Cytologic diagnosis of small cell carcinoma of the ovary: A case report with review of the literature

Small cell carcinoma of the ovary (SCCO) is an exceedingly rare malignant neoplasm. It has been classified into two types: hypercalcemic and pulmonary type, the former being relatively more common. These are highly aggressive neoplasms with rapid down‐hill course and poor disease‐outcome. A high index of clinical suspicion, systematic radiological evaluation, and an early tissue diagnosis are a must for timely patient management and a better outcome. A definitive diagnosis can be established by demonstration of the characteristic morphologic and immunochemical features. We report a case of SCCO of pulmonary type in a peri‐menopausal female, presenting with a large abdomino‐pelvic mass, which was diagnosed by fine needle aspiration cytology (FNAC), by immunocytochemistry on cell‐block. In addition, cytological features of metastatic SCCO, pulmonary type, in the Papanicolaou stained liquid‐based cytology (SurePath) preparation are also presented. The current report highlights the diagnostic utility of FNAC in the diagnosis of such rare gynecological malignancies.     

Multiparametric MRI Evaluation of Complex Ovarian Masses

ObjectiveTo assess the role of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in the categorization of complex ovarian masses into benign and malignant.Materials and MethodsThis prospective study was done on 33 complex ovarian masses. T1 and T2-weighted sequences, diffusion-weighted imaging, apparent diffusion coefficient, and dynamic contrast-enhanced magnetic resonance imaging were performed on 1.5 T MRI. Time-intensity curves, tissue signal intensity on unenhanced T1 images (SI₀), maximum absolute contrast enhancement (SI_max), time to reach SI_max (T_max), maximum relative SI (SI_rel = [SI_max ? SI₀]/SI₀ ×100), maximum Slope (Slope_max = SI_rel/T_max ×100), and wash in rate (WIR = [SI_max ? SI₀]/T_max) were calculated. Histopathological diagnosis was taken as gold standard.ResultsA total of 20/33 masses were benign, 2/33 were borderline tumors, and 11/33 were malignant. Diffusion restriction was seen in all malignant masses and 13/20 benign masses. The mean apparent diffusion coefficient values showed a significant difference between malignant and benign, with 81.8% sensitivity and 63.6% specificity. Type III curve showed 100% specificity for malignant lesions. T_max and Slope_max were useful in differentiating benign and malignant masses; with T_max cut-off at 73.5 seconds having a high specificity (81.8%) and Slope_max cut-off at 0.83%/s having high sensitivity (91%) and negative predictive value (94.4%).ConclusionMultiparametric MRI confers high diagnostic accuracy in stratifying complex ovarian masses.     

TrkB inhibition by GNF-4256 slows growth and enhances chemotherapeutic efficacy in neuroblastoma xenografts

Purpose

Neuroblastoma (NB) is one of the most common and deadly pediatric solid tumors. NB is characterized by clinical heterogeneity, from spontaneous regression to relentless progression despite intensive multimodality therapy. There is compelling evidence that members of the tropomyosin receptor kinase (Trk) family play important roles in these disparate clinical behaviors. Indeed, TrkB and its ligand, brain-derived neurotrophic factor (BDNF), are expressed in 50–60 % of high-risk NBs. The BDNF/TrkB autocrine pathway enhances survival, invasion, metastasis, angiogenesis and drug resistance.

Methods

We tested a novel pan-Trk inhibitor, GNF-4256 (Genomics Institute of the Novartis Research Foundation), in vitro and in vivo in a nu/nu athymic xenograft mouse model to determine its efficacy in inhibiting the growth of TrkB-expressing human NB cells (SY5Y-TrkB). Additionally, we assessed the ability of GNF-4256 to enhance NB cell growth inhibition in vitro and in vivo, when combined with conventional chemotherapeutic agents, irinotecan and temozolomide (Irino–TMZ).

Results

GNF-4256 inhibits TrkB phosphorylation and the in vitro growth of TrkB-expressing NBs in a dose-dependent manner, with an IC₅₀ around 7 and 50 nM, respectively. Furthermore, GNF-4256 inhibits the growth of NB xenografts as a single agent (p < 0.0001 for mice treated at 40 or 100 mg/kg BID, compared to controls), and it significantly enhances the antitumor efficacy of irinotecan plus temozolomide (Irino–TMZ, p < 0.0071 compared to Irino–TMZ alone).

Conclusions

Our data suggest that GNF-4256 is a potent and specific Trk inhibitor capable of significantly slowing SY5Y-TrkB growth, both in vitro and in vivo. More importantly, the addition of GNF-4256 significantly enhanced the antitumor efficacy of Irino–TMZ, as measured by in vitro and in vivo growth inhibition and increased event-free survival in a mouse xenograft model, without additional toxicity. These data strongly suggest that inhibition of TrkB with GNF-4256 can enhance the efficacy of current chemotherapeutic treatment for recurrent/refractory high-risk NBs with minimal or no additional toxicity.

