A Histological Analysis and Detection of Complement Regulatory Protein CD55 in SARS-CoV-2 Infected Lungs.

BACKGROUND: A complement imbalance in lung alveolar tissue can play a deteriorating role in COVID-19, leading to acute respiratory distress syndrome (ARDS). CD55 is a transmembrane glycoprotein that inhibits the activation of the complement system at the intermediate cascade level, blocking the activity of the C3 convertase. OBJECTIVE: In our study, lung specimens from COVID-19 and ARDS-positive COVID+/ARDS+ patients were compared with COVID-19 and ARDS-negative COVID-/ARDS- as well as COVID-/ARDS+ patients. METHODS: Histochemical staining and immunolabeling of CD55 protein were performed. RESULTS: The COVID-/ARDS- specimen showed higher expression and homogeneous distribution of glycosaminoglycans as well as compactly arranged elastic and collagen fibers of the alveolar walls in comparison to ARDS-affected lungs. In addition, COVID-/ARDS- lung tissues revealed stronger and homogenously distributed CD55 expression on the alveolar walls in comparison to the disrupted COVID-/ARDS+ lung tissues. CONCLUSIONS: Even though the collapse of the alveolar linings and the accumulation of cellular components in the alveolar spaces were characteristic of COVID+/ARDS+ lung tissues, evaluating CD55 expression could be relevant to understand its relation to the disease. Furthermore, targeting CD55 upregulation as a potential therapy could be an option for post-infectious complications of COVID-19 and other inflammatory lung diseases in the future.

Application of the 5th WHO Guidelines for the Diagnosis of Lung Carcinoma in Small Lung Biopsies in a Tertiary Care Center: Is Insecurity of Pathologists for the Accurate Diagnosis Justified?

BACKGROUND/OBJECTIVES: The diagnosis of lung carcinoma (LC) is currently performed in small biopsies and according to the WHO classification by using limited stains to spare tissue for molecular testing. This procedure, however, often causes diagnostic uncertainty among pathologists. METHODS: In this retrospective analysis, we compared the diagnosis made by these guidelines in 288 lung biopsies with that using more stains, as retrieved from our archive. We also compared the results of p63 and p40 immunoexpression and investigated the diagnostic role of p53/Rb1. RESULTS: In our investigation, we reached a definite diagnosis with a mean number of one stain compared with six stains in the original diagnostic procedure, with a 97.3% concordance rate. Only in the case of metastases, a clear advantage is proven in the use of more stains, especially in the absence of clinical information. We also found a comparable utility of p40 and p63 for the diagnosis of squamous cell carcinoma, despite the higher p63 expression in other histological types. Moreover, normal p53/Rb1 expression could be utilized for the exclusion of small-cell LC. CONCLUSIONS: Our study confirms the diagnostic certainty achieved by the suggestions of the WHO classification and justifies the potential insecurity in the absence of adequate communication with the treating clinician.

The Impact of DAXX, HJURP and CENPA Expression in Uveal Melanoma Carcinogenesis and Associations with Clinicopathological Parameters.

Uveal melanomas (UMs) represent rare malignant tumors associated with grim prognosis for the majority of patients. DAXX (Death Domain-Associated Protein), HJURP (Holliday Junction Recognition Protein) and CENPA (Centromere Protein A) proteins are implicated in epigenetic mechanisms, now in the spotlight of cancer research to better understand the molecular background of tumorigenesis. Herein, we investigated their expression in UM tissues using immunohistochemistry and explored possible correlations with a multitude of clinicopathological and survival parameters. The Cancer Genome Atlas Program (TCGA) was used for the investigation of their mRNA levels in UM cases. Nuclear DAXX expression correlated with an advanced T-stage (p = 0.004), while cytoplasmic expression marginally with decreased disease-free survival (DFS) (p = 0.084). HJURP nuclear positivity also correlated with advanced T-status (p = 0.054), chromosome 3 loss (p = 0.042) and increased tumor size (p = 0.03). More importantly, both nuclear and cytoplasmic HJURP immunopositivity correlated with decreased overall survival (OS) (p = 0.011 and 0.072, respectively) and worse DFS (p = 0.071 and 0.019, respectively). Lastly, nuclear CENPA overexpression was correlated with presence of irido-corneal angle involvement (p = 0.015) and loss of chromosome 3 (p = 0.041). Nuclear and cytoplasmic CENPA immunopositivity associated with decreased OS (p = 0.028) and DFS (p = 0.018), respectively. HJURP and CENPA mRNA overexpression exhibited strong association with tumor epithelioid histology and was linked to worse prognosis. Our results show the compounding role of DAXX, HJURP and CENPA in UM carcinogenesis, designating them as potential biomarkers for assessing prognosis and possible targets for novel therapeutic interventions.

