Search

Hepatitis B virus (HBV) infection is associated with many extrahepatic malignancies, but its association with and impact on ovarian cancer has not been examined. We therefore examined the prevalence of HBV infection among women with primary ovarian carcinoma in an endemic area, and whether this impacts the presentation and survival of these patients. In a retrospective study, we reviewed 523 patients presenting with primary ovarian cancer and known HBV status between 1 January 2006 and 31 December 2017. Patients were divided into HBV-positive and negative groups for the comparison of the patient characteristics and presentation, including staging and histological types, and short term (2 years) mortality from ovarian cancer. Among the 10.1% (53/523) patients screened positive for HBV, more of them presented with advanced staging at FIGO stage 3 or above (OR 1.378, 95% CI 1.063-1.787), although there were no significant differences in patient characteristics. Within 24 months from presentation, there were more deaths due to malignancy in the HBV-positive group (73.3% vs 44.2%, OR 1.659, 95% CI 1.135-2.425). On multivariate analysis after adjusting for nulliparity status, previous use of oestrogens, presence of metastases, histological type (epithelial or others) and grading (high grade or not), whether optimal debulking was performed, and chemotherapy, HBV infection was independently associated with increased death within 24 months of presentation (aOR 2.683, 95% CI 1.015-7.091). In conclusion, the findings of this study suggested an adverse effect of chronic HBV infection on survival within two years of presentation in patients with primary ovarian cancer.

To investigate the role of DNA mismatch repair status (MMR) in survival of endometrioid endometrial cancer in Hong Kong Chinese women and its correlation to clinical prognostic factors, 238 patients with endometrioid endometrial cancer were included. Tumor MMR status was evaluated by immunohistochemistry. Clinical characteristics and survival were determined. Association of MMR with survival and clinicopathological parameters were assessed. MMR deficiency (dMMR) was found in 43 cases (16.5%). dMMR was associated with poor prognostic factors including older age, higher stage, higher grade, larger tumor size and more radiotherapy usage. Long-term survival was worse in dMMR compared to the MMR proficient group. The dMMR group had more deaths, shorter disease-specific survival (DSS), shorter disease-free survival (DFS), less 10-year DSS, less 10-year DFS, and more recurrence. The 5-year DSS and 5-year DFS in the dMMR group only showed a trend of worse survival but did not reach statistical significance. In conclusion, dMMR is present in a significant number of endometrioid endometrial cancers patients and is associated with poorer clinicopathological factors and survival parameters in the long run. dMMR should be considered in the risk stratification of endometrial cancer to guide adjuvant therapy and individualisation for longer follow up plan.

Simple Summary There is limited information about genomic markers, especially for cervical adenocarcinoma treatment decisions. In this prospective study, it was found that nonsynonymous PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. It is the first indication of the predictive power of PIK3CA aberration in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for the prolonged strategy of surveillance and indicates the possibility of tailoring management of this particular women’s cancer. Abstract Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient’s circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women’s cancer.

Background A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. Objectives To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. Study design Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. Results The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 μL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. Conclusions HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Introduction Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. Methods One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. Results PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size ( p PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival ( p Conclusions As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.

Enlarged pelvic nodes are commonly found during preoperative imaging studies in cervical cancer patients and may represent tumor metastasis. It remains controversial whether debulking of these enlarged nodes prior to definitive radiotherapy offers any survival benefit to the patient.Enlarged suspicious pelvic nodes identified by imaging studies in stage 1B to stage IIA (early-stage) cervical cancer patients prior to scheduled radical hysterectomy and in stage 1B2 or above (advanced-stage) cervical cancer patients destined for radiotherapy were debulked. Patients with confirmed nodal metastasis (node-positive) were primarily treated by radiotherapy and patients with no evidence of nodal metastasis (node-negative) were treated as planned. Clinical outcomes of these two groups of patients are reported after a long-term follow-up.Sixteen of 110 early-stage and 37 of 97 advanced-stage cervical cancer patients had their enlarged metastatic nodes removed before they were treated by radiotherapy. Microscopic metastatic pelvic nodes were found in six additional patients after the radical hysterectomy and four of them received postoperative adjuvant radiotherapy. After a median follow-up of 62 months, the rates of recurrence inside the pelvis are not significantly different between node-positive and node-negative patients with both early-stage and advanced-stage disease. Recurrences outside the pelvis occurred in 59.1% early-stage and 44.8% advanced-stage node-positive patients, and were the primary cause of poor survival.Debulking enlarged metastatic pelvic nodes may help reducing pelvic recurrence but does not seem to benefit survival.

