Development and validation of novel digitalized cervicography system.

OBJECTIVE: Digital cervicography systems would be expected to reduce the costs of film cervicography, and provide the opportunity for "telemedicine-based" screening. We aimed to develop web-based digital cervicography system, and validate it compared with conventional film cervicography. METHODS: A hundred cases from five centers were prospectively included, and cervical images (analogue, digitalized by scanning analogue, and digital) were taken separately using both analogue (Cerviscope) and digital camera (Dr. Cervicam) in each patient. Nine specialists evaluated the three kinds of images of each case with time interval between evaluations of each image. To validate novel digitalized system, we analyzed intra-observer variance among evaluation results of three kinds of images. RESULTS: Sixty-three cases were finally analyzed after excluding technically defective cases that cannot be evaluable on analogue images. The generalized kappa for analogue versus digital image was 0.83, for analogue versus scanned image 0.72, and for digital versus scanned image was 0.71; all were in excellent consensus. CONCLUSION: Digitalized cervicography system can be substituted for the film cervicography very reliably, and can be used as a promising telemedicine tool for cervical cancer screening.

Management of Endometrial Hyperplasia With a Levonorgestrel-Releasing Intrauterine System: A Korean Gynecologic-Oncology Group Study.

OBJECTIVE: The aim of the study was to evaluate the efficacy of the levonorgestrel intrauterine system (LNG-IUS) for treatment of endometrial hyperplasia (EH). METHODS: A prospective multicenter study was conducted from November 2010 to March 2014. Patients with histologically confirmed EH were treated with LNG-IUS. At 3, 6, and 9 months after LNG-IUS insertion, follow-up endometrial aspiration biopsies with the LNG-IUS in the uterus were undertaken. At the 12th month of follow-up, endometrial tissues were obtained via 2 methods: endometrial aspiration biopsy with the LNG-IUS in the uterus, followed by dilatation and curettage (D&C) after LNG-IUS removal. The primary outcome was the regression rate at 12 months after LNG-IUS insertion, and the secondary outcome was the consistency of the results between the endometrial aspiration biopsy and the D&C. RESULTS: The study population comprised 75 patients, including 37 with simple hyperplasia without atypia; 3 with atypical simple hyperplasia; 23 with complex hyperplasia without atypia, and 12 with atypical complex hyperplasia. Of these patients treated with the LNG-IUS, 38 (50.7%) were followed up at 12 months after LNG-IUS insertion. The complete regression rate at 12 months was 94.7% (36/38): 100% (6/6) of patients with atypical EH and 93.7% (30/32) with EH without atypia. In all of the cases (100%, 36/36), patients achieved complete regression within 3 months of LNG-IUS insertion. A comparison of the pathologic results from endometrial aspiration biopsy and D&C was carried out for 15 patients. In the histologic results by endometrial aspiration biopsy, 14 patients were diagnosed as "normal endometrium" and 1 as "insufficient tissue for pathologic evaluation." Among the 14 cases of normal endometrium by endometrial aspiration biopsy, 1 was diagnosed as "residual EH" by D&C, and the 1 case with insufficient tissue was diagnosed as normal endometrium by D&C. CONCLUSIONS: Levonorgestrel intrauterine system is an effective and favorable method for treatment of EH.

Serous borderline tumor of the fallopian tube.

Serous borderline tumors of the ovary are fairly common, making up between 4% and 14% of ovarian epithelial tumors. While to our knowledge serous borderline tumor of the fallopian tube occurs rarely with only ten previously reported cases in literature. We report the case of the serous borderline tumor of the fallopian tumor in a 25-year-old woman and review the literature.

Prognostic value of serum CA-125 in patients with advanced epithelial ovarian cancer followed by complete remission after adjuvant chemotherapy.

