Perianal Angioleiomyoma: A Case Report and Review of the Literature.

Angioleiomyomas are rare benign tumors, which take origin from smooth muscle fibers of the tunica media of veins. Even though angioleiomyomas can appear anywhere in the body, these masses are rarely occurred in the gastrointestinal system. This is the first reported case of perianal angioleiomyomas, where the tumor in close relation with the anal canal was investigated with endoanal ultrasonography. Local excision of such lesion is generally curative.

Utilizing Exosomal-EPHs/Ephrins as Biomarkers and as a Potential Platform for Targeted Delivery of Therapeutic Exosomes.

Exosomes are cell-secreted nanoparticles containing various molecules including small vesicles, microRNAs (miRNAs), messenger RNAs or bioactive proteins which are thought to be of paramount importance for intercellular communication. The unique effects of exosomes in terms of cell penetration capacity, decreased immunogenicity and inherent stability, along with their key role in mediating information exchange among tumor cells and their surrounding tumor microenvironment (TME), render them a promising platform for drug targeted delivery. Compared to synthetic drugs, exosomes boast a plethora of advantages, including higher biocompatibility, lower toxicity and increased ability of tissue infiltration. Nevertheless, the use of artificial exosomes can be limited in practice, partly due to their poor targeting ability and partly due to their limited efficacy. Therefore, efforts have been made to engineer stem cell-derived exosomes in order to increase selectiveness and effectivity, which can then become loaded with various active substances depending on the therapeutic approach followed. Erythropoietin-producing human hepatocellular receptors (EPHs), along with their ligands, the EPH family receptor interacting proteins (ephrins), have been extensively investigated for their key roles in both physiology and cancer pathogenesis. EPHs/ephrins exhibit both tumorigenic and tumor suppressing properties, with their targeting representing a promising, novel therapeutic approach in cancer patients' management. In our review, the use of ephrin-loaded exosomes as a potential therapeutic targeted delivery system in cancer will be discussed.

Platelet-Rich Plasma for Pleurodesis: An Experimental Study in Rabbits.

Background and Objectives: This study was designed to evaluate platelet-rich plasma (PRP) as a method of pleurodesis in a rabbit model. Pleurodesis with PRP was compared against the gold-standard use of talc. The secondary evaluation assessed the ideal time for achieving pleurodesis. Materials and Methods: 25 healthy New Zealand white rabbits were assigned to three groups, as follows: 12 animals in the first and second groups, as well as one animal with no intervention in the final group, which was used as a control. The talc pleurodesis group (baseline) underwent pleurodesis with sterile talc, which is the gold-standard sclerosing agent used for pleurodesis. The PRP group underwent pleurodesis using autologous PRP. The last group had one rabbit with no intervention. A total of 12 rabbits (n = 6 for the talc pleurodesis group and n = 6 for the PRP group) were sacrificed 3 days (72 h) after the intervention, and 12 rabbits (n = 6 for the talc pleurodesis group and n = 6 for the PRP group) were sacrificed 6 days (144 h) after the intervention. In both the talc and PRP group, FBC and CRP were measured before the intervention and in 3 or 6 days afterwards, respectively. The pleura and the lungs were evaluated histopathologically. Results: Macroscopically, there were no statistically significant differences between the two groups. In terms of microscopic findings, there were no statistically significant differences in inflammatory reactions provoked in the visceral and parietal pleura between the PRP and talc. In addition, with talc pleurodesis, a foreign-body reaction was observed in about 50% of the cases, which was not observed with PRP. In terms of inflammation between 3 and 6 days, there were no statistically significant differences with PRP, there was only a statistically significant difference between 3 and 6 days regarding the parietal pleura in the talc group. Conclusions: The instillation of autologous PRP in the pleural cavity shows promise in achieving pleurodesis. The efficacy of PRP as a pleurodesis agent should be examined further.

A comparative autopsy study of the injury distribution and severity between suicidal and accidental high falls.

Falls are the second cause of accidental deaths worldwide. Falls from height are also a common method of suicide. The aim of this study is to compare the characteristics of the victims, the circumstances of the fall and the severity and distribution of the injuries reported in an autopsy case series of falls from height. This study is a retrospective analysis of consecutive autopsy cases of suicidal and accidental falls from height which were investigated in the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens during the period 2011-2019. The recorded variables included demographic data of the victim, height of fall, length of hospital stay, toxicological results, the existence and location of injuries and Injury Severity Score (ISS). Victims of suicidal falls were younger (55.53 vs. 62.98, p = 0.001), they fell from higher heights (12.35 vs. 5.18 m, p < 0.001), and they sustained more severe injuries compared with victims of accidental falls (ISS 51.01 vs. 40.88, p < 0.001). Injuries in the thorax, abdomen, pelvis, upper and lower extremities were more frequently observed after a suicidal fall (93.6% vs. 67.3%, 72.1% vs. 21.4%, 72.1% vs. 27.6%, 42.9% vs. 15.3%, 45.7% vs. 13.3%, respectively-p < 0.001), probably due to the higher height of fall. Our study outlines the differences in the profile of the victims and in the severity of injuries caused by falls from height depending on the intention of the victim to fall. However, a distinctive injury pattern in victims of suicidal falls was not demonstrated.