Objective We undertook a prospective cohort study to ascertain the risk factors for the development of squamous intraepithelial lesions (SIL) in patients with systemic lupus erythematosus (SLE). Methods One hundred thirty-seven SLE patients with a normal Papanicolaou (Pap) smear at baseline were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap smear, human papillomavirus (HPV) DNA test, and clinical assessment were performed. Results Among the 137 patients, there were 12 incident cases (8.8%) of SIL over a median followup duration of 30.7 months (interquartile range 25.5–31.7). Among the 30 patients with HPV infection detectable by DNA testing at baseline, 9 (30%) developed SIL. The independent risk factors for the incident SIL in this group of SLE patients included the use of cyclophosphamide (CYC) ever (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 1.1–29.3; P = 0.041) and persistent high-risk HPV infection (OR 26.9, 95% CI 3.2–222.3; P = 0.002). The use of baseline HPV testing has a higher sensitivity than abnormal cytology (defined as atypical squamous cells of undetermined significance; 47.7% versus 33.3%) in predicting the development of SIL. Conclusion Independent risk factors associated with the development of SIL in SLE patients included persistent high-risk HPV infection and the use of CYC. Low-risk patients who receive negative test results on both cervical cytology screening and HPV DNA testing may not need to be rescreened within 3 years.

Objective.To ascertain the incidence, cumulative prevalence, persistence, and clearance of human papilloma virus (HPV) infection in patients with systemic lupus erythematosus (SLE), and to assess the risk factors for the acquisition and persistence of HPV infection.Methods.One hundred forty-four patients with SLE were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap test, a test for HPV DNA, and clinical assessment were performed.Results.The cumulative prevalence of HPV infection increased significantly (12.5% at baseline to 25.0% after 3 years; p = 0.006). Regarding type-specific HPV infection, 18.8% patients experienced 68 incident infections. The cumulative prevalence of high-risk HPV infection (11.1% at baseline to 20.8% after 3 years; p = 0.02) and multiple HPV infection also increased significantly (6.9% at baseline to 16.7% after 3 years; p = 0.009). Half (33/68, 48.5%) of the incident infections persisted for ≥ 6 months. Overall, 29/32 (90.6%) of the preexisting infection and 10/68 (14.7%) of the incident infections were cleared. Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (p = 0.025) and baseline Systemic Lupus International Collaborating Clinics score ≥ 1 (p = 0.038). Independent risk factor associated with persistent HPV infection included preexisting HPV infection (p = 0.04) and multiple HPV infection during first incident infection (p = 0.02).Conclusion.High frequency of persistent HPV infection, especially high-risk and multiple HPV infection, may explain why squamous intraepithelial lesions occurred frequently in patients with SLE. Patients with high inflammatory burden are at risk of acquiring HPV infection.

Background: Postcoital bleeding is a common gynaecological problem that impacts on a woman's quality of life and sexual function. There is little systematic research into its management. Aims: To assess the efficacy and side-effects of cryotherapy as treatment for postcoital bleeding. Methods: A prospective randomised controlled trial was conducted in a tertiary referral hospital in Hong Kong. A total of 85 women who presented with postcoital bleeding were recruited, and randomised to cryotherapy or no treatment. The treatment group received cryotherapy with compressed carbon dioxide through a cryoprobe placed on the cervix, and controls had cryoprobe on the cervix without compressed carbon dioxide flow. All recruited women were followed up two weeks, three months and six months to review their symptoms and response to the treatment. Results: The treatment group had a significantly better long-term cure rate and improvement rate. At six months, the cryotherapy group reported a cure rate of 72.1% while that in the control group the cure rate was 50.0% (P = 0.04). The number needed to treat was 5. The mean improvement rate of the cryotherapy group was 82.88% ± 35.87 but was only 61.62% ± 55.30 in the control group (P = 0.04). The results were more significant in women with the defined pathological cervix. Apart from the vaginal discharge at second week follow up in the treatment group, there was no statistical significant difference in side-effects and complications among two groups. Conclusion: Our study demonstrated that cryotherapy is a safe and an effective treatment for postcoital bleeding.

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.

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.

To examine the association between human leukocyte antigen-A (HLA-A) allele polymorphism human papillomavirus (HPV) infection and risk for cervical neoplasia in Chinese women 263 patients (155 with cervical intraepithelial neoplasia [CIN] II/III and 108 with invasive cervical cancer [ICC]) were compared with 572 controls. Overall regardless of HPV status a decreased risk for ICC was observed for patients with A*0207/ 0215N or A*2402 and an increased risk was observed for patients with A*1104. The protective association of A*0207/0215N was reproduced in HPV-16-positive patients with ICC but not in subgroups infected with other HPV types. The risk association between A*1104 and both HPV-16 and HPV-18 was reproduced in the subgroups with CIN III/ICC. The protective association between A*2402 and HPV-16 HPV-18 HPV-52 and HPV-58 was consistently observed in all subgroups with CIN III/ICC suggesting a linkage with a general antioncogenic genetic factor. The results of the present study indicate that HLA-A polymorphism is one of the host genetic factors that alter the risk for the development of cervical cancer in Chinese women. (authors)

Objectives We studied the loss of heterozygosity (LOH) in chromosome 1 in squamous cell carcinoma (SCC) of the uterine cervix and evaluated its clinical and pathological significance. Methods Sixty-three highly polymorphic markers were used to study the LOH in 84 SCC. Microdissection was performed to enrich the tumor cells population before the alleotyping study. The findings were correlated with clinicopathologic findings. Results LOH was detected in all but one SCC. The number of loci showing LOH in each case ranged from 0 to 41. Five loci showed LOH in ≥30% SCC and 28 other loci had an LOH frequency between 20% and 30%. Six of the eight markers located at 1p36.21 to 1p36.33 had a frequency of LOH >20%. Shortened total survival was associated with LOH at 14 loci and shortened disease-free survival was associated with LOH at 11 loci while LOH at nine loci were associated with both. A high frequency of LOH was associated with stage as well as shortened total and disease-free survival. Conclusions LOH is a common and early event in the development of cervical SCC. Tumor suppressor genes may be present at 1p36. The incidence of LOH increases as the tumor progresses but a high frequency of LOH is not an independent prognostic factor.

