Achaiki Iatriki : official publication of the medical society of western Greece and Peloponnesus

In the current issue, the editorial by Cauchi et al. argues for eco-friendly measures in endoscopy and emphasies the role of healthcare providers in reducing waste. The editorial adeptly employs the three Rs (Reduce, Reuse, Recycle) framework to tackle waste management, offering practical solutions. The editorial by Milionis et al. focuses on the reverse cascade screening for paediatric familial hypercholesterolaemia (FH), which is an upcoming tool for public health. Advantages, practices, and challenges regarding FH are thoroughly discussed. Lastly, the editorial by Fousekis et al. presents the main aspects of a chronic immune-mediated cutaneous disease, dermatitis herpetiformis (DH), which constitutes an extraintestinal manifestation of celiac disease, including its diagnosis, pathogenesis, and management. Moreover, this issue includes three review articles. The review article by Krontira et al. discusses the evolving data on the epidemiology, diagnostic approach and appropriate management of foreign body and caustic substance ingestion, based on updated guidelines published by gastroenterological and endoscopic societies. The review by Halliasos et al. provides data on the clinical presentation, diagnosis, and management of metastatic acute spinal cord compression, focusing on the importance of a multidisciplinary team approach, including spine surgeons, radiation oncologists, medical oncologists, palliative care clinicians, physiotherapists, and psychologists. Lastly, the review by Schinas et al. outlines the potential of immune modulation in the treatment of infections and the need for individualised approaches in the modern world of personalised medicine by examining some of the key strategies and immune-based therapies being developed to combat infectious diseases.peer-reviewe

Prostate Cancer: Pathophysiology, Pathology and Therapy

Prostate cancer (PCa) is a major health care challenge in the developed world, being the most common type of cancer in men in the USA [...

Ανάπτυξη μεθοδολογίας για τη λήψη αποφάσεων για βιο-ενεργειακές μετασκευές βιομηχανικών μονάδων

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Περιβάλλον και Ανάπτυξη

Morphologic study of the crosstalk between the epithelium and the microenvironment during colorectal carcinogenesis in view of the development of chemopreventive and targeted therapeutic strategies

