Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

The Significance of Mismatch Repair Deficiency in Young Patients With Endometrial Cancer.

The objective of this study was to identify the tumor characteristics associated with mismatch repair deficiency in young patients with endometrial carcinoma. Young patients (45 yr old or younger) with endometrial carcinoma treated by hysterectomy in our institution between July 2001 and June 2009 were identified. The clinical and pathologic data were obtained by review of clinical records. Among the 122 cases identified, paraffin sections were available in 67 cases for immunohistochemical staining and frozen tissue available in 62 cases for microsatellite instability (MSI) analysis. Both paraffin sections and frozen tissue were available in 36 cases. Among the 67 cases with immunohistochemical staining, 22 (32.8%) showed loss of expression of at least 1 mismatch repair protein. Defective MLH1 or MSH2 expression was associated with poor prognostic factors, including a higher incidence of pelvic lymph nodes metastasis (P=0.018) and higher stage (P=0.022) for MLH1, and an increased risk of lymphovascular permeation (P=0.015) for MSH2. On the contrary, defective MSH6 protein expression was associated with a lower incidence of high-grade tumors (P=0.04). Among the 62 cases with MSI analysis, 12 (19.4%) tumors were classified as microsatellite-high (MSI-H), whereas 2 (3.2%) were classified as microsatellite-low (MSI-L). There was no difference in the pathologic characteristics between MSI-stable and MSI-H tumor. We concluded that defective mismatch repair expression is important in young patients with endometrial carcinoma, with MSH6 protein being most commonly affected. The phenotype resulting from defective MSH6 expression was different from that caused by MLH1 or MSH2 loss.

BRCA1 deficiency induces protective autophagy to mitigate stress and provides a mechanism for BRCA1 haploinsufficiency in tumorigenesis.

Stress adaptation has profound impacts on malignant progression and response to treatment. BRCA1 is an important modulator of cellular stress, but our understanding of its mechanisms of action remains incomplete. Here we identify autophagy as an essential mechanism protecting BRCA1 deficient cancer cells from metabolic stress and allow their survival, which may underlie its significant cancer-promoting properties. We showed that targeted inhibition of endogenous BRCA1 using small interfering RNA caused significant autophagy in response to serum starvation and endoplasmic reticulum stress, whereas overexpression of BRCA1 did not, confirming that the effect was BRCA1 specific. We demonstrated that Beclin 1 was activated in BRCA1 deficient cells, suggesting involvement of a canonical pathway. Importantly, BRCA1 deficient cells were highly dependent on autophagy for survival, and rapidly underwent cell death upon disruption of autophagy. Notably, this dependence on protective autophagy extended to their tissue of origin, as ovarian surface epithelial cells from women testing positive for BRCA1 mutations, in contrast to those with no mutations, robustly induced autophagy to mitigate the stress and promote their survival. These findings highlight a novel role for BRCA1 in protective autophagy, which may make its essential contribution to tumorigenesis and prognosis.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIMS: To identify risk factors for major adverse events (AEs) and to develop a nomogram to predict the probability of such AEs in patients who have surgery for apparent early stage endometrial cancer. METHODS: We used data from 753 patients who were randomised to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analysed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6weeks of surgery and the nomogram was internally validated. RESULTS: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson's medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline Eastern Cooperative Oncology Group (ECOG) score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. CONCLUSIONS: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimise the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Assessment of knowledge and stigmatizing attitudes related to human papillomavirus among Hong Kong Chinese healthcare providers.

