Treatment of vaginal intraepithelial neoplasia with the carbon dioxide laser.

The carbon dioxide laser was used to treat vaginal intraepithelial neoplasia in 24 patients. Initially, partial or complete ablation of vaginal epithelium was performed, the extent of the procedure depending upon the distribution of disease. Later in the series complete ablation was performed routinely because of recurrences among patients treated with only partial ablation. Fifteen patients had severe dysplasia or carcinoma in situ (vaginal intraepithelial neoplasia III), and nine had moderate dysplasia (vaginal intraepithelial neoplasia II). Of the 24 patients, 20 had satisfactory removal of vaginal intraepithelial neoplasia after a single operation. Four patients with vaginal intraepithelial neoplasia III who underwent partial vaginal epithelial ablation had persistence of abnormal tissue detected within six months of treatment. These patients were re-treated successfully with the laser. Average length of hospitalization for vaginal epithelial ablation with the carbon dioxide laser was two days. Excellent postoperative healing occurred and all patients have resumed their pretreatment sexual pattern. Follow-up ranges from six to 27 months, with an average follow-up of 15 months. The carbon dioxide laser can be used cost-effectively to remove vaginal intraepithelial neoplasia.

Endometrial carcinoma diagnosed by examination of peritoneal dialysate.

Well-differentiated adenocarcinoma of the endometrium was diagnosed by cytologic examination of peritoneal dialysate during continuous ambulatory peritoneal dialysis in a 70-year-old woman. The patient had undergone estrogen therapy for 16 years. The carcinoma was localized, noninvasive, and apparently at an early stage of development. Surgical removal was followed by megestrol acetate chemotherapy and the patient currently remains on peritoneal dialysis, free of recurrence, at 14 months. This case suggests that cellular material from the endometrium can be retrieved from intraperitoneal dialysate in patients undergoing peritoneal dialysis. Therefore, cytologic examination should be performed on peritoneal fluid with elevated counts associated with sterile cultures or atypical features.

Use of the human tumor stem cell assay to study chemotherapy sensitivity in cancer of the cervix.

Two questions concerning chemotherapy of cervical cancers are addressed in this study. 1) Can the human tumor stem cell assay identify active chemotherapeutic agents?; and 2) Can the human tumor stem cell assay predict which patient's tumors will demonstrate clinical responsiveness to chemotherapy? Sixty-seven of 76 cervical cancer specimens (88.2%) were grown in the human tumor stem cell assay, resulting in 159 separate drug assays. Based on the known activity of standard chemotherapeutic agents demonstrated in clinical trials, cisplatin, bleomycin, vincristine, and mitomycin C were chosen for testing. In vitro sensitivity patterns, seen at one-tenth of the peak plasma drug concentration, were similar to those seen in historic clinical trials. Retrospective correlations between in vitro drug sensitivity data and patient responses to chemotherapy are available from 13 patients, demonstrating clinically helpful predictive capabilities of the assay. Two conclusions were made: 1) The human tumor stem cell assay can determine single agent activity, which is often dose related; and 2) Useful correlations with clinical responses were observed.

Treatment of advanced ovarian malignancy with chemoimmunotherapy using autologous tumor and Corynebacterium parvum.

Fourteen patients with advanced ovarian epithelial carcinoma were treated with a combination of chemotherapy and immunotherapy. The chemotherapy consisted of either melphalan or a combination of adriamycin, cytoxan, and cisplatin. The immunotherapy consisted of the injection of autologous radiation-attenuated tumor and Corynebacterium parvum. No significant toxicity occurred as a result of the immunotherapy, and there was no evidence of tumor growth at the sites of injection. The autologous tumor skin test showed prognostic value. Skin testing with C parvum was of less prognostic value than tumor. All other studies of immunologic status, including T- and B-cell enumeration and blastogenic responsiveness of the patients' lymphocytes to autologous tumor and mitogens, were of no prognostic value.

