LKB1 Loss Correlates with STING Loss and, in Cooperation with ß-Catenin Membranous Loss, Indicates Poor Prognosis in Patients with Operable Non-Small Cell Lung Cancer.

To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRß, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (ß-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAFV600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16 downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low ß-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumors yielding LKB1 loss and concomitant nonexistent or low ß-catenin membrane expression experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71-6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and ß-catenin in NSCLC, in prognosis.

Retroperitoneal Soft Tissue Sarcoma: Emerging Therapeutic Strategies.

Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is usually unfeasible in RPS due to its large size, indistinct tumour borders, anatomical constraints and the thinness of the overlying peritoneum. Local recurrence is the leading cause of death for low-grade RPS, whereas high-grade tumours are prone to distant metastases. In recent decades, the role of emerging therapeutic strategies, such as more extended surgery and (neo)adjuvant treatments to improve oncological outcome in primary localised RPS, has been extensively investigated. In this review, the recent data on the evolving multidisciplinary management of primary localised RPS are comprehensively discussed. The heterogeneity of RPS, with their different histological subtypes and biological behaviour, renders a standard therapeutic 'one-size-fits-all' approach inappropriate, and treatment should be modified according to histological type and malignancy grade. There is sufficient evidence that frontline extended surgery with compartmental resection including all ipsilateral retroperitoneal fat and liberal en bloc resection of adjacent organs and structures, even if they are not macroscopically involved, increases local tumour control in low-grade sarcoma and liposarcoma, but not in leiomyosarcoma for which complete macroscopic resection seems sufficient. Additionally, preoperative radiotherapy is not indicated for all RPSs, but seems to be beneficial in well-differentiated liposarcoma and grade I/II dedifferentiated liposarcoma, and probably in solitary fibrous tumour. Whether neoadjuvant chemotherapy is of benefit in high-grade RPS remains unclear from retrospective data and is subject of the ongoing randomised STRASS 2 trial, from which the results are eagerly awaited. Personalised, histology-tailored multimodality treatment is promising and will likely further evolve as our understanding of the molecular and genetic characteristics within RPS improves.

Retroperitoneal Hemorrhage Due to Spontaneous Renal Rupture as the First Presentation of Antiphospholipid Syndrome: A Case Report.

Spontaneous renal rupture (SRR) with retroperitoneal hemorrhage is an extremely rare medical emergency and is rather challenging for the surgical team. Management of SRR often requires surgical intervention and nephrectomy as it is life-threatening. Antiphospholipid syndrome (APLS) is an autoimmune disease that affects several organs, including kidneys, causing significant abnormalities. Current data suggest that APLS can result in renal artery stenosis, renal vein thrombosis, arterial hypertension, thrombotic microangiopathy, and antiphospholipid syndrome nephropathy where there is renal involvement. Here, we report the case of a 49-year-old man who presented to the Emergency Department with sudden-onset abdominal pain in the context of retroperitoneal bleeding due to SRR. The patient developed hemodynamic instability and underwent a total nephrectomy. The surgical specimen revealed APLS-related lesions. Serological tests confirmed the diagnosis of APLS, which was managed with acenocoumarol and hydroxychloroquine. Since then, he has not experienced any thromboembolic or hemorrhagic episodes. This article aims to present for the first time a case of SRR as the first presentation of APLS as well as to analyze the possible associated mechanisms.

Clinical Controversy Surrounding the Differential Diagnosis of Branchiogenic Carcinoma.