Patients diagnosed to have endometrial carcinoma without prior hysteroscopic examination were recruited from March 2000 to August 2003. Normal saline was used to distend the uterine cavity during the hysteroscopic examination to look for endocervical spread before the definitive surgical treatment. We performed laparotomy, clamped both fallopian tubes, and collected peritoneal washing before the hysteroscopic examination was performed. Peritoneal washing was collected once more after the hysteroscopic examination. Hysteroscopic assessment was performed in 103 patients. Of them, 10 patients were excluded from the study due to previous history of tubal sterilization or blockage. The final analysis was confined to 93 patients. Positive peritoneal cytology was found in 10 (10.8%) patients and this finding was significantly related to the tumor grading (P = 0.023), adnexal involvement (P = 0.003), cervical invasion (P = 0.01), and the presence of peritoneal seedlings (P = 0.001). In five of the 10 patients with positive peritoneal cytology before the hysteroscopic examination, malignant cells could also be recovered in the peritoneal washing collected after the hysteroscopic examination. For patients with negative peritoneal cytology before hysteroscopy, none exhibited positive peritoneal cytology after the procedure. Our data suggested that complete occlusion of both fallopian tubes can effectively prevent the dissemination of endometrial malignant cells into the peritoneal cavity during hysteroscopy.

The case histories of 95 patients with endometrial carcinoma treated between July 1998 and December 2002 were reviewed. These patients were staged according to FIGO classification and included peritoneal cytology, total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAHBSO), and pelvic with or without para-aortic lymphadenectomy. The FIGO surgical stages were as follow: IA, 9 (9.5%); IB, 35 (36.8%); IC, 16 (16.8%); IIB, 10 (10.5%); IIIA, 5 (5.3%); IIIB, 1 (1.1%); IIIC, 19 (20.0%). In addition to TAHBSO, 47 (49.5%) patients had pelvic lymphadenectomy whereas 48 (50.5%) had both pelvic and para-aortic lymphadenectomy. Nineteen (20.0%) of 95 patients had nodal metastases. Positive pelvic and para-aortic lymph nodes were found in 15 (15.8%) of 95 and 12 (25.0%) of 48 patients, respectively. According to the result of the lymphadenectomy, 19 (20.0%) patients had their surgical stage upgraded to stage IIIC and 61 (64.2%) patients had a change in their management plan. Twelve (12.6%) patients required extended field irradiation due to para-aortic nodal metastases and 49 (51.6%) patients with negative nodes avoided postoperative external radiotherapy. By defining the lymphatic spread via surgical staging, postoperative radiotherapy can be recommended to patients with nodal metastases, while it can be withheld from those patients with negative nodes, irrespective of the presence of risk factors.

Objectives: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. Methods: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. Results: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (−0.02±0.03 g/cm2) while it increased by 2% in the 1 mg (0.02±0.03 g/cm2) and 3% in the 2 mg group (0.03±0.03 g/cm2). Mean changes in BMD over 12 months in the hip were −0.02±0.02 g/cm2 (−2%), 0.01±0.02 g/cm2 (+1%) and 0.01±0.03 g/cm2 (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P

Objectives: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. Methods: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. Results: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. Conclusions: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.

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

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 N DAO 1.37 (0.36) versus 1.15 (0.37): Student t test: P 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.

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.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.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 (P0.001). 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.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.

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.

The benefit of treating postmenopausal women with established cardiovascular disease with combined estrogen-progestogen hormone replacement therapy (HRT) is controversial. This study investigated the effect of treatment with estradiol and norethisterone acetate on exercise tolerance and on the frequency and severity of ischemic attacks in postmenopausal women with stable angina pectoris. A total of 74 Chinese women were recruited for this 16-week double-blind, placebo-controlled trial. They were randomly allocated into two groups; one group received placebo/placebo/placebo and the other group received placebo/estrogen-progestogen/placebo. Estrogen-progestogen continuous combined HRT increased both time to 1-mm ST depression (99.1 s, p < 0.05) compared with a mean decrease of 22.9 s with placebo (p < 0.05), and total exercise duration also showed a significant increase (32.7 s, p < 0.05) after treatment compared with placebo (2.5 s, p < 0.05). In addition, the total number of ischemic events/24 h during ambulatory electrocardiographic monitoring decreased by 0.82 events after treatment (p < 0.05) compared with an increase in the placebo group (0.94), a highly significant difference (p = 0.006). These results suggest that the administration of this particular combined hormone replacement preparation may have a beneficial effect on myocardial ischemia in postmenopausal women with established coronary disease.

