Central versus distal pancreatectomy for low-grade and benign pancreatic neck-body tumours.

PURPOSE: Central pancreatectomy (CP) offers parenchymal preservation compared to conventional distal pancreato-splenectomy for pancreatic neck and body tumours. However, it is associated with more morbidity. This study is aimed at evaluating the peri-operative and long-term functional outcomes, comparing central and distal pancreatectomies (DPs). METHODS: Retrospective analysis of patients undergoing pancreatic resections for low-grade malignant or benign tumours in pancreatic neck and body was performed (from January 2007 to December 2022). Preoperative imaging was reviewed for all cases, and only patients with uninvolved pancreatic tail, whereby a CP was feasible, were included. Peri-operative outcomes and long-term functional outcomes were compared between CP and DP. RESULTS: One hundred twenty-two (5.2%) patients, amongst the total of 2304 pancreatic resections, underwent central or distal pancreatectomy for low-grade malignant or benign tumours. CP was feasible in 55 cases, of which 23 (42%) actually underwent CP and the remaining 32 (58%) underwent DP. CP group had a significantly longer operative time [370 min (IQR 300-480) versus 300 min (IQR 240-360); p = 0.002]; however, the major morbidity (43.5% versus 37.5%; p = 0.655) and median hospital stay (10 versus 11 days; p = 0.312) were comparable. The long-term endocrine functional outcome was favourable for the CP group [endocrine insufficiency rate was 13.6% in central versus 42.8% in distal (p = 0.046)]. CONCLUSION: Central pancreatectomy offers better long-term endocrine function without any increased morbidity in low malignant potential or benign pancreatic tumours of neck and body region.

Imaging of central nervous system emergencies in oncology.

Central nervous system (CNS) may be predisposed to devastating complications in cancer patients which may add to morbidity and mortality in this group. Majority of the complications are vascular in nature due to the altered coagulation profile and pro-inflammatory state in these patients. However, there are a host of other conditions which may affect the clinical course of these patients including metabolic and toxic encephalopathies, infections, and paraneoplastic syndromes. Moreover, multimodality management of these patients, which is often used in majority of the cancers, exposes them to treatment related complications. This pictorial review aims to enlighten the reader regarding the various complications affecting the CNS as seen at our tertiary cancer care institute. We aim to highlight the emergent nature of these complications and the need to identify them quickly and accurately on imaging which helps to institute early appropriate management and prevents further morbidity and mortality.

Endolymphatic sac tumor: single-institution series of seven cases with updated review of literature.

BACKGROUND: Endolymphatic sac tumour (ELST) is a rare low-grade locally aggressive neoplasm arising from the endolymphatic duct or sac. It presents mostly with vestibulo-cochlear symptoms either sporadically or as part of von Hippel-Lindau (VHL) syndrome. Micro-neurosurgical excision remains the cornerstone of therapy with the role of radiotherapy (RT) being controversial. This is a clinico-pathological analysis of consecutive ELST patients presenting to a single-institution in India. METHODS: Neuropathology database of a tertiary-care comprehensive cancer centre was searched electronically to identify consecutive patients with histopathological diagnosis of ELST registered at the institute over last one decade. Data regarding demographic profile, clinical presentation, histopathological features, treatment details and outcomes were retrieved from electronic medical records for this retrospective analysis. RESULTS: Electronic search identified seven unique patients with biopsy-proven ELST registered at the institute between 2009 and 2020. Median age of the study cohort was 39 years (range 24-65 years) with strong male predilection (5:2 ratio) and left-sided preponderance (71%). Most common presenting symptoms were hearing loss (86%) and earache (71%) on affected side followed by headache (43%). All patients underwent maximal safe resection at initial diagnosis and were followed-up closely with periodic surveillance imaging. Two patients underwent salvage RT using high-precision conformal techniques at recurrence/progression. CONCLUSION: ELST is a rare low-grade locally aggressive neoplasm that arises generally as part of VHL syndrome or sometimes sporadically. Gross total resection provides the best chance of cure with RT being reserved for unresectable disease, large residue, medical inoperability, or as salvage therapy for recurrent/progressive tumor.

Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents.

