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.
ABSTRACT
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.
Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Squamous Cell/diagnosis , DNA, Viral/analysis , Liquid Biopsy/methods , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adenocarcinoma/virology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Capsid Proteins/genetics , Carcinoma, Squamous Cell/virology , Cervix Uteri/pathology , Cervix Uteri/virology , Female , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Middle Aged , Papillomaviridae , Papillomavirus E7 Proteins/genetics , Papillomavirus Infections/blood , Papillomavirus Infections/complications , Recurrence , Retrospective Studies , Uterine Cervical Neoplasms/virology , Viral LoadABSTRACT
OBJECTIVES: To identify clinical risk factors for dislodgment of vaginal pessary within one year in women with symptomatic pelvic organ prolapse. STUDY DESIGN: This was a prospective observational study which recruited consecutive women with symptomatic pelvic organ prolapse in a tertiary urogynecology center. Basic demographics, clinical symptoms and staging of pelvic organ prolapse were assessed. A vaginal pessary was offered where appropriate. MAIN OUTCOME MEASURES: Demographics and clinical parameters were compared between women who were able to use a vaginal pessary for one year and those whose pessaries were dislodged within one year. RESULTS: A total of 779 women were recruited and had a vaginal pessary inserted. Of them, 528 women, with a mean age of 64.7 (SD 10.1) years, returned for one-year follow-up; 177 (33.5%) had their pessary dislodged within one year and 351 (66.5%) had been able to retain the pessary. Stage III or IV prolapse (OR 1.76), prolapse predominant at the apical compartment (OR 2.14) and larger genital hiatus (OR 1.63) were factors associated with dislodgment of the vaginal pessary. Age, body mass index, previous hysterectomy and short vagina were not associated with dislodgment. Nevertheless, 47.6% of women with stage III/IV prolapse could still keep the pessary for one year. CONCLUSION: Higher staging of prolapse, larger genital hiatus and apical compartment prolapse are clinical predictors for dislodgment of a vaginal pessary. Despite this, nearly half of women with stage III/IV prolapse were able to use a vaginal pessary for one year. Therefore, a vaginal pessary should be offered despite their staging of prolapse.
Subject(s)
Pelvic Organ Prolapse/therapy , Pessaries/adverse effects , Aged , Body Mass Index , Female , Humans , Hysterectomy , Middle Aged , Pessaries/statistics & numerical data , Prospective Studies , Risk Factors , VaginaABSTRACT
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<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). 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.
Subject(s)
Adenocarcinoma/blood , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , DNA, Neoplasm/blood , Phosphatidylinositol 3-Kinases/genetics , Uterine Cervical Neoplasms/blood , Adenocarcinoma/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Asian People , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Class I Phosphatidylinositol 3-Kinases , DNA Mutational Analysis , Disease-Free Survival , Feasibility Studies , Female , Hong Kong , Humans , Middle Aged , Polymerase Chain Reaction , Tumor Burden , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathologyABSTRACT
We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients' plasma: 60-64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.
Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Osteopontin/metabolism , Uterine Cervical Neoplasms/blood , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Monoclonal/metabolism , Biomarkers, Tumor/blood , Female , Humans , Mice , Middle Aged , Osteopontin/genetics , Osteopontin/immunology , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Thrombin/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathologyABSTRACT
OBJECTIVE: To compare pelvic floor symptoms, quality of life, and complications in women with symptomatic pelvic organ prolapse (POP) with or without vaginal pessaries in addition to those who do pelvic floor exercises for 12 months. METHODS: This was a parallel-group, single-blind, randomized controlled trial with 12 months of follow-up. Women with symptomatic stage I to stage III POP were randomized to either pelvic floor exercises training (control group) or pelvic floor exercises training and insertion of a vaginal pessary (pessary group). The primary outcome was the change of prolapse symptoms and quality of life by using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaires. Secondary outcomes included bothersome of prolapse symptoms, desired treatment, and any complications. RESULTS: From December 2011 through November 2014, 311 women were screened and 276 were randomized as follows: 137 to the control and 139 to the pessary group. One hundred thirty-two (95.0%) women in the pessary group and 128 (93.4%) in the control group completed the study. The Pelvic Organ Prolapse Distress Inventory of Pelvic Floor Distress Inventory and the Pelvic Organ Prolapse Impact Questionnaire of Pelvic Floor Impact Questionnaire scores decreased in both groups after 12 months, but the mean score differences were higher in the pessary group (Pelvic Organ Prolapse Distress Inventory: -29.7 compared with -4.7, P<.01; Pelvic Organ Prolapse Impact Questionnaire: -29.0 compared with 3.5, P<.01). Complication rates were low and similar in both groups. CONCLUSION: We provided further evidence in nonsurgical treatment for POP. Prolapse symptoms and quality of life were improved in women using a vaginal pessary in addition to pelvic floor exercises. CLINICAL TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics-Clinical Trials Registry, https://www2.ccrb.cuhk.edu.hk/web/?page_id=746, ChiCTR-TRC-11001796.