Development of novel real-time PCR methodology for quantification of COL11A1 mRNA variants and evaluation in breast cancer tissue specimens.

BACKGROUND: Collagen XI is a key structural component of the extracellular matrix and consists of three alpha chains. One of these chains, the α1 (XI), is encoded by the COL11A1 gene and is transcribed to four different variants at least (A, B, C and E) that differ in the propensity to N-terminal domain proteolysis and potentially in the way the extracellular matrix is arranged. This could affect the ability of tumor cells to invade the remodeled stroma and metastasize. No study in the literature has so far investigated the expression of these four variants in breast cancer nor does a method for their accurate quantitative detection exist. METHODS: We developed a conventional PCR for the general detection of the general COL11A1 transcript and real-time qPCR methodologies with dual hybridization probes in the LightCycler platform for the quantitative determination of the variants. Data from 90 breast cancer tissues with known histopathological features were collected. RESULTS: The general COL11A1 transcript was detected in all samples. The developed methodologies for each variant were rapid as well as reproducible, sensitive and specific. Variant A was detected in 30 samples (33 %) and variant E in 62 samples (69 %). Variants B and C were not detected at all. A statistically significant correlation was observed between the presence of variant E and lymph nodes involvement (p = 0.037) and metastasis (p = 0.041). CONCLUSIONS: With the newly developed tools, the possibility of inclusion of COL11A1 variants as prognostic biomarkers in emerging multiparameter technologies examining tissue RNA expression should be further explored.

The microvascular anatomy of superior and inferior gluteal artery perforator (SGAP and IGAP) flaps: a fresh cadaveric study and clinical implications.

BACKGROUND: Our study aimed to highlight anatomical similarities, differences, and variations in the microvascular anatomy between superior and inferior gluteal artery perforator (SGAP and IGAP) flaps. METHOD: Thirty gluteal flaps (15 SGAP and 15 IGAP) were studied on 22 adult fresh cadavers. We recorded the number and location of perforators, the characteristics of the main perforator (course, length, and diameter at the level of division at the greater sciatic foramen), and the anatomical variations of the submuscular venous plexus. RESULTS: The mean number of perforators was similar in both flaps (n = 7). We found a statistically significant difference in the total length of the vascular pedicle between SGAP (mean = 9.80 cm) and IGAP (mean = 13.36 cm) flaps, which correlated strongly with the difference in the intramuscular length (mean difference = 3.40 cm) of the perforator. There was no statistically significant difference in the diameter of the superior and inferior gluteal vessels at the point of pedicle division. The complex submuscular venous plexus, which is typically found on SGAP flaps deep to the sacral fascia, was never encountered on IGAP flaps. Perforators originating from the inferior gluteal artery were found on the lower half of five superior gluteal flaps. These were dominant perforators in two cases. We also report a rare anatomical communication between superior and inferior gluteal vessels deep to the piriformis muscle and a case of atheromatous disease of the inferior gluteal artery. CONCLUSION: Our findings are highly relevant to clinical practice and contribute to the understanding of the vascular anatomy of SGAP and IGAP flaps and the successful use of these challenging flaps. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Extended Stanford Type-A Aortic Dissection with Multivessel Coronary and Peripheral Artery Involvement: An Autopsy Case Report.

We report the case of a 64-year-old male who died suddenly short after his admission to hospital because of strong chest pain and before any clinical diagnosis was established. His medical history included coronary disease with coronary by-pass surgery at the age of 40 years old, uncontrolled hypertension, diabetes mellitus, and elevated levels of cholesterol. The autopsy revealed quite a rare case of Stanford A aortic dissection with extension to the common and internal carotid arteries; the subclavian, axillary, brachial, and radial arteries; three coronary arteries; the superior mesenteric artery; and the iliac arteries. There was no histological evidence of aortitis or connective tissue disease. The death did not result from the rupture of the aortic dissection, but from myocardial ischemia due to coronary occlusion in combination with hemodynamic disturbance from stress caused by the extended aortic dissection.