Objective. The aim of this study was to evaluate the efficacy of hysteroscopy, using normal saline (NS) or carbon dioxide (CO 2 ) 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 CO 2 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 2 . 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 CO 2 .

To compare postoperative wound pain associated with the radially expanding access device and the conventional disposable cutting-tip trocar.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.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.The radially expanding access device was associated with less postoperative wound pain and more patient satisfaction than the conventional cutting-tip trocar.

Laparoscopic ultrasound is initially developed to facilitate surgery for hepatobiliary and pancreatic cancers. With the advancement of laparoscopic surgery, laparoscopic ultrasound has been incorporated into laparoscopic surgery in order to combat against the limitation of laparoscopic surgery. In the management of gynecological malignancy, its role is mainly on the assessment of lymph nodes.

Background —Gonadotropin-releasing hormone agonists (GnRHas) are a group of drugs that with long-term use induce a pseudomenopausal state in which estrogen production is suppressed. They are commonly used in the treatment of sex steroid–dependent conditions. “Add-back” hormone replacement therapy is used to prevent menopause-like symptoms and bone loss during GnRHa treatment, but it is also recognized that hypoestrogenism adversely affects vascular function. The aim of this study was to examine the effect of GnRHa and add-back therapy on vascular reactivity. This model serves as a paradigm for the effect of hormone replacement therapy in postmenopausal women. Methods and Results —Measurements of endothelium-dependent and endothelium-independent vascular reactivity were compared in 2 groups of women treated with a GnRHa for 6 months. One group received estrogen/progestogen add-back therapy during the second 3 months of GnRHa treatment. Vascular reactivity was examined by use of ultrasound measurements of changes in brachial artery diameter. Endothelium-dependent changes were assessed during reactive hyperemia, whereas endothelium-independent changes were measured after the administration of glyceryl trinitrate sublingual spray. Treatment with the GnRHa alone had an inhibitory effect on endothelium-dependent relaxation. However, endothelium-dependent relaxation significantly improved in the group receiving add-back therapy (14.6%) compared with the group treated with GnRHa alone (8.6%) ( P Conclusions —These results suggest that the administration of add-back therapy has a protective effect on vascular function in GnRHa-induced hypoestrogenism. As a model for the menopause, these results also suggest that the long-term administration of hormone replacement therapy would result in endothelium-dependent arterial relaxation, an observation previously attributed only to the acute administration of estrogen.

Our purpose was to quantify and compare the metabolic and inflammatory changes after laparoscopic and abdominal hysterectomy.Forty-four patients with no major medical disease requiring abdominal hysterectomy for benign disorders were randomly assigned to have laparoscopic hysterectomy (n = 20) and abdominal hysterectomy (n = 24). Venous blood and 24-hour urine samples were collected the day before and for each of the first 3 postoperative days.No differences were present in demographic characteristics, operating time, and uterine weight between the two groups. No major complications were encountered. The laparoscopic hysterectomy group had a significantly lower postoperative morphine consumption (median 5.5 vs 14 mg, P.05), lower febrile morbidity rate (15% vs 45.8%, P.05), and shorter hospital stay (median 4 vs 6 days, P.001) and demonstrated a less intense stress response in terms of serum interleukin-6 (median 50.6 vs 73.9 pg/mL x hour x 10, P = .01), C-reactive protein (median 28.1 vs 44.7 mg/L x hour x 10(2), P = .005), cortisol (median 23.4 vs 27.2 mg/mL x hour x 10(3), P = .04), white blood cell count (median 59.5 vs 69.8 10(9)/L x hour x 10, P = .009), 24-hour urinary excretion of cortisol (median 34.8 vs 44.2 nmol/L x hour x 10(3), P = .02), and norepinephrine (median 80.8 vs 132.4 nmol/L x hour x 10(2), P = .001). No significant difference was detected in plasma glucose (median 41.5 vs 45.6 mmol/L x hour x 10, P = 6) and 24-hour urinary excretion of epinephrine (median 32.2 vs 34.1 nmol/L x hour x 10(2), P = .3).Laparoscopic hysterectomy is associated with a lower morbidity and a less intense stress response than abdominal hysterectomy for benign diseases.

Chromosome 9 abnormalities have been found in primary tumors and cell lines from human gynecologic malignancy. Alterations of p16 INK4 and p15 INK4B genes mapped on the band p21 of chromosome 9 have been detected in various human tumors, but the role of these genes as tumor suppressors in vivo appear to be dependent on tumor type. Polymerase chain reaction (PCR)-based analysis was performed to search for lesions of these genes in 202 primary gynecologic malignancies. Homozygous deletions of p16 INK4 were detected in 7 of 128 (5%) cervical, 1 of 41 (2%) endometrial, 2 of 27 (7%) ovarian, and 3 of 6 (50%) vulvar carcinomas, while homozygous deletions of p15 INK4B were detected in 19 of 128 (15%) cervical, 1 of 41 (2%) endometrial, 9 of 27 (33%) ovarian, and 3 of 6 (50%) vulvar carcinomas, respectively. No mutations were found in exon 2 of p16 INK4 from 161 cases of gynecologic malignancy without deletion of p16 INK4 . All 3 cases of vulvar carcinoma showing homozygous deletions of p16 INK4 and p15 INK4B were at advanced clinical stage (stage III–IV), while all 7 cases of cervical carcinoma and 2 cases of ovarian carcinoma showing homozygous deletion of p16 INK4 were at early stage (stage I–II). The results indicate that homozygous deletions of p16 INK4 and/or p15 INK4B genes may play a role in a subset of primary gynecologic malignancy.

