Panhellenic Association for Continual Medical Research PACMeR

Athens, Greece

Panhellenic Association for Continual Medical Research PACMeR

Athens, Greece
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Polyzos N.P.,University of Thessaly | Polyzos N.P.,Panhellenic Association for Continual Medical Research PACMeR | Mauri D.,Sections of Obstetrics and Gynaecology | Mauri D.,Panhellenic Association for Continual Medical Research PACMeR | And 6 more authors.
International Journal of Gynecological Cancer | Year: 2010

Introduction: Hysteroscopy is a diagnostic procedure with a high accuracy in diagnosing endometrial cancer. Because of the increase of intrauterine pressure during distention media inflation, several retrospective studies postulated that it may result in cancer cell dissemination within the peritoneal cavity through the fallopian tubes. We therefore set to estimate whether hysteroscopy increases the risk for intraperitoneal cancer cell dissemination in patients with endometrial cancer and the risk of disease upstaging in patients with clinically early-stage disease. Methods: We searched the PubMed, the ISI Web of Science, and the Cochrane Library through July 2009. Eligible trials were all controlled clinical trials in which patients were allocated to hysteroscopy (alone or after other diagnostic procedure, eg, dilation and curettage and biopsy) versus any other diagnostic procedure except hysteroscopy or no procedure before surgery for endometrial carcinoma. Results: Nine trials were included in our analysis. One thousand fifteen patients with histologically proven endometrial carcinoma were allocated to hysteroscopy or no hysteroscopy before surgery. Hysteroscopy resulted in a significantly higher rate of malignant peritoneal cytology (odds ratio [OR], 1.78;95% confidence interval [CI], 1.13-2.79;P = 0.013) and significantly higher disease upstaging owing solely to the presence of malignant cells in the peritoneal cavity (OR, 2.61;95% CI, 1.47-4.63;P = 0.001) compared with no hysteroscopy. When isotonic sodium chloride was used as distention medium, hysteroscopy resulted in a statistically significant higher rate of malignant peritoneal cytology (OR, 2.89;95% CI, 1.48-5.64;P = 0.002), whereas a nonsignificant trend for higher malignant cells was observed in patients allocated to the hysteroscopy group (OR, 3.23;95% CI, 0.94-11.09;P = 0.062) when inflated media pressure reached or exceeded 100 mm Hg. Conclusions: Hysteroscopy in patients with endometrial cancer hints a risk for cancer cell dissemination within the peritoneal cavity. Prospective and sufficiently powered trials are needed to clarify whether the risk of cancer cell spreading is correlated with worse prognosis. Copyright © 2010 by IGCS and ESGO.


Papanikolaou E.G.,Aristotle University of Thessaloniki | Humaidan P.,Skive Regional Hospital | Polyzos N.P.,Panhellenic Association for Continual Medical Research PACMeR | Tarlatzis B.,Aristotle University of Thessaloniki
Seminars in Reproductive Medicine | Year: 2010

Ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication of ovarian stimulation for assisted reproduction, is a potentially life-threatening condition. Exogenous human chorionic gonadotropin (hCG) administered for final oocyte maturation and endogenous hCG produced by a developing pregnancy are fundamental in the development of the disease. Vascular endothelial growth factor is the key molecule mediating the pathophysiology of the syndrome, and genetic predisposition might play a role. Because the most severe cases are usually the late OHSS cases that occur when a pregnancy is established, several predictive markers have been introduced to identify the high-risk patient profile and consequently develop preventive strategies. This article reviews the most recent evidence evaluating the accuracy of different OHSS prediction parameters. Stratification was attempted according to the phase of the ovarian stimulation that the patients undergo. Anti-Müllerian hormone and the number of follicles seen on ultrasound seem promising discriminating factors, whereas prediction models that include age, antral follicle count, and estrogen levels on the day of ovulation triggering provide variable sensitivity and specificity. Until reliable genetic tests are available, and considering that the occurrence of pregnancy is unpredictable, the use of prognostic factors will be mainly indicative of risk rather than preventive of OHSS. Copyright © 2010 by Thieme Medical Publishers, Inc.


