MicroRNA-29b-3p degenerates terminally differentiated dopaminergic SH-SY5Y cells by perturbation of mitochondrial functions.

Mitochondrial dysfunction is the main cause of gradual deterioration of structure and function of neuronal cells, eventually resulting in neurodegeneration. Studies have revealed a complex interrelationship between neurotoxicant exposure, mitochondrial dysfunction, and neurodegenerative diseases. Alteration in the expression of microRNAs (miRNAs) has also been linked with disruption in mitochondrial homeostasis and bioenergetics. In our recent research (Cellular and Molecular Neurobiology (2023) https://doi.org/10.1007/s10571-023-01362-4), we have identified miR-29b-3p as one of the most significantly up-regulated miRNAs in the blood of Parkinson's patients. The findings of the present study revealed that neurotoxicants of two different natures, that is, arsenic or rotenone, dramatically increased miR-29b-3p expression (18.63-fold and 12.85-fold, respectively) in differentiated dopaminergic SH-SY5Y cells. This dysregulation of miR-29b-3p intricately modulated mitochondrial morphology, induced oxidative stress, and perturbed mitochondrial membrane potential, collectively contributing to the degeneration of dopaminergic cells. Additionally, using assays for mitochondrial bioenergetics in live and differentiated SH-SY5Y cells, a reduction in oxygen consumption rate (OCR), maximal respiration, basal respiration, and non-mitochondrial respiration was observed in cells transfected with mimics of miR-29b-3p. Inhibition of miR-29b-3p by transfecting inhibitor of miR-29b-3p prior to exposure to neurotoxicants significantly restored OCR and other respiration parameters. Furthermore, we observed that induction of miR-29b-3p activates neuronal apoptosis via sirtuin-1(SIRT-1)/YinYang-1(YY-1)/peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)-regulated Bcl-2 interacting protein 3-like-dependent mechanism. Collectively, our studies have shown the role of miR-29b-3p in dysregulation of mitochondrial bioenergetics during degeneration of dopaminergic neurons via regulating SIRT-1/YY-1/PGC-1α axis.

A systematic review and meta-analysis of diagnostic performance of fluorescein-guided sentinel lymph node biopsy in early breast cancer.

BACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.

Carbon Dots-Embedded Silica Tubes: An Excitation-Independent Yellow-Emitting Turn-On Probe for Simultaneous Detection and Removal of Inorganic Arsenic with In Vivo Tracking in Living Organisms.

The environmental monitoring and remediation of highly toxic inorganic arsenic species in natural water are needed for the benefit of the ecosystem. Current studies on arsenic detection and removal often employ separate materials, which exhibit blue luminescence with fluorescence quenching, making them unsuitable for biological and environmental samples. In this study, carbon dot-embedded mesoporous silica tubes functionalized with melamine are synthesized to address these limitations and enable specific and turn-on probing of inorganic arsenic. The newly synthesized material demonstrates excitation-independent yellow luminescence and can effectively detect both As (III) and As (V) at low detection limits (11 × 10-9 m, 11.2 × 10-9 m), well below the prescribed threshold limits in drinking water. It also exhibits a high adsorption capacity (≈125, 159 mg g-1 ) with fast kinetics. The material's applicability in environmental samples is validated through the successful quantification of arsenic in real samples with satisfactory recoveries. Moreover, the material shows recyclability for reuse, as demonstrated by its arsenic adsorption and desorption for several cycles under basic conditions. Additionally, the material's capability for monitoring arsenic in a biological sample (Artemia salina) is demonstrated through fluorescence imaging. The encouraging outcomes underscore the material's potential use in monitoring and mitigating arsenic in aqueous systems.

Screening for protein energy wasting in children with chronic kidney disease using dual energy x-ray absorptiometry as an additional tool.

