Evaluating the potential role of human papilloma virus infection in breast carcinogenesis via real-time polymerase chain reaction analyzes of breast fine needle aspiration samples from Greek patients.

BACKGROUND: Human papilloma virus (HPV), in addition to its known clinical contribution to cervical cancer is probably actively involved in the development of breast tumors in various populations worldwide. Predominant HPV types in breast cancer patients vary geographically. The present study further examines HPV incidence in Greece, based on molecular analysis of clinical cytological samples. METHODS: Greek patient fine needle aspiration (FNA) biopsy samples were examined using RT-PCR and immunohistological staining. FNA biopsy samples were collected from 114 female patients, diagnosed between the years 2018 and 2021, 57 with C5 diagnosed breast cancer lesions and 57 diagnosed with benign diseases. RESULTS: A total of three different HPV types were identified within the patient sample. HPV-39 was found only in the control group, in 1.8% of patients, while HPV-59 was present in both control and study groups in 1.8% and 3.5% respectively. HPV-16, on the other hand, was present only in the study group in 12.3% of cases. HPV type presence was statistically differentiated between histological groups. HPV-16 was exclusively in IDC, HPV-39 was present in one cyst diagnosed sample and HPV-59 was present in 3 samples that included fibroadenoma, IDC and LN diagnosis. CONCLUSION: More international comparative studies are required to investigate population differences and HPV genotype distribution to offer definite answers to the effect that certain HPV types might have a role in breast cancer, as this study also supports, albeit in a cofactory role.

Oral anticoagulation patterns and prognosis in octogenarian patients with atrial fibrillation.

The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF) has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5 years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion, in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.

Dilatation and curettage in endometrial cancer. What is the correlation with hysterectomy histology? A 14 years retrospective cohort study.

PURPOSE: The aim of the present study is to evaluate the concordance between preoperative endometrial sampling histopathology performed by conventional dilatation and curettage (D&C) and final histopathological diagnosis after total hysterectomy concerning tumor grade and subtype in patients with endometrial cancer (EC). METHODS: In this comparative retrospective study, 203 women with endometrial cancer were included who underwent at first dilatation and curettage and then total hysterectomy. The preoperative histopathological report obtained by dilatation and curettage was compared with the final histopathology after total hysterectomy to assess the accuracy of endometrial sampling. RESULTS: Comparison of preoperative with postoperative histopathological results showed an overall 5.9% and 10.9% discordance regarding endometrial cancer histological subtype and grade, respectively. Six (4.9%) of the patients with preoperative grade 1 were grade 2 and 1 (0.8%) was found to be grade 3. Three (8.3%) of the patients with preoperative grade 2 were found to be grade 3 after hysterectomy. Discordance is higher for endometrioid endometrial cancer grade 2 (25%) compared with grade 1 (5.7%) and 3 (18.8%). CONCLUSION: Patients should be informed and consent for the potential discrepancy between the pre and postoperative histopathological features of malignancy. This discrepancy may result in either under or overtreatment. Thus, it should be accounted for when counseling for a major operation.

Treatment of endometriosis: a review with comparison of 8 guidelines.

BACKGROUND: Endometriosis, the presence of endometrial-like tissue outside the uterus, is a common clinical entity between women of reproductive age, with a prevalence of about 10%. Due to the variety of endometriosis-associated symptoms, a great variety of treatments have been implemented. The aim of this review is to give an overview on therapeutical approaches of eight national and international widely used guidelines. METHODS: Six national (College National des Gynecologues et Obstetriciens Francais, National German Guideline (S2k), Society of Obstetricians and Gynaecologists of Canada, American College of Obstetricians (ACOG) and Gynecologists, American Society for Reproductive Medicine (ASRM) and National Institute for Health and Care (NICE) and two international (World Endometriosis Society, European Society of Human Reproduction and Embryology) guidelines are included in this review. CONCLUSION: All the above-mentioned guidelines agree that the combined oral contraceptive pill, progestogens are therapies recommended for endometriosis associated pain. Concerning infertility, there is no clear consensus about surgical treatment. Discrepancies are also found on recommendation of the second- and third-line treatments.

