We report an observational study of chemotherapeutic regression of ovarian tumor implants according to decrements in residual mass size after surgical cytoreduction. Cytoreductive operations were attempted on 74 consecutive patients with stages IIIB-IV disease referred for this purpose. Thirty-two patients had received one to four courses of preoperative chemotherapy (22 responses, no progressions). Postoperative chemotherapy followed current protocols at Dana Farber Cancer Institute (n=61) or referring institutions (n=13); 57 regimens contained cisplatin. Postchemotherapy response was assessed clinically or by second-look procedures. Negative findings were considered a complete remission. Masses > 1 cm were excised from 62 patients. Twelve patients were inoperable. Twenty-eight patients had complete remissions and the correlation between these and decrements in residual mass size was highly significant (P < 0.0001). Complete remissions had a uniform effect and were the only outcome predictive of survival. Preoperative treatment greatly facilitated cytoreduction but only masses 0-0.2 cm were senstitive to postoperative chemotherapy. Masses 0.5 cm or less were optimal. They made up 77% of operable patients and supplied 25 (89%) of the complete remissions. Cytoreduction is not always required but even large-volume disease in the upper abdomen can be safely excised. The concept that masses larger than 10 cm indicate general chemoresistance has not been sustained.

An 80-year-old nullipara had a 2.0-cm cystic tumor of the right labium majus. Histologic diagnosis was mucinous eccrine carcinoma. Seventy-five percent of these rare skin adnexal tumors arise on the face, eyelid, or scalp; but none has been reported on the vulva. Indolent localized growth is usual with regional nodal spread in 11% and distant metastases in 3%. A 67-year-old multi-para had a 1.2-cm polypoidal nodule of the posterior fourchette. Histologically, a colonic type mucinous carcinoma was arising within a villous adenoma. Mucicarmine and CEA stains were positive. Extensive workup failed to reveal other primary cancers in either patient. Both patients are well 19 and 17 months after radical vulvectomies and node-negative groin dissections. These cases illustrate further the diversity in cell type and biologic behavior of vulvar adenocarcinomas.

In a 2-year period 12 diaphragmatic resections were performed on 11 patients with invasive metastases from ovarian carcinoma without significant complications, via transabdominal approach in 10 instances and thoracoabdominal incision in 1. Full-thickness penetration of the diaphragm by tumor occurred in all instances without prior evidence of pleural involvement (occult Stage IV). Six patients had primary disease (Group A) and 5 had recurrent disease (Group B). Ten patients who underwent excision of nonpenetrating diaphragmatic metastases were analyzed for comparison (Group C). Mean diameters of the metastases were as follows: Group A, 7.84 +/- 1.60 cm; Group B, 7.00 +/- 2.24 cm; Group C, 2.51 +/- 1.08 cm. The difference in mean diameter between the penetrating (Groups A and B) and nonpenetrating (Group C) tumors was highly significant (P less than 0.01). Penetrating tumors were 5.0 cm or greater; nonpenetrating tumors were 4.0 cm or less. Invasiveness of diaphragmatic metastases was inversely related to survival in patients with primary but not recurrent disease. Group A patients had a marked survival disadvantage (median survival time of 8 months; range 7-25 months) compared to Group C (median survival time of 26 months; range 13-96+ months; P less than .05). In contrast, Group B patients appeared to gain salutory palliation despite large diaphragmatic masses involving the pleural surface (4/5 alive at 16(+)-33+ months following surgery). Previous reports of response and survival in patients with Stage III Ovarian cancer may have included patients with "occult Stage IV" disease.

