Clinical Implication of p16, Ki-67, and Proliferating Cell Nuclear Antigen Expression in Cervical Neoplasia: Improvement of Diagnostic Accuracy for High-grade Squamous Intraepithelial Lesion and Prediction of Resection Margin Involvement on Conization Spe

BACKGROUND: Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although the use of p16INK4a (p16) staining has been proven to improve diagnostic accuracy for high-grade squamous intraepithelial lesion (HSIL), the clinical evidence for use of Ki-67 and proliferating cell nuclear antigen (PCNA) is insufficient to make an independent recommendation for use, alone or in combination. The primary objective was to evaluate clinical utility of Ki-67 and PCNA in combination with p16 in diagnosing HSIL. Also, we assessed the correlation between expressions of three biomarkers and resection margin status of conization specimen. METHODS: The expressions of p16, Ki-67, and PCNA were evaluated by immunohistochemical methods in 149 cervical tissues encompassing 17 negative lesion, 31 CIN 1, 25 CIN 2, 41 CIN 3, and 35 invasive squamous cell carcinoma. The immunohistochemical staining results were classified into four grades: 0, 1+, 2+ and 3+. RESULTS: The expression of three biomarkers was positively associated with CIN grade. Ki-67 immunostaining did not increase the accuracy of HSIL diagnosis when combined with p16 immunostaining compared with p16 immunostaining alone. In contrast, combining the staining results for p16 and PCNA (p16 = 3+ and PCNA > or =2+) increased its specificity (66.7% vs. 75.0%, P = 0.031) without decrease of its sensitivity (98.7% vs. 98.7%) for diagnosis of CIN 3 and more sever lesion. Subgroup analysis for conization specimen with CIN 2 and CIN 3 showed that positive Ki-67 immunostaining was an independent risk factor for predicting resection margin positivity (odds ratio = 6.52, 95% confidence interval 1.07-39.64). CONCLUSIONS: We found that the combined use of p16 and PCNA immunostaining enhanced diagnostic accuracy for HSIL. Positive Ki-67 immunostaining was associated with incomplete excision.

Prediction of Prolonged Pregnancy in Nulliparous Women by Transvaginal Ultrasonographic Measurement of Cervical Length at 20-24 Weeks and 37 Weeks

This study was done to evaluate transvaginal ultrasonographic measurement of cervical length at 20 to 24 weeks and 37 weeks as a predictor of prolonged pregnancy (defined as a pregnancy that extended beyond 41+2 weeks of gestation [289 days]) in nulliparous women. This prospective observational study enrolled 149 consecutive nulliparous women with singleton gestation at 37 weeks. Cervical length was measured by transvaginal ultrasonography at 20 to 24 weeks and 37 weeks. Cervical length at 37 weeks, but not at 20 to 24 weeks, was significantly longer in women delivered at >41+2 weeks than in those delivered at < or =41+2 weeks (p<0.005). There was a significant correlation between cervical length at 37 weeks and gestational age at delivery (Pearson correlation coefficient, r=0.387, p<0.0001). In the receiver operating curve, the best cut-off value of cervical length at 37 weeks for the prediction of prolonged pregnancy was 30 mm, with a sensitivity of 78% and a specificity of 62%. Cervical length assessed by transvaginal ultrasonography at 37 weeks can predict the likelihood of prolonged pregnancy in nulliparous women. However, there is no association between cervical length at 20 to 24 weeks and the occurrence of prolonged pregnancy.