Background: Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue mediated mainly through estrogen receptor beta (ERβ). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Methods: Expression of Era, ERβ1 and the ER coregulators AIB-1, TIF-2, PELP1 and NCoR were evaluated in 107 colorectal carcinomas, 77 paired samples of normal mucosa and 29 adenomas by immunohistochemistry. Additionally, the expression pattern of ALDH1 in 98 specimens of colorectal carcinomas and 66 paired samples of normal mucosa was analyzed. Results: Nuclear expression of ERβ1, AIB-1, TIF-2 and PELP1 in myofibroblasts gradually increased from normal mucosa through adenomas to carcinomas. Regarding the epithelium, no difference was noted in the expression of ERs AIB-1, TIF-2 and PELP1 between normal mucosa adenomas and carcinomas. However, nuclear expression of NCoR in epithelial cells was more common in normal mucosa, whereas cytoplasmic expression was higher in carcinomas. Cytoplasmic expression of NCoR in epithelial cells correlated with better disease free and overall survival on univariate analysis and was an independent prognostic marker for disease free survival on multivariate analysis. Rare nuclear NCoR positive cells may represent the cancer stem cells of colorectal carcinomas ALDH1 has been proposed as a promising functional marker of normal and cancer stem cells of various origins. In our study ALDH1 expression displayed a specific pattern of localization in epithelial cells of normal mucosa. Staining was intensified in the epithelial cells located at the basal portion of the crypts, whereas expression was fainter in cells of the surface epithelium. Carcinomas displayed lower levels of ALDH1 expression in epithelial cells. Regarding myofibroblasts ALDH1 expression in pericryptal myofibroblasts of normal mucosa was very rare whereas carcinoma associated myofibroblasts displayed higher levels of ALDH1 expression. Increased expression of ALDH1 in malignant epithelial cells correlated with metastasis increased probability of relapse and shorter disease free survival whereas increased expression in myofibroblasts correlated with lower probability of relapse and longer disease free survival on univariate analysis. Notably the combination of increased expression in epithelial cells and decreased expression in myofibroblasts was associated with worse disease free and overall survival. Our findings imply that ERβ1 dependent signal transduction in myofibroblasts may be involved in the initiation and progression of colorectal carcinomas. Additionally, increased expression of ALDH1 in normal mucosa might delineate the stem cell/progenitor cell compartment of colonic epithelium. During colorectal carcinogenesis distinct functions of ALDH1 might be noted depending on the cell where it is expressed.Σκοπός: Οι μέχρι τώρα ενδείξεις από τη βιβλιογραφία εισηγούνται ένα πιθανό προστατευτικό ρόλο των οιστρογόνων στην καρκινογένεση στο παχύ έντερο. Η έκφραση των οιστρογονικών υποδοχέων στο φυσιολογικό βλεννογόνο του παχέος εντέρου στα αδενώματα και τα καρκινώματα και οι αλληλεπιδράσεις τους με διάφορους συμπαράγοντες θα πρέπει να μελετηθούν υπό το πρίσμα των πολύπλοκων μοριακών δικτύων μεταξύ επιθηλιακών κυττάρων και μυοϊνοβλαστών (MF) του στρώματος. Μέθοδος: Οι οιστρογονικοί υποδοχείς ERa και ERβ1 και οι συν-ρυθμιστές της μεταγραφής ΑΙΒ-1, TIF-2 PELP1 και NCoR μελετήθηκαν ανοσοϊστοχημικά σε 107 καρκινώματα παχέος εντέρου, 77 δείγματα φυσιολογικού βλεννογόνου και 29 αδενώματα. Επίσης μελετήθηκε η έκφραση ALDH1 σε 98 καρκινώματα και 66 συζευγμένα δείγματα φυσιολογικού βλεννογόνου. Εκτιμήθηκαν τόσο τα επιθηλιακά κύτταρα όσο και οι MF. Αποτελέσματα: Η έκφραση των ERβ1, ΑΙΒ-1, TIF-2 και PELP1 ήταν πιο συχνή σε MF του στρώματος των καρκινωμάτων σε σχέση με τα αδενώματα και το φυσιολογικό βλεννογόνο. Αντίθετα δεν υπήρχε διαφορά μεταξύ του φυσιολογικού βλεννογόνου των αδενωμάτων και των καρκινωμάτων στο ποσοστό έκφρασης των δεικτών αυτών στα επιθηλιακά κύτταρα. Επίσης ο NCoR εκφραζόταν πιο συχνά στο κυτταρόπλασμα και σπανιότερα στον πυρήνα των κακοήθων επιθηλιακών κυττάρων σε σχέση με τα φυσιολογικά επιθηλιακά κύτταρα. Η κυτταροπλασματική έκφραση του NCoR στα επιθηλιακά κύτταρα σχετιζόταν με μεγαλύτερη ελεύθερη νόσου και συνολική επιβίωση και αποτελούσε ανεξάρτητο προγνωστικό δείκτη της ελεύθερης νόσου επιβίωσης. Τα αποτελέσματά μας υποδεικνύουν ένα πιθανό ρόλο της ενεργοποίησης του μονοπατιού των οιστρογονικών υποδοχέων στους MF του στρώματος στην ανάπτυξη των καρκινωμάτων του παχέος εντέρου. Δεδομένου ότι η πυρηνική έκφραση του NCoR έχει προταθεί ως δείκτης των stem κυττάρων, τα ελάχιστα κύτταρα στα οποία παρατηρήθηκε πυρηνική έκφραση στον καρκίνο παχέος εντέρου πιθανότατα αντιστοιχούν σε καρκινικά stem κύτταρα. Η αλδεϋδική δεϋδρογενάση (ALDH1) αποτελεί δείκτη φυσιολογικών και καρκινικών stem κυττάρων σε διάφορα όργανα. Στη μελέτη μας η ALDH1 εκφράστηκε έντονα στα κύτταρα του φυσιολογικού βλεννογόνου που βρίσκονταν στη βάση των κρυπτών περιοχή όπου εντοπίζονται τα stem/προγονικά κύτταρα του εντερικού επιθηλίου. Κατά αντιστοιχία, η έκφραση της ALDH1 στα καρκινικά κύτταρα σχετιζόταν με παρουσία μεταστάσεων και χειρότερη ελεύθερη νόσου επιβίωση. Αντίθετα, η έκφραση ALDH1 στους MF των καρκινωμάτων σχετιζόταν με ευνοϊκούς προγνωστικούς παράγοντες και μεγαλύτερο ελεύθερο νόσου διάστημα. Επίσης, περιστατικά με χαμηλή έκφραση ALDH1 στους MF και υψηλή έκφραση στα επιθηλιακά κύτταρα σχετιζόταν με μικρότερο διάστημα ελεύθερης νόσου και συνολικής επιβίωσης. Τα ευρήματα αυτά υποδεικνύουν το σημαντικό ρόλο των πολύπλοκων αλληλεπιδράσεων επιθηλίου στρώματος κατά την καρκινογένεση στο παχύ έντερο και επισημαίνουν τα πολύπλοκα μοριακά δίκτυα που ρυθμίζουν τη λειτουργία των επιθηλιακών κυττάρων

