Caspase 3 Expression Profiles in Meningioma Subtypes Based on Tissue Microarray Analysis.

Background/Aim: Concerning primary central nervous system neoplasms, meningiomas demonstrate the most common type in adults worldwide. Deregulation of apoptotic pathways in malignancies, including meningiomas, is correlated with chemoresistance and poor prognosis. Caspases represent crucial proteins that induce cell apoptosis. This study aimed to correlate caspase 3 protein expression levels to meningioma clinic-pathological features. Materials and Methods: A set of fifty (n=50) meningioma lesions was included in the current analysis including a broad spectrum of histopathological subtypes (meningotheliomatous, psammomatus, transitional, fibrous, angiomatous, microcystic, atypical and anaplastic). Immunohistochemistry was implemented on tissue microarray cores of selected paraffin blocks by applying an anti-caspase 3 antibody. Additionally, an image analysis protocol was also performed in the corresponding immunostained slides. Results: Caspase 3 protein over-expression was detected in 17/50 (34%) cases, whereas the remaining 33 cases (66%) were characterized by medium to low levels of the molecule. Caspase 3 expression was statistically significantly associated with the grade of the analyzed tumors and the mitotic index (p=0.002, p=0.001, respectively). Caspase 3 expression status was also correlated with the histotype of the selected meningiomas (p=0.016). Conclusion: Caspase 3 demonstrated low expression levels in a significant subset of the examined meningiomas correlated with differentiation grade, mitotic activity, and partially with specific histotypes. Agents that could enhance caspase 3 expression - inducing its apoptotic activity - represent a very promising area in oncology for developing novel treatment regimens.

Precision medicine in breast cancer (Review).

Precision medicine in breast cancer is a revolutionary approach that customizes diagnosis and treatment based on individual and tumor characteristics, departing from the traditional one-size-fits-all approach. Breast cancer is diverse, with various subtypes driven by distinct genetic mutations. Understanding this diversity is crucial for tailored treatment strategies that target specific vulnerabilities in each tumor. Genetic testing, particularly for mutations in breast cancer gene (BRCA) DNA repair-associated genes, helps assess hereditary risks and influences treatment decisions. Molecular subtyping guides personalized treatments, such as hormonal therapies for receptor-positive tumors and human epidermal growth factor receptor 2 (HER2)-targeted treatments. Targeted therapies, including those for HER2-positive and hormone receptor-positive breast cancers, offer more effective and precise interventions. Immunotherapy, especially checkpoint inhibitors, shows promise, particularly in certain subtypes such as triple-negative breast cancer, with ongoing research aiming to broaden its effectiveness. Integration of big data and artificial intelligence enhances personalized treatment strategies, while liquid biopsies provide real-time insights into tumor dynamics, aiding in treatment monitoring and modification. Challenges persist, including accessibility and tumor complexity, but emerging technologies and precision prevention offer hope for improved outcomes. Ultimately, precision medicine aims to optimize treatment efficacy, minimize adverse effects and enhance the quality of life for patients with breast cancer.

AKT and PERP Show Higher Expression in Precancerous than in Malignant Skin Neoplasms: Profiling in an Animal Model of Sequential Skin Carcinogenesis.

The primary aim of this study was to evaluate the activation of the PERP and Akt oncogenes in the induction of skin cancer in FVB/N mice by a stepwise chemical process. Forty four-week-old female FVB/N mice were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). In the study, the groups were subjected to a two-stage carcinogenesis procedure. This consisted of an initial application of 97.4 nmol DMBA to shaved skin on the back, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group received no treatment. Skin conditions were monitored weekly for tumor development. At the end of the experiment, the animals were euthanized for further tissue sampling. Examination of the skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were examined both histologically and immunohistochemically. Notably, and PERP expression was higher in precancerous than in malignant tumors. The differences in expression between precancerous and benign tumors provide further evidence of a role for PERP and Akt in the transition from benign to malignant states. Our findings underscore the critical roles of PERP and Akt in the pathogenesis of skin cancer and suggest their potential as biomarkers for early detection and targets for therapeutic intervention.