OBJECTIVE: To assess knowledge and stigmatizing attitudes related to human papillomavirus (HPV) and HPV testing among Chinese healthcare providers in Hong Kong. METHODS: Between May and September 2010, an anonymous self-administered questionnaire was sent to 247 doctors, nurses, and smear-taking trainees providing cervical screening in Hong Kong. RESULTS: In total, 137 questionnaires were returned. Most participants had basic knowledge about HPV infection and HPV vaccination. Only about 33% knew that high-risk HPV does not cause genital warts, infection is most common among young women, or infected individuals might not have any identifiable sexual risk factors. Regarding HPV testing, 6 of 7 knowledge items were answered incorrectly by many participants (≥ 50%), highlighting a lack of understanding of the indications for HPV testing and the implications of a positive result. About 30% of participants agreed that individuals with HPV infection were sexually easy, responsible for their infection, or had more than 1 sexual partner. More knowledge about HPV infection predicted less stigmatizing attitudes. CONCLUSION: Continued education on HPV and HPV testing is needed for frontline healthcare providers of screening in Hong Kong. The stigmatizing attitudes toward HPV-infected individuals warrant further exploration of the impact of HPV infection on patient care and interventions.

Psychological burden of testing positive for high-risk human papillomavirus on women with atypical cervical cytology: a prospective study.

OBJECTIVE: To assess the psychological burden of testing positive for high-risk human papillomavirus (HPV) on Chinese women with atypical squamous cells of undetermined significance (ASCUS). DESIGN: Prospective observational study. SETTING: Five community women's health clinics in Hong Kong. POPULATION: Ethnic Chinese women (n=299) with ASCUS who underwent reflex HPV testing (of whom 142 tested HPV negative and 157 tested HPV positive). METHODS: Women's psychological condition was assessed by self-administered questionnaires at smear result notification and by structured telephone interviews six months after notification. All women who tested positive for HPV were referred for colposcopy. MAIN OUTCOME MEASURES: State anxiety, cervical cancer worry and psychosocial burden. RESULTS: At result notification, the HPV-positive group had significantly higher state anxiety, cervical cancer worry and psychosocial burden than the HPV-negative group (all p<0.001). Irrespective of the HPV results, all outcome scores decreased over time. About 80% of the women who were HPV positive attended colposcopy as recommended. At six months, the two groups did not differ in state anxiety, cervical cancer worry, perceived risk of cervical cancer and satisfaction with intimate relationship, but psychosocial burden remained higher in the HPV-positive group (p=0.001). CONCLUSIONS: A concurrent positive HPV result intensified the distress of women with ASCUS at result notification. With time and after colposcopy, their initial heightened anxiety and cervical cancer worry were significantly lowered. However, HPV positivity may pose a prolonged psychosocial burden on women even after having had the necessary follow-up for their cervical abnormalities.

The effect of school-based cervical cancer education on perceptions towards human papillomavirus vaccination among Hong Kong Chinese adolescent girls.

OBJECTIVE: To evaluate the effects of school-based cervical cancer education on Hong Kong Chinese adolescent girls. METHODS: Adolescent girls (n=953) in local secondary schools attended a tailored educational program on cervical cancer prevention. Self-administered questionnaires were used before and after the program to measure its effects on participants' knowledge, attitude and perceived social norms towards human papillomavirus (HPV) vaccination and their intention to be HPV vaccinated. RESULTS: Before the program, HPV vaccine acceptance was favorable but relevant knowledge was low. After the program, participants had greater knowledge and a more positive attitude (both p<0.001), with more girls anticipating family (41.6% before vs. 58.9% after) and peer support (32.8% before vs. 56.9% after). There were 11.3% more girls who indicated an intention to accept the vaccine afterward. More knowledge, a more positive attitude and perceived support from significant others predicted a stronger intention to be HPV vaccinated. CONCLUSION: The educational program had a positive impact on participants' perceptions towards HPV vaccination and their intention to be vaccinated. PRACTICE IMPLICATIONS: School-based cervical cancer education is a viable means to meet the substantial educational needs of adolescents. Promotion of HPV vaccination should also include educating and influencing perceptions of families and peers.

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial.

