Measurement of endometrial thickness in premenopausal women in office gynecology.

Purpose: To define the median endometrial thickness (ET) in office gynecology is thought to be important for clinical practice. However, there are few reports about ET that have included the general female population on a large scale. The median ET was determined prospectively in premenopausal women who attended office gynecology for cervical cancer screening. Methods: In total, 849 women were enrolled. The median ET was determined by using transvaginal ultrasound and the relationships between the ET and various clinical factors were analyzed. Results: The participants' median age was 38.5 years. The median ET was 8.6 mm (90% and 95% quantiles: 13.8 and 15.8 mm). The ET was not related to their age, symptoms, obstetric history, geographical location, or risk factors for endometrial cancer. In the women with a menstrual cycle length of 28-30 days, the ET was 7 mm on days 1-6, but it increased from 5.4 mm immediately after menstruation (day 7 or 8) to 9.2 mm on days 13-14. Subsequently, the ET increased further to 11.1 mm on day 18. Conclusion: In all the women, the upper limit of the ET was 13.8 mm and 15.8 mm in the 90% and 95% quantile, respectively, in office gynecology.

Risk factors for postoperative lower-extremity lymphedema in endometrial cancer survivors who had treatment including lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the incidence rate of lower-extremity lymphedema after systematic lymphadenectomy in patients with uterine corpus malignancies and to elucidate risk factors for this type of lymphedema. METHODS: A retrospective chart review was carried out for all patients with uterine corpus malignant tumor managed at Hokkaido Cancer Center between 1991 and 2007. Patients who did not undergo lymphadenectomy as a treatment or died of cancer/intercurrent disease were excluded from this study. All living patients included in this study had hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy and their medical records were reviewed. We identified patients with postoperative lower-extremity lymphedema (POLEL). Logistic regression analysis was used to select the risk factors for POLEL. RESULTS: Of 286 patients evaluated, 103 (37.8%) had POLEL. Multivariate analysis confirmed that adjuvant radiation therapy (OR=5.2, 95% CI=2.1-12.7), resection of more than 31 lymph nodes (OR=2.6, 95% CI=1.4-4.9), and removal of circumflex iliac nodes to the distal external iliac nodes (CINDEIN) (OR=6.1, 95% CI=1.3-28.2) were independent risk factors for POLEL. CONCLUSION: Adjuvant radiation therapy should be avoided in patients who undergo systematic lymphadenectomy if an alternative postoperative strategy is possible. Although reducing the number of resected lymph nodes is not appropriate from a therapeutical point of view, elimination of CINDEIN dissection may be helpful in reducing the incidence of POLEL. The clinical significance of CINDEIN dissection needs to be investigated by a randomized controlled trial.

Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema.

BACKGROUND: Complex decongestive physiotherapy (CDP) consists of a two-phase treatment program and is the international standard therapy for lymphedema. However, this therapy is not performed at most hospitals in Japan. METHODS: The subjects of the present study were 82 Japanese women with lymphedema of an extremity (median age, 64 years; range, 40-86 years). The volume of the affected extremity was compared before and after therapy, and the duration of the CDP treatment phase and rate of edema reduction were ascertained. The associations between the effect of CDP and duration of lymphedema, operative procedure, and radiotherapy were also investigated. RESULTS: For patients with upper-extremity lymphedema, the median duration of the CDP treatment phase was 6 treatment days (range, 3-26 days), median reduction of edema volume was 328.7 ml (range, 76.6-1258.0 ml; P = 0.0014), and median rate of edema reduction was 58.9% (range, 42.7%-97.1%). For patients with lower-extremity lymphedema, the median duration of the CDP treatment phase was 10 treatment days (range, 2-35 days), median reduction of edema volume was 1573.7 ml (range, 293.9-3471.1 ml; P < 0.0001), and median rate of edema reduction was 73.4% (range, 29.2%-117.3%). Although no correlation was seen between duration of lymphedema and duration of the CDP treatment phase or rate of edema reduction, the degree of lymph node dissection tended to influence rate of edema reduction in patients with lower-extremity lymphedema. CONCLUSION: In a study of Japanese women with lymphedema, CDP comprising a two-phase treatment program was clearly effective.