BACKGROUND: The current diagnosis of protein energy wasting (PEW) is based on scoring systems that lack precision in measuring muscle deficits. We undertook this cross-sectional study to determine the prevalence of PEW in children with chronic kidney disease (CKD) using a scoring system that included dual energy x-ray absorptiometry (DEXA) for measuring lean body mass (LBM) and to determine the prevalence of selected markers in PEW. METHODS: Thirty CKD and 20 healthy children (1-18 years) were evaluated for (1) reduced dietary protein intake (DPI); (2) BMI < fifth centile for height age (BMI/HA); (3) serum albumin < 3.8 g/dl, cholesterol < 100 mg/dl, or CRP > 3 mg/L; (4) LBM < fifth centile for height age [LBMr] on DEXA. PEW was scored as minimal-one parameter positive in 2/4 categories; standard-one parameter positive in 3/4 categories; or modified-standard plus height < 2 SD. RESULTS: Twenty children with CKD (66.7%) had PEW, (5/9) 55% in CKD 3, and (15/21) 71% in advanced CKD; minimal 12, standard 1, and modified 7. LBMr was seen in 20 (100%), reduced DPI in 16 (80%), and BMI/HA in 6 (30%) children with PEW. LBMr had 100% sensitivity and BMI/HA 100% specificity. LBMr was seen in 8 who had no other criteria for PEW. None of the parameters were positive in controls (p < 0.01). CONCLUSIONS: PEW prevalence in CKD was high. Both prevalence and severity were higher in advanced CKD. LBMr was a highly sensitive marker to detect PEW. LBMr seen in some children with CKD who were negative for other markers could represent subclinical PEW.

Double blind randomized controlled trial of efficacy of ormeloxifene for the treatment of fibroadenoma (The FIBROCENT study).

BACKGROUND: We evaluated the effectiveness of Ormeloxifene (Centchroman) on regression of Fibroadenoma in a double-blind randomized controlled trial. METHODS: Patients with biopsy proven Fibroadenoma were enrolled between March 2023 and October 2023 and divided in two arms- Ormeloxifene group and Placebo group. Effectiveness of the treatment was evaluated using USG. No residual mass was defined as complete regression and more than 30% decrease in size was considered as partial regression. RESULTS: A total of 130 consecutive patients with Fibroadenoma were randomized to Ormeloxifene group (n = 65) and Placebo Group (n = 65). Complete regression was observed in 9% (6/65) patients in Ormeloxifene group and 10.8% (7/65) in Placebo Group at the end of 12 weeks (p = 0.49). Twenty one patients taking Ormeloxifene reported adverse events as compared to none in the other group. CONCLUSION: In our study Ormeloxifene was not found to be effective in treatment of fibroadenoma and had concerning side effects.

A comparison of swallowing related quality of life in patients undergoing transoral endoscopic versus open thyroid surgery.

INTRODUCTION: It is important for the endoscopic thyroid surgeon to understand the pros and cons of trans-oral endoscopic thyroidectomy-vestibular approach (TOETVA) vis-à-vis, open conventional thyroidectomy (OTx) so he/she can help patients in making informed choices regarding the type of procedure to opt for. Swallowing related quality of life (SWAL-QoL) has not been compared between the two approaches. Using a rigorous qualitative methodology and validated reliable tool, this study set out to compare the swallowing related quality of life in patients undergoing TOETVA versus OTx. METHODS: Prospective study at 3 time points in patients planned for hemithyroidectomy (Preoperative, 1 week and 12 weeks). Data were collected on patients at a tertiary teaching institute in India. Participants ranged from age 18-60 years with a diagnosis of benign euthyroid nodule undergoing hemithyroidectomy. Exclusion criteria were-(1) pre-existing vocal cord abnormalities, (2) undergoing surgery for recurrent nodules, and (3) any neuro-muscular disease affecting swallowing ability. Main outcome measure was comparison of swallowing related quality of life domain scores between patients undergoing hemithyroidectomy via either endoscopic trans-oral or open approach. RESULTS: Of the 82 included patients, 40 underwent TOETVA and 42 OTx. Both the groups were comparable in terms of demographic and clinicopathological profile. The mean preoperative SWAL-QOL scores were comparable in all domains. Mean SWAL-QoL scores for all domains on postoperative day 7 were significantly better in TOETVA group with domains burden, eating desire, mental health and communication having medium effect sizes. Physical symptom domain was better in the OTx group but had a small effect size. The difference in SWAL-QoL domains between the two groups persisted for 3 months also. CONCLUSION: Swallowing related quality of life after trans-oral endoscopic thyroidectomy compared to conventional open surgery has not been reported in the literature. Our findings suggest that trans-oral endoscopic thyroidectomy results in significant superior swallowing related quality of life in the majority of domains.