OBJECTIVE: The aim of this study was to evaluate the prognostic value of serum CA-125 in advanced epithelial ovarian cancer with complete remission after primary adjuvant chemotherapy. METHODS: We reviewed the records of 120 patients with advanced epithelial ovarian cancer who underwent primary surgery followed by adjuvant therapy at our institution between January 1998 and December 2005. RESULTS: The median progression free survival was 21.6 months and 12.5 months in patients with nadir CA-125 levels ≤10 U/mL and 10 to 35 U/mL, respectively. Median overall survival in the same respective order was 130.2 months and 35.3 months. The level of serum CA-125 after the first cycle of adjuvant chemotherapy was most significantly higher in the recurrent group compared with the non-recurrent group. The optimal cut point of CA-125 on the receiver operating characteristic curve was 35 U/mL. Median progression free survival was 64.6 months and 12.8 months in patients with nadir CA-125 levels ≤35 U/mL and >35 U/mL, respectively, after first cycle of adjuvant chemotherapy. CONCLUSION: Serum CA-125 level after the first cycle of adjuvant chemotherapy is a strong independent prognostic factor for advanced epithelial ovarian cancer with complete response.

Clinical Usefulness of (18)F-FDG PET/CT in the Detection of Early Recurrence in Treated Cervical Cancer Patients with Unexplained Elevation of Serum Tumor Markers.

We investigated the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for restaging of treated uterine cervix squamous cell cancer with tumor maker elevation that was not explained by other conventional evaluation. We enrolled 32 cases who underwent PET/CT for the restaging of treated cervical cancer with tumor marker elevation that was not explained by recent conventional evaluation. All enrolled cases had squamous cell carcinoma. Increased tumor markers included squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA). PET/CT findings were determined by pathologic confirmation or clinical follow-up. We compared PET/CT accuracy and clinical parameters including normalization of tumor markers in both the SCC Ag elevation group and the CEA elevation group. The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT in detecting recurrence were 100%, 83.3%, 82.4%, and 100%, respectively. Accuracy was significantly different between the SCC Ag elevation group and the CEA elevation group (p=0.0169). PET/CT with SCC Ag elevation was more accurate (100%) than PET/CT with CEA elevation (66.7%). Normalization of tumor markers was observed more often in the SCC Ag elevation group than in the CEA elevation group (p=0.0429). PET/CT showed high negative predictive value and sensitivity in the restaging of cervical cancer with unexplained tumor marker elevation. PET/CT was more accurate in patients with SCC Ag elevation than in those with CEA elevation.

Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)?

OBJECTIVES: This study was conducted to determine whether vaccination with the quadrivalent human papillomavirus (HPV) vaccine after loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2-3) is effective in preventing recurrence of CIN2-3. METHODS: Between August 2007 and July 2010, 737 patients aged 20-45 years who were diagnosed with CIN2-3 were treated by LEEP and followed. Three hundred and sixty patients were vaccinated with the quadrivalent HPV vaccine after LEEP (vaccination group), and 377 patients were followed without vaccination (non-vaccination group). The vaccination group received the first dose at 1 week after LEEP and the remaining two doses two and six months later. Post-LEEP follow-up was performed at 3, 6, 9, 12, 18, and 24 months during the first 2 years and yearly thereafter. RESULTS: Irrespective of causal HPV type, 36 (4.9%) patients developed recurrence. In the vaccination group (360 patients), 9 patients (2.5%) developed recurrence, whereas 27 patients (7.2%) in the non-vaccination group (377 patients) developed recurrence. In patients infected with HPV of 16 and/or 18 type, 5 patients (2.5%) in the vaccination group (197 patients) and 18 patients (8.5%) in the non-vaccination group (211 patients) developed recurrent disease related to vaccine HPV types (HPV 16 or 18 types) after LEEP (P<0.01). Multivariate analysis showed that no vaccination after LEEP was an independent risk factor for recurrent CIN2-3 (HR=2.840; 95% confidence interval, 1.335-6.042; P<0.01). CONCLUSIONS: Vaccination with the quadrivalent HPV vaccine after treatment may be considered in preventing recurrence of CIN2-3.

Prevalence and type distribution of human papillomavirus in cervical adenocarcinoma in Korean women.