Subject(s)
Exercise Therapy/methods , Pelvic Organ Prolapse , Pessaries/adverse effects , Quality of Life , Aged , Female , Humans , Middle Aged , Pelvic Floor/physiopathology , Pelvic Organ Prolapse/diagnosis , Pelvic Organ Prolapse/physiopathology , Pelvic Organ Prolapse/psychology , Pelvic Organ Prolapse/therapy , Severity of Illness Index , Surveys and Questionnaires , Symptom Assessment/methods , Treatment OutcomeABSTRACT
OBJECTIVES: To compare the 5-year subjective and objective outcomes of transobturator tension-free vaginal tape alone versus the same procedure with concomitant pelvic floor repair surgery for pelvic organ prolapse in women with urinary stress incontinence. DESIGN: Prospective cohort study. SETTING: Urogynaecology unit at a university hospital in Hong Kong. PATIENTS: Of 218 women, 96 (44%) received transobturator tension-free vaginal tape alone and 122 (56%) received transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery from September 2004 to December 2009. The women were followed up annually for up to 5 years after the operation. MAIN OUTCOME MEASURES: The 5-year subjective and objective cure rates were assessed. Subjective cure was defined as no urine loss during physical activity and objective cure was defined as no urine leakage on coughing during urodynamic study. RESULTS: Overall, 88 women receiving transobturator tension-free vaginal tape alone and 101 women receiving transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery were followed up for 5 years after operation. The subjective and objective cure rates of the two groups were 70.5% versus 94.1% (P<0.01) and 80.3% versus 85.7% (P=0.58), respectively. CONCLUSIONS: Transobturator tension-free vaginal tape is an effective treatment for urinary stress incontinence in women who received it alone or with concomitant pelvic floor repair surgery for pelvic organ prolapse, providing high subjective and objective efficacy for up to 5 years after operation. Transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery achieved similar, if not better, long-term outcome compared with transobturator tension-free vaginal tape alone.
Subject(s)
Pelvic Floor/surgery , Pelvic Organ Prolapse/surgery , Suburethral Slings/statistics & numerical data , Urinary Incontinence, Stress/surgery , Vagina/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Adenocarcinoma/genetics , High-Throughput Nucleotide Sequencing , Uterine Cervical Neoplasms/genetics , Adenocarcinoma/pathology , Adenocarcinoma/virology , Adult , Aged , Exome , Female , Hong Kong , Humans , Middle Aged , Mutation , Neoplasm Staging , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virologyABSTRACT
Each year, â¼25â000 women are newly diagnosed with ovarian cancer in the USA. The vast majority (>90%) of cases are of epithelial origin. This highly lethal cancer carries a mortality rate of >50% and a high risk of recurrence after conventional, first-line chemotherapy. Müllerian-inhibiting substance (MIS) is a gonadal hormone that causes regression of the Müllerian ducts. A series of studies have demonstrated that MIS also has multiple extra-Müllerian functions including inhibition of epithelial ovarian cancer cells in vitro and in vivo. Accumulating evidence has shown that many human cancers are organized hierarchically and contain a small population of cancer stem cells (CSCs) that are inherently resistant to common chemotherapy and radiation therapy. The effect of MIS on ovarian CSC seems to be particularly useful in rescuing ovarian cancer patients with resistance to conventional treatment. Based on recent studies evaluating MIS, this review updates our current understanding of the molecular genetic aspects of MIS, its pathophysiology, as well as its potential to treat chemoresistant epithelial ovarian cancer.
