Morphology and Navigational Landmarks of the Cranio-orbital Foramen in a Portuguese Population.

PURPOSE: The cranio-orbital and accessory foramina are located in the lateral wall of the orbit and adjacent to the superior orbital fissure. In the literature, there is a lack of consistency concerning the location and morphology of these foramina in different populations. Therefore, considering its clinical importance during orbital surgeries, it was the authors' aim to determine the incidence, location, and number of cranio-orbital and accessory foramina in a Portuguese population and compare the findings with data from other studies. METHODS: A total of 310 orbits from 155 dry skulls from the collection of the Museum of Anatomy of the Faculty of Medicine of Porto were studied. The characterization of both cranio-orbital and accessory cranio-orbital foramina was performed. RESULTS: The cranio-orbital foramen was present in at least 1 orbit per skull in 58.17% with a median diameter of 0.60 ± 0.33 mm. No relation was found between the presence of this foramen and the gender of the individuals or a tendency for laterality. However, it was found that the presence of 1 or more accessory foramina was related to higher diameters of the cranio-orbital foramen. CONCLUSIONS: There might be a relationship between the localization, diameter, and communication of foramina with the cranial fossae. Foramina located on the greater wing of the sphenoid bone presented a larger diameter and communicated with the middle cranial fossa. High diameters of the main vessel in the cranio-orbital foramen may imply more developed branches and collateral irrigation of the orbital structures using 1 or more accessory foramina. Surgeons should be aware of the location of the cranio-orbital foramen to reduce potential sources of hemorrhage during orbital dissections.

Peripheral T-Cell Lymphoma, Not Otherwise Specified - a case report and short literature review.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is the most common subgroup of peripheral T-cell lymphomas (PTCL), and constitutes a diagnosis of exclusion. At presentation, most patients exhibit B symptoms and generalized lymphadenopathy, with or without concomitant extra-nodal involvement. We present a case of a man admitted to the hospital with B symptoms, generalized lymphadenopathy and a pruritic exanthema. Laboratory workup reveled persistent eosinophilia and malignant hypercalcemia. The excisional lymph node biopsy diagnosed PTCL-NOS, and the skin biopsy demonstrated a lichenoid dermatitis, compatible with the presumptive clinical diagnosis of a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The patient was treated with topical betamethasone with good overall response, and initiated the first cycle of chemotherapy before discharge. This case report describes a PTCL-NOS with a concomitant non-lymphoproliferative disease, the challenging diagnostic workup of the two diseases and reinforces the most important features of the lymphoproliferative neoplasm.

Hypoxia enhances the malignant nature of bladder cancer cells and concomitantly antagonizes protein O-glycosylation extension.

Invasive bladder tumours express the cell-surface Sialyl-Tn (STn) antigen, which stems from a premature stop in protein O-glycosylation. The STn antigen favours invasion, immune escape, and possibly chemotherapy resistance, making it attractive for target therapeutics. However, the events leading to such deregulation in protein glycosylation are mostly unknown. Since hypoxia is a salient feature of advanced stage tumours, we searched into how it influences bladder cancer cells glycophenotype, with emphasis on STn expression. Therefore, three bladder cancer cell lines with distinct genetic and molecular backgrounds (T24, 5637 and HT1376) were submitted to hypoxia. To disclose HIF-1α-mediated events, experiments were also conducted in the presence of Deferoxamine Mesilate (Dfx), an inhibitor of HIF-1α proteasomal degradation. In both conditions all cell lines overexpressed HIF-1α and its transcriptionally-regulated protein CA-IX. This was accompanied by increased lactate biosynthesis, denoting a shift toward anaerobic metabolism. Concomitantly, T24 and 5637 cells acquired a more motile phenotype, consistent with their more mesenchymal characteristics. Moreover, hypoxia promoted STn antigen overexpression in all cell lines and enhanced the migration and invasion of those presenting more mesenchymal characteristics, in an HIF-1α-dependent manner. These effects were reversed by reoxygenation, demonstrating that oxygen affects O-glycan extension. Glycoproteomics studies highlighted that STn was mainly present in integrins and cadherins, suggesting a possible role for this glycan in adhesion, cell motility and invasion. The association between HIF-1α and STn overexpressions and tumour invasion was further confirmed in bladder cancer patient samples. In conclusion, STn overexpression may, in part, result from a HIF-1α mediated cell-survival strategy to adapt to the hypoxic challenge, favouring cell invasion. In addition, targeting STn-expressing glycoproteins may offer potential to treat tumour hypoxic niches harbouring more malignant cells.

P53 and cancer-associated sialylated glycans are surrogate markers of cancerization of the bladder associated with Schistosoma haematobium infection.

BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. METHODOLOGY/PRINCIPAL FINDINGS: Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewisa/x (sLea/sLex), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. CONCLUSION/SIGNIFICANCE: This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests.