Comparison Study of Self-Sampled and Physician-Sampled Specimens for High-Risk Human Papillomavirus Test and Cytology.

OBJECTIVE: The objective of this study was to calculate the positive rate and overall concordance rate of high-risk human papillomavirus (hrHPV) test and cytology using self-sampled and physician-sampled cervicovaginal tests and to compare both specimens. METHODS: In collaboration with 3 private hospitals in Sapporo city, 300 women visiting these organizations were enrolled in the study by previously signing an informed consent. From these women, both types of samples (self-obtained and physician-sampled) were obtained at the same time. HrHPV test and cytology were performed on both specimens, and the positive rate and overall concordance rate were calculated to compare both specimens. RESULTS: HrHPV-positive women were 13.7% in physician-sampled specimens and 14.7% in self-sampled specimens, with an overall concordance rate of 96.3% (95% confidence interval [CI]: 94-98%). On the other hand, the positive rate of the cases higher than or equal to atypical squamous cells of undetermined significance (ASCUS) on cytology was different between both groups, that is, 12.3% in physician-obtained and 5.3% in self-sampled specimens; the overall concordance rate was 90.7% (95% CI: 87-94%), indicating an apparent decrease in the positive rate of cytology in self-obtained specimens. CONCLUSION: HrHPV test and cytology were performed on parallel samples obtained by the patients with a self-sampling tool and by the physician. The positive rate of cytology was considerably different between these specimens, while almost equivalent results were obtained for hrHPV test in both specimens. It was concluded that hrHPV test may be safely and accurately performed on self-obtained cervicovaginal samples by the help of a self-sampling device in the Japanese population as a first screening tool, with equivalent results to physician-obtained specimens.

Postpartum migraines: a long-term prospective study.

OBJECTIVE: There are many reports regarding the course of migraines during pregnancy. However, the prevalence and characteristics of migraines during the postpartum period have not been adequately investigated. We prospectively investigated the patients suffering from migraines over a long postpartum period in an obstetrics department in Japan. METHODS: We investigated the course of migraines experienced during the postpartum period by patients in a postnatal ward. The patients were surveyed during the first postpartum week and 1, 3, 6 and 12 months after delivery. The patients were provided a headache diary to assess medication use and migraine attack frequency, severity (the faces pain scale) and duration. RESULTS: The migraine remission rate was 63%, 83% and 85% during the first, second and third trimesters, respectively. No patient experienced a worsening of headaches during pregnancy. Headache recurrence during the first month after delivery was more frequent in the patients >30 years of age than in those ≤30 years of age (p<0.05). The percentage of women experiencing recurrence at 1, 3, 6 and 12 months after delivery was 63%, 75%, 78% (n=60) and 87.5% (n=40), respectively. In breastfeeding patients, the rates were 50%, 65.8%, 71.1% and 91.7% and in bottle feeding patients, the rates were 86.4%, 90.9%, 95.5% and 81.3%, respectively. CONCLUSION: We found that 85% of the patients with migraines experience remission during pregnancy and that more than 50% experience recurrence during the first month after delivery. Until six months after delivery, breastfeeding is associated with a lower recurrence rate than bottle feeding.

Lipopolysaccharide (LPS)-induced Interferon (IFN)-gamma production by decidual mononuclear cells (DMNC) is interleukin (IL)-2 and IL-12 dependent.

PROBLEM: Th1-shifted immune response is believed to be harmful for successful pregnancy because of activation of maternal cytotoxic T lymphocytes and natural killer cells. However, its effects on Toll-like receptor (TLR)-mediated innate immune response are so far unknown and this study has been undertaken to address the issue. METHOD OF STUDY: decidual tissues were obtained from 16 pregnant women undergoing elective termination during the first trimester pregnancy for socioeconomic reasons. Decidual Mononuclear Cells (DMNC) were stimulated with suboptimal doses of IL-2 and IL-12 with/without LPS, considered to be a TLR4 ligand, for 48 hr. Productions of IFN-γ and tumor necrosis factor (TNF)-α in culture supernatant were measured with ELISA. RESULTS: (i) IFN-γ production was induced with LPS alone which was strongly up-regulated in the presence of IL-2 and IL-12. (ii) TNF-α was also induced by LPS but was not affected by the presence of IL-2 and IL-12. CONCLUSION: IL-2 and IL-12 up-regulated the production of IFN-γ in DMNC through increasing their susceptibility to LPS. TNF-α production is independent of such a mechanism.