A study of oligosaccharide variants of alpha-fetoproteins produced by normal fetuses and fetuses with trisomy 21.

BACKGROUND: The mechanisms of the increase in the percentage of alpha-fetoproteins (AFPs) that strongly binds to Lens culinaris agglutinin (AFP-L3) in pregnancies with a trisomy 21 fetus have not been analyzed. To investigate the oligosaccharide variants of AFP produced by normal fetuses and fetuses with trisomy 21, the lectin reactivity of AFP was analyzed. METHODS: Fetal liver tissue, amniotic fluid, and maternal serum were obtained from five normal pregnancies and five pregnancies with a trisomy 21 fetus. The percentages of AFP reactive to lectins were determined by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: The percentages of AFP-L3 in the fetal liver and the maternal serum were 23.9 and 27.0%, respectively, in normal pregnancies, and 28.7 and 38.5%, respectively, in pregnancies with a trisomy 21 fetus. There was no statistically significant difference between the percentage in the fetal liver and the percentage in the maternal serum in normal pregnancies; however, a significant difference (P < 0.01) was found in pregnancies with a trisomy 21 fetus. In regard to the percentage of AFP-L3 in the fetal liver, there was no significant difference; however, a significant difference (P < 0.05) was found in the maternal serum between normal pregnancies and pregnancies with a trisomy 21 fetus. CONCLUSIONS: The transference of the AFP-L3 fraction might be relatively high in the placentas of women carrying a trisomy 21 fetus, and this could be the one of the reasons for the increase in the percentage of AFP-L3 in the maternal serum in pregnancies with a trisomy 21 fetus.

WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma.

BACKGROUND: Ovarian clear cell adenocarcinoma is associated with one of the poorest prognoses among human epithelial ovarian cancers. The authors hypothesized that Wilms tumor suppressor 1 gene (WT1) sense and antisense (WT1-AS) expression and their promoter methylation status could characterize ovarian clear cell adenocarcinoma from ovarian serous adenocarcinoma. METHODS: To test this hypothesis, ovarian cancer cell lines and 42 cancer tissues (17 clear cell and 25 serous adenocarcinoma) were analyzed for expression and methylation of WT1 and WT1-AS genes. RESULTS: These experiments demonstrated that all serous adenocarcinoma tissues expressed both WT1 and WT1-AS genes, although expression of these genes was lacking in clear cell adenocarcinoma. The WT1 and WT1-AS promoter were significantly methylated in clear cell adenocarcinoma (88.2% and 88.2%, respectively) compared with serous adenocarcinoma (24.0% and 20.0%, respectively). Significant correlation between methylation and mRNA expression status was observed for each gene. Also in agreement with these data, WT1 and WT1-AS negative ovarian cancer cell lines reexpressed these genes after treatment with the demethylating agent, 5-aza-2'-deoxycytidine. CONCLUSIONS: The current study shows that CpG hypermethylation is an important mechanism of WT1 and WT1-AS gene inactivation in ovarian clear cell adenocarcinoma. This is the first report that has demonstrated differential expression and methylation of WT1-AS in ovarian clear cell and serous adenocarcinomas. This study presents new molecular characterizations between these two types of adenocarcinoma and may provide insight as to why clear cell adenocarcinoma has a poorer prognosis than serous adenocarcinoma of the ovary.

Functional analysis of p53 gene and the prognostic impact of dominant-negative p53 mutation in endometrial cancer.

