M Varras’s research while affiliated with Elena Venizelou Hospital and other places

Multiple sclerosis (MS) is a widespread neurodegenerative disease, affectingyoung and middle-aged individuals, with clinical symptoms that involve theentire sensory, motor and mental spectrum. MS is associated with inflamma-tory and oxidative processes, in the Central Nervous System but also periph-erally on the systemic circulation, with many cytokines and immune cellsinvolved in its manifestation. Accordingly, obesity is a metabolic disease withmany mechanistic ramifications, at the level of increased oxidative stress,hormonal inflammation and metabolic activity of adipose tissue. Obesityand MS appear to share common mechanisms of their promotion, relatedto inflammation, oxidative imbalance and adipokine function. The presentreview aims to highlight the effect of obesity and adipokines secreted by ad-ipose tissue on the manifestation and progression of MS, mainly at a mecha-nistic but also at clinical level. Furthermore, due to the nature of MS, antiox-idant elements and compounds, natural or not, derived from the diet, could,thanks to their multifunctional role, positively intervene in pathways relatedto obesity and which are generally involved in the manifestation of biologicalstress, regardless of their triggering factor. Examples of such substances willbe described, with their mechanisms of involvement in MS, with the aim ofclarifying their possible contribution, as components of supplements, in theadjuvant treatment of the disease, emphasizing, at the same time, the role ofnutrition and the intestinal microbiome (PDF) Mechanistic Interrelation between Multiple Sclerosis and the factors related to Obesity: Involvement of antioxidants. Available from: https://www.researchgate.net/publication/390236804_Mechanistic_Interrelation_between_Multiple_Sclerosis_and_the_factors_related_to_Obesity_Involvement_of_antioxidants [accessed Mar 28 2025].

Sleep disorders and the resultant sleep deprivation (SD) are very common nowadays, resulting in depressed mood, poor memory and concentration, and various important changes in health, performance and safety. They may provoke further impairment of the cell lining of the blood vessels, as acting as a risk factor for cardiovascular disease (CVD) onset and progression. SD may lead to low neuronal regaining and plasticity, drastically affecting brain function. Thus, SD is a known risk factor for mental, behavioral and developmental disorders. Due to the inflammatory and oxidative stressful nature of SD, immune response modulation and antioxidants could be another therapeutic approach, apart from the already known symptomatic treatment with sedatives. Additionally, many drugs approved for other indications and under investigation, have been revisited due to their wide array of pharmacological activities. This review summarizes the main aspects of SD pathology and SD interrelated comorbidities and presents direct and indirect antioxidant molecules and drugs with multi-targeting potential that could assist in the prevention or management of these factors. A number of research groups have investigated well-known antioxidant compounds with multi-targeting cores, combining structural characteristics with properties including antiinflammatory, metal chelatory, gene transcription and immune modulatory that may add towards the effective SD and its associated comorbidities treatment.