Consensus primers targeting human papillomaviruses (HPVs) have biases in sensitivity toward certain HPV types. We applied 3 primer sets (GP5+/6+, MY09/11, PGMY09/11) in parallel on 120 Chinese cervical cancer specimens. GP5+/6+ exhibited a poor sensitivity for HPV52, for which the prevalence among squamous cell cervical cancer was underestimated from 14.6% to 0%. The fact that HPV52 should rank second in prevalence among squamous cell cervical carcinoma in Hong Kong could be missed if GP5+/6+, a worldwide commonly used primer set, was selected for HPV detection. Biases in HPV type-specific sensitivity may result in misprioritization of vaccine candidates.

Peritoneum is the commonest site for ovarian cancer metastasis. In peritoneum, stromal fibroblasts are the second most common cell types. In this study, we aimed to investigate the role of tumor-stromal interaction in peritoneal metastasis of ovarian cancer. Using three-dimensional (3D) organoid co-culture model, we found that the interaction between metastatic human ovarian cancer cells and normal human stromal fibroblasts promotes cancer colony formation. Using cytokine antibody array, we identified a group of cytokines are de novo produced in the 3D co-culture. Among them, transforming growth factor alpha (TGF-α) was produced anew from normal stromal fibroblasts in the 3D co-culture. In the co-culture, transcription of TGF-α in normal stromal fibroblasts is activated by tumor necrosis factor alpha (TNF-α) that derived by ovarian cancer cells. By epigenetic studies, we discovered that over-expression of TNF-α in human ovarian cancer cells is due to DNA hypomethylation and chromatin remodeling in TNF-α promoter. TGF-α is a ligand of epidermal growth factor receptor (EGFR), and we confirmed EGFR is over-expressed in a significant portion of human ovarian cancer. When applying EGFR-specific inhibitors (AG1478, Gefitini, and Erlotinib) in our 3D organoid models (3D mono-cultures and 3D co-cultures), we further found that the fibroblast-derived TGF-α promotes colony formation of metastatic ovarian cancer cells in vitro through EGFR activation. In fact, TGF-α activates Hippo/YAP signaling pathway in human ovarian cancer cells via EGFR. In addition, our in vivo experiments showed that normal stromal fibroblasts promote peritoneal metastasis of ovarian cancer through EGFR activation in a xenograft model. Finally, the TNFα-TGFα-EGFR interacting loop was detected in cancer-stroma-cancer compartments of omental metastases of ovarian cancer patients by immunohistochemistry. Based on our experimental results, we proposed a cancer-stroma-cancer interacting loop that promotes peritoneal metastasis of ovarian cancer through TNFα-TGFα-EGFR. The proposed mechanism involves: 1) TNF-α is over-expressed in human ovarian cancer cells by promoter DNA hypomethylation and chromatin remodeling; 2) the ovarian cancer cell-derived TNF-α induces de novo TGF-α production in normal human omental stromal fibroblasts; and 3) the fibroblast-derived TGF-α, in turn, promotes colony formation of metastatic ovarian cancer cells through EGFR-mediated Hippo/YAP signaling pathway. Our results thereby suggest that peritoneal metastasis in the ovarian cancer patients after cytoreductive surgery can be prevented by EGFR-targeted therapy. Citation Format: Tat-San Lau, Loucia Kit-Ying Chan, Chi-Hang Wong, Chi-Wai Man, Tak-Hong Cheung, So-Fan Yim, Jacqueline Ho-Sze Lee, Tony Kwok-Hung Chung, Joseph Kwong. A cancer-stroma-cancer interacting loop promotes peritoneal metastasis of ovarian cancer through TNFα-TGFα-EGFR. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1566.

