Search

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.

Abnormal uterine bleeding (AUB) is defined as abnormal volume, duration, or frequency of menstrual period and is a common symptom in women of all ages (premenopausal, perimenopausal, and postmenopausal). The acronym PALM-COEIN, introduced by the International Federation of Gynecology and Obstetrics (FIGO), facilitates the evaluation and differential diagnosis of AUB, mostly in premenopausal women with AUB. Endometrial evaluation (including ultrasound or hysteroscopic imaging and tissue sampling) for subtle pathology is proposed in patients who are at high risk for endometrial cancer and in patients at low risk who present with AUB and who present poor correspondence in medical treatment. Many new diagnostic modalities are available in clinicians in order to help the assessment of women presenting with abnormalities in their menstrual pattern. The present study reviews the optimal management of women presenting with AUB, taking into consideration the actual need for invasive management in these women, who of them require it, and who can be diagnosed without histological verification. The importance of endometrial tissue sampling in women who present with AUB as well as the best timing for a clinician to conduct a biopsy are two axons analyzed below, according to the latest worldwide guidelines and major publications about this subject.

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 received no medication. At the end of consultation, all participants completed a 2-page questionnaire. Results: More patients of the interventional arm did not experience any pain at all during colposcopy compared with the control group. However, this difference was statistically not significant, probably because of the small number of patients. Moreover, there were no differences in mild and moderate pain rates between the interventional and control groups. Severe pain was only experienced by patients in the control group. Further data analysis from the first time as and for repeat colposcopy patients showed similar findings regarding pain intensity rates in the interventional and control group. When considering anxiety levels, no differences were observed between the two groups. Conclusion: The preliminary administration of low dose paracetamol in a pilot sample of colposcopy patients did not illustrate significant benefits in terms of experienced pain and anxiety levels.

Background: In Greece the population-level impact of HPV vaccination is unknown due to lacking official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy. Materials and Methods: This is an observational prospective cohort study performed in 7 academic Obstetrics & Gynaecology departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. Results: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. Conclusion: Despite potential bias, this study’s message is clear: HPV vaccination at a proper age can markedly reduce development of severe cervical precancer and consequently, the need for treatments with their long-term related obstetrical morbidity.

Objective: To assess the reliability of thyroglobulin (Tg) as a marker of iodine status during pregnancy. Design: 299 women aged 30.5 ± 4.8 years (mean ± SD) were studied. Methods: In every subject, we measured urinary iodine concentration (UIC), serum thyrotropin (TSH), Tg, free thyroxine (fT4), Tg autoantibodies (TgAbs) and human chorionic gonadotropin (hCG) levels. We excluded samples with increased TgAbs from the analysis. Results: According to WHO criteria, the study population was iodine deficient in every trimester. Serum Tg levels did not differ during the three trimesters of pregnancy. Serum hCG levels fell significantly as pregnancies advanced. A weak, significantly negative correlation (limited to the 3rd trimester) was found between Tg and UIC (ρ = -0.187, p = 0.039). Serum fT4 decreased as pregnancies advanced and TSH increased. Serum fT4 was negatively correlated with TSH (ρ = -0.161, p = 0.006) and positively with hCG (ρ = +0.165, p = 0.005). The multiple regression equation of Tg based on hCG, TSH, UIC and trimester of pregnancy was significant but weak (F = 4.057, p = 0.003; R2 = 0.055), with hCG as a significant predictor Tg (p for log hCG = 0.041). Conclusions: Tg cannot be considered as a valid marker of iodine deficiency in pregnancy, at least in a mildly iodine-deficient environment. Further studies in a larger patient cohort with differences in iodine status, as well as studies on Tg changes after improving iodine status in pregnant women, are needed in order to corroborate these results.