BACKGROUND: An increase in incidence of cervical adenocarcinoma (CADC) has been reported in many countries, including Korea. However, few studies describe human papillomavirus (HPV) type distribution among CADC in Asia. OBJECTIVE AND METHODS: This was a retrospective, hospital-based observational study between 2005 and 2010 to estimate the overall prevalence and distribution of HPV types among CDAC in Korean women. The study used hematoxylin & eosin and immunohistochemical staining (for the two biomarkers p16 and progesterone receptor [PR]) to diagnose and subtype CADC samples. HPV DNA was amplified by polymerase chain reaction (PCR) and HPV genotypes were identified using reverse hybridization. RESULTS: Of 196 cases submitted, 89.3% of the cases were confirmed as CADC. The mean age at diagnosis was 47.1 (standard deviation [SD] 11.9) years. No statistically significant differences in mean age at diagnosis by histological subtype were found. HPV DNA was detected in 90.3% (177/196) of CADC. HPV-18 was the most prevalent type (54.2%), followed by HPV-16 (44.1%) and HPV-45 (3.4%). Infection with any high-risk HPV type was identified in 97.7% of HPV-DNA-positive CADC. The biomarker p16 was positive in 92% of CADC cases and PR was positive in 19.6% of CADC. CONCLUSION: HPV DNA was found in the large majority of CADC in Korean women, with HPV-18 being the most common type followed by HPV-16 and HPV-45. This study is among the first in Asia to specifically report HPV type distribution in CADC. This information will help inform policy decisions concerning HPV vaccination for the prevention of CADC.

Establishment of a Korea HPV cohort study.

We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies.

Prediction of persistent gestational trophobalstic neoplasia: the role of hCG level and ratio in 2 weeks after evacuation of complete mole.

OBJECTIVE: The aim of this study was to determine whether or not the serum human chorionic gonadotropin (hCG) level and ratio during 2 weeks after evacuation is predictive of persistent gestational trophoblastic neoplasia (GTN) in patients with complete molar pregnancies. METHODS: Between January 2000 and June 2010, a total of 467 patients with complete molar pregnancies were diagnosed. Seventeen patients, who had prophylactic chemotherapy and in whom insufficient data were available, were excluded. A receiver operating characteristic curve was used to determine the most useful predictive factor for persistent GTN and multivariate logistic regression was used for analyses. RESULTS: Persistent GTN was diagnosed in 109 of the 450 patients (24.2%) on the basis of the 2000 FIGO criteria. The optimal cut-off point for hCG 1 and 2 weeks after evacuation was 6400 mIU/mL (sensitivity, 54.1%; specificity, 65.1%) and 2400 mIU/mL (sensitivity, 64.2%; specificity, 78.3%), respectively. The optimal cut-off point for the ratio of pre-evacuation hCG to hCG 2 weeks after evacuation was 30 (sensitivity, 63.3%; specificity, 86.5%). Based on multivariate analysis, this ratio<30 was an independent predictive factor for persistent GTN (odds ratio=6.885; 95% confidence interval, 4.006-11.832; P<0.001). CONCLUSIONS: The decline ratio in hCG level 2 weeks after evacuation in patients with complete molar pregnancies is the most reliable predictor of persistent GTN. Our analysis may allow clinicians to stratify risk in patients with complete molar pregnancies and to provide more accurate counseling based on the hCG levels obtained 2 weeks after evacuation.

A sclerosing stromal tumor of the ovary with masculinization in a premenarchal girl.