EDITORIAL COMMENT: There seems no doubt that Chinese women have a low incidence of premature delivery (less than 37 weeks) although the 5% quoted in this paper is similar to the 5.9% for Victoria in 1992 (3,874 of 65,252 confinements). Drew and Chan have confirmed the lower incidence of prematurity in Chinese women living in Hong Kong and in Melbourne than in non-Chinese women living in MelbourneA. The Chinese women in this study had a remarkably low incidence of group B streptococcal isolation (0.8%) and a very high rate of detection of Candida (30.2%). It is of interest that the authors did not treat women with tests positive for Candida. Sexual practices could understandably influence the vaginal microbiological environment. Recently we reported on the frequency of anal intercourse and other sex practices in pregnancy in a small series from South AustraliaB. Also recently the Editor was privileged to visit a number of maternity hospitals in the Jiansu province in China. When discussing premature rupture of the membranes and prematurity we were told, repeatedly (via our interpreter), that in China it was customary to abstain totally from intercourse during pregnancy even in the absence of complications such as bleeding, ruptured membranes or evidence of infection in one or other partner. Should we disbelieve what we are told when the information seems unexpected? We need more information regarding sexual activity (frequency and route) and associated complications such as premature rupture of the membranes and otherwise uncomplicated spontaneous premature labour, so that we can advise our patients appropriately. A. Drew JH, Chan DP. Incidence of prematurity and low birth-weight in an immigrant Chinese population. Aust NZ J Obstet Gynaecol 1989; 29: 303-305. B. Barclay LM, McDonald P, O'Loughlin JA. Sexuality and Pregnancy. An Interview Study. Aust NZ J Obstet Gynaecol 1994; 34: 1-7.

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.

Many reports have provided evidence to support the effective use of diagnostic laparoscopy and laparoscopic ultrasonography (LUS) to determine if patients with upper abdominal malignant diseases are operable so that unnecessary laparotomy can be avoided. LUS is less frequently applied to patients with pelvic malignancies and this is probably related to the technical difficulties. We have developed the LUS technique in examining the pelvic nodes for metastasis systematically and have applied it to 241 cervical cancer patients. The procedure is safe and not associated with any major morbidity. The mean duration of pelvic node assessment by LUS is 14 minutes and the procedure can be satisfactorily completed in 98% of patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LUS in detecting pelvic nodal metastasis were 81.2%, 55.6%, 88.4%, 57.7%, and 87.5%, respectively, in patients scheduled for radical hysterectomy. In this report, we describe the LUS technique in detail and demonstrate important landmarks that provide useful orientation during an LUS examination. The technical limitations and pitfalls are also discussed.

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.

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.

Objective To assess the clinical use of a laparoscopic ultrasound scan (LUS) to identify pelvic and para-aortic node metastasis in patients with advanced-stage cervical cancer. Methods After examination under general anesthesia and cystoscopy, LUS was used to examine the pelvic nodes of patients with advanced-stage cervical cancer. Abnormal nodes were excised before definitive treatment to confirm the nodal status. Patients without abnormal para-aortic nodes on preoperative computer tomography/magnetic resonance imaging in the past 3 years were surgically staged via laparoscopic extraperitoneal aortic node sampling, and the findings were correlated with LUS findings. The predictive values of abnormal pelvic nodes on LUS for pelvic and aortic node metastasis were determined. Results A total of 119 advanced-stage cervical cancer patients underwent LUS of pelvic nodes. Abnormal pelvic nodes were found in 62 (52.1%) patients, and metastasis was confirmed by histology in 38 (31.9%) patients. Three patients had micro-metastasis in para-aortic nodes, and all of these patients had abnormal pelvic lymph nodes on LUS. Conclusion Abnormal pelvic nodes are commonly found on LUS in patients with advanced-stage cervical cancer, and selective excision biopsy is needed to confirm pelvic node metastasis. Surgical staging of aortic nodes might be considered for patients with abnormal pelvic nodes on LUS.

The primary goals of this study are to improve the accuracy of noninvasive diagnosis of early cervical cancer. In this study, a novel 3-D optical imaging system based on active stereo vision and motion tracking is developed to track the motion of patient and to register the time-sequenced images of cervix recorded during the examination of colposcopy. This technology can quantify the acetic acid induced optical signals associated with early cancer development at cervix. The results of a preliminary clinical study of 65 patients demonstrate that the accuracy to differentiate pre-cancerous cervical tissue from normal tissue can be significantly increased.

The clinical utility of viral-load and integration status of human papillomavirus (HPV) infection remains uncertain. We examined 75 women infected with HPV58, a worldwide rare type found to be prevalent in cervical cancers in eastern Asia. Viral load was significantly higher for cervical intraepithelial neoplasia (CIN) 1/2, but those for a normal control group and for CIN 3 or cancer overlapped substantially. A pure integrated genome was found for all lesion grades, giving a poor positive predictive value (23.1%) for cancer. The pure episomal form's negative predictive value for cancer was only 76.3%. Mixed patterns of E2 gene disruption were common and often involved the amino-terminal and hinge regions. Disruption of the whole E2 gene was rare and was restricted to high-grade lesions. The HPV58 variant E67-HK-2 was more likely to exist in the pure episomal form. Routinely collected cervical samples contain a heterogeneous population of viruses, hampering the application of viral load and integration testing in clinical settings.

