Comparison of operative risks associated with radical hysterectomy in pregnant and nonpregnant women.

OBJECTIVE: To compare the operative data and complications of radical hysterectomy performed on pregnant women versus nonpregnant women. STUDY DESIGN: Following institutional review board approval, we reviewed our surgical databases to identify pregnant women who had undergone a radical hysterectomy for cervical carcinoma from 1992-2005 (n = 7). A nonpregnant control group (n = 35) of women undergoing radical hysterectomy during the study interval were identified and matched for age, year of surgery, and surgeon. Pertinent operative and outcome data were abstracted and compared. RESULTS: Of the 7 women who had undergone a radical hysterectomy during pregnancy, 4 had a cesarean radical hysterectomy at a mean gestational age of 35.4 weeks (range, 32.3-38 weeks) and 3 had a radical hysterectomy with a previable fetus in situ at a mean gestational age of 14.2 weeks. Demographics were similar between groups. Transfusion rates were significantly higher among pregnant women (57%) as compared to nonpregnant controls (9%) (p = 0.0009). The overall incidence of operative complications was similar between the pregnant women (43%) and nonpregnant controls (40%) (p = NS). CONCLUSION: Radical hysterectomy performed in pregnant women was associated with higher blood loss and increased need for transfusion as compared to nonpregnant controls. No differences were observed in regards to other operative surgical complications between the two groups.

Patterns of failure for conservatively managed surgical stage I uterine carcinosarcoma: implications for adjuvant therapy.

To evaluate patterns of failure and overall survival for patients with surgical stage I uterine carcinosarcoma managed conservatively without adjuvant therapy. A computerized database identified 27 patients whose conditions have been diagnosed with surgical stage I uterine carcinosarcoma from 1993 to 2002. Charts were abstracted for patient demographics, tumor characteristics, recurrence, and survival. Of 27 patients, 23(85%) did not receive adjuvant therapy after undergoing total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and paraaortic lymphadenectomy. Five patients were stage IA, 14 were stage IB, and 4 were stage IC. Fourteen patients had either poorly differentiated endometrioid carcinoma alone or in combination with papillary serous carcinoma (61%) as their epithelial tumor component. The median nodal count was 9 (range, 3-21). Eleven patients are alive without evidence of disease with a median follow-up of 63 months (range, 12-164 months). Eleven patients had recurrence with a median time to recurrence of 13 months (range, 6-39 months), and all are dead of disease. Univariate analysis demonstrated that poorly differentiated epithelial or papillary serous histologic diagnosis was the only predictor variable associated with recurrence and, consequently, death (P = 0.04). Approximately 50% of patients with surgical stage I carcinosarcoma who are observed without adjuvant therapy will experience a recurrence. Because most patients will recur distantly, systemic chemotherapy should be considered for patients with early stage uterine carcinosarcoma.

The risk of gastrointestinal perforation and/or fistula in patients with recurrent ovarian cancer receiving bevacizumab compared to standard chemotherapy: a retrospective cohort study.

OBJECTIVE: To determine the rate of gastrointestinal perforation and/or fistula in patients with recurrent ovarian cancer treated with and without bevacizumab. METHODS: A retrospective chart review from January 2004 to August 2007 identified two cohorts of patients with recurrent ovarian cancer: 1) patients who were receiving bevacizumab either alone or in combination with standard chemotherapy; 2) patients who were receiving standard chemotherapy alone. Gastrointestinal toxicity (perforation and fistula) was assessed using NCI Common Toxicity Criteria. Relative risk and 95% confidence intervals were calculated. Chi square test and student's t test were used for statistical analysis. RESULTS: Sixty-eight patients receiving bevacizumab for recurrent ovarian cancer were identified. 67% of these patients received chemotherapy in combination with bevacizumab. For comparison, 195 patients receiving standard chemotherapy alone for recurrent ovarian cancer were identified. A history of previous gastrointestinal resection (40% vs. 37%; p=0.79) and gastrointestinal obstruction (30% vs. 27%; p=0.74) was similar in both cohorts. Five patients (7.2%) developed a gastrointestinal perforation and/or fistula in the bevacizumab cohort compared to 13 patients (6.5%) in the chemotherapy alone cohort. The relative risk for developing a perforation and/or fistula is 1.09 (95% CI, 0.40 to 2.96). CONCLUSIONS: Although a substantial number of patients with recurrent ovarian cancer experience gastrointestinal obstruction, the rate of gastrointestinal perforation and/or fistula is relatively low. Treatment with bevacizumab does not significantly increase gastrointestinal toxicity compared to standard salvage chemotherapy.

The safety and efficacy of day 1 versus day 2 administration of pegfilgrastim in patients receiving myelosuppressive chemotherapy for gynecologic malignancies.

OBJECTIVE: Pegfilgrastim is indicated to decrease the incidence of febrile neutropenia in patients with gynecologic malignancies who are receiving myelosuppressive chemotherapy. We sought to compare the safety and efficacy of day 1 pegfilgrastim administration to day 2 administration in patients with gynecologic malignancies. METHODS: We retrospectively evaluated patients receiving both chemotherapy and pegfilgrastim from June 1, 2006 to August 31, 2007 for a gynecologic malignancy. Abstracted data included patient demographics, pathology, blood counts, toxicity, and chemotherapy. After administration of chemotherapy, all patients either received 6 mg of pegfilgrastim subcutaneously on day 1 or day 2. RESULTS: 1226 administrations of pegfilgrastim in 230 patients were identified. 490 administrations of pegfilgrastim were given on day 1 compared to 736 on day 2. 70% of patients had ovarian cancer with a median age of 64 years (range 15-88). 79% of patients had stage III, IV, or recurrent disease and 67% were undergoing primary chemotherapy. The most common chemotherapy was docetaxel/carboplatin (53%) followed by paclitaxel/carboplatin (19%). The mean absolute neutrophil count (ANC) nadir was 4810/mm(3) in the day 1 cohort compared to 4212/mm(3) in the day 2 cohort (p=.004). The incidence of Grade 3/4 neutropenia was similar in both groups (4.9% in day 1 vs. 5.7% in day 2; p=.63). Grade 3/4 febrile neutropenia was uncommon in both cohorts (0 episodes vs. 3 episodes; p=.41). Treatment delays were similar in both cohorts (5.9% vs. 7.5%; p=.35). Dose modifications were also similar in both cohorts (2.8% vs. 5.3%; p=.06). CONCLUSION: Day 1 administration of pegfilgrastim is as effective as day 2 administration in the prevention of neutropenia in patients with gynecologic malignancies. Treatment delays and dose modifications were not increased after day 1 administration of pegfilgrastim. Administering pegfilgrastim on day 1 appears to be safe, effective, and convenient in selected patients receiving myelopsuppressive chemotherapy for gynecologic malignancies.

Conservative management of postoperative Fever in gynecologic patients undergoing major abdominal or vaginal operations.

BACKGROUND: To develop a standardized protocol for management of postoperative fever in gynecology patients to decrease unnecessary diagnostic workups and empiric use of antibiotics. STUDY DESIGN: A prospective analysis of postoperative gynecology patients identified those who experienced fever (maximum temperature [T(max)] > 100.4 degrees F). Patients were triaged into low- and high-risk groups. High-risk patients were managed independent of the protocol. High-risk criteria included bowel operation, preoperative infection, immunodeficiency, indwelling vascular access, mechanical heart valves, and intensive care unit admissions. Low-risk patients were treated with observation and antipyretics. Patients with persistent or high fever, defined as T(max) > 101 degrees F for > 48 hours, were evaluated and treated based on physical examination findings. RESULTS: We evaluated 292 postoperative patients. Forty-seven percent of patients had a final diagnosis of malignancy. Sixty-four patients were high-risk and 33% of these patients experienced fever. Using the standardized protocol, 228 low-risk patients were managed. Thirty-seven of the 228 patients (16%) had fever postoperatively. Nineteen patients had low-grade fever (100.4 to 101 degrees F); none of these patients required antibiotics. Seventeen patients had fever (101.1 to 102 degrees F) and one patient had fever > 102 degrees F. Using the protocol, 6 of 37 patients (16%) were treated with antibiotics for an infectious diagnosis. CONCLUSIONS: Although postoperative fever is common in gynecologic patients, the incidence of infection is low (3%). A standardized postoperative fever protocol in low-risk gynecology patients decreases use of empiric antibiotics without compromising morbidity.