In addition to the loss of function, mutant p53 can possess a dominant-negative effect on wild-type p53 and may also exert gain-of-function activity. It is not clear whether the functional status of p53 mutation contributes to differences in outcome in endometrial cancer. We collected a total of 92 RNA samples of high quality from endometrial cancer tissues, and the samples were subjected to yeast functional assay and sequencing for p53 mutations. The detected mutant p53 genes were further investigated for their dominant-negative activity using a yeast-based transdominance assay. p53 mutation was found in 24 out of 92 (26.1%) tumors, of which 10 exhibited no dominant-negative activity (recessive mutation) and 14 showed dominant-negative activity. Dominant-negative p53 mutation was related to advanced stages (p = 0.01), nonendometrioid type tumors (p = 0.01) and grade 3 tumors (p = 0.04). The patients with dominant-negative mutation had significantly shorter survival than patients with no mutation (p < 0.0001) and those with a recessive mutation (p = 0.01) in the p53 gene. No difference in survival was found between the patients with tumors harboring a recessive p53 mutation and those with tumors harboring a wild-type p53. Multivariate analysis revealed that dominant-negative p53 mutation (p = 0.019), FIGO stage (p = 0.0037) and histologic subtype (p = 0.014) were independently related to patient survival. Dominant-negative p53 mutation was the most important prognostic factor for stage III/IV endometrial cancer (p = 0.0023). In conclusion, dominant-negative p53 mutation is often found in advanced stages and aggressive histologic subtypes of endometrial cancer and it is a strong predictor of survival of patients with advanced endometrial cancer. To elucidate further the role of p53 mutation in endometrial cancer, it is necessary to investigate gain-of-function activity involving dominant-negative p53 mutant proteins.

A case of pure-type ovarian squamous cell carcinoma for which combination chemotherapy consisting of paclitaxel and carboplatin was not effective.

BACKGROUND: There has been no report on the effectiveness of combination chemotherapy consisting of paclitaxel and carboplatin for pure-type ovarian squamous cell carcinoma (POSCC). CASE: A 56-year-old Japanese woman diagnosed as having pT2c pN1 M0 pure-type ovarian squamous cell carcinoma was treated with combination chemotherapy consisting of paclitaxel and carboplatin every 3 weeks. Four months after the initial chemotherapy, multiple lung tumors appeared and a new tumor in the internal iliac area appeared. She died of disease 12 months after the first treatment. CONCLUSION: Adjuvant chemotherapy consisting of paclitaxel and carboplatin for ovarian squamous cell carcinoma were not effective in this case.

Lymph-vascular space invasion and number of positive para-aortic node groups predict survival in node-positive patients with endometrial cancer.

OBJECTIVE: The aim of this study was to determine pathologic variables associated with disease-specific survival of node-positive patients with endometrial carcinoma treated with combination of surgery including pelvic and para-aortic lymphadenectomy and adjuvant chemotherapy. METHODS: Survival of 55 node-positive endometrial carcinoma patients prospectively treated with surgery and adjuvant chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared to various histopathologic variables. All patients underwent primary surgical treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection. RESULTS: Among 303 consecutive endometrial cancer patients treated during the period of this study, 55 patients (18.2%), including 44 without peritoneal metastasis (FIGO stage IIIc) and 11 with peritoneal metastasis (FIGO stage IV), were found to have retroperitoneal lymph node metastasis. Multivariate Cox regression analysis revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were independently related to poor survival in node-positive endometrial carcinoma. The estimated 5-year survival rate of stage IIIc patients with or without moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically significant difference (P=0.0024). The estimated 5-year survival rate of stage IV patients was 20.0%. Prognosis of stage IIIc patients could be stratified into three groups by the number of positive para-aortic node (PAN) with an estimated 5-year survival rate of 86.4% for no positive PAN (n = 23), 60.4% for one positive PAN (n = 13), and 20.0% for > or = 2 positive PAN (n = 8). The difference of survival rate between no or one positive PAN and > or = 2 positive PAN was statistically significant (P = 0.0007 for no positive PAN vs > or = 2 positive PAN, P = 0.0319 for one positive PAN vs > or = 2 positive PAN). Multivariate analysis including number of positive PAN groups showed that LVSI, number of positive PAN groups were independent prognostic factors for survival. Survival of patients with stage IIIc disease could be stratified into three groups by combination of LVSI and number of positive PAN groups with an estimated 5-year survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI, 62.6% for no or one positive PAN group with intermediate or prominent LVSI, and 20.0% for > or = 2 positive PAN groups irrespective of LVSI (P = 0.0002 for no or one positive PAN group with nil or minimal LVSI vs > or = 2 positive PAN groups, P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs no or one positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one positive PAN group with intermediate or prominent LVSI vs > or = 2 positive PAN groups). CONCLUSIONS: LVSI and number of positive PAN groups were independent prognostic factors for stage IIIc endometrial cancer patients. Postoperative therapy and follow-up modality need to be individualized according to LVSI and the number of positive PAN for stage IIIc patients. New molecular markers to predict the prognosis of endometrial cancer patients preoperatively should be found for individualization of treatment. New chemotherapy regimen including taxane needs to be considered as an adjuvant therapy for patients with node-positive endometrial cancer.

