Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1.

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3'-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.

Hysterectomy for recurrent postmenopausal bleeding revisited: missed sclerosing stromal ovarian tumour.

Sclerosing stromal tumour of the ovary is rare. Patients present with menstrual irregularities, pelvic pain, abdominal distension, and presence of a large pelvic mass during their twenties or thirties. We report a rare case of an ovarian sclerosing stromal tumour with an atypical presentation, in that it gave rise to recurrent postmenopausal bleeding.

CHD5 Downregulation Associated with Poor Prognosis in Epithelial Ovarian Cancer.

BACKGROUND: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene candidate. This study investigated the involvement of CHD5 in ovarian cancer and its clinicopathological significance. METHODS: CHD5 expression in ovarian cancer and its counterpart were determined by quantitative RT-PCR. The correlation of CHD5 expression to clinicopathological features of the tumor was analyzed. RESULTS: CHD5 expression was downregulated by at least twofold in 32 of 72 (41%) invasive epithelial ovarian carcinomas when compared to 12 controls in Hong Kong Chinese women. CHD5 downregulation was correlated to clinical status (p < 0.05), but not to patient age, tumor type and grade, recurrence and clinical stage (p > 0.05). Survival analysis showed that patients with CHD5 downregulation in their tumors were associated with shorter disease-free and total survival times compared to those without CHD5 downregulation (p < 0.05). Cox proportional-hazards regression analysis indicated that downregulation of CHD5 is an independent adverse prognostic factor in ovarian cancer. CONCLUSION: This study shows that CHD5 is downregulated in a certain number of ovarian cancers and appears to be an adverse predictor candidate of ovarian cancer disease-free and total survival.

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling.

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (>or=4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

Is aortic lymphadenectomy necessary in the management of endometrial carcinoma?

OBJECTIVE: To evaluate the role of aortic lymphadenectomy in the management of endometrial carcinoma. METHODS: Clinical notes of 163 patients with endometrial carcinoma were reviewed. All patients had peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy with or without aortic lymphadenectomy. RESULTS: Seventy-five (46.0%) patients had pelvic lymphadenectomy alone whereas 88 (54.0%) had both pelvic and aortic lymphadenectomy. Thirty-five (21.5%) patients had nodal metastases with positive pelvic and aortic nodes in 26 (16.0%) and 24 (27.3%) patients, respectively. Isolated aortic metastases were found in 17 cases (19.3%). Among 35 patients with nodal metastases, recurrence developed in 15 (42.9%) patients and all except one died within five to 50 months. The remaining patients had a median disease-free period of 55 months (13-93 months). The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases, and all those who recurred died of disease within seven to 28 months. CONCLUSIONS: Our data suggest that aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high metastatic risk. After surgical removal and adjuvant radiotherapy, patients with nodal metastases achieved a better survival chance.

A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.

Peritoneum is the most common site for ovarian cancer metastasis. Here we investigate how cancer epigenetics regulates reciprocal tumor-stromal interactions in peritoneal metastasis of ovarian cancer. Firstly, we find that omental stromal fibroblasts enhance colony formation of metastatic ovarian cancer cells, and de novo expression of transforming growth factor-alpha (TGF-α) is induced in stromal fibroblasts co-cultured with ovarian cancer cells. We also observed an over-expression of tumor necrosis factor-alpha (TNF-α) in ovarian cancer cells, which is regulated by promoter DNA hypomethylation as well as chromatin remodeling. Interestingly, this ovarian cancer-derived TNF-α induces TGF-α transcription in stromal fibroblasts through nuclear factor-κB (NF-κB). We further show that TGF-α secreted by stromal fibroblasts in turn promotes peritoneal metastasis of ovarian cancer through epidermal growth factor receptor (EGFR) signaling. Finally, we identify a TNFα-TGFα-EGFR interacting loop between tumor and stromal compartments of human omental metastases. Our results therefore demonstrate cancer epigenetics induces a loop of cancer-stroma-cancer interaction in omental microenvironment that promotes peritoneal metastasis of ovarian cancer cells via TNFα-TGFα-EGFR.

The effect of continuous combined hormone replacement therapy on arterial reactivity in postmenopausal women with established angina pectoris.

