ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ ΗΤΑΝ ΝΑ ΑΞΙΟΛΟΓΗΘΕΙ Ο ΣΥΝΔΥΑΣΜΟΣ ΤΟΥ ΠΡΟΣΔΙΟΡΙΣΜΟΥ ΤΟΥ CA-125 ΣΤΟΝ ΟΡΟ ΤΟΥ ΑΙΜ... more ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ ΗΤΑΝ ΝΑ ΑΞΙΟΛΟΓΗΘΕΙ Ο ΣΥΝΔΥΑΣΜΟΣ ΤΟΥ ΠΡΟΣΔΙΟΡΙΣΜΟΥ ΤΟΥ CA-125 ΣΤΟΝ ΟΡΟ ΤΟΥ ΑΙΜΑΤΟΣ, ΤΗΣ ΓΥΝΑΙΚΟΛΟΓΙΚΗΣ ΕΞΕΤΑΣΗΣ ΚΑΙ ΤΟΥ ΥΠΕΡΗΧΟΓΡΑΦΗΜΑΤΟΣ ΣΤΗΝ ΠΡΩΙΜΗ ΑΝΙΧΝΕΥΣΗ ΤΟΥ ΚΑΡΚΙΝΟΥ ΤΩΝ ΩΟΘΗΚΩΝ. ΤΟ ΥΛΙΚΟ ΤΗΣ ΜΕΛΕΤΗΣ ΑΠΟΤΕΛΕΣΑΝ 1500 ΑΣΥΜΠΤΩΜΑΤΙΚΕΣ ΓΥΝΑΙΚΕΣ ΗΛΙΚΙΑΣ > 45. ΟΛΕΣ ΟΙ ΓΥΝΑΙΚΕΣ ΥΠΟΒΛΗΘΗΚΑΝ ΣΕ ΓΥΝΑΙΚΟΛΟΓΙΚΗ ΕΞΕΤΑΣΗ ΚΑΙ ΠΡΟΣΔΙΟΡΙΣΜΟ ΤΟΥ CA-125 ΣΤΟΝ ΟΡΟ ΤΟΥ ΑΙΜΑΤΟΣ. ΟΙ ΓΥΝΑΙΚΕΣ ΜΕ ΠΑΘΟΛΟΓΙΚΗ Η "ΑΜΦΙΒΟΛΗ" ΓΥΝΑΙΚΟΛΟΓΙΚΗ ΕΞΕΤΑΣΗ ΚΑΘΩΣ ΚΑΙ ΕΚΕΙΝΕΣ ΜΕ CA-125 > 35 U/ML ΥΠΟΒΑΛΛΟΤΑΝ ΣΕ ΥΠΕΡΗΧΟΓΡΑΦΗΜΑ ΚΑΙ ΑΝΑΛΟΓΑ ΜΕ ΤΑ ΕΥΡΗΜΑΤΑ ΣΕ ΠΕΡΑΙΤΕΡΩ ΧΕΙΡΟΥΡΓΙΚΗ ΔΙΕΡΕΥΝΗΣΗ. ΑΠΟ ΤΙΣ 1500 ΓΥΝΑΙΚΕΣ, 18 ΕΙΧΑΝ CA-125 > 35 U/ML ΑΠΟ ΤΙΣ ΟΠΟΙΕΣ ΟΙ 12 ΕΙΧΑΝ ΑΡΝΗΤΙΚΗ. ΑΠΟ ΤΙΣ 180 ΓΥΝΑΙΚΕΣ ΠΟΥ ΕΚΑΝΑΝ ΥΠΕΡΗΧΟΓΡΑΦΗΜΑ ΟΙ 16 ΕΙΧΑΝ ΘΕΤΙΚΟ ΚΑΙ ΟΙ 165 ΕΙΧΑΝ CA-125 > 35 U/ML. ΜΕΤΑ ΤΗΝ ΟΛΟΚΛΗΡΩΣΗ ΤΟΥ ΕΛΕΓΧΟΥ ΚΑΙ ΜΕ ΤΗΝ ΧΕΙΡΟΥΡΓΙΚΗ ΔΙΕΡΕΥΝΗΣΗ 15 ΓΥΝΑΙΚΩΝ, ΑΝΙΧΝΕΥΘΗΚΑΝ ΜΙΑ ΠΕΡΙΠΤΩΣΗ ΟΡΩΔΟΥΣ ΚΥΣΤΑΔΕΝΟΚΑΡΚΙΝΩΜΑΤΟΣ ΩΟΘΗΚΗΣ ΣΤΑΔΙΟΥ ΙΑ, ΜΙΑ ΠΕΡΙΠΤΩΣΗ ΟΓΚΟΥ ΩΟΘΗΚΗΣ ΟΡΙΑΚΗΣ ΚΑΚΟΗΘΕΙΑΣ ΣΤΑΔΙΟΥ ΙΑ ΚΑΙ ΜΙΑ ΠΕΡΙΠΤΩΣΗ ΜΕΤΑΣΤΑΤΙΚΟΥ ΚΑΡΚΙΝΩΜΑΤΟΣ ΩΟΘΗΚΗΣ.
