High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Cushing's syndrome with small cell carcinoma of the uterine cervix.

A 28 year old white women was found to have a cervical tumor in the 25th week of pregnancy. Pathologic examination revealed a nonkeratinizing small cell carcinoma. After delivery by cesarean section, pelvic lymph node exploration was carried out, and all 15 nodes were free of tumor. Her condition was staged as II-A, and she was treated with local radiation. Metastatic disease became manifest almost a year later and was histologically similar to her primary disease. A Cushingoid appearance was noticed and plasma cortisol levels were elevated. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) levels were elevated and failed to suppress with dexamethasone. Plasma adrenocorticotropin (ACTH) level was elevated. Electron microscopic examination of the tumor tissue revealed neurosecretory granules. Immunoperoxidase stains for ACTH were positive. The patient's course was one of progressive decline and eventual death. A literature review revealed two other cases in which carcinoma of the uterine cervix was considered to be the source of ectopic ACTH. Some small cell carcinomas of the cervix may arise from cells of the APUD series. Small cell carcinoma of the uterine cervix may behave differently from the more commonly encountered keratinizing and large cell nonkeratinizing carcinomas of the cervix and may not respond as well to standard therapy. Ectopic hormone production, production of abnormal peptides or of vasoactive amines may be more common in small cell carcinoma of the cervix than is currently recognized, and these products may be clinically useful as tumor markers.

Radioactive phosphorus and external radiation as an adjuvant to surgery for ovarian carcinoma.

At the Johns Hopkins Hospital between the years 1967 and 1973, 40 patients with primary ovarian carcinoma were treated with radioactive phosphorus. Of these, 19 were treated with external radiation in addition. The morbidity from the radioactive phosphorus alone was negligible. Dosages of less than 5000 rads to the pelvis were usually well tolerated even when given in combination with the isotope. Pathologic changes in the bowel are discussed.

Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.

The safety and efficacy of a daily combination of micronized estradiol (E2) (0.7-1.05 mg) and progesterone (200-300 mg) were evaluated in ten menopausal women with moderate to severe vasomotor symptoms and/or vaginal atrophy over a 12-month study interval. For comparison, five similar women were placed on conjugated estrogens, 0.625 mg daily, and medroxyprogesterone acetate, 10 mg daily, for the first 10 days of each calendar month for 12 months. Patients were evaluated at 0, 1, 3, 6, and 12 months. Estrogens rose significantly from baseline in both groups (P less than .01). Progesterone increased significantly above baseline in the E2 and progesterone group (P less than .01), but did not change in the conjugated estrogens and medroxyprogesterone acetate users. All women on E2 and progesterone had a decrease in total cholesterol and an increase in high-density lipoprotein cholesterol from baseline (P less than .01). Those on conjugated estrogens and medroxyprogesterone acetate had no significant change from baseline in total cholesterol; however, they did have an increase in high-density lipoprotein cholesterol values (P less than .01). In the E2 and progesterone group, the endometrial histology became completely quiescent and there was no uterine bleeding after 6 months of observation. Four of five women on conjugated estrogens and medroxyprogesterone acetate continued regular withdrawal bleeding throughout the study period, but no endometrial hyperplasia was encountered. This study demonstrates that the daily administration of a combination of micronized E2 and progesterone results in symptomatic improvement, minimal side effects, an improved lipid profile, and amenorrhea without endometrial proliferation or hyperplasia in menopausal women.

Occurrence of ovarian malignancy in childhood and adolescence: a community-wide evaluation.

During childhood and adolescence, the rate of malignancy in ovarian enlargement is reported to be high-approximately 35% in many large series from tertiary centers. To assess whether this represents an overestimation because of the referral patterns of these institutions, a retrospective review was conducted at five hospitals in Nashville, Tennessee. In females 21 years of age and under, borderline or malignant ovarian neoplasms were identified in only eight (5.8%) of 137 individuals with ovarian enlargement and eight (9.8%) of 82 females with ovarian neoplasms. All six malignant neoplasms were of germ-cell origin. The borderline neoplasms were of epithelial origin, and occurred in females in their late teens. We conclude that the frequency with which ovarian enlargement represents malignancy in this age group appears to be much smaller than previously suggested. Nevertheless, because of the potential for malignant ovarian neoplasia in young females, the presence of an abdominal-pelvic mass requires prompt and thorough attention.