Role of glucocorticoid receptor in the inhibitory effect of medroxyprogesterone acetate on the estrogen-induced endothelial nitric oxide synthase phosphorylation in human umbilical vein endothelial cells.

We aimed to clarify which steroid receptor is involved in the inhibitory effect of medroxyprogesterone acetate (MPA) on estrogen-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVEC). The progesterone/glucocorticoid receptor (GR) antagonist RU-486 and introduction of GR siRNA caused attenuation of the inhibitory effect of MPA on the estrogen-induced eNOS phosphorylation and eNOS activity in HUVEC.

[HIV infected pregnant women in Japan and prevention of mother-to-child transmission].

By the investigation of our study group 595 HIV infected pregnant women have been confirmed in Japan since 1984. In recent years, around 40 pregnant women a year were diagnosed as HIV positive. These HIV infected pregnant women were not concerned with a value of CD4 and received antiretroviral therapy such as zidovudine (AZT) monotherapy or highly active antiretroviral therapy (HAART) starting from the second trimester of pregnancy. According to recommendations and current data, cesarean delivery before the onset of labor is performed around 37 weeks of pregnancy and prophylactic AZT syrups are given to infants starting 8-12 hrs after birth for 6 weeks. These preventive managements such as antiretroviral therapy, elective cesarean delivery and formula feeding significantly reduced mother-to-child transmission (MTCT) of HIV. The transmission rate of HIV fell to 0.5% in Japan, but the problem of the teratogenicity of antiretroviral drugs remain unclear. Further studies are needed.

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition.

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

Randomized phase II trial of paclitaxel plus carboplatin therapy versus irinotecan plus cisplatin therapy as first-line chemotherapy for clear cell adenocarcinoma of the ovary: a JGOG study.

INTRODUCTION: Paclitaxel plus carboplatin (TC) is generally considered to be the "gold standard" regimen for treatment of epithelial ovarian carcinomas. Little data are available, however, on the use of this regimen in patients with clear cell adenocarcinoma of the ovary (CCC). Combination chemotherapy with irinotecan hydrochloride plus cisplatin has been reported to be effective for primary and recurrent or resistant CCC. We compared these 2 combinations in patients with CCC. METHODS: Patients (n = 99) with CCC were randomly assigned to receive either 180 mg/m2 paclitaxel on day 1 plus AUC 6 mg/mL x minute carboplatin on day 1 every 21 days (TC arm) or 60 mg/m2 irinotecan hydrochloride on days 1, 8, 15 plus 60 mg/m2 cisplatin on day 1 every 28 days (CPT-P arm). RESULTS: Percentages of patients receiving the scheduled 6 cycles of chemotherapy in the TC and CPT-P arms were 70.8% and 72.0%, respectively. Although toxicity was well tolerated in both arms, the toxicity profile of each arm differed. Progression-free survival (PFS) showed no significant difference between the 2 treatment groups. Because there were more patients with large residual disease in the CPT-P arm, we performed a subset analysis by removing those patients, and then compared the PFS with that of patients without residual disease or with residual disease less than 2 cm. The PFS tended to be longer in the CPT-P group, although the difference was not statistically significant. CONCLUSIONS: A phase III randomized trial is required to elucidate the effectiveness of CPT-P combination chemotherapy for CCC.

A human immunodeficiency virus screening algorithm to address the high rate of false-positive results in pregnant women in Japan.

BACKGROUND: Prenatal human immunodeficiency virus (HIV) testing is essential for the prevention of mother-to-child transmission. However, false-positive results of screening testing are a concern as they may cause unnecessary emotional stress to pregnant women waiting for confirmatory test results. In regions with an extremely low prevalence, the positive predictive values of screening are unacceptably low rate. Here, we propose a HIV screening algorithm consisting of serial two fourth-generation enzyme immunoassays to reduce the number of false-positive screening results. METHODOLOGY/PRINCIPAL FINDINGS: When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive. Confirmatory Western blots and nucleic acid amplification test also showed that one was positive and the remaining 26 were negative; the subject who was positive with the confirmatory tests was identical to the subject who was positive with the second screening test. Thus, by adding the second screening test, the false-positive rate was improved from 0.4% to 0%, and the positive predictive value from 3.7% to 100%, compared with the single screening test. CONCLUSION: By applying our serial screening algorithm to HIV testing in maternity hospitals, many uninfected pregnant women would not need to receive confirmatory tests and be subjected to emotional turmoil while waiting for their confirmatory test results. This algorithm would be suitable for HIV testing of pregnant women living in low prevalence regions such as Japan.

