Ethinylestradiol and Levonorgestrel as Active Agents in Normal Skin, and Pathological Conditions Induced by UVB Exposure: In Vitro and In Ovo Assessments.

The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human-A375 and murine-B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells-A375 and improved viability rates of healthy and B164A5 cells. A weak irritant potential exerted by EE and EE + LNG (10 µM) was assessed by the means of a chick chorioallantoic membrane assay. Further studies are required to elucidate the hormones' cell type-dependent antimelanoma effect and the role played by melanin in this context.

The Impact of Covid-19 on Surgical Training and Outcomes: A Multicenter Experience (Greece and Romania).

BACKGROUND: The COVID-19 pandemic has posed unprecedented challenges to health systems worldwide-in delivering care to patients and in maintaining training of their care providers. Surgical specialties have particularly struggled to maintain sufficient levels of training as we have seen significant reductions in the number of surgical beds, operating lists and redeployment of surgical staff to COVID-19 departments or Intensive Treatment Units. METHODS: Comparison of the number of surgical operations performed between January 1st 2019 and December 31st 2020 in 3 surgical departments in Romania (Craiova, Timisoara and Bucharest) and 1 surgical department in Thessaloniki, Greece. Cases were compared on a month to month basis, both elective and emergency operations were included and divided into three main categories based on severity (Minor, Medium, Major). RESULTS: Between 2019 and 2020, there was a 37.04% decrease in the number of surgical procedures, 36.95% for open procedures and 37.20% for laparoscopic procedures. Statistically significant overall reduction was observed in all three centers for both open and laparoscopic operations. In all centers, a statistically significant reduction in medium severity procedures was also observed. CONCLUSION: Globally felt detrimental effect on surgical training, patient contact and mental well-being reflected similarly across surgical specialties in both countries.

Primary parahiatal hernias: A case report and review of the literature.

BACKGROUND: Parahiatal hernias (PHHs) are rare occurring disease, with a reported incidence of 0.2%-0.35% in patients undergoing surgery for hiatal hernia. We found only a handful of cases of primary PHHs in the literature. The aim of this paper is to present a case of a primary PHH and perform a systematic review of the literature. CASE SUMMARY: We report the case of a 60-year-old Caucasian woman with no history of thoraco-abdominal surgery or trauma, which accused epigastric pain, starting 2 years prior, pseudo-angina and bloating. Based on imagistic findings the patient was diagnosed with a PHH and an associated type I hiatal hernia. Patient underwent laparoscopic surgery and we found an opening in the diaphragm of 7 cm diameter, lateral to the left crus, through which 40%-50% of the stomach had herniated in the thorax, and a small sliding hiatal hernia with an anatomically intact hiatal orifice but slightly enlarged. We performed closure of the defect, suture hiatoplasty and a "floppy" Nissen fundoplication. Postoperative outcome was uneventful, with the patient discharged on the fifth postoperative day. We performed a review of the literature and identified eight articles regarding primary PHH. All data was compiled into one tabled and analyzed. CONCLUSION: Primary PHHs are rare entities, with similar clinical and imagistic findings with paraesophageal hernias. Treatment usually includes laparoscopic approach with closure of the defect and the esophageal hiatus should be dissected and analyzed. Postoperative outcome is favorable in all cases reviewed and no recurrence is cited in the literature.

Decreased sEng plasma levels in hypertensive patients with endothelial dysfunction under chronic treatment with Perindopril.

Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction. Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage. Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p<0.01). Conclusion: Decreased sEng plasma levels were found in patients under chronic treatment with perindopril, when compared with other antihypertensive regimens of treatment (beta blockers, calcium channel blockers, and/or diuretics).

Evaluation of Vascular Proliferation in Molecular Subtypes of Breast Cancer.

