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Although BRCA1 and BRCA2 play important roles in hereditary ovarian cancers, the extent of their role in sporadic ovarian cancers and their mechanisms of inactivation are not yet well understood. Our goal was to characterize BRCA2 mutations and mRNA expression in a group of ovarian tumors previously evaluated for BRCA1 mutations and mRNA expression. Methods: The tumors of 92 unrelated women with 'ovarian' cancer (i.e., ovarian, peritoneal, or fallopian tube cancer) were screened for BRCA2 null mutations using a protein truncation test. Methylation-specific polymerase chain reaction (PCR) was used to examine the BRCA2 promoter for hypermethylation in tumors that did not express BRCA2 mRNA. All statistical tests were two-sided. Results: Nine tumors had a germline (n = 5) or somatic (n = 4) BRCA2 mutation; each was associated with loss of heterozygosity. All of the somatic (1445delC, E880X, 4286del8, and 5783delT) and one of the germline (5984ins4) mutations were unique to this study. One tumor had somatic mutations in both BRCA1 and BRCA2. Two tumors are, to our knowledge, the first cases of germline BRCA2-associated peritoneal cancer. Twelve additional tumors lacked detectable BRCA2 mRNA, but the BRCA2 promoter was hypermethylated in only one of them, suggesting that other mechanisms effect transcriptional silencing of BRCA2. Tumors lacking BRCA1 mRNA were more likely to lack BRCA2 mRNA than tumors expressing BRCA1 mRNA (P

Background: Ovarian cancer is one of the most common hereditary cancers in women. Mutations in the BRCA1 gene increase a woman's risk of ovarian cancer. Testing for BRCA1 mutations is cumbersome and impractical for large populations. Therefore, we developed an efficient strategy to detect various types of BRCA1 dysfunction and also determined the relative frequency of BRCA1 dysfunction in ovarian cancer. Methods: Tumors from 221 patients with epithelial ovarian cancer were screened for loss of heterozygosity (LOH) at the BRCA1 locus. BRCA1 complementary DNA (cDNA) and genomic DNA from all cancers with BRCA1 LOH (106 tumors) or noninformative status (15 tumors) were polymerase chain reaction (PCR) amplified and analyzed for protein truncation in a coupled transcription/ translation test. When truncated BRCA1 protein was detected, the BRCA1 gene from both the tumor and a paired blood sample was sequenced. When BRCA1 expression in tumor cDNA was not detected with a protein truncation test, a methylation-specific PCR was used to determine whether the promoter region of BRCA1 was methylated and thus inactivated. All statistical tests were two-sided. Results: Fifty-one (23.1%) of 221 tumors had BRCA1 dysfunction, including 18 with germline mutations, 15 with somatic mutations, and 18 with monoallelic or biallelic hypermethylated promoters. By the consideration of only tumors with LOH or that were noninformative, the efficiency for detecting BRCA1 dysfunction improved to 45 (37.2%) of 121 tumors. Therefore, LOH/noninformative was a strong predictor of mutation status (Fisher's exact test, P

Microsatellite instability is very common in ovarian cancer and can cause mutations in the p53 gene. Microsatellites are short repeated DNA sequences that occur throughout the chromosomes.

Many cases of recurrent ovarian cancer may not be ovarian cancer at all but some other new tumor. Researchers used molecular techniques to analyze tissue samples from 13 ovarian cancer patients who developed recurrent cancer two to five years later. Samples from both tumors were analyzed. In 10 cases, the molecular characteristics of the recurrent tumor differed from those of the first tumor. This indicates that they were not recurrent ovarian cancer but a second tumor of a different organ, most likely the peritoneum.

A significant reduction in the level of cancer indicator CA 125 after chemotherapy may indicate a good chance of survival after ovarian cancer. Researchers computed the slope of the curve of CA 125 reduction after chemotherapy for ovarian cancer for 126 women. The slope of CA 125 reduction was found to be a more important indicator of survival than age, stage or grade of cancer, amount of chemotherapy, or remaining cancer. The ideal slope of CA 125 reduction was computed from the 11 women whose cancers were eliminated for an average of 62 months. Chemotherapy may be initiated immediately after surgery to remove tumors to maximize the chance of survival. The slope of CA 125 reduction after chemotherapy may be useful in making decisions about additional cancer treatments.