A sclerosing stromal tumor of the ovary is an extremely rare benign tumor; it usually is found during the second and third decades of life. Patients present with pelvic pain or a palpable abdominal mass. Hormonal effects such as masculinization are uncommon. Here, an 11-year old premenarchal girl presented with deepening of the voice. In addition, clitoromegaly and hirsutism with a male suprapubic hair pattern were observed. The laboratory findings showed that the testosterone level was elevated to 3.67 ng/mL, andostenedione to above 10 ng/mL, dehydroepiandrosterone-sulfate to 346 µg/dL and 17-hydroxy progesterone (17-OHP) to 11.28 ng/mL. The chromosome evaluation revealed a 46,XX female karyotype. An adrenocorticotropic hormone stimulation test was performed. The 17-OHP to cortisol ratio in 30 minutes was 0.045, which suggested a heterozygote for the 21-hydroxylase deficiency. However, the CYP21A2 gene encoding steroid 21-hydroxylase showed normal. The pelvic ultrasound showed a heterogeneous mass consisting of predominantly solid tissue in the pelvic cavity. The pelvic magnetic resonance imaging revealed an 8.9×6.2×6.6 cm mass of the left ovary. A left oophrectomy was performed and microscopic examination confirmed a sclerosing stromal tumor. Immunohistochemical studies showed that the tumor was positive for smooth muscle actin and vimentin, but negative for S-100 protein and cytokeratin. Following surgery, the hormone levels returned to the normal range and the hirsutism resolved.

HPV-18 is a poor prognostic factor, unlike the HPV viral load, in patients with stage IB-IIA cervical cancer undergoing radical hysterectomy.

OBJECTIVES: This study was conducted to determine the prognostic significance of the human papillomavirus (HPV) genotype using the HPV DNA chip (HDC) test and the HPV viral load by the hybrid capture II assay (HC2) in FIGO stage IB-IIA cervical cancer undergoing radical hysterectomy. METHODS: Between January 2001 and December 2005, 204 consecutive patients who underwent radical hysterectomy with pelvic lymphadenectomy for International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IIA cervical cancer were retrospectively reviewed. The Cox proportional hazard models adjusted for covariates were used for analyses and a receiver operating characteristic (ROC) curve was used to determine the HPV viral load in predicting disease progression. RESULTS: Of the 204 cases, the HDC was positive in 195 (95.6%) and the HC2 was positive in 192 (94.1%). The 5-year progression-free survival (PFS) was 78.4%. On multivariate analysis, HPV-18 positivity was an independent prognostic factor predictive for disease progression. The risk of recurrence was higher for HPV-18 positivity (hazard ratio=2.664; 95% confidence interval [CI], 1.437-4.938; P=0.003). The 5-year PFS rate for patients who were HPV-18-negative was 83.8%, which was higher than the 5-year PFS for patients who were HPV-18-positive (54.1%; P<0.001). The area under the ROC curve for the HPV viral load was 0.550 (P=0.314; 95% CI, 0.455-0.644). CONCLUSIONS: The HPV-18 genotype is a reliable prognostic factor of early-stage cervical cancer; however, the HPV viral load may not be helpful in predicting disease prognosis.

Serum hCG level and rising world health organization score at second-line chemotherapy (pulse dactinomycin): poor prognostic factors for methotrexate-failed low-risk gestational trophoblastic neoplasia.

INTRODUCTION: The aim of this study was to determine the factors associated with failure in patients receiving pulse dactinomycin as second-line chemotherapy for low-risk gestational trophoblastic neoplasia (GTN) according to the revised International Federation of Obstetrics and Gynecology 2000 scoring system at a single institution. METHODS: Between January 1997 and June 2007, 37 patients with methotrexate-failed low-risk GTN were treated with pulse dactinomycin (1.25 mg/m intravenously every 2 weeks). All patients had low-risk GTN based on the revised International Federation of Obstetrics and Gynecology 2000 scoring system at the time of second-line chemotherapy. A logistic regression model was used to analyze the relationship between covariates and treatment failure. RESULTS: There were 28 (75.7%) patients who achieved primary remission with pulse dactinomycin. All 9 treatment failures achieved complete remission after receiving subsequent chemotherapy; 1 patient also underwent hysterectomy. Patients successfully treated with pulse dactinomycin required a median of 4.0 cycles (range, 2-7) to achieve a complete response. The risk of failure with pulse dactinomycin was higher for serum hCG levels 10 or higher when initiating pulse dactinomycin (odds ratio, 8.91; 95% confidence interval, 1.08-73.53) and a rising World Health Organization score of 2 or higher after first-line chemotherapy (odds ratio, 12.59; 95% confidence interval, 1.60-99.25). With respect to the previous methotrexate regimen and cause of failed methotrexate chemotherapy, there were no differences between those who were successfully treated and those who failed pulse dactinomycin. CONCLUSIONS: Serum hCG level and a rising World Health Organization score at the time of initiating pulse dactinomycin are important prognostic factors in patients with methotrexate-failed low-risk GTN receiving pulse actinomycin as second-line chemotherapy.

