Prolonged oral etoposide in recurrent or advanced leiomyosarcoma of the uterus: a gynecologic oncology group study.

OBJECTIVE: In a previous study by the Gynecologic Oncology Group only modest activity was seen with bolus etoposide in leiomyosarcoma of the uterus (an 11% response rate). To exploit the schedule dependency of etoposide, which favors longer exposure, a Phase II trial of prolonged oral etoposide was conducted in this tumor. METHODS: Eligibility included leiomyosarcoma of the uterus, measurable disease, one prior chemotherapy regimen which did not include etoposide, WBC >/= 3000/microliter, platelet count >/=100, 000/microliter, serum creatinine

Spontaneous preoperative internal jugular and subclavian vein thrombosis associated with an early-stage synchronous ovarian/endometrial malignancy.

A case of preoperative spontaneous internal jugular/subclavian vein thrombosis documented with magnetic resonance imaging associated with a synchronous stage II ovarian/stage I endometrial malignancy is presented. This unusual deep venous thrombosis site is classically associated with trauma, infection, head and neck malignancies, or central venous catheterization and is rarely associated with distant malignancies. Neck pain and swelling in a gynecologic oncology patient should prompt consideration of this diagnosis.

Ineffectiveness of continuous 5-fluorouracil as salvage therapy for ovarian cancer.

5-Fluorouracil (5-FU) is an antimetabolite chemotherapy, which selectively functions at the S phase of the cell cycle. It is a short-acting agent with a serum half-life of approximately 11 minutes. Increased efficacy with this drug could theoretically be provided by sustained infusion over the doubling time of a tumor. Ovarian cancer that recurs or persists after treatment with platinum-based chemotherapy has a poor prognosis. This study examines the use of long-term infusional 5-FU as a salvage chemotherapy for ovarian cancer. 14 patients with epithelial ovarian cancer were studied. All were stage III or IV disease and all were initially treated with platinum-based chemotherapy with either persistence or recurrence of disease. Patients received 5-FU as 300 mg/m2/day via a continuous infusion for a 10-week cycle with discontinuation occurring for severe toxicity or documented progression. The average infusion per patient was 8 weeks (3-10). Three patients had drug discontinued secondary to toxicity (severe mucositis) and 4 patients had progression prior to the completion of 10 weeks. All patients had progression by the end of the first cycle. The average survival post-5-FU was 8.9 months (range: 0.75-22 months). The lack of response in 14 patients indicates that, statistically, the likelihood of an overall response rate of 20% is less than 0.05. Infusional 5-FU appears to be ineffective as salvage therapy for ovarian cancer.

Vulvar reconstruction using a mons pubis pedicle flap.

The treatment of early vulvar carcinoma has moved toward less radical surgery with reconstruction. This report describes our preliminary experience with a mons pubis flap that is simple and appears safe, reliable, and gives excellent cosmetic and functional results following radical hemivulvectomy. Four patients have undergone this procedure with excellent results. The flap brings pliable, hair-bearing skin which authentically mimics the normal side, thus providing good sexual function. The mons pubis pedicle flap should be considered in patients undergoing radical hemivulvectomy where an excellent cosmetic result is desirable.

Second-look laparotomy.

The second-look laparotomy has become an important means of assessing therapy response in ovarian cancer patients. This procedure enables the gynecologic oncologist to diligently search for small volume persistent disease, which often escapes detection by less invasive means. Subsequent treatment, if required, may then be tailored to the initial biologic response to therapy. However, many patients with negative findings at second look will develop recurrent disease, dampening enthusiasm for the operation. Although controversial, this procedure remains the gold standard for the detection of disease status following chemotherapy for ovarian cancer.

Preservation of multiple oncogenic human papillomavirus types in recurrences of early-stage cervical cancers.

OBJECTIVES: Our purpose was to determine the relationship between human papillomavirus genotypes contained in primary early stage cervical cancers and those contained in the respective recurrences. STUDY DESIGN: Six early-stage cervical cancers that were considered cured by surgical extirpation subsequently recurred within 21 months of the original surgery. The primary tumors and the recurrences underwent polymerase chain reaction for human papillomavirus typing with confirmation of types performed by means of diagnostic restriction fragments. RESULTS: All primary tumors and recurrences contained human papillomavirus, with all primary tumors positive for multiple types. The concordance rate between the primary tumors and recurrences for specific types was 73% (11/15). Among the highly oncogenic types 16 and 18 there was 100% concordance between primary and recurrent tumors. CONCLUSIONS: Highly oncogenic types of human papillomavirus are preserved between primary tumors and their recurrences in cervical cancers. This further supports the role of oncogenic types in the maintenance of the malignant state and supports the clonogenic nature of cervical cancer recurrence.