Women with uterine cancer who are very obese may have a better chance of survival than women who are less obese or of normal weight. Researchers studied 492 women with uterine cancer and correlated the survival outcome with the Quetelet index, a measure of obesity. Very obese women with a Quetelet index over 40 were found to have less aggressive cancer and 4.8% cancer-positive lymph nodes. Obese women with a Quetelet index of 30 to 40 had 13.2% positive lymph nodes, and women with an index below 30 had 10.5% positive nodes. Obese women had lower grade and stage tumors which were better defined than those of more slender women. Slender women may experience more aggressive cancer, and may benefit from lymph node analysis more than obese women may.

Background. Resistance to chemotherapy is common in bulky hypoxic tumors such as epithelial ovarian cancer. Hyperbaric oxygen (HBO) oxygenates hypoxic tissues and promotes neovascularization. These unique properties of HBO may help overcome chemotherapy resistance by increasing both tumor perfusion and cellular sensitivity. This study was undertaken to determine if HBO increases the response of epithelial ovarian cancer to cisplatin chemotherapy. Methods. In Phase 1, 64 nu/nu mice were divided into four groups and subcutaneously inoculated with cells from the A2780 human epithelial ovarian cancer cell line. Group 1 served as controls. Group 2 received weekly intraperitoneal cisplatin (3.15 mg/kg). Group 3 was exposed to HBO (dives) at 2.4 atmospheres absolute pressure for 90 minutes, 7 days a week. Group 4 received both cisplatin and HBO. In Phase II, 72 mice were divided into two groups and similarly inoculated. Both groups received weekly intraperitoneal cisplatin (2.5 mg/kg). Group 1 was not exposed to HBO. Group 2 was exposed to HBO for 5 days a week. Results. Dramatic tumor neovascularization was found in tumors of mice exposed to HBO (P = 0.0001). There was significant (P = 0.014) tumor growth retardation in Phase I for mice receiving both cisplatin and HBO compared with those treated with cisplatin alone. This significance was noted after just two doses of cisplatin but subsequently lost due to reduced numbers of mice. In Phase II, neovascularization was detectable after 10 HBO treatments (2 weeks) and was maximal after 15 treatments (3 weeks). Conclusions. Hyperbaric oxygen increases vascularity in bulky tumors such as epithelial ovarian cancer. There appears to be a relationship between increased vascularity and enhanced response to chemotherapy that merits further investigation. Cancer 1995; 75:2313-22. Key words: ovarian cancer, tumor hypoxia, chemotherapy resistance, chemosensitizer, hyperbaric oxygen, neovascularization, bulky tumor, angiogenesis.

Cancer of the ovary ranks fourth as a cause of death among women in the US. Surgical removal of the tumor and treatment with the anticancer agent cisplatin have increased the survival time of women with ovarian cancer. CA 125 is a substance released by the epithelial form of ovarian cancer and can be used to assess the progression of disease and response to treatment. Increased levels of CA 125 suggest progression of the cancer or lack of response to chemotherapy. However, in most cases, the effectiveness of chemotherapy is assessed by surgery, in which the abdomen is examined for any residual cancer cells following treatment. Measurement of CA 125 levels before repeat surgery is not very effective in predicting disease progression in advanced cases of epithelial ovarian cancer. However, CA 125 levels may be useful in evaluating the initial response of tumor cells to chemotherapy and to compare the effectiveness of different drug regimens. A model was developed in which CA 125 levels decline with decreasing numbers of tumor cells. The average time for initial CA 125 levels to decrease by 50 percent following surgery to remove the tumor was 10.4 days. It was predicted that the response of tumor cells to drug therapy was greater with high doses of cisplatin compared with lower doses. This initial response of tumor cells as indicated by CA 125 may be used to predict the outcome of repeat surgery and overall survival. (Consumer Summary produced by Reliance Medical Information, Inc.)

EDITOR--The process of X chromosome inactivation was identified as early as 1960 when Ohno and Hauschka [1] described the presence of a pyknotic X chromosome in both benign and malignant [...]