Valachis A.,Central Hospital of Eskilstuna | Tsali L.,General Hospital of Lamia | Tsali L.,Aristotle University of Thessaloniki | Pesce L.L.,University of Chicago | And 5 more authors.
Obstetrical and Gynecological Survey | Year: 2010

Background: An increased number of women are expected to conceive after the diagnosis of early breast cancer. Most physicians recommend that pregnancy be delayed by 2 to 3 years after diagnosis of early breast cancer, but this recommendation is based on data from trials with small patient cohorts. Furthermore, a healthy mother effect (HME) selection bias may be operative in most of these studies, because women undergoing childbearing after treatment were healthier when compared with the control group. AIM:: To perform a systematic review and meta-analysis of published trials corrected for HME bias so as to assess the effect of pregnancy (at least 10 months after diagnosis) versus no pregnancy on overall survival of primary breast cancer patients less than 45 years. METHODS:: We searched MEDLINE and Thomson Reuters (ISI) Web of Knowledge for eligible studies. From each study we extracted the relative hazard ratio or, if not provided, all the necessary data to impute it. In cases where the duration from diagnosis to pregnancy was not reported, we extracted relevant data to estimate it. RESULTS:: Our electronic search strategy yielded 1623 hits pertaining to 20 potentially eligible studies involving 49,370 premenopausal breast cancer patients. Ten studies were eligible after considering HME potential bias in matching controls. Among these, 9 studies (pregnant 1089, matched-controls 13051) contained data appropriate for analysis. Overall survival was statistically higher among patients who became pregnant compared to controls: fixed effect model estimated pooled hazard ratio for death 0.51 (95% confidence interval: 0.42-0.62). No study heterogeneity was observed: Q = 10.4, P = 0.17; I = 48%. Conclusion: The pooled available evidence indicates that in early breast cancer patients, pregnancy that occurs at least 10 months after diagnosis does not jeopardize prognosis and may actually confer significant survival benefit. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completing this CME activity, physicians should be better able to assess the effect pregnancy has on long-term survival in primary breast cancer patients under age 45; counsel patients on the safety of pregnancy after breast cancer diagnosis and treatment; and interpret how pregnancy may be associated with improved breast cancer survival. Copyright © 2011 by Lippincott Williams & Wilkins.


Humaidan P.,University of Southern Denmark | Papanikolaou E.G.,Aristotle University of Thessaloniki | Kyrou D.,Aristotle University of Thessaloniki | Alsbjerg B.,Skive Regional Hospital | And 3 more authors.
Reproductive BioMedicine Online | Year: 2012

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid concentrations and consecutive inhibition of LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis. With the introduction of the gonadotrophin-releasing hormone-(GnRH) antagonist, an alternative to human chorionic gonadotrophin triggering of final oocyte maturation is the use of GnRH agonist (GnRHa) which reduces or even prevents ovarian hyperstimulation syndrome (OHSS). Interestingly, the current regimens of luteal support after HCG triggering are not sufficient to secure the early implanting embryo after GnRHa triggering. This review discusses the luteal-phase insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates. Stimulation of the ovaries for IVF treatment induces the growth of multiple follicles, resulting in the aspiration of several oocytes. During the early years of IVF treatment it became obvious that the stimulation per se induced an unphysiological hormonal level during the luteal phase - the phase after egg transfer - necessitating hormonal support with vaginally applied progesterone to obtain ongoing pregnancies. With the introduction of the gonadotrophin- releasing hormone (GnRH) antagonist protocol (short protocol) it became possible to perform final oocyte maturation with a GnRH agonist instead of human chorionic gonadotrophin (HCG). The first studies applying this concept, however, showed a very poor pregnancy rate, despite standard luteal-phase support with progesterone. This review discusses the reason for the poor results and the newest studies, using GnRH agonist instead of HCG, now showing a normalization of pregnancy rates due to modifications of the luteal-phase support and with the benefit of a protocol which has a reduced risk of ovarian hyperstimulation syndrome. © 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.


Polyzos N.P.,Vrije Universiteit Brussel | Polyzos N.P.,University of Thessaly | Polyzos N.P.,Panhellenic Association for Continual Medical Research PACMeR | Valachis A.,Panhellenic Association for Continual Medical Research PACMeR | And 5 more authors.
Human Reproduction | Year: 2011

BACKGROUND: Treatment decisions should ideally be based on well-designed randomized controlled trials (RCTs). Here we determine the rate of full publication of RCTs presented at annual meetings of the European Society of Human Reproduction and Embryology (ESHRE), identify potential bias against publishing non-significant results and results not favoring the experimental arm, quantify this bias in case it exists, and identify factors associated with time to publication. Methods RCTs presented at ESHRE meetings 2003 and 2004 were recorded. Subsequent search in Medline, Cochrane Library and EMBASE was performed through December 2010 to identify full-text publication in a peer-review journal. Results Among 155 abstracts describing RCTs 89 (57%) were published in full-text in a peer-review journal. Median time from presentation to publication was 15 months (range: 0-75). In bivariate analysis, only type of presentation and presence of outcomes favoring the experimental arm were related to publication rate. Studies presented orally or reporting a positive outcome in favor of the experimental arm were more likely to be published (P = 0.018 and 0.014, respectively). Results were consistent in a multivariable logistic regression, with odds ratio (OR) 2.51 [95 confidence interval (CI), 1.25-5.03] for oral versus poster presentations and OR 2.46 (95% CI, 1.23-4.95) for trials favoring versus not favoring the experimental arm. Kaplan-Meier curves revealed time to publication was shorter for oral presentations (log-rank test = 0.013) and trials favoring the experimental arm, compared with all others (log rank = 0.007). CONCLUSIONS RCTs with significant results in favor of the experimental arm are more likely to be published and are published sooner. Publication bias in reproductive medicine is a fact. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Kamposioras K.,Panhellenic Association for Continual Medical Research PACMeR | Kamposioras K.,University General Hospital Attikon | Pentheroudakis G.,University of Ioannina | Pectasides D.,University General Hospital Attikon | Pavlidis N.,University of Ioannina
Critical Reviews in Oncology/Hematology | Year: 2011