A series of spirochromenocarbazole tethered 1,2,3-triazoles were synthesized via click chemistry based one-pot, five component reaction between N-propargyl isatins, malononitrile, 4-hydroxycarbazole, aralkyl halides and sodium azide using cellulose supported CuI nanoparticles (Cell-CuI NPs) as the heterogeneous catalyst. Antiproliferative activity of all the synthesized compounds was investigated against panel of cancer cell lines such as MCF-7, MDA-MB-231, HeLa, PANC-1, A-549, and THP-1. Many of the synthesized compounds exhibited good anti-proliferative activity against breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cells with IC50 values less than 10 µM. In case of MCF-7 cells, among the nine compounds that showed good anti-proliferative activity, compounds 6f and 6j were found to be highly potent (IC50 = 2.13 µM and 4.80 µM, respectively). In case of MDA-MB-231, three compounds (6k, 6j and 6s) showed antiproliferative activity amongst which 6k was the most potent one (IC50 = 3.78 µM). On the other hand, in cervical cancer HeLa cells, compounds 6b, 6g, 6s and 6u showed excellent antiproliferative activity (IC50 = 4.05, 3.54, 3.83, 3.35 µM, respectively). All the compounds were found to be nontoxic to the human umbilical vein endothelial cells (HUVECs). AO and EtBr staining and fluorescence microscopy studies of the active compounds (IC50 < 5 µM) suggested that these compounds induce cell death by apoptosis.

Design, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents.

Cinnamic acid and its derivatives are known for anti-tubercular activity. The present study reports the synthesis of cinnamic acid derivatives via bioisosteric replacement of terminal carboxylic acid with "oxadiazole". A series of cinnamic acid derivatives (styryl oxadiazoles) were designed and synthesized in good yields by reaction of substituted cinnamic acids (2, 15a-15s) with amidoximes. The synthesized styryl oxadiazoles were evaluated in vitro for anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Ra strain. The structure-activity relationship (SAR) study has identified several compounds with mixed anti-tubercular profiles. The compound 32 displayed potent anti-tubercular activity (IC50 = 0.045 µg/mL). Molecular docking studies on mycobacterial enoyl-ACP reductase enzyme corroborated well with the experimental findings providing a platform for structure based hit-to-lead development.

Synthesis and biological evaluation of some new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives as potential antitubercular agents.

A series of new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 8a-l were synthesized and characterized by IR, NMR (1 H and 13 C), and mass spectral analysis. The newly synthesized compounds 8a-l were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37 Ra using an established XTT reduction menadione assay (XRMA). The title compounds exhibited minimum inhibitory concentrations (MIC90 ) ranging from 0.09 to >30 µg/mL. Five compounds (8c, 8i-l) were further confirmed for their dose-dependent effect against MTB. These compounds were evaluated in the THP-1 infection model, where 8i (MIC90 = 0.35 µg/mL), 8j (MIC90 = 1.17 µg/mL), 8k (MIC90 = 2.38 µg/mL), and 8l (MIC90 = 1.17 µg/mL) demonstrated significant antitubercular activity. All the ex vivo active compounds showed insignificant cytotoxicity against the human cancer cell lines, HeLa, MCF-7, and THP-1. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity. Molecular docking studies in the active site of the sterol 14alpha-demethylase (CYP51) enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping to understand the ligand-protein interactions and to establish a structural basis for inhibition of MTB. The results suggest novel pharmacophores as selective and specific inhibitors against MTB that can be explored further to synthesize lead compounds against tuberculosis. In summary, the results clearly indicate the identification of some novel, selective, and specific inhibitors against MTB that can be explored further for potential antitubercular drugs.

Multifocal Tuberculosis Presenting as Metastatic Tumour.

A middle aged female presented with multiple lesions in the bone mimicking as multiple metastasis. In such cases detection of lesion should be confirmed by soft tissue diagnosis and appropriate culture. In our case, the lesions were responsive to anti-tuberculous treatment.

Spark Plasma Sintering of Pure Titanium: Microstructure and Mechanical Characteristics.

The versatility of titanium (Ti) allows it to be employed in various industries, from aerospace engineering to medical technology, highlighting its significance in modern manufacturing and engineering processes. Spark plasma sintering (SPS) is currently being explored to enhance its properties further and broaden its application range. The current study focuses on exploring and optimizing the effect of SPS temperature (800, 900, 1000, 1100, 1200, and 1400 °C) on pure Ti sintered at 60 MPa in a controlled argon environment with a dwell time of 5 min. All the prepared samples were highly dense with a relative density above 99%, but exhibited significant variations in grain size (10 to 57 µm), tensile yield strength (488 to 700 MPa), ultimate tensile strength (597 to 792 MPa), and ductility (4 to 7%). A microstructural investigation was performed using XRD, SEM, and EDS to predict the influence of sintering temperature on the formation of different phases. The XRD patterns of all sintered samples showed the presence of single-phase α-Ti with hexagonally close-packed Ti. This work is a step forward in optimizing SPS-processed Ti's physical and mechanical properties for enhanced structural and biomedical applications.