Subject(s)
Anti-Mullerian Hormone/therapeutic use , Mullerian Ducts/drug effects , Ovarian Neoplasms/drug therapy , Animals , Female , HumansABSTRACT
OBJECTIVE: To investigate the effects of 4-month treatment of medroxyprogesterone acetate (MPA) and Diane-35 on the clinical and biochemical features of hyperandrogenism and quality of life of adolescent girls with polycystic ovarian syndrome (PCOS). DESIGN: A prospective, randomized, cross-over study. SETTING: An accredited pediatric and adolescent gynecology clinic of a university-affiliated tertiary hospital. PARTICIPANTS: 76 adolescents girls aged 14 to 19 years old with PCOS were recruited from July 2007 to July 2010. INTERVENTIONS: Girls were randomized into 2 groups. Group 1 received oral MPA for 4 months, followed by a washout period of 4 months, and then Diane-35 for another 4 months. Group 2 received the same combination but in the reverse order. MAIN OUTCOME MEASURES: Clinical and biochemical features of hyperandrogenism and quality of life were assessed. RESULTS: There was no significant difference between the 2 groups at baseline. No significant difference was found in the clinical and biochemical parameters of hyperandrogenism before and after treatment with MPA. Significant reduction of the acne score, LH/FSH ratio, and testosterone level was seen after taking Diane-35. Hirsutism was also improved but it did not reach statistical significant. When comparing post-MPA and post-Diane-35, the post-Diane-35 group had significantly improved acne score and LH/FSH ratio. No significant difference was found on quality of life between both groups after treatment. CONCLUSION: Diane-35 may be a more suitable treatment option in adolescent girls diagnosed with PCOS when compared to MPA.
Subject(s)
Androgen Antagonists/therapeutic use , Cyproterone Acetate/therapeutic use , Ethinyl Estradiol/therapeutic use , Hyperandrogenism/drug therapy , Medroxyprogesterone Acetate/therapeutic use , Polycystic Ovary Syndrome/drug therapy , Quality of Life , Acne Vulgaris/drug therapy , Adolescent , Cross-Over Studies , Drug Combinations , Female , Follicle Stimulating Hormone/blood , Hirsutism/drug therapy , Humans , Hyperandrogenism/blood , Hyperandrogenism/etiology , Luteinizing Hormone/blood , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/complications , Prospective Studies , Severity of Illness Index , Testosterone/blood , Young AdultABSTRACT
INTRODUCTION AND HYPOTHESIS: To evaluate the effect of levator ani muscle (LAM) injury on pelvic floor disorders and health-related quality of life in Chinese primiparous women during the first year after delivery. METHODS: At 8 weeks and 12 months after delivery, 328 women were assessed for symptoms of pelvic floor disorders and quality of life using the standardised questionnaire, POP-Q; and translabial ultrasound to detect LAM injury. Descriptive analysis, independent sample t test, non-parametric testing, Chi-squared test and two-sided Fisher's exact test were used. RESULTS: At 8 weeks after delivery, 48 (19.0% [95% CI, 14.2-23.8%]) women with vaginal delivery had LAM injury; 38 women (79.2%) had persistent LAM injury at 12 months. At 8 weeks, LAM injury was associated with prolapse symptoms, descent at Pelvic Organ Prolapse Quantification (POP-Q) Aa and Ba points and a higher Pelvic Organ Prolapse Distress Inventory (POPDI) general and Urinary Distress Inventory (UDI) Obstructive subscale score. At 12 months, it was not associated with prolapse symptoms, Pelvic Floor Distress Inventory (PFDI) or Pelvic Floor Impact Questionnaire (PFIQ). There was also no association between stress urinary incontinence (SUI), urge urinary incontinence (UUI), mixed urinary incontinence (UI), faecal incontinence (FI) with LAM injury at both time points. CONCLUSIONS: Seventy-nine per cent of women who had LAM injury at 8 weeks after vaginal delivery had persistent LAM injury at 12 months. LAM injury was associated with prolapse symptoms, lower POP-Q Aa and Ba points at 8 weeks after delivery and a higher POPDI general and UDI Obstructive subscale scoring. However, we are not able to confirm the association between LAM injury and SUI, UUI, mixed UI, FI at 8 weeks or 12 months after delivery; or prolapse symptoms, PFDI or PFIQ scores at 12 months after delivery.