Cervical Length and the Risk of Microbial Invasion of the Amniotic Cavity in Women with Preterm Premature Rupture of Membranes

The aims of this study were to determine whether sonographically measured cervical length is of value in the identification of microbial invasion of the amniotic cavity in women with preterm premature rupture of membranes (PPROM) and to compare its performance with maternal blood C-reactive protein (CRP), white blood cell count (WBC), and amniotic fluid (AF) WBC. This prospective observational study enrolled 50 singleton pregnancies with PPROM. Transvaginal ultrasound for measurement of cervical length was performed and maternal blood was collected for the determination of CRP and WBC at the time of amniocentesis. AF obtained by amniocentesis was cultured and WBC determined. The prevalence of a positive amniotic fluid culture was 26% (13/50). Patients with positive amniotic fluid cultures had a significantly shorter median cervical length and higher median CRP, WBC, and AF WBC than did those with negative cultures. Multiple logistic regression indicated that only cervical length had a significant relationship with the log odds of a positive AF culture. Transvaginal sonographic measurement of cervical length is valuable in the identification of microbial invasion of amniotic cavity in women with PPROM. Cervical length performs better than AF WBC, maternal blood CRP, and WBC in the identification of a positive amniotic fluid culture.

Reference range for fetal orbital parameters: A prospective longitudinal study / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to establish reference ranges for the fetal orbital diameters (OD) and outer orbital diameters at 16 to 38 weeks' gestation. METHODS: This prospective longitudinal study enrolled 41 consecutive women with uncomplicated singleton gestations during their first trimester of pregnancy. Serial measurements of the fetal orbits by ultrasound examination were performed at intervals of 4 weeks until 28 weeks, and then every 2 weeks until 36 weeks, and weekly thereafter. Linear regression was used for statistical analysis. RESULTS: A total of 331 fetal orbital diameters and 298 outer orbital diameters were measured. The reference ranges for orbital diameters and outer orbital diameters were presented as mean, 95% confidence interval of the mean and percentiles. A linear growth function was observed between gestational age (GA), orbital diameter (Y=0.654 x GA - 0.856; r2=0.948; p<0.0001) and outer orbital diameter (Y=1.679 x GA+0.510; r2=0.942; p<0.0001). Significant correlation was also found between orbital diameter and outer orbital diameter (Y=2.451 x OD+4.840; r2=0.906; p<0.0001). CONCLUSION: We have presented percentile tables and regression formulas for fetal orbital diameters and outer orbital diameters. These results provide normative data of the growth of the fetal orbit and may be useful in assessing fetal orbital architecture in patients at risk of ocular abnormalities.

Ultrasound assessment of fetal colon development during the third trimester of pregnancy: A prospective longitudinal study / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to establish a normal range for the outer diameter of the fetal transverse colon from 28 to 40 weeks' gestation. METHODS: This prospective longitudinal study enrolled 38 consecutive women with uncomplicated singleton gestations during their first trimester of pregnancy. Ultrasound for serial measurements of the fetal transverse colon diameter were performed at intervals of 2 weeks from 28 weeks to 36 weeks and then weekly until delivery. Linear regression was used for statistical analysis. RESULTS: A total of 201 transverse colon diameters were measured in all 38 fetuses. The normal range for the outer diameter of the transverse colon from 28 to 40 weeks' gestation was presented as mean, 95% confidence interval of the mean and range. A linear growth function was observed between gestational age (GA) and transverse colon diameter (TCD) (TCD=0.499 x GA - 0.5504, r2=0.65; p<0.0001). CONCLUSION: We have presented a table of normal range and a regression formula for outer diameter of the fetal transverse colon from 28 to 40 weeks' gestation. These data may serve as reference values in the detection of abnormalities of the fetal colon.

The prevalence and clinical characteristics of the metabolic syndrome in middle-aged Korean adults / 대한내과학회지