Human papillomavirus in breast cancer of patients with cervical intraepithelial neoplasia or cervical cancer history. A systematic review and meta-analysis.

PURPOSE: Many cohort studies and meta-analyses support the oncogenic role of the human papilloma virus (HPV) on breast tissue. However, only a few studies examine the association between HPV-positive breast cancer and the prior history of high grade cervical intraepithelial neoplasia (CIN) or cervical cancer. The present systematic review and meta-analysis aimed to determine whether women with a history of high grade CIN or cervical cancer are at a higher risk of developing HPV-positive breast cancer. METHODS: MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources were searched for case-control studies, detecting and genotyping HPV genome in breast cancer patients with and without a history of CIN or cervical cancer, from inception to October 23, 2020. RESULTS: The meta-analysis included three case-control studies with 265 breast cancer patients in total. HPV related breast cancer was associated with a history of high grade CIN or cervical cancer [pooled odds ratio (OR) =7.98, 95% confidence interval (CI), 1.84 to 34.67]. This association remained regarding HPV-16 related breast cancer (pooled OR =7.60, 95% CI, 1.75 to 33.00). CONCLUSIONS: HPV was detected more frequently in breast cancer patients with CIN or cervical cancer history. Therefore, further research is necessary to understand better the HPV transmission route to the breast.

Breast Disorders in Adolescence: A Review of the Literature.

BACKGROUND: Adolescence is accompanied by a variety of changes in young breast development, which greatly affects the adolescent's psychology and socialization. SUMMARY: PubMed, EMBASE, and the Cochrane Library were searched for studies relative to epidemiology, clinical characteristics, diagnosis, and management of all breast disorders in adolescence and their consequences. Development disorders are breast asymmetry, breast atrophy, breast hypoplasia, hypomastia, juvenile breast hypertrophy, and tuberous breast. Breast congenital abnormalities include athelia, amastia, accessory breast tissue, polymastia, polythelia, and congenital disorders of nipples. Breast infections are commonly caused from Gram-positive coccus rather than Gram-negative bacteria. Breast abscess occurs when breast infections are not promptly treated. Nipple discharge is caused by a variety of conditions and should be managed carefully. Fibrocystic changes, cysts, and fibroadenomas are the most common benign masses in adolescence. Primary, secondary, or metastatic breast cancer is extremely rare in adolescence. However, clinicians should include breast cancer in the differential diagnosis of a breast mass in adolescence. KEY MESSAGES: Clinicians should be aware of all breast disorders that may occur in adolescence. Early diagnosis and treatment will result in the reassurance of adolescents and their families without any detrimental effect on their psychology, sexual behavior, and socialization. Adolescents with breast disorders may require a multidisciplinary approach by a pediatrician, a gynecologist specializing in pediatric-adolescent gynecology, a plastic surgeon, and a psychologist for the best management of breast disorders.

DNA methylation patterns of RAR-ß2 and RASSF1A gene promoters in FNAB samples from Greek population with benign or malignant breast lesions.

BACKGROUND: Promoter hypermethylation is common in Breast Cancer (BC) with studies mainly in histological specimens showing frequent methylation of tumor suppressor genes (TSGs) compared with normal tissues. The aim of this study was to estimate the frequency of promoter methylation of RAR-ß2 and RASSF1A genes in breast FNAB material aiming to evaluate the methylation status of these two genes as biomarker for detecting BC in Greek population. METHODS: FNAB material from 104 patients was collected for cytological evaluation and epigenetic analysis. DNA was extracted and subjected to bisulfite conversion. A methylation-specific PCR was carried out and the final products were separated with electrophoresis in 2% agarose gels. RESULTS: From 104 samples, RASSF1A hypermethylation was observed in 78 (75%) and RAR-ß2 hypermethylation in 64 (61.6%). 84% and 78% of the cases diagnosed with breast malignancy (n = 50) were methylated for RASSF1A and RAR-ß2, respectively. Methylated RASSF1A and RAR-ß2 were also detected in 88.3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR-ß2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy. CONCLUSION: To optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.