Radical or Not-So-Radical Prostatectomy: Do Surgical Margins Matter?

Prostate cancer is the second most common malignancy in men, and prostatectomy is the treatment of choice for most patients with at least low risk of progression. The presence of positive margins in the radical prostatectomy specimen is considered an adverse pathologic feature, and may prompt additional therapeutic intervention in the patients. The absence of a distinct capsule around the prostate and intraoperative manipulations that aim to minimize postoperative adverse effects, complicate its wide removal. Proper handling of the specimen during the gross processing is essential for accurate determination of the status of margins or resection. Positive margins, defined as the presence of neoplastic glands in the highlighted-with-ink margin of resection, range from 6–38%. The surgical technique, surgeon’s expertise and tumor (i.e., grade and stage) and patients’ (i.e., BMI) characteristics affect the rate of margin positivity. Extensive or multifocal and nonanterior/nonapical positive margins are linked with higher recurrence rates, especially in organ-confined disease, underscoring the need for treating these patients more aggressively. In summary, detailed description of the status of the margins should be performed in every pathology report to determine patients’ prognosis and the most appropriate therapeutic plan

Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review

Prostate cancer (PC) is a common malignancy among elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant of prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in the tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53), and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice

Cribriform Patterned Lesions in the Prostate Gland with Emphasis on Differential Diagnosis and Clinical Significance

Cribriform glandular formations are characterized by a continuous proliferation of cells with intermingled lumina and can constitute a major or minor part of physiologic (normal central zone glands), benign (clear cell cribriform hyperplasia and basal cell hyperplasia), premalignant (high-grade prostatic intraepithelial neoplasia), borderline (atypical intraductal cribriform proliferation) or clearly malignant (intraductal, acinar, ductal and basal cell carcinoma) lesions. Each displays a different clinical course and variability in clinical management and prognosis. The aim of this review is to summarize the current knowledge regarding the morphological features, differential diagnosis, molecular profile and clinical significance of the cribriform-patterned entities of the prostate gland. Areas of controversy regarding their management, i.e., the grading of Intaductal Carcinoma, will also be discussed. Understanding the distinct nature of each cribriform lesion leads to the correct diagnosis and ensures accuracy in clinical decision-making, prognosis prediction and personalized risk stratification of patients

