Michael A. Bidus

Cost-effectiveness analysis of liquid-based cytology and human papillomavirus testing in cervical cancer screening

OBJECTIVE: To compare the outcomes of several cervix cancer screening strategies in a military population using a model that considers both direct and indirect costs of health care. METHODS: A Markov model of the natural history of cervical cancer was used to simulate an age-stratified cohort of 100,000 active duty women in the U.S. Army. Total costs and incremental cost-effectiveness ratios were estimated for different modalities of screening: liquid-based cytology with testing for human papillomavirus (HPV) irrespective of cytologic results compared with liquid-based cytology with HPV detection for cytologic results of atypical cells of undetermined significance (reflex HPV). The costs and outcomes of these screening methods were evaluated separately as well as in combination (liquid-based cytology and reflex HPV before age 30 years and DNA and Pap test every 3 years thereafter). Each of these screening methods was evaluated at 1-, 2-, and 3-year intervals. RESULTS: A screening strategy of liquid-based cytology and reflex HPV every 2 or 3 years is the least costly strategy among active duty women irrespective of age, especially when accounting for time costs associated with screening, diagnosis, and treatment of cervix cancer. A strategy of liquid-based cytology and HPV testing irrespective of cytology results is the most effective strategy; however, it is also the most costly of the strategies tested, even when performed in patients older than 30 years of age. CONCLUSION: In the U.S. Army, cervix cancer screening performed with liquid-based cytology and reflex HPV testing of atypical squamous cells of undetermined significance performed every 2 years is cost-effective, especially when indirect costs are considered. LEVEL OF EVIDENCE: III

Prediction of Lymph Node Metastasis in Patients with Endometrioid Endometrial Cancer Using Expression Microarray

Purpose: To characterize the gene expression profiles of endometrioid endometrial cancers associated with lymph node metastasis in an effort to identify genes associated with metastatic spread. Experimental Design: Tumors from 41 patients with endometrioid endometrial cancer grossly confined to the uterine cavity were evaluated. Positive lymph nodes were noted in 12 of 41 patients. RNA was analyzed for gene expression using the Affymetrix HG133A and HG133B GeneChip set, representing 45,000 array features covering >28,000 UniGene clusters. Data analysis was done using multidimensional scaling, binary comparison, and hierarchical clustering. Gene expression for several differentially expressed genes was examined using quantitative PCR. Results: Gene expression data was obtained from 30,964 genes that were detected in at least 5% of the cases. Supervised analysis of node-positive versus node-negative cases indicated that 450 genes were significantly differentially expressed between the two classes at P < 0.005, 81 of which were differentially expressed by at least 2-fold at P < 0.005. Overexpressed genes included two cell cycle checkpoint genes, CDC2 and MAD2L1, which have previously been described in association with lymph node metastasis in other cancer types. The ZIC2 zinc finger gene was overexpressed in endometrial cancers with positive nodes versus those with negative nodes. Conclusion: Gene expression profiling of the primary tumors in patients with endometrioid endometrial cancers seems promising for identifying genes associated with lymph node metastasis. Future studies should address whether the status of nodal metastasis can be determined from the expression profiles of preoperative tissue specimens.

Cervical biopsy and excision procedure specimens lack sufficient predictive value for lymph-vascular space invasion seen at hysterectomy for cervical cancer.