A phase I study of lapatinib in combination with carboplatin in women with platinum sensitive recurrent ovarian carcinoma.

OBJECTIVES: To determine the maximum tolerated dose (MTD), spectrum of toxicities, clinical activity, and pharmacokinetics of carboplatin given in combination with lapatinib in women with a first recurrence of platinum sensitive epithelial ovarian carcinoma. METHODS: Patients with measurable, platinum sensitive recurrent epithelial ovarian carcinoma were eligible. Cohorts of 3-6 patients were to receive up to 6 cycles of intravenous carboplatin AUC of 6 every 21 days in combination with escalating dosages of oral lapatinib (starting at a dose of 750 mg daily). Toxicity was assessed using NCI CTC for Adverse Events. Clinical response was monitored using RECIST criteria. Pharmacokinetic (PK) analysis was performed for the second cohort of patients. RESULTS: Twelve patients were enrolled. No dose limiting toxicity was noted. Two of 6 patients in the first cohort had unanticipated excessive delays in treatment due to non-dose limiting G3 neutropenia. Therefore, the study was modified to reduce the carboplatin dose in the second cohort. The median number of courses administered to the 11 evaluable patients in these two cohorts was 2.8 (range 1-6). Drug-related grade 3 or 4 toxicities included non-dose limiting G4 thrombocytopenia (n=1), and non-dose limiting G3 neutropenia (n=3). Of the 11 patients who received >or=1 course of therapy, 3 (27%) had a partial response, and 3 (27%) had stable disease. The pharmacokinetics of carboplatin were not significantly altered by concomitant administration of lapatinib. CONCLUSIONS: This regimen of lapatinib and carboplatin was associated with unacceptable non-dose limiting toxicities, excessive treatment delays and limited clinical responses.

A prospective evaluation of a simulator-based laparoscopic training program for gynecology residents.

BACKGROUND: To determine prospectively if simulator-based laparoscopic training could improve laparoscopic skills of gynecology residents. STUDY DESIGN: Twenty-six gynecology residents were enrolled in a laparoscopy training curriculum involving didactics, self-paced learning modules, and graded simulator-based laparoscopic training modules. Six simulator tasks were developed to introduce incremental levels of difficulty. Residents were tested on bead/peg manipulation, passing of a specially designed "key," cutting of lines and circles on a two-layer latex glove, and laparoscopic suturing followed by both intra- and extracorporeal knot tying. Times for each task and penalties for errors were assessed at baseline and after 3 months of training. RESULTS: Twenty-six residents completed initial baseline and 3-month evaluations. Average summary time (including 30-seconds penalties for each error) at baseline was 64 minutes and 36 minutes at 3-month evaluation (p < 0.001). For PGY1 baseline summary times averaged 83 minutes compared with 50 minutes at 3 months (p = 0.006). For PGY4 baseline summary times averaged 49 minutes compared with 28 minutes at 3 months (p = 0.05). All individual tasks demonstrated substantial improvement (p < 0.001) from baseline to 3-month evaluation. Baseline summary scores demonstrated correlation between PGY training year and overall score (p < 0.001) consistent with earlier ability and training. Three-month scores demonstrated equalization of skill level across PGY2 through PGY4. CONCLUSIONS: A dedicated simulator-based laparoscopic training curriculum has the ability to improve basic laparoscopic skills in a gynecologic residency, as measured by timed and scored simulator tasks. Construct validity was demonstrated by measuring substantial improvement in performance with increasing residency training, and with practice.

Improved anti-tumor therapy based upon infectivity-enhanced adenoviral delivery of RNA interference in ovarian carcinoma cell lines.