Vaccination with a human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in Korean girls aged 10-14 years.

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Significance of human papillomavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure.

OBJECTIVE: This study was conducted to determine whether the human papillomavirus (HPV) genotype by the HPV DNA chip test (HDC) is predictive of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) 2-3 following a loop electrosurgical excision procedure (LEEP). STUDY DESIGN: Between January 2001-February 2007, 672 patients with CIN2-3 were treated by a LEEP and followed up with cytology, the hybrid capture II assay, and the HDC. RESULTS: A total of 37 (5.5%) patients developed a recurrence, and those who developed a recurrence tested positive for the same high-risk (HR) HPV genotype before and after the LEEP. The same HR-HPV genotype by the HDC during the follow-up had a sensitivity and negative predictive value of 100% for detecting residual/recurrent disease. Persistent HPV-16 and HPV-18 were significantly associated with recurrent CIN2-3 (P < .05). CONCLUSION: Persistent infection with the same HR-HPV genotype, especially HPV-16 and HPV-18, should be considered a risk factor for developing residual/recurrent CIN2-3.

Weekly methotrexate (50mg/m(2)) without dose escalation as a primary regimen for low-risk gestational trophoblastic neoplasia.

OBJECTIVES: The aim of this study was to compare the efficacy and toxicity of an 8-day methotrexate-folinic acid regimen and a weekly methotrexate regimen (50mg/m(2) without dose escalation) for low-risk gestational trophoblastic neoplasia (GTN) according to the revised FIGO 2000 scoring system in a single institution. METHODS: Between January 1997 and June 2007, 107 patients with low-risk GTN were treated with an 8-day methotrexate-folinic acid regimen (MTX-FA group; n=59) or a weekly methotrexate regimen (50mg/m(2) without dose escalation) (MTX group; n=48). The primary remission rate, change of chemotherapy because of drug resistance or toxicity, and relapse rate were compared. RESULTS: All 107 patients with low-risk GTN were cured. The primary remission rates were 69.5% and 70.8% for the MTX-FA and MTX groups, respectively (P>0.99). The commonly reported toxic effects in the MTX-FA and MTX groups, respectively, were as follows: hepatotoxicity (31/59 and 9/48), neutropenia (7/59 and 4/48), stomatitis (3/59 and 2/48), alopecia (2/59 and 2/48), and thrombocytopenia (2/59 and 0/48). Drug toxicity necessitating changes in chemotherapy were reported to be 13.6% (8/59) in the MTX-FA group and 2.1% (1/48) in the MTX group (P<0.05). The overall duration of treatment was 8.6 weeks in the MTX-FA group and 6.4 weeks in the MTX group (P<0.001). CONCLUSIONS: The weekly methotrexate regimen was as effective as the 8-day methotrexate-folinic acid regimen for low-risk GTN. The weekly methotrexate regimen was less toxic, better tolerated, and more convenient for patients compared to the 8-day methotrexate-folinic acid regimen.

Human papillomavirus L1 capsid protein and human papillomavirus type 16 as prognostic markers in cervical intraepithelial neoplasia 1.