Objectives Contrary to the optimistic forecasts, existing until 2008 and despite the incorporation of the vaccine into the Greek National Immunization Program, six years later, the percentage of HPV vaccination coverage in Greece remains disappointingly low. The aim of this extended study was to investigate the knowledge, behaviour and attitude of a representative sample of the initial target group; young female students of Greek higher education institutions to Pap cervical screening, biology of HPV infection and principles of HPV vaccination. Study design Cross-sectional study. Methods One thousand two hundred ten (1210) questionnaires were completed by young female students aged 17–24 years. The survey questionnaire sought data relating to sociodemographic characteristics, health behaviour and knowledge about HPV, as well as vaccination status. Results 79.6% of the sample reported at least one annual gynaecologic examination and 92.6% were familiar with the rationale of cervical screening; however only 52.9% had undergone a Pap smear. 69.7% reported adequate knowledge about HPV and 89.3% were aware of the possible course of HPV infection. Despite most (95.9%) were aware of vaccine availability, vaccinated students represented only 33.1%. According to the multivariate analysis, vaccination status was associated with university studies (OR 1.96; 95% CI: 1.19–3.20), parental area of expertise (OR 2.77; 95% CI: 1.18–6.53, OR 2.03; 95% CI: 1.05–3.94), and adequate knowledge of the reasons for which women should undergo regular cervical screening (OR 4.23; 85% CI: 1.55–11.55). Fear of side-effects and equivocal information were the main reasons of non-vaccination (52.2% and 33.1% respectively). Finally, the majority of unvaccinated individuals showed a positive attitude towards prospective HPV vaccination, providing they received well-documented advising. Conclusions Young women attending Greek higher education exhibit a good level of knowledge about HPV and its correlation with cervical cancer. These data highlight the need for further sensitization of the general population.

Necrotizing fasciitis is a rare, life-threatening surgical infection in pregnancy with high rates of morbidity and mortality. A 15-year-old primigravid woman, at 28 weeks of gestation with no significant previous medical history, was admitted to our hospital complaining of severe left lower extremity pain and high fever the last 72 hours. During clinical examination, she had a swollen, erythematous and tender to palpation inflamed skin over the medial aspect of the upper thigh without any evidence of injury. Incision drainage was performed immediately and she received broad spectrum antibiotics. During initial laboratory examinations, diabetes mellitus was diagnosed. There was no clinical improvement over the following days. Magnetic resonance imaging (MRI) revealed subcutaneous tissue inflammation and edema of infected tissues confirming the disease entity. Multidisciplinary therapy with immediate aggressive surgical debridement of necrotic tissues, multiple antibiotics, and intensive care monitoring was performed successfully. The patient’s postoperative course was uncomplicated and skin defect was closed with split thickness skin grafting. Our case emphasized the potential immunosuppressive role of pregnancy state in conjunction with diabetes mellitus in the development of severe necrotizing soft tissue infections.

The Epidermal Growth Factor system is present in human organs and plays an 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. Dysregulation of the Epidermal Growth Factor signaling network is implicated in the pathogenesis of various disorders. Especially in cancer, the Epidermal Growth Factor system becomes hyperactivated with various mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). EGFR overexpression may have a dual role in endometrial cancer. It seems that in type I endometrial cancer, EGFR overexpression did not affect disease progression. However in type II endometrial cancer, EGFR overexpression associated with high grade disease and adverse clinical outcome. Moreover ErbB-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: anti-ErbB monoclonal antibodies (MoAbs) and ErbB-specific tyrosine kinase inhibitors (TKIs). ErbB targeted therapies have still shown modest effect in unselected endometrial cancer patients. However, they may be clinically active as adjuvant therapy in well-defined subgroups of type II endometrial cancer patients with EGFR and ErbB-2 overexpression.