Clinical Impact of Connexin 43 Deregulation on Myocardial Infraction.

INTRODUCTION: Coronary artery disease (CAD) is a major and multifaceted health problem but also the first cause of death in modern Western societies. Furthermore, myocardial infarction (MI) constitutes a challenge for analysis in the field of molecular mechanisms, early diagnosis and therapeutic approaches, as its incidence increases every year worldwide. Concerning the histopathological diagnosis in the corresponding cases, a variety of immunohistochemistry (IHC) markers and methods are available to support conventional histology diagnosis. Immunohistochemistry techniques are effective for use in forensic pathology, expanding the limits of differential diagnoses in borderline cases, as they can be applied to tissue samples fixed in formalin and embedded in paraffin. OBJECTIVE: The purpose of the current review was to explore the role of connexin 43 (gene locus: 6q22.31) as a reliable biomarker of myocardial disease/infarction and its impact on MI pathology. MATERIAL AND METHOD: A systematic review of the literature was carried out based on the international database PubMed. The majority of medical data referred to articles published after the year 2020, whereas specific references of great importance and value were also included. The following keywords were used: coronary, artery, myocardial, infarction, connexin and immunohistochemistry. RESULTS: A pool of 38 significant articles focused on the mechanisms and novel experimental biomarkers was selected for the present study at the basis of combining molecular knowledge with new clinical features in CAD, and MI histodiagnosis. CONCLUSIONS: The role of connexin 43 - as a significant gap junction intermediate protein - in MI pathology, clinical symptoms and prognosis is critical because its dysfunction is involved in myocardial conduction and the onset of ventricular arrhythmias due to a crucial interruption of the intra-cardiomyocyte's conjunction.

The Role of Platelets and Aneurysm Thrombus in the EVAR Post Implantation Syndrome.

BACKGROUND: Post implantation syndrome (PIS) is a well-defined entity with unclear etiology, complicating a number of patients with abdominal aortic aneurysms treated with endovascular aortic repair (EVAR). The aim of this study was to assess the platelets' role and the influence of aneurysmal sac thrombus volumes in the development of PIS. A retrospective analysis of prospectively collected data was performed, and 76 patients who were treated by EVAR (2011-2013) were studied. Aneurysms with endoleak were not included in the study. Based on the criteria for systemic inflammatory response syndrome (SIRS), 17 patients (22%) developed PIS (which is considered a SIRS analogue), while 59 (78%) did not. METHODS: The 2 groups were compared in relation to the following parameters: baseline platelet count (PLT), decrease of platelet count (PLT drop), volume of the arterial flow before the procedure (V flow), volume of thrombus of the aneurysm (V thromb), ratio of thrombus volume to aneurysm sac volume (V ratio), and the volume of newly formed thrombus (V new). Volume flow measurements were calculated by Osirix software preoperatively and in the first month postoperatively. Parametric and nonparametric techniques (unpaired t-test, Mann-Whitney U test) were used accordingly. RESULTS: Baseline platelets absolute count was greater in the PIS group (239,000 ± 17,000) versus the non-PIS group (194,000 ± 6,900, P = 0.004), and the PLT drop was larger in the PIS group (74,000 ± 15,600 versus 45,000 ± 5,300, P = 0.019). No difference was found regarding the aneurysm volumes (V flow, V thromb, V ratio, and V new) between the 2 groups. CONCLUSIONS: Platelets, in terms of their absolute baseline count and their decrease after the procedure, seem to be an important factor in developing PIS after EVAR. Further, more tailored studies are needed to elucidate the role of platelets and flow or thrombus volumes in the development of PIS.

FGFR2 and NOTCH1 Expression Inversely Correlated in Progressive Cutaneous Carcinogenesis in an Experimental Mouse Model.