Objectives. To define clinically relevant reference ('normal') values for cerebrospinal fluid (CSF) protein concentrations in pediatric patients who were evaluated for meningitis by traditional criteria and by enterovirus--polymerase chain reaction (EV-PCR). Design and Patients: A cohort of 906 consecutive pediatric patients to receive CSF analysis at St Louis Children's Hospital, St Louis, Mo, from June 1, 1998, to December 31,1998, was studied for clinical and laboratory data. Age-dependent CSF protein concentrations were then derived from a reference group of 225 patients in whom meningitis and other neurologic diseases were excluded by traditional clinical or laboratory criteria (excluding EV-PCR). Available CSF samples from 132 patients of the reference group were subsequently tested for EV-PCR. Results: In the reference group, the CSF protein concentration was highest and most variable in neonates, with a maximum of approximately 1.0 g/L. Cerebrospinal fluid protein concentration decreased rapidly to a nadir by 6 months and remained low throughout childhood, rarely exceeding 0.3 g/L and, finally, increasing in adolescence toward adult values. Enterovirus--polymerase chain reaction was positive in CSF of 11% of the reference group, with EV-PCR-positive patients having significantly higher CSF protein concentrations than EV-PCR-negative patients aged between 4 months and 14 years. Conclusions: Reference values for CSF protein exhibit a characteristic age dependence in pediatric patients. Continued standard use of adult reference values in the pediatric population is inappropriate. The unexpected finding of a positive EV-PCR in patients not diagnosed with meningitis by traditional criteria further emphasizes the importance of selecting the most clinically relevant reference group for age and other variables when defining normal laboratory values. Arch Pediatr Adolesc Med. 2000;154:827-831

ABSTRACTInfluenza A and B viruses and respiratory syncytial virus (RSV) are three common viruses implicated in seasonal respiratory tract infections and are a major cause of morbidity and mortality in adults and children worldwide. In recent years, an increasing number of commercial molecular tests have become available to diagnose respiratory viral infections. The Luminex Aries Flu A/B & RSV assay is a fully automated sample-to-answer molecular diagnostic assay for the detection of influenza A, influenza B, and RSV. The clinical performance of the Aries Flu A/B & RSV assay was prospectively evaluated in comparison to that of the Luminex xTAG respiratory viral panel (RVP) at four North American clinical institutions over a 2-year period. Of the 2,479 eligible nasopharyngeal swab specimens included in the prospective study, 2,371 gave concordant results between the assays. One hundred eight specimens generated results that were discordant with those from the xTAG RVP and were further analyzed by bidirectional sequencing. Final clinical sensitivity values of the Aries Flu A/B & RSV assay were 98.1% for influenza A virus, 98.0% for influenza B virus, and 97.7% for RSV. Final clinical specificities for all three pathogens ranged from 98.6% to 99.8%. Due to the low prevalence of influenza B, an additional 40 banked influenza B-positive specimens were tested at the participating clinical laboratories and were all accurately detected by the Aries Flu A/B & RSV assay. This study demonstrates that the Aries Flu A/B & RSV assay is a suitable method for rapid and accurate identification of these causative pathogens in respiratory infections.

The Scientific Board of the California Medical Association presents the following inventory of items of progress in obstetrics and gynecology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, research workers, or scholars to stay abreast of these items of progress in obstetrics and gynecology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another The items of progress listed below were selected by the Advisory Panel to the Section on Obstetrics and Gynecology of the California Medical Association, and the summaries were prepared under its direction., AN ANTIGEN COMMON to fetal coelomic epithelium and its adult derivatives, CA 125, has received intensive research and now practical clinical scrutiny in the management of ovarian carcinomas of an [...]

ABSTRACTWe have developed and evaluated a real-time reverse transcriptase PCR (RT-PCR) assay for the detection of human enterovirus D68 (EV-D68) in clinical specimens. This assay was developed in response to the unprecedented 2014 nationwide EV-D68 outbreak in the United States associated with severe respiratory illness. As part of our evaluation of the outbreak, we sequenced and published the genome sequence of the EV-D68 virus circulating in St. Louis, MO. This sequence, along with other GenBank sequences from past EV-D68 occurrences, was used to computationally select a region of EV-D68 appropriate for targeting in a strain-specific RT-PCR assay. The RT-PCR assay amplifies a segment of the VP1 gene, with an analytic limit of detection of 4 copies per reaction, and it was more sensitive than commercially available assays that detect enteroviruses and rhinoviruses without distinguishing between the two, including three multiplex respiratory panels approved for clinical use by the FDA. The assay did not detect any other enteroviruses or rhinoviruses tested and did detect divergent strains of EV-D68, including the first EV-D68 strain (Fermon) identified in California in 1962. This assay should be useful for identifying and studying current and future outbreaks of EV-D68 viruses.