BACKGROUND: This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Here, we present the results of stage 1. METHODS: Between Oct 7, 2005, and April 16, 2008, 361 participants were enrolled in the QoL substudy at 19 centres across Australia, New Zealand, and Hong Kong; 332 completed the QoL analysis. Randomisation was done centrally and independently from other study procedures via a computer-generated, web-based system (providing concealment of the next assigned treatment), using stratified permuted blocks of three and six patients. Patients with histologically confirmed stage I endometrioid adenocarcinoma and Eastern Cooperative Oncology Group performance status less than 2 were randomly assigned to TLH (n=190) or TAH (n=142), stratified by histological grade and study centre. Patients and study personnel were not masked to treatment assignment. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery, using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between groups in QoL change from baseline at early and late timepoints (a 5% difference was considered clinically significant). Analysis was done according to the intention-to-treat principle. Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. The LACE trial is registered with ClinicalTrials.gov, number NCT00096408. FINDINGS: Eight of 332 patients (2.4%) had treatment conversion-seven from TLH to TAH and one from TAH to TLH (patient preference). In the early phase of recovery, patients who had TLH reported significantly greater improvement in QoL from baseline compared with those who had TAH, in all subscales apart from emotional and social wellbeing. Improvements in QoL up to 6 months after surgery continued to favour TLH, except in the emotional and social wellbeing measures of FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Operating time was significantly longer in the TLH group (138 min [SD 43]) than in the TAH group (109 min [34]; p=0.001). Although the proportion of intraoperative adverse events was similar between groups (TAH eight of 142 [5.6%] vs TLH 14 of 190 [7.4%]; p=0.53); postoperatively, twice as many patients in the TAH group experienced adverse events of grade 3 or higher (33 of 142 [23.2%] vs 22 of 190 [11.6%] in the TLH group; p=0.004). Postoperative serious adverse events occurred more in the TAH group (27 of 142 [19.0%]) than in the TLH group (16 of 190 [7.9%]; p=0.002). INTERPRETATION: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favour TLH compared with TAH for treatment of stage I endometrial cancer. FUNDING: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.

De-stigmatising human papillomavirus in the context of cervical cancer: a randomised controlled trial.

OBJECTIVE: To identify the components of a human papillomavirus (HPV) message contributing to reducing the stigma of HPV in cervical cancer. METHODS: 294 ethnic Chinese women attending a community-based clinic in Hong Kong were randomly allocated to read one of three written HPV messages: Group 'lr+hrHPV': low-risk and high-risk HPVs facts, Group 'hrHPV': high-risk HPV facts only and Group 'ds+hrHPV': high-risk HPV facts and de-stigmatising components, namely being anti-stereotypical, motivational and low in complexity. Main outcome measures were high-risk HPV-related sexual stigma, knowledge, attitude towards message, and intention to be HPV-tested measured by self-administered questionnaires immediately before and after reading. RESULTS: Message allocation had a significant effect on sexual stigma (F = 5.219, p = 0.006). Participants who read message ds+hrHPV showed the least stigma, and were significantly less likely to believe that high-risk HPV infection implicated promiscuity, non-monogamy or that monogamy offered complete protection against high-risk HPV. The genital HPV-focused message was more stigmatising than cervical cancer-focused messages. Of all participants, 93% (237/254) and 97% (260/269) indicated a positive intention to be HPV-tested before and after reading, respectively. There were no between-group differences noted in terms of knowledge and intention to be HPV-tested before or after reading. CONCLUSIONS: Our findings show that an HPV message containing specific de-stigmatising components may reduce public stigma towards high-risk HPV. Also, focusing solely on high-risk HPV in the context of cervical cancer helps to avoid the stigmatising effect of genital warts from tainting perceptions about high-risk HPV infection.

Coexistence of struma ovarii with marked ascites and elevated CA-125 levels: case report and literature review.