Cutaneous squamous cell carcinoma (cSCC) is a common and increasingly prevalent form of skin cancer, posing significant health challenges. Understanding the molecular mechanisms involved in cSCC progression is crucial for developing effective treatments. The primary aim of this research was to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process. Forty female FVB/N mice, aged four weeks, were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). This study involved subjecting the groups to a two-stage carcinogenesis procedure. This included an initial application of 97.4 nmol DMBA on shaved skin on their backs, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group did not receive any treatment. Their skin conditions were monitored weekly to detect tumor development. After the experiment, the animals were euthanized for further tissue sampling. The examination of skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were assessed both histologically and immunohistochemically. Notably, FGFR2 expression was higher in benign, precancerous, and malignant tumors compared to normal tissue. NOTCH1 expression was only elevated in benign tumors compared to normal tissue. This study demonstrates a clear correlation of FGFR2 expression and the progression of cutaneous neoplasms, while NOTCH 1 expression is inversely correlated in FVB/N mice. This suggests an early involvement of these oncogenes in the development of skin tumors.

Symptomatic Unilateral Carotid Artery Disease: An Uncommon but Reversible Cause of Corticobasal Syndrome.

INTRODUCTION: Symptomatic carotid artery disease (CAD) represents an uncommon but treatable cause of corticobasal syndrome. CASE REPORT: We present the clinical details and successful management of a previously healthy 77-year-old patient who presented with 1-year cognitive dysfunction, alien limb syndrome, limb kinetic apraxia, and ipsilateral cortical sensory deficit, fulfilling the criteria of the diagnosis of probable corticobasal syndrome. Imaging modalities, including magnetic resonance imaging and time-of-flight magnetic resonance angiography, revealed acute external borderzone infarcts of the right hemisphere due to symptomatic CAD causing near occlusion of the vessel. The patient underwent a right carotid endarterectomy, leading to a marked improvement in mobility and neuropsychological evaluation. CONCLUSION: This case highlights the importance of swift diagnosis of symptomatic CAD in patients with corticobasal syndrome. Moreover, it emphasizes the efficacy of carotid endarterectomy in achieving symptom improvement in such cases.

Clinical, Histopathological, and Immunohistochemical Characteristics of Predictive Biomarkers of Breast Cancer: A Retrospective Study.

Background/Aim: Breast cancer is a complex disease with variability in clinical manifestation, response to current therapy, and biochemical and histological features among various subgroups. Histologic grading and immuno-histochemical evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index play a crucial role in increasing the differential diagnostic value among various types of breast carcinoma. The aim of this study was to determine the histopathological and immuno-histochemical characteristics of breast tumors from a University Laboratory of Pathology in Greece. Patients and Methods: The study included female patients over 18 years of age, whose histopathological and immunohistochemical reports were stored in the archives of the First Department of Pathology of National and Kapodistrian University of Athens. The study involved 197 female patients with a median age of 70 years and median tumor size of 2.6 cm. Results: Most tumors were located at the left breast and ductal carcinoma was the most common histologic type (35.5%). Most tumors had histologic grade 2 (106, 53.8%), and were classified as TNM stage IIA (65, 33%). Most grade 1 and 2 tumors exhibited high expression of PR, whereas most grade 3 tumors had no PR expression. Moreover, patients with triple-negative cancer presented with grades 2 and 3 at a lower percentage compared to patients without a triple-negative phenotype (p=0.001). Conclusion: The study provided valuable insights into the histopathological and immuno-histochemical characteristics involved in the development and progression of breast cancer.

Treatment with Umbilical Cord Blood Platelet Lysate Gel Improves Healing of Diabetic Foot Ulcer.