Co-administration of cholera toxin and apple polyphenol extract as a novel and safe mucosal adjuvant strategy.

Although native cholera toxin (CT) is an extremely effective adjuvant, its toxicity prevents its use in humans. We report here that apple polyphenol extract (APE), obtained from unripe apples, reduces CT-induced morphological changes and cAMP accumulation. Based upon this finding, we have attempted to design a novel, effective and safe mucosal vaccine by using CT with several dosages of APE as nasal adjuvants. Mice nasally immunized with OVA plus CT and an optimal dosage of APE showed significantly reduced levels of inflammatory responses as well as total and OVA-specific IgE antibodies when compared with mice given without APE. However, levels of both mucosal and systemic OVA-specific antibody responses were maintained. Further, APE significantly down-regulated accumulation of CT in the olfactory nerves and epithelium. In summary, an optimal dosage of APE would take full advantage of mucosal adjuvanticity of native CT without any toxicity for application in humans.

Throughput expression of multiple G-protein coupled receptors for HIV infection in choriocarcinoma cells, trophoblasts, and breast milk cells.

The chemokine receptors, which belong to G-protein coupled receptors (GPCRs) and become co-receptors when HIV enters the cell, have been mentioned in recent research. Numerous studies have reported that the cellular mechanism of HIV crossing the placental barrier is still not totally understood. This study was conducted to investigate whether the mRNAs of nineteen typs of GPCRs and CD4 were expressed in choriocarcinoma cell lines, trophoblasts, and breast milk cells by using RT-PCR. It was found that the expression of GPCRs varied in different cell lines. Of note is that CD4 could not be expressed in either choriocarcinoma cells or trophoblasts. It was noteworthy that mRNAs of multiple GPCRs were identified in choriocarcinoma cells, trophoblasts, and breast milk cells for the first time. The expression amounts of these mRNAs were further measured by quantitative RT-PCR. Interestingly, mRNAs of CCR9/CCR10 were strongly expressed in trophoblasts. This study provided further insights to the cellular mechanism of mother-to-child transmission of HIV.

Large angioleiomyoma, rich of mast cell and sex hormone receptor expression.

BACKGROUND: Angioleiomyoma is a rare benign solitary tumor, arising from the vascular smooth muscle. This tumor usually occurs in the subcutis of extremities, uncommonly in abdomen, often presents as a small (<2 cm) and is treated with excision. CASE: We report an extremely rare case of unusually large angioleiomyoma, first diagnosed as an ovarian tumor with some malignant possibilities by diagnostic imaging. We resected 1.7 kg of tumor from the extra-peritoneal cavity in the lower abdomen. Histological study revealed that this case's angioleiomyoma had abundant mast cells and sex hormone receptor expression. CONCLUSION: This angioleiomyoma is not an obvious malignant tumor because of low mitosis, coagulative necrosis and cellular atypia. However, it seems to have low potential malignancy, because it has massive size, marked degeneration and abundant mast cells. There are some possibilities that sex hormones are related with the growth and degeneration of this case's tumor, because those receptors are strongly expressed in the nucleus of tumor cells.

Retrorectal epidermoid cyst with unusually elevated serum SCC level, initially diagnosed as an ovarian tumor.

Retrorectal epidermoid cyst is one of the developmental cysts which arise from remnants of embryonic tissues. We report a rare case of retrorectal epidermoid cyst, initially diagnosed as an ovarian tumor. Serum SCC value as tumor marker was elevated to the high level. Laparoscopy revealed ovaries, uterus and other pelvic organs were all normal. This tumor existed in the retroperitoneal cavity and compressed the rectum. Later, complete tumor resection was performed by laparotomy. Histological study revealed the epithelium of this tumor consisted of only squamous cells without atypia, and the diagnosis of this tumor was retrorectal epidermoid cyst. Retrorectal epidermoid cyst is very rare, and difficult to diagnose before surgery. However, if we have-knowledge of developmental cysts, and by careful digital examination and image diagnosis, a differential diagnosis can be made.