BACKGROUND: To evaluate the prevalence and clinical characteristics of metabolic syndrome as defined by the NCEP-ATP III criteria in middle aged Korean rural people. METHODS: Cross-sectional study including 5330 participants (2197 males, 3133 females), over the age 40. Metabolic syndrome according to NCEP-ATP III criteria was defined if three or more of the following criteria were satisfied: 1) Abdominal obesity: Waist circumference (WC) in men > 102 cm and in women > 88 cm. 2) Hypertriglyceridemia: >or= 150 mg/dL. 3) Low HDL cholesterol: or= 130/85 mmHg. 5) High fasting glucose: >or= 110 mg/dL. We also applied WHO-APR (Asian Pacific Region) criteria for abdominal obesity (WC in men > 90 cm and in women > 80 cm) instead of NCEP-ATP III criteria. Insulin resistance was analysed by HOMA-IR. RESULTS: Age-adjusted overall prevalence of metabolic syndrome by NCEP-ATP III criteria was 24.8% (17.6% in men, 30.0% in women). The prevalence of metabolic syndrome for each age group in men was as follows: age 40 through 49 (18.8%), 50 through 59 (17.4%), 60 through 69 (18.3%), and over 70 (14.5%). In women: age 40 through 49 (22.3%), 50 through 59 (32.7%), 60 through 69 (39.9%), and over 70 (39.3%). In men, the prevalence decreased with aging, but not in women with consistent increment. Age-adjusted prevalence of abdominal obesity was 1.6% (men) and 25.3% (women) by NCEP-ATP III criteria, but 22.5% (men) and 55.6% (women) by WHO-APR criteria. Among various components of metabolic syndrome, the prevalence of hypertriglyceridemia was well correlated with the changing pattern of the prevalence of metabolic syndrome. Relative risk of metabolic syndrome increased as HOMA-IR and fasting insulin levels did. CONCLUSION: In middle aged Korean adults, metabolic syndrome defined as NCEP-ATP III criteria was strongly correlated to the degree of insulin resistance. The peak age of metabolic syndrome in men was age 40 through 49, and the prevalence decreased with aging. Therefore, early intervention for risk factors of metabolic syndrome might be required in men. On the other hand, prevention for cardiovascular disease will be needed for perimenopausal women due to considerably increased prevalence in the age 50 through 59.

Prevalence and Clinical Characteristics of the Metabolic Syndrome in Middle-Aged Korean Adults

BACKGROUND: The aim of this study was to analyze the prevalence and clinical characteristic of the metabolic syndrome of adults, over 40 years old, living in Korea. METHODS: This study was carried out for 2 years, 2003-2004, on total 5, 330 individuals (2, 197 men and 3, 133 women) selected by the stratified random cluster sampling among adults over 40 years old. Metabolic syndrome was defined based on both the NCEP-ATP III criteria and Modified ATP III criteria applying the WHO-APR (Asian Pacific Region) 's abdominal obesity criteria (waist circumference > 90 cm in men, 80 cm in women) instead of NCEP-ATP III criteria. RESULTS: Using NCEP-ATP III criteria, the age-adjusted overall prevalence of metabolic syndrome was 24.8% (17.6% in men, 30.0% in women). Age-adjusted overall prevalence of metabolic syndrome as defined by modified-ATP III criteria was 34.3% (26.3% in men, 40.1% in women). The prevalence of metabolic syndrome for each age group (40-49, 50-59, 60-69, > or= 70) in men was as follows: 18.8%, 17.4%, 18.3%, 14.5%. In women: 22.3%, 32.7%, 39.9%, 39.3%. The prevalence of hypertriglyceridemia (triglycerides > or= 1.7 mmol/l) was well correlated with the changing pattern of the prevalence of metabolic syndrome both in men and women. CONCLUSIONS: The peak age of metabolic syndrome in men was age 40 through 49, and the prevalence decreased with aging. Therefore, early intervention for risk factors of metabolic syndrome might be required in men. On the other hand, prevention for cardiovascular disease will be needed for perimenopausal women due to considerably increased prevalence in the age 50 through 59.

An Analysis of Clinicopathologic Prognostic Factors Affecting Survival in Patients with Uterine Endometrial Cancer / 대한산부인과학회잡지