Subject(s)
Anal Canal/injuries , Asian People , Fecal Incontinence/ethnology , Pelvic Floor/injuries , Pelvic Organ Prolapse/ethnology , Puerperal Disorders/ethnology , Urinary Incontinence/ethnology , Adult , China , Delivery, Obstetric , Female , Humans , Parity , Quality of Life , Surveys and Questionnaires , Time FactorsABSTRACT
OBJECTIVE: To assess perioperative and short-term outcomes after tension-free vaginal mesh repair of pelvic organ prolapse in local Chinese women. DESIGN: Case series. SETTING: The urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS: All women with stage III or more pelvic organ prolapse who underwent tension-free vaginal mesh repair with or without vaginal hysterectomy from May 2007 to June 2011. MAIN OUTCOME MEASURES: Perioperative and short-term outcomes. RESULTS: In all, 47 women underwent the procedure during the study period. The mean operating time was 94 minutes, the mean estimated blood loss was 163 mL, and the mean hospital stay was 4 days. Four patients had visceral injuries, all of which were identified and repaired during the operation; all four patients recovered uneventfully. The mean duration of follow-up was 25 (standard deviation, 13) months. Pelvic organ prolapse quantification improved significantly; nine (19%) of the patients had recurrent stage II prolapse but only one was symptomatic, six (13%) had postoperative mesh exposure, three of whom underwent mesh excision. There were five (11%) who had de-novo urodynamic stress incontinence, which was mostly mild and managed conservatively. Overall 91% (43/47) were satisfied with their operative outcome. CONCLUSIONS: The success rate of tension-free vaginal mesh repair for the treatment of pelvic organ prolapse in local Chinese women was comparable to rates reported internationally. There was a high degree of subjective satisfaction with the procedure. There were low rates of mesh exposure and de-novo stress incontinence that was mostly asymptomatic or mild.
Subject(s)
Hysterectomy, Vaginal , Pelvic Organ Prolapse/surgery , Surgical Mesh , Urinary Incontinence, Stress/epidemiology , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hong Kong , Humans , Middle Aged , Operative Time , Patient Satisfaction , Recurrence , Retrospective Studies , Treatment Outcome , UrodynamicsABSTRACT
AIMS: To evaluate the risk of missing a malignancy in surgical specimens following hysterectomy for uterine prolapse if routine pathological examination is not performed. Additionally, information on the risk of missing an hitherto unsuspected malignancy if uterine preservation is the preferred management option will be provided. MATERIALS AND METHODS: A retrospective study was performed on all cases of surgery performed for uterine prolapse in a tertiary referral institution from 2003 to 2011. Those with confirmed malignancy before operation were excluded. The study subjects had their clinical history, investigations, the type of operations and histopathology report analysed. They were classified into symptomatic or asymptomatic, depending on whether they reported symptoms that were suggestive of uterine malignancy. RESULTS: A total of 640 women were studied. Three cases of hitherto unsuspected uterine malignancy were found, giving an incidence of 0.47%. Among the 456 asymptomatic women, both pre- and postmenopausal, the risk of incidental malignancy was 0.22%. Within the postmenopausal group, risk of incidental malignancy was 0.26%. Another 3 cases of uterine premalignant conditions were identified, giving an overall risk of premalignant and malignant uterine condition of 0.94%. Five cases of cervical intra-epithelial neoplasia were found, contributing to a risk of 0.78%. CONCLUSIONS: The risk of missing an uterine malignancy in patients with uterine prolapse is low if appropriate investigations are carried out prior to surgery. If hysterectomy is to be performed, we recommend that all surgical specimens be subjected to histopathological examination.
Subject(s)
Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Leiomyosarcoma/pathology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Uterine Prolapse/surgery , Uterus/pathology , Adult , Aged , Aged, 80 and over , Asymptomatic Diseases , Female , Humans , Hysterectomy , Incidental Findings , Middle Aged , Retrospective StudiesABSTRACT
INTRODUCTION AND HYPOTHESIS: This study evaluated factors and their prevalence associated with urinary (UI) and fecal (FI) incontinence during and after a woman's first pregnancy. METHODS: Nulliparous Chinese women with no UI or FI before pregnancy were studied with a standardized questionnaire for UI and FI from early pregnancy until 12 months after childbirth. Maternal characteristics and obstetric data were analyzed using descriptive analysis, independent sample t test, chi-square test, and logistic regression. RESULTS: Three hundred and twenty-eight (74.2 %) women completed the study. The prevalence of antenatal UI increased with gestation. Overall, 192 (58.5 %), 60 (18.3 %), and 76 (23.1 %) had normal vaginal delivery, instrumental delivery, and cesarean section, respectively. Twelve months after delivery, prevalence of stress urinary incontinence (SUI) and urge urinary incontinence (UUI) was 25.9 % [95 % confidence interval (CI) 21.5-30.6] and 8.2 % (95 % CI 5.2-11.2), respectively. In those who delivered vaginally, the prevalence was 29.7 % and 9.1 %, respectively. Prevalence of FI was 4.0 % (95 % CI 1.9-6.1). On logistic regression, vaginal delivery [odds ratio (OR) 3.6], antenatal SUI (OR 2.8), and UUI (OR 2.4) were associated with SUI. Antenatal UUI (OR 6.4) and increasing maternal body mass index (BMI) at the first trimester (OR 1.2) were associated with UUI. Antenatal FI was associated with FI (OR 6.1). CONCLUSIONS: The prevalence of SUI, UUI, and FI were 25.9 %, 8.2 %, and 4.0 %, respectively, 12 months after delivery. Vaginal delivery, antenatal SUI, and UUI were associated with SUI; antenatal UUI and increasing maternal BMI at the first trimester were associated with UUI. Antenatal FI was associated with FI. Pregnancy, regardless of route of delivery and obstetric practice, had an effect on UI and FI.