Clinical Significance of the Immunohistochemical Expression of Histone Deacetylases (HDACs)-2, -4, and -5 in Ovarian Adenocarcinomas.

BACKGROUND: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC-2, -4, and -5 expression in epithelial ovarian carcinoma (EOC). METHODS: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics. RESULTS: HDAC-2 was the most frequently (94.4%) expressed isoform, being marginally higher in serous tumors compared with other types (p = 0.08). HDAC-5 was the less frequently expressed (28.1%), being positively associated with HDAC-4. HDAC-4 positivity was associated with lower FIGO-stage (p = 0.045) and T-category (p = 0.043) and the absence of lymph node (p = 0.05) or distant metastasis (p = 0.09) in serous carcinomas. HDAC-2 positivity was correlated with the absence of lymph node metastasis in serous tumors (p = 0.045). On the contrary, HDAC-5 nuclear positivity was correlated with lymph node metastasis in the entire cohort (p = 0.048). HDAC-4 positivity was marginally associated with favorable prognosis in serous carcinomas in univariate survival analysis (p = 0.086), but this correlation was not significant in multivariate analysis. CONCLUSIONS: These findings suggest a differential expression among HDAC-2, -4, and -5 in ovarian adenocarcinomas in terms of immunolocalization, positivity rate, and associations with clinicopathological parameters, providing evidence for a potential role in the pathobiology of EOC.

Feasibility and Satisfaction With the Word Catheter in Treatment of Bartholin's Cyst and Abscess.

BACKGROUND/AIM: The Word catheter is a silicone device with a balloon system that may be inserted into a Bartholin's cyst or abscess in order to provide drainage and epithelization. The aim of this study was to evaluate the Word catheter as a therapy for Bartholin's cyst and abscess. Both patient and physician satisfaction, as well as the feasibility in an outpatient setting, were examined. PATIENTS AND METHODS: A total of 51 women with a Bartholin's cyst or abscess were given the option of Word catheter insertion in an outpatient setting between August 2013 and March 2018. Both the patients and the consulting physicians were asked to complete two questionnaires, before, during and after treatment, with a view to evaluating the overall pain level, any discomfort symptoms and sexual activity, as well as satisfaction levels. RESULTS: The insertion procedure seemed to constitute a short yet quite painful procedure. In most cases, the consulting physicians and the patients were content with the results. Nevertheless, dislodgement of the catheter or abscess recurrence were common. The removal of the Word catheter seemed to be short, painless, and uncomplicated. Most patients experienced pain and discomfort after catheter placement over the first days, with the symptoms fading over time. Sexual intercourse appeared to be negatively influenced. CONCLUSION: The Word catheter was frequently well tolerated for the treatment of Bartholin's cysts and abscesses, with few non-serious side-effects, however, it did interfere with sexual health. Nonetheless, it may not be possible to make general recommendations based on this exploratory study.