Objectives and methods. HLA II DQB1 polymorphisms have been shown to associate with cervical cancer risk, but results varied among different populations. In this study, the HLA DQB1 alleles among 221 southern Chinese women with cervical intraepithelial neoplasia grade III (CIN III)/invasive cervical carcinoma (ICC) were compared to 191 controls. Results. The frequency of DQB1*03 was significantly lower among ICC overall as compared to controls (65.4% vs. 79.1%, odds ratio [95% confidence interval]: 0.50 [0.28–0.88], corrected p -value: 0.04). The protective association of DQB1*03 remained significant for human papillomavirus (HPV) 16-positive ICC, but not for HPV16-negative cases. This is in contrast to studies on European populations where DQB1*03 was associated with an increased risk for ICC. In the current study, 70.1% of the HPV16 isolates were Asian variants, and 28.0% were European variants. However, no significant association between HPV16 variant and DQB1*03 distribution was observed. HPV52 and HPV58 were found respectively in 16.3% and 10.0% of CIN III/ICC, which were higher compared to that of Europe and North America. Further analyses revealed a positive risk association between DQB1*06 and HPV58-positive CIN III/ICC (3.68 [1.37–9.92], corrected p -value: 0.012). Conclusion. The host genetics and the distribution of HPV types/variants may account for the observed differences among southern Chinese and other populations.

To determine whether serum vascular endothelial growth factor (VEGF) concentration is correlated with arterial reactivity in postmenopausal women.An observational study was conducted on 24 postmenopausal women who did not receive any hormone therapy in the 6 months preceding the study and had no pre-existing cardiovascular diseases or cardiovascular risk factors. Serum samples were obtained from all participants and analyzed for VEGF concentrations. Arterial reactivity was assessed by the measurement of endothelium-dependent dilatation and endothelium-independent dilatation of the brachial artery, using color duplex Doppler ultrasound.The study population was aged 50.8 years on average, with about 2 years of menopause. Serum VEGF concentration in postmenopausal women was significantly correlated with both endothelium-dependent dilatation (r = -0.66, p0.01) and endothelium-independent dilatation (r = -0.65, p0.01) of the brachial artery.Serum VEGF level may be a potential indicator of arterial reactivity in postmenopausal women.

The aim of this study was to find the optimal set of microsatellite markers for diagnosis of the microsatellite instability (MSI) phenotype in endometrial cancers. We compared the sensitivity, specificity and ease of use of a reference panel of five markers originally recommended by the National Cancer Institute (NCI) for colorectal cancer and a panel of five quasi-monomorphic mononucleotide repeat markers (pentaplex PCR system). We used these panels for establishing the MSI status of a series of 80 sporadic endometrial adenocarcinomas by comparing the allelic profiles of the markers between tumor and matching germline DNA. Both panels detected the same subset of 21 out of 80 (26%) endometrial MSI carcinomas. However, in the MSI cases, the mean instability of the five mononucleotide repeats was 96.1% as compared with a mean instability of 69.8% for the three dinucleotide repeats of the NCI panel, indicating a superiority of mononucleotide repeats over dinucleotide repeats in detecting MSI. The fact that the two panels of markers detect the same set of MSI tumors is due to the presence of two mononucleotide repeats within the NCI panel. As demonstrated previously in gastric and colon MSI cases, the pentaplex PCR reaction using mononucleotide repeats is thus an easier and more sensitive method than the NCI panel, for the screening of MSI status in endometrial tumors.

A population-based study was conducted on 256 southern Chinese with cervical intraepithelial neoplasia grade III (CIN III) or invasive cervical cancer (ICC) and on 258 controls to examine the associations between HLA-B alleles, infection with high-risk human papillomaviruses (HPVs) and the development of cervical neoplasia. HLA-B15 was found to be protective for CIN III/ICC overall (pcorrected = 0.003), and for HPV52-positive CIN III/ICC (pcorrected = 0.003). A marginal protective effect of B15 was observed for HPV16-positive CIN III/ICC, but no significant associations were revealed for HPV18- or HPV58-positive cases. None of the HLA-B alleles were found to confer an increased risk for cervical neoplasia. HLA-B15 is common among Asian for whom HPV52, a worldwide uncommon HPV type, also exists in a relatively high prevalence. It would also be worthwhile to assess the association between HLA-B15, HPV52 and cervical cancer in other Asian populations. © 2005 Wiley-Liss, Inc.

Objectives. Nodal metastasis is one of the most important prognostic factors in early stage cervical carcinoma and has an immense impact on the subsequent management. Thus, searching for nodal metastasis by pelvic lymphadenectomy is an integral part in the surgical management of cervical carcinoma. Complete nodal clearance of lymphatic tissue up to 2 cm above the bifurcation of common iliac vessels is therefore performed as a routine in our unit. The aim of this study is to investigate the incidence and pattern of pelvic lymph node metastases in patients with early stage cervical carcinoma to determine the role of common iliac node dissection in the surgery. Methods. We retrospectively reviewed 174 operation and histopathology reports of patients who underwent pelvic lymphadenectomy because of stage IA2 to IIA cervical carcinoma. Lymph nodes collected below and above the bifurcation of common iliac vessels were labeled as pelvic nodes and common iliac nodes, respectively. The incidence and distribution of nodal metastases were analyzed. Results. Complete and selective pelvic lymphadenectomy was performed in 163 and 11 patients, respectively. Nodal metastasis was documented in 35 (20.1%) patients. Pelvic and common iliac nodes were involved in 34 and 8 cases, respectively. All except one patient with common iliac node metastases were also found to have pelvic node metastasis. Conclusions. In early stage cervical carcinoma, isolated common iliac lymph node metastasis is rare, especially in cases without associated high risk factors. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operation morbidity and time.