Subject(s)
Asian People , Fecal Incontinence/epidemiology , Postpartum Period , Pregnancy Complications/epidemiology , Urinary Incontinence/epidemiology , Adult , Chi-Square Distribution , China , Fecal Incontinence/ethnology , Female , Humans , Logistic Models , Longitudinal Studies , Pregnancy , Pregnancy Complications/ethnology , Prevalence , Prospective Studies , Surveys and Questionnaires , Urinary Incontinence/ethnologyABSTRACT
Grief following miscarriage is a complex psychological response. This study was conducted to examine the psychometric properties of the Chinese version of the Perinatal Grief Scale (PGS). A total of 280 Chinese women completed the PGS immediately following a diagnosis of miscarriage (baseline) and were reassessed at 12 months follow-up. The factor structure of the Chinese PGS was explored. The convergent validity of the PGS was established by examining its correlations with the General Health Questionnaire-12 and Beck Depression Inventory at baseline. The reliability of the Chinese PGS was satisfactory. A two-factor structure accounting for 45% of the variance was identified. The Chinese PGS was positively correlated with General Health Questionnaire-12 and Beck Depression Inventory scores. The Chinese PGS was found to be a reliable and valid tool to measure grief following miscarriage.
Subject(s)
Abortion, Spontaneous/psychology , Cross-Cultural Comparison , Grief , Personality Assessment/statistics & numerical data , Psychometrics/statistics & numerical data , Adaptation, Psychological , Adult , Bereavement , Culture , Factor Analysis, Statistical , Female , Follow-Up Studies , Hong Kong , Humans , Longitudinal Studies , Prospective Studies , Social Values , Surveys and QuestionnairesABSTRACT
MicroRNAs (miRNAs) play an important role in a variety of physiological as well as pathophysiological processes, including carcinogenesis. The aim of this study is to identify a distinct miRNA expression signature for cervical intraepithelial neoplasia (CIN) and to unveil individual miRNAs that may be involved in the development of cervical carcinoma. Expression profiling using quantitative real-time RT-PCR of 202 miRNAs was performed on micro-dissected high-grade CIN (CIN 2/3) tissues and compared to normal cervical epithelium. Unsupervised hierarchical clustering of the miRNA expression pattern displayed a distinct separation between the CIN and normal cervical epithelium samples. Supervised analysis identified 12 highly differentially regulated miRNAs, including miR-518a, miR-34b, miR-34c, miR-20b, miR-338, miR-9, miR-512-5p, miR-424, miR-345, miR-10a, miR-193b and miR-203, which distinguished the high-grade CIN specimens from normal cervical epithelium. This miRNA signature was further validated by an independent set of high-grade CIN cases. The same characteristic signature can also be used to distinguish cervical squamous cell carcinoma from normal controls. Target prediction analysis revealed that these dysregulated miRNAs mainly control apoptosis signaling pathways and cell cycle regulation. These findings contribute to understanding the role of microRNAs in the pathogenesis and progression of cervical neoplasm at the molecular level.
