Modified uterine manipulator and vaginal rings for total laparoscopic radical hysterectomy.

At present, there is no standard technique that allows surgeons performing total laparoscopic radical hysterectomy to complete the colpotomy and remove an adequate (2-cm) margin of upper vaginal tissue while maintaining adequate pneumoperitoneum. We evaluated the feasibility and safety of using a modified uterine manipulator for total laparoscopic radical hysterectomy in patients with cervical or endometrial cancer. A retrospective review was performed in all patients who underwent total laparoscopic radical hysterectomy using a modified uterine manipulator at our institution during the period April 2004 to December 2006. This analysis included 30 patients who underwent surgery with the modified uterine manipulator. There were no reports of difficulty with placement of the instrument, multiple attempts at placement, difficulty with uterine manipulation, or uterine perforation. In no patient was a vaginal incision or episiotomy required to fit the instrument through the introitus. In no case was there loss of pneumoperitoneum during colpotomy. Additional upper vaginal tissue had to be removed after intraoperative assessment of the adequacy of the surgical specimen in five (16.7%) of 30 patients. Use of the modified uterine manipulator according to our technique is safe and feasible, allowing for adequate vaginal resection and maintenance of pneumoperitoneum.

Analysis of 96 patients with advanced ovarian carcinoma treated with high-dose chemotherapy and autologous stem cell transplantation.

The purpose of this study was to identify characteristics significant to survival and progression-free survival in patients with advanced ovarian cancer receiving high-dose chemotherapy. In all, 96 patients received autologous stem cell transplantation. Regimens included paclitaxel with carboplatin (PC), topotecan, melphalan, cyclophosphamide (TMC) and cyclophosphamide, BCNU, thiotepa (CBT). At the time of transplantation, 43% of patients were in clinical CR, 34% were in clinical PR, 18% had progressive disease and 5% had stable disease. There were no treatment-related deaths. The 6-year survival by Kaplan-Meier was 38%. For patients who received transplantation for remission consolidation, the 6-year survival was 53% with a PFS of 29%. On univariate analysis, the CBT regimen, clear cell histology and disease status other than CR prior to treatment were statistically significant adverse prognostic factors. This analysis has demonstrated that patients in clinical remission are most likely to benefit from autologous transplantation, with the exception of patients with clear cell histology. The TMC combination appeared to be superior to the PC and CBT combinations. Comparative studies of different consolidation approaches will be necessary to determine if autologous transplantation is the preferred treatment for this patient population.

High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell support: a new regimen for the treatment of advanced ovarian cancer.

OBJECTIVE: The goal of this study was to determine the optimal dose of topotecan when used in combination with high-dose melphalan and cyclophosphamide (TMC), and to assess the toxicity and efficacy of the regimen in patients with advanced ovarian cancer. METHODS: Fifty-three patients with persistent or recurrent ovarian cancer were treated. Disease status at study entry included: platinum-sensitive recurrent disease (15 patients), platinum-resistant or refractory recurrent disease (15 patients), positive second-look surgery (16 patients), failure to achieve a primary clinical complete response (CR) (7 patients). Following stem cell mobilization and collection, patients were given cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on Days -6 to -2. Peripheral blood stem cells were infused on Day 0. RESULTS: The optimal topotecan dose selected for future trials was 4.0 mg/m(2)/day x 5 days. The regimen had acceptable toxicity with no regimen-related death. Toxicity (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and diarrhea. The overall response rate of patients with measurable or evaluable disease was 93%. Median survival has not yet been reached, but with a median follow up of 18 months (range: 11-37) 77% of patients are alive. CONCLUSION: With a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regimen has acceptable toxicity and produces high response rates. In the setting of ovarian cancer, high-dose chemotherapy should be administered only as part of well-designed clinical trials. TMC should be considered a potential regimen for future randomized trials in patients with advanced ovarian cancer.

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

Posttherapy surveillance of women with cervical cancer: an outcomes analysis.

OBJECTIVE: The aim of this study was to develop a surveillance program that optimizes clinical outcome following primary treatment of women with cervical cancer. METHODS: The records of 1096 patients with FIGO stage IB cervical cancer treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed by site, presence or absence of symptoms, method of detection, and survival. Univariate and multivariate analyses using a Cox proportional hazards model were performed. RESULTS: One hundred thirty-three patients (13%) developed recurrent disease. Of these, 114 were symptomatic and 19 were asymptomatic at the time of recurrence. Thirty-seven patients recurred in the central pelvis, 21 each in the lung or pelvic wall, 22 in nodes, and 35 in other sites. The median disease-free interval was 17 months for symptomatic patients and 16 months for asymptomatic patients. The median survival from initial diagnosis was 31 months for symptomatic and 83 months for asymptomatic patients (P = 0.001). The median survival from recurrence was 11 months for symptomatic and 42 months for asymptomatic patients (P < 0.001). Multivariate analysis revealed that symptom status at time of recurrence was a significant predictor of survival, even when known prognostic factors were considered (P < 0.001). All asymptomatic pelvic recurrences were diagnosed by pelvic exam; all asymptomatic pulmonary recurrences were detected by chest radiographs. Pap smears did not detect a single asymptomatic recurrence. CONCLUSIONS: Posttherapy surveillance programs are directed toward asymptomatic patients in whom early detection of recurrence may impact survival. These data indicate that a subset of women may benefit from surveillance. A model for surveillance is proposed.

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.

The current status of surgical staging of ovarian serous borderline tumors.

BACKGROUND: The purpose of the current study was to evaluate the current practice of surgical staging of ovarian serous borderline tumors. METHODS: Women with a diagnosis of ovarian serous borderline tumors whose pathology slides were sent to the M. D. Anderson Cancer Center for second-opinion diagnostic consultation between 1990-1996 were identified. The original pathology reports and M. D. Anderson Cancer Center consultation reports of 255 cases were reviewed for the frequencies of frozen-section analyses and staging biopsies, biopsy results, the specialty of the surgeon, and hospital type. RESULTS: The majority (78%) of ovarian borderline tumors primarily were encountered and staged by general obstetrician-gynecologists. Overall, 66% of patients had at least 1 staging biopsy performed. Approximately 12% of subjects underwent complete surgical staging, defined as having biopsy samples taken from pelvic and abdominal peritoneum, omentum, and retroperitoneal lymph nodes. Gynecologic oncologists performed complete staging in 50% of cases, obstetrician-gynecologists performed complete staging in 9% of cases, and general surgeons performed complete staging in 0% cases. The overall frequency of a positive staging biopsy was 37%. Approximately 47% (80 of 169) of patients who underwent biopsies were upstaged as a result of positive biopsies, - with 41% (70 of 169) having extrapelvic spread. CONCLUSIONS: Currently, surgical staging for women with ovarian serous borderline tumors remains inadequate, although a significant proportion of patients who undergo staging are noted to have extrapelvic spread.