Cytology in the otorhinolaryngologist’s domain - a study of 150 cases, emphasizing diagnostic utility and pitfalls

150 patients with mass lesions in the head and neck area, excluding the CNS and thyroid gland were subjected to FNA cytodiagnosis. II out of 150 smears were considered unsatisfactory for diagnostic evaluation. Out of the 139 patients who yielded satisfactory smears, cytodiagnosis led to the following broad categories - inflammatory and non- neoplastic (24/139, 17.3%), benign neoplasm (60/139, 43.2%), suspicious for malignancy (14/139. 10%) and malignant neoplasms (41/139, 29.5%). Histopathologic follow- up was available in 120 cases. 15/24 with inflammatory lesions were not subjected to biopsy, rest 4 were lost to follow up (I had a suspicious smear and 3 the diagnosis of benign neoplasm). Correlation of cytodiagnoses with histopathology yielded the following results - 52 out of 57 patients with the cytodiagnosis of benign neoplasm and having, histologic follow up had concordance, while 39 out of 41 cytologic diagnoses of malignancy, correlated with histopathology. Out of surgically sampled 9 patients, with inflammatory smears, 8 were benign and 1 malignant. In the suspicious category 2 out of 13 surgically sampled patients had malignancy. Thus, excluding the suspicious smears the accuracy of diagnosis by FNAC in this study came to 93% and a sensitivity for cancer detection of 95%. We encountered a false negative rate of 9.0% and a false positive rate of 4.9%. The results are discussed, especially in the light of the misdiagnoses and ways at avoiding diagnostic : error.     

Understanding Malignancies of the Thyroid Gland: Institutional Experience

To study the epidemiological, pathological characters and determine survival in patients diagnosed of having thyroid gland malignancies. Retrospective chart review of patients having thyroid gland malignancies, which were managed by the two senior authors at our tertiary care institute from January 2000 to December 2006, were performed and evaluated in terms of various clinical, operative and histological parameters. Patients in which follow up of at least 10 years are available were included in the study. Survival was enquired telephonically in those patients who got cured and did not consent to come for follow up. Slides were reviewed. Statistical analysis was done using SPSS statistical software. Kaplan–Meier method was used for calculating survival. A total of 182 patients were included in the study. Papillary carcinoma was the commonest malignant lesion with a frequency of 87.91% followed by follicular carcinoma (7.69%), medullary carcinoma (3.29%) and anaplastic carcinoma (1.09%). Female predominance was seen (F:M–5.06:1). The 5 year and 10 year survival rates were 89% and 73% respectively. The most common postoperative squeal was transient hypocalcaemia, seen in (27/182) 15% patients which was followed by permanent hypocalcaemia 16/182 (8.79%), transient recurrent laryngeal nerve paresis 12/182 (6.59%) and permanent recurrent laryngeal nerve palsy 8/182 (4.39%). Thyroid malignancies affect all age groups and have good long term prognosis. Management yields promising results and hence early and adequate treatment is emphasized.     

Monocytes transduced with lentiviral vectors expressing hepatitis C virus non-structural proteins and differentiated into dendritic cells stimulate multi-antigenic CD8 T cell responses

Halting the spread of hepatitis C virus (HCV) and also eradicating HCV in subjects with chronic infection are major goals for global health. To this end, several years of research on HCV vaccine development have led to the conclusion that multi-antigenic and multi-functional vaccine types are necessary for effectiveness against HCV infection. In this study, we evaluated lentiviral vectors (LV) expressing clusters of HCV structural (LV-HCV-S) and non-structural (LV-HCV-NS) genes for future vaccine development. Batches of high titer LV were used to transduce differentiated dendritic cells (DC) and monocytes. We report successful delivery of HCV gene clusters, particularly into monocytes, leading to >80% LV-HCV-NS and >70% LV-HCV-S and transduced cells, respectively. Intracellular expression of HCV proteins in monocyte-derived DC resulted in immunophenotypic changes, such as downregulation of CD83 and CD86. Monocytes expressing NS proteins and differentiated into DC stimulated allogeneic and autologous CD8⁺ and CD4⁺ T cells in vitro and resulted in antigen-specific CD8⁺ T cell responses against NS3, NS4a and NS5b. Hence, lentiviral-mediated expression of the multi-antigenic HCV-NS cluster in monocytes subsequently differentiated into DC is a novel potential anti-HCV vaccine modality.     

