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Biomedical subjects

Michael A Bidus

Publications and source records attributed to Michael A Bidus.

10 recordsLinked to original sources

A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma.

OBJECTIVE: Oxaliplatin and topotecan have demonstrated activity as single agents against recurrent platinum-sensitive and -resistant ovarian cancer, as well as synergy in vitro. This was a dose-finding study of combination therapy with weekly topotecan and alternating-week oxaliplatin in patients with recurrent epithelial ovarian cancer. METHODS: Eligible patients had a diagnosis of recurrent ovarian or primary peritoneal carcinoma, a performance status of 0-2, and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day cycle, patients received a fixed dose of oxaliplatin (85 mg/m2) via intravenous infusion. On days 1, 8, and 15, patients received an escalating dose of intravenous topotecan (2.0-4.0 mg/m2). Five dose levels were planned with a minimum cohort of 3 patients at each level. RESULTS: Thirteen patients were enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated dose was 85 mg/m2 of oxaliplatin and 3.0 mg/m2 of topotecan, and grade 3 neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients had stable disease or a partial response to the drug combination as assessed by cancer antigen-125 levels. CONCLUSIONS: A 28-day schedule of oxaliplatin and topotecan is safe and well tolerated. Because of the in vitro synergy observed between topoisomerase I inhibitors and platinum derivatives and the tolerability reported in the current study, this regimen warrants further investigation.

Adult↗

Sustained response to bevacizumab in refractory well-differentiated ovarian neoplasms.

BACKGROUND: Bevacizumab has demonstrated activity against a variety of solid tumors, including ovarian carcinoma. However, there have not been reproducible prognostic features associated with its activity. CASES: One patient each with recurrent, refractory well-differentiated serous-endometrioid ovarian carcinoma, micropapillary serous carcinoma of the ovary, and primary peritoneal micropapillary serous carcinoma were treated with single agent bevacizumab (15 mg/kg [DOSAGE ERROR CORRECTED] intravenously every 3 weeks). All three have had dramatic sustained responses of 15, 15, and 22 months' duration. CONCLUSION: Bevacizumab may have significant activity against well-differentiated ovarian carcinoma and micropapillary serous carcinomas of the ovary or peritoneum. Since these tumors are generally indolent and not responsive to adjuvant therapy, further investigation is warranted.

Adult↗

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.

Carcinoma, Endometrioid↗

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.

Adolescent↗

The prevalence of HR-HPV DNA in ASC-US Pap smears: A military population study.

OBJECTIVE: To determine the prevalence of HR-HPV DNA in ASC-US Pap smears following implementation of the Bethesda 2001 classification system. METHODS: A computer database of Pap smears obtained within Department of the Army medical facilities was queried for the study period August 2002 to June 2004. All ASC-US Pap smears that underwent reflex testing for HR-HPV DNA were included. Additional clinical and demographic data were obtained from facilities within the US northeast region to evaluate the differences in ASC-US and SIL rates between the current and former Bethesda classification systems. RESULTS: 550,000 Pap smears were collected during the study period. The HR-HPV prevalence was 40.8% (95% confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC-US Pap smears. Within the northeast region, the HR-HPV prevalence in ASC-US Pap smears decreased from 61.2% (95% CI = 57.4 to 64.8%) in patients 18-22 years old to 24.9% (95% CI = 23.1 to 26.8%) in patients age 29 and older. When comparing the two classification systems, significant increases in both ASC-H and SIL and decreases in ASC-US were appreciated after the institution of Bethesda system 2001. CONCLUSION: In our large, diverse cohort, the implementation of the Bethesda II system has resulted in a decrease in ASC-US Pap smear results. Additionally, the prevalence of HR-HPV in the ASC-US population was 40.8%, significantly lower than the rate noted in the ALTS trial under the Bethesda I classification system.

Cohort Studies↗

Spontaneous pregnancy following cytoreduction with peritonectomy and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Spontaneous pregnancy is rare after radical cytoreduction and intraperitoneal chemotherapy. CASE: We present a case of a 28-year-old female with extensive, bulky malignant peritoneal epitheliod mesothelioma who underwent optimal cytoreduction with peritonectomy followed by intraoperative hyperthermic cisplatin and postoperative intraperitoneal paclitaxel and fluorouracil. Fourteen months after the conclusion of her therapy, she spontaneously conceived, resulting in an uneventful term pregnancy and spontaneous vaginal delivery. CONCLUSION: Fertility may be preserved in select patients after radical cytoreduction and hyperthermic intraperitoneal chemotherapy.

Adult↗

Markedly elevated beta-hCG levels in a normal singleton gestation with hyperreactio luteinalis.

BACKGROUND: Human chorionic gonadotropin (hCG) is produced by the trophoblast early in pregnancy and peaks at a level of approximately 100,000 IU/liter around the ninth week of gestation. Abnormally high levels are usually noted in association with multiple gestation, molar gestation, and specific ovarian or gestational malignancies. CASES: A multiparous patient in the second trimester was referred for evaluation after a maternal triple marker screen was incalculable due to a beta-hCG level of 2.1 million IU/L. Targeted sonography revealed bilateral complex adnexal masses with a solid component of the left ovary, a normal fetus, and normal placenta. The patient underwent an exploratory laparotomy at 18 weeks' gestational age. A left oophorectomy was performed. Pathology confirmed hyperreactio luteinalis. The remainder of the pregnancy was remarkable for preterm labor and delivery at 35 weeks' gestational age. At delivery, the hCG level was noted to be 24,210 IU/L, and the fetus and placenta were normal. CONCLUSION: Markedly elevated hCG levels rarely occur in normal singleton pregnancy and can be associated with hyperreactio luteinalis. When noted, a work-up to evaluate possible malignancy, molar gestation, and multiple gestation should be pursued.

Adult↗