Combined effects of 1,25-dihydroxyvitamin D3 and platinum drugs on the growth of MCF-7 cells.

The effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and platinum treatments (both singly and combined) on the growth inhibition of MCF-7 cells, an epithelial cell line shown to possess specific receptors for 1,25(OH)2D3, were evaluated. The inhibitory effects of 1,25(OH)2D3 and platinum on MCF-7 cell proliferation in vitro were time and dose related. The data showed that 10 nM and 100 nM 1,25(OH)2D3 inhibited MCF-7 cell growth by 10.8 +/- 2.4% and 34.9 +/- 0.5% (mean +/- SE), respectively. The degrees of growth inhibition induced by 0.2 to 200 micrograms/ml of cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin) were slightly less than those induced by 0.02 to 20 micrograms/ml of cis-diamminedichloroplatinum(II) (cisplatin). The combined administration of 10 nM and 100 nM 1,25(OH)2D3 with either carboplatin (200 to 0.2 micrograms/ml) or cisplatin (20 to 0.02 micrograms/ml) was evaluated. Addition of 1,25(OH)2D3 to the platinum resulted in marginal to marked enhancement of growth inhibition over that observed with either platinum alone. The strength of these interactions varied inversely with the dose of the platinum drugs. Evaluation of drug interactions with isobolograms showed that at near-serum levels, carboplatin or cisplatin interacted synergistically with 1,25(OH)2D3 to inhibit MCF-7 cell growth. Our findings suggest potential usefulness in combining 1,25(OH)2D3, a biological modifier, with cytotoxic agents for the treatment of malignant disease.

Detoxifying enzymes in human ovarian tissues: comparison of normal and tumor tissues and effects of chemotherapy.

Many anticancer drugs exert their cytotoxic effects via formation of oxygen free radicals. Cellular thiols, glutathione (GSH)-dependent enzymes and other redox enzymes are involved in the metabolism of these anticancer drugs and of the oxygen free radicals that may be generated during their metabolism. We quantified these biochemical parameters in cytosol from human ovarian tissues. We compared non-protein thiol levels, GSH transferase, GSH peroxidase, superoxide dismutase, catalase, DT diaphorase and aldehyde dehydrogenase activity in serous ovarian tumors (n = 15), other malignant ovarian tumors (n = 12), benign ovarian tissue (n = 10) and histologically normal ovarian tissue (n = 12). Mean GSH transferase and DT diaphorase activities were similar in serous and other malignant ovarian tumors. GSH transferase activity was decreased in malignant tissues relative to normal and benign tissues. Mean DT diaphorase and superoxide dismutase activities were increased in the malignant tissues, although this was not statistically significant. The mean levels of all enzymes except superoxide dismutase and aldehyde dehydrogenase in benign tissues were fairly similar to the mean levels found in normal tissue samples. Tissues from patients with serous ovarian tumors, who had received cyclophosphamide and cisplatin prior to surgery, also were analyzed (n = 7). Except for aldehyde dehydrogenase, all the parameters measured were decreased in these samples relative to serous tissue from untreated patients. These biochemical analyses may be useful in understanding the mechanisms involved in the response to chemotherapy.

Control of intraoperative hemorrhage in gynecology with the use of fibrin glue.

Fibrin glue, a biodegradable tissue adhesive, is a valuable topical hemostatic agent and an effective tissue sealant. We describe the use of fibrin glue in controlling life-threatening hemorrhage in three gynecology patients. Simultaneous injection of equal amounts of cryoprecipitate and bovine thrombin at bleeding sites results in formation of the glue, which effectively controls the bleeding. When used in conjunction with good surgical technique, fibrin glue may decrease the need for blood transfusions and may shorten operating room time.

Trichloroacetic acid in the treatment of human papillomavirus infection of the cervix without associated dysplasia.

Human papillomavirus-induced cytologic changes were found in 379 (10.9%) of 3461 Papanicolaou smears done at the Gynecology Clinic at Wayne State University. Of these 379 patients, 98 (25.8%) had no cytologic evidence of dysplasia. Forty-six of the 98 patients, who had colposcopic and histologic evidence of human papillomavirus without dysplasia, agreed to participate in this study. All patients underwent a Q-Tip application of 85% trichloroacetic acid to the entire cervix, including the endocervical canal and the transformation zone, until the mucosa turned white. Coexistent vaginal and vulvar condyloma were treated simultaneously in six patients. The patients were reexamined at two-week intervals to ascertain the need for reapplication of trichloroacetic acid. No colposcopic evidence of human papillomavirus was found in 18 patients at the first visit, whereas 28 patients required reapplication of trichloroacetic acid. Three months after treatment, a follow-up Papanicolaou smear and colposcopic examination revealed no human papillomavirus infection in 31 patients. Seven patients had persistent infection and eight patients were lost to follow-up. Our preliminary data from this study suggest that 85% trichloroacetic acid is effective treatment of human papillomavirus infection of the cervix without dysplasia.

Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator.

Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques.

Ovarian cancer. Advances in management.

Substantial progress has been made in understanding the biologic behavior of ovarian cancer and in assessing disease states and response to therapy with transvaginal sonography, CT scan, and tumor markers such as CA-125. There is no longer controversy regarding the importance and feasibility of adequate surgical staging, the need for cytoreduction, and the utility of cisplatin- or carboplatin-based combination chemotherapy in the management of patients with ovarian cancer. Increasing chemotherapy dose through escalated systemic doses or intraperitoneal administration, revising multidrug resistance, the use of biologic response modifiers, and the development of new methods of chemosensitivity testing may help improve the current 5-year survival rate of less than 30% for patients with stage III ovarian cancer. Significant improvement in screening tests and diagnostic capabilities will be necessary for a dramatic increase in survival.

Treatment of recurrent cervical cancer with cis-platinum and mitomycin C: a phase II study.

Twenty-three patients with nonresectable, recurrent cancer of the cervix were treated with a combination of cis-platinum and Mitomycin C. The overall response rate was 35% in 20 evaluable patients. Four patients (20%) achieved a complete response with a median duration of 9 months. Three patients (15%) achieved a partial response with a median duration of 11 months. The objective response rate was 33.4% for tumors within previously irradiated sites and 45% for distant metastases. The overall median survival was 10.3 months, and median progression-free interval was 6.7 months. Toxicity with this regimen was acceptable and consisted of nausea, vomiting, marrow suppression, and peripheral neuropathy. We conclude that this regimen is well tolerated with a low incidence of toxicity and can be safely administered on an out-patient basis. However, the superiority of this combination over cis-platinum alone remains to be determined.

Concurrent radiation therapy, cis-platinum, and mitomycin C in patients with poor prognosis cancer of the cervix: a pilot study.

Nineteen patients with poor prognosis squamous cell cancer of the cervix were treated with concurrent radiation therapy (RT) and chemotherapy between February 1986 and July 1988. Treatment consisted of intravenous Mitomycin C 10 mg/m2 on days 1 and 43 and cis-platinum 50 mg/m2 on days 1, 22, and 43. All patients received external RT (5,000 cGy in 28 fractions) and brachytherapy (6,000 cGy to point A.) Additionally, patients with paraaortic lymph node involvement received 4,000 cGy paraaortic RT. The toxicity of this regimen was assessed using Southwest Oncology Group criteria. Toxicity was acceptable and did not significantly delay RT. In addition, complete pelvic response was noted in 18 of 19 (95%) patients within month of completion of therapy and maintained despite distant metastases. At the time of this report, 14 of the 19 patients are alive 9-22 months after initiation of treatment. Chemotherapy with cis-platinum and Mitomycin C concurrently with RT is feasible in patients with locally advanced cervical cancer. Further follow-up of our patients is required to determine whether this regimen will have a favorable impact on survival.

Evaluation of amonafide in cervical cancer, phase II. A SWOG study.

The Southwest Oncology Group conducted a Phase II study of amonafide in patients with metastatic or recurrent squamous cell cervical cancer. Twelve of the 15 patients were fully evaluable for response and toxicity. There were no clinical responses seen; 2 patients had stable disease while 13 had progressive disease. The major complication of this therapy was myelosuppression. Four patients had life-threatening granulocytopenia (less than 500/microliters), 3 patients had life-threatening leukopenia (less than 1000/microliters), while 2 patients had life-threatening thrombocytopenia (less than 25,000/microliters). Amonafide has significant toxicity but appears to be an inactive drug in metastatic or recurrent squamous cell cancer of the cervix.

Phase II trial of amonafide in patients with advanced metastatic or recurrent endometrial adenocarcinoma. A Southwest Oncology Group study.