Molecular evaluation of a multiplex methylation panel for epigenetic analysis of FNAB samples from Greek patients with suspicious breast lesions.

PURPOSE: Aberrant DNA methylation in promoter regions has been found in many cancers, including breast cancer (BC). A Methylation Specific PCR (MSP) was applied in breast Fine Needle Aspiration Biopsy (FNAB) material, which has been rarely used in the literature, to estimate the methylation frequencies of CND2, APC, HIN1 & CDH13 and to assess whether this multiplex methylation panel can be possibly used as an indicator-biomarker for BC detection in a Greek population. METHODS: A total of 104 participants were subjected to FNAB and both cytological evaluation and epigenetic analysis were carried out. DNA was extracted from FNAB samples and was subjected to bisulfite conversion. MSP was carried out with primers specific for either the methylated or unmethylated status for each gene. The final MSP products were analyzed in 2% agarose gels with electrophoresis. RESULTS: Hypermethylation was observed in 74%, 69.2%, 59.6% and 63.4% of the samples for CND2, HIN1, APC and CDH13, respectively. CND2 was the most hypermethylated in C5 cases (90%) and APC and HIN1 in C4 cases (88.2%). A significant correlation between histologic evaluation and the methylation frequencies for all 4 genes was calculated (p<0.001). Odds ratio for breast malignancy was 8.267 for CND2, 5.235 for APC, 7.852 for HIN1 and 22.920 for CDH13, underlying that their methylation is positively related to breast malignancy. Also, it seems that the combination of all genes into a multiplex methylation panel has significantly higher SP and PPV than any single gene methylation. CONCLUSIONS: Our study shows that breast FNAB combined with methylation data from the collected aspirates has a promising potential as a biomarker for the early detection of BC risk in women with suspicious lesions.

Bisphosphonate's Effect on Tongue Mucosa: An Experimental Electron Microscopy Study.

BACKGROUND AND OBJECTIVES: Bisphosphonates (BPs) are selective inhibitors of osteoclasts, used for the treatment of bone disorders. The objective of this study is to investigate the possible effects of BPs on the tongue's mucosa. MATERIALS AND METHODS: Specimens of the tongue of 20 female 12-month old Wistar rats were taken. Ten were used as control group, while in the remaining alendronate (Fosamax, Merck) was administered per os from 13 weeks. Observation of the harvested samples was made by Transmission Electron Microscopy (TEM). RESULTS: In the experimental group, focal alterations were observed to various extent in all specimens. The basement membrane was intact. Furthermore, an increase at the intercellular space was observed, predominantly at the middle layer, and the desmosomes were disorganized. In the lamina propria focal edema was observed. CONCLUSIONS: Investigation on the effect of BPs on the tongue's mucosa through TEM hasn't been documented in the past. According to our results, BPs seem to cause mild mucosal lesions on the tongue.

Prevention of gestational diabetes mellitus in overweight or obese pregnant women: A network meta-analysis.