Unveiling perceptions regarding post mastectomy breast reconstruction: A questionnaire-based survey of patients from central India.

INTRODUCTION: Post mastectomy breast reconstruction uptake remains low in the developing countries. We examined patient perspectives about it in a cohort of Indian breast cancer patients. METHODS: This prospective study was conducted at a tertiary care center in central India. All post mastectomy patients for breast cancer were interviewed via a survey questionnaire to assess their perspective regarding post mastectomy breast reconstruction. RESULTS: None of the 192 patients underwent immediate or delayed reconstruction by the end of 24 months follow-up. Age, education level, occupation and marital status did not affect the uptake of post mastectomy breast reconstruction. The most common patient-reported reasons for not having reconstruction were the desire to avoid additional surgery and the belief that it was not important (80% for each). System related factors such as additional cost of surgery and additional length of stay were reported to be important by 55% and 65% patients respectively. CONCLUSION: Our survey of 192 post mastectomy breast cancer patients showed that none opted for post mastectomy reconstruction, suggesting significant barriers to it. Understanding and addressing these barriers are crucial to ensuring comprehensive care for these breast cancer patients.

Ageing at Molecular Level: Role of MicroRNAs.

The progression of age triggers a vast number of diseases including cardiovascular, cancer, and neurodegenerative disorders. Regardless of our plentiful knowledge about age-related diseases, little is understood about molecular pathways that associate the ageing process with various diseases. Several cellular events like senescence, telomere dysfunction, alterations in protein processing, and regulation of gene expression are common between ageing and associated diseases. Accumulating information on the role of microRNAs (miRNAs) suggests targeting miRNAs can aid our understanding of the interplay between ageing and associated diseases. In the present chapter, we have attempted to explore the information available on the role of miRNAs in ageing of various tissues/organs and diseases and understand the molecular mechanism of ageing.

Transcriptomics and Proteomics Approach for the Identification of Altered Blood microRNAs and Plasma Proteins in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by the selective destruction of dopaminergic neurons (DA-nergic). Clinically, PD is diagnosed based on developing signs and symptoms. A neurological and physical examination and sometimes medical and family history also help in the diagnosis of PD. However, most of these features are visible when more than 80% of the dopaminergic neurons have degenerated. An understanding of the selective degeneration process at the cellular and molecular level and the development of new biomarkers are required for effective PD management. Several studies have been carried out using a selected set of miRNAs/ mRNAs and proteins to develop biomarkers of PD; however, an unbiased and combined miRNA-protein profiling study was required to identify the markers of progressive and selected degeneration of dopaminergic neurons in PD patients. In the present study, we have carried out global protein profiling through LC-MS/MS and miRNA profiling by using a "brain-specific" miRNA array panel of 112 miRNAs in PD patients and healthy controls to find the unprejudiced group of proteins and miRNAs that are deregulating in PD. In the whole blood samples of PD patients compared to healthy controls, the expression of 23 miRNAs and 289 proteins was significantly increased, whereas the expression of 4 miRNAs and 132 proteins was considerably downregulated. Network analysis, functional enrichment, annotation, and analysis of miRNA-protein interactions were also performed as part of the bioinformatics investigation of the discovered miRNAs and proteins revealing several pathways that lead to PD development and pathogenesis. Based on the analysis of miRNA and protein profiling, we have identified four miRNAs (hsa-miR-186-5p, miR-29b, miR-139 & has-miR-150-5p) and four proteins (YWHAZ, PSMA4, HYOU1, & SERPINA1), which can be targeted for the development of new biomarkers of PD. In vitro studies have identified the role of miR-186-5p in regulating the levels of the YWHAZ/YWHAB & CALM2 gene, which has shown maximum downregulation in PD patients and is known for its role in neuroprotection from apoptotic cell death & calcium regulation. In conclusion, our research has identified a group of miRNA-proteins that can be developed as PD biomarkers; however, future studies on the release of these miRNAs and proteins in extracellular vesicles circulating in the blood of PD patients can further validate these as specific biomarkers of PD.