Enhancing Quality Control: Image-Based Quantification of Carbides and Defect Remediation in Binder Jetting Additive Manufacturing.

While binder jetting (BJ) additive manufacturing (AM) holds considerable promise for industrial applications, defects often compromise part quality. This study addresses these challenges by investigating binding mechanisms and analyzing common defects, proposing tailored solutions to mitigate them. Emphasizing defect identification for effective quality control in BJ-AM, this research offers strategies for in-process rectification and post-process evaluation to elevate part quality. It shows how to successfully process metallic parts with complex geometries while maintaining consistent material properties. Furthermore, the paper explores the microstructure of AISI M2 tool steel, utilizing advanced image processing techniques like digital image analysis and SEM images to evaluate carbide distribution. The results show that M2 tool steel has a high proportion of M6C carbides, with furnace-cooled samples ranging from ~2.4% to 7.1% and MC carbides from ~0.4% to 9.4%. M6C carbides ranged from ~2.6% to 3.8% in air-cooled samples, while water-cooled samples peaked at ~8.52%. Sintering conditions also affected shrinkage, with furnace-cooled samples showing the lowest rates (1.7 ± 0.4% to 5 ± 0.4%) and water-cooled samples showing the highest (2 ± 0.4% to 14.1 ± 0.4%). The study recommends real-time defect detection systems with autonomous corrective capabilities to improve the quality and performance of BJ-AM components.

Advances in Nickel-Containing High-Entropy Alloys: From Fundamentals to Additive Manufacturing.

High-entropy alloys (HEAs) are recognized as a class of advanced materials with outstanding mechanical properties and corrosion resistance. Among these, nickel-based HEAs stand out for their impressive strength, ductility, and oxidation resistance. This review delves into the latest advancements in nickel-containing HEAs, covering their fundamental principles, alloy design strategies, and additive manufacturing techniques. We start by introducing HEAs and their unique properties, emphasizing the crucial role of nickel. This review examines the complex relationships between alloy composition, valence electron concentration (VEC), and the resulting crystal structures. This provides insights into design principles for achieving desired microstructures and mechanical properties. Additive manufacturing (AM) techniques like selective laser melting (SLM), electron beam melting (EBM), and laser metal deposition (LMD) are highlighted as powerful methods for fabricating intricate HEA components. The review addresses the challenges of AM processes, such as porosity, fusion defects, and anisotropic mechanical properties, and discusses strategies to mitigate these issues through process optimization and improved powder quality. The mechanical behavior of AM-processed nickel-based HEAs is thoroughly analyzed, focusing on compressive strength, hardness, and ductility. This review underscores the importance of microstructural features, including grain size, phase composition, and deformation mechanisms, in determining the mechanical performance of these alloys. Additionally, the influence of post-processing techniques, such as heat treatment and hot isostatic pressing (HIP) on enhancing mechanical properties is explored. This review also examines the oxidation behavior of nickel-containing HEAs, particularly the formation of protective oxide scales and their dependence on aluminum content. The interplay between composition, VEC, and oxidation resistance is discussed, offering valuable insights for designing corrosion resistant HEAs. Finally, this review outlines the potential applications of nickel-based HEAs in industries such as aerospace, automotive, and energy, and identifies future research directions to address challenges and fully realize the potential of these advanced materials.

Evaluation of an Objective MRI-Based Tumor Regression Grade (mrTRG) Score and a Subjective Likert Score for Assessing Treatment Response in Locally Advanced Rectal Cancers-A Retrospective Study.

Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods: Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results: The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion: An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.

Tata Memorial Centre Evidence Based Management of Colorectal cancer.

ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.

Single non-ionic surfactant based self-nanoemulsifying drug delivery systems: formulation, characterization, cytotoxicity and permeability enhancement study.