The Contribution of Lipidomics in Ovarian Cancer Management: A Systematic Review

Lipidomics is a comprehensive study of all lipid components in living cells, serum, plasma, or tissues, with the aim of discovering diagnostic, prognostic, and predictive biomarkers for diseases such as malignant tumors. This systematic review evaluates studies, applying lipidomics to the diagnosis, prognosis, prediction, and differentiation of malignant and benign ovarian tumors. A literature search was performed in PubMed, Science Direct, and SciFinder. Only publications written in English after 2012 were included. Relevant citations were identified from the reference lists of primary included studies and were also included in our list. All studies included referred to the application of lipidomics in serum/plasma samples from human cases of OC, some of which also included tumor tissue samples. In some of the included studies, metabolome analysis was also performed, in which other metabolites were identified in addition to lipids. Qualitative data were assessed, and the risk of bias was determined using the ROBINS-I tool. A total of twenty-nine studies were included, fifteen of which applied non-targeted lipidomics, seven applied targeted lipidomics, and seven were reviews relevant to our objectives. Most studies focused on the potential application of lipidomics in the diagnosis of OC and showed that phospholipids and sphingolipids change most significantly during disease development. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management

Contemporary Grading of Prostate Cancer: The Impact of Grading Criteria and the Significance of the Amount of Intraductal Carcinoma

(1) Background: Prognostic grade group (PGG) is an important prognostic parameter in prostate cancer that guides therapeutic decisions. The cribriform pattern and intraductal carcinoma (IDC) are two histological patterns, that have additional prognostic significance. However, discrepancies exist regarding the handling of IDC according to the guidelines published by two international genitourinary pathology societies. Furthermore, whether, in addition to its presence, the amount of IDC is also of importance has not been studied before. Lastly, the handling of tertiary patterns has also been a matter of debate in the literature. (2) Methods: A total of 129 prostatectomy cases were retrieved and a detailed histopathologic analysis was performed. (3) Results: Two cases (1.6%) upgraded their PGG, when IDC was incorporated in the grading system. The presence and the amount of IDC, as well as the presence of cribriform carcinoma were associated with adverse pathologic characteristics. Interestingly, in six cases (4.7%) there was a difference in PGG when using the different guidelines regarding the handling of tertiary patterns. In total, 6.2% of the cases would be assigned a different grade depending on the guidelines followed. (4) Conclusions: These findings highlight a potential area of confusion among pathologists and clinicians and underscore the need for a consensus grading system

Elucidating the role of PRMTs in prostate cancer using open access databases and a patient cohort dataset

Protein arginine methylation is an understudied epigenetic mechanism catalyzed by enzymes known as Protein Methyltransferases of Arginine (PRMTs), while the opposite reaction is performed by Jumonji domain- containing protein 6 (JMJD6). There is increasing evidence that PRMTs are deregulated in prostate cancer (PCa). In this study, the expression of two PRMT members, PRMT2 and PRMT7 as well as JMJD6, a demethylase, was analyzed in PCa. Initially, we retrieved data from The Cancer Genome Atlas (TCGA) project and the Gene Expression Omnibus (GEO) database to explore the differential expression of various PRMT family members in patients with PCa and then applied immunohistochemistry in a patient cohort across the spectrum of PCa, including non-neoplastic prostate tissue and lymph node metastatic foci. The results from the TCGA analysis revealed that PRMT7, PRMT6 and PRMT3 expression increased while PRMT2, PRMT9 and JMJD6 levels decreased in the tumor compared to non-neoplastic prostate. Results from the GEO datasets were similar, albeit not identical with the TCGA results, with PRMT7 and PRMT3 being upregulated and PRMT2 and JMJD6 being downregulated in the tumor compared to non-neoplastic tissue in some of them. In addition, PRMT7 levels decreased with stage and grade progression in the TCGA analysis. In the patient cohort, both PRMTs and JMJD6 were overexpressed in PCa compared to non-neoplastic tissue, and nuclear PRMT2 and JMJD6 were upregulated in lymph node metastasis, too. PRMT7 and JMJD6 expression were upregulated with the progression of stage and JMJD6 was also increased with the elevation of grade. After androgen ablation therapy, nuclear expression of PRMT7 and JMJD6 were elevated compared to untreated tumors. PRMT2, PRMT7 and JMD6 were also correlated with markers of EMT and cell cycle regulators. Finally, our findings indicate that PRMTs and JMJD6 are involved in prostate cancer progression and revealed a potential interplay of PRMTs with EMT mediators, underscoring the need for therapeutic targeting of arginine methylation in prostate cancer