High dose three-dimensional conformal boost (3DCB) using an orthogonal diagnostic X-ray set-up for patients with gynecological malignancy: a new application of real-time tumor-tracking system.

The feasibility and accuracy of high dose three-dimensional conformal boost (3DCB) using three internal fiducial markers and a two-orthogonal X-ray set-up of the real-time tumor-tracking system on patients with gynecological malignacy were investigated in 10 patients. The standard deviation of the distribution of systematic deviations (Sigma) was reduced from 3.8, 4.6, and 4.9 mm in the manual set-up to 2.3, 2.3 and 2.7 mm in the set-up using the internal markers. The average standard deviation of the distribution of random deviations (sigma) was reduced from 3.7, 5.0, and 4.5 mm in the manual set-up to 3.3, 3.0, and 4.2 mm in the marker set-up. The appropriate PTV margin was estimated to be 10.2, 12.8, and 12.9 mm in the manual set-up and 6.9, 6.7, and 8.3 mm in the gold marker set-up, respectively, using the formula 2Sigma + 0.7sigma. Set-up of the patients with three markers and two fluoroscopy is useful to reduce PTV margin and perform 3DCB.

Lymphatic mapping and sentinel node identification as related to the primary sites of lymph node metastasis in early stage ovarian cancer.

OBJECTIVE: We evaluated the primary sites of lymph node (LN) metastasis in patients during the early stage of ovarian cancer. METHODS: Study 1: patients with clinical stage I and II common epithelial ovarian carcinoma (n = 150) underwent systematic retroperitoneal LN dissection of the pelvic and paraaortic areas. The relationship between the incidence and location of LN metastasis and clinical and histological characteristics was examined. Study 2: we studied 11 women with endometrial or fallopian tube tumors. At laparotomy, activated charcoal solution was injected into the unilateral cortex of the ovary. Ten minutes later, the retroperitoneal spaces were opened and charcoal uptake within the pelvic lymph node (PLN) and paraaortic node (PAN) as far as the level of renal vein was examined. RESULTS: Study 1: The incidence of LN metastasis by stage was 6.5% (8/123) in stage I and 40.7% (11/27) in stage II. Among 19 patients with LN metastasis, 14 had only PAN, 2 had only pelvic LN, and 3 had both PAN and PLN metastases. Metastasis was limited to the ipsilateral side in 12 (63%) patients, but was bilateral in 5 (26%) and contralateral to the neoplastic ovary in 2 (11%). Positive peritoneal cytology was significantly (P < 0.05) correlated with lymph node metastasis. Study 2: Lymphatic channels along the ovarian vessels were identified in all injected ovaries. Charcoal was deposited in the LN of all patients. The locations of these nodes included PAN in all patients, common iliac node in three, and external iliac node in one. CONCLUSION: PAN is the primary site of LN metastasis in ovarian cancer. Bilateral PAN dissections are necessary to determine the extent of tumors even in stage I ovarian carcinoma.

Prenatal trisomy 21 screening using the Lens culinaris agglutinin-reactive alpha-fetoprotein ratio.

For the purpose of improving the clinical efficacy of alpha-fetoprotein (AFP)-L3% in prenatal screening for trisomy 21, we calculated the multiple of the median (MoM) of AFP-L3% (L3 MoM) and the ratio of L3 MoM to AFP MoM (L3 MoM/AFP MoM) in maternal serum. Maternal serum samples from 1822 women (maternal age 37.3 +/- 3.8 years, and weeks of gestation 16.0 +/- 1.0; mean +/- SD) with unaffected pregnancies and 28 women (37.6 +/- 4.6 years, 16.6 +/- 3.1) pregnant with of trisomy 21 fetuses were obtained. The AFP concentration and AFP-L3% in maternal serum were measured using a liquid-phase binding assay. The areas under the receiver operating characteristic curves (AUCs) of AFP MoM, AFP-L3%, L3 MoM, and L3 MoM/AFP MoM were 0.750, 0.868, 0.949 and 0.946, respectively. The AUCs of L3 MoM and L3 MoM/AFP MoM were significantly higher than AFP-L3% (P < 0.05) and AFP MoM (P < 0.0005). However, no statistical difference was observed between the AUCs of L3 MoM and L3 MoM/AFP MoM. In conclusion, the L3 MoM should be an effective replacement for AFP-L3% in prenatal trisomy 21 screening.