Most epidemiological studies have suggested that the administration of estrogen reduces cardiovascular risk in healthy postmenopausal women. More recently, however, in the large Heart Estrogen/progestin Replacement Study (HERS), it was unexpectedly found that in women with established cardiovascular disease, there was overall no difference in cardiovascular events between those treated with combined oestrogen/progestin hormone replacement therapy and those on placebo. The aim of this study was to examine the effect of combined hormone replacement therapy on arterial reactivity in women with existing angina pectoris. Seventy-four postmenopausal women with angina pectoris were recruited into a 16 week double-blind, placebo-controlled study of treatment with 2 mg of estradiol combined with 1 mg of norethisterone acetate daily. The median endothelium-dependent change in arterial relaxation increased from 5.00 to 7.69% in the treatment group and decreased from 5.57 to 3.64% in the controls. The median endothelium-independent change in arterial relaxation increased from 6.49 to 7.27% in the treatment group and decreased from 4.39 to 2.07% in the controls. The changes in arterial relaxation between the treatment and control groups were not statistically significant. The administration of estrogen/progestin did not significantly improve either endothelium-dependent or -independent arterial relaxation in postmenopausal women with established cardiovascular disease. We have previously shown that estrogen/progestin treatment improves endothelium dependent relaxation in healthy women. The results of our study provide one possible explanation for the clinical findings of the HERS study. In women with established cardiovascular disease, arterial relaxation does not increase significantly in response to treatment with combined hormone replacement therapy.

Aberrant expression of p21(WAF1/CIP1) and p27(KIP1) in cervical carcinoma.

An immuno-histochemical study of p21 and p27 expression in cervical carcinoma was performed in 73 patients. Positive p21 and p27 staining was detected in 35.6 and 11% of tumour tissues, respectively. p21 expression was significantly correlated with advanced disease stage and negative human papilloma virus infection whilst positive p27 staining was not correlated with any clinical and pathological parameters studied. Kaplan-Meier estimation indicated that survival might be related to disease stage, tumour grade and p21 expression. Cox regression analysis confirmed that advanced stage disease and poorly differentiated tumour are independent prognostic factors for cervical carcinoma.

Alteration of cyclin D1 and CDK4 gene in carcinoma of uterine cervix.

Amplification and overexpression of cyclin D1 and CDK4 genes in cervical carcinoma were studied by semi-quantitative differential polymerase chain reaction assay and an immunostaining technique, respectively. Amplifications of cyclin D1 and CDK4 genes were found in 24% (27/113) and 26% (29/112) of tumors, respectively. Overexpression of cyclin D1 and CDK4 was demonstrated in 32% (21/66) and 73% (45/62) of tumors, respectively. No tumor showed CDK4 gene mutation on single strand conformational polymorphism. Sixteen percent (8/49) of the tumor specimens showed neither amplification nor overexpression. Disease stage, tumor grade and overexpression of cyclin D1 were found to be independent poor prognostic factors in cervical carcinoma.

Expression of apoptotic regulators and their significance in cervical cancer.

Insufficient apoptosis is implicated in many human cancers, including cervical carcinoma. The objectives of this study were to explore changes of apoptosis-regulating gene expression and their clinical significance in cervical cancer. The expression of apoptosis-regulating genes, including five Bcl-2 family and two caspase family members, was evaluated in 43 cervical invasive squamous cell carcinomas, using immunohistochemistry. Specimens in which >or=10% of the neoplastic cells showed cytosolic immunoreactivity were considered to be immunopositive. Results were correlated with clinico-pathologic characteristics of the subjects. All seven apoptotic regulators examined were positive in a proportion of the tumors. The percentage of cases expressing Bax was higher in the patients without evidence of disease after treatment than in the patients alive with disease or who died of disease (P<0.05). A significant difference in disease-free survival was detected between Bax-positive and -negative groups (P<0.05), and in overall survival between Mcl-1-positive and -negative groups (P<0.05). Significant association between the seven markers tested was only found for caspase 3 and Bak immunoreactivity in cervical carcinoma (P<0.05). The results demonstrate expression of multiple apoptosis-modulating proteins in cervical cancer. There appears to be complex regulation of apoptosis protein levels in association with clinical behavior of cervical squamous cell carcinoma.

Randomized double-masked comparison of radially expanding access device and conventional cutting tip trocar in laparoscopy.