OBJECTIVE The purpose of this study was to determine whether lymph-vascular space invasion (LVSI) that is discovered in cervical biopsy and excision specimens is associated with LVSI in the hysterectomy specimen of patients with cervical cancer. STUDY DESIGN A retrospective pathologic review to determine the presence of LVSI in cervical biopsy specimens, cold-knife cone biopsy (CKC biopsy), and loop electrical excision procedure (LEEP) specimens that contained cervical cancer was performed if subsequent hysterectomy results were available for review. Data were analyzed with chi-square analysis testing. RESULTS One hundred six patients were identified. The negative predictive value of the biopsy is lower at 0.45 than either the CKC biopsy (0.83) or LEEP (0.57); however, the positive predictive value (0.83) is higher than either CKC biopsy (0.50) or LEEP (0.75). LVSI, when present in cervical biopsy (odds ratio, 4.13; 95% CI, 0.414-98.446), CKC biopsy (odds ratio, 4.8; 95% CI, 0.542-46.280), and LEEP (odds ratio, 4.0; 95% CI, 0.439-43.793) specimens, is associated with a statistically insignificant increased risk of LVSI in the hysterectomy specimen. CONCLUSION Cervical biopsy and excision specimens lack sufficient negative predictive value for the detection of LVSI in the hysterectomy specimen.

Hematologic changes after splenectomy for cytoreduction: implications for predicting infection and effects on chemotherapy

Postsplenectomy leukocytosis and thrombocytosis are common findings in trauma patients. The intent of this study is to describe postsplenectomy hematologic changes in gynecological oncology surgery and subsequent chemotherapy. We performed a retrospective record review of gynecological oncology patients at our institutions. Postsurgical hematologic changes, infectious morbidity, and pre- and post-chemotherapy hematologic changes were noted. Data were analyzed using repeated measures analysis of variance. We identified 27 patients who underwent cytoreductive surgery with splenectomy. Thirteen patients with splenectomy had postoperative chemotherapy data available, and we matched these patients with 13 control patients who underwent cytoreduction surgery without splenectomy and postoperative chemotherapy. Nine of the 27 splenectomy patients had documented infectious morbidity. There was a significant difference in postoperative platelet counts between the infected and the noninfected splenectomy patients (P= 0.037), and a significant difference between splenectomy and control patients for white blood cell (WBC) counts (P= 0.007). Patients with splenectomy had higher precycle WBC, absolute neutrophil count (ANC), platelet counts, and higher postcycle nadir levels in all cycles compared to control patients. There was a significant overall difference between splenectomy patients and controls with regard to WBC (P= 0.001), ANC (P= 0.005), and platelet counts (P= 0.016) during chemotherapy cycles. Median postchemotherapy nadir WBC was 4.4 (range: 3.4–4.8) for the splenectomy group versus 2.8 (range: 2.5–3.0) for the control group. Median postchemotherapy nadir ANC was 1800 (range: 1320–2450) for the splenectomy group and 1001 (range: 864–1064) for the control group. Median postchemotherapy nadir platelet count was 222 (range: 181–277) for the splenectomy patients and 169 (range 164–215) for the control patients. In conclusion, the patients who undergo splenectomy as part of cytoreductive surgeries have a statistically significant leukocytosis and insignificant thrombocytosis relative to the control patients. Leukocytosis alone is not an accurate indicator of infection. Splenectomy is not associated with an increased risk of chemotherapy-related neutropenia and thrombocytopenia.

The use of acellular dermal allograft for vulvovaginal reconstruction.

Background: Many different techniques that require the surgeon to harvest autologous tissue to create a neovagina have been described in the literature. Technique: We describe a technique for creating a neovagina with the use of an acellular dermal allograft as a replacement for split-thickness skin graft. Three patients are presented who had a successful creation of a neovagina with this technique. The indications for vaginoplasty include vaginal agglutination from lichen planus, squamous cell carcinoma of the vagina, and vaginal agenesis. Conclusion: The creation of a neovagina using an acellular dermal allograft can be successfully accomplished in patients undergoing constructive and exenterative procedures. The use of an acellular dermal allograft decreases operative time and decreases the incidence of postoperative morbidity because harvesting autologous tissue for the neovagina is not required.

Sentinel Lymph Node Detection in Gynecologic Malignancies

Learning Objectives: After reading this issue, the participant should be able to:1. Describe currently used techniques for identifying sentinel lymph nodes.2. Explain the role of sentinel lymph node identification in gynecologic malignancies.3. Explain the importance of ultrastaging and micrometastatic disease in gynecologic malignancies.