BACKGROUND: This study was conducted to examine the hypothesis that umbilical cord blood platelet lysate (UCB-PL) gel has a significant impact on the healing rate of DFU. Μethods: In this open-labeled, randomized controlled trial, 110 patients were randomized to treatment with UCB-PL gel (UCB-PL group, n = 52) every three days for one month or dressing with normal saline (control group, n = 58). All participants were followed up for 20 weeks post treatment. Ulcer surface area was assessed with the imitoMeasure application at two, four, and six weeks, and two, four and six months. This study's main outcome was the reduction in ulcer size over the six-month study period. RESULTS: The mean ulcer area at baseline was 4.1 cm2 in the UCB-PL group and 1.7 cm2 in the control group. At six months post treatment, patients on the UCB-PL treatment displayed a significant reduction in ulcer size compared to baseline 0.12 (0-8.16) in contrast to a more modest change in the control group 1.05 (0-24.7). The ulcer area was decreased at the end of the study in 40 patients (97.6%) in the UCB-PL group and 27 (73%) in the control group (Fisher's p = 0.002). CONCLUSIONS: The application of UCB-PL gel in DFU resulted in a significant reduction in ulcer size compared to regular saline dressing.

A Successful Endovascular Treatment of Massive Hematuria Caused by Aorto-Ureteric Fistula: A Report of a Rare Case.

Fistula formation between the urinary tract and the arterial system is very rare, and usually involves the ureter and the adjacent iliac vessels. Communication of the ureter with the aorta has been described a few times worldwide, and most of them had a fatal outcome. In our case, a 79-year-old man had a history of total cystectomy for malignancy and diversion of both ureters to a single site in the right hypogastrium with the left one crossing over the aorta. He was admitted elsewhere several times for intermittent hematuria, and four months ago the diagnosis of communication of the left ureter with a mycotic aortic pseudoaneurysm was made. He was then referred to an interventional radiologist who sealed the communication. He was admitted to our hospital four months later in a state of hypovolemic shock and massive hematuria. In lack of information, it seemed to us that he had been treated with endovascular aneurysm repair (EVAR) for uretero-aortic communication, and was experiencing a regression because of endoleak formation. We attempted to treat him as type I endoleak with a proximal extension, and upon failure, with distal extensions, but finally we had to 'build' the entire previous graft from the inside to achieve hemodynamic stability. Our patient remained stable, without endoleak on the post-intervention computed tomography angiography (CTA). Post-operatively, we discovered that the initial operation was the formation of a bifurcated graft with multiple bare stents and coil embolization through them. This was done in an attempt to avoid material infection by the mycotic aneurysm. This is an example of a case where 'things got rough' in a lack of information on patients' medical records. Maybe the time has come to adopt the concept of implanting microchips into humans which would enable doctors to access their medical records. This will only serve as a tool for the benefit of the suffering patients, especially when we are dealing with life-threatening situations with no time to be lost.

Visceral Artery Revascularization With the "Roof-Top" Approach: An Alternative Technique With Great Exposure of the Suprarenal Aorta.

Due to the extensive collateral arterial network, symptomatic chronic mesenteric ischemia is a relatively uncommon condition and is associated with severe atherosclerotic disease of all major visceral arteries. Open surgical repair has been commonly used to restore blood supply to the visceral arteries, and the "roof-top" approach has been advocated as an alternative technique to traditional midline incision, mainly because of the great exposure of the suprarenal aorta that it offers. Roof-top approach, in other words, bilateral subcostal incision, is a totally abdominal approach to the suprarenal aorta, and as the title says, it is like a roof-top on the abdominal wall. We present a case of a female patient with intestinal angina that was deemed unsuitable for endovascular repair (ER) and was treated with open surgical repair utilizing the "roof-top" approach.

EGFR and HER-2 oncogenes expression in an experimental model of two-stage chemically induced carcinogenesis in mouse skin.