PD-L1 Expression in Neoplastic and Immune Cells of Thymic Epithelial Tumors: Correlations with Disease Characteristics and HDAC Expression.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression in neoplastic and immune cells of the tumor microenvironment determines the efficacy of antitumor immunity, while it can be regulated at the epigenetic level by various factors, including HDACs. In this study, we aim to evaluate the expression patterns of PD-L1 in thymic epithelial tumors (TETs), while we attempt the first correlation analysis between PD-L1 and histone deacetylases (HDACs) expression. METHODS: Immunohistochemistry was used to evaluate the expression of PD-L1 in tumor and immune cells of 91 TETs with SP263 and SP142 antibody clones, as well as the expressions of HDCA1, -2, -3, -4, -5, and -6. RESULTS: The PD-L1 tumor proportion score (TPS) was higher, while the immune cell score (IC-score) was lower in the more aggressive TET subtypes and in more advanced Masaoka-Koga stages. A positive correlation between PD-L1 and HDAC-3, -4, and -5 cytoplasmic expression was identified. CONCLUSIONS: Higher PD-L1 expression in neoplastic cells and lower PD-L1 expression in immune cells of TETs characterizes more aggressive and advanced neoplasms. Correlations between PD-L1 and HDAC expression unravel the impact of epigenetic regulation on the expression of immune checkpoint molecules in TETs, with possible future applications in combined therapeutic targeting.

The Molecular Landscape of Thymic Epithelial Tumors: A Comprehensive Review.

Thymic epithelial tumors (TETs) are characterized by their extreme rarity and variable clinical presentation, with the inadequacy of the use of histological classification alone to distinguish biologically indolent from aggressive cases. The utilization of Next Generation Sequencing (NGS) to unravel the intricate genetic landscape of TETs could offer us a comprehensive understanding that is crucial for precise diagnoses, prognoses, and potential therapeutic strategies. Despite the low tumor mutational burden of TETS, NGS allows for exploration of specific genetic signatures contributing to TET onset and progression. Thymomas exhibit a limited mutational load, with prevalent GTF2I and HRAS mutations. On the other hand, thymic carcinomas (TCs) exhibit an elevated mutational burden, marked by frequent mutations in TP53 and genes associated with epigenetic regulation. Moreover, signaling pathway analyses highlight dysregulation in crucial cellular functions and pathways. Targeted therapies, and ongoing clinical trials show promising results, addressing challenges rooted in the scarcity of actionable mutations and limited genomic understanding. International collaborations and data-sharing initiatives are crucial for breakthroughs in TETs research.

SOX11 and Epithelial-Mesenchymal Transition in Metastatic Serous Ovarian Cancer.

BACKGROUND: Ovarian cancer is the leading cause of death from gynecological malignancies, with serous carcinoma being the most common histopathologic subtype. Epithelial-mesenchymal transition (EMT) correlates with increased metastatic potential, whereas the transcription factor SRY-box transcription factor 11 (SOX11) is overexpressed in diverse malignancies. METHODS: In the present study, we aimed to evaluate the potential role of the immunohistochemical expression of SOX11 in 30 serous ovarian carcinomas in association with E-cadherin and vimentin expression as well as with patients' clinicopathological data. RESULTS: Most of the examined cases showed concurrent expression of E-cadherin and vimentin, whereas SOX11 was expressed in a minority of the cases (26.7%). Interestingly, the positive cases more frequently had a metastatic disease at the time of diagnosis compared with the negative cases (p = 0.09), an association, however, of marginal significance. Moreover, there was a negative correlation between E-cadherin and SOX11 expression (p = 0.0077) and a positive correlation between vimentin and SOX11 expression (p = 0.0130). CONCLUSIONS: The present work, for the first time, provides preliminary evidence of a possible implication of SOX11 overexpression in the promotion of EMT in metastatic serous ovarian cancer, thereby endorsing tumor metastasis.

Searching for Novel Biomarkers in Thymic Epithelial Tumors: Immunohistochemical Evaluation of Hippo Pathway Components in a Cohort of Thymic Epithelial Tumors.