OBJECTIVE: To compare postoperative wound pain associated with the radially expanding access device and the conventional disposable cutting-tip trocar. METHODS: Our randomized, double-masked, self-controlled study involved 34 women scheduled for laparoscopic adnexal surgery. In each, a 10-mm radially expanding access device was inserted laterally on one side of the lower abdomen and a size-matched disposable cutting-tip trocar was placed on the other side, using random assignment. Postoperative pain for each studied wound and patient satisfaction toward the wounds were assessed using a visual analog scale. Any bleeding complication associated with insertion of the trocar was also recorded. RESULTS: The radially expanding access device was associated with significant reduction in severity (median 1.4 versus 5.0, P <.001) and duration (median 11 versus 21 days, P <.001) of postoperative wound pain, shorter wound scars (14 versus 17 mm, P <.001), a lower incidence of wound induration (0 versus 9, P <.01), and a higher patient satisfaction (median 9.7 versus 6.2, P <.001). There were four inferior epigastric artery injuries, all at the conventional trocar wound. CONCLUSION: The radially expanding access device was associated with less postoperative wound pain and more patient satisfaction than the conventional cutting-tip trocar.

Prospective, randomized, controlled study of the effect of hormone replacement therapy on peripheral blood flow velocity in postmenopausal women.

OBJECTIVE: To investigate the effect of different types and methods of delivery of hormone replacement therapy (HRT) on peripheral vascular flow velocity in postmenopausal women. DESIGN: A prospective, randomized, operator-blinded, controlled study. SETTING: A hormone replacement clinic in a university teaching hospital. PATIENT(S): Sixty-eight women who had undergone surgical menopause. INTERVENTION(S): No treatment, oral estrogen, continuous combined estrogen and progestogen, or percutaneous estrogen. MAIN OUTCOME MEASURE(S): The pulsatility indices of the brachial, dorsalis pedis, popliteal, and radial arteries were measured under standardized conditions before the commencement of HRT and after 2 and 6 months of treatment. Serum E2 levels were measured at each visit. RESULT(S): There was an inverse correlation between the serum E2 levels and the pulsatility indices. There was a significant reduction in the pulsatility index in at least one of the four arteries after 2 months of HRT in all the treatment groups but not in the control group. The effect of HRT on the pulsatility index persisted until the completion of the study in all the treatment groups. CONCLUSION(S): These results confirm that the administration of HRT is associated with a reduction of the pulsatility index, and hence an increase in blood flow in the peripheral arteries; this change in the pulsatility index is related directly to serum E2 levels. The percutaneous route of administration of estrogen was at least as effective as oral treatment in improving peripheral vascular flow velocity. The beneficial effect of estrogen was not affected by the addition of a progestogen.

Intramyometrial abscess complicating pregnancy. A report of two cases.

BACKGROUND: Intramyometrial abscess in pregnancy is a rare event. Little information is available on the presentations and potential complications. CASES: Two asymptomatic patients underwent complications with failed instrumental delivery in the second stage of labor. Intramyometrial abscesses were found during lower segment cesarean section. In the first case, incision and drainage was done, and the culture of the pus revealed multiple organisms, including Escherichia coli, group B Streptococcus and Klebsiella species. The patient was successfully treated with antibiotics, while the infant did not show any evidence of infection. In the second case, removal of the abscess was performed, and pathology showed evidence of chronic abscess, but the culture did not reveal any organisms. The patient was treated with prophylactic antibiotics. The infant was treated with antibiotics for clinical sepsis, but no organism was revealed. CONCLUSION: Intramyometrial abscess complicating pregnancy can be asymptomatic. Obstructed labor can be a potential complication when the abscesses are located in the lower uterine segment. Antibiotics, together with incision and drainage or removal of the abscess, is the first choice for treatment.

Gene expression pattern associated with radiotherapy sensitivity in cervical cancer.

UNLABELLED: The objective of the present preliminary study was to determine if a difference in the pattern of gene expression exists between tumors that were subsequently found to be sensitive to radiotherapy and tumors found to be resistant to radiotherapy. PATIENTS AND METHODS: A total of 16 patients with invasive squamous cell carcinoma of the uterine cervix were included in this study. All patients were treated with standardized radiotherapy alone. Ten of the tumors were clinically radiosensitive and six were radioresistant. Total RNA, extracted from tumor specimens obtained prior to treatment, was hybridized onto an oligonucleotide microarray with probe sets complementary to over 20,000 transcripts. The genes were first subjected to a statistical filter to identify genes with statistically significant differential expression levels between those that were radiosensitive and those that were radioresistant. A back-propagation neural network was then constructed to model the differences so that patterns could be easily identified. RESULTS: Although a number of genes were found to express differentially between radiosensitive and radioresistant tumors; the 10 most discriminating genes were used to construct the model. Using the expressions from these 10 genes, we found that neural networks constructed from random subsets of the whole data were capable of predicting radiotherapy responses in the remaining subset, which appears stable within the dataset. DISCUSSION: This study shows that such an approach has the potential to differentiate tumor radiosensitivity, although confirmation of such a pattern using other larger independent datasets is necessary before firm conclusions can be drawn.