The clinical aspects and pathologic findings in 44 cases of pure clear cell carcinoma of the ovary are presented. The patients ranged in age from 28 to 78 years (mean, 50.6 years); 54% were nulliparous. Thirty-three percent of the patients had endometriosis in the involved ovary, and an additional 25% had endometriosis only in sites distant from the tumor. Microscopically, three architectural patterns (papillary, tubulocystic, and solid) and four cell types (clear, hobnail, eosinophilic, and flattened) were seen. A predominant tubulocystic architectural pattern was a good prognostic factor (p less than 0.01); however, no significant difference in survival by cell type was found. Grading of the tumors by conventional architectural and cytologic criteria had no predictive value for survival. Stage at presentation was the most important prognostic factor (p less than 0.001), with a 5-year overall survival of 34% and stage I survival of 55%. The poor stage I survival reflects the 15 patients (34%) in the study with stage Iaii lesions. In the 25 patients who developed recurrence, both distant organ involvement (40%) and lymph node involvement (40%) were frequent. Ovarian clear cell carcinoma has unusual pathologic and clinical features, and it represents a distinct histologic type of ovarian carcinoma.

A total of 107 patients with carcinoma of the ovary were entered in a study combining extensive primary surgery and intensive chemotherapy. Because of evidence supporting the effectiveness of both single agent platinum (P) and the combination of cyclophosphamide and doxorubicin (CA), patients were treated with alternating cycles of CA and CP. Primary surgery to remove the bulk of tumor to less than 2 cm was possible in 45% of the 85 eligible patients, and an additional 17% had similar surgery after two to four cycles of chemotherapy. Fifteen percent of patients progressed on chemotherapy. Of the 68 who were clinically and radiologically without disease at the completion of chemotherapy, 91% had second-look surgery. Forty-eight percent of these women had residual disease. All patients but one are at risk for greater than 60 months, with a median follow-up of 86 months. Overall 5-year survival is 26%, with a median survival of 33 months. Twenty patients survived over 5 years with 11 continuing to be free of disease (13% of all eligible patients). Patients with modified Broder's grade I,II tumors have not yet reached a median survival. Grade, stage, and primary mass size were the only variables with independent prognostic value in a Cox multivariate analysis.

Forty-four patients with clear cell adenocarcinoma of the ovary diagnosed between 1944 and 1981 were compared with a matched cohort of 55 patients with the most common epithelial malignant lesion, serous adenocarcinoma, in terms of their presentation and clinical course. None were lost to follow-up. Median follow-up was 9 years. Fifty percent of clear cell patients presented in Stage I versus 31% of serous patients. Patients with clear cell carcinoma presented more often with pelvic masses (84% vs 65%) and had larger (diameter > 10 cm) primary tumors (73% vs 29%). Fortynine percent of clear cell patients were nulligravid compared with 24% of serous patients and endometriosis was strikingly more common in clear cell patients (58% vs 12%). When compared stage for stage, clear cell tumors were uniformly associated with poorer 5-year survival rates with an overall rate of 34%. In patients with recurrent disease, lymph node involvement was much more common in patients with clear cell carcinoma (40% vs 7%). Parenchymal organ involvement was also more common in the clear cell group (40% vs 13%). Ovarian clear cell adenocarcinoma has distinctly different clinical behavior compared to serous carcinoma and should be regarded as an aggressive epithelial histologic type.

Elevations in CA 125 levels have been reported in approximately 80% of patients with epithelial ovarian cancer. Studies demonstrate that elevations of CA 125 at the time of second-look procedures correlate with the presence of tumor in 100% of cases. Two cases are reported with elevated CA 125 in which clinical examination and noninvasive studies with CAT scans failed to demonstrate tumor. In both cases laparotomy was performed because of the elevation of CA 125. Although intraabdominal exploration did not reveal the source of the CA 125 elevation, extensive retroperitoneal dissection demonstrated microscopic tumor in retrocaval lymph nodes in both cases. The ability to monitor patients with CA 125 is demonstrated and the importance of elevated antigen levels emphasized. Benign conditions associated with falsely positive CA 125 are discussed.