Background: Most human female cells contain two X chromosomes, only one of which is active. The process of X-chromosome inactivation, which occurs early in development, is usually random, producing tissues with equal mixtures of cells having active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation may occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function. This scenario could represent a previously unrecognized mechanism for development of hereditary cancers. We investigated whether such a mechanism might contribute to the development of hereditary ovarian cancers. Methods: Patterns of X-chromosome inactivation were determined by means of polymerase chain reaction amplification of the CAG-nucleotide repeat of the androgen receptor (AR) gene after methylation-sensitive restriction endonuclease digestion of blood mononuclear cell DNA from patients with invasive (n = 213) or borderline (n = 44) ovarian cancer and control subjects without a personal or family history of cancer (n = 50). BRCA1 gene status was determined by means of single-strand conformational polymorphism analysis and DNA sequencing. All statistical tests were two-sided. Results and Conclusions: Among individuals informative for the AR locus, nonrandom X-chromosome inactivation was found in the DNA of 53% of those with invasive cancer versus 28% of those with borderline cancer (P = .005) and 33% of healthy control subjects (P = .016). Nonrandom X-chromosome inactivation can be a heritable trait. Nine of 11 AR-informative carriers of germline BRCA1 mutations demonstrated nonrandom X-chromosome inactivation (.0002 [is less than] P [is less than] .008, for simultaneous occurrence of both). Implications: Nonrandom X-chromosome inactivation may be a predisposing factor for the development of invasive, but not borderline, ovarian cancer. [J Natl Cancer Inst 1999;91:339-46]

ABSTRACTHigh-throughput multiplex assays for respiratory viruses are an important step forward in diagnostic virology. We compared one such assay, the PLx Multi-Code Respiratory Virus Panel (PLx-RVP), manufactured by Eragen Biosciences, Inc. (Madison, WI), with conventional virologic testing, consisting of fluorescent-antibody staining plus testing with the R-mix system and fibroblast tube cultures. The test set consisted of 410 archived respiratory specimens, mostly nasopharyngeal swabs, including 210 that had been positive by conventional testing for a balanced selection of common respiratory viruses. Specimens yielding discrepant results were evaluated using a panel of respiratory virus PCR assays developed, characterized, and validated with clinical specimens. PLx-RVP increased the total rate of detection of viruses by 35.8%, and there was a 25.7% increase in the rate of detection of positive specimens. Reference PCR assay results corroborated the PLx-RVP result for 54 (82%) of 66 discrepancies with conventional testing. Of the 12 specimens with discrepancies between PLx-RVp and the reference PCRs, 6 were positive for rhinovirus by PLx-RVP and the presence of rhinovirus was confirmed by nucleotide sequencing. The remaining six specimens included five in which the PLx-RVP failed to detect parainfluenza virus and one in which the detection of influenza A virus by PLx-RVP could not be confirmed by the reference PCR. Taking the results of the reference PCR assay results into account, the sensitivities of the PLx-RVP for individual viruses ranged from 94 to 100% and the specificities ranged from 99 to 100%. We conclude that PLx-RVP is a highly accurate system for the detection of respiratory viruses and significantly improves the rate of detection of these viruses compared to that by conventional virologic testing.

Studies have reported the presence of KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in respiratory secretions of young patients. So far, evidence has not supported a link between infections with either virus and respiratory tract disease; however, there has not been a large comparison of KIPyV-infected patients to age-matched patient groups.

ABSTRACTThe MultiCode-PLx system (EraGen Biosciences, Inc., Madison, WI) for the detection of respiratory viruses uses an expanded genetic alphabet, multiplex PCR chemistry, and microsphere flow cytometry to rapidly detect and specifically identify 17 different respiratory viruses directly in clinical specimens. The MultiCode-PLx system was tested in parallel with direct fluorescent-antibody (DFA) staining and rapid shell vial culture (R-mix cells; Diagnostic Hybrids, Inc. Athens, OH) with 354 respiratory specimens from adult patients that were submitted to the clinical virology laboratory at the Emory University Hospital. Single-target PCRs were performed with retained samples to confirm the positive results obtained with the MultiCode-PLx system for viruses not covered by DFA and R-mix culture (metapneumovirus, coronaviruses [CoV], parainfluenza viruses 4a and 4b, and rhinoviruses) and to resolve any discrepancies between the DFA and R-mix culture and the MultiCode-PLx results for viruses common to both systems. Respiratory viruses were detected in 77 (21.8%) and 116 (32.7%) specimens by DFA and R-mix culture and with the MultiCode-PLx system, respectively. Among the viruses common to both systems, the MultiCode-PLx system detected significantly more influenza A viruses (P= 0.0026). An additional increased diagnostic yield with the MultiCode-PLx system resulted from the detection of human metapneumovirus (HMPV) in 9 specimens, human CoV (HCoV) in 3 specimens, and human rhinovirus (HRV) in 16 specimens. Also, two mixed viral infections were detected by the MultiCode-PLx system (HCoV OC43 and HRV infections and HMPV and HRV infections), but none were detected by DFA and R-mix culture. Single-target PCRs verified the results obtained with the MultiCode-PLx system for 73 of 81 (90.1%) specimens that had discordant results or that were not covered by DFA and R-mix culture. The MultiCode-PLx system provides clinical laboratories with a practical, rapid, and sensitive means for the massively multiplexed molecular detection of common respiratory viruses.