Single non-ionic surfactant based self-nanoemulsifying drug delivery system (SNEDDS) was formulated and characterised for poor water soluble drug, Atorvastatin calcium. Capmul MCM oil showing highest solubility for Atorvastatin calcium was selected as oil phase. Self-nanoemulsifying capacity of Cremophor RH 40, Cremophor EL, Tween 20, Tween 60, Tween 80 and Labrasol were tested for the selected oil. In vitro dissolution studies were performed and were characterized by t85% and dissolution efficiency (DE). Cytotoxicity of the formulations and permeation enhancement of the drug across caco-2 cell monolayer was assessed. Capmul MCM was found to be better nanoemulsified in decreasing order of Cremophor RH 40 > Cremophor EL > Tween 20 > Tween 60 > Tween 80. Values of droplet size (range 11-83 nm), polydispersity index (range 0.07-0.65); zeta potential (range -3.97 to -19.0) and cloud point (60-85°C) before and after drug loading proves the uniformity and stability of the formulations. SNEDDS formulated with Tween 20 surfactant showed enhanced dissolution with t85% and DE values at 10 min and 78.70, respectively. None of the formulation showed cytotoxicity at the concentration tested. Tween 20 based SNEDDS enhanced permeation of the drug as compared with pure drug across cell lines. It can be concluded that SNEDDS can be formulated by using single non-ionic surfactant system for enhance dissolution and absorption of poorly soluble drug, Atorvastatin calcium.

Outcomes of coronary artery bypass grafting based on myocardial perfusion imaging.

Introduction: Coronary artery disease (CAD) is the foremost single cause of mortality and loss of disability-adjusted life years globally and a large percentage of this burden is found in low and middle income countries, with the treatment strategies based on revascularisation, based on studies that have shown that on revascularisation of viable myocardium there is an improvement of function over a period of time. Aim: To evaluate the utilization of myocardial perfusion imaging (MPI) for identifying viable myocardium and assessing the improvement. Material and methods: This prospective observational study was conducted in patients having CAD planned for coronary artery bypass grafting. The patients were evaluated using 2D ECHO and MPI preoperatively and postoperatively after 1 year. Results: Mean ejection fraction preoperatively was 40.6 ±9.72% and postoperatively it improved to 41.32 ±10.64% and ejection fraction was calculated using MPI and an average improvement from 35.98 ±12.72% to 45.51 ±12.61% (p ≤ 0.0001). Summed rest score was calculated and an improvement was noted from 24.28 ±8.47 to 18.02 ±8.75 (p ≤ 0.0001). Total perfusion deficit was calculated and was found to have reduced from 32.44 ±11.98 to 25.61 ±12.23 (p ≤ 0.0001). Conclusions: MPI was able to accurately assess the improvement, which correlated not only with the 2D echocardiography data but also with the clinical wellbeing of the patients. Being a non-invasive, quick procedure, it should be added to the arsenal of the cardiac surgeon for evaluation of patients with diffuse diseases, low ejection fractions, patients who might generally be considered inoperable.

Implications of use of different intraoperative ultrasound modalities during glioma surgery - A comparative study of factors affecting outcomes.

BACKGROUND: The main goal of glioma surgery is to remove the maximum amount of tumor without worsening the patient's neurological condition. Intraoperative ultrasound (US) imaging technologies (2D and 3D) are available to assist surgeons, providing real-time updates. Considering additional time, personnel, and cost, we investigate if comparable outcomes can be achieved using basic (2D) and advanced (3D) technology. OBJECTIVE: We propose predictive models for (i) glioma tumor resectability (ii) surgical outcome, and (iii) a model to predict the outcome of surgery aided with a particular ultrasound and compare outcomes between 2D and 3D US. METHODOLOGY: We used real-world surgery data from a tertiary cancer centre. Three groups of cases were analyzed (2D US used, 3D US used, and no US used during resection). The data analysis uses hypothesis testing, bootstrap sampling, and logistic regression. RESULTS: The preoperatively anticipated extent of tumor removal correlated with the postoperative MRI measurement of tumor removal for US-supported surgery (p=0.01) but not for no US-supported surgeries (p = 0.13). A combination of delineation, eloquence, and the multifocal/multicentric nature of the tumor effectively predicted resectability. The eventual outcome of surgery (actual extent of resection achieved) can be predicted by prior treatment status, delineation, eloquence, and satellite nodules. Based on our prediction model (training set of 350 cases and test of 40 cases of US-guided surgeries), we identify some cases where 3D US seems to offer superior EORs. CONCLUSION: The resectability of glioma tumors is crucial in determining surgical objectives, and the type of ultrasound used as support impacts tumor removal. The findings in this study aid informed decision-making and optimize imaging technology usage, providing a decision flow for selecting ultrasound based on tumor characteristics.

MRI in rectal cancer patients on 'watch and wait': patterns of response and their evolution.