Undifferentiated-dedifferentiated endometrial carcinoma; the reappearance of an old friend with insights into the new data.

Endometrial carcinoma is a common malignancy in women and shows increasing incidence. Except for its two main pathogenetic types I and II, the continuing evolution on molecular genetics have led to a new classification system (TCGA), that includes four main molecular subtypes: (i) POLE-mutant (ultramutated), (ii) hypermutated (MSI), (iii) copy-number low/MSS (p53wt) and (iv) copy-number high/serous-like (p53mut). The undifferentiated and dedifferentiated endometrial carcinomas are rare and clinically aggressive variants, comprising about 10% of the high-grade endometrial carcinomas and 2% of the endometrial carcinomas in general. Until recently, they were under-recognized and not fully described morphologically and immunohistochemically/molecularly. Their recognition diagnostically is crucial because of their poor prognosis; approximately 40% of patients with these subtypes will die within 0.5-20 months after diagnosis, so additional therapeutic strategies are important for an effective management. Because of their rarity, the responsiveness to other than conventional treatment, such as immunotherapy, has not been sufficiently investigated yet. The aim of this review is to provide an update on the knowledge about these two uncommon subtypes according to the current literature.

Domestic and Community Violence in Greece After the First COVID-19 Quarantine: A Clinical Forensic Approach.

Many scientists expressed their concerns regarding the impact of COVID-19-related quarantine measures on interpersonal violence, mainly concerning children and intimate partners, as well as other negative psychological effects. During early 2020, free circulation in Greece was prohibited for 42 days, up until May 4th. The aim of our study was to investigate characteristics of bodily harm allegation cases referred to the Department of Forensic Medicine and Toxicology of the Medical School of the National and Kapodistrian University of Athens, Greece, during the first month succeeding free circulation re-establishment in the broader Attica region. We also aimed to detect any possible differences regarding bodily harm allegations by comparing the corresponding time period of 2019. A decrease in community violence (CV) allegations, especially youth violence incidents, was observed in 2020. Females' victimization, as well as allegations against strangers, were also decreased. No differences were observed concerning the injury mechanism. Victims of 2020 filed the allegations faster and, thus, were examined almost one day earlier than their 2019 counterparts. During lockdown, domestic violence (DV) hotline reporting was significantly increased, but paradoxically DV cases referred to our Department were decreased. In Greece, the legislators did not foresee any specific exemption from circulation restriction for DV victims attempting to escape abuse. Our results revealed a small, but notable, impact on non-fatal interpersonal violence.

The Anaphylactoid Syndrome of Pregnancy: Two Autopsy Cases.

The anaphylactoid syndrome of pregnancy (ASP) is a rare emergency with significant mortality and morbidity, in which the amniotic fluid and fetal cells enter the maternal circulation leading to respiratory failure, altered mental status, hypotension, and disseminated intravascular coagulation. The term ASP was recently introduced to replace the term amniotic fluid embolism since the clinical manifestations of the entity were more similar to a septic or anaphylactic shock rather than that of an embolic event. Two autopsy cases are described, regarding a 35-year-old gravida 2 para 1 and a 34-year-old gravida 1 para 0, where the cause of death was determined to be ASP.

Infant Pneumonitis Due to a Tracheoesophageal Fistula: A Presentation of Two Autopsy Cases.

Both esophageal atresia (EA) and tracheoesophageal fistula (TEF) represent a rather uncommon congenital abnormality that is the result of abnormal tracheoesophageal organogenesis. Although EA, with or without TEF, is relatively uncommon, it represents the most common upper gastrointestinal birth defect. Esophageal atresia and tracheoesophageal fistula are anatomically classified into five types according to the Gross classification (types A, B, C, D, E/H). As in type E/H, the continuity of the esophagus is not interrupted, the symptom onset is consequently delayed, and therefore diagnosis is difficult. Aspiration pneumonitis is a chemical injury caused by inhaled sterile gastric contents, while aspiration pneumonia is, in part, an infectious process because the inhaled oropharyngeal secretions are rich in bacteria. This paper aims to report two infant autopsy cases of aspiration pneumonitis with TEF involvement. The main histopathological finding was interstitial pneumonitis. Upon histopathological examination, lymphocytes, plasma cells, and macrophages were discovered on the alveolar walls, which were compatible with the chemical origin of interstitial pneumonitis. No eosinophils were detected; therefore, hypersensitivity-originating interstitial pneumonitis was ruled out. The cause of death in both cases was interstitial pneumonitis.

Immunohistochemical Study of Bladder Cancer Molecular Subtypes and Their Association with PD-L1 Expression.