INTRODUCTION: The aim of the study was to determine whether human papillomavirus (HPV) L1 capsid protein and the HPV genotype can predict the disease course as prognostic markers for cervical intraepithelial neoplasia 1 (CIN1). METHODS: Immunohistochemical staining was performed for HPV L1 capsid protein in 101 women who had been confirmed to have CIN1 by histologic examination and HPV high-risk infection by HPV genotyping. The disease course was analyzed by follow-up histologic examination according to the HPV L1 capsid protein and HPV genotype over a minimum of 12 months. RESULTS: The CIN1 regressed spontaneously in 60.4% of the women; most cases of regression occurred within 1 year (90.9% of regression cases). The HPV L1 capsid protein-positive patients had a spontaneous regression rate of 72.7% (48/66) and a rate of persistent disease or progression to higher grade disease of 27.3% (18/66). The HPV L1 capsid protein-negative women had a regression rate of 37.1% (13/35) and a rate of persistent disease or progression of 62.9% (22/35; P < 0.001). The HPV-16-infected patients had a regression rate of 38.6% (17/44) and a rate of persistent disease or progression of 61.4% (27/44), whereas the non-HPV-16-infected patients had a regression rate of 77.2% (44/57) and a rate of persistent disease or progression of 22.8% (13/57; P < 0.001). CONCLUSIONS: The HPV L1 protein expression is closely related to spontaneous disease regression, but HPV-16 infection is related to persistent disease or progression to high-grade lesions in patients with CIN1.

Value of serum CA125 levels in patients with high-risk, early stage epithelial ovarian cancer.

OBJECTIVES: The aim of this study was to ascertain whether serum CA125 level is predictive of disease progression in patients with high-risk, early stage (stage IA/B grade 3, stage IC any grade, stage I clear cell, or stage II) epithelial ovarian cancer who have achieved a complete response to chemotherapy. METHODS: Between January 1998 and April 2004, we reviewed the records of 95 patients with high-risk, early stage epithelial ovarian cancer who had elevated CA125 levels at the time of diagnosis and were complete responders after 6 cycles of adjuvant paclitaxel/carboplatin chemotherapy. A receiver operating characteristic curve was used to determine the most useful CA125 level in predicting disease progression and Cox proportional hazards models adjusted for covariates were used for analyses. RESULTS: The 5-year progression-free survival (PFS) was 70.5%. The optimal cutoff point of CA125 after completing adjuvant chemotherapy to predict disease progression was 12 U/mL (sensitivity, 71.4%; specificity, 82.1%). On multivariate analysis, CA125 level>12 U/mL after completing adjuvant chemotherapy was an independent prognostic factor predictive for disease progression. The risk of recurrence was higher for CA125 level>12 U/mL (hazards ratio=10.567; P<0.001). The 5-year PFS rate for patients with CA125 level< or =12 U/mL was 83.3%, which was higher than a PFS of 37.5% for CA125>12 U/mL (P<0.001). CONCLUSIONS: CA125 level after 6 cycles of adjuvant chemotherapy is a strong independent prognostic factor for high-risk, early stage epithelial ovarian cancer after achieving a complete response.

Phase delaying the human circadian clock with a single light pulse and moderate delay of the sleep/dark episode: no influence of iris color.

BACKGROUND: Light exposure in the late evening and nighttime and a delay of the sleep/dark episode can phase delay the circadian clock. This study assessed the size of the phase delay produced by a single light pulse combined with a moderate delay of the sleep/dark episode for one day. Because iris color or race has been reported to influence light-induced melatonin suppression, and we have recently reported racial differences in free-running circadian period and circadian phase shifting in response to light pulses, we also tested for differences in the magnitude of the phase delay in subjects with blue and brown irises. METHODS: Subjects (blue-eyed n = 7; brown eyed n = 6) maintained a regular sleep schedule for 1 week before coming to the laboratory for a baseline phase assessment, during which saliva was collected every 30 minutes to determine the time of the dim light melatonin onset (DLMO). Immediately following the baseline phase assessment, which ended 2 hours after baseline bedtime, subjects received a 2-hour bright light pulse (~4,000 lux). An 8-hour sleep episode followed the light pulse (i.e. was delayed 4 hours from baseline). A final phase assessment was conducted the subsequent night to determine the phase shift of the DLMO from the baseline to final phase assessment.Phase delays of the DLMO were compared in subjects with blue and brown irises. Iris color was also quantified from photographs using the three dimensions of red-green-blue color axes, as well as a lightness scale. These variables were correlated with phase shift of the DLMO, with the hypothesis that subjects with lighter irises would have larger phase delays. RESULTS: The average phase delay of the DLMO was -1.3 +/- 0.6 h, with a maximum delay of ~2 hours, and was similar for subjects with blue and brown irises. There were no significant correlations between any of the iris color variables and the magnitude of the phase delay. CONCLUSION: A single 2-hour bright light pulse combined with a moderate delay of the sleep/dark episode delayed the circadian clock an average of ~1.5 hours. There was no evidence that iris color influenced the magnitude of the phase shift. Future studies are needed to replicate our findings that iris color does not impact the magnitude of light-induced circadian phase shifts, and that the previously reported differences may be due to race.