Impact of Topical Epinephrine with Xylocaine on Drainage After Axillary Lymph Node Dissection: A Randomized Controlled Trial.

INTRODUCTION: We evaluated the impact of topical epinephrine with xylocaine on drainage after axillary lymph node dissection. METHODS: Fifty-two women were randomized into two groups, epinephrine with xylocaine drainage (ED) and conventional drainage group (CD). The amount of drainage, duration of drainage catheter, incidence of seroma formation and wound infection were noted. RESULTS: The mean total drainage volume was less in ED group as compared to CD group (195 ml vs. 353 ml; p = .002). Drainage catheter was removed earlier in ED group as compared to CD group (5.07 + / - 0.99 days vs. 6.65 + / - 1.07 days; p = 0.0001). The incidence of seroma and wound infection was similar in two groups. CONCLUSION: Topical epinephrine with xylocaine after axillary lymph node dissection results in significantly decreased drainage volume and duration of drainage.

A Systematic Review and Meta-analysis of Touch Imprint Cytology and Frozen Section Biopsy and Their Comparison for Evaluation of Sentinel Lymph Node in Breast Cancer.

INTRODUCTION: Evaluation of axillary lymph nodes after sentinel lymph node biopsy (SLNB) in breast cancer is mostly done by intra-operative frozen section biopsy (FSB) and/ or touch imprint cytology (TIC). In this systematic review and meta-analysis, we have compared the accuracy of the two modalities. METHODS: PubMed, EMBASE, and Cochrane electronic databases were searched for articles comparing TIC with FSB. Articles were assessed for methodological and reporting quality. The main summary measures were pooled sensitivity, pooled specificity, and diagnostic accuracy using bivariate generalized linear mixed models using random effects. RESULTS: Fourteen studies were included. The pooled sensitivity, specificity, and diagnostic accuracy for FSB were 78%, 100%, and 98.57%. For TIC, the pooled sensitivity, specificity, and diagnostic accuracy were 74%, 98%, and 98.37%. For both methods, visual inspection of summary ROC curves and of forest plots did not show significant heterogeneity. CONCLUSION: TIC showed comparable sensitivity, specificity, and accuracy to FSB and hence can be used as its substitute as a rapid and economical test for the detection of axillary lymph node metastasis during SLNB especially in low-resource settings.

Total vs less than total thyroidectomy for benign multinodular non-toxic goiter: an updated systematic review and meta-analysis.

BACKGROUND: We have performed an updated meta-analysis of randomized controlled trials (RCT) comparing total thyroidectomy (TT) with less than total thyroidectomy (LTT) for benign multinodular non-toxic goiter (BMNG). OBJECTIVES: The objective was to evaluate the effects and outcomes of TT as compared to LTT. METHODS: Eligibility criteria: RCTs comparing TT vs LTT. INFORMATION SOURCES: PubMed, Embase, Cochrane Library and online registers were searched for articles comparing TT with LTT. Risk of bias: Articles were assessed for risk of bias using the Cochrane's revised tool to assess risk of bias in randomized trials (RoB 2 tool). SYNTHESIS OF RESULTS: The main summary measures were risk difference using a random effects model. RESULTS: Five randomized controlled trials were included in the meta-analysis. Recurrence rate was lower for TT compared to LTT. Adverse events like temporary or permanent recurrent laryngeal nerve (RLN) palsy and permanent hypoparathyroidism were similar in both groups except for the rate of temporary hypoparathyroidism which was lower in the LTT group. DISCUSSION: All studies had unclear risk of bias for blinding of the participants and personnel and high risk of bias for certain selective reporting. This meta-analysis did not show any clear benefit or harm of either procedure (TT vs LTT) for goiter recurrence and re-operation rates (for both recurrence and incidental thyroid cancer). However, re-operation for goiter recurrence was significantly higher in the LTT group based on a single RCT. Evidence suggests increased rates of temporary hypoparathyroidism with TT but there was no difference in the rate of RLN palsy and permanent hypoparathyroidism between the two methods. The overall quality of evidence was low to moderate.

Diaryl ether derivative inhibits GPX4 expression levels to induce ferroptosis in thyroid cancer cells.

Papillary thyroid carcinoma contributes to about 80% of the total thyroid cancer cases. BRAFV600E is a frequently occurring mutation in PTCs. Although several BRAF inhibitors are available, many thyroid cancer patients acquire resistance to BRAF inhibitors. Therefore, new targets and drugs need to be identified as therapies. Ferroptosis is a recently discovered type of cell death, and inhibiting glutathione peroxidase 4 (GPX4) using small molecules was found to trigger ferroptosis. But it is unknown whether inhibiting GPX4 renders thyroid cancer cells susceptible to ferroptosis. To identify novel GPX4 inhibitors, we focused on our previously reported cohort of diaryl ether and dibenzoxepine molecules. In this study, we asked whether diaryl ether and dibenzoxepine derivatives trigger ferroptosis in thyroid cancer cells. To answer this question, we screened diaryl ether and dibenzoxepine derivatives in cell-based assays and performed mechanism of action studies. We found that a diaryl ether derivative, 16 decreased thyroid cell proliferation and triggered ferroptosis by inhibiting GPX4 expression levels. Molecular modeling and dynamics simulations showed that 16 binds to the active site of GPX4. Upon deciphering the mode of 16-induced ferroptosis, we found that 16 treatments decrease mitochondrial polarization and reduce mitochondrial respiration similar to a ferroptosis inducer, RSL3. We conclude that the diaryl ether derivative, 16 inhibits GPX4 expression levels to induce ferroptosis in thyroid cancer cells. Based on our observations, we suggest that 16 can be lead-optimized and developed as a ferroptosis-inducing agent to treat thyroid cancers.

Expression of miR-145 and miR-18b in Peripheral Blood Samples of Head and Neck Cancer Patients.

Head and neck squamous cell carcinomas (HNSCC) is one of the most prevalent type of cancer known in Indian population. Studies are needed to identify the early biomarkers for HNSCC. MicroRNAs (miRNAs) are non-coding RNA molecules, expression of which can be used as biomarker for early diagnosis of HNSCC. For miRNA profiling total RNA, which also contained small RNAs were isolated from ten HNSCC tissue samples and adjacent control. Purity and concentration of eluted RNA was assessed using the NanoDrop1000® spectrophotometer, Reverse Transcription reaction was carried out with megaplex RT primers of pool A and pool B and the expression of selected miRNAs (miR-143/145 and miR-18a/b) was measured using TaqMan primers specific for mature miRNAs. Our study showed dramatic downregulation in expression of two miRNAs, miR-18b and miR-145 in blood samples of HNSCC patients, which are inhibitor of tumorigenesis and can be targeted as biomarker of HNSCC pathogenesis therefore developing avenues for miRNA role in prognosis and therapeutics. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01119-2.