AIMS: Several interventions have been implemented to prevent the development of gestational diabetes mellitus (GDM) in obese pregnant women, including physical exercise programs, and administration of metformin, vitamin D and probiotics. The aim of this network meta-analysis was to compare the efficiency of these interventions and identify the optimal. MATERIALS: A network meta-analysis of randomized trials was performed comparing the different interventions for the development of GDM in overweight or obese women, either to each other or placebo/no intervention. A search was conducted in four electronic databases and grey literature sources. The primary outcome was the development of GDM; secondary outcomes were other complications of pregnancy. RESULTS: The meta-analysis included 23 studies (4237 participants). None of the interventions was superior compared with placebo/no intervention for the prevention of GDM. Metformin and physical exercise were superior to placebo/no intervention for gestational weight gain (MD -1.21, 95% CI -2.14 to -0.28 and MD -0.96, 95% CI -1.69 to -0.22, respectively). Metformin was superior to placebo/no intervention for caesarean sections and admission to NICU. CONCLUSIONS: Interventions aiming to prevent the development of GDM in overweight/obese women are not effective, when applied during pregnancy.

Thyroid nodules as a risk factor for thyroid cancer in patients with Graves' disease: A systematic review and meta-analysis of observational studies in surgically treated patients.

OBJECTIVE: Graves' disease (GD) is an autoimmune thyroid disorder characterized by hyperthyroidism. The incidence of thyroid cancer in patients with GD varies from 0.15% to 15%. There is conflicting evidence on the role of thyroid nodules as a risk factor for thyroid cancer in patients with GD. DESIGN: Three electronic databases (PubMed, Cochrane Library, Scopus) as well as grey literature sources were searched, from inception until 25 February 2019, for observational studies about the prevalence of thyroid cancer in patients with GD. PATIENTS: Clinical and ultrasonographic examination was necessary preoperatively for all patients to be classified depending on the presence/absence of thyroid nodules. MEASUREMENTS: Primary outcome was the incidence of thyroid cancer. The latter was determined after total or near-total thyroidectomy by the histopathologic report. Statistical analysis was performed with revman 5.3 software. RESULTS: The systematic review and meta-analysis included 7 studies with 2582 patients overall. The prevalence of any thyroid cancer was 11.5%. The presence of at least one thyroid nodule in patients with GD was associated with higher risk for thyroid cancer (odds ratio [OR] 5.3, 95% confidence interval [CI] 2.4-11.6, I2 83%). A subgroup analysis showed no difference in thyroid cancer risk in patients with GD according to the number of nodules (solitary versus multiple) (OR 1.4, 95% CI 0.9-2.3, I2 0%). CONCLUSIONS: The presence of thyroid nodules is positively associated with the prevalence of thyroid cancer in surgically treated patients with GD. However, further prospective research is needed as the heterogeneity among the studies is high.

Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density. AIM: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women. METHODS: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software. RESULTS: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I2 95%). CONCLUSION: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error.

Non-Hormonal Replacement Therapy Regimens: Do they have an Effect on Cardiovascular Risk?

INTRODUCTION: Menopause is associated with adverse effects on quality of life of perimenopausal and post-menopausal women. It also has an impact on the development of cardiovascular disease (CVD). Hormonal treatments are the most effective medications for menopausal symptoms relief. Given the fact that hormonal treatments are contraindicated for many women, non-hormonal treatment, such as Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), gabapentin, pregabalin, clonidine and phytoestrogens, constitute alternative treatments. Nevertheless, little is known about their effects on CVD risk. METHODS: PubMed, EMBASE and Cochrane Library were searched for the effects of non-hormonal treatment on CVD risk, blood pressure, heart rate, lipids and glucose concentrations, weight gain, cardiovascular events, stroke, mortality and morbidity. RESULTS: Phytoestrogens, pregabalin and gabapentin seem to have no adverse effects on the cardiovascular system. Phytoestrogens, in particular, seem to reduce CVD risk through many pathways. On the other hand, SSRIs and SNRIs, although effective in reducing menopausal vasomotor symptoms, should be cautiously administered to women with known CVD (e.g. with cardiac arrhythmias, atherosclerotic disease or stroke). As clonidine has been associated with cardiovascular adverse effects, it should be administered only in cases where blood pressure regulation is mandatory. CONCLUSION: Further research is needed to produce definite conclusions regarding the cardiovascular safety of non-hormonal medications for menopausal symptoms relief.