The depth-resolved autofluorescence ofrabbit oral tissue, normal and dysplastic human ectocervical tissue within l20μm depth were investigated utilizing a confocal fluorescence spectroscopy with the excitations at 355nm and 457nm. From the topmost keratinizing layer of oral and ectocervical tissue, strong keratin fluorescence with the spectral characteristics similar to collagen was observed. The fluorescence signal from epithelial tissue between the keratinizing layer and stroma can be well resolved. Furthermore, NADH and FADfluorescence measured from the underlying non-keratinizing epithelial layer were strongly correlated to the tissue pathology. This study demonstrates that the depth-resolved fluorescence spectroscopy can reveal fine structural information on epithelial tissue and potentially provide more accurate diagnostic information for determining tissue pathology.

Summary A 36-year-old primigravida presented to us with symptoms and signs of ectopic pregnancy repeatedly but was misdiagnosed to have an intrauterine pregnancy based on 1 early ultrasound examination showing an ‘intrauterine sac’. She suffered the morbidity due to ectopic pregnancy which included hysterectomy which may have been prevented had the correct diagnosis been made.

Objectives This study was conducted to define the role of microsatellite instability (MSI) in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC) of the cervix. We also tested the validity of using markers recommended for MSI study in colonic carcinoma by the National Cancer Institute (NCI) for cervical neoplasm. Methods Twenty normal cervical, 24 low-grade CIN (CIN-L), 59 high-grade CIN (CIN-H), and 93 SCC tissues were examined for MSI after microdissection. A polymerase chain reaction based MSI detection was performed using five markers recommended by the NCI for colonic cancer (panel one) as well as five other markers (panel two) found to be informative in earlier studies. High-frequency MSI (MSI-H) was defined as instability in ≥2 of 5 loci if one panel was used and ≥30% of loci when more than five loci were used. Low-frequency MSI (MSI-L) was diagnosed if instability was noted but did not meet the criteria of MSI-H. Findings were correlated with clinicopathologic information. Results The combined use of panel one and two markers showed no MSI in normal cervical or CIN-L tissue, MSI-L in 1 CIN-H (1.7%), MSI-L in 16 (17.2%), and MSI-H in 11 (11.8%) SCC, respectively. The NCI-recommended panel alone detected 19 of 27 MSI-positive SCC. MSI-positive was not related to patient age, disease stage, and tumor grade. The overall survival of MSI-positive patients was significantly worse than that of microsatellite stable patients (P = 0.02). An increasing trend of MSI-H rate with higher disease stages was noted (P = 0.035) but MSI-H was not associated with poor prognosis. Conclusions The NCI recommended panel of markers might not be useful in MSI study for SCC and using more than five markers improves the MSI detection. MSI is rare in cervical dysplasia but is present in a subset of SCC. The association between MSI-positivity and prognosis awaits future confirmation.

Objective To determine whether raloxifene has an effect on serum vascular endothelial growth factor (VEGF) concentration in postmenopausal women. Design A randomized, placebo-controlled trial. Setting University-based obstetrics and gynecology unit. Patient(s) Fifty postmenopausal women who did not receive any hormone therapy in the 6 months preceding the study. Intervention(s) The participants were randomly assigned on a one-to-one basis to receive either raloxifene (60 mg daily) or placebo for 36 weeks. Main outcome measure(s) Serum VEGF concentrations at baseline and at 12 weeks and 36 weeks after the commencement of intervention. Result(s) The serum VEGF concentrations in the raloxifene group were significantly reduced from 247 ± 16 pg/mL at baseline to 195 ± 11 pg/mL at 36 weeks after starting raloxifene. The placebo group showed no significant change in the serum VEGF concentrations throughout the intervention period. Conclusion(s) Raloxifene therapy in postmenopausal women is associated with a significant reduction in serum VEGF concentration.

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.

We aimed to investigate the association between whole blood mercury concentrations and semen quality in sub-fertile men. Fifty-nine male partners of infertile couples attending the Assisted Reproduction Unit of the Chinese University of Hong Kong between 1997 and 1998 were recruited into our study. Blood was taken from each subject for whole blood mercury concentration and hormone profile. Semen samples were obtained for computer assisted semen analysis using the Hobson sperm tracker. The semen parameters and hormone profile were compared between subjects with normal and those with elevated mercury concentrations. Twenty-one subjects (35.6%) had a whole blood mercury concentration higher than the normal range (0-50 nmol/l). All parameters of the semen analysis including the concentration of sperm, percentage of morphologically normal sperm, percentage of motile sperm, curvilinear velocity, straight-line velocity, average path velocity, and amplitude of lateral head displacement, were reduced in those with elevated blood mercury concentrations, although the difference was not statistically significant. We failed to demonstrate a statistically significant effect on the measurement of semen quality, but other adverse effects cannot be excluded. From a public heath perspective, these findings confirm that mercury toxicity is a potentially serious problem affecting the local community.