BACKGROUND: Hec1 (Highly Expressed in Cancer gene 1) has recently been shown to play an important role in the proper segregation of chromosomes during mitosis. Recently, an adenovirus delivery system carrying RNA interference (RNAi) of Hec1 has been reported in a cervical adenocarcinoma model. Adenoviral delivery systems, however, have the main limitation of poor viral infectivity due to lack of the native receptor, Coxsackie-Adenovirus Receptor (CAR), on the surface of tumor cells. We hypothesize that the viral infectivity of the adenovirus vector would be enhanced via a CAR-independent pathway by altering the targeting tropism, thus increasing the knockdown effect of Hec1 expression in ovarian carcinoma cells. METHODS: Two adenoviruses (Ad-siRNA-Hec1 and Ad-siRNA-Hec1.F5/3), along with a negative control (Ad-siRNA-GAPDH.F5/3), were created using homologous recombination. HEY and SKOV3.ip1 cell lines were used to perform experiments. The following assays were then used to determine RNAi knockdown efficiency: (1) quantitative PCR (QPCR), (2) Western blot, (3) MTS assay, (4) Annexin V-FITC FACS, (5) crystal violet staining. In all experiments, a negative control served as a baseline measure. RESULTS: QPCR demonstrated a 2-log viral infectivity enhancement with Ad-siRNA-Hec1.F5/3 over Ad-siRNA-Hec1. QPCR at 72 h revealed mRNA knockdown induced by Ad-siRNA-Hec1 and Ad-siRNA-Hec1.F5/3 in SKOV3.ip1 and HEY cells, respectively (71%/60%, and 32%/78% mRNA knockdown compared to negative control). Western blot revealed translational inhibition induced by both Hec1 Ads with the least knockdown seen with Ad-siRNA-GAPDH.F5/3. FACS analysis revealed increased annexin V positivity in RNAi-infected cells, suggesting a higher rate of apoptosis. MTS assay indicated increased cell death 8 days post-infection with Ad-siRNA-Hec1 and Ad-siRNA-Hec1.F5/3 in SKOV3.ip1 and HEY cell lines, respectively (75% vs. 35% and 43% vs. 12% viable cells). Crystal violet staining revealed increased cell death with Ad-siRNA-Hec1.F5/3 in all tested cell lines. CONCLUSIONS: RNAi against Hec1 results in gene expression knockdown and apoptosis in vitro. The infectivity-enhanced adenovirus as delivery mechanism shows potential application in future gene therapy models of RNAi in ovarian cancer.

Fertility-sparing radical abdominal trachelectomy for clear cell adenocarcinoma of the upper vagina: a case report.

BACKGROUND: Clear cell adenocarcinoma (CCA) of the vagina is traditionally treated with radical surgical resection with tailored postoperative radiation when indicated. Due to a bimodal distribution, women of reproductive age are frequently affected and could benefit from radical trachelectomy to preserve fertility. CASE: A 22 year old female was diagnosed with clinical stage I vaginal clear cell adenocarcinoma in the left fornix abutting the cervix. The patient desired future fertility; therefore, she underwent radical abdominal trachelectomy and upper vaginectomy. Twenty-eight months after initial surgery, she has no evidence of recurrence with regular menstrual cycles. CONCLUSION: For patients with CCA of the upper vagina, where removal of the cervix is necessary, a radical trachelectomy with upper vaginectomy should be considered to conserve fertility.

Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma.

PURPOSE: Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to inefficient virus delivery to the tumor site. The present study addresses the utility of human mesenchymal stem cells (hMSCs) as intermediate carriers for conditionally replicating adenoviruses (CRAds) to target metastatic breast cancer in vivo. EXPERIMENTAL DESIGN: HMSC were transduced with CRAds. We used a SCID mouse xenograft model to examine the effects of systemically injected CRAd loaded hMSC or CRAd alone on the growth of MDA-MB-231 derived pulmonary metastases (experimental metastases model) in vivo and on overall survival. RESULTS: Intravenous injection of CRAd loaded hMSCs into mice with established MDA-MB-231 pulmonary metastatic disease homed to the tumor site and led to extended mouse survival compared to mice treated with CRAd alone. CONCLUSION: Injected hMSCs transduced with CRAds suppressed the growth of pulmonary metastases, presumably through viral amplification in the hMSCs. Thus, hMSCs may be an effective platform for the targeted delivery of CRAds to distant cancer sites such as metastatic breast cancer.