Clinical evaluation, differential diagnosis, and management of a neck mass constitute commonly encountered problems for the head and neck surgeon. An asymptomatic neck mass in adults may be the only clinical sign of head and neck cancer. A 50-year-old female patient presented with a painless, slowly enlarging, left lateral neck lump. Ultrasonography described a possible lymph node with cystic degeneration, and fine needle aspiration biopsy only detected atypical cells of squamous epithelium. An open biopsy under general anesthesia was performed. Histopathological findings suggested the diagnosis of lymph node infiltration by squamous cell carcinoma of an unknown primary site, but differential diagnosis also included branchiogenic carcinoma arising in a branchial cleft cyst. A diagnostic algorithm for metastatic squamous cell carcinoma of an unknown primary site was followed, including positron emission tomography with computed tomography. The patient underwent panendoscopy and bilateral tonsillectomy, and an ipsilateral p16 positive tonsillar squamous cell carcinoma was detected. Further appropriate management followed. The existence of true branchiogenic carcinoma is controversial. When such a diagnosis is contemplated, every effort should be made to detect a possible primary site. Branchiogenic carcinoma, if exists at all, remains a diagnosis of exclusion.

Factors Associated with Healthcare Workers' (HCWs) Acceptance of COVID-19 Vaccinations and Indications of a Role Model towards Population Vaccinations from a Cross-Sectional Survey in Greece, May 2021.

A Knowledge, Attitudes and Practices (KAP) study was conducted at the end of May 2021 engaging 1456 healthcare workers (HCWs) from 20 hospitals throughout Greece. Acceptance of vaccination against coronavirus disease 2019 (COVID-19) was estimated at 77.7%, with lower vaccine acceptance identified in nurses compared to physicians. Fears related to vaccine safety, lack of information and general knowledge about vaccinations, influenza vaccine acceptance, education level and years of practice were among the factors independently associated with vaccine acceptance. A strong association was identified between vaccination of HCWs in each health region and the population coverage, indicating that HCWs may be role models for the general population. Information campaigns should continue despite decisions taken regarding mandatory vaccinations.

Apocrine and eccrine hidrocystomas: a clinicopathological study.

INTRODUCTION: Eccrine and apocrine hidrocystomas are uncommon, benign, cystic proliferations of the sweat glands usually located on the head and neck area. OBJECTIVES: To describe the key clinical and histopathological characteristics of a large series of hidrocystomas in Greece to improve diagnostic accuracy, and to perform a historical review of the medical term hidrocystoma. METHODS: A case series of 22 hidrocystomas from 20 consecutive patients treated with surgery at University Hospital of Heraklion in Crete, Greece, from January 1, 1998 to January 1, 2020 was performed along with a comprehensive historical literature review of the term hidrocystoma and its corresponding term hydatis from ancient Greek literature to the present. Data were obtained from medical records. All patients had a histopathologically confirmed diagnosis of hidrocystoma. Formalin-fixed paraffin-embedded (FFPE) sections of 22 tumors of the 20 consecutive patients were retrieved from the pathology laboratory archive and stained for SMA, p63, and GCDFP-15 with immunochemistry and periodic acid-Schiff (PAS) histochemical stain. RESULTS: Overall, 22 hidrocystomas (11 apocrine and 11 eccrine hidrocystomas) surgically excised from 20 patients were included in this study. Of the 20 patients, 10 (50%) were male and 10 (50%) were female, with a mean age of 56 ± 15 years. Hidrocystomas commonly occurred on the eyelids (73%), inner canthus (9%), eyebrow (4.5%), neck (4.5%), nose (4.5%), and ear (4.5%). All apocrine hidrocystomas stained positive for SMA, GCDFP-15, CAM 5.2, PAS, and PAS-D. No recurrence was observed. CONCLUSIONS: Here we have presented the clinicopathological characteristics of the largest case series of hidrocystomas in Europe and the Mediterranean region. Only apocrine hidrocystomas stained positive for SMA, GCDFP-15, CAM 5.2, PAS, and PAS-D.

Differentiating low from high-grade soft tissue sarcomas using post-processed imaging parameters derived from multiple DWI models.

