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.

Novel educational training of para medical professionals in cervical cancer screening.

Background: Cervical cancer is a public health problem in India due to weak national screening policy compounded by lack of resources including scarcity of trained personnel to carry out community-based screening program. Para medical professionals (PMPs) are closely related to women in local communities. Hence, training PMPs by incorporating novel technology and reduced time duration to achieve adequate competence in screening is an area underutilized and needs to be explored. Materials and methods: A pilot cross sectional analytical study was conducted at a tertiary referral cancer center using a shorter version of educational intervention of 2 weeks duration (EI2W) involving PMPs. Pre- and post-training assessment of knowledge, attitude, and practice (KAP) was done using questionnaires consisting of 5 domains viz. awareness of cervical cancer, awareness of cervical pre-cancer, practical screening methodology (practice oriented), data management and aspects of human papilloma virus (HPV). Wilcoxon signed-rank test was used for comparison and the degree of change was measured using analysis of covariance (ANCOVA). A p value of <0.05 was considered significant. Results: 118 PMPs were included. There was a significant improvement in scores of all domains (except cervical pre-cancer domain), following introduction of EI2W. Knowledge scores, post EI2W was better in Auxiliary Nurse Midwives (ANMs) than other participants. Awareness regarding cervical cancer was higher with more years of experience. The KAP analysis showed excellent interrater reliability in the practice 0.726 (0.649-0.792) followed by knowledge domain 0.711 (0.626-0.783). Conclusion: EI2W was effective in significantly improving the competence of PMPs, thus reducing human resource constraints in cervical cancer prevention and elimination.

Choice of intraoperative ultrasound adjuncts for brain tumor surgery.

BACKGROUND: Gliomas are among the most typical brain tumors tackled by neurosurgeons. During navigation for surgery of glioma brain tumors, preoperatively acquired static images may not be accurate due to shifts. Surgeons use intraoperative imaging technologies (2-Dimensional and navigated 3-Dimensional ultrasound) to assess and guide resections. This paper aims to precisely capture the importance of preoperative parameters to decide which type of ultrasound to be used for a particular surgery. METHODS: This paper proposes two bagging algorithms considering base classifier logistic regression and random forest. These algorithms are trained on different subsets of the original data set. The goodness of fit of Logistic regression-based bagging algorithms is established using hypothesis testing. Furthermore, the performance measures for random-forest-based bagging algorithms used are AUC under ROC and AUC under the precision-recall curve. We also present a composite model without compromising the explainability of the models. RESULTS: These models were trained on the data of 350 patients who have undergone brain surgery from 2015 to 2020. The hypothesis test shows that a single parameter is sufficient instead of all three dimensions related to the tumor ([Formula: see text]). We observed that the choice of intraoperative ultrasound depends on the surgeon making a choice, and years of experience of the surgeon could be a surrogate for this dependence. CONCLUSION: This study suggests that neurosurgeons may not need to focus on a large set of preoperative parameters in order to decide on ultrasound. Moreover, it personalizes the use of a particular ultrasound option in surgery. This approach could potentially lead to better resource management and help healthcare institutions improve their decisions to make the surgery more effective.

Estimation of plasma and RBC acetylcholinesterase in children: An evaluation tool for Hirschsprung's disease?