Gene therapy for ovarian cancer.

Ovarian cancer remains the leading cause of death due to gynecologic cancer in women in the United States. Gene and viral-based therapies represent novel therapeutic approaches for cancer. The manipulation of genetic content of tumor cells toward a therapeutic end has been divided into several general strategies, including molecular chemotherapy, mutation compensation, immunopotentiation, and virotherapy. Improvements in delivery vehicles and in evaluation of gene transfer and viral replication remain important areas of investigation. We highlight the most recent advances in these novel therapeutic approaches for ovarian cancer and include a summary of recent clinical trials.

Synchronous primary endometrial and ovarian carcinoma in a patient with marantic endocarditis.

BACKGROUND: Nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, is a rare form of endocarditis found in patients with advanced malignancy and collagen-vascular disorders. There is limited information about the clinical course of patients with NBTE because the majority of cases are found at the time of autopsy. CASE: A 38-year-old woman presented to the emergency department with recent onset of chest pain and fatigue. Initial evaluation revealed cardiac valvular disease, and the patient underwent aortic valve replacement. Final pathology revealed nonbacterial thrombotic endocarditis. A metastatic work-up revealed a complex pelvic mass and elevated CA 125. The patient underwent an exploratory laparotomy and was subsequently found to have synchronous primary endometrial and ovarian carcinoma. CONCLUSION: Nonbacterial thrombotic endocarditis is rare and carries a high mortality. This case is unusual in that the diagnosis of nonbacterial thrombotic endocarditis led to the diagnosis of a gynecologic malignancy.

Fertility sparing therapy in a patient with placental site trophoblastic tumor: a case report.

BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic disease (GTD) that is generally resistant to conventional chemotherapeutic treatment. Patients with localized disease are usually managed with hysterectomy. CASE: A 29-year-old female presented with vaginal bleeding and an elevated serum human chorionic gonadotropin (HCG). After initial observation, the patient experienced continued vaginal bleeding and a persistently elevated HCG. Therefore, she underwent a dilation and curettage and final pathology revealed PSTT. Since the patient desired future fertility, the patient received combination chemotherapy with etoposide, methotrexate, actinomycin-D followed by etoposide and cisplatin (EMA-EP). The patient had a complete response to chemotherapy and subsequently delivered a term infant 2 years after completion of therapy. CONCLUSION: PSTT is thought to be a chemoresistant disease and the preferred method of treatment is hysterectomy or local uterine resection. However, combination chemotherapy is a reasonable option in a properly counseled patient who strongly desires future fertility.

The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma.

OBJECTIVE: To evaluate our experience with the use of bevacizumab in patients with heavily pretreated recurrent ovarian carcinoma who have symptomatic ascites. METHODS: Four patients were identified who were previously heavily pretreated for recurrent ovarian carcinoma. Each had symptomatic ascites and required frequent therapeutic paracenteses. Each was treated with bevacizumab with the intent to palliate symptomatic ascites. Clinical data including demographic data and clinicopathologic variables was abstracted. RESULTS: The four patients demonstrated symptomatic relief of ascites. Toxicity was manageable in all patients with no grade 3/4 toxicity observed. In addition to symptomatic relief of ascites, no therapeutic paracenteses were required after initiation of therapy with bevacizumab. CONCLUSIONS: Bevacizumab may be a viable palliative option in patients with end stage ovarian carcinoma who have symptomatic ascites.

The use of adjuvant radiation therapy in patients with intermediate-risk Stages IC and II uterine corpus cancer: a patient care evaluation study from the American College of Surgeons National Cancer Data Base.