Diagnostic accuracy of integrated FDG-PET/contrast-enhanced CT in staging ovarian cancer: comparison with enhanced CT.

PURPOSE: The purpose of the study is to evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) with (18)F-fluorodeoxyglucose (FDG) with IV contrast for preoperative staging of ovarian cancer, in comparison with enhanced CT, using surgical and histopathological findings as the reference standard. MATERIALS AND METHODS: Forty patients with ovarian cancer underwent FDG-PET/contrast-enhanced CT scans for staging before primary debulking surgery. PET/CT and the CT component separately, were interpreted by two experienced radiologists by consensus for each investigation. Status with regard to lesion inside and outside the pelvis was determined on the basis of histopathology. The significance of differences between the two imaging modalities was determined using the McNemar test. RESULTS: Staging revealed stage I in 18 patients (IA, n=9; IB, n=3; IC, n=6), stage II in seven (IIA, n=2; IIB, n=3; IIC, n=2), stage III in 14 (IIIA, n=1; IIIB, n=3; IIIC, n=10), and stage IV in one. The results of CT and PET/CT were concordant with the final pathological staging in 22 out of 40 (55%) and 30 out of 40 (75%) cases, respectively. The overall lesion-based sensitivity improved from 37.6% (32 out of 85) to 69.4% (59 out of 85), specificity from 97.1% (578 out of 595) to 97.5% (580 out of 595), and accuracy from 89.7% (610 out of 680) to 94.0% (639 out of 680) between CT and PET/CT. There were significant differences in sensitivity and accuracy, with p values of 5.6 x 10(-7) and 1.2 x 10(-7), respectively. CONCLUSION: Integrated FDG-PET/contrast-enhanced CT is a more accurate imaging modality for staging ovarian cancer and useful for selecting appropriate treatment than enhanced CT.

Analysis of immunological markers associated with pregnancy and HIV-1 infection: relevance in perinatal transmission in HIV-1-infected pregnant women with low plasma viral load.

PROBLEM: In HIV-1-infected pregnant women with low plasma viral load, risk factors associated with perinatal HIV-1 transmission are not clearly understood. METHOD OF STUDY: We analyzed distribution of peripheral CD8 T-cell subsets, plasma cytokines and measured secretory leukocyte peptidase inhibitor (SLPI) and myeloid-related protein (MRP)-8 levels in whole-blood and cervico-vaginal fluid (CVF) specimens obtained from 35 HIV-1-infected pregnant women (group 1), 12 HIV-1-infected non-pregnant women (group 2) and 15 HIV-1 uninfected pregnant women (group 3). RESULTS: The group 1 women had higher expression of CD38, human leukocyte antigen-DR and CD95 on CD8 T-cells and higher levels of plasma tumor necrosis factor-alpha and epidermal growth factor. CVF-SLPI levels were the highest in group-3, while MRP-8 levels were the highest in group 1 women in plasma and CVF (P < 0.01). Although there were no cases of perinatal HIV-1 transmission, group 1 women undergoing HIV-1-indicated cesarean section had lower levels of CVF-SLPI as compared with those undergoing normal vaginal delivery. CONCLUSION: Pregnancy contributes to the activation of peripheral CD8 T cells and increase in pro-inflammatory cytokines. Production of protective mucosal secretory factors such as SLPI is affected by HIV-1 infection in pregnant women and down-regulated SLPI levels may indirectly indicate a higher possibility of perinatal HIV-1 transmission.

Accuracy of 18F-FDG PET/CT in detecting pelvic and paraaortic lymph node metastasis in patients with endometrial cancer.