PURPOSE: Evaluate MR patterns of response and their evolution in rectal cancer patients on watch and wait (WW). METHODS: We retrospectively reviewed 337 MRIs of 60 patients (median follow-up: 12 months; range: 6-49 months). Baseline MRIs (available in 34/60 patients) were evaluated for tumor morphology, location, thickness, circumferential involvement, nodal status and EMVI. First post-treatment MRIs (in all patients) were additionally evaluated for pattern of response on T2 and DWI. Change in post-treatment scar thickness and scar depth angle between the first and second post-treatment scans was also evaluated. Evolution of the response pattern/recurrence were evaluated till the last available scan. RESULTS: On the baseline scans, 20/34 (59%) patients had polypoidal tumor with 12/20 having ≤ 25% circumferential wall involvement. We saw five patterns of response-normalized rectal wall (2/60-3%), minimal fibrosis (23/60-38%), full thickness fibrosis (16/60-27%), irregular fibrosis (11/60-18%) and split scar (6/60-10%), with 2/60 (3%) showing possible residual disease. On the first post-treatment scans, 12/60 (20%) had restricted diffusion, with 3/12 having persistent restriction till last follow-up. Post-treatment fibrosis/split scar remained stable in 44/60 (73%) cases and improved further in the rest. 9/60 (15%) patients developed regrowth/recurrence. Patients with recurrence had < 10 mm scar thickness and < 21° change in scar angle between the first and second post-treatment MRIs. CONCLUSION: Most patients on WW protocol developed minimal or full thickness fibrosis, majority of which remained stable on follow-up.

Deep learning based clinico-radiological model for paediatric brain tumor detection and subtype prediction.

Aim: Early diagnosis of paediatric brain tumors significantly improves the outcome. The aim is to study magnetic resonance imaging (MRI) features of paediatric brain tumors and to develop an automated segmentation (AS) tool which could segment and classify tumors using deep learning methods and compare with radiologist assessment. Methods: This study included 94 cases, of which 75 were diagnosed cases of ependymoma, medulloblastoma, brainstem glioma, and pilocytic astrocytoma and 19 were normal MRI brain cases. The data was randomized into training data, 64 cases; test data, 21 cases and validation data, 9 cases to devise a deep learning algorithm to segment the paediatric brain tumor. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the deep learning model were compared with radiologist's findings. Performance evaluation of AS was done based on Dice score and Hausdorff95 distance. Results: Analysis of MRI semantic features was done with necrosis and haemorrhage as predicting features for ependymoma, diffusion restriction and cystic changes were predictors for medulloblastoma. The accuracy of detecting abnormalities was 90%, with a specificity of 100%. Further segmentation of the tumor into enhancing and non-enhancing components was done. The segmentation results for whole tumor (WT), enhancing tumor (ET), and non-enhancing tumor (NET) have been analyzed by Dice score and Hausdorff95 distance. The accuracy of prediction of all MRI features was compared with experienced radiologist's findings. Substantial agreement observed between the classification by model and the radiologist's given classification [K-0.695 (K is Cohen's kappa score for interrater reliability)]. Conclusions: The deep learning model had very high accuracy and specificity for predicting the magnetic resonance (MR) characteristics and close to 80% accuracy in predicting tumor type. This model can serve as a potential tool to make a timely and accurate diagnosis for radiologists not trained in neuroradiology.

Self-microemulsifying smaller molecular volume oil (Capmul MCM) using non-ionic surfactants: a delivery system for poorly water-soluble drug.

The main purpose of this work is to formulate self-microemulsifying drug delivery system (SMEDDS) using smaller molecular oil with Atorvastatin calcium as a model drug. Solubility of the selected drug was accessed in oils and surfactants. Percent transmittance (%T) test study was performed to identify the efficient self-microemulsifying formulations. Those formulations which showed higher value for %T were evaluated for droplet size, polydispersity index, ζ potential, refractive index and cloud point measurement. Effect of drug loading on droplet size, increasing dilution in different media, thermodynamic stability and in vitro dissolution was performed to observe the performance of the selected formulation. Further cytotoxicity and permeation enhancement studies were carried out on Caco2 cell lines. Of all the oils accessed for drug solubility, Capmul MCM showed higher solubility capacity for Atorvastatin calcium. Capmul MCM was better microemulsified using combination of Tween 20 and Labrasol surfactant. Droplet size was as low as 86.93 nm with polydispersity index and ζ potential at 0.195 ± 0.011 and -7.27 ± 3.11 mV respectively. The selected undiluted formulation showed refractive index values ranging from 1.40 to 1.47 indicating the isotropicity of the formulation. The selected formulation was robust to dilution in different media and thermodynamically stable. Dissolution profile was enhanced for the selected drug as compared to marketed formulation with t85% and DE values at 10 min and 80.15 respectively. Also cytotoxicity measurement showed minimum effect with good permeation enhancing capacity. Thus our study demonstrates the use of smaller molecular oil (Capmul MCM) for developing self-microemulsifying drug delivery system for better in vitro and in vivo performance.

