Differential retinoic acid radiosensitization of cervical carcinoma cell lines.

The potential of retinoic acid as a radiosensitizer was investigated using SiHa and CC-1 human uterine cervical carcinoma cell lines, representative of high- and low-grade lesions, respectively. SiHa was significantly (P < 0.05) radiosensitized, whereas CC-1 was not. Although 48 h of treatment with 5 microM 13-cis-retinoic acid prior to irradiation was sufficient to induce radiosensitization, continuation of treatment after irradiation significantly increased the effect (P < 0.05). Three hypotheses were tested to explain the different responses of the two lines. One hypothesis was that SiHa is more sensitive to retinoic acid than CC-1. Measurement of growth revealed that SiHa was more sensitive to growth inhibition by retinoic acid than CC-1. The second hypothesis was that retinoic acid increases the proportion of G1-phase cells in SiHa but not in CC-1. This was found not to be true, because a retinoic acid treatment schedule that induced radiosensitization did not alter cell cycle distribution profiles in the absence of radiation. The third hypothesis was that retinoic acid alters the cell cycle response of SiHa but not CC-1 to radiation. Postirradiation cell cycle profiles revealed that retinoic acid increased G1 delay in SiHa, whereas CC-1 exhibited no significant G1 delay. Both lines exhibited G2 delays that were unaffected by retinoic acid. In conclusion, radiosensitization of SiHa but not CC-1 may be explained by different sensitivities to retinoic acid and differences in postirradiation cell cycle responses. Radiosensitization at radiation doses used clinically was observed when retinoic acid was administered both before and after irradiation.

Laparoscopically assisted vaginal hysterectomy. Single-surgeon technique with minimal assistance.

OBJECTIVE: To prospectively evaluate parameters of surgical outcome of a novel technique of laparoscopically assisted vaginal hysterectomy performed by a single surgeon with minimal surgical help from an inexperienced assistant. STUDY DESIGN: Four women who had indications for hysterectomy but relative contraindications to the strictly vaginal approach were consecutively entered into the study. The hysterectomy was accomplished with the Endo GIA 30, O'Connor-O'Sullivan self-retaining vaginal retractor, the ligature vaginal hysterectomy technique and one surgical assistant. RESULTS: The average operative time was 133 minutes (range, 105-167). Blood loss averaged 288 mL (range, 150-350). The average length of hospitalization was 62 hours (range, 36-72). The average time of convalescence was two weeks (range, one to three). CONCLUSION: Preliminary results from a series of four patients suggest that this procedure may be a viable and safe alternative for the single surgeon.

Hepatic venoocclusive disease as a complication of whole abdominopelvic irradiation and treatment with the transjuglar intrahepatic portosystemic shunt: case report and literature review.

We report the novel use of the transjugular intrahepatic portosystemic shunt (TIPS) procedure for the treatment of intractable ascites due to hepatic venooclusive disease as a result of whole abdominopelvic radiotherapy. A patient with Stage III endometrioid carcinoma of the endometrium treated with postoperative whole abdominopelvic irradiation developed intractable ascites. Multiple paracenteses and computerized tomography were negative for recurrent carcinoma. Liver biopsy demonstrated hepatic venoocclusive disease, a rare complication of therapeutic radiation involving the liver. Successful relief of ascites and its adverse symptomology were achieved with the transjugular intrahepatic portosystemic shunt. Relevant literature regarding the pathogenesis, prognosis, and treatment of radiotherapy-related hepatic venoocclusive disease are reviewed.

Laparoscopic paraaortic lymphadenectomy using laparosonic coagulating shears.

With marked innovations in endosurgical instrumentation, operative laparoscopy to include lymphadenectomy has become feasible and has a valuable role in the management of gynecologic malignancy. We used laparosonic coagulating shears (LCS) for laparoscopic paraaortic lymphadenectomy in two women with cervical carcinoma. Operating times for the laparoscopic portion were 55 and 65 minutes and blood loss was 20 and 30 ml, respectively. No surgical complications were encountered. Lymphatic tissues were evaluated histologically and no thermal artifacts were identified. The major advantage of the ultrasonically activated scalpel of the LCS is the ability to cut and coagulate tissues simultaneously without electrical current. The LCS may afford the surgeon a greater margin of safety than unipolar electrocoagulation scissors by eliminating potential thermal and electrical injury to vital structures. Ultrasonic-activated technology deserves extended clinical investigation in laparoscopic lymphadenectomy to substantiate our preliminary findings, as well as to explore its potential in gynecologic oncology.

Biological assay for activity and molecular mechanism of retinoids in cervical tumor cells.

The composition and response of the retinoid signaling pathway in a human cell line (CC-1), representative of a low grade cervical carcinoma, were evaluated. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated expression of cytoplasmic retinol binding protein, CRBPI, cytoplasmic retinoic acid binding protein, CRABPII, and nuclear retinoic acid receptors, RAR alpha, RARgamma, RXR alpha, and RXRbeta, but not CRABPI or RARbeta. This pattern is similar to that of the ectocervix. Activation of endogenous nuclear receptors was evaluated in a reporter subline of CC-1, called CC-B, containing a reporter gene controlled by a retinoic acid responsive element (RARE) and thymidine kinase promoter. Retinoid treatment of CC-B resulted in dose-dependent increases in reporter gene expression. Retinoids inhibited growth at concentrations greater than 100 nM. 9-cis retinoic acid (1 nM) significantly stimulated growth. Immunohistochemical analysis of CC-B organotypic cultures demonstrated a high level of epidermal growth factor receptor (EGF-R) expression that was decreased by retinoids. The degree of RARE transactivation induced by retinoids significantly correlated with the degree of inhibition of growth (R = -0.96) and EGF-R expression (R = -0.92). The dose-dependent and retinoid-specific responses of CC-1 at the molecular and biological levels demonstrate the utility of this reporter cell line for evaluation of retinoid activities.

Paget's disease of the vulva: pathology, pattern of involvement, and prognosis.

OBJECTIVE: The aim of this study was to determine prognostic factors and risk factors for recurrence in patients with Paget's disease of the vulva. METHODS: The medical records of 76 patients with a diagnosis of Paget's disease of the vulva were retrospectively reviewed. The diagnosis in each case was confirmed by reviewing the pathology. Patients were then divided into four groups by diagnosis: intraepithelial Paget's disease (IEP) (n = 46), invasive Paget's disease (IP) (n = 9), intraepithelial Paget's disease with underlying adenocarcinoma (IEPUA) (n = 13), and intraepithelial Paget's disease with a coexisting cancer (CCA) (n = 8). Comorbid conditions, location of disease, pathologic diagnosis, method of treatment, margin status, and current status of the patient were evaluated. Descriptive statistical data and univariate analysis were generated using the Statview statistical package. RESULTS: A diagnosis of IEPUA, IP, or CCA predicted a poor survival (P = 0. 0017). Patients who had received chemotherapy or radiation as treatment had a poor survival (P < 0.0001 and 0.0002). Patients with clitoral Paget's disease had a higher incidence of death from disease (P = 0.026). When death from all causes was considered, patients treated with wide local excision (WLE) had a significantly longer survival than patients treated with other more radical treatments (P = 0.02). Risk factors for recurrence included treatment with WLE (P = 0.004). CONCLUSIONS: Patients with IP, IEPUA, or CCA have a poorer prognosis than patients with IEP. Location of Paget's disease is important for prognosis; and patients with clitoral Paget's disease may require more aggressive treatment. WLE is associated with a higher risk of recurrence, but overall patients with WLE tend to survive longer than patients treated more radically.