Intrauterine growth restriction (IUGR) is the second most common obstetric complication after preterm labor. Appropriate trophoblast differentiation and placental structure, growth and function are key for the maintenance of pregnancy and normal fetal growth, development and survival. Extravillous trophoblast cell proliferation, migration and invasion are regulated by molecules produced by the fetomaternal interface, including autocrine factors produced by the trophoblast, such as insulin-like growth factor (IGF)-1. The aim of the present study was to investigate expression patterns of IGF-1Ea isoform in IUGR placenta compared with appropriate for gestational age (AGA) pregnancies. Placental frozen tissues were collected from 13 AGA and 15 IUGR third trimester pregnancies for detection of IGF-1Ea mRNA expression using reverse transcription-quantitative PCR. Formalin-fixed paraffin-embedded samples from 15 AGA and 47 IUGR pregnancies were analyzed immunohistochemically for the identification and localization of the IGF-1Ea peptide and comparison of clinical and histopathological parameters. To the best of our knowledge, the present study is the first to show IGF-1Ea expression in third trimester human placenta. The results indicated that similar IGF-1Ea mRNA expression levels were present in placental specimens from both groups. Cytoplasmic IGF-1Ea expression was localized in the perivillous syncytiotrophoblast, extravillous trophoblast and endothelium of the villous and decidual vessels in both groups. No significant difference in the scores and intensity of IGF-1Ea expression in perivillous syncytiotrophoblasts were noted in the IUGR vs. AGA pregnancies. Most IUGR cases showed negative IGF-1Ea expression in the extravillous trophoblast, whereas AGA pregnancies showed predominantly positive immunostaining. A sex-specific expression pattern was noted in the extravillous trophoblast, with negative IGF-1Ea expression in the placentas of female IUGR cases. Additionally, positive immunostaining for IGF-1Ea peptide in fetal villous and maternal decidual vessels, was more frequently observed in the IUGR group compared with AGA. In conclusion, no difference in total IGF-1Ea mRNA placental expression was observed between IUGR and AGA pregnancies, likely due to heterogeneity of histological structures expressing this isoform. Negative IGF-1Ea immunohistological expression in the extravillous trophoblast from IUGR placentas, associated with histological changes of maternal malperfusion, may reflect the involvement of this isoform in defective placentation. The presence of IGF-1Ea peptide in the endothelium of the villous vessels in IUGR placentas may indicate a reactive autocrine regulation to compensate for malperfused villi in IUGR pregnancy by regulating angiogenesis and vasodilation. The observed sex differences in IGF-1Ea expression between IUGR and AGA placentas may indicate interactions between sex hormones and selective IGF-1 binding proteins in regulating IGF-1Ea synthesis; however, this requires further elucidation.

Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co-morbidities, including type-2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non-alcoholic fatty liver disease, kidney diseases, respiratory disorders, sleep apnea, musculoskeletal disorders and osteoarthritis, subfertility, psychosocial problems and certain types of cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro-inflammatory polarization of macrophages toward the M1 phenotype, in adipose tissue (AT), with subsequent increased production of pro-inflammatory cytokines and adipokines, inducing therefore an overall, systemic, low-grade inflammation, which contributes to metabolic syndrome (MetS), insulin resistance (IR) and T2DM. Targeting inflammatory mediators could be alternative therapies to treat obesity, but their safety and efficacy remains to be studied further and confirmed in future clinical trials. The present review highlights the molecular and pathophysiological mechanisms by which the chronic low-grade inflammation in AT and the production of reactive oxygen species lead to MetS, IR and T2DM. In addition, focus is given on the role of anti-inflammatory agents, in the resolution of chronic inflammation, through the blockade of chemotactic factors, such as monocytes chemotractant protein-1, and/or the blockade of pro-inflammatory mediators, such as IL-1β, ΤΝF-α, visfatin, and plasminogen activator inhibitor-1, and/or the increased synthesis of adipokines, such as adiponectin and apelin, in obesity-associated metabolic dysfunction.

Vulvar sarcomas located in the Bartholin's gland area are extremely uncommon mesenchymal vulvar tumors. These neoplasms can be mistaken as Bartholin' gland benign lesions such as cysts or abscesses, leading to a delay in the diagnosis of underlying malignancy. Currently, only a few cases of these aggressive cancers have been reported in the literature. A 42-year-old female patient without any previous complaint presented to Obstetrics and Gynecology Department of 'G. Chaztikosta' General Hospital due to a vulvar lump in the area of the left Bartholin's gland with a 6-month history of progressive swelling. Pelvic examination showed a solid mass of 6.5-cm in maximum diameter, localized in the left Bartholin's gland. The patient underwent wide local excision and histopathological examination of hematoxylin and eosin-stained sections indicated intersecting fascicles of spindle cells, with moderate to severe atypia. The number of mitoses was up to 8 per 10 high power fields. The neoplasm to its greatest extent was circumscribed and in places had an invasive growth pattern. Tumoral necrosis was not seen. Involved Bartholin' gland by the tumor was identified. The tumor extended focally to the surgical margin. The neoplastic cells showed positive staining for smooth muscle actin, desmin, HHF35, caldesmon, vimentin and estrogen and progesterone receptors. Immunohistochemistry was negative for S100, myoglobulin, keratin 116, CD117, CD34 and CD31. The patient denied further surgery or/and local radiotherapy, although the mass was >5-cm and a focally infiltrative surgical margin was found. During the close follow-up, no local recurrences or metastases were observed 53 months after surgery. In conclusion, wide local tumor excision with free surgical margins is a good option of surgery for vulvar leiomyosarcomas. In recurrences, a new extensive surgical resection of the lesion and radiotherapy are suggested. Ipsilateral lympadenectomy is indicated when there is a pathologic lymph node. Chemotherapy is provided in cases of distal metastases.