Iatrogenic cardiac tamponade during pregnancy.

A 26-year-old primigravida who presented to us with threatened preterm labour which was suppressed successfully with sulindac, was found to have a pericardial effusion. Pericardiocentesis was performed because of evidence of right ventricular compression. However, it was complicated by inadvertent puncture of the left ventricle causing cardiac tamponade, and hypovolaemic shock shortly afterwards. An emergency pericardiotomy was performed to rescue the patient.

A randomised double blind comparison of Syntometrine and Syntocinon in the management of the third stage of labour.

OBJECTIVE: To compare the effect of intramuscular Syntometrine and Syntocinon in the management of the third stage of labour. DESIGN: A randomised double blind prospective study. SETTING: Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong. SUBJECTS: One thousand consecutive patients with singleton pregnancy and vaginal delivery in February and March 1993. RESULTS: The use of Syntometrine in the management of the third stage not only reduced the blood loss after delivery but was associated with a 40% reduction in the risk of postpartum haemorrhage (odds ratio 0.60; 95% CI 0.21-0.88), and the need for repeat oxytocic injections (odds ratio of 0.63; 95% CI 0.44-0.89). The two drugs did not differ in their effect on the duration of the third stage. However, the incidence of manual removal of the placenta was higher when Syntometrine was used (odds ratio 3.7; 95% CI 1.03-12.5), although the overall incidence remained low. Side effects from both drugs, such as nausea, vomiting, headache and hypertension, were uncommon. CONCLUSION: Intramuscular Syntometrine is a better choice than Syntocinon in the management of the third stage of labour.

A prospective study of the microbiological environment of the genitourinary tract in Hong Kong Chinese women during pregnancy.

Microbiological colonization of the genitourinary tract in pregnancy is associated with an increased risk of preterm labour and delivery. In our population, the risk of preterm labour is relatively low, and the purpose of this study was to examine the microbiological environment of the genitourinary tract to determine whether it differed from that reported in populations where the rate of preterm delivery is higher. A prospective study was made in 367 unselected women between 16 and 24 weeks' gestation. Although the rate of colonization with Candida species was higher than in most other studies (30.2%), colonization with Gardnerella, Group B Streptococcus, Trichomonas and Chlamydia was uncommon (1.9%, 0.8%, 0.6% and 3.5% respectively). Significant bacteriuria was also uncommon, occurring in only 4.9% of cases. The results of this study confirmed a relatively low incidence of colonization of the genitourinary tract in this population of women with a low incidence of preterm delivery. These findings suggest that low levels of colonization may be related to a low incidence of preterm delivery in our patients.

Preoperative hysteroscopic assessment of cervical invasion by endometrial carcinoma: a retrospective study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of hysteroscopy, using normal saline (NS) or carbon dioxide (CO2) as the distention medium, in assessing tumor invasion of the uterine cervix by endometrial carcinoma. METHODS: A retrospective study was conducted in 200 consecutive patients with endometrial carcinoma diagnosed from 1993 to 2000. Prior to definitive surgical treatment, hysteroscopy was performed using either NS or CO2 as the distention medium to determine whether the tumor had spread to the cervix. The uterine specimens obtained after hysterectomies were cut open for gross examination. Tumor invasion of the cervix as determined by hysteroscopy and gross examinations was compared with the pathological findings. RESULTS: Tumor invasion of the cervix was found in 41 (20.5%) cases on pathological examination. Hysteroscopy has an accuracy of 92.5% (185/200), a sensitivity of 68.3% (28/41), and a specificity of 98.7% (157/159), with a PPV of 93.3% (28/30) and a NPV of 92.4% (157/170) in determining cervical involvement. Assessment by gross inspection had 93.0% (186/200) accuracy, 68.3% (28/41) sensitivity, 99.4% (158/159) specificity, 96.6% (28/29) PPV, and 92.4% (158/171) NPV. There was no significant difference between the two assessment methods. When the results of hysteroscopy performed with different distention mediums were compared, the use of NS had a higher accuracy in determining tumor spread to the cervix (96.8% vs 88.7%, P = 0.03) and NPV (96.4% vs 88.4%, P < 0.05) than the use of CO2. CONCLUSIONS: Hysteroscopic assessment and gross examination of the uterine specimen had similar efficacy in detecting cervical invasion by endometrial carcinoma. Hysteroscopic examination using NS is more accurate than that which uses CO2.