     

Impact of Argemone mexicana extracts on the cidal, morphological, and behavioral response of dengue vector, Aedes aegypti L. (Diptera: Culicidae)

The larvicidal, behavioral, and morphological response of dengue vector, Aedes aegypti treated with deleterious weed, Argemone mexicana, was explored. The 1,000 ppm extracts of A. mexicana leaf, stem, and roots prepared in five different solvents (petroleum ether, hexane, benzene, acetone, and ethanol) were screened for their larvicidal activity against dengue vector establishing the efficacy of petroleum ether and hexane extracts. Other extracts, unable to give 100 % mortality, were considered ineffective and discarded from further study. Larvicidal bioassay conducted with selected extracts confirmed the higher efficacy of hexane extracts exhibiting 1.1- to 1.8-fold more potential than the petroleum ether extracts. The results further revealed 1.6- to 2.4-fold higher efficacy of root extracts than those prepared from the leaves and stem of A. mexicana. The hexane root extract of A. mexicana was found to be the most effective larvicide with LC₅₀ value of 91.331 ppm after 24 h of exposure causing 1.8 and 2.4 fold more toxicity as compared to the hexane leaf and stem extracts, respectively. Prolonged exposure of the larvae to the extracts resulted in increased toxicity potential of the extracts. Observations of the treated larvae revealed excitation, violent vertical, and horizontal movements with aggressive anal biting behavior suggesting effect of extracts on their neuromuscular system. Morphological studies of the treated larvae revealed the demelanization of cuticle and shrinkage of internal cuticle of anal papillae indicating the anal papillae as the probable action sites of the A. mexicana extracts. The potential of A. mexicana as new larvicides against dengue vector are being explored.     

Contribution of sudden cardiac death to total mortality in India - a population based study

Introduction

Epidemiology of sudden cardiac death (SCD) in India is understudied.

Methods

We assessed proportion of SCD among total mortality in a population in Southern India using a staged, questionnaire-based kindred-wide approach. Detailed questionnaires (DQs) were completed by medical trainees from 8 medical colleges. Preliminary questionnaires evaluated total deaths in the kindred of a respondent. Deaths due to obvious non-cardiac causes were excluded. DQs were completed for the remaining deaths and categorized using a three-member adjudication system.

Results

A total population of 22,724 was evaluated by 478 respondents, (278 M and 200 F). Out of a total of 2185 deaths, 1691 (77.4%) were recallable. A total of 173 (10.3%; 128 M and 45 F; mean age — 60.8 ± 14 years) deaths were adjudicated as SCD. Of these, 82 (47.3%) were ≤ 60 years of age. Prior MI, LV dysfunction and prior aborted SCD were found in 33.5%, 22.5% and 5.7% respectively. Coronary artery disease (CAD) was observed in 66 (38%) and acute myocardial infarction documented in 30 (17%). At least 1 of 3 CAD risk factors — hypertension, diabetes, or smoking was observed in 80.6%. Proportion of subjects with at least one risk factor for CAD were similar in the age groups above and below 50 years (67.6% vs. 81.7%, p = 0.065).

Conclusions

SCD contributed to 10.3% of overall mortality in this population from Southern India. On an average, SCD cases were 5-8 years younger compared to populations reported in the western hemisphere, with a high prevalence of major risk factors for CAD.     

Interferon γ and glycemic status in diabetes associated with chronic pancreatitis

Background/aimsAlthough the role of cytokines in the etiopathology of chronic pancreatitis (CP) is well recognized, information on pancreatic tissue cytokines in CP with/without associated diabetes is unavailable. The aim of the present study was to identify the differences in pancreatic cytokines and observe their correlations with the glycemic status in CP.MethodsPancreata were obtained from CP patients (n = 44), with/without associated diabetes and non-diabetic control subjects (n = 20). Patients with CP were classified into two groups after ascertaining their diabetic status. Pancreatic cytokines (IL 1β, IL 6, IL 8, IL 10, IL 12P70, TNF α, IFN γ) were analyzed by flow cytometer. The influence of individual and cocktail of cytokines on glucose stimulated insulin release (GSIR) was examined by challenging the islets from control subjects.ResultsThe pancreatic IFN γ levels in diabetic and non diabetic CP patients were significantly higher in comparison to controls. The glucose stimulated insulin release (GSIR) in response to high glucose concentration in control islets, islets from non-diabetic and diabetic CP patients was 8.2, 5.67 and 3.15 μU × 10^?3/min/islet equivalent respectively. IFN γ resulted in 82.35% decrease in GSIR from the control islet cells at a concentration of >20 pg/ml which was reversed by epigallocatechin-3-gallate (EGCG).ConclusionThese results suggest that IFN γ among other cytokines, play a major role in β-cell dysfunction associated with CP.     

Comparison of Binocular Vision Parameters Pre- and Post-EPILASIK Laser Vision Correction Surgery for Myopia in a Pilot Study – Can Vision Therapy Augment Refractive Results?

Purpose:To analyze the changes in the binocular vision parameters after bilateral Epilasik laser vision correction surgery (LVCS).Setting:Medical Research Foundation, Tamil Nadu, India.Study design:Prospective cohort study.Methods:Subjects with a best corrected visual acuity of ≤ 0.0 Log MAR scale and refractive error: < 6.00DS of myopia, < 0.75D of astigmatism, and < 1D of anisometropia were included in the study. All subjects underwent a comprehensive eye examination, LVCS workup which included corneal topography, tomography, aberrometry, and dry eye assessment prior to binocular vision assessment. Complete Binocular vision assessment which included stereopsis, fusion for distance and near, near point of convergence, phoria measurement, vergence amplitudes and facility, accommodative amplitudes, response, and facility was performed with the best corrected vision prior to LVCS, one month and six months after the surgery.Results:Twenty-five subjects of age 23.8 ± 2.9 years were included. Age ranged from 20 to 32 years. Ten were female and 15 were male. The median spherical power was –2.00DS with an inter quartile range (IQR) of –1.50DS to –3.00DS for both eyes. The median cylindrical power was plano with IQR –0.50DC to –1.00DC for both eyes. There was a statistically significant decrease in monocular and binocular accommodative amplitudes (accounting for age-related changes) as well as positive fusional vergence recovery for near between baseline and one month after surgery (p < 0.05).Conclusion:Though subjects were asymptomatic post LVCS, still there is an indication that myopic LVCS could precipitate or aggravate an existing non-strabismic binocular vision anomaly. Comprehensive binocular vision assessment and appropriate management is recommended before and after LVCS.