: Ovarian cancer is an aggressive disease and only a few cases are diagnosed at early stages due ... more : Ovarian cancer is an aggressive disease and only a few cases are diagnosed at early stages due to the absence of symptoms. Τhe majority of malignant ovarian tumors (>90%) are of epithelial origin and subdivided in five histological sybtypes with different molecular pathogenesis and clinical behavior. High-grade serous ovarian cancer is the most common subtype (70%), however, the different histotypes of ovarian cancer should be viewed as separate diseases both clinically and in biomarker studies. At present, surgical debulking and platinum/taxane - based chemotherapy is the standard of care for epithelial ovarian cancer. Most patients show initial response to this therapeutic approach, but the majority of them experience disease recurrence at which point cure is no longer possible, due to acquired resistance in those chemotherapeutic regimens. Nevertheless, the current treatment model is still a “one size fits all” approach. Epigenetic modifications represent heritable modifications in gene expression without alteration of the DNA sequence. DNA methylation is the best studied epigenetic mechanism and in epithelial ovarian cancer, the methylenome is widely altered. In addition, patterns of DNA methylation may represent potential diagnostic and prognostic markers as well as markers predictive of chemoresistance and potential therapeutic targets. This article systematically reviews the complicated era of DNA methylation in ovarian carcinoma and summarizes the current implications and future perspectives of its use as a screening, diagnostic, prognostic and predictive tool as well as in personalized cancer therapy.
The aim of our study was to describe the expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 ... more The aim of our study was to describe the expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of the patients. One hundred and six cases of endometrial cancer were identified from the archives of the Department of Obstetrics and Gynecology of the University of Patras. Tissue specimens from endometrial lesions were immunostained for c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4. Statistical analyses were performed using the chi square test, Kaplan-Meier method and Cox analysis. We found a significant association between c-erbB-1 expression and patient survival. A reverse correlation was found between tumor grade and c-erbB-1 expression. Tumor grade was not significantly correlated with the expression of the remaining three receptors. Stage of the tumor showed no relationship with the expression of these receptors. The ability to predict increased risks of advanced disease, recurrence, and death from abnormal molecular markers detected in curettage or endometrial biopsy specimens will facilitate pretreatment referral of these patients to gynecologic oncologists for definitive surgical treatment.
Primary malignant melanoma of the vagina is a very rare, but very aggressive tumor. We describe a... more Primary malignant melanoma of the vagina is a very rare, but very aggressive tumor. We describe a case of primary vaginal melanoma and review the literature. The patient, a 73-year-old, gravida 2, para 2 postmenopausal Greek woman, presented with abnormal vaginal bleeding for 30 days. On vaginal examination there was a 5.5 x 5 x 2 cm raised, ulcerated and irregular lesion on the posterior vaginal wall. Pathology examination of the entire specimen demonstrated a nodular vaginal melanoma. The histologic diagnosis was confirmed by positive immunostaining. The patient began postoperative immunotherapy with interferon-a2b. She died 25 months later because of cerebral metastases. In conclusion, the prognosis of vaginal melanoma is very poor, despite the treatment modality, because most cases are diagnosed at a late stage.