Expression and methylation status of 14-3-3 sigma gene can characterize the different histological features of ovarian cancer.

We hypothesize that 14-3-3 sigma gene expression and its regulation by methylation can characterize histological types of primary human epithelial ovarian cancer. To test this hypothesis, ovarian cancer cell lines and 54 ovarian cancer tissue samples were analyzed for expression and methylation of 14-3-3 sigma gene using methylation specific PCR. The results of our experiments demonstrate that 14-3-3 sigma gene was methylated and inactivated in ES-2 ovarian cell line, which was derived from clear cell adenocarcinoma. Treatment of this cell line with demethylating agent 5-aza-2'-deoxycytidine restored the expression of 14-3-3 sigma gene. In human ovarian cancer tissues, the expression of 14-3-3 sigma protein was inactivated in most of the ovarian clear cell carcinoma tissues. Interestingly, 14-3-3 sigma protein expression was positive in significantly higher percentages of serous (89.5%), endometrioid (90%), and mucinous (81.8%) ovarian adenocarcinoma tissues. The ovarian clear cell carcinoma samples with inactivated 14-3-3 sigma protein were highly methylated, suggesting that inactivation of 14-3-3 sigma gene is through DNA methylation. Using direct DNA sequencing, 14-3-3 sigma gene methylation on all the 17 CpG sites was significantly higher in ovarian clear cell carcinoma as compared to other histological types of ovarian cancer (serous, endometrioid, and mucinous). This is the first report suggesting that 14-3-3 sigma gene expression and methylation status can characterize histological features of different types of ovarian cancer.

Resveratrol suppresses growth of Ishikawa cells through down-regulation of EGF.

Resveratrol and other polyphenols have anti-carcinogenic and anti-tumorigenic activities in various carcinomas. However, such studies are limited in endometrial cancer. We hypothesize that resveratrol suppresses cancer growth through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with resveratrol (1, 10, 50 and 100 micro M) for 1, 3, 5 and 7 days, and analyzed for growth signal genes (EGF and VEGF), cell cycle regulatory genes (p53 and p21), and apoptosis-related genes (bcl-2 and bax). Results of these experiments demonstrate that after resveratrol treatment, the growth of Ishikawa cells was inhibited in a dose dependent manner. The gene and protein expression data suggest that resveratrol treatment significantly decreased EGF, whereas VEGF was up-regulated in Ishiwaka cell lines. Interestingly, protein expressions of p21 and Bax were decreased, even though their mRNA expressions did not show significant changes. The present study suggests that resveratrol can suppress proliferation of Ishikawa cells through down-regulation of EGF.

A study on the microheterogeneity of alpha-fetoproteins produced by yolk sac and germ cell tumors.

BACKGROUND: It is generally believed that the lower the grade of differentiation of glycoprotein-producing cells, the more often modification by bisecting N-acetylglucosamine (GlcNAc) or fucose (Fuc) at the sugar chain of the glycoprotein or increase in branching of side chains occurs. We examined the characteristics of the alpha-fetoprotein (AFP) sugar chain stored in amniotic and exocoelomic fluid during 5-9 weeks of gestation and analyzed serum-derived AFP of patients with germ cell tumors. METHODS: Total AFP concentrations in embryonic fluid at 5-9 weeks of gestation (n = 11) and serum of patients with germ cell tumors (n = 7) were measured using a radioimmunoassay (RIA) method. The percentages of AFPs reactive with Lens culinaris agglutinin (LCA), concanavalin A (Con A), erythroagglutinating phytohemagglutinin-E4 (E-PHA) and Ricinus communis agglutinin-120 (RCA 120) were obtained by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: It was revealed that at 5-9 weeks of gestation, AFP variants that had been modified by the Fuc residue, which bound to the GlcNAc residue at the reducing end of the sugar chain, and bisecting GlcNAc residues gradually decreased as pregnancy advanced; however, the presence of N-acetylneuraminic acid (Neu5Ac) at the nonreducing ends changed little. CONCLUSIONS: It appears very likely that the changes in the relative amounts of AFP variants in the embryonic fluid during early pregnancy were due to differentiation of the yolk sac. The grade of differentiation of yolk sac tumors was very similar to that of the normal yolk sac at around 6 weeks of gestation.