ABSTRACTWe performed a blinded study to compare repetitive-sequence PCR and multilocus sequence typing for genotyping hospital- and community-acquired methicillin-resistant Staphylococcus aureus(MRSA). The MRSA strains that were sequence type 8 (ST8), staphylococcal cassette chromosome mec(SCCmec) type IV, and Panton-Valentine leukocidin-positive clustered separately from those that were ST5 and SCCmectype II.

BACKGROUND: Almost 70% of all patients with lung cancer in the United States are 65 years of age, and the incidence of small-cell lung cancer (SCLC) increases with age until the eighth decade of life. However, elderly patients are underrepresented in clinical trials and are often suboptimally treated. The validity of age as a prognostic factor for toxicity or survival remains controversial. PATIENTS AND METHODS: To investigate the safety and efficacy of topotecan (an approved treatment for relapsed SCLC) in older patients, we performed a retrospective analysis in patients ≤ 65 years of age versus patients < 65 years of age from 5 large topotecan trials. In all 5 trials, patients received topotecan 1.5 mg/m2per day via a 30-minute intravenous infusion on days 1 through 5 of a 21-day cycle. Efficacy and tolerability outcomes were assessed for both age groups. RESULTS: Topotecan was similarly tolerated in both age groups, with generally manageable hematologic toxicity. The incidence, duration, and onset of severe hematologic toxicities did not vary significantly with age. In the < 65 age group, grade 4 neutropenia and leukopenia were reported in 72% and 32% of patients, respectively; in the ≤ 65 age group, grade 4 neutropenia and leukopenia were reported in 77% and 31% of patients, respectively. Grade 4 thrombocytopenia was less common in the < 65 age group. Nonhematologic toxicities, median time to progression, and overall survival were comparable between groups. CONCLUSION: This is the first demonstration of the safety and efficacy of topotecan in older patients with recurrent SCLC. Future studies are needed to fully characterize the role of topotecan in the treatment of older patients.

ABSTRACTDuring the 2001, 2002, and 2003 enterovirus seasons, we investigated the correlations between cerebrospinal fluid (CSF) nucleated cell counts and elevated CSF protein levels and the detection of enteroviral RNA by reverse transcription (RT)-PCR. Our objective was to determine if pleocytosis and/or elevated protein levels were predictive of positive RT-PCR results for enterovirus. We were also interested in determining if the presence of West Nile virus during the 2002 enteroviral season contributed to a change in these correlations. We found that in the group of patients aged >2 months, the absence of pleocytosis was highly predictive of a negative RT-PCR result. Elevated CSF protein level was not a good predictor of RT-PCR positivity for enterovirus and did not add to the diagnostic sensitivity or specificity of pleocytosis.

Telomerase activation and p53 dysfunction are important events in the development and progression of most cancers including ovarian cancer. However, many cancer cell lines and human tumors have been shown to lack telomerase, and maintain telomerase through the ALT (alternative lengthening of telomeres). It is not known whether specific types of p53 mutations are correlated with telomerase activity in human tumors. Invasive ovarian cancers (109) were analyzed for telomerase by ELISA and its subunits human telomerase RNA (hTR), and human telomerase reverse transcriptase (hTERT) by RT-PCR. p53 protein was analyzed in the same samples using immunohistochemistry, and p53 exons 2-11 were analyzed using SSCP and sequence analysis. Telomerase activity was detected in 80 (74%) of 109 tumors. The subunit hTR was consistently present in all ovarian cancer samples, and hTERT was expressed in 96 (88%) tumors. Thirteen (16%) tumors were negative for hTERT and none of these expressed telomerase. Fifty-seven (52%) tumors stained positive for p53, and there was no correlation with telomerase activity based on p53 staining (p = 0.08). Eighty-two (75%) tumors were found to have a p53 mutation, and 40 (36%) tumors contained a null mutation. Only 14% of the tumors with wild type or missense p53 were negative for telomerase activity. In contrast, 19 (48%) of 40 tumors with a p53 null mutation were negative for telomerase activity (p

Objectives.The coexistence of carcinomas of the endometrium and ovary occurs in about 10% of women with ovarian carcinoma. It is often unclear whether this represents synchronous primary tumors or metastasis from endometrium to ovary, or from ovary to endometrium; consequently, staging, therapy, and expected outcome are uncertain. The Gynecologic Oncology Group sought to study patients with simultaneously detected adenocarcinomas in the endometrium and ovary with disease grossly confined to the pelvis to explore the possible correlation among discrete tumor subsets, natural history, and survival.