BACKGROUND: Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the most common method used for evaluation of angiogenesis, it has several limitations. Our aim was to evaluate MVD and microvessel proliferation (MVP) in a series of invasive breast carcinomas and analyze whether angiogenesis is influenced by the molecular phenotype of each tumor. MATERIALS AND METHODS: We examined vascular proliferation using double immunohistochemistry (CD34/Ki67) in a series of 54 invasive breast carcinomas and compared the results with standard MVD, molecular subtypes and other classical parameters. RESULTS: Increased MVD and MVP values were recorded in basal-like subtype, but only the MVP value reached significance among this group of patients (p=0.0001). For all cases combined, increased MVP was significantly correlated with negative estrogen receptor (ER) status (p=0.010) and higher histological grade (p=0.002). CONCLUSION: MVP more accurately reflects the state of angiogenesis in breast cancer, compared with standard MVD. Vascular proliferation was associated with aggressive tumor features, indicating its contribution to tumor progression. The strong association between vascular proliferation and basal-like tumors suggests that this marker can be used for stratification of patients who might benefit from therapies targeting angiogenesis.

Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

Hormone receptors and HER2 expression in primary breast carcinoma and corresponding lymph node metastasis: do we need both?

BACKGROUND: Scattered studies report on controversial results concerning evaluation of primary breast tumors and their matched lymph node metastases. Aim. To investigate the molecular profile of primary breast tumors and corresponding lymph node metastases (LNM) based on estrogen receptor (ER), progesterone receptor (PR) and human epiderma growth factor receptor-2 (HER2 protein). MATERIALS AND METHODS: Sixty-six primary tumors and corresponding axillary lymph node metastases were evaluated by immunohistochemistry for ER, PR and HER2 protein. According to these markers, cases were stratified as Luminal A, B, HER2 subtypes and triple-negative. Results. Thirteen out of 66 cases (19.7%) exhibited different tumor cell phenotypes in nodal metastases compared to primary breast tumors. All cases with hybrid phenotype had metastases with a pure HER2 phenotype. The most frequent switching was observed from luminal A to luminal B phenotype. CONCLUSION: The high rate of discrepancy between primary tumor and nodal metastasis phenotype imposes the need for a comparative assessment of both primary tumor and nodal metastasis before any therapeutic decision, in order to avoid recurrence and to improve patient prognosis and overall survival.

Pathological assessment of tumor biopsy specimen and surgical sentinel lymph node dissection in patients with melanoma.

INTRODUCTION: Actual trends of cutaneous malignant melanoma show a faster increase then other forms of cancer. Early detection and diagnosis, and accurate pathologic interpretation of the biopsy specimen is extremely important for the treatment and prognosis of clinically localized melanoma. The surgical approach to cutaneous melanoma patients with clinically uninvolved regional lymph nodes remains controversial. MATERIALS AND METHODS: A retrospective study of melanoma cases was conducted in the "Casa Austria" Department of Plastic and Reconstructive Surgery, Emergency County Hospital, Timisoara, Romania. We have analyzed the medical records of 21 patients that underwent surgical treatment for different stages of melanoma in the period 2008-2012. For histopathological diagnosis of melanoma and the sentinel lymph node(s) status, tissular fragments were routinely processed. For the difficult cases, additional immunohistochemical investigation was done. RESULTS: A positive family history was noted in two cases. The presence of different sizes and localization of pigmented nevi was found in 38% of the cases. Different types of melanoma like superficial spreading melanoma, nodular melanoma or lentigo malignant melanoma and acral lentiginous melanoma was described. The surgical treatment consisted in all cases in wide excision of the primary tumor and prophylactic dissection of sentinel lymph node after lymphoscintigraphy examination. A positive biopsy of the sentinel lymph node was noted in 4.9% of the cases. CONCLUSIONS: The surgical treatment combining the wide excision of the primary tumor with respect to safe oncological limits with the prophylactic dissection of sentinel lymph node after lymphoscintigraphy examination had the confirmation done by the pathologic interpretation of the biopsy specimen showing that all the patients had a Breslow index more than 1.5 mm.