Introduction: Although more than 90% of melanomas have a cutaneous origin, occasionally it is discovered as a secondary deposit without evident primary site. The aim of this study was to systematically review published literature and analyse data on incidence, presentation, therapeutic interventions, survival and prognostic factors. Methods: We searched MEDLINE, (search terms Melanom*, unknown origin, unknown primary, indolent, occult) and the abstracts from major congresses of the last 4 years and perused the references of the retrieved relevant articles. Results: 4348 patients with MUP were reported along with 132,. 643 patients with Melanoma of Known Primary (MKP). The incidence of MUP was 3.2%. The male to female ratio was 2:1 while the age peak was in the 4th and 5th decades. MUP patients harbouring nodal disease had a median overall survival ranging between 24 and 127 months, 5-year survival rate between 28.6% and 75.6% and 10-year survival rate between 18.8% and 62.9%. MUP patients with visceral disease had median survival times between 3 and 16 months, and 5-year survival rates between 5.9% and 18%. Presence of tumour regression in metastatic sites and low nodal burden were associated with favourable outcome. Potentially curative surgical treatment offered survival advantage in comparison to patients with residual metastatic foci. MUP patients who received adjuvant chemotherapy or radiotherapy paradoxically seemed to fare worse compared to patients observed. Conclusions: This is the first review to bring together the information of 89 years and to analyze all the potential information accumulated. Although a well know entity no consensus is reached in order to describe MUP presentation, management or prognosis. © 2010 Elsevier Ireland Ltd.


Mauri D.,General Hospital of Lamia | Mauri D.,Panhellenic Association for Continual Medical Research PACMeR | Kamposioras K.,Panhellenic Association for Continual Medical Research PACMeR | Tsali L.,General Hospital of Lamia | And 9 more authors.
Cancer Treatment Reviews | Year: 2010

Background: Taxanes have been extensively tested in patients with advanced breast cancer, but it is unclear whether their weekly use might offer any benefits against standard every three weeks administration. We therefore performed a meta-analysis of randomized controlled trials that compared weekly and every three weeks taxanes regimens in advanced breast cancer. Methods: The endpoints that we assessed were objective response rate, progression free survival (PFS) and overall survival. Efficacy data for paclitaxel and docetaxel were separately analyzed. Trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. Results: Οbjective response rate was notably better when paclitaxel was used as every three weeks regimen (7 studies, 1772 patients, fixed effect model pooled RR 1.20 95%CI 1.08-1.32 p < 0.001). No difference were found for PFS (6 studies, 1610 patients, random effect model HR 1.02, 95%CI 0.81-1.30 p = 0.860); while OS was statistically higher among patients receiving weekly paclitaxel (5 studies, 1471 patients, fixed effect model pooled HR 0.78, 95%CI 0.67-0.89 p = 0.001). No differences were observed for the weekly compared to the every three weeks use of docetaxel either for objective response, PFS and OS. Overall, the incidence of serious adverse events, neutropenia, neutropenic fever, and peripheral neuropathy were significantly lower in weekly taxanes schedules. The incidence of nail changes and epiphora were significantly lower in the every three weeks docetaxel regimens. Conclusions: Use of paclitaxel in weekly regimen give overall survival advantages compared with the standard every three weeks regimen. The observed survival benefit does not seem to stem from an increased potency of the drug with weekly regimens. The use of weekly paclitaxel regimens is therefore recommended for the treatment of locally advanced/metastatic breast cancer. © 2009 Elsevier Ltd. All rights reserved.


Valachis A.,General Hospital of Eskilstuna | Valachis A.,Uppsala University | Polyzos N.P.,Vrije Universiteit Brussel | Polyzos N.P.,Panhellenic Association for Continual Medical Research PACMeR | And 10 more authors.
Oncologist | Year: 2013

Background. The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I-III) breast cancer. Materials and Methods. We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes. Results. Fifteen studieswereconsidered eligibleandwerefurther analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR,0.86;95%CI, 0.70-1.06)orincidenceofbonemetastases(sevenstudies,7,543patients;oddsratio[OR],0.94;95%CI, 0.64-1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%. Conclusion. Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment. © AlphaMed Press 2013.