Cryotherapy and laser treatment for intraepithelial neoplasia of the cervix, vagina, and vulva.

Over the past 20 years, the incidence of invasive genital neoplasia has decreased, while the incidence of preinvasive, or intraepithelial, neoplasia has increased. These trends are the result of increased cancer screening women and the widespread application of improved diagnostic techniques by physicians. The rapid increase in genital human papillomavirus infections over the past 10 years may also be a factor influencing the increased incidence of intraepithelial neoplasia. The average age at diagnosis of genital intraepithelial neoplasia has decreased, thereby heightening the need for more conservative treatment options. The application of cryosurgical techniques during the 1970s and the introduction of lasers in the 1980s have fulfilled this need for less mutilative, organ-preserving treatment.

Chemotherapy of advanced squamous carcinoma of the cervix: a phase I-II study of high-dose cisplatin and cyclophosphamide. A pilot study of the Gynecologic Oncology Group.

Sixteen patients with recurrent squamous cell carcinoma of the cervix were treated with a combination of cyclophosphamide and cisplatin to determine a tolerable dose schedule, major adverse effects, and a general estimate of response rate and duration. Toxicity was substantial with a dose of cyclophosphamide 1000 mg/m2 and cisplatin 100 mg/m2 given intravenously every 3 weeks. Renal, hematologic, and gastrointestinal toxicities were severe. Of the 12 patients with measurable disease, there were two complete responses and three partial responses for a response rate of 42%. The median duration of response was 24 weeks. Six patients remained stable during therapy and one patient had progression of disease. Use of cyclophosphamide and cisplatin in combination chemotherapy for recurrent carcinoma of the cervix was tolerable but associated with substantial toxicity. The responses seen in this study are encouraging and warrant further comparative trials with this combination of drugs.

Vaginal laser surgery.

Vaginal epithelial lesions including endometriosis, cysts, septae, human papillomavirus (HPV) disease, and vaginal intraepithelial neoplasia (VaIN) can be successfully treated by laser surgery. The carbon dioxide laser with a wavelength of 10,600 nm is the ideal laser for these clinical applications. Pretreatment evaluation using colposcopically directed biopsies is mandatory. Adherence to surgical techniques including the selection of a delivery system, control of thermal injury, depth of destruction and bleeding, as well as determination of treatment margins and therapeutic endpoints are critical for optimal clinical outcome. After treatment of HPV disease and VaIN, long-term follow-up is essential for this group of patients who are at risk for invasive cancer.

Use of colposcopically directed, four-quadrant cervical biopsy by the colposcopy trainee.

Colposcopically directed cervical biopsies performed by experienced colposcopists have greatly reduced the need for conization of the cervix to evaluate patients with cervical intraepithelial neoplasia (CIN). Because of the subjectivity of the colposcopic technique and variable time required to become skilled, continued reliance on cervical conization is often recommended to validate colposcopic findings for novice colposcopists . We assessed the colposcopic skill of residents in training in obstetrics and gynecology who had received 9-12 months of instruction in colposcopic techniques. Biopsies of each quadrant of the ectocervix were done after the resident recorded his or her colposcopic diagnosis. In 26% of the patients there was overestimation or underestimation of the histologic findings by more than one grade in the cervical quadrant suspected on colposcopy to contain the most advanced CIN lesion. In 30% of patients the histologically most advanced CIN lesion was not identified by the colposcopist . In 11% of patients with histologic findings of CIN both cytology and colposcopy were negative. Only 69% of the histologically confirmed lesions were diagnosed colposcopically by the resident colposcopists . The four-quadrant, colposcopically directed biospy technique is recommended as an effective training method for the beginning colposcopist .

Evaluating the acquisition of colposcopy skills in an obstetric-gynecologic residency program.

Instruction in colposcopic technique is now an integral component of residency training in obstetrics and gynecology. No statistical method for assessing colposcopy skills has been reported on before. The statistical calculations of sensitivity, specificity and kappa were applied to determine if there was any progressive acquisition of colposcopy skills by the colposcopy trainee during the four-year residency program.