Reactivation blastomycosis presenting as a tuboovarian abscess.

A 32-year-old Korean woman presented with a rapidly enlarging abdominal mass six months after an undiagnosed illness of fever and a large pleural effusion. Exfoliative cytology of a cervical discharge revealed Blastomyces dermatiditis. At laparotomy, a large peritoneal inclusion cyst was found surrounding a tuboovarian abscess with involvement from the cervix to the peritoneum. B dermatiditis was cultured from the excised uterus and fallopian tube. Female genital blastomycosis has rarely been described. The importance of cytology in making the diagnosis in the present case is emphasized.

The management of midtrimester abortion failures by vaginal evacuation.

The management of 58 failed midtrimester primary abortion procedures by vaginal uterine evacuation is described. The indications, technic, and complications of this procedure are presented. This method was the only means of managing failed primary abortion over a 3-year period in which 2045 elective midtrimester abortions were performed. With the development of experience this technic offers significant advantages over other procedures, such as hysterotomy, in the management of such patients.

The possible deleterious effects of the intramyometrial injection of hypertonic urea.

Hypertonic urea has been shown to be an effective midtrimester abortifacient. Although safer than hypertonic saline when injected intravascularly, it has not been compared to saline in the case of inadvertent intramyometrial injection. This report documents that intramyometrial injection of hypertonic urea will result in the same type of muscle necrosis as that produced by saline.

PIP: The effects of intramyometrial injection of hypertonic urea were stu died in 4 rhesus monkeys in the second trimester of pregnancy. In all cases where there was no efflux of the hypertonic solution, muscle necrosis, histologically similar to that observed with hypertonic saline, was observed. It was also evident that small amounts of urea or saline were able to produce considerable necrosis of the endometrium. An injection procedure that obviates the possibility of myometrial puncture, along with very low levels of injection pressure, are recommended for abortion procedures of this type.

Abdominopelvic computed tomography: evaluation in patients undergoing second-look laparotomy for ovarian carcinoma.

Preoperative abdominopelvic computed tomography results and operative findings were compared in 52 patients undergoing second-look laparotomy to confirm tumor status. Seventeen true-negative, 22 false-negative, and 13 true-positive scans were found. The sensitivity was 0.38, specificity was 1.0, and diagnostic accuracy was 0.58. Negative studies were associated with positive findings at laparotomy in 42% of all cases. Fourteen patients were identified who had computed tomography that would have enabled an attempt at the diagnosis of persistent cancer by computed tomography-directed needle aspiration or biopsy, thus avoiding laparotomy. Assuming 80% accuracy of needle aspiration, the cost of computed tomography in all 52 patients is considerably outweighed by the savings that could have been realized by eliminating the need for second-look surgery in these 11 women.

Advanced minimal residual ovarian carcinoma: abdominopelvic irradiation following combination chemotherapy.

Seventeen patients with advanced ovarian carcinoma who had minimal residual intraabdominal disease after six months of combination chemotherapy were treated with abdominopelvic irradiation. All 17 patients had residual intraabdominal tumor nodules with a cross-sectional diameter of less than 2 cm. Eleven had only microscopic residual disease at the time of irradiation. Fourteen have relapsed at a median of eight months after the completion of radiotherapy. All but two had intraabdominal recurrences. Myelosuppression was common and severe, causing marked delays or discontinuation of radiotherapy in ten of 17 patients. Patients receiving the entire planned dose of radiotherapy had longer disease-free survival (14 months median) than did patients receiving only partial doses (seven months median). However, six of seven patients receiving full dose irradiation have relapsed. Abdominopelvic irradiation in the schedule employed here is poorly tolerated and is not an effective salvage treatment in patients with limited or microscopic residual tumor following initial combination chemotherapy.