Radiolabeled monoclonal antibodies may be useful for radioimmunotherapy of gynecologic tumors. Iodine 131-labeled F(ab')2 fragments of a monoclonal antibody, OC 125, with specificity for ovarian carcinoma, were used to study the distribution and pharmacokinetics of this antibody in patients with gynecologic tumors. The radiolabeled antibody was injected intravenously or intraperitoneally into 10 patients suspected of having ovarian cancer. Blood and urine samples were used for pharmacokinetic studies, and biopsy specimens were examined for the uptake of antibody. The serum half-life of the labeled antibody was 30 hours after intravenous administration, with 20% of the injected dose per liter detected at 24 hours. After intraperitoneal injection, the appearance of antibody in serum was slow, with a maximum level of 1.4% of the injected dose per liter at 24 hours. Urinary excretion of the radiolabeled antibody was similar for intravenous and intraperitoneal administration, with approximately 50% of the injected dose excreted after 48 hours. Intraperitoneal administration of the radiolabeled antibody resulted in a higher uptake of antibody in the tumor and a lower uptake of antibody in normal tissues. On the basis of this limited study, intraperitoneal administration of radiolabeled antibody is preferred over intravenous administration for radioimmunotherapy of ovarian cancer.

Fifteen patients with or suspected of having ovarian carcinoma were injected intravenously (i.v.) or intraperitoneally (i.p.) with 131I-labelled OC125 F(ab')2. Radioimmunoscintigraphy after i.v. injection revealed 50% of the tumor sites. After i.p. injection all tumor sites were visualized, except in one case in which the antibody remained loculated because of adhesions. One patient with endometrial cancer showed no specific uptake of the antibody after i.p. injection. The serum half-life of the radiolabelled antibody after i.v. injection was 30 hr. After i.p. injection there was a slow appearance of radiolabelled antibody in the blood with a maximum level of 1.4% dose per liter at 24 hr after injection. Urinary excretion of the radiolabel was the same for both routes of administration, with 50% of the dose excreted in approximately 48 hr. Tumor uptake was slightly higher after i.p. injection. Liver and bone marrow uptake after i.p. injection were one-half of the uptake after i.v. injection.

Corynebacterium parvum was administered intraperitoneally to 21 patients with epithelial ovarian cancer. Nineteen patients had surgically measurable disease and two received adjuvant therapy. Surgically confirmed responses were documented in six of 19 patients (31.6%), with two complete responses (10.5%) and four partial responses (21.1%). Three patients (15.8%) had stable disease, and 10 patients (52.6%) had disease progression. The mean survival of the patients who had a complete response was 35.5 months; the four patients who had a partial response the mean survival was 26.6 months, and of the nonresponders the mean survival was 12.6 months (p < 0.02). The mean survival of the entire group was 18.2 months. Initial response and patient survival correlated with the amount of disease pretreatment. Thus six responding patients had ≤5 mm maximum diameter tumors, that is, minimal residual disease. Toxicity in the 86 courses of therapy included abdominal pain in 78% of cases, fever in 56%, nausea in 40%, and vomiting in 22%. Stimulation of cytotoxic lymphocytes resulted from the administration of C. parvum, which induced a significant increase of both intraperitoneal natural killer lymphocyte cytotoxicity and antibody-dependent cell-mediated cytotoxicity in six of nine patients tested; these two types of cytotoxicity correlated with response to therapy and may be partially responsible for the surgically documented tumor regression. While the clinical usefulness of intraperitoneal C. parvum is limited because of its toxicity, intraperitoneal immunotherapy may prove useful in patients with minimal residual ovarian cancer when more refined agents become available.

Although second-look laparotomy to ascertain primary therapeutic effect on ovarian cancer has been generally accepted, laparoscopy for this purpose has been controversial. Between 1974 and 1978, 119 consecutive laparoscopic examinations were performed on 57 patients with ovarian cancer to monitor the effect of chemotherapy or to determine disease status. Most procedures included intraperitoneal biopsy and cytologic evaluation of peritoneal washings. Seventy-three percent of the procedures were successful. Fourteen percent of the patients had major complications requiring laparotomy, most of which involved bowel perforation. Complications were significantly reduced when routine laparoscopy was preceded by needle laparoscopy. A negative laparoscopy including biopsy and cytologic evaluation was associated with a significant increase in survival when compared with the entire patient group. Repetitive laparoscopy permitted early detection of recurrence and identified patients whose risk of recurrence after 24 months was low. With each successive negative laparoscopy, the mean duration of remission was longer and the probability of recurrence lower.