Primary Liver Perivascular Epithelioid Cell Tumor (PEComa): Case Report and Literature Review.

A primary liver perivascular epithelioid cell tumor (PEComa) is an extremely rare entity. In this article, we present a case report with a review of the literature on the patients diagnosed with primary liver PEComa and an elaboration of diagnostic and treatment modalities. A systematic literature search was conducted using the terms "perivascular epithelioid cell tumor", "PEComa", "liver", and "hepatic". All articles describing patients diagnosed with primary liver PEComa were included. We identified a total of 224 patients of primary liver PEComa from 75 articles and a case from the present study with a significant preponderance of females (ratio 4:1) and with a mean age of 45.3 ± 12.1 years. Most of the patients (114 out of 224, 50.9%) were asymptomatic. A total of 183 (81.3%) patients underwent surgical hepatic resection at the time of diagnosis, while 19 (8.4%) underwent surveillance. Recurrence and metastases were detected in seven (3.1%) and six (2.7%) patients, respectively. In conclusion, surgical resection remains the cornerstone of therapy; however, the presence of nonspecific imaging features makes it difficult to reach a definite diagnosis preoperatively. Therefore, a multidisciplinary approach should be the gold standard in selecting the treatment modality.

Melatonin and Glycine Reduce Uterus Ischemia/Reperfusion Injury in a Rat Model of Warm Ischemia.

Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, Sprague-Dawley rats were assigned to eight groups, including sham and IRI (n = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin (p = 0.019) and glycine (p = 0.044) alone as well as their combination (p = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin (p = 0.004), glycine (p < 0.001) or their combination (p < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin (p = 0.027), glycine (p = 0.038) and combined treatment groups (p = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.

Custodiol-N Is Superior to Custodiol® Solution in Experimental Rat Uterus Preservation.

Uterus transplantation (UTx) is the first and only available treatment for women with absolute uterine factor infertility. However, clinical application is limited by the lack of organs, ischemia/reperfusion injury, as well as immunosuppression after UTx. Several different preservation solutions are used in experimental and clinical UTx, including Custodiol® solution. Recently, the novel Custodiol-N solution was developed with superior results in organ preservation. However, the solution was not tested yet in UTx. Therefore, the aims of this study were to evaluate the effect of Custodiol-N in uterus prolonged cold preservation time (8 and 24 h), compared to Custodiol® solution. Uterus tissue samples were obtained from adult Sprague Dawley rats (n = 10/group). Cold ischemic injury was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. After 8 h of cold ischemia, higher percentage of tissue edema, necrosis signs and myeloperoxidase expression, as well as lower superoxide dismutase activity were found in Custodiol® compared to Custodiol-N (p < 0.05). These differences were more pronounced after 24 h of cold preservation time (p < 0.05). This study demonstrated that Custodiol-N protects uterus grafts from cold ischemic injury better than standard Custodiol® most likely via inhibition of oxidative stress and tissue edema. It seems that iron chelators in the composition of Custodiol-N play an important protective role against cold ischemia.

Defining Melanoma Immune Biomarkers-Desert, Excluded, and Inflamed Subtypes-Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns.

The spatial distribution of tumor infiltrating lymphocytes (TILs) defines several histologically and clinically distinct immune subtypes-desert (no TILs), excluded (TILs in stroma), and inflamed (TILs in tumor parenchyma). To date, robust classification of immune subtypes still requires deeper experimental evidence across various cancer types. Here, we aimed to investigate, define, and validate the immune subtypes in melanoma by coupling transcriptional and histological assessments of the lymphocyte distribution in tumor parenchyma and stroma. We used the transcriptomic data from The Cancer Genome Atlas melanoma dataset to screen for the desert, excluded, and inflamed immune subtypes. We defined subtype-specific genes and used them to construct a subtype assignment algorithm. We validated the two-step algorithm in the qPCR data of real-world melanoma tumors with histologically defined immune subtypes. The accuracy of a classifier encompassing expression data of seven genes (immune response-related: CD2, CD53, IRF1, and CD8B; and stroma-related: COL5A2, TNFAIP6, and INHBA) in a validation cohort reached 79%. Our findings suggest that melanoma tumors can be classified into transcriptionally and histologically distinct desert, excluded, and inflamed subtypes. Gene expression-based algorithms can assist physicians and pathologists as biomarkers in the rapid assessment of a tumor immune microenvironment while serving as a tool for clinical decision making.

Successful treatment of diffuse pulmonary lymphangiomatosis with sirolimus.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease characterized by uncontrolled proliferation of anastomosing lymphatic channels in the lungs, pleura and mediastinum. Several palliative treatment options have been suggested for this condition, such as surgical interventions, radiotherapy and systemic medications. However, the existing treatment modalities yield inconsistent results, and their use is often limited by toxic side effects. The aim of this case report is to demonstrate the diagnostic challenges of a rare disease and improvement in the condition of a DPL patient treated with sirolimus. A 27-year-old man presented to the pulmonologist with exertional dyspnea, chronic cough and intermittent hemoptysis. Upon medical investigation, a chest computed tomography (CT) scan revealed soft tissue masses infiltrating the mediastinum and bilateral interlobular septal thickening. A surgical biopsy was performed, and pathological tissue analysis showed findings consistent with the diagnosis of DPL. Treatment with sirolimus was initiated, maintaining trough concentrations between 10 and 15 ng/ml. At 21 months of treatment, the patient reported reduced symptoms of cough and dyspnea. A CT scan showed decreased interstitial thickening and reduced infiltrations in the mediastinum. Moreover, pulmonary function tests revealed a significant increase in FEV1 and FVC. The authors believe this is the first article reporting pulmonary function improvement in an adult DPL patient treated with sirolimus. Therefore, sirolimus therapy should be considered for DPL patients as it may be effective in improving their condition and preventing disease progression.