Mauri D.,General Hospital of Lamia | Mauri D.,Panhellenic Association for Continual Medical Research PACMeR | Valachis A.,Panhellenic Association for Continual Medical Research PACMeR | Valachis A.,University of Crete | And 5 more authors.
JNCCN Journal of the National Comprehensive Cancer Network | Year: 2010

To address whether the use of bisphosphonates in the adjuvant setting of breast cancer might have any effect on the natural course of the disease, a meta-analysis was conducted of published and unpublished randomized controlled trials found in PubMed, the Cochrane Central Register of Controlled Trials, the ISI Web of Knowledge, and abstracts of major international conferences up to January 2009. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with any bisphosphonate versus non-use were considered eligible. Analysis included data from 13 eligible trials involving 6886 patients randomized to treatment with bisphosphonates (n = 3414) or either placebo or no treatment (n = 3472). Compared with no use, adjuvant breast cancer treatment with bisphosphonates did not reduce the overall number of deaths (odds ratio [OR], 0.708; 95% Cl, 0.482-1.041; P = .079), bone metastases (OR, 0.925; 95% Cl, 0.768-1.114; P = .413), overall disease recurrences (OR, 0.843; 95% Cl, 0.602-1.181; P = .321), distant relapse (OR, 0.896; 95% Cl, 0.674-1.192; P = .453), visceral recurrences (OR, 1.051; 95% Cl, 0.686-1.609; P = .820), or local relapses (OR, 1.056; 95% Cl, 0.750-1.487; P = .756). No significant heterogeneity was observed among the trials except for estimates of deaths and disease recurrences (P = .034 and P = .016, respectively). In subgroup analyses, use of zoledronic acid was associated with a statistically significant lower risk for disease recurrence (OR, 0.675; 95% Cl, 0.479-0.952; P = .025). However, these results should be interpreted with caution because the statistical significance for this association was weak and might be attributed to chance from multi-test analyses. Use of zoledronic acid was not associated with any significant difference in death (OR, 0.642; 95% Cl, 0.388-1.063) and bone metastasis rates (OR, 0.661; 95% Cl, 0.379-1.151). Currently available evidence does not support the hypothesis that use of bisphosphonates in adjuvant treatment of early breast cancer will alter the natural course of the disease. Nonetheless, a nonsignificant trend seems to exist for better outcomes in patients undergoing bisphosphonate treatment. Until further evidence from new clinical trials becomes available, adjuvant bisphosphonates should not be recommended routinely. © Journal of the National Comprehensive Cancer Network.


Polyzos N.P.,Panhellenic Association for Continual Medical Research PACMeR
BMJ (Clinical research ed.) | Year: 2010

To examine whether treatment of periodontal disease with scaling and root planing during pregnancy is associated with a reduction in the preterm birth rate. Systematic review and meta-analysis of randomised controlled trials. Cochrane Central Trials Registry, ISI Web of Science, Medline, and reference lists of relevant studies to July 2010; hand searches in key journals. Randomised controlled trials including pregnant women with documented periodontal disease randomised to either treatment with scaling and root planing or no treatment. Data were extracted by two independent investigators, and a consensus was reached with the involvement a third. Methodological quality of the studies was assessed with the Cochrane's risk of bias tool, and trials were considered either high or low quality. The primary outcome was preterm birth (<37 weeks). Secondary outcomes were low birthweight infants (<2500 g), spontaneous abortions/stillbirths, and overall adverse pregnancy outcome (preterm birth <37 weeks and spontaneous abortions/stillbirths). 11 trials (with 6558 women) were included. Five trials were considered to be of high methodological quality (low risk of bias), whereas the rest were low quality (high or unclear risk of bias). Results among low and high quality trials were consistently diverse; low quality trials supported a beneficial effect of treatment, and high quality trials provided clear evidence that no such effect exists. Among high quality studies, treatment had no significant effect on the overall rate of preterm birth (odds ratio 1.15, 95% confidence interval 0.95 to 1.40; P=0.15). Furthermore, treatment did not reduce the rate of low birthweight infants (odds ratio 1.07, 0.85 to 1.36; P=0.55), spontaneous abortions/stillbirths (0.79, 0.51 to 1.22; P=0.28), or overall adverse pregnancy outcome (preterm births <37 weeks and spontaneous abortions/stillbirths) (1.09, 0.91 to 1.30; P=0.34). Treatment of periodontal disease with scaling and root planing cannot be considered to be an efficient way of reducing the incidence of preterm birth. Women may be advised to have periodical dental examinations during pregnancy to test their dental status and may have treatment for periodontal disease. However, they should be told that such treatment during pregnancy is unlikely to reduce the risk of preterm birth or low birthweight infants.

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