PURPOSE: To investigate and histopathologically validate the role of model selection in the design of novel parametric meta-maps towards the discrimination of low from high-grade soft tissue sarcomas (STSs) using multiple Diffusion Weighted Imaging (DWI) models. METHODS: DWI data of 28 patients were quantified using the mono-exponential, bi-exponential, stretched-exponential and the diffusion kurtosis model. Akaike Weights (AW) were calculated from the corrected Akaike Information Criteria (AICc) to select the most suitable model for every pixel within the tumor volume. Pseudo-colorized classification maps were then generated to depict model suitability, hypothesizing that every single model underpins different tissue properties and cannot solely characterize the whole tumor. Single model parametric maps were turned into meta-maps using the classification map and a histological validation of the model suitability results was conducted on several subregions of different tumors. Several histogram metrics were calculated from all derived maps before and after model selection, statistical analysis was conducted using the Mann-Whitney U test, p-values were adjusted for multiple comparisons and performance of all statistically significant metrics was evaluated using the Receiver Operator Characteristic (ROC) analysis. RESULTS: The histologic analysis on several tumor subregions confirmed model suitability results on these areas. Only 3 histogram metrics, all derived from the meta-maps, were found to be statistically significant in differentiating low from high-grade STSs with an AUC higher than 89 %. CONCLUSION: Embedding model selection in the design of the diffusion parametric maps yields to histogram metrics of high discriminatory power in grading STSs.

Hybrid autofluorescence and photoacoustic label-free microscopy for the investigation and identification of malignancies in ocular biopsies.

We demonstrate the development and application of a prototype hybrid microscopy system integrating autofluorescence (AF) and photoacoustic (PA) label-free contrast modes, for the differentiation of ocular tumors in human surgical biopsies. Hybrid imaging was performed in conjunctival nevi and uveal melanomas tissue sections to acquire quantified data for each molecular background. The AF and PA signals were spatially correlated to establish a novel malignancy indicator that could detect melanomas with high accuracy (t-test; p<0.01). The proposed methodology has the potential to simplify relevant diagnostic procedures and paves the way for the development of novel ophthalmoscopes aiming to the early diagnosis of ocular malignancies in a clinical setting.

Multiexponential T2 relaxometry of benign and malignant adipocytic tumours.

BACKGROUND: We investigated a recently proposed multiexponential (Mexp) fitting method applied to T2 relaxometry magnetic resonance imaging (MRI) data of benign and malignant adipocytic tumours and healthy subcutaneous fat. We studied the T2 distributions of the different tissue types and calculated statistical metrics to differentiate benign and malignant tumours. METHODS: Twenty-four patients with primary benign and malignant adipocytic tumours prospectively underwent 1.5-T MRI with a single-slice T2 relaxometry (Carr-Purcell-Meiboom-Gill sequence, 25 echoes) prior to surgical excision and histopathological assessment. The proposed method adaptively chooses a monoexponential or biexponential model on a voxel basis based on the adjusted R2 goodness of fit criterion. Linear regression was applied on the statistical metrics derived from the T2 distributions for the classification. RESULTS: Healthy subcutaneous fat and benign lipoma were better described by biexponential fitting with a monoexponential and biexponential prevalence of 0.0/100% and 0.2/99.8% respectively. Well-differentiated liposarcomas exhibit 17.6% monoexponential and 82.4% biexponential behaviour, while more aggressive liposarcomas show larger degree of monoexponential behaviour. The monoexponential/biexponential prevalence was 47.6/52.4% for myxoid tumours, 52.8/47.2% for poorly differentiated parts of dedifferentiated liposarcomas, and 24.9/75.1% pleomorphic liposarcomas. The percentage monoexponential or biexponential model prevalence per patient was the best classifier distinguishing between malignant and benign adipocytic tumours with a 0.81 sensitivity and a 1.00 specificity. CONCLUSIONS: Healthy adipose tissue and benign lipomas showed a pure biexponential behaviour with similar T2 distributions, while decreased adipocytic cell differentiation characterising aggressive neoplasms was associated with an increased rate of monoexponential decay curves, opening a perspective adipocytic tumour classification.