Cervical intraepithelial neoplasia.

Proper technique and competent cytopathology are important in obtaining and evaluating the Pap smear. Colposcopy and directed biopsies, combined with endocervical curettage, will permit outpatient diagnosis in about 85 percent of patients with cervical intraepithelial neoplasia. Other patients will require knife conization for diagnosis. A wide range of treatment options exists. Selection of therapy is based on both the patient's reproductive plans and the severity of the disease. Regular follow-up with Pap smears is mandatory after any treatment.

Advanced and recurrent carcinoma of the ovary treated with a combination of cyclophosphamide, doxorubicin, and cytosine arabinoside.

Twenty-six patients with advanced or recurrent epithelial ovarian carcinoma, FIGO Stages III and IV, were treated with combination chemotherapy using cyclophosphamide, doxorubicin, and cytosine arabinoside (CARA). In 17 cases, CARA was initiated following failure to single-agent chemotherapy, in all cases, melphalan. Nine patients with advanced cancer received CARA as their primary chemotherapy after maximum cytoreductive surgery. The overall response rate was 27%; however, in patients without prior chemotherapy the response rate was 44%. There were 6 complete responders, 1 partial responder, 13 patients with stable disease, and 6 who failed to respond to therapy. Four of six complete responders had remission durations greater than 10 months. The median progression free interval (PFI) of patients with residual tumor diameters less than 2 cm was significantly longer (P less than or equal to 0.04) than the PFI of patients with greater initial tumor burden. The median PFI of complete responders was significantly longer (P = 0.007) than PFI of patients with less than complete response. Previously untreated patients had longer median PFI than those who had failed previous chemotherapy (P = 0.07). The major dose-limiting toxicity of CARA was thrombocytopenia. Other myelosuppression was moderate and no cardiotoxicity was encountered.

In vitro chemotherapy testing of gynecologic tumors: basis for planning therapy?

The human tumor stem cell assay (HTSCA) has broad research applications in the field of cell biology as well as in clinical chemotherapy. This report examines the applicability of the HTSCA to patient treatment planning, asking: (1) How often will gynecologic tumors grow in the assay? (2) What kinds of therapeutically useful information can be gained from the assay? (3) What are the correlations between in vitro results and patient treatment responses? Tumor specimens from 207 patients having ovarian, cervical, or endometrial carcinomas have been studied with the HTSCA, 183 of which have grown in vitro. Of 103 ovarian cancer specimens which grew in culture, 564 separate drug assays have been done, looking for patterns of sensitivity among "first line" drugs as well as drugs used for relapsing patients. More than half of the patients studied had one or more drugs which showed in vitro activity. Nineteen patients have had single-agent chemotherapy prospectively selected on the basis of the HTSCA results with a "sensitive" predictive accuracy of 90% and a "resistant" predictive accuracy of 100%.

Neoadjuvant therapy for advanced squamous cell carcinoma of the cervix: cisplatin followed by radiation therapy--a pilot study of the Gynecologic Oncology Group.

Eleven patients with untreated advanced squamous cell carcinoma of the cervix (FIGO Stage IIIB and IVA, or positive paraaortic nodes) were treated with cisplatin 50 mg/m2 every 3 weeks for six courses prior to irradiation therapy (RT). Six patients completed six courses of cisplatin prior to RT with one complete and two partial responses (PR). Five other patients did not complete cisplatin therapy; two progressed after two and three courses, one had a PR after three courses and refused further therapy, one refused treatment after two courses and one elected to begin RT after one course. Two patients had reversible nephrotoxicity. No other major toxicity was noted. Six patients had stem cell assay prior to treatment and assay results were predictive of cisplatin response in five. Only one patient remains alive at 44+ months. Cisplatin chemotherapy prior to irradiation therapy is feasible and without substantial toxicity but is unlikely to be of benefit in patients with advanced cervical cancer.