ABSTRACTPCR was used to amplify a 537-bp region of an Ehrlichia ewingiigene encoding a homologue of the 28-kDa major antigenic protein (P28) of Ehrlichia chaffeensis. The E. ewingii p28gene homologue was amplified from DNA extracted from whole blood obtained from four humans and one canine with confirmed cases of infection. Sequencing of the PCR products (505 bp) revealed a partial gene with homology to outer membrane protein genes from Ehrlichiaand Cowdriaspp.:p30of Ehrlichia canis(=71.3%),p28of E. chaffeensis(=68.3%), andmap1of Cowdria ruminantium(67.3%). The peptide sequence of the E. ewingiipartial gene product was deduced (168 amino acids) and the antigenicity profile was analyzed, revealing a hydrophilic protein with =69.1% identity to P28 of E. chaffeensis, =67.3% identity to P30 of E. canis, and =63.1% identity to MAP1 of C. ruminantium. Primers were selected from the E. ewingii p28sequence and used to develop a species-specific PCR diagnostic assay. The p28PCR assay amplified the expected 215-bp product from DNA that was extracted from EDTA-treated blood from each of the confirmed E. ewingiiinfections that were available. The assay did not produce PCR products with DNA extracted from E. chaffeensis-, E. canis-, or E. phagocytophila-infected samples, confirming the specificity of the p28assay forE. ewingii. The sensitivity of the E. ewingii-specific PCR assay was evaluated and determined to detect as few as 38 copies of the p28gene.

During development, the formation and remodeling of primary vascular networks occurs by vasculogenesis and angiogenesis. Recently, the term “vasculogenic mimicry” has been used by our laboratory and collaborators to reflect the embryonic-like ability of aggressive, but not nonaggressive, melanoma tumor cells to form a pattern of matrix-rich networks (containing channels) surrounding spheroids of tumor cells in three-dimensional culture, concomitant with their expression of vascular cell markers. Ovarian cancer is usually diagnosed as advanced stage disease in most patients when widespread metastases have already been established within the peritoneal cavity. In this study, we explored whether invasive ovarian carcinoma cells could engage in molecular vasculogenic mimicry reflected by their plasticity, compared with their normal cell counterparts. The data revealed that the invasive ovarian cancer cells, but not normal ovarian surface epithelial cells, formed patterned networks containing solid and hollow matrix channels when grown in three-dimensional cultures containing Matrigel or type I collagen, in the absence of endothelial cells or fibroblasts. Immunohistochemical analysis showed that matrix metalloproteinases (MMP)-1, -2, and -9, and MT1-MMP were discretely localized to these networks, and the formation of the networks was inhibited by treatment with MMP inhibitors. Furthermore, the RNase protection assay revealed the expression of multiple vascular cell-associated markers by the invasive ovarian cancer cells. In patient tumor sections from high-stage, high-grade ovarian cancers, 7 to 10% of channels containing red blood cells were lined by tumor cells. By comparison, all vascular areas in benign tumors and low-stage cancers were endothelial lined. These results may offer new insights and molecular markers for consideration in ovarian cancer diagnosis and treatment strategies based on molecular vascular mimicry by aggressive tumor cells.

Objective.Our previous analysis found a high rate of early menopause in cervical cancer patients with ovarian transposition (OT) compared to a group that underwent radical hysterectomy (RH) alone. The current study evaluates ovarian function in the same group for a prolonged follow-up period and analyzes predictive factors for early menopause.

Background: To assess the utility and safety of three different longterm indwelling intravenous catheters in patients with gynecologic malignancies.