Multiparametric Magnetic Resonance Imaging Correlates of Isocitrate Dehydrogenase Mutation in WHO high-Grade Astrocytomas.

Purpose and background: Isocitrate dehydrogenase (IDH) mutation and O-6 methyl guanine methyl transferase (MGMT) methylation are surrogate biomarkers of improved survival in gliomas. This study aims at studying the ability of semantic magnetic resonance imaging (MRI) features to predict the IDH mutation status confirmed by the gold standard molecular tests. Methods: The MRI of 148 patients were reviewed for various imaging parameters based on the Visually AcceSAble Rembrandt Images (VASARI) study. Their IDH status was determined using immunohistochemistry (IHC). Fisher's exact or chi-square tests for univariate and logistic regression for multivariate analysis were used. Results: Parameters such as mild and patchy enhancement, minimal edema, necrosis < 25%, presence of cysts, and less rCBV (relative cerebral blood volume) correlated with IDH mutation. The median age of IDH-mutant and IDH-wild patients were 34 years (IQR: 29−43) and 52 years (IQR: 45−59), respectively. Mild to moderate enhancement was observed in 15/19 IDH-mutant patients (79%), while 99/129 IDH-wildtype (77%) had severe enhancement (p-value <0.001). The volume of edema with respect to tumor volume distinguished IDH-mutants from wild phenotypes (peritumoral edema volume < tumor volume was associated with higher IDH-mutant phenotypes; p-value < 0.025). IDH-mutant patients had a median rCBV value of 1.8 (IQR: 1.4−2.0), while for IDH-wild phenotypes, it was 2.6 (IQR: 1.9−3.5) {p-value = 0.001}. On multivariate analysis, a cut-off of 25% necrosis was able to differentiate IDH-mutant from IDH-wildtype (p-value < 0.001), and a cut-off rCBV of 2.0 could differentiate IDH-mutant from IDH-wild phenotypes (p-value < 0.007). Conclusion: Semantic imaging features could reliably predict the IDH mutation status in high-grade gliomas. Presurgical prediction of IDH mutation status could help the treating oncologist to tailor the adjuvant therapy or use novel IDH inhibitors.

Mebendazole plus lomustine or temozolomide in patients with recurrent glioblastoma: A randomised open-label phase II trial.

Background: Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) has activity in glioma both in-vivo and in-vitro, and is well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. Methods: In this phase II randomized open-label trial, adult patients with ECOG PS 0-3, with recurrent GBM who were not eligible for re-radiation, were randomized 1:1 to the CCNU-MBZ and TMZ-MBZ arms. CCNU was administered at 110 mg/m2 every 6 weeks with MBZ 800 mg thrice daily and TMZ was administered at 200 mg/m2 once daily on days 1-5 of a 28 days cycle with MBZ 1600 mg thrice daily. The primary endpoint was OS at 9 months. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. OS was analyzed using intention to treat (ITT) and per-protocol (PP) analyses. Per-protocol analysis was used for safety analysis. Clinical Trials Registry-India number, CTRI/2018/01/011542. Findings: Participants were recruited from 14th March 2019 to 18th June 2021, 44 patients were randomised on each arm. At 17.4 months, 68 events for OS analysis had occurred, 33 in the TMZ-MBZ and 35 in the CCNU-MBZ arm. The 9-month OS was 36.6% (95% CI 22.3-51.0) and 45% (95% CI 29.6-59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively, in the ITT population. ECOG PS was the only independent prognostic factor impacting OS (HR-0.48, 95% CI 0.27-0.85; P = 0.012). Grade 3-5 adverse events were seen in 8 (18.6%; n = 43) and 4 (9.5%; n = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. There were no treatment related deaths. Interpretation: The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients having poor PS of 2-3. Funding: Brain Tumor Foundation (BTF) of India, Indian Cooperative Oncology Network (ICON), and India Cancer Research Consortium (ICRC) under ICMR (Indian Council of Medical Research).