The aim of the study was to investigate the expression of EGFR and HER-2 oncogenes using an experimental two stage chemically induced carcinogenesis protocol on the dorsal skin in FVB/N mice. Forty female FVB/N mice 4 weeks old, were grouped into one control (n = 8) and two experimental groups (Group A: n = 16, Group B: n = 16) following a randomization process. Two-stage carcinogenesis protocol, was implicated, including an initial treatment with 97.4 nmol DMBA on their shaved dorsal skin and subsequent treatments of 32.4 nmol TPA applications after 13 weeks for Group A and after 20 weeks for Group B. The control group C, received no treatment. Skin was examined weekly for tumor development. Post-experiment, animals were euthanized for tissue analysis. The histological status of the skin lesions in the experimental groups corresponded well with tumour advancement (from dysplasia to poorly-differentiated carcinoma). Tumour sections were evaluated histologically and immunohistochemically. EGFR expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 008 respectively), while tended to be higher in benign tumours (p = 079), compared to normal histology. Moreover, mean percentage of EGFR positive expression in malignant tumours was significantly higher than in benign tumours (p < 001). HER-2 expression was found significantly higher in precancerous and malignant tumours (p = 042 and p = 015 respectively), while tended to be higher in benign tumours (p = 085), compared to normal histology. Furthermore, mean percentage of HER-2 positive expression in malignant tumours was significantly higher than in benign tumours (p = 005). The study demonstrated that in FVB/N mice subjected to a two-stage chemically induced carcinogenesis protocol, there was a significant increase in the expression of EGFR and HER-2 oncogenes in precancerous and malignant skin lesions compared to normal tissue. This suggests a potentially early role of these oncogenes in the progression of skin tumours in this model.

Associations of long non-coding RNAs HOTAIR, LINC00951, POLR2E and HULC polymorphisms with the risk of esophageal and esophagogastric junction cancer in a western population: a case-control study.

BACKGROUND: The incidence of single-nucleotide-polymorphisms with malignant potential in esophageal cancer tissues has only been sparsely investigated in the west. Hence, we explored the contribution of four long non-coding RNAs' polymorphisms HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016 and HULC rs7763881 in esophageal cancer susceptibility. METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated for esophageal/esophagogastric junction carcinoma during 25/03/2014-25/09/2018 were processed. Demographic data, histopathological parameters, surgical and oncological outcomes were collected. DNA findings of the abovementioned population were compared with 121 healthy community controls. Both populations were of European/Greek ancestry. Sixty-seven patients underwent Ivor Lewis/McKeown esophagectomy for either squamous cell esophageal carcinoma (N = 6) or esophageal/esophagogastric junction Siewert I or II adenocarcinoma (N = 61). Twenty-eight patients were subjected to extended total gastrectomy for esophagogastric junction Siewert III adenocarcinoma. Neither LINC00951 rs11752942 nor HULC rs7763881 polymorphisms were detected more frequently in esophageal cancer patients compared with healthy community subjects. A significantly higher presence of HOTAIR rs920778 TT genotype in esophagogastric junction Siewert I/II adenocarcinoma was identified. POLR2E rs3787016 C allele and CC genotypes were overrepresented in the control group, and when found in esophageal cancer carriers were associated with earlier disease stages, as well as with minor lymph node involvement and lesser metastatic potential. CONCLUSIONS: HOTAIR rs920778 may serve as a potential therapeutic suppression target, while POLR2E rs3787016 may represent a valuable biomarker to evaluate esophageal cancer predisposition and predict treatment response and prognosis. Clinical implications of these findings need to be verified with further prospective studies with larger sample-size.

Genetic Impact of HOTAIR, LINC00951, POLR2E and HULC Polymorphisms in Histopathological and Laboratory Prognostic Factors in Esophageal Cancer in the West: A Case-Control Study.

Long non-coding RNAs' HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016, and HULC rs7763881 are progressively reported having a close genetic affinity with esophageal carcinogenesis in the East. Nonetheless, their correlation with variables already endorsed as significant prognostic factors in terms of staging, guiding treatment and predicting recurrence, metastasis, and survival have yet to be explored. Herein, we investigated their prognostic value by correlating them with clinicopathological and laboratory prognostic markers in esophageal cancer in the West. Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated on for esophageal cancer between 2014 and 2018 were compared with 121 healthy community controls. HULC was not detected differently in any of the cancer prognostic subgroups. LINC00951 was underrepresented in Ca19.9 elevated subgroup. HOTAIR was more frequent in both worse differentiation grade and positive Signet-Ring-Cell and Ca19.9 subgroups. POLR2E was identified less frequently in Adenocarcinoma, Signet-Ring-Cell, and Diffuse histologies, as well as in Perineural, Lymphovascular, and Perivascular Invasion positive, while it was overrepresented in CEA positive subgroup. These lncRNAs polymorphisms may hold great potential not only as future therapeutic agents but also as novel markers for predictive analysis of esophageal cancer risk, clinical outcome, and survival. Clinical implications of these findings need to be validated with prospective larger sample-size studies.