Traditional inguinal lymphadenectomy includes the removal of a portion of the saphenous vein. The authors hypothesized that preserving the saphenous vein would decrease morbidity without affecting treatment outcome. A retrospective review of 83 patients with carcinoma of the vulva who underwent inguinal lymphadenectomy between 1990–1998 was performed. Postoperative short term and long term complications were evaluated. A total of 139 inguinal dissections were performed in 83 patients. The saphenous vein was preserved in 62 patients and ligated in 77 patients. The clinical characteristics of the patients, the operating time, and the estimated blood loss were not significantly different between the two groups. The incidence rate of short term complications including fever, seroma, phlebitis, lymphocyst, and deep venous thrombosis also was similar. Cellulitis occurred in 39% of the patients who underwent vein ligation compared with 18% of the patients who underwent a vein-sparing procedure (P = 0.006). Short term (&lt; 6 months) lower extremity lymphedema occurred in 70% of the vein-ligated group compared with 32% of the vein-spared group (P &lt; 0.001). Chronic edema (≥ 2 years) was present in only 3% of the patients who underwent saphenous vein preservation compared with 32% of those who underwent vein ligation (P = 0.003). Chronic lymphedema in the vein-spared group was observed in only one patient who received postoperative radiation. Overall, individuals with preservation of the saphenous vein were less likely to develop complications (56% vs. 23%; P &lt; 0.001). There was no difference in the rate of incidence of recurrent disease between the two groups. Preservation of the saphenous vein during inguinal lymphadenectomy reduces both the short term and long term postoperative complications without affecting treatment outcome. The saphenous vein should be preserved routinely in patients undergoing inguinal lymphadenectomy. Cancer 2000;89:1520–5. © 2000 American Cancer Society.

ABSTRACTBroad-range PCR primers were used to amplify part of thegroESLoperon of the canine pathogen Ehrlichia ewingii, recently recognized as a human pathogen, and the murine pathogen Ehrlichia muris. Phylogenetic analysis supported the relationships among Ehrlichiaspecies previously determined by comparison of 16S rRNA gene sequences. These sequences provide additional PCR targets for species for which few gene sequences have been determined.

To compare the prognoses of women diagnosed with cervical cancer during pregnancy with the prognoses of those diagnosed within 6 months after delivery and to assess the effect of vaginal delivery on recurrence risk and prognosis.

Objective.X-Chromosome loss of heterozygosity (LOH) occurs in approximately 40% of ovarian cancers. We have previously demonstrated an association between nonrandom X-chromosome inactivation and germline BRCA1mutation. The current study examines the association between X-chromosome LOH and BRCA1mutation.

Objective: To determine the value of computed tomography (CT) scans for preoperatively detecting extrauterine-nodal disease and postoperative recurrent disease in patients with endometrial cancer.

ABSTRACTHuman monocytic ehrlichiosis is an emerging infectious disease caused by Ehrlichia chaffeensis, a gram-negative obligatory intracellular bacterium closely related to E. canis. The immunoreactive recombinant fusion proteins rP28 and rP30 have become available after cloning and expressing of the 28- and 30-kDa major outer membrane protein genes of E. chaffeensisand E. canis, respectively. Western immunoblotting was performed to analyze the antibody responses of the 37 E. chaffeensisindirect fluorescent-antibody assay (IFA)-positive and 20 IFA-negative serum specimens with purified whole organisms, rP28, and rP30. All IFA-negative sera were negative with purified whole organisms, rP28, or rP30 by Western immunoblot analysis (100% relative diagnostic specificity). Of 37 IFA-positive sera, 34 sera reacted with any native proteins of E. chaffeensisranging from 44 to 110 kDa, and 30 sera reacted with 44- to 110-kDa native E. canisantigens. The 28-kDa E. chaffeensisand 30-kDa E. canisnative proteins were recognized by 25 IFA-positive sera. Fifteen IFA-positive sera reacted with rP28 by Western blot analysis, whereas 34 IFA-positive sera reacted with rP30 (92% relative diagnostic specificity), indicating that rP30 is more sensitive than rP28 for detecting the antibodies in IFA-positive sera. These 34 IFA-positive sera were positive by the dot blot assay with rP30, distinguishing them from IFA-negative sera. Except for three rP30-negative but IFA-positive specimens that instead showed anE. ewingiiinfection-like profile by Western immunoblotting, the results of Western and dot blot assays with rP30 matched 100% with the IFA test results. Densitometric analysis of dot blot reactions showed a positive correlation between the dot density and the IFA titer. These results suggest that rP30 antigen would provide a simple, consistent, and rapid serodiagnosis for human monocytic ehrlichiosis.

BRCA1 mutation research in ovarian and breast cancer 17q21-linked families has yielded a large number of germline sequence variations. Somatic mutations have been uncommonly reported. We screened 81 probands with primary ovarian, peritoneal, or fallopian tube carcinoma for BRCA1 mutations. The study group was intentionally biased by the inclusion of 29 probands with a family history of ovarian and/or breast carcinoma, 13 probands diagnosed on or before age 45, seven individuals with a metachronous breast cancer and 51 tumors with BRCA1 LOH. Tumor and/or germline DNA was screened by modified techniques of single-strand confirmation polymorphism analysis, and abnormal banding patterns were sequenced to confirm mutations. Twenty-one (25.9%) BRCA1 sequence variations were identified. Eight mutations were somatic including seven null mutations. Apart from classical hereditary ovarian/breast cancer, a family history of ovarian/breast cancer defines a subset of ovarian cancer individuals with a significant likelihood of either a germline or a somatic BRCA1 gene sequence variation.