To present experience with the percutaneous management of iatrogenic ureteral injuries.Eighteen women and six men with a mean age of 59.3 years (range 33-80 years) received a diagnosis of ureteral injury sustained during gynecologic, urologic, and general surgical procedures. In a total of 25 injured ureters, 12 had interruption of continuity of their lumen, 10 were associated with contrast extravasation, and 3 were related to both. A standard percutaneous nephrostomy tract was established on the side of the afflicted kidney. Combined use of hydrophilic guidewires and balloon dilations were performed to achieve antegrade recanalization of the ureteral lesion. Then, a ureteral stent was inserted to assure patency.Average stricture length was 1.21 (range 0.5-1.9 cm). Success of the aforementioned technique was possible in 18 ureters. Successful management in one session took place in 14 ureters. Average hospitalization time was 1.8 days (range 0-5 d). The follow-up period ranged between 12 and 18 months, with mean follow-up time of 12.9 months. Ureteral patency was evident at 1 week follow-up in six patients with obstructed ureters. In the remaining patients, balloon dilation of the stricture was repeated, and another stent was placed. Extravasation of contrast was observed in two patients with extravasating ureters in the same period. Nephrostomy tubes were removed after a mean indwelling period of 5.9 weeks (range 1-12 wks). Two patients treated by the described method died during their hospitalization in the intensive care unit because of sepsis from peritonitis that was related to colon injury and multiple concomitant injuries. Major complications were not observed in the remaining 22 patients during the follow-up period.The minimally invasive management of ureteral injuries is a safe and efficient method for both ureteral obstruction and/or laceration in a wide range of iatrogenic ureteral injuries.

The Akt/mTOR and MAPK pathways are frequently activated in various tumor types but data on endometrial carcinoma are limited. The aim of the present study was to investigate the clinical significance of the expression of phosphorylated MAPK, Akt and mTOR (p-MAPK, p-Akt, p-mTOR) in type I endometrial carcinoma.The study comprised of 103 formalin-fixed paraffin-embedded (FFPE) type I endometrial carcino ma cases, retrospectively retrieved and assessed by immuno histochemistry for p-MAPK, p-Akt and p-mTOR expression. The expression of these proteins was also studied in non-neoplastic endometrial tissue adjacent to the tumor.The expression patterns of these molecules differed between malignant and non-tumorous tissue specimens. The immuno reactivity for p-Akt was exclusively detected in the neoplastic tissues. Expression levels of p-MAPK were higher in tumors compared to non-neoplastic endometrium (p0.001), while p-mTOR was found to be over-expressed in non-neo plastic endometrium compared to carcinomas (p=0.001). Expression of p-Akt was correlated with p-MAPK protein levels (p=0.022, r=0.229). On the other hand, no association was found with clinicopathological parameters and with disease-free (DFS) or overall survival (OS) of the patients.Our findings support the de-regulation of the PI3K/Akt/mTOR and MAPK signaling pathways in type I endometrial carcinomas suggesting involvement of these pivotal pathways in endometrial carcinogenesis.

It should be mentioned that pelvic and para-aortic lymphadenectomy, are absolutely necessary in EC patients for the diagnosis of stage IIIc disease [3-5,8,9,11-13,20,21]. Moreover the application of pelvic and para-aortic lymphadenectomy in patients with advanced stage type I EC and in all patients with type II EC, associated with improved survival [2-5,11,22-26]. However the application of pelvic and para-aortic lymphadenectomy in patients with early stage type I EC, do not improve survival [25,11,12,27,28].

OBJECTIVE: Adequate dietary iodine intake is necessary for normal thyroid gland function at all times, and most particularly during pregnancy. Increased iodine loss is cited, among other factors, as responsible for the increased iodine demand in this period. Our aim was to compare renal iodine excretion between women during all three pregnancy trimesters with that of their spouses and thereby to estimate the iodine intake in an a large sample of pregnant women in urban areas in Greece. DESIGN: Four hundred twenty-four healthy pregnant women were included prospectively (residents of Athens n=218, residents of Patras n=206). The spouses of 177 of these women following the same diet were also studied. Determinations included serum FT4, TSH and aTPO and urinary iodine excretion (UIE). RESULTS: No difference was found either in median UIE throughout pregnancy or between the UIE of the pregnant women and their spouses during the trimesters. Throughout pregnancy, mild iodine deficiency was noted and was classified as mild in 60%, moderate in 30% and severe in 10% of the women studied. Users of iodized salt had significantly higher median UIE compared with non-users. Serum FT4 levels decreased and TSH increased as pregnancy progressed. CONCLUSIONS: Our study indicates that renal iodine excretion is not increased during pregnancy. This finding needs to be confirmed by further investigation in other populations with different iodine intakes. Thus, increased iodine requirements in pregnancy are possibly due to extra-renal causes. The population of pregnant women in Greek urban areas is mildly-and often moderately and severely-iodopenic and needs to be treated accordingly.