Comparison of the hybrid capture II assay with the human papillomavirus DNA chip test for the detection of high-grade cervical lesions.

Cervical intraepithelial neoplasia (CIN) 2 is used as the threshold for treatment decisions. This study was conducted to evaluate the clinical efficacy of the Hybrid Capture II assay (HC2) and the human papillomavirus (HPV) DNA chip test (HDC) for detecting HPV in high-grade cervical lesions CIN2 or greater, including adenocarcinoma (CIN2+). Seven hundred forty-one women with abnormal cervical cytology were evaluated with the HC2, the HDC, and histological assessment of the cervix. The overall agreement of the 2 HPV tests was 88.8% (kappa value, 0.61). Of 615 high-risk HPV-positive specimens by the HC2, 571 (92.8%) were HDC-positive. Both tests were performed similarly on CIN2+ samples; the sensitivities of the HC2 and HDC as predictors of CIN2+ were 93.4 and 92.6%, respectively. In 83 cases of discrepancies between the HC2 and HDC, genotyping of 39 HC2-negative/HDC-positive cases revealed 13 HPV-53, 8 HPV-58, 7 HPV-16, 6 HPV-18, 2 HPV-68, 1 HPV-31, 1 HPV-45, and 1 HPV-66. In 515 patients with CIN2+, HPV-16 (45.0%) was the most common type; the next most common types were HPV-58 (20.8%), HPV-18 (16.1%), HPV-31 (6.6%), and HPV-33 (6.6%). Human papillomavirus types 16, 58, and 18 were more likely associated with CIN2+ (P < 0.05). In conclusion, the HDC is a reliable diagnostic tool for the detection of CIN2+. In addition, the HDC provides useful information regarding viral genotypes.

Lymphadenectomy for low-risk endometrial cancer based on preoperative and intraoperative assessments.

INTRODUCTION: The aim of this study was to ascertain whether lymphadenectomy is necessary when endometrial cancer is considered low risk based on preoperative and intraoperative assessments. METHODS: Between 2000 and 2004, a total of 122 patients with low-risk endometrial cancer who underwent preoperative endometrial sampling and magnetic resonance imaging (MRI) were treated surgically. All 122 patients were considered eligible for the study if they fulfilled the following criteria: (a) grade 1 or 2 endometrioid corpus cancer by endometrial sampling, (b) no lymphadenopathy by MRI, (c) myometrial invasion of 50% or less by MRI, and (d) no intraoperative evidence of macroscopic extrauterine spread. We divided the 122 patients into 2 groups (the total abdominal hysterectomy and bilateral salpingo-oophorectomy [TH/bilateral salpingo-oophorectomy] with lymphadenectomy [THND group, n = 64] and the TH/bilateral salpingo-oophorectomy without lymphadenectomy [TH group, n = 58]). RESULTS: The concordance rate between preoperative and postoperative grades was 92.6% (113/122, kappa = 0.805). Evaluation of the depth of myometrial invasion with MRI had an accuracy of 95.1% (116/122) for ruling out deep myometrial invasion. In the THND group, the operative time, the hospital stay, the estimated blood loss during surgery, and the incidence of perioperative complications were significantly higher than those in the TH group. The 5-year progression-free survival rates were similar (96.9% in the THND group and 98.3% in the TH group). CONCLUSIONS: The present findings suggest that MRI and office endometrial sampling may accurately categorize patients into low- or high-risk groups. Lymphadenectomy should be limited to patients with high-risk endometrial cancer.