To provide a review of the basic mechanisms of drug resistance in ovarian cancer and novel strategies to modulate drug resistance for the general obstetrician-gynecologist.

Data regarding the value of cytoreduction and cell histology in ovarian sarcomas are limited. The goal of this study was to assess the value of surgical cytoreduction, preoperative CA 125 levels, stage, histology, and platinum-based chemotherapy in the primary treatment of ovarian sarcomas. A retrospective analysis of 47 women with primary ovarian sarcomas was performed. Forty-one patients (87%) presented with advanced stage disease (International Federation of Gynecology and Obstetrics Stage III or IV). Optimal surgical cytoreduction (&lt;1 cm residual tumor burden) was achieved in 25 patients (53%). Forty patients (85%) had a malignant mixed müllerian tumor whereas 7 patients had a pure sarcoma. Eighteen women with mixed müllerian tumors had homologous tumors and 22 had heterologous elements. Patients treated with platinum-based chemotherapy were significantly more likely to have a response (P = 0.008) compared with those treated with other regimens. Treatment with platinum-based chemotherapy also showed a survival advantage (P = 0.03). Preoperative CA 125 levels were elevated (>35 U/mL) in 93% of patients with ovarian sarcomas. A preoperative CA 125 level &lt; 75 U/mL was significantly associated with better survival (P = 0.01). In univariate analysis, other significant predictors of improved survival were early stage (P = 0.04), homologous tumors (P &lt; 0.05), and optimal surgical cytoreduction (P &lt; 0.001). In multivariate analysis of various prognostic variables, optimal surgical cytoreduction (P &lt; 0.001) was the most significant factor, followed by histologic subtype (P &lt; 0.02). Ovarian sarcomas are rare malignancies with a poor prognosis. All women with suspected ovarian carcinoma or sarcoma should have a preoperative CA 125 level taken. Surgical cytoreduction to a residual tumor burden of ≤1 cm improves outcome and should be the goal of surgery. Although the optimal consolidation chemotherapy regimen remains unknown, platinum should be included as part of the regimen. Cancer 1998;82:1731-7. © 1998 American Cancer Society.

Totally implanted central venous access devices provide reliable delivery of repetitive chemotherapy courses. However, placement of these ports requires special expertise and facilities, and is not without risk of major complications. This paper reports the technique of placing a new peripherally accessed, totally implantable, central venous port in 22 patients for the repeated administration of systemic chemotherapy. All ports were successfully placed under local anesthesia, with catheter tip location determined by an electronic sensor wand. The ports have been in use for a total of 387 patient-weeks. One port required removal secondary to an infection at the port site. Twenty-one ports have remained functional for infusion and blood sampling through 99 courses of chemotherapy. Acceptance by patients, nurses, and physicians has been excellent.

Wound complications were investigated in 100 patients undergoing chemotherapy for epithelial ovarian cancer and compared with wound complications in patients with other gynecologic malignancy who did not receive chemotherapy but were operated on by the same gynecologic oncologists. The incidence of wound complications in the chemotherapy-treated population was 11. Complications developed with equal frequency regardless of when postoperative chemotherapy was initiated. Thus, chemotherapy did not increase the risk of wound complications despite efforts to begin chemotherapy as soon as possible after cytoreductive surgery. Low postoperative albumin levels (P< .01), postoperative hemoglobin of 10 g/dL or less (P< .02), advanced stage of disease (P< .004), and electrocautery use (P< .05) were all risk factors for development of wound complications, whereas the frequency of bowel resection and type of fascial or skin closure did not adversely influence the risk. Patients who received chemotherapy and developed wound breakdown actually healed faster than our control population. They healed at the same rate as did obstetric and gynecologic patients from the literature. Because delays in administering chemotherapy postoperatively have been associated with decreased survival, we recommend that chemotherapy for advanced-stage epithelial cancer not be delayed solely because of concern for wound healing.

An unusual extrauterine (pelvic) variant of adenosarcoma is presented. A benign-appearing epithelium resembling fallopian tube epithelium is integrally mixed with malignant stroma that in all areas sampled is low-grade leiomyosarcoma. The tumor has behaved as a low-grade malignancy with four local recurrences over a 16-year period. Extrauterine adenosarcomas have rarely been reported in the literature; and one in which the stromal component is histologically all of smooth muscle differentiation is more unusual.