A 32-year-old primigravida with primary Addison's disease was followed up from the early stages of pregnancy to delivery and puerperium by a multidisciplinary medical board. Besides fetal surveillance, great attention was given to steroid replacement therapy in order to avoid complications. Vaginal labor resulted in the birth of a healthy neonate that performed well.

Objective: Endometrial cancer is the most common malignancy of the female genital tract. Based on clinical and pathological features, endometrial cancer is classified into 2 types. The aim of our study was to describe the expression and the potential clinical role of ErbB receptors in Greek patients with type II endometrial cancer. Study Design: Between 1991 and 2008, 10 women with histologically confirmed type II endometrial cancer were referred to the Department of Gynecologic Oncology of the University of Patras Medical School. Tissue specimens from endometrial lesions were immunostained for EGFR, ErbB-2, ErbB-3 and ErbB-4. Results: For EGFR, 5 cases were positive (50%) and 5 cases were negative (50%). For ErbB-2, 9 cases were positive (90%) and 1 case was negative (10%). For ErbB-3, all cases were positive (100%). For ErbB-4, 7 cases were positive (70%) and 3 cases were negative (30%). Also for all ErbB receptors, 5 cases were positive (50%). During follow up, 3 patients died from their disease. All of them had papillary serous endometrial cancer and 2 of them were positive for all ErbB receptors (66.7%). Conclusion: Although our study was based on a small number of cases, it is obvious that we had high expression levels of ErbB receptors in patients with type II endometrial cancer. Also the majority of patients with dismal outcome were positive for all ErbB receptors. This is very important, as ErbB-targeted therapies may be clinically active as adjuvant therapy in well-defined subgroups of type II EC patients with EGFR and ErbB-2 overexpression.

The Role of ErbB Receptors in Endometrial Cancer

Objective. The aim of our study was to describe the expression of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of the patients. Study Design. 106 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 cerbB-1, cerbB-2, cerbB-3 and cerbB-4. Statistical analyses were performed using chi square test, Kaplan-Meier method and Cox analysis. Results. We found a significant association between cerbB-1 expression and patients’ survival. A reverse correlation was found between tumor grade and cerbB-1 expression. The tumor grade was not significantly correlated with the expression of the rest three receptors. The stage of the tumor showed no relationship with the expression of these receptors. Conclusion. 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.

Sarcoidosis of the vulva is a very rare condition. Until now, only 4 cases has been reported in English literature. The patient, a 48-year-old, gravida 3, para 2 postmenopausal Greek woman presented with a 6 months history of perineal pain. The patient underwent a wide local excision of the painful lesion. The histopathology revealed sarcoidosis of the vulva. She remains well without evidence of disease 9 months after operation. &nbsp

In 1% to 3% of patients with cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VAIN) will either coexist or occur at a later date. The time interval from an earlier diagnosis of CIN 3 to a current diagnosis of VAIN 3 varied from 2 to 17 years. An invasive vaginal cancer occurred in a woman 5 years after total abdominal hysterectomy for cervical intraepithelial neoplasia. In women who have undergone total hysterectomy for cervical intraepithelial neoplasia or cervical cancer, it is necessary the postoperative cytologic and colposcopic follow up of the vagina.