Insertion of Groshong central venous catheters utilizing fluoroscopic techniques.

Groshong central line indwelling catheters are extensively used in gynecologic oncology patients for administration of chemotherapy, intravenous fluids, and pain medications. They are easy to maintain and have a good safety record. We report on the placement of these central venous catheters under direct fluoroscopic visualization as a method which is safe, inexpensive, and efficacious in high-risk patients. Fluoroscopic visualization during insertion provides several advantages: visualization of bony landmarks, placement of the guidewire into the subclavian vein and superior vena cava under direct visualization, and confirmation of appropriate distal placement of the Groshong catheter. Patient advantages include the following: (1) avoidance of unnecessary punctures to access the subclavian vein; (2) verification of guidewire placement to avoid cephalic placement; (3) passage of the guidewire only as far as the right atrium to avoid potential dysrrhythmias secondary to right ventricular irritation; and (4) a savings of approximately 60% over insertion in the general operating room. Thirty patients had placement under fluoroscopic visualization in the angiography suite of Georgetown University Hospital. The average age of the patients was 58 years (42-78). Sixteen patients had ovarian cancer, 6 had endometrial cancer, 5 had cervical cancer, and 3 had other gynecologic malignancies. Fifteen patients had catheters placed for chemotherapy, 14 for hydration, and 1 for pain control. Ten patients had had previous central venous catheters: 6 had been removed for infection, 2 for thrombus, 1 for completion of chemotherapy, and 1 for catheter kinkage. All 10 with previous catheters had successful placement of catheters in the angiography suite. Complications from insertion were minimal with one asymptomatic pneumothorax and one proximal port in an extravascular position. We present the technique of fluoroscopic insertion of Groshong catheters which is an effective method of placement in high-risk patients.

Colonic surgery in gynecologic oncology. Risk factor analysis.

Colonic surgery is a critical part of gynecologic oncology care. A 12-year review of colonic surgery on a gynecologic oncology service was performed evaluating risk factors and their impact on postoperative morbidity. There were 124 procedures performed on 92 patients; 9 patients had no prior surgery, chemotherapy or radiation. Fifty-six percent of the patients were considered malnourished on the basis of a serum albumin level < 3.5 g/dL. The 124 procedures consisted of 57 colon resections with primary reanastomosis, 10 small bowel-colon bypass procedures and 57 colostomies. Of the 57 (67%) colostomy operations, 38 also had concomitant abdominal-pelvic procedures. There were 15 major bowel complications and 17 major systemic postoperative complications. Prior surgery and poor nutritional status significantly correlated with postoperative morbidity; however, prior radiation did not reveal an increased risk for postoperative complications.

Prognostic significance of polymerase chain reaction detected human papillomavirus of tumors and lymph nodes in surgically treated stage IB cervical cancer.

This study describes the prognostic role of polymerase chain reaction detected human papillomavirus (HPV) in Stage IB cervical cancer patients treated with radical hysterectomy and pelvic and paraaortic node dissection. All tumors were confined to the cervix and all margins and nodes were disease free. Twenty-one patients were analyzed: 6 patients recurred within 20 months of initial therapy, while 15 had no evidence of disease with a minimum follow-up of 36 months. Polymerase chain reaction (PCR) was performed on paraffin-block tissue of the hysterectomy specimen cervical tumor and lymph nodes. Oligonucleotide probes for HPV types 6, 11, 16, 18, 31, 33, and 35 were used with consensus primers for uncharacterized HPV types created from an L1 constant region. Control tissues were run with each tumor sample to assure against contamination. HPV type confirmation was performed using diagnostic restriction sites. HPV was detected in all cervical tumors. Recurring tumors were infected with multiple types of HPV in all 6 tumors versus only 5 of 15 nonrecurring tumors being multiply infected (P = 0.023). No tumor had HPV 6 or 11, and the incidence of HPV 16, 31, 33, and 35 was not significantly different for recurrent versus nonrecurrent groups. HPV 18 was found in 5 of 6 recurring cancers versus 1 of 15 nonrecurring tumors (P = 0.0029). PCR typing of the histologically negative nodes that had been obtained at radical hysterectomy was done in all 6 recurring patients and in 6 nonrecurring patients. The recurrent patients had a significantly higher incidence of lymph nodes positive for HPV DNA (71%) than the nonrecurring patients (35%) (P = 0.0047). These observations suggest that HPV 18 cervical cancer patients, those with infections of multiple types, and those with HPV DNA in histologically negative lymph nodes may be at increased risk for recurrence.

Radical hysterectomy morbidity in relation to age.

The complications of radical hysterectomy in patients 65 years and older were compared with those in women younger than 65. There was no statistical difference in complication rates between the two groups, although the older women had a significantly higher incidence of preoperative medical problems. No surgical deaths occurred in either group. Our data indicate that selected older women can tolerate radical hysterectomy as well as younger ones.

Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine.

The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor.

Diagnosis and treatment of pulmonary metastases from cervical carcinoma.

The records of 2116 patients treated for cervical malignancy from 1969 to 1984 at the University of Alabama at Birmingham were reviewed and 88 (4.16%) had pulmonary lesions consistent with metastatic cervical cancer. The data were analyzed to characterize risk factors for developing lung metastases, to determine radiographic patterns, to assess methods of documentation, and to determine response to chemotherapy. Platinum-type chemotherapy has a 67.7% response rate on chest X ray, with one-third of the responses being complete. The prognosis is poor with a median survival of 0.69 year (8.3 months); only 2 of these 88 patients were long-term survivors. Although the survival is poor, a few statistically significant factors could be identified as prognostic. Our data do not support use of surveillance chest X rays, as there is no statistically significant survival difference in symptomatic versus asymptomatic patients. The development of more effective salvage therapy may alter this recommendation.

Treatment of nonmetastatic gestational trophoblastic disease with sequential intramuscular and oral methotrexate.

Thirty-seven patients with nonmetastatic gestational trophoblastic disease (NMGTD) were treated with one or more cycles of oral methotrexate following intramuscular methotrexate as part of induction chemotherapy. Remission was achieved in 31 patients (83.8%). All failures were readily cured with alternate regimens. Prospective studies using this safe, easily administered modality are needed to verify its apparent efficacy.

A phase I/II study of intraperitoneally administered doxorubicin entrapped in cardiolipin liposomes in patients with ovarian cancer.

A phase I and II clinical trial of intraperitoneally administered liposome-encapsulated doxorubicin in patients with advanced ovarian cancer is being evaluated. Doxyrubicin liposomes were prepared with cardiolipin, phosphatidyl choline, cholesterol, and sterarylamine and sized by flow cytometry before administration. Fifteen patients have been treated with 42 cycles of intraperitoneal liposome-encapsulated doxrubicin. Liposome-encapsulated doxorubicin in 2 L of normal saline solution was infused over 1 hour through an infusaport into the peritoneal cavity with a dwell time of 4 hours every 21 days. Liposome-encapsulated doxorubicin has been administered at escalating doses up to 100 mg/2 L and has been well tolerated. Increased bowel motility with mild-to-moderate abdominal distress has been encountered during the first 24 hours after administration. There has been one patient with presumed chemically induced peritonitis after a temperature elevation to 39.5 degrees C. There has been no myelosuppression, abnormalities of liver function tests, or alopecia. Nausea and vomiting were minimal. Liposome-encapsulated doxorubicin was extravasated in two patients without sequelae. Drug levels were measured after completion of infusion. At a dose of 70 mg, the peak intraperitoneal concentration was 28.6 micrograms/microliter, which was reduced to 23.6 micrograms/microliter by 2 hours. Concurrent plasma levels were in the range of 0.2 to 0.5 micrograms/microliter. A similar pattern was observed at other doses. The maximum tolerable dose has not yet been obtained. There were three responders in the 10 evaluable patients. The preliminary experience with intraperitoneal liposome-encapsulated doxorubicin is encouraging.

Complications of combined radical hysterectomy-postoperative radiation therapy in women with early stage cervical cancer.

Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications.

Melanosis of the cervix.

Benign and malignant melanotic cervical lesions are rare and require biopsy to rule out melanoma. Reported is a case of cervical melanosis, defined as benign epithelial pigmentation.

Treatment of nonmetastatic gestational trophoblastic disease with oral methotrexate.

Fifteen patients with nonmetastatic gestational trophoblastic disease were treated solely with methotrexate given orally rather than intramuscularly. Remission, defined as a beta-human chorionic gonadotropin titer of less than 5 mIU/ml for 3 consecutive weeks, was attained in 13 (87%) of the 15 patients. Level of toxicity was acceptable. Patient comfort, convenience, and less time off work and in the physician's office are significant advantages to this efficacious, well-tolerated method of therapy.

Uterine leiomyomas with retroperitoneal lymph node involvement.

We have presented a case of benign metastasizing leiomyoma (BML) involving pelvic lymph nodes found at the time of hysterectomy for uterine leiomyomas. The patient received postoperative adjunctive therapy with methotrexate, actinomycin D, chlorambucil, and irradiation, and has no evidence of disease 11 years later.

Psammoma bodies in a cervicovaginal smear associated with an intrauterine device. A case report.

Psammoma bodies were found in a cervicovaginal smear, presumably related to the patient's use of an intrauterine device. Colposcopy, endocervical and uterine curettage, and laparoscopy with pelvic washings ruled out other conditions that may be associated with psammoma bodies.