procedures compared to classic hand-sutured procedures include reduced tissue trauma, shorter operating time, and improved blood supply to the stapled bowel segment. A technique for creation of an end colostomy using the end-to-end anastomosis stapler (EEA instrument) is described. This technique was used in 11 gynecologic oncology patients who required colostomy. Postoperative stomal function was normal in all cases. No patient developed stomal necrosis, peristomal hematoma, or abscess. No delayed complications have been observed. Colostomy creation with the EEA instrument is a safe, simple and rapid procedure. Possible advantages of the stapled colostomy are enhanced blood flow to the stomal site, reduced incidence of peristomal infection, and improved appliance fit.

To determine the natural course of cervical human papillomavirus infection, we prospectively studied all new patients referred to the colposcopy clinic at the Naval Hospital Bethesda, from April 1981 to August 1983, whose screening cervical cytology demonstrated features consistent with human papillomavirus infection as the only abnormality. Histologic confirmation of human papillomavirus infection was required for entry into the study. All patients were evaluated by repeat cytology, colposcopy, endocervical curettage, and colposcopically directed biopsy as indicated at intervals of three to six months. Patients who developed classic features of cervical intraepithelial neoplasia were treated by standard modalities, whereas patients with evidence of human papillomavirus infection without associated cervical intraepithelial neoplasia were not treated. Confirmation of the resolution of human papillomavirus infection required negative cytology and colposcopy on two consecutive evaluations. Of the 45 patients for whom complete follow-up data are available, five (11.1%) had cervical intraepithelial neoplasia at the time of their initial evaluation, 15 (33.3%) progressed to cervical intraepithelial neoplasia over an average of 10.9 months, 18 (40%) resolved over an average of 13.7 months, and seven (15.6%) persisted with neither progression nor resolution for an average of 21 months. These data suggest that about one-third of patients who have histologically confirmed human papillomavirus cervical infection can be expected to develop cervical intraepithelial neoplasia within a year.