INTRODUCTION: Struma ovarii is a rare form of ovarian neoplasm and consists mainly of thyroid tissue. Ascites has been reported in approximately one-third of all the cases. However, the combination of struma ovarii and elevated CA-125 has rarely been reported. MATERIALS AND METHODS: We described a case of benign struma ovarii, presenting with the clinical features of ovarian cancer: large complex pelvic mass, gross ascites and markedly elevated serum CA-125 levels. Surgical excision of the ovarian mass was followed by rapid resolution of the ascites and reduction of the serum CA-125 level. CONCLUSION: Struma ovarii can mimic ovarian malignancy clinically, when presented with ascites and an elevated CA-125 level.

Promoter methylation of death-associated protein kinase and its role in irradiation response in cervical cancer.

This study was aimed at investigating the death-associated protein kinase (DAPK) promoter methylation and its clinical relevance in cervical cancer. The DAPK promoter methylation was detected by methylation-specific PCR (MSP) and correlated with DAPK mRNA and protein expression. The effect of DAPK expression on the radiosensitivity of the cervical cancer cell line was assessed by overexpressing DAPK in the radioresistant cell line SiHa. DAPK hypermethylation was found in 56.08% of the cervical cancer samples and was associated with the tumor histological cell type of squamous cell carcinoma (p=0.002) and advanced tumor stage (p=0.005). Subsequently, DAPK protein expression was found to significantly decrease in cervical cancer samples when compared to normal tissues. The DAPK mRNA and protein expression levels were absent or remarkably reduced in SiHa and HeLa in which the DAPK promoter was hypermethylated. The expression levels of DAPK could be restored after demethylation treatment with 5-aza-2'-deoxycytidine. Overexpressing DAPK in vitro had no significant influence to the survival of the radioresistant SiHa cell after being challenged by irradiation. Our findings suggest that DAPK might not directly be responsible for the cellular radiosensitivity, however, DAPK hypermethylation appeared to be of prognostic significance in the advanced stages of cervical cancer.

Relapsed gestational trophoblastic neoplasia: A 20-year experience.

OBJECTIVE: To review relapsed gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Patients who had relapsed GTN between 1978 and 2001 at Queen Mary Hospital were included in the study. Records were reviewed and data analyzed regarding treatment, follow-up and survival. RESULTS: Eighteen patients with relapsed GTN were identified. Patients' ages ranged from 21 to 56 years, with a median of 34. Eight were classified as low risk, 1 as medium risk and 9 as high risk at the time of diagnosis. Seven, 3 and 8 patients were treated with single-, dual- and multiple-agent chemotherapy, respectively. The median interval between remission and relapse was 6.5 months (range, 1-132). The time interval to relapse did not correlate with patient mortality (Mann-Whitney U test, p = 0.873). Four patients died of the disease, and all of them were classified and treated as low risk at the time of diagnosis. Three were lost to follow-up at some point. The remaining patient had relapsed choriocarcinoma and developed progressive disease despite intensive multiple-modality treatment. The overall survival rate for relapsed GTN was 77.8%. CONCLUSION: Patients with relapsed GTN are salvageable. Failure of treatment seems attributable to patients who defaulted treatment or follow-up and presented late with massive disease.

Methotrexate, bleomycin, and Etoposide in the treatment of gestational trophoblastic neoplasia.

OBJECTIVE: The combination of methotrexate (1 g/m(2) day 1), bleomycin (10 mg day 3), and etoposide (100 mg/m(2) days 1-5) (MBE) has been used for disease relapse or as a second-line chemotherapy in the treatment of gestational trophoblastic neoplasia (GTN) resistant to multiple-agent chemotherapy. With the identification of ultra-high-risk GTN, MBE has also been used as first-line chemotherapy. The current study is to review the use of MBE in the treatment of GTN. METHODS: Patients who received MBE for GTN between 1985 and 2003 in Queen Mary Hospital were included in this study. Records were reviewed and data were analyzed. Outcomes including response rate, treatment complications, and survival were assessed. RESULTS: Methotrexate, bleomycin, and etoposide therapy was given as first line to 4 patients with ultra-high-risk GTN. Three responded to the treatment and remained disease free. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who had drug resistance to the initial therapy. Seven responded, and 6 remained disease free at 5 years. Methotrexate, bleomycin, and etoposide were given as a second-line therapy to 8 patients who relapsed 2-18 months after their initial therapy. Seven patients responded, and 4 remained disease-free at 5 years, 2 defaulted, and one died of carcinoma of the colon. Of the 20 patients who received MBE, 12 developed grade 3/4 neutropenia, and 4 developed grade 3/4 thrombocytopenia. The overall response rate for MBE was 85%. CONCLUSION: Methotrexate, bleomycin, and etoposide should be considered as a second-line therapy in patients who have drug-resistant or recurrent GTN.