The Immunohistochemical Expression of REV-7 in Various Human Cancer Pathology Specimens: A Systematic Review.

The purpose of this systematic review is to summarize all existing evidence, regarding the immunohistochemical expression of REV-7 in different human cancer pathology specimens. Moreover, the association of REV-7 expression with disease severity (clinical course), patients' survival, prognosis, and response to various treatments, such as chemotherapy and irradiation, was investigated. Three databases (PubMed, Scopus, and Cochrane) were systematically screened, from inception to September 2, 2023, as suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies using immunohistochemical staining for REV-7 in paraffin-embedded cancer tissues were included. Nine studies met the inclusion criteria and were included in the final qualitative synthesis. All nine studies were retrospective and non-comparative ones. Selected studies reported immunohistochemical expression of REV-7 in different types of cancer, including testicular cancer, ovarian cancer, esophagus squamous cell carcinoma, prostate cancer, colorectal cancer, diffuse large B-cell lymphoma, breast cancer, lung cancer, and skin cancer. High REV-7 expression was associated with faster disease progression, resistance to available treatment options, and worse prognosis in the majority of included studies. These results indicate that immunohistochemical staining of REV-7 protein could potentially be used as a predictive tissue marker in certain cases. Promising results, arising from REV-7 inactivation experiments, render REV-7 targeting a potential therapeutic strategy for future cancer management, especially in the cases of chemoresistant or radioresistant disease.

Predictive tissue markers in testicular germ cell tumors: Immunohistochemical expression of MLH1 and REV-7 proteins.

PURPOSE: Testicular Germ Cell Tumors (TGCTs) are the most frequent solid malignancies in young adult men. Regardless of differences in their cell of origin, all TGCTs are considered highly curable malignancies. However, approximately 3-5% of all TGCTs do not respond to platinum-based chemotherapies. The purpose of our paper is to investigate whether immunohistochemical expression of MLH1 and REV-7 can be used as predictive tissue markers for TGCTs. MATERIAL AND METHODS: The main demographic and clinicopathological characteristics of 64 male patients with TGCTs who underwent orchiectomy from 2007 to 2022 were retrospectively obtained from two large Oncology Clinics in Greece. Both patients with chemosensitive and chemoresistant disease were included. Immunohistochemical staining for MLH1 and REV-7 proteins was applied in specimens of these patients. RESULTS: 31 seminomas and 33 non-seminomas were included. 48 patients had chemosensitive disease, while 16 had chemoresistant disease. 53 specimens showed preserved MLH1 expression, while 11 specimens had lost MLH1 expression. Expression of MLH1 was only significantly associated with patients' age. 16 specimens showed positive REV-7 expression, while 48 specimens were REV-7 negative. Interestingly, 50% of patients with chemoresistant disease and 16,7% of patients with chemosensitive disease were REV-7 positive. This difference was statistically significant. Moreover, REV-7 positivity was significantly associated with chemoresistance, various clinicopathological parameters and patients' prognosis and survival. CONCLUSION: Loss of MLH1 expression was only found to be significantly associated with lower patients' age. Positive immunohistochemical REV-7 expression was significantly associated with various clinicopathological parameters, while it was also associated with significantly lower survival and greater hazard. REV-7 positive percentages were significantly higher in patients with chemoresistant disease. Our findings imply that immunohistochemical staining for REV-7 could potentially be used as a predictive tissue marker for TGCT tumors. Moreover, targeting of REV-7 protein, could represent a potential therapeutic strategy for chemoresistant TGCT cases. The implementation of well-designed studies on a larger scale is of utmost importance, in order to draw safer conclusions. Additional studies are needed so as to draw safer conclusions.