Subject(s)
MicroRNAs/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Cell Transformation, Neoplastic/genetics , Cervix Uteri/metabolism , Disease Progression , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/pathologyABSTRACT
OBJECTIVES: To evaluate the quality of life in women with urinary incontinence (categorised by urodynamic findings). DESIGN: Prospective cohort study on patients. SETTING: Urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS. Female patients presenting to our clinic from July 2008 to December 2009 and having their urinary incontinence categorised by urodynamic study. MAIN OUTCOME MEASURES: Patient's quality of life was assessed using the Medical Outcomes Study Short Form, Urogenital Distress Inventory Short Form, and Incontinence Impact Questionnaire Short Form. Their quality of life was compared according to their urodynamic category and a subgroup analysis was performed on patients having continence surgery for urodynamic stress incontinence. RESULTS: Among the 223 women studied, 46% had urodynamic stress incontinence, 18% had detrusor overactivity, 2% had both urodynamic stress incontinence and detrusor overactivity, and 34% had no urodynamic abnormality. In all, the Medical Outcomes Study Short Form scoring was lower than normal local population. The Medical Outcomes Study Short Form score in detrusor overactivity group was significantly lower than urodynamic stress incontinence group in vitality and mental health domains. Detrusor overactivity group also had higher scores in Incontinence Impact Questionnaire Short Form in travel, social and emotional health subscales and total score (46.3 vs 29.1; P<0.01). Women with urodynamic stress incontinence and required continence surgery had higher scores in Incontinence Impact Questionnaire Short Form. CONCLUSION: Women with urinary incontinence had impaired quality of life and it was comparable to other chronic medical diseases. Women with detrusor overactivity have more impaired quality of life than women with urodynamic stress incontinence. Severity of urodynamic stress incontinence did not correlate with quality of life. Women who opted for continence surgery had poorer quality of life.
Subject(s)
Chronic Disease/psychology , Quality of Life , Urinary Incontinence/psychology , Female , Hong Kong , Humans , Middle Aged , Prospective Studies , Surveys and Questionnaires , UrodynamicsABSTRACT
OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems.
Subject(s)
Menstrual Cycle , Menstruation Disturbances/diagnosis , Menstruation Disturbances/etiology , 46, XX Disorders of Sex Development/complications , Abnormalities, Multiple , Adolescent , Adult , Anorexia Nervosa/complications , Body Mass Index , Congenital Abnormalities , Exercise , Female , Humans , Kidney/abnormalities , Logistic Models , Longitudinal Studies , Mullerian Ducts/abnormalities , Polycystic Ovary Syndrome/complications , Primary Ovarian Insufficiency/complications , Prospective Studies , Risk Factors , Somites/abnormalities , Spine/abnormalities , Stress, Psychological/complications , Surveys and Questionnaires , Time Factors , Uterus/abnormalities , Vagina/abnormalities , Weight Loss , Young AdultABSTRACT
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.
Subject(s)
DNA Helicases/genetics , Gene Expression Regulation, Neoplastic , Neoplasms, Glandular and Epithelial/genetics , Nerve Tissue Proteins/genetics , Ovarian Neoplasms/genetics , Carcinoma, Ovarian Epithelial , Case-Control Studies , Down-Regulation , Female , Humans , Middle Aged , Neoplasm Staging , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Prognosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Survival AnalysisABSTRACT
BACKGROUND: Miscarriage is common and may result in significant psychological morbidity for women. Recent research has revealed that health care professionals often tend to neglect this factor. This negligence may lead to delayed diagnosis and appropriate care. AIMS: To assess health care professionals' and patients' attitudes towards the psychological impact of miscarriage. METHODS: A prospective, cross-sectional survey of nearly 3000 subjects was conducted. Of these, 1269 were health care professionals and 1519 were pregnant women or their spouses. Their perceptions of the psychological impact of miscarriage, in comparison with postnatal depression were studied. RESULTS Health care professionals were less aware of the psychological impact of miscarriage compared with postnatal depression (91.9 vs 98.4%, P = 0.02). Furthermore, they believed that the psychological impact of miscarriage was less than that of postnatal depression (79.9 vs 88.9%, P < 0.001). However, more patients believed that psychological impact after miscarriage can seriously affect women (59.0 vs for health care professionals 38.3%, P < 0.001). A higher proportion of patients compared with health care professionals (85.2 vs 74.3%, P < 0.001) believed that routine psychological support should be provided after miscarriage, but few agreed that primary health professionals were the most suitable people to provide this care although most health care professionals thought this to be appropriate (9.1 vs 59.7%, P < 0.001). CONCLUSION: Health care professionals should be more aware of the psychological morbidity associated with miscarriage and also be sensitive to a currently unmet need for psychological care.