Cervical intraepithelial neoplasia is associated with increased polyamine oxidase and diamine oxidase concentrations in cervical mucus.

OBJECTIVE: The aim of this study was to establish whether reactive oxygen species, generated during oxidation of amines, catalyzed by polyamine oxidase (PAO) and diamine oxidase (DAO) in cervical secretions may play a role in the etiology of cervical cancer. METHODS: Cervical mucus was obtained from women attending the gynecological outpatient department: 139 with and 154 without cytological evidence of cervical intraepithelial neoplasia were recruited. The mucus was freeze dried in liquid nitrogen, weighed, and later resuspended for assay of PAO and DAO concentrations using a chemiluminescence method. The two groups were compared by group sequential analysis using PEST3 software. RESULTS: Patients with a colposcopic diagnosis of a high-grade squamous intraepithelial lesion (SIL) had significantly higher enzyme activities than control cases (L(N)PAO 1.37 (0.37) versus 1.18 (0.35): Student t test: P < 0.001; L(N)DAO 1.37 (0.36) versus 1.15 (0.37): Student t test: P < 0.001). CONCLUSION: It is probable that this rise in enzyme activity precedes cytological changes and plays some part in the etiology of cervical cancer, as the cells that undergo premalignant change are normally squamous in origin, whereas mucus is a product of columnar epithelium. Higher enzyme activity in patients with SIL than in controls may be a reflection of higher risk of exposure to amine substrates in semen through multiple sexual partners.

Hysteroscopic dissemination of endometrial carcinoma using carbon dioxide and normal saline: a retrospective study.

OBJECTIVE: The aim of this study was to compare the likelihood of disseminating endometrial carcinoma cells into the peritoneal cavity by hysteroscopic examination using carbon dioxide (CO(2)) or normal saline (NS) as the distension medium. METHODS: A retrospective study of 162 consecutive patients with endometrial carcinoma treated at a university teaching hospital from 1994 to 1999 was undertaken. All patients had a hysteroscopic examination, using either CO(2) or NS as the distension medium, as part of the investigation for abnormal uterine bleeding or in determining whether the uterine cervix was invaded by tumor. Peritoneal fluid for cytology was collected immediately upon entry into the abdominal cavity. Positive peritoneal cytology was considered the primary statistical endpoint. RESULTS: Among 162 patients, 39 cases were excluded from the study because of macroscopic intraperitoneal diseases (n = 32) or pathology other than endometrioid adenocarcinoma (n = 7). Another 3 cases were excluded because both distension mediums had been used in the hysteroscopy. Analysis was therefore based on the data of 120 patients. There was no statistically significant difference between the two groups of patients undergoing hysteroscopy using either CO(2) (n = 70) or NS (n = 50) with regard to age, pathologic stage, International Federation of Gynecology and Obstetrics grading, myometrial invasion, tumor size, cervical involvement, nodal involvement, and 2-year progression-free survival. However, there was a mean of 13.0 plus minus 5.0 days (range 3-21 days) time gap between laparotomy for definitive surgery and CO(2) hysteroscopy compared to immediate laparotomy after NS hysteroscopy (P < 0.001). Positive peritoneal cytology was noticed in 8 (6.7%) patients of which 7 were in the NS group and 1 was in the CO(2) group. Positive cytology was significantly more common among patients after hysteroscopy using NS than CO(2) (14.0% versus 1.4%, odds ratio = 11.2, 95% confidence interval = 1.3-94.5, P = 0.009). The presence of positive peritoneal cytology was not associated with age, tumor grade, tumor size, myometrial invasion, cervical involvement, or nodal metastasis. All 8 patients with positive cytology received no additional treatment and are disease free at 12 to 34 months of follow-up. CONCLUSIONS: Our data suggested that endometrial malignant cells were introduced into the peritoneal cavity during hysteroscopy and might be more likely after the use of NS rather than CO(2). This report emphasizes the need for prospective evaluation for further clarification of this hypothesis. The clinical significance of the dissemination awaits the long-term follow-up of these patients.