Combined use of magnetic resonance imaging, CA 125 assay, histologic type, and histologic grade in the prediction of lymph node metastasis in endometrial carcinoma.

OBJECTIVE: The aim of this study was to predict retroperitoneal lymph node metastasis during the preoperative examination of patients with endometrial carcinoma and to determine whether lymphadenectomy must be performed. STUDY DESIGN: This study was carried out on 214 patients with endometrial carcinoma. Preoperative evaluators were volume index, depth of myometrial invasion (as assessed by magnetic resonance imaging), serum CA 125 level, histologic type, and histologic grade. With the use of receiver operating characteristic curves, cutoff values of volume index and serum CA 125 levels were determined. The relationships of these evaluators with pelvic lymph node metastasis were investigated by multivariate analysis with a logistic regression model. The relationships of these evaluators with para-aortic lymph node metastasis were investigated in the same way. RESULTS: Histologic type, volume index, histologic grade, and serum CA 125 level were found to be independent risk factors for pelvic lymph node metastasis; serum CA 125 level and volume index were found to be independent risk factors for para-aortic lymph node metastasis. Among 110 cases with no risk factors for pelvic lymph node metastasis, pelvic lymph node metastasis was observed in 4 cases (3.6%). On the other hand, only 1 case of 128 cases (0.7%) with no risk factors for para-aortic lymph node metastasis actually had metastasis. CONCLUSION: Careful consideration of the possibility of the elimination of the requirement of retroperitoneal lymphadenectomy is needed in cases with no risk factors for lymph node metastasis. However, our results suggest that para-aortic lymphadenectomy may not be necessary in cases with no risk factors for para-aortic lymph node metastasis.

Cytoreductive surgery combined with organ resection for advanced ovarian carcinoma.

BACKGROUND: The survival effects of combined organ resection in cytoreductive surgery for advanced ovarian carcinoma with regard to the site and the number of organs involved have not yet been clarified. METHODS: Data obtained from 143 patients with stage III/IV ovarian carcinoma were used for analysis. Combined organ resection (COR) was employed in 21 patients in whom optimal cytoreduction (defined as a residuum

Cytological features of cervical smears in serous adenocarcinoma of the endometrium.

OBJECTIVE: Serous adenocarcinoma (SAC) of the endometrium has a poor prognosis compared with that of typical endometrioid adenocarcinoma (EAC). The objective of this study was to determine whether SAC can be distinguished from EAC preoperatively by cervical or endometrial cytology. STUDY DESIGN: Cervical smears and endometrial smears obtained from 128 patients with endometrial carcinoma were reviewed. Histological types included 117 cases of EAC and 11 cases of SAC. The positive rates of cervical smears and those of endometrial smears in SAC and EAC cases were compared. Papillary clusters and bare nuclei of malignant cells in positive cervical smears were also investigated for their diagnostic significance in discriminating between EAC and SAC. RESULTS: The positive rate of cervical smears in SAC was significantly higher than that in EAC (72.7 vs 27.4%, P < 0.05). Among cases with positive cervical smears, there were significantly more cases with papillary clusters and/or bare nuclei in cases of SAC than in cases of EAC. CONCLUSION: When endometrial carcinoma is clinically suspected and a cervical smear is positive, the predominance of either papillary clusters or features of bare nuclei of malignant cells in the smear may indicate the presence of SAC.

Thromboprophylaxis with low molecular weight heparin in thrombophilia-complicated pregnancy.

We treated three thrombophilia-complicated pregnant women (two antiphospholipid antibody syndrome, one protein C deficiency) with low molecular weight heparin (dalteparin). All three pregnancies including one twin pregnancy ended in live births without a decrease in bone mineral density. This treatment modality was effective and safe preventing thrombosis during their pregnancies.