OBJECTIVE: This study was performed to evaluate the clinicopathologic characteristics and prognostic factors of uterine endometrial cancer affecting survival of the patients. METHODS: Form Jan. 1995 to Dec. 2001, medical records including operation record and pathologic reports of 111 patients with histologically proven endometrial cancer at Samsung Medical Center were reviewed. The survival of patients was determined by description of last follow up date in medical records or phone calls. RESULTS: The median age of all patients was 52 years and the most common presenting symptom was abnormal vaginal bleeding (74.0%). Histologic type of endometrioid adenocarcinoma was the most common (90%) type of all endometrial cancers. The grades were classified into G1 (65.7%), G2 (17.1%), G3 (12.6%) and unknown (4.5%). The FIGO surgical stage was also classified into stage I(75.7%), stage II (14.4%), stage III (9.0%), and stage IV (0.9%). All patients were treated by primary surgery and postoperative adjuvant therapy including radiation therapy (54.1%), chemotherapy (4.5%) was applied. The overall 5-year disease free survival rate (DFSR) was 86.5% and overall 5-year survival rate was 87.8%. The age (p=0.04), grade (p=0.04), myometrial invasion (p=0.047), FIGO surgical stage (p=0.0067), lymph node metastasis (p=0.0001), lymphovascular space invasion (p=0.01) and C-erb B2 (p=0.04) were significant prognostic factors by univariate analysis. CONCLUSION: The age, grade, myometrial invasion, FIGO surgical stage, lymph node metastasis, lymphovascular space invasion and C-erb B2 were significant prognostic factors of uterine endometrial cancer affecting survival of the patients.

A Clinical Analysis of Intrauterine Fetal Death / 대한주산의학회잡지

OBJECTIVE: To evaluate the causes, methods of delivery, and maternal complications in cases of fetal death in utero(FDIU) at Samsung Medical Center. METHODS: There were 92 cases of FDIU among 25,195 deliveries at Samsung Medical Center during 7 years from 1994 to 2001. In these cases, perinatal autopsy and placental biopsy was performed in 35 and 71 cases, respectively. All the clinical informations were obtained by reviewing medical records retrospectively. RESULTS: The overall incidence of FDIU was 0.37%. Most of FDIU occurred in 25 to 29 years old group(43.5%). Recurrence rate of FDIU was 3.3%. Most of FDIU were low birth weight(79.3%) and preterm(79.6%). The modes of delivery were induced labor(68.5%), laparotomy(18.5%), and the spontaneous delivery(13.0%). The causes of FDIU were chorioamnionitis(15.2%), placental abruption(14.1%), severe preeclampsia(11.9%), congenital and chromosomal anomaly(6.5%), but it was unexplained in 27.2%. There were 25 cases with maternal complications and the most common complications were intra-/postpartum fever(18.5%), postpartum hemorrhage(8.7%) and DIC(8.7%). CONCLUSION: The causes of FDIU could not be determined in only about 1/4 cases at Samsung Medical Center. Since FDIU recurred in 3.3%, thorough studies including perinatal autopsy and chromosomal study must be made on stillborn infants and placenta to determine the recurrent causes.

A Case of Malignant Struma Ovarii / 대한산부인과학회잡지

Struma Ovarii is a teratoma with thyroid tissue as the predominant (>50%) constituent. It is rare, representing about 2% of all teratomas, and its malignant transformation, less than 5% of struma ovarii. Presenting symptoms are not specific, therefore pre-operative diagnosis of malignant struma ovarii is difficult and most diagnosis of malignant struma ovaii is determined by post-operative histologic findings. Because of the rarity of malignant struma ovarii, there is considerable confusion concerning diagnosis and management. A postmenopausal woman presented with pelvic mass and lower abdominal pain and explo-laparotomy was performed. Then, pathologic report was identified as malignant struma ovarii. We report a case of malignant struma ovarii with brief review of literature

A Case of Glassy Cell Carcinoma of the Uterine Cervix / 대한부인종양콜포스코피학회잡지

Glassy cell carcinoma (GCC) of the uterine cervix is a rare and highly malignant tumor, accounting for only 1%~2% of all cervical carcinomas. It is typically composed of malignant cells having a moderate amount of cytoplasm with "ground glass" appearance, distinct cell membranes that stain with eosin or periodic acid-Schiff, and large nuclei with prominent nucleoli. Since its original description in 1956 by Glucletmann and Cherry, 200 - 250 cases of GCC of the uterine cervix have been listed in the literature. We report here the clinicopathological study of one case of glassy cell carcinoma with brief review of the literature.