Differentiated thyroid cancer invading the hypopharynx: A case report

Most thyroid cancers (90–95%) are well differentiated. Well differentiated cancers of the thyroid are usually confined to the thyroid capsule, making them amenable to isolated thyroid resection. Invasion of the upper aerodigestive tract by these cancers is infrequent and hypopharyngeal invasion is still rare. We report a 51 year old man with thyroid cancer invading the hypopharynx, who was successfully managed with complete resection along with a partial pharyngectomy. He is asymptomatic and disease free eighteen months after surgery. We advocate aggressive surgical extirpation of thyroid carcinoma invading the upper aerodigestive tract.     

Immunohistochemical and molecular genetic study on epithelioid glioblastoma: Series of seven cases with review of literature

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.     

Comparative effectiveness of videotape and handout mode of instructions for teaching exercises: skill retention in normal children

Hemophagocytic lymphohistiocytosis is a potentially fatal disease characterized by excessive macrophage and lymphocyte activity. Patients can be affected following immune activation after an oncologic, autoimmune or infectious trigger. An associated gene mutation may be found which impairs cytolytic lymphocyte function. We describe a pediatric case of hemophagocytic lymphohistiocytosis with a novel mutation of MUNC 13?C4 whose diagnosis was confounded by concurrent immunosuppression. Clinical reassessment for hemophagocytic lymphohistiocytosis is necessary in persistently febrile patients with laboratory derangements in the setting of immunosuppressive agent exposure.     

Management of Reproductive Tract Anomalies

Reproductive tract malformations are rare in general population but are commonly encountered in women with infertility and recurrent pregnancy loss. Obstructive anomalies present around menarche causing extreme pain and adversely affecting the life of the young women. The clinical signs, symptoms and reproductive problems depend on the anatomic distortions, which may range from congenital absence of the vagina to complex defects in the lateral and vertical fusion of the Müllerian duct system. Identification of symptoms and timely diagnosis are an important key to the management of these defects. Although MRI being gold standard in delineating uterine anatomy, recent advances in imaging technology, specifically 3-dimensional ultrasound, achieve accurate diagnosis. Surgical management depend on the type of anomaly, its complexity and the proper embryological interpretation of the anomaly and involves multiple specialties; thus, patients should be referred to centres with experience in the treatment of complex genital malformations.     

Molecular interactions of dioxins and DLCs with the ketosteroid receptors: an in silico risk assessment approach

Dioxins and dioxin-like compounds (DLCs) are the ones with poor water solubility and low volatility, resistant to physical, chemical and biological processes, persistent in the environment even under extreme conditions. Due to lipophilic nature, they get adhered to the fatty material and concentrate through biomagnification and bioaccumulation, thereby easily getting incorporated into food chains, paving the way to endocrine disruption via modulation of various human receptors. This in turn leads to certain adverse health effects. In the present study, a total of 100 dioxins and DLCs were taken and their binding pattern was assessed with the ketosteroid receptors, i.e. androgen (hAR), glucocorticoid (hGR), progesterone (hPR) and mineralocorticoid (hMR) in comparison to the corresponding natural steroids and a known endocrine disrupting xenobiotic, Bisphenol A (BPA). Most of the DLCs, particularly those bearing hydroxyl (-OH) group showed considerable affinities with ketosteroid receptors. On comparing D scores of all the dioxins and DLCs against all four receptors, compound 8-hydroxy-3,4-dichlorodibenzofuran(8-OH-DCDF) exhibited least D score of -9.549?kcal mol^?1 against hAR. 3,8-Dihydroxy-2-chlorodibenzofuran(3,8-DiOH-CDF), 4′-hydroxy-2,3,4,5-tetrachlorobiphenyl (4′-OH-TCB) and 4-hydroxy-2,2′,5′-trichlorobiphenyl(4-OH-TCB) also showed comparable molecular interactions with the ketosteroid receptors. These interactions mainly include H-bonding, π–π stacking, hydrophobic, polar and van der Waals’ interactions. In contrast, BPA and some natural ligands tested in this study showed lower binding affinities with these receptors than certain DLCs reported herein, i.e. certain DLCs might be more toxic than the proven toxic agent, BPA. Such studies play a pivotal role in the risk assessment of exposure to dioxins and DLCs on human health.     

Targeting myocardial reperfusion injuries with cyclosporine in the CIRCUS Trial – pharmacological reasons for failure

The mitochondrial permeability transition (mPTP) is a key feature of cardiac cell death in ischaemia‐reperfusion injury (I/R). The mPTP blocker, cyclosporine A (CsA), has been shown to give protection against reperfusion‐induced myocardial necrosis and troubles generated by acute coronary artery repermeabilization. Nevertheless, the results of the CIRCUS trial (Does Cyclosporine Improve Clinical Outcome in ST‐Elevation Myocardial Infarction Patients) seem to go against this hypothesis. Pharmacological reasons linked to CsA pharmacokinetics and pharmacodynamics could be suggested. First, it could be explained by a limited diffusion of the drug in the area at risk, due to the only inclusion of patients with a TIMI 0 or 1 coronary blood flow in the anterior territory and the absence of collateral perfusion. Second, to explain a low tissue diffusion of the compound, blood cell capture and high metabolism could be suggested. Moreover, CsA is highly metabolized by cytochrome P450 3A4 (CYP3A4), a polymorphic enzyme leading to variations of C_max and AUC between 10–20% in patients using CsA. Finally, CsA blocks calcineurin, a protein implied in I/R damage but calcineurin inhibition could contribute to protection towards I/R damage only when Rcan1, a calcineurin natural inhibitor, expression is low. The results of the CIRCUS trial are disappointing and could contribute to the withdrawal of the mPTP blockade pharmacological strategy as a way to protect the myocardium from I/R lesions. Nevertheless, many pharmacological insights could have contributed to an increased variability and, as a consequence, an important reduction of the pharmacological power of the study.     

Non small cell lung cancer (NSCLC): current status and future prospects

The incidence of lung cancer is rising dramatically and it is now the commonest cause of mortality and morbidity not only in the industrialised countries, but in developing nations like India as well. Tobacco smoking has consistently been demonstrated to be an important aetiological factor, though lung cancer occurs in non-smokers also. In spite of great advances in radiological and molecular diagnostic techniques, the ideal screening marker for early detection of lung cancer has still not been found. Histological diagnosis and staging is essential for selecting the mode of therapy in patients with lung cancer. Stages I and II are amenable to surgery. However, advanced stage III and IV need an individualised combination of surgery, chemotherapy and radiotherapy. With a better understanding of the cellular mechanisms operating in carcinogenesis, newer target specific modalities are being developed and tested in order to stem this disease, which threatens to assume epidemic proportions.