Autoimmune hemolytic anemia and ovarian dermoid cysts: case report and review of the literature.

A case of autoimmune hemolytic anemia (AIHA) associated with an ovarian dermoid cyst is presented. Early recognition and specific therapy for this entity is stressed for optimal results since conventional forms of therapy of AIHA are ineffectual. Unusual features of the case are discussed. The literature is reviewed and possible mechanisms of the hemolytic process are discussed.

Single dose carbenicillin versus T-tube drainage in patients undergoing vaginal hysterectomy.

In this study, a prospective, randomized, non-blinded report, single dose carbenicillin prophylaxis preoperatively is compared with T-tube suction drainage postoperatively in 50 patients undergoing vaginal hysterectomy. A higher incidence of febrile morbidity, fever index units, cellulitis of the vaginal cuff and prolonged hospitalization postoperatively was experienced by the group patients with T-tube suction drainage, P less than 0.05. Our satisfactory results with single dose carbenicillin prophylaxis preoperatively are similar to those of previous studies using more extended antibiotic prophylaxis perioperatively.

Tubal microsurgery with the carbon dioxide laser.

Thirty New Zealand White female rabbits underwent tubal resection and reanastomosis for comparison of conventional microsurgery and laser microsurgical techniques. The rabbits were divided into three groups. The first group of 10 rabbits had 3 cm of tissue resected by knife from each uterine horn; the cut ends were then reanastomosed in one layer with 8-0 Vicryl sutures with the use of the operating microscope. The second group of 10 rabbits had 3 cm of tissue resected by laser from each uterine horn; the cut ends were then reanastomosed in one layer with 8-0 Vicryl. The third group of 10 rabbits had 3 cm of tissue resected by laser from each uterine horn; the cut ends were then reanastomosed by "welding" the tissues with the laser. All rabbits in the first group became pregnant. Only four in the second group became pregnant, but none in the third group became pregnant. It is concluded that the carbon dioxide laser beam as used in this study has no place in tubal resection and reconstruction.

Vincristine infusion in refractory gynecologic malignancies.

Prolonged intravenous infusion of vincristine was evaluated in 26 patients with advanced, refractory gynecologic malignancies. Most patients (88%) had progressive disease following treatment with one or more chemotherapeutic agents. Treatment consisted of a 0.5 mg intravenous bolus injection followed immediately by continuous infusion of 0.25-0.50 mg/m2 vincristine given daily for 5 days. There were no objective responses observed among 14 patients with carcinoma of the cervix, 7 patients with carcinoma of the ovary, or 5 patients with carcinoma of the endometrium. Toxicity was mild when present and consisted of paresthesias and myalgias. Vincristine infusion appears to be a well-tolerated but ineffective treatment for refractory gynecologic malignancies.

Intravenous vincristine infusion: phase I trial.

In an attempt to sustain potentially cytotoxic concentrations of vincristine in man, a five-day continuous infusion of vincristine after an initial intravenous bolus injection was administered to 30 patients with refractory malignancies. Three dosage levels were explored (0.5 mg/m2, 0.75 mg/m2, and 1.0 mg/m2 daily for five days). Neurologic and hematologic toxicity were severe at the high dose level, whereas mild to moderate toxicity occurred at the 0.5 and 0.75 mg/m2 dose levels. Objective responses were noted in 11 patients (37%) with the following malignancies: non-Hodgkin's lymphoma (4), acute non-lymphoblastic leukemia (2), chronic granulocytic leukemia in blast crisis (1), carcinoma of the breast (3), and small cell carcinoma of the lung (1). Responses were observed at each infusion dose level. Nine of the 11 responders had previously progressed while receiving conventional intravenous bolus injection of vincristine. These data suggest that the clinical usefulness of vincristine may be enhanced by the use of infusion techniques. A maximum daily dose of 0.5 mg/m2 given for five days is recommended for future trials of intravenous vincristine infusion.