Primary sarcoma of the vulva is a rare tumor. Leiomyosarcoma is the most common histologic varian... more Primary sarcoma of the vulva is a rare tumor. Leiomyosarcoma is the most common histologic variant of vulvar sarcoma. The patient, a 55-year-old, gravida 4, para 2 postmenopausal Greek woman, presented with a 5-year history of progressive enlargement of the right labia majora. On vaginal examination there was a 8 x 9 cm raised, ulcerated and irregular mass of the right labia majora. Despite surgery, the patient died six months later because of multiple metastases.
The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population... more The clinical management of COVID-19 in pregnant women, who are considered a vulnerable population, remains uncertain even as the pandemic subsides. SARS-CoV-2 affects pregnant individuals in multiple ways and has been associated with severe maternal morbidity and mortality, as well as neonatal complications. The unique anatomy and physiology of gestation make managing COVID-19 in this population a complex and challenging task, emphasizing the importance of spreading knowledge and expertise in this area. Therapeutic interventions require distinct clinical consideration, taking into account differences in pharmacokinetics, vertical transmission, drug toxicities, and postnatal care. Currently, there is limited data on antiviral and immunomodulating COVID-19 pharmacotherapy in pregnancy. Some medication has been shown to be safe and well tolerated among pregnant women with COVID-19; however, the lack of randomized clinical trials and studies in this patient population is evident. Availa...
Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling part... more Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA resu...
Background: Colposcopy has a key role in the diagnostic work-up and management of abnormal cervic... more Background: Colposcopy has a key role in the diagnostic work-up and management of abnormal cervical cytology, but it might generate negative feelings of mainly anxiety and pain to the patients undergoing such examination. These feelings are interrelated, with the anxiety fueling the painful sensations. The aim of our study was to investigate the effects of preliminary administration in terms of pain and anxiety relief that the preliminary administration of paracetamol would have on patients undergoing diagnostic colposcopy. Materials & Methods: We conducted a single center prospective study which enrolled 112 patients with diagnosed or suspected cervical pathology who were examined at the Outpatient Colposcopy Clinic of Patras University Hospital, over a 7-months period. Patients were randomly assigned to one of the two groups. The interventional group received 1gr of paracetamol (acematiminofen) in pill form, 30 to 60 minutes before colposcopic assessment; the control group receive...
Endometrial cancer: current epidemiology, detection and management, Jan 1, 2015
The Epidermal Growth Factor system is present in human organs and play important role in cell pro... more The Epidermal Growth Factor system is present in human organs and play important role in cell proliferation, differentiation and apoptosis during embryogenesis and postnatal development. It has four receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands.
ErbB receptors are trans-membrane glycoproteins. Their dimerization leads to intracellular kinase activation. As a result, a number of tyrosine residues in the COOH-terminal portion of ErbB receptors become phosphorylated. Those phosphorylated tyrosine residues function as docking sites for cytoplasmic proteins. Recruitment of proteins initiates intracellular signaling via several pathways:
1. Ras / Raf / mitogen-activated protein kinase (MAPK) pathway (regulates cell proliferation and survival).
2. Phosphatidylinositol 3-kinase (PI3K) / Akt pathway (regulates cell growth, apoptosis, tumor invasion, migration and resistance to chemotherapy).
3. Signal transducers and activators of transcription (STAT) pathway (regulates oncogenesis and tumor progression).
4. Src Kinase pathway (regulates cell proliferation, migration, adhesion, angiogenesis and immune function).
5. Phospholipase Cγ / protein kinase C pathway.
Dysregulation of the Epidermal Growth Factor system signaling network, is implicated in the pathogenesis of various disorders. Especially in cancer, it becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). It is also contributes in proliferation, transformation, angiogenesis, migration and invasion.
During menstrual cycle, ErbB receptors have different levels in normal endometrium. Moreover due to the inactive status of postmenopausal endometrium, it is expectable to find significantly higher expression of the 4 ErbB receptors in endometrial cancer tissue.
