To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) ...levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis.
Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4-EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated.
Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort.
We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.
Bladder profile in boys with Posterior Urethral Valves can be very varied with a spectrum going from high pressure, unstable, hypocompliant small bladders to hypercompliant, large acontractile ...bladders, with some being near-normal. Our question was whether appearance, specifically of the bladder, on initial VCUG was correlated to prenatal features and whether it could predict early postnatal outcome.
We used a prospectively gathered database of boys with prenatally suspected PUV. We analyzed whether the appearance, specifically of the bladder, was related to date of prenatal diagnosis, presence of a megacystis on prenatal ultrasound, presence of vesico-ureteral reflux (VUR), presence of abnormal DMSA scan, nadir creatinine or presence of febrile urinary tract infection (fUTI) during the first two years of life.
The database comprised 90 cystograms. 15% of bladders were judged normal/regular, 54 % were small/diverticular and 31% were large/diverticular. Bladder appearance was not associated with presence of prenatal megacystis, abnormal DMSA scan, VUR, nor rate of fUTI. The only significant associations were normal/regular bladder and early prenatal diagnosis (
= 0.04) and normal/regular bladder and elevated nadir creatinine (>75µmol/l) (
= 0.01).
We believe that when focusing solely on the appearance of the bladder, excluding information about the urethra and presence of reflux, the cystogram alone is insufficient to inform on future bladder function. This could be used as an argument in favor of performing early urodynamics in this population.
Carcinoma of the Cervix Uteri QUINN, MA; BENEDET, JL; ODICINO, F ...
International journal of gynecology and obstetrics,
November 2006, Letnik:
95, Številka:
S1
Journal Article
Abstract The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the ...mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51 Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p = 0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.
In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the ...quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs’ results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16–26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%–99·8%). Bridging efficacy was demonstrated for males and females aged 9–15 years and males aged 16–26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.
Carcinoma of the Corpus Uteri CREASMAN, WT; ODICINO, F; MAISONNEUVE, P ...
International journal of gynecology and obstetrics,
November 2006, Letnik:
95, Številka:
S1
Journal Article
Abstract Objective The aim of this study was to evaluate the outcome benefit of follow-up protocols for patients with recurrent endometrial and cervical cancer. Methods A retrospective review on ...patients primarily treated at the Division of Gynecologic Oncology, University of Brescia, was performed. We focused our attention on recurrent patients and we evaluated the pattern of relapse and the presence of symptoms or signs of disease at recurrence and evidence of disease on routine follow-up test or visits. Results The vast majority of recurrences occurred within the first 3 years after primary treatment (78% and 87% in endometrial and cervical cancers, respectively). A better overall survival from relapse was observed when vaginal relapse was compared to other sites in endometrial cancer patients and when pelvic recurrence was compared to distant sites in cervical cancer cases. Recurrent endometrial and cervical cancer patients were symptomatic in 52% and 65% of cases, respectively. Among asymptomatic recurrent endometrial cancer cases, pelvic examination, abdominal or pelvic ultrasound and CT could detect 92% of relapses, while the vast majority of cervical cancer relapses could be diagnosed by pelvic examination and/or CT (85%). Conclusion Endometrial cancer patients showed a significantly better prognosis when the recurrence was detected during follow-up visits, thus supporting the real advantage of our surveillance programs, while no statistically significant differences were found in survival of cervical cancer patients between the symptomatic and the asymptomatic group.
Background: All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant ...chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging. Methods: Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan–Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were two-sided. Results: After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio HR = 0.69, 95% confidence interval CI = 0.44 to 1.08; P = .10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P = .02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 95% CI = 1.08 to 4.96; P = .03 and HR = 1.82 95% CI = 1.02 to 3.24 P = .04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 95% CI = 1.04 to 2.95; P = .03 and HR = 1.78 95% CI = 1.15 to 2.77; P = .009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen. Conclusion: Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.
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