The significant heterogeneity in clinical outcomes among patients with bladder cancer has highlighted the existence of different biological subtypes of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Meanwhile, immune checkpoint proteins and their interference with tumor-related immune-evasive strategies has led to the development of several immunotherapeutic drugs targeting programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1). However, the lack of any known biomarker that could predict responses to immunotherapy has led to a more agnostic therapeutic approach. Here, we present a study conducted in 77 bladder cancer (BC) patients (n = 77), ranging from stages pTa to pT2. Tumor specimens were resected via transurethral resection of bladder tumor (TURBT) and consistuted of 24 low-grade (LG) and 53 high-grade (HG) tumors. Patients' tumors were then categorized into molecular subtypes, via immunohistochemistry (CK5/6 and GATA3). Furthermore, all tumor specimens were stained with anti-PD-L1 and demonstrated significant correlations with basal immunophenotype, stage pT2 and HG tumors. As such, we attempted to stratify patients into groups of likely-responders and likely-not-responders to immunotherapy with anti-PD-L1, based on their molecular phenotype. Finally, in acknowledging the fact that there is a universal lack of biomarkers associated with predicting BC response to immunotherapeutic drugs, we tested all tumors for deficiency of mismatch repair proteins (MMR).

Breast angiosarcoma that is not related to radiation exposure: a comprehensive review of the literature.

Breast angiosarcomas that are not related to previous radiotherapy are very rare. Surgical resection is the primary treatment for these tumors, but there is no general agreement on the extent of surgery. The role of multimodality adjuvant treatment also remains controversial. The aim of this study was to summarize the available data from the largest published series of patients in terms of management and outcome. We also sought to identify prognostic factors influencing patient survival. We have included studies presenting detailed data on multimodality therapy and survival of patients with breast angiosarcoma. Ten studies presenting data on 280 patients were included in the review. Seventy-five percent of patients underwent a total mastectomy and 25% had breast-conserving treatment (BCT). In 42% of patients, an axillary node dissection was combined with mastectomy or BCT. Thirty-six percent of patients received chemotherapy and 35% were treated with radiotherapy in an adjuvant or neoadjuvant setting. Survival varied significantly according to tumor size and grade. Adjuvant multimodality therapy may improve the outcome in selected patients with breast angiosarcoma. Tumor size, grade, and margin status are the most important prognostic factors for survival.

Divulging the Critical Role of HuR in Pancreatic Cancer as a Therapeutic Target and a Means to Overcome Chemoresistance.

Pancreatic cancer is set to become the most lethal and common type of cancer worldwide. This is partly attributed to the mutational burden that affects core signaling pathways and the crosstalk of tumor cells with their surrounding microenvironment, but it is also due to modern eating habits. Hyperadiposity along with the constant rise in metabolic syndrome's incidence contribute to a state of metaflammation that impacts immune cells and causes them to shift towards an immunosuppressive phenotype that, ultimately, allows tumor cells to evade immune control. Unfortunately, among the conventional therapeutic modalities and the novel therapeutic agents introduced, pancreatic cancer still holds one of the lowest response rates to therapy. Human antigen R (HuR), an RNA binding protein (RBP), has been repeatedly found to be implicated in pancreatic carcinogenesis and chemotherapy resistance through the posttranscriptional binding and regulation of mRNA target genes. Additionally, its overexpression has been linked to adverse clinical outcomes, in terms of tumor grade, stage, lymph node status and metastasis. These properties suggest the prospective role that HuR's therapeutic targeting can play in facilitating pancreatic neoplasia and could provide the means to overcome chemoresistance.

Primary Large Cell Neuroendocrine Carcinoma of the Parotid Gland. Report of a Rare Case.

Primary neuroendocrine carcinomas of the salivary glands are very rare neoplasms that present light microscopic, ultrastructural, and immunohistochemical features of neuroendocrine differentiation. Twelve cases have been published in the English language literature. We describe the pathologic features of a case of primary large cell neuroendocrine carcinoma of the parotid gland in a 91-year old male and summarize the immunophenotype of previously reported LCNECs of the major salivary glands. It is concluded that primary LCNEC of the salivary glands presents as a high-grade undifferentiated carcinoma, whose diagnosis may be hindered by its rarity and non-specific light microscopic features. A high level of awareness, immunohistochemical staining for neuroendocrine markers synaptophysin and CD56, and a thorough diagnostic work-up in order to exclude metastasis from a primary neuroendocrine carcinoma will allow its diagnosis.