Given the pivotal role of the Hippo pathway in different facets of tumorigenesis, which has been vigorously established in multiple heterogenous malignancies, we attempted to evaluate its potential utility as a prognostic-predictive biomarker in thymic epithelial tumors (TETs). For this purpose, we performed a comprehensive immunohistochemical analysis of four Hippo cascade components (YAP, TAZ, TEAD4 and LATS1) in a sizeable cohort of TETs and attempted to identify possible correlations of their H-score with various clinicopathological parameters. TAZ and TEAD4 displayed both cytoplasmic and nuclear immunoreactivity in almost equal frequency, with their cytoplasmic H-score being strongly associated with more aggressive high-grade tumors (type B3, thymic carcinoma) and more advanced pathological stages. On the other hand, a primarily nuclear staining pattern was encountered in both YAP and LATS1, with the YAP nuclear H-score being higher in more indolent (type A) and earlier stage tumors. Interestingly, none of the four examined factors displayed any statistically significant correlation with patient overall (OS) or disease-free survival (DFS). In summary, our results provide some initial insight into the expression profile of these core Hippo pathway components in thymic neoplasms and point towards some clear associations with tumor characteristics, which are of paramount translational-clinical research with profound implications in therapeutic targeting of this pathway in the context of precision medicine.

Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors.

Accumulating data shows that altered metabolic activity contributes to glioma development. Recently, modulation of SSADH (succinic semialdehyde dehydrogenase) expression, implicated in the catabolism of GABA neurotransmitter, was shown to impact glioma cell properties, such as proliferation, self-renewal and tumorigenicity. The purpose of this study was to investigate the clinical significance of SSADH expression in human gliomas. Using public single-cell RNA-sequencing data from glioma surgical resections, we initially grouped cancer cells according to ALDH5A1 (Aldehyde dehydrogenase 5 family member A1) expression, which encodes SSADH. Gene ontology enrichment analysis of genes differentially expressed between cancer cells expressing high or low levels of ALDH5A1, highlighted enrichment in genes implicated in cell morphogenesis and motility. In glioblastoma cell lines, ALDH5A1 knockdown inhibited cell proliferation, induced apoptosis and reduced their migratory potential. This was accompanied by a reduction in the mRNA levels of the adherens junction molecule ADAM-15 and deregulation in the expression of EMT biomarkers, with increased CDH1 and decreased vimentin mRNA levels. Evaluation of SSADH expression in a cohort of 95 gliomas using immunohistochemistry showed that SSADH expression was significantly elevated in cancer tissues compared to normal brain tissues, without any significant correlation with clinicopathological characteristics. In summary, our data show that SSADH is upregulated in glioma tissues irrespective of the histological grade and its expression sustains glioma cell motility.

Histone Deacetylases (HDACs): Promising Biomarkers and Potential Therapeutic Targets in Thymic Epithelial Tumors.

Histone deacetylases (HDACs) are core epigenetic factors, with pivotal roles in the regulation of various cellular procedures, and their deregulation is a major trait in the acquisition of malignancy properties. In this study we attempt the first comprehensive evaluation of six class I (HDAC1, HDAC2, HDAC3) and II HDACs (HDAC4, HDAC5, HDAC6) expression patterns in thymic epithelial tumors (TETs), with the aim of identifying their possible association with a number of clinicopathological parameters. Our study revealed higher positivity rates and expression levels of class I enzymes compared to class II. Sub-cellular localization and level of staining varied among the six isoforms. HDAC1 was almost exclusively restricted to the nucleus, while HDAC3 demonstrated both nuclear and cytoplasmic reactivity in the majority of examined specimens. HDAC2 expression was higher in more advanced Masaoka-Koga stages, and displayed a positive correlation with dismal prognoses. The three class II HDACs (HDAC4, HDAC5, HDAC6) exhibited similar expression patterns, with predominantly cytoplasmic staining, that was higher in epithelial rich TETs (B3, C) and more advanced tumor stages, while it was also associated with disease recurrence. Our findings could provide useful insights for the effective implementation of HDACs as biomarkers and therapeutic targets for TETs, in the setting of precision medicine.

Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms.

Background: Recent advances demonstrate the role of chromatin regulators, including histone variants and histone chaperones, in cancer initiation and progression. Methods: Histone H3K4me3, histone variant centromere protein (CENP-A) and histone chaperones Holliday junction recognition protein (HJURP) as well as DAXX expression were examined immunohistochemically in 95 thymic epithelial tumor (TET) specimens. Our results were compared with the expression profile of DAXX, HJURP and CENP-A in gene expression profiling interactive analysis (GEPIA2). Results: The lymphocyte-poor B3- and C-type TETs were more frequently DAXX negative (p = 0.043). B3 and C-Type TETs showed higher cytoplasmic and nuclear CENP-A (p = 0.007 and p = 0.002) and higher cytoplasmic HJURP H-score (p < 0.001). Higher nuclear CENP-A and cytoplasmic HJURP expression was associated with advanced Masaoka−Koga stage (p = 0.048 and p < 0.001). A positive correlation between HJURP and CENP-A was also observed. The presence of cytoplasmic CENP-A expression was correlated with a favorable overall survival (p = 0.03). CENP-A overexpression in survival analysis of TCGA TETs showed similar results. H3K4me3 expression was not associated with any clinicopathological parameters. Conclusions: Our results suggest a significant interaction between CENP-A and HJURP in TETs. Moreover, we confirmed the presence of a cytoplasmic CENP-A immunolocalization, suggesting also a possible favorable prognostic value of this specific immunostaining pattern.

Unraveling the Immune Microenvironment of Thymic Epithelial Tumors: Implications for Autoimmunity and Treatment.

Thymic Epithelial Tumors (TETs) represent a rare tumor family, originating from the epithelial component of the thymus gland. Clinicopathologically, they are segregated into six major subtypes, associated with distinct histological features and clinical outcomes. Their emergence and evolution are accompanied by the generation of a complex tumor microenvironment (TME), dominated by phenotypically and functionally divergent immune cellular subsets, in different maturation states and in analogies that vary significantly among different subtypes. These heterogenous leukocyte populations exert either immune-permissive and tumor-suppressive functions or vice versa, and the dynamic equilibrium established among them either dictates the tumor immune milieu towards an immune-tolerance state or enables the development of a productive spontaneous tumoricidal response. The immunologically "hot" microenvironment, defining a significant proportion of TETs, makes them a promising candidate for the implementation of immune checkpoint inhibitors (ICIs). A number of phase I and II clinical trials have already demonstrated significant, type-specific clinical efficacy of PD-L1 inhibitors, even though substantial limitations in their utilization derive from their immune-mediated adverse effects. Moreover, the completed clinical studies involved relatively restricted patient samples and an expansion in the enrolled cohorts is required, so that more trustworthy conclusions regarding the benefit from ICIs in TETs can be extracted.

Infection as a Differential Diagnosis of Solid Retroperitoneal Masses: A Case Series and Review of the Literature.

The differential diagnosis of retroperitoneal masses includes a variety of benign and malignant conditions, among which infections constitute a significant subgroup. Familiarity with these infectious pseudotumours could facilitate prompt diagnosis. In this report, we describe three patients with an infectious pseudotumour, which was clinically and radiologically highly suggestive of a neoplasm. The first patient was a 62-year-old woman with a history of Richter syndrome, who seven months after allogeneic haematopoetic stem cell transplantation from an unrelated donor presented with a renal mass. A renal biopsy at that time revealed necrotic tissue. The patient displayed multiple relapses of Richter syndrome (for which she received also chimeric antigen receptor T-cell therapy salvage chemotherapy) and remissions of the lymphoma as well as an Aspergillus pneumonia for which she was treated with intravenous ambisome and afterwards oral posaconazole. Since the renal mass persisted and to exclude malignancy, nephrectomy was performed which revealed the presence of fungal hyphae. The second patient was a 51-year-old man with a history of a low-grade non-muscle-invasive bladder urothelial carcinoma, who after Mycobacterium bovis Calmette-Guerin instillation presentedwith fever and a suspicious renal mass. A partial nephrectomy was performed. Intraoperative frozen section analysis and routine histology suggested a Mycobacterium bovis-associated lesion, which was confirmed by polymerase chain reaction (PCR) analysis. The third patient was an 85-year-old man who presented with loss of appetite, fatigue, and significant weight loss (24 Kg in less than a year) as well as a travel history. The laboratory tests showed a low sodium and a high potassium level. CT scans revealed a solitary lesion in the right lung, a small liver lesion as well as bilateral adrenal lesions. A CT-guided biopsy revealed the presence of Histoplasma capsulatum, which was confirmed by PCR analysis. A retrospective review of all parameters indicates that all three patients presented with some risk factors, such as immunosuppression, travel, or clinical history that could raise the suspicion of infection in order to be included in the differential diagnosis, thus providing an additional tool for timely diagnosis.

EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia.

Uveal melanomas (UMs) comprise the most common primary intraocular malignancies in adults, with the eye representing the second most common site for melanoma, following the skin. Prognosis remains poor, with approximately half of the cases presenting with metastatic disease at the time of diagnosis. Erythropoietin-producing human hepatocellular receptors (EPHs) comprise the largest known family of tyrosine receptors, in which, along with their ligands, ephrins, play an important role in a plethora of processes in human physiology, and are implicated in key steps of carcinogenesis. In the present study, EPHA2, EPHA4, and EPHA6 immunohistochemical expressions were investigated in UM tissues and further correlated to a multitude of clinicopathological parameters, including disease stage and patients' overall survival (OS). High levels of EPHA2 expression were significantly associated with increased tumor vertical thickness (p = 0.03) and the presence of intrascleral involvement (p = 0.05), whereas high EPHA6 nuclear expression was associated with older age at diagnosis (p = 0.03) and absence of retinal detachment (p = 0.05). In a multivariate survival analysis, increased EPHA4 expression was associated with shortened OS along with the presence of metastasis (p < 0.001) and monosomy 3 (p = 0.02). In a separate model, the concurrent overexpression of at least two of the investigated EPHs (HR = 14.7, p = 0.03) also proved to be an independent poor prognostic factor. In conclusion, our results implicate these specific members of the EPHA group as potential biomarkers for disease prognosis as well as possible targets for the development of novel therapeutic interventions.

Histone Deacetylase (HDAC)-1, -2, -4, and -6 in Uveal Melanomas: Associations with Clinicopathological Parameters and Patients' Survival.

BACKGROUND: Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults, exerting high metastatic potential and poor prognosis. Histone deacetylases (HDACs) play a key role in carcinogenesis, and HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical settings. The aim of this study was to evaluate the clinical significance of HDAC-1, -2, -4, and -6 expression in UM. METHODS: HDAC-1, -2, -4, and -6 expression was examined immunohistochemically in 75 UM tissue specimens and was correlated with tumors' clinicopathological characteristics, the presence of tumor-infiltrating lymphocytes (TILS), as well as with our patients' overall survival (OS). RESULTS: HDAC-2 was the most frequently expressed isoform (66%), whereas we confirmed in addition to the expected nuclear expression the presence of cytoplasmic expression of class I HDAC isoforms, namely HDAC-1 (33%) and HDAC-2 (9.5%). HDAC-4 and -6 expression was cytoplasmic. HDAC-1 nuclear expression was associated with increased tumor size (p = 0.03), HDAC-6 with higher mitotic index (p = 0.03), and nuclear HDAC-2 with epithelioid cell morphology (p = 0.03) and presence of tumor-infiltrating lymphocytes (p = 0.04). The association with the remaining parameters including Monosomy 3 was not significant. Moreover, the presence as well as the nuclear expression pattern of HDAC-2 were correlated with patients' improved OS and remained significant in multivariate survival analysis. CONCLUSIONS: These findings provide evidence for a potential role of HDACs and especially HDAC-2 in the biological mechanisms governing UM evolution and progression.

HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment.

Hu-antigen R (HuR) is a post-transcriptional regulator that belongs to the embryonic lethal abnormal vision Drosophila-like family (ELAV). HuR regulates the stability, translation, subcellular localization, and degradation of several target mRNAs, which are implicated in carcinogenesis and could affect therapeutic options. HuR protein is consistently highly expressed in hepatocellular carcinoma (HCC) compared to the adjacent normal liver tissue and is involved in the post-transcriptional regulation of various genes implicated in liver malignant transformation. Additionally, HuR protein seems to be a putative prognosticator in HCC, predicting worse survival. This review summarizes the recent evidence regarding the role of HuR in primary liver tumors, as presented in clinical studies, in vitro experiments and in vivo animal models. In conclusion, our review supports the consistent role of HuR protein in the development, prognosis, and treatment of HCC. Additional studies are expected to expand current information and exploit its putative employment as a future candidate for more personalized treatment in these tumors.

Consensus statement of the Hellenic and Cypriot Gastric Cancer Study Group on the diagnosis, staging and management of gastric cancer.

Gastric Cancer epidemics have changed over recent decades, declining in incidence, shifting from distal to proximal location, transforming from intestinal to diffuse histology. Novel chemotherapeutic agents combined with modern surgical operations hardly changed overall disease related survival. This may be attributed to a substantial inherent geographical variation of disease genetics, but also to a failure to standardize and implement treatment protocols in clinical practice. To overcome these drawbacks in Greece and Cyprus, a Gastric Cancer Study Group under the auspices of the Hellenic Society of Medical Oncology (HeSMO) and Gastrointestinal Cancer Study Group (GIC-SG) merged their efforts to produce a consensus considering ethnic parameters of healthcare system and the international proposals as well. Utilizing structured meetings of experts, a consensus was reached. To achieve further consensus, statements were subjected to the Delphi methodology by invited multidisciplinary national and international experts. Sentences were considered of high or low consensus if they were voted by ≥ 80%, or < 80%, respectively; those obtaining a low consensus level after both voting rounds were rejected. Forty-five statements were developed and voted by 71 experts. The median rate of abstention per statement was 9.9% (range: 0-53.5%). At the end of the process, one statement was rejected, another revised, and all the remaining achieved a high consensus. Forty-four recommendations covering all aspects of the management of gastric cancer and concise treatment algorithms are proposed by the Hellenic and Cypriot Gastric Cancer Study Group. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and individualization are emphasized.

Alterations of the Short-Term Variation of the Fetal Heart Rate after Antenatal Maternal Betamethasone Administration: Validation with Two Different Computational Algorithms.

INTRODUCTION: Antenatal betamethasone administration in the context of foetal lung maturity enhancement has a transient impact on the short-term variation (STV) of the foetal heart rate. There are currently various algorithms for computing the STV, each one resulting in different STV values. We studied the results of betamethasone administration on the STV using 2 different algorithms in order to investigate whether the effects of steroids on the STV depend on the algorithm used or not. MATERIALS AND METHODS: In the context of a larger, single-centre, prospective, observational study, we gathered CTG traces under and without the influence of steroids in order to study their effect on the STV using 2 different computational algorithms (STV240 and STV16). RESULTS: A total of 285 CTGs were registered and subsequently analysed with both algorithms. When compared to the STV240 and STV16 without or at least 72 h after the first intramuscular corticosteroid administration, a transient increase of both the STV240 and STV16 was documented in the first 24 h, followed by a transient decrease of both the STV240 and STV16 between 24 h and 72 h after the first intramuscular corticosteroid injection. CONCLUSION: Our results confirmed that betamethasone administration has a transient but significant effect on the STV independently of the algorithm used. These observations stress once again the fact that a decreased STV within the first 72 h after maternal bethametasone administration should not be an indication for early delivery.