M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in Sprague-Dawley and Wistar rats.

In a recent study using Wistar rats, the serotonergic 5-HT2 receptor antagonists ketanserin and risperidone reduced the disruptive effects of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine on prepulse inhibition (PPI), suggesting that there is an interaction between serotonin and glutamate in the modulation of PPI. In contrast, studies using the noncompetitive NMDA antagonist phencyclidine (PCP) in Sprague-Dawley rats found no effect with 5-HT2 antagonists. To test the hypothesis that strain differences might explain the discrepancy in these findings, risperidone was tested for its ability to reduce the PPI-disruptive effects of dizocilpine in Wistar and Sprague-Dawley rats. Furthermore, to determine which serotonergic receptor subtype may mediate this effect, the 5-HT2A receptor antagonist M100907 (formerly MDL 100,907) and the 5-HT2C receptor antagonist SDZ SER 082 were tested against dizocilpine. Recent studies have found that the PPI-disruptive effects of PCP are reduced by the alpha 1 adrenergic receptor antagonist prazosin. Furthermore, the alpha 1 receptor agonist cirazoline disrupts PPI. As risperidone and M100907 have affinity at the alpha 1 receptor, a final study examined whether M100907 would block the effects of cirazoline on PPI. Risperidone partially, but nonsignificantly, reduced the effects of dizocilpine in Wistar rats, although this effect was smaller than previously reported. Consistent with previous studies, risperidone did not alter the effects of dizocilpine in Sprague-Dawley rats. Most importantly, M100907 pretreatment fully blocked the effect of dizocilpine in both strains; whereas SDZ SER 082 had no effect. M100907 had no influence on PPI by itself and did not reduce the effects of cirazoline on PPI. These studies confirm the suggestion that serotonin and glutamate interact in modulating PPI and indicate that the 5-HT2A receptor subtype mediates this interaction. Furthermore, this interaction occurs in at least two rat strains.     

Radiomics signature for temporal evolution and recurrence patterns of glioblastoma using multimodal magnetic resonance imaging

Glioblastoma is a highly infiltrative neoplasm with a high propensity of recurrence. The location of recurrence usually cannot be anticipated and depends on various factors, including the surgical resection margins. Currently, radiation planning utilizes the hyperintense signal from T2-FLAIR MRI and is delivered to a limited area defined by standardized guidelines. To this end, noninvasive early prediction and delineation of recurrence can aid in tailored targeted therapy, which may potentially delay the relapse, consequently improving overall survival. In this work, we hypothesize that radiomics-based phenotypic quantifiers may support the detection of recurrence before it is visualized on multimodal MRI. We employ retrospective longitudinal data from 29 subjects with a varying number of time points (three to 13) that includes glioblastoma recurrence. Voxelwise textural and intensity features are computed from multimodal MRI (T1-contrast enhanced [T1CE], FLAIR, and apparent diffusion coefficient), primarily to gain insights into longitudinal radiomic changes from preoperative MRI to recurrence and subsequently to predict the region of relapse from 143 ± 42 days before recurrence using machine learning. T1CE MRI first-order and gray-level co-occurrence matrix features are crucial in detecting local recurrence, while multimodal gray-level difference matrix and first-order features are highly predictive of the distant relapse, with a voxelwise test accuracy of 80.1% for distant recurrence and 71.4% for local recurrence. In summary, our work exemplifies a step forward in predicting glioblastoma recurrence using radiomics-based phenotypic changes that may potentially serve as MR-based biomarkers for customized therapeutic intervention.