Cardiac Involvement and Subsequent Death due to Extranodal NK/T Cell Cutaneous T-Cell Lymphoma: An Autopsy Case and Brief Review of the Literature.

Cardiac tumors range from benign to high grade malignancies. The incidence of cardiac involvement either by primary, or secondary tumors during autopsy is reported to be extremely low. Extranodal NK/T-cell lymphoma (ENKTL), nasal type is an unusual type of lymphoma. The skin is the second most common site of involvement after the respiratory tract. We present a case of a 63-year-old male, who was recently diagnosed with ENKTL, nasal type, who received chemotherapy, and died without any evident cause. The corpse was referred for routine medicolegal examination. Macroscopical determination of the cause of death was not feasible and subsequent histopathological examination revealed heart infiltration by ENKTL that was found in vivo in cutaneous lesions. Similar infiltrations existed in the pancreatic tissue. To the best of our knowledge, myocardial infiltration of ENKTL, inducing severe myocardial lesions that eventually caused death, is rare, with limited cases reported in the literature.

Biological rhythms of fatal myocardial infarction in Greece: an autopsy study.

BACKGROUND: Biological rhythms, acting as an endogenous clock, prepare and assist the organism to function optimally during predictable seasonal and daily cycles. Many elements of the cardiovascular system exhibit specific rhythmical patterns. Besides genetic mechanisms, external stimuli may alter biological rhythms. METHODS: The aim of this study was to investigate the patterns of biological rhythms in patients who suffered a fatal myocardial Infarction (MI), ascertained by macroscopical or histopathological examination. Cases of fatal MI examined during the time 2010-2017 were included in our study sample (827 cases in total). Medical History was also obtained for each case. The assessment of seasonal variation of fatal MI was accomplished by employing three different methods, Rayleigh Uniformity Test, X2 Goodness-of-fit test and Edward's Seasonality Test. Statistical significance was defined as a 2-sided p value of <0.05. RESULTS: Regarding the distribution of total cases, fatal MIs onset occurs more often during winter, with higher incidence in December and January. The weekly distribution of cases seems uniform. The circadian pattern presents higher frequencies of fatal MIs between 08:00 and 12:00 with the acrophase between 11:00 and 12:00. Further analysis was conducted separately, depending on the method of time-of-death reporting. CONCLUSIONS: Taking under consideration the variation of the occurrence of MI related deaths, in accordance with the respective biological rhythms, public health policies more suitable to the individual requirements of every country's population may be adopted.

Interpersonal Violence Against Children and Adolescents: A Forensic Study From Greece.

OBJECTIVE: To investigate differences in victimization of minors after allegations of domestic violence and community violence. METHODS: This retrospective study was conducted by reviewing the archive of clinical examinations after allegations for interpersonal violence against minors that were performed at the Department of Forensic Medicine and Toxicology of our Medical School from 2012 to 2016. RESULTS: 216 cases of allegations for victimization of minors' were referred to our department, representing 8.8% of all clinical forensic examinations. Boys community violence victims were affected mainly on the head, whilst girls mainly on the genital area. Upper limbs were the predominant site of injuries on domestic violence victims of both sexes. CONCLUSIONS: Adolescents were in greater danger of sustaining injuries than younger children. Upper limb injuries may prove to be a useful screening tool for domestic violence in school-age children and adolescents, while trunk injuries may indicate domestic violence in preschool children.

SDH-deficient renal cell carcinoma: A case report associated with a novel germline mutation.

The highly syndromic nature of succinate dehydrogenase-deficient RCCs constitutes their active surveillance and molecular profiling the alpha and omega.

Atypical kawasaki disease presenting with symptoms from the genitourinary system: an autopsy report.

Symptoms from the genitourinary system are unusual in Kawasaki disease (KD). Renal involvement is even rarer and it is confirmed by biopsy when the person is alive. We describe the case of an 11-year-old boy admitted to the hospital complaining about prolonged fever (5 days) and hematuria. His urinalysis showed also pyuria, proteinuria and urinary renal tubular epithelial cells concentrations. During the next days, the patient presented limb edema. After almost 2 weeks of hospitalization the patient was transferred to the intensive care unit because of melena and intense abdominal pain. Upon admission, the patient collapsed and died. The diagnosis of KD was established during autopsy. The macroscopical and histopathological examination of the heart showed increased dimensions and weight and multiple thrombi in the coronary arteries with intramural dense polymorphonuclear inflammatory infiltration and necrosis. Histological examination of the kidneys revealed normal glomerulus, mild expansion of mesangial matrix, interstitial infiltration with lymphocytes, plasmatocytes and eosinophiles, normal vessels and normal immunofluorescence.