OBJECTIVE: To determine the outcomes of patients with intermediate-risk Stages IC and II uterine corpus cancer treated with surgery alone or surgery followed by radiation therapy. METHODS: Patients with uterine corpus cancer diagnosed in 1995 were identified from hospitals in the United States with tumor registry databases. Data were collected on histology, surgical treatment, radiation therapy, recurrence, and survival. Survival analysis was performed using life-table computational method. RESULTS: 713 hospitals submitted data on 10,726 patients with uterine corpus cancer. 9977 patients (93.0%) underwent surgery, and 2624 patients (26.3%) received radiation therapy. Patients with clinical Stages IC and IIA disease who underwent surgery followed by radiation therapy compared to surgery alone had a trend toward improved 5-year relative survival (RS) (81.2% vs. 92.5%; 74.3% vs. 96.0%, respectively). The 5-year RS of patients with surgical Stage IC disease was not statistically different between the surgery alone group and the radiation group (93.9% vs. 91.7%). Patients with surgical Stage IIA and IIB disease did not benefit from radiation therapy compared to surgery alone (5-year RS; 83.7% vs. 98.0% and 82.3% vs. 81.8%, respectively). CONCLUSION: There is a trend toward improved survival in patients with clinical Stages IC and IIA uterine corpus cancer when radiation therapy is utilized following surgery. The survival of patients with surgical Stages IC and II uterine corpus cancer is not improved with adjuvant radiation therapy.

Outcomes of Stage I/II vulvar cancer patients after negative superficial inguinal lymphadenectomy.

OBJECTIVES: To investigate the patterns of recurrence associated with superficial inguinal lymphadenectomy (SupIL) and vulvectomy for patients with Stage I/II vulvar cancer. METHODS: A retrospective chart review identified patients from 1990-2001 with Stage I/II vulvar cancer that underwent SupIL and vulvectomy. Survival was analyzed using the Kaplan-Meier method with Fisher Exact and Chi-square tests for comparisons between groups. RESULTS: 65 patients with Stage I/II vulvar cancer with a pathologically negative SupIL were identified (30 Stage I, 35 Stage II). Three patients recurred in the inguinal region, (4.6%) and 11 patients (16.9%) recurred on the vulva. Two of the 11 patients died of disease, six patients are alive without evidence of disease after additional therapy. Five-year disease-free survival and overall survival were 66% and 97%, respectively. Risk of recurrence was not associated with smoking status, stage, or margin status. CONCLUSIONS: SupIL and vulvectomy for Stage I/II vulvar cancer have a low recurrence rate in the inguinal region when nodes are negative. The local recurrence rate (17%) is acceptable, and overall survival is good using this conservative approach.

A prospective evaluation of "see and treat" in women with HSIL Pap smear results: is this an appropriate strategy?

OBJECTIVE: The evaluation of abnormal cervical cytologic results is time consuming and costly. Most patients with high-grade squamous intraepithelial lesion (HSIL)-cervical intraepithelial neoplasia 3 (CIN 3) Pap smear results require an excisional procedure for diagnostic or therapeutic reasons. "See and treat" is a surgical procedure that involves a loop electrosurgical excisional procedure (LEEP) simultaneously to diagnose and to treat premalignant cervical disease in one visit. This procedure eliminates a second visit that typically is required for treatment. Data is lacking on the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2) Pap smear result. The objective of this study was to determine the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2) Pap smear using a see-and-treat protocol. METHODS: Women referred from local health departments to our university-based colposcopy clinic for evaluation of an HSIL (CIN 2) Pap smear result were evaluated for inclusion in a see and treat protocol. All eligible patients underwent colposcopy to rule out an obvious cervical carcinoma followed by an immediate LEEP to remove the transformation zone. A colposcopic impression was made using the Reid colposcopic index. Pathologic specimens were analyzed for the presence of CIN and the incidence of CIN 2 and CIN 3 was determined. RESULTS: To date, 51 patients have been enrolled in the study. Exclusion criteria included age less than 19 years, pregnancy, or medical contraindications. The mean age of the patients was 26 years (range, 19-45 years). Forty-seven percent were white, 47% were black, and 6% were Hispanic. Of the 51 patients who underwent LEEP, 43 of 51 (85%) had satisfactory colposcopy and no patient had a lesion suspicious for cervical carcinoma. The average Reid colposcopic index was 3.5. Of the 51 LEEP specimens, 4 of 51 had no evidence of CIN (8%), 4 of 51 (8%) had CIN 1, 18 of 51 (35%) had CIN 2, and 25 of 51 (49%) had CIN 3. Eighty-four percent of patients had either CIN 2 or CIN 3, resulting in an overtreatment rate (CIN 1 or less) of 16%. CONCLUSIONS: The use of a see and treat protocol for patients with HSIL (CIN 2) Pap smear results may be an acceptable treatment option because of a high incidence of CIN 2 and CIN 3.

Occult choriocarcinoma discovered by positron emission tomography/computed tomography imaging following a successful pregnancy.

BACKGROUND: Positron emission tomography (PET) is commonly used to detect occult or recurrent malignancy, including tumors of the female genital tract. Recently, there have been reports of PET scans used in patients with Gestational Trophoblastic Disease (GTD). CASE: A 22-year-old female presented with vaginal bleeding and elevated beta-hCG 7 months after a spontaneous vaginal delivery of a healthy infant. She had a history of molar pregnancy and persistent GTD requiring multi-agent chemotherapy. Metastatic evaluation with computed tomography and magnetic resonance imaging showed no evidence of GTD. A positron emission tomography/computed tomography (PET/CT) scan revealed a focus of metabolic activity in the left pelvis. The patient underwent an exploratory laparotomy that revealed metastatic choriocarcinoma in the left broad ligament. CONCLUSION: PET/CT may be useful in the evaluation of occult choriocarcinoma when conventional imaging fails to identify metastatic disease.

Targeted gene therapy for ovarian cancer.

Despite advances in therapy, advanced ovarian cancer maintains a dismal overall survival of 15-30%. Thus, the need for novel therapeutic modalities exists. Gene therapy represents one such approach and the purpose of this review is to present a logical rationale for the investigation of gene therapy for the treatment of ovarian cancer. The different strategies of gene therapy (molecular chemotherapy (prodrugs), mutation compensation, immunotherapy approaches, altered drug sensitivity, and virotherapy) for cancer treatment are discussed separately with attention to investigations with clinical applicability. Furthermore, the different viral vectors utilized for improvements in targeted therapy are presented. The advancements, discovery, and shortcomings are reviewed which lend itself to future directions. These future directions involve coxsackie-adenovirus receptor (CAR) independent pathways to improve infectivity and specificity to ovarian tumor cells, the potential of utilizing gene therapy as an imaging modality in detecting cancer, and incorporating the recently described technique of RNA interference. Due to the advancements in detection and targeting of ovarian cancer, coupled with the containment to the intraperitoneal cavity, gene therapy remains a promising treatment modality for ovarian cancer.

A cost-effectiveness analysis of screening strategies for cervical intraepithelial neoplasia.

OBJECTIVE: To assess the costs and usefulness of colposcopy using three screening strategies for cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: A decision model compared three screening strategies for CIN: (1) patients were screened annually with a conventional Pap smear, (2) patients were screened annually with a liquid-based cytologic method and reflex human papillomavirus testing for atypical squamous cells of undetermined significance results, and (3) patients were screened biennially with a liquid-based cytologic method and reflex human papillomavirus testing for atypical squamous cells of undetermined significance results. RESULTS: Biennial liquid-based screening was the least expensive strategy with a cost of $9.5 million per 100,000 patients. Annual liquid-based screening was the most expensive strategy at $13.7 million. Annual conventional screening had an intermediate cost of $11.6 million. Biennial liquid-based screening referred the fewest patients to colposcopy (11.8%), followed by annual conventional screening and annual liquid-based screening (15.2% and 15.6%, respectively). CONCLUSIONS: Each of these treatment strategies is reasonable; however, biennial liquid-based screening would reduce medical costs significantly.