OBJECTIVE: To compare the efficacy of GnRH antagonist vs. GnRH agonist administration for controlled ovarian hyperstimulation (COH) in assisted reproduction. DESIGN: A prospective, randomized trial. SETTING: Clinical research unit at a tertiary care medical center. PATIENT(S): Sixty-five patients with unexplained infertility or mild male subfertility undergoing COH for IUI. INTERVENTION(S): Twenty-nine women (group A) were randomized to receive 600 microg of busereline acetate per day starting in the midluteal phase of the cycle (long protocol), whereas 36 women (group B) were treated with 0.25 mg/d of the GnRH antagonist Cetrorelix starting from day 6 of the cycle. The starting dose of recombinant FSH was 150 IU in women of both groups. Insemination was performed 34 hours after hCG injection. MAIN OUTCOME MEASURE(S): Clinical and successful ongoing pregnancy rate (PR), measurements of serum FSH, LH, E2, and P, number of recruited follicles, duration of stimulation period, and amount of gonadotropins used. RESULT(S): Women in group A required significantly more days of treatment (median: 12.0 vs. 9.0) and significantly more total units of recombinant FSH (median 1,800 vs. 1,550) as compared with the corresponding values of the antagonist group (group B). Serum FSH, LH, E2, and P were significantly higher on the antagonist group on days 2 and 6 of stimulation. However, these differences regress until the day of hCG administration. CONCLUSION(S): The GnRH antagonists have facilitated short and simple treatment, and are particularly attractive for administration in women undergoing COH, achieving comparable PR with the long protocol regimen. Fertil Steril

We report a case of malignant mixed müllerian tumor (MMMT) (carcinosarcoma) of the right fallopian tube in a 69-year-old Greek woman who presented with a history of right lower quadrant abdominal pain and was found to have a palpable right adnexal mass. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy with adjuvant chemotherapy and is without evidence of disease 10 months postoperatively. The tumor was composed of in situ serous adenocarcinoma of the fallopian tube evolving in high grade serous and undifferentiated carcinoma, leiomyosarcoma and undifferentiated sarcoma. Expression of the neuroendocrine markers CD56 and Leu-7 and p53 was observed in both elements. Nuclear WT1 and calretinin expression was observed in the epithelial elements while the mesenchymal cells showed negative nuclear and strong cytoplasmic staining. HBME was observed focally in the epithelial element only. The tumor was negative for ER, PR, c-kit and cerbB2. The expression of the mesothelial-associated antigens WT1, calretinin and HBME likely reflects the common embryologic derivation of mesothelium and urogenital ridge but in addition loss of nuclear WT1 expression in the mesenchymal component may be related to tumor progression.

Background: Scleroderma is a chronic, multisystem, autoimmune disease. Previous studies have shown an increased risk of malignancy in scleroderma. The most common cancers were lung cancer and breast cancer. Case: The patient, a 43-year-old nulliparous premenopausal Greek woman suffering of scleroderma, presented with a history of abdominal pain and atypical vaginal bleeding. She underwent total hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, appendectomy and pelvic lymph node dissection. The histopathology revealed synchronous primary cancers of the endometrium and left ovary. She underwent to postoperative chemotherapy and remains well without evidence of disease 25 months after operation. Conclusion: Synchronous primary cancers of the endometrium and ovary are relatively uncommon in general population. Only few cases of cancer of the female genital tract in women with scleroderma have been reported in the English literature.

Synchronous primary cancers of the endometrium and ovary are relatively uncommon in general population. The patient, a 49-year-old postmenopausal Greek woman presented with abdominal pain and pelvic mass. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, total omentectomy, appendectomy and pelvic lymph node dissection. The histopathology revealed synchronous primary cancers of the endometrium and right ovary. She underwent postoperative chemotherapy. Thirty nine months after surgery, she remains well without evidence of recurrence.

The aim of our study was to describe the expression of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 in endometrial cancer tissue and its correlation with clinicopathologic features and prognosis of endometrial cancer patients diagnosed during or after tamoxifen treatment for breast cancer. Thirteen tamoxifen-related endometrial cancers were identified from the archives of the Department of Obstetrics and Gynecology of the University of Patras, Medical School. Tissue specimens from endometrial lesions were immunostained for cerbB-1, cerbB-2, cerbB-3 and cerbB-4. For cerbB-1, 5 cases were positive and 8 were negative. For cerbB-2, 10 cases were positive and 3 were negative. For cerbB-3, 9 cases were positive and 4 were negative. For cerbB-4, 8 cases were positive and 5 were negative. However, a limitation of our study is that the number of cases was small, and further investigations are necessary to allow a more focused evaluation of cerbB-1, cerbB-2, cerbB-3 and cerbB-4 status, as a prognostic factor for endometrial cancer after tamoxifen treatment.