Especially in patients with type II endometrial cancer (papillary serous or clear cell), there are high expression levels of ErbB receptors. Among them, many patients with dismal outcome are positive for all ErbB receptors.
EGFR overexpression in type I endometrial cancer, did not affect disease progression. However EGFR overexpression in type II endometrial cancer, associated with high grade and adverse clinical outcome.
Moreover ΕrbB-2 overexpression, especially in type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival.
The potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for cancer therapy has been investigated for over 20 years. There are 2 major classes of ErbB targeted therapies:
1. anti-ErbB monoclonal antibodies (MoAbs): Anti-EGFR MoAbs bind to the extracellular domain of EGFR and prevent ligand binding and ligand dependent receptor activation. Anti-ErbB-2 MoAb binds to the extracellular domain of ErbB-2 and interferes with ligand independent receptor activation.
2. ErbB-specific tyrosine kinase inhibitors (TKIs): TKIs block the binding of ATP to the intracellular domain of EGFR and/or ErbB-2 and blocks ErbB activity and subsequent intracellular signaling.
The overall response rate to ErbB targeted therapies is modest, unless they are associated with chemotherapy or radiotherapy. Moreover molecular targeted therapies have still shown modest effect, in unselected endometrial cancer patients. However, preclinical data suggest that ErbB targeted therapies may be clinically active as adjuvant therapy, in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.
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ErbB receptors are trans-membrane glycoproteins. Their dimerization leads to intracellular kinase activation. As a result, a number of tyrosine residues in the COOH-terminal portion of ErbB receptors become phosphorylated. Those phosphorylated tyrosine residues function as docking sites for cytoplasmic proteins. Recruitment of proteins initiates intracellular signaling via several pathways:
1. Ras / Raf / mitogen-activated protein kinase (MAPK) pathway (regulates cell proliferation and survival).
2. Phosphatidylinositol 3-kinase (PI3K) / Akt pathway (regulates cell growth, apoptosis, tumor invasion, migration and resistance to chemotherapy).
3. Signal transducers and activators of transcription (STAT) pathway (regulates oncogenesis and tumor progression).
4. Src Kinase pathway (regulates cell proliferation, migration, adhesion, angiogenesis and immune function).
5. Phospholipase Cγ / protein kinase C pathway.
Dysregulation of the Epidermal Growth Factor system signaling network, is implicated in the pathogenesis of various disorders. Especially in cancer, it becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). It is also contributes in proliferation, transformation, angiogenesis, migration and invasion.
During menstrual cycle, ErbB receptors have different levels in normal endometrium. Moreover due to the inactive status of postmenopausal endometrium, it is expectable to find significantly higher expression of the 4 ErbB receptors in endometrial cancer tissue.
Especially in patients with type II endometrial cancer (papillary serous or clear cell), there are high expression levels of ErbB receptors. Among them, many patients with dismal outcome are positive for all ErbB receptors.
EGFR overexpression in type I endometrial cancer, did not affect disease progression. However EGFR overexpression in type II endometrial cancer, associated with high grade and adverse clinical outcome.
Moreover ΕrbB-2 overexpression, especially in type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival.
The potential role of ErbB receptors (especially EGFR and ErbB-2) as targets for cancer therapy has been investigated for over 20 years. There are 2 major classes of ErbB targeted therapies:
1. anti-ErbB monoclonal antibodies (MoAbs): Anti-EGFR MoAbs bind to the extracellular domain of EGFR and prevent ligand binding and ligand dependent receptor activation. Anti-ErbB-2 MoAb binds to the extracellular domain of ErbB-2 and interferes with ligand independent receptor activation.
2. ErbB-specific tyrosine kinase inhibitors (TKIs): TKIs block the binding of ATP to the intracellular domain of EGFR and/or ErbB-2 and blocks ErbB activity and subsequent intracellular signaling.
The overall response rate to ErbB targeted therapies is modest, unless they are associated with chemotherapy or radiotherapy. Moreover molecular targeted therapies have still shown modest effect, in unselected endometrial cancer patients. However, preclinical data suggest that ErbB targeted therapies may be clinically active as adjuvant therapy, in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.