Chronic hyperinsulinemia due to insulin resistance and elevated levels of insulin-like growth factor (IGF)-1 and IGF-2 are suggestive of a significantly higher risk of endometrial carcinoma. There is a wealth of evidence showing differential expression of IGF-1 isoforms in various types of cancer. In the present study, 99 archived endometrial carcinoma tissue sections were retrospectively assessed by immunohistochemistry for IGF-1Ec isoform expression. Expression of IGF-1Ec was also assessed in nine cases of non-neoplastic endometrial tissue adjacent to the tumor, in 30 cases with normal endometrium and in 30 cases with endometrial hyperplasia. Furthermore, the association between IGF-1Ec and the concurrent expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53 or survivin was assessed, as well as their combined expression in association with clinicopathological variables. In endometrial carcinoma, IGF-1Ec expression was high in non-endometrioid carcinoma (serous papillary or clear cell carcinoma) compared with that in endometrioid adenocarcinoma. IGF-1Ec expression was also high in the presence of tumoral necrosis. Furthermore, there was a significant correlation between the histological differentiation and the sum of staining intensity and the number of IGF-1Ec immunopositive cells in endometrial carcinoma. There was a moderate negative correlation between co-expression of IGF-1Ec and PTEN, for both the number of immunopositive cells (P=0.006, ρ=-0.343) and the sum of staining (scores and intensity; P=0.006, ρ=-0.343). Furthermore, there was a positive correlation between the sum of staining (scores and intensity) and co-expression of IGF-1Ec and survivin (P=0.043, ρ=0.225). However, there was no association between concomitant expression of IGF-1Ec and p53. These results emphasized the importance of IGF-1Ec expression during development of non-estrogen dependent endometrial adenocarcinoma. IGF-1Ec and PTEN may function opposingly during endometrial carcinogenesis. By contrast, IGF-1Ec and survivin may share common molecular pathways and may promote, in parallel, tumoral development.

Background/Aims: It is well known that laparoscopic surgery requires the demonstration of a different set of technical skills when compared to open surgery. Laparoscopic training using simulators has been shown to accelerate learning in an efficient and standardized manner. Significant research has been conducted for skills acquisition in abdominal surgery, but in the field of gynecologic laparoscopy the relevant studies are limited. The aim of this study was to compare the training efficacy of virtual reality (VR) simulators and box-trainers (BTs) for skills acquisition in gynecologic surgery, and also to study the transferability of these skills in the performance of more advanced gynecologic operations. Methods: Twenty residents in obstetrics-gynecology with minimal laparoscopic experience were randomized into two equal groups to be trained on either a VR simulator (Group-A) or a BT (Group-B). Group-A was trained on basic tasks (clipping, peg transfer, and cutting), whereas Group-B was trained on ovarian cystectomy and salpingotomy using custom training models. After training, the two groups were assessed on the performance of two laparoscopic gynecologic procedures on a VR simulator (salpingotomy and salpingectomy). Performance metrics included time, instrument pathlength, and various task-specific errors. Results: Both groups demonstrated significant performance improvement in all training tasks, for all but one of the metrics (p < 0.05). After training, both groups had improved performance in the laparoscopic operations using the VR simulator, but this trend was not statistically significant in any metric considered (p > 0.05). Similarly, the post-training performance between the two groups was not statistically different (p > 0.05). Conclusions: Basic skills training on either a VR simulator or BT results in equivalent but not statistically significant performance improvement with more advanced gynecologic laparoscopic tasks on a VR simulator.