Amonafide, a benzisoquinoline-1,3-dione was administered to 38 patients with recurrent or metastatic, bidimensionally measurable endometrial cancer. There were 34 patients with no prior cytotoxic chemotherapy, performance status of 0-2, and normal bone marrow, renal, and hepatic function were eligible for response and toxicity evaluation. Amonafide, 300 mg/m2, was administered intravenously over 1 hour daily for 5 consecutive days. Courses were repeated every 21 days. The major grade 3 or 4 toxicities were hematologic with granulocytopenia in 18 patients (53%), thrombocytopenia in 6 patients (18%), and anemia in 8 patients (24%). Infectious complications occurred in 3 patients (9%). Other side effects included cardiac dysrhythmias, hypotension, pain and phlebitis at the site of injection, nausea, vomiting, and flu-like symptoms. The overall objective response rate was 6% (95% confidence interval of 1-20%); 2 patients had a complete response (6%), 9 patients had stable disease (26%) and 21 patients had progressive disease (62%). Two patients had insufficient follow-up for response determination and are assumed to be nonresponders. The median survival of the eligible patients was 8 months. With the toxicity observed and the low response rate, amonafide at this dose and schedule has no efficacy in the treatment of endometrial cancer.

Endometrial carcinoma presenting as a large inguinal mass.

Patients with endometrial cancer usually present with vaginal bleeding. A case of endometrial cancer presenting as an asymptomatic, large, inguinal mass is reported. This unusual clinical picture and its management are discussed.

Life threatening complications of endometriosis.

Endometriosis affects 5-20% of menstruating women and occurs primarily within the pelvis. Although histologically benign, ectopic endometrial tissue possesses the ability to grow, infiltrate and disseminate with life threatening results/consequences. This is illustrated by a case of asymptomatic endometriosis involving the ureters and rectum. The importance of evaluating the integrity of the urinary tract in endometriosis, especially cases involving the uterosacral ligaments, is stressed. Appropriate therapy followed by periodic surveillance for progression of the disease is discussed.

Small cell anaplastic lung cancer presenting as an ovarian metastasis.

An unusual case of small cell anaplastic carcinoma of the lung, presenting as a pelvic mass, is presented. Histochemical and electron microscopic findings confirmed the diagnosis. The pathologic features and unique clinical characteristics are discussed with comments on the topic of metastatic ovarian tumors.

Actinomycosis mimicking pelvic malignancy.

Pelvic actinomyces, usually a complication of an intrauterine device (IUD), is uncommon and may present a diagnostic dilemma because of an atypical clinical presentation. We present a patient with a cervical tumor, extensive parametrial induration with involvement of the posterior bladder wall, and regional lymph nodes which mimicked advanced cervical cancer and presented a significant diagnostic problem.

Meigs's syndrome and ovarian thecoma in pregnancy. A case report.

Ovarian thecoma is a rare tumor, accounting for less than 1% of all ovarian tumors. Thecomas occur even more infrequently during pregnancy, as evident from the fact that there are only 16 such case reports. A 16-year-old, pregnant, black woman presented with ovarian thecoma, pleural effusion and ascites at 32 weeks' gestation. To our knowledge, this was the first reported case that fulfills the criteria of Meigs's syndrome during pregnancy. Ovarian tumors in pregnancy may have very subtle clinical manifestations, making the diagnosis a challenge. Delivery by cesarean section at term is recommended in these patients for the best maternal and fetal outcome.

Extragonadal, mature, solid teratoma with omental implants. A case report.

A well-encapsulated paracervical teratoma was resected. It consisted entirely of histologically mature elements, including thyroid tissue. The greater omentum was found to contain a metastatic implant of mature thyroid tissue. This case illustrates the natural history of teratomas.

Retroperitoneal pelvic lipoma.

A patient with a retroperitoneal pelvic lipoma is presented. Preoperative assessment with computed axial tomography led to the presumptive diagnosis of a fat-containing tumor. Management and differential diagnosis of retroperitoneal tumors are described.

Pericardial metastases in squamous cell cancer of the cervix. A report of two cases.

In patients with pericardial metastases of squamous cell cancer of the cervix, the metastases represented a preterminal event and were a part of widespread metastatic disease.

Adenocarcinoma in a mature cystic teratoma. A case report.

A mucin-producing adenocarcinoma arose in a well-differentiated, mature, cystic teratoma. The patient underwent a total abdominal hysterectomy, left salpingo-oophorectomy, omentectomy and paraaortic lymph node biopsy. The prognosis is unfavorable when the tumor extends through the cyst wall and involves intraperitoneal structures.

Obstructive mucocele of the cervix after subtotal hysterectomy. A case report.

A benign obstructive mucocele of the cervix presented as a pelvic mass after a subtotal hysterectomy. Hypertrophy of the smooth muscle of the leiomyoma, under the influence of circulating estrogen, resulted in distortion and obstruction of the endocervical canal, forming a mucocele.