BACKGROUND: Increased acetylcholinesterase (AChE) activity on frozen sections of rectal mucosal biopsies accurately diagnoses Hirschsprung disease (HD). But the quest for a biomarker in blood as a screening test prompts one to look for AChE in blood and study its role in HD diagnosis. AIM: To develop a low-cost reliable method to estimate the AChE activity in plasma and red blood cells (RBCs) in normal children (control) and study its role in HD (test). MATERIALS AND METHODS: Optimized method derived after modifying and standardizing known AChE assay protocols for blood were employed on 30 controls to define the AChE cut-off range, on 40 suspected HD cases to categorize them as HD/non-HD based on cut-off values and later compared with gold standard tissue AChE histochemistry of rectal mucosal biopsies. RESULTS: An optimal in-house modified methods of Ellman's was found best suited to analyze plasma AChE activity, method by Wilson and Henderson was optimal for extraction and AChE estimation in RBCs. AChE levels (controls) obtained were 1.03 ± 0.31 U/mL and 5.17 ± 1.52 U/mL in plasma and RBCs, respectively while the plasma AChE was 1.35 ± 0.84 U/mL (HD) and 1.62 ± 0.85 U/mL (non-HD) while RBC AChE was 4.29 ± 3.2 U/mL (HD) and 6.48 ± 4.31 U/mL (non-HD). Sensitivity was 66.67% and 55.56%, specificity was 22.73% and 45.45%, and an accuracy rate of 42.5% and 50% for plasma and RBC, respectively. CONCLUSIONS: Mutually exclusive AChE activity range identified for test blood samples overlapped with the normal and hence, not considered a diagnostic tool for HD.

Evaluation of autoantibody signatures in meningioma patients using human proteome arrays.

Meningiomas are one of the most common tumors of the Central nervous system (CNS). This study aims to identify the autoantibody biomarkers in meningiomas using high-density human proteome arrays (~17,000 full-length recombinant human proteins). Screening of sera from 15 unaffected healthy individuals, 10 individuals with meningioma grade I and 5 with meningioma grade II was performed. This comprehensive proteomics based investigation revealed the dysregulation of 489 and 104 proteins in grades I and II of meningioma, respectively, along with the enrichment of several signalling pathways, which might play a crucial role in the manifestation of the disease. Autoantibody targets like IGHG4, CRYM, EFCAB2, STAT6, HDAC7A and CCNB1 were significantly dysregulated across both the grades. Further, we compared this to the tissue proteome and gene expression profile from GEO database. Previously reported upregulated proteins from meningioma tissue-based proteomics obtained from high-resolution mass spectrometry demonstrated an aggravated autoimmune response, emphasizing the clinical relevance of these targets. Some of these targets like SELENBP1 were tested for their presence in tumor tissue using immunoblotting. In the light of highly invasive diagnostic modalities employed to diagnose CNS tumors like meningioma, these autoantibody markers offer a minimally invasive diagnostic platform which could be pursued further for clinical translation.

Autoantibody Profiling of Glioma Serum Samples to Identify Biomarkers Using Human Proteome Arrays.

The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma.

Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway.

AIM: Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on clinical parameters is inadequate for accurate prognostication. MicroRNA expression is known to be deregulated in various cancers and has been found to be useful in predicting tumor behavior. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with expression profiling of protein-coding genes. MATERIALS AND METHODS: miRNA profiling of medulloblastomas was carried out using Taqman Low Density Array v 1.0 having 365 human microRNAs. In parallel, genome-wide expression profiling of protein-coding genes was carried out using Affymetrix gene 1.0 ST arrays. RESULTS: Both the profiling studies identified four molecular subtypes of medulloblastomas. Expression levels of select protein-coding genes and miRNAs could classify an independent set of medulloblastomas. Twelve of 31 medulloblastomas were found to overexpress genes belonging to the canonical WNT signaling pathway and carry a mutation in CTNNB1 gene. A number of miRNAs like miR-193a, miR-224/miR-452 cluster, miR-182/miR-183/miR-96 cluster, and miR-148a having potential tumor/metastasis suppressive activity were found to be overexpressed in the WNT signaling associated medulloblastomas. Exogenous expression of miR-193a and miR-224, two miRNAs that have the highest WNT pathway specific upregulation, was found to inhibit proliferation, increase radiation sensitivity and reduce anchorage-independent growth of medulloblastoma cells. CONCLUSION: Expression level of tumor/metastasis suppressive miRNAs in the WNT signaling associated medulloblastomas is likely to determine their response to treatment, and thus, these miRNAs would be important biomarkers for risk stratification within the WNT signaling associated medulloblastomas.