Endometrial carcinoma is one of the most common types of gynecological cancer. A total of 99 cases of primary endometrial carcinoma were investigated for survivin expression by immunohistochemistry. Furthermore, the association between concomitant survivin, PTEN and p53 expression, and clinicopathological parameters was examined. Immunopositivity for survivin was identified in 88% of cases. Concomitant survivin, PTEN and p53 expression (staining scores and intensity) was observed in 60% of endometrial adenocarcinomas. A significant association was identified between the sum of staining intensity and scores of survivin immunopositive cells, and patient age (P=0.028), histological grade (P<0.001), clinical stage (P=0.018) and fallopian tube and/or ovarian invasion (P=0.039). A negative tendency for correlation was observed between surivin and PTEN immunostaining scores (P=0.062; ρ=-0.238). Specimens with high scores of survivin expression tended to show decreased scores of PTEN immunostaining, and vice versa. However, in circumstances with an increased co-expression of survivin and PTEN, a statistically significant association with histological types was observed (P=0.020). A statistically significant positive correlation was identified between survivin and p53 sum co-expression (P=0.008; ρ=0.300). Furthermore, a significant association was identified between survivin and p53 concomitant sum expression and age of patients (P=0.001), histological type (P=0.020), clinical stage (P=0.037), histological differentiation (P=0.001) and presence of fallopian tube and/or ovarian invasion (P=0.026). The present findings suggested that survivin may be an indicator of unfavorable outcome in older patients with endometrial carcinoma, in specific circumstances that are dependent on different concomitant genetic alterations and different combinations of molecular signaling pathways. Increased expression levels of survivin and PTEN may serve a role in the development of more aggressive endometrial carcinoma during their interaction. In addition, protein expression levels of survivin and p53 are positively correlated and may share a common molecular pathway to promote endometrial carcinogenesis. These findings provided evidence that survivin and p53 combined may be useful markers for the prediction of tumor behavior and prognosis.

Thanatophoric dysplasia (TD) is a rare form of lethal skeletal dysplasia with underdevelopment of skeleton and dwarfism. The femur is curved in subtype 1, and straight in subtype 2 TD. Other characteristics include a narrow chest, small ribs and hypoplastic lungs. TD is due to activating mutations in fibroblast growth factor receptor 3 (FGFR3), which result in increased receptor activation and alterations in the process of endochondral ossification in all long bones. The aim of the present study was to present the perinatal ultasonographic findings at the 1st and 2nd trimester of a pregnancy and the underlying molecular defect in a fetus with TD type 1, due to a rare mutation in the FGFR3 gene. Ultrasonography performed at the 12w2d of gestation showed increased nuchal translucency (NT). Prenatal karyotype was normal for the XX fetus. Ultrasonography at 17 weeks and 5 days of gestation revealed narrow thorax, abdominal protrusion and a decreased rate of development of the femur (Femur Length, FL < 5th percentile). Molecular genetic analysis to exclude possible overlapping syndromes was performed and revealed de novo c.2419T > G (p. Ter807Gly) (X807G) gene mutation in FGFR3. Fetal autopsy confirmed the prenatal prediction of lethality. We conclude that a fetus with a heterozygous c.2419T > G mutation in FGFR3, presented characteristic biometric parameters and ultrasonographic and autopsy findings consistent with the diagnosis of TD type 1. In addition, the combination of ultrasonography, molecular genetic analysis and autopsy is helpful for the appropriate genetic counselling and perinatal management.