OBJECTIVE: The objective of our study was to evaluate the accuracy of integrated PET and CT (PET/CT) using (18)F-FDG in detecting pelvic and paraaortic lymph node metastasis in patients with endometrial cancer, using surgical and histopathologic findings as the reference standard. SUBJECTS AND METHODS: Forty patients with clinical stages IA to IIIC underwent radical hysterectomy, including pelvic lymphadenectomy with or without paraaortic lymphadenectomy, after FDG PET/CT. Lymphadenectomy involved removing all visible lymph nodes in the surgical fields. PET/CT findings were interpreted by two experienced radiologists in consensus and compared with histopathologic results. The criterion for malignancy on PET/CT images was increased radiotracer uptake by a lymph node independent of node size. RESULTS: In total, 62 pathologically positive nodes were found in 10 patients and 60 of 62 dissected metastatic nodes were identified on the CT component. The overall node-based sensitivity, specificity, and accuracy of PET/CT for detecting nodal metastases were 53.3% (32/60), 99.6% (1,419/1,424), and 97.8% (1,451/1,484), respectively. The sensitivity for detecting metastatic lesions 4 mm or less in diameter was 16.7% (4/24), that for lesions between 5 and 9 mm was 66.7% (14/21), and that for lesions 10 mm or larger was 93.3% (14/15). The overall patient-based sensitivity, specificity, and accuracy were 50% (5/10), 86.7% (26/30), and 77.5% (31/40), respectively. CONCLUSION: Integrated FDG PET/CT is superior to conventional imaging techniques, but it is only moderately sensitive in predicting lymph node metastasis preoperatively in patients with endometrial cancer. Even PET/CT should not replace lymphadenectomy.

Performance of integrated FDG-PET/contrast-enhanced CT in the diagnosis of recurrent ovarian cancer: comparison with integrated FDG-PET/non-contrast-enhanced CT and enhanced CT.

PURPOSE: The aim of this study was to evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using (18)F-fluorodeoxyglucose with IV contrast for depiction of suspected recurrent ovarian cancer and to assess the impact of PET/contrast-enhanced CT findings on clinical management, compared with PET/non-contrast-enhanced CT and CT component. METHODS: One hundred thirty-two women previously treated for ovarian cancer underwent PET/CT consisting of non-enhanced and contrast-enhanced CT for suspected recurrence. PET/contrast enhanced CT, PET/non-contrast-enhanced CT, and enhanced CT were interpreted by two experienced radiologists by consensus for each investigation. Lesion status was determined on the basis of histopathology, radiological imaging, and clinical follow-up for longer than 6 months. RESULTS: Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET/contrast-enhanced CT were 78.8% (52 of 66), 90.9% (60 of 66), and 84.8% (112 of 132), respectively, whereas those of PET/non-contrast-enhanced CT were 74.2% (49 of 66), 90.9% (60 of 66), and 82.6% (109 of 132), respectively, and those of enhanced CT were 60.6% (40 of 66), 84.8% (56 of 66), and 72.7% (96 of 132), respectively. Sensitivity, specificity, and accuracy differed significantly among the three modalities (Cochran Q test: p = 0.0001, p = 0.018, and p < 0.0001, respectively). The findings of PET/contrast-enhanced CT resulted in a change of management for 51 of the 132 patients (39%) and had an effect on patient management in 16 patients (12%) diagnosed by enhanced CT alone and three patients (2%) diagnosed by PET/non-contrast-enhanced CT. CONCLUSION: Integrated PET/contrast-enhanced CT is an accurate modality for assessing ovarian cancer recurrence and led to changes in the subsequent appropriate therapy.

Performance of FDG-PET/CT in the diagnosis of recurrent endometrial cancer.

OBJECTIVE: To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18-F-fluorodeoxyglucose (FDG), compared with PET alone, in the diagnosis of suspected endometrial cancer recurrence. METHODS: Thirty women who had undergone primary surgery for histopathologically proven endometrial cancer with suspected recurrence because of clinical, cytological, biochemical, and/or radiological findings were enrolled in this study. PET and integrated PET/CT images were evaluated by two different experienced radiologists by consensus for each modality. A final diagnosis of recurrence was confirmed by histopathology, other imaging and clinical follow-up for longer than 1 year. The statistical significance of differences between PET and PET/CT was determined by the McNemar test. RESULTS: Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET/CT were 93% (14/15), 93% (14/15), and 93% (28/30), respectively, whereas for PET, the corresponding data were 80% (12/15), 80% (12/15), and 80% (24/30), respectively (P=0.479, 0.479, and 0.134, respectively). CT from PET/CT resolved the false-positive PET results because of hyper-metabolic activity of benign inflammatory lesions and physiological variants and moreover detected lung metastasis and para-aortic lymph node metastasis that PET missed. However, tiny para-aortic lymph node metastasis could not be detected even with PET/CT. CONCLUSIONS: Integrated FDG-PET/CT is a useful complementary modality for providing good anatomic and functional localization of sites of recurrence during follow-up of patients with endometrial cancer.