Hepatic arteriogram for gestational trophoblastic tumor: is it useful?

The presence of liver metastasis will be staged as IV in the FIGO 1992 Gestational Trophoblastic Tumor (GTT) staging. This study was to determine the role of hepatic arteriogram (HAG) in the management of GTT. It is a retrospective analysis of 309 patients treated from 1981 to 2001. Patients were restaged according to the FIGO 1992 classification with or without taking into account the HAG result. Outcome measures including mortality, drug resistance and recurrence of disease, as well as treatment with and without the HAG result were compared. Eighty-one (26.2 percent) patients had HAG and 11 (3.6 percent) also had ultrasound (USG) features of liver metastasis. Interval between diagnosis and treatment were significantly different between USG and HAG positive groups (Mann-Whitney U test, P < 0.05). Seventeen (5.5 percent) of the 309 patients died of the disease and 7 (41.2 percent) of them had liver metastasis. Three (27.3 percent) of the 11 patients who had USG features of liver metastasis died of the disease; mortality is significantly higher than those without USG features of metastasis (Chi-square test, P < 0.05). Patients classified as medium to high risk with or without taking HAG as a feature of liver metastasis were associated with higher mortality and recurrent rate (Chi-square test, P < 0.05). On the other hand, the chance of drug resistance was higher in the medium to high risk group after reclassifying all HAG positive patients as negative for liver metastasis (Chi-square test, P < 0.05). HAG evidence of liver metastasis did not correlate with patient mortality. HAG was not an appropriate investigation in the management of GTT.

p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy.

Apoptosis is one of the causes of cell death in cervical cancer following radiotherapy. By studying the gene expression profile with cDNA apoptotic array, the p73 gene was found overexpressed in radiosensitive cervical cancers when compared with radioresistant ones. To investigate the role of the p73 gene in relation to clinical assessment of radiosensitivity in cervical cancer based on the findings of residual tumor cells in cervical biopsies after completion of radiotherapy, we studied the protein expression of p73 in 59 cervical cancers after radiotherapy and 68 normal cervices using immunohistochemistry. The expression of p73 was found to be significantly increased in cancer samples and, more importantly, in those samples sensitive to radiotherapy (P < 0.001). The overexpression of p73 actually predicted a better prognosis in cervical cancer patients (P < 0.001). To investigate the possible involvement of p73 downstream genes, the protein expressions of p21 and Bax were studied. The expression of p21, but not Bax, was found to be positively correlated with the expression of p73 (P = 0.001). Furthermore, the epigenetic regulation of p73 expression via DNA methylation was also investigated in 103 cervical cancers and 124 normals. Hypermethylation of p73 gene was observed in 38.8% of cervical cancers, and it was significantly associated with reduced or absent p73 expression (P < 0.001). Reactivation of p73 expression in two cervical cancer cell lines by demethylation treatment supported the role of methylation in the regulation of p73 expression. Our findings suggested that p73 expression was related to the radiosensitivity of cervical cancer cells and may play an important role in the regulation of cellular radiosensitivity.

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women.

OBJECTIVE: To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. RESEARCH DESIGN AND METHODS: A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. RESULTS: The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. CONCLUSIONS: Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.