A Greek Multicentre Study Assessing the Outcome of Late Rupture After Endovascular Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Late rupture after endovascular aortic aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA) is an increasing complication associated with a high mortality rate. This study aimed to analyse the causes and outcomes in patients with AAA rupture after EVAR. METHODS: A multi-institutional Greek study of late ruptures after EVAR between 2008 - 2022 was performed. Primary outcomes were intra-operative and in hospital death. RESULTS: A total of 70 patients presented with late rupture after EVAR (proportion of ruptured EVARs among all EVARs, 0.6%; 69 males; mean age 77.2 ± 6.7 years). The mean time interval between EVAR and late rupture was 72.3 months (range 6 - 180 months). In all cases the cause of rupture was the presence of an endoleak (type I, 73%) with sac enlargement. Moreover, 34% of subjects with rupture after EVAR had been lost to follow up and 32% underwent a secondary intervention. Additionally, 57 patients (81%) were treated by conversion to open surgical repair (COSR) and the remainder by endovascular correction of endoleak (ECE). Eleven intra-operative deaths (16%) were recorded. The overall in hospital mortality rate was 41% (23% ECE vs. 46% COSR; p = .21). Of the patients who presented as initially haemodynamically stable, 23% died during hospitalisation, while the respective mortality rate for patients who presented as unstable was 78% (odds ratio [OR] 11.8, 95% confidence interval [CI] 3.6 - 39.1; p < .001). Multivariable logistic regression analysis revealed that severity of haemodynamic shock was the most significant risk factor for intra-operative (OR 7.15, 95% CI 1.58 - 32.40; p = .010) and in hospital death (OR 9.53, 95% CI 2.79 - 32.58; p < .001). CONCLUSION: These data underline the devastating prognosis of late rupture after EVAR. Haemodynamic status at presentation was an important predictive factor for death both in the ECE and COSR groups. Rigorous follow up and prompt evaluation of an unstable patient in case of rupture after EVAR is recommended.

Understanding the Role of Radio-Sensitizing Nanoparticles in Enhancing Pathologic Response in Soft Tissue Sarcomas.

High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes.

Incorporating Medical Museum Specimens Into the Training of Environmental Health Students.

Xenobiotics, radiation, and other environmental health risk factors leave their mark on human organs. This can be demonstrated through the use of pathology museum specimens. Upon completing two semesters of postgraduate studies in environmental health, a tour of the Museum of Pathology is offered to postgraduate students at Athens Medical School who are being trained in environmental health. A structured questionnaire is employed to assess the specimens' impact on several aspects: improving students' observational skills, reinforcing the taught material, acquiring new relevant knowledge, and cultivate the social-cognitive ability of empathy. Additionally, students are asked to evaluate the necessity of preserving metadata associated mainly with the social context of the specimens. This research-educational initiative, a component of an ongoing larger project, underscores the significant educational and research value of museum specimens pertaining to environmental health. Furthermore, effectively utilizing such exhibits can enrich the museum experience for visitors and increase public awareness of environmental health issues.

Heat Shock Proteins' Expression Profiles in Odontogenic Ameloblastomas and Cysts.

Tumors and cysts with odontogenic origin represent a family of lesions with specific histo-genetic and clinical characteristics. Among them, ameloblastomas are common benign neoplasms, predominantly detected in the anatomic areas of the jaws and also in the mandible and maxilla. Although they are characterized by a slow and stable growing pattern, a subset of them shows a tendency for local tissue invasiveness and partially increased recurrence rates after surgical excision. Furthermore, heat shock proteins (HSPs) are potentially implicated in ameloblastoma onset and progression. HSPs regulate the folding and refolding of proteins and are induced in response to oxidative stress. They are crucial members of the chaperone intracellular system and are categorized based on their molecular weight (i.e., HSP27, HSP60, HSP70, HSP90). In the current review, we describe HSPs origin and function, focusing on their deregulation mechanisms and impact predominantly on ameloblastomas and also on inflammatory and developmental odontogenic cystic lesions.