Validation sentinel lymph node biopsy study in cN0 axilla using low-cost dual dye technique: potential solution for resource poor settings.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical and a blue dye is gold standard for axillary staging in clinically node-negative breast cancer. High costs and limited availability of radio-pharmaceutical and/or gamma probe are major deterrents in performing SLNB in developing countries. In this study, we evaluated feasibility of SLN identification (SLN-IR) of fluorescein-guided (FG) SLNB in combination with methylene blue dye (MBD). METHODS: This was a prospective cross-sectional non-randomized validation study in patients with clinically node-negative axilla. Patients underwent validation SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and False Negative Rate (FNR) were assessed for both groups. RESULTS: The SLNs were identified in 29 (96.6%) pre-chemotherapy patients and 23 (82%) post Neoadjuvant Chemotherapy (NACT) patients. The median number of sentinel lymph nodes identified was 3 (range of 1-5) in pre-chemotherapy patients and 1 (range of 1-3) in post NACT patients. The SLN-IR using MBD was 90%, FD was 86.7% and combined MBD FD was 96.7% in pre-chemotherapy patients. The SLN-IR using MBD was 82%, FD was 71% and combined MBD FD was 82% in in post NACT patients. The false negative rate (FNR) in pre-chemotherapy group was 8.0% (MBD), 8.3% (FD) and 7.4% (MBD + FD). The FNR in post NACT group was 8.7% (MBD), 10% (FD) and 8.7% (MBD + FD). CONCLUSION: This prospective validation study showed adequate SLN-IR and FNR using low-cost dual dyes in early breast cancer patients and can be used in low resource settings. However, SLNB in post NACT axilla though viable along with a satisfactory FNR, is associated with low identification rate and needs further evaluation.

Low-Cost Vacuum Assisted Core Needle Biopsy Technique for Breast Lumps.

BACKGROUND: Core biopsy has replaced fine needle aspiration cytology in the assessment of breast lumps to diagnose malignancy and is now standard of care in developed countries. Unfortunately, cost of core biopsy system is a major limitation in low-and middle-income countries (LMICs). This prompted us to devise and appraise a low-cost technique of core biopsy using negative pressure. METHODS: We devised and prospectively evaluated a simple model of core biopsy (vacuum assisted core needle biopsy-VACNB) using a 50 ml syringe, a 10 ml syringe and a 14G needle. RESULTS: 57 consecutive women (median age 42.66 years) with breast lumps (median diameter 5.2 cm) underwent VACNB. The sensitivity for diagnosing malignancy was 92%, specificity was 100%, and diagnostic accuracy was 92.98%. The positive predictive value of this technique was 100%, and negative predictive value was 63.64%. The cost (~ 5.5 USD) of the system was significantly less than the cost of core biopsy needle (~ 41.00 USD) and vacuum assisted breast biopsy needle (~ 341.00 USD) in India. CONCLUSION: Frugal innovations are needed to overcome cost constraints in LMICs. Our low-cost VACNB technique is easy to use and accurate.

Personal financial literacy among Indian postgraduate residents.

Background Postgraduate residents' ability to understand and effectively manage their finances is variable. We conducted this study to assess the awareness of personal financial literacy among Indian residents. Methods We circulated a web-based cross-sectional Google Forms multiple-choice questionnaire having questions in three categories including financial awareness, current financial status and plans among 400 Indian residents. Results A total of 215 Indian residents (53.75%) responded to the survey (men 80.9%, unmarried 74.4% and pursuing broad specialties 83.3%). The majority were unaware of stocks, special student/doctor loans, tax planning, life insurance, professional indemnity and tax/financial planning. The majority opined that personal finance and investing should be taught at medical school/residency. A financial pyramid based on the hierarchy of needs is proposed. Conclusion Lack of financial literacy and planning was seen among the majority of Indian residents. Our study highlights this gap in the medical curriculum and the need for formal structured financial education during training.

A 10-Year Study of the Outcome of Wilms' Tumor in Central India and Identifying Practice Gaps.

Introduction: Despite remarkable improvement in Wilms' tumor (WT) survival in Western world, sub-optimal outcome in resource-constrained settings is influenced by late presentation, larger size, and poor access to treatment. This prompted us to study the outcome at a tertiary care center and to identify the global and local practice gaps. Materials and Methods: A retrospective, observational study of WT was conducted from October 2009 to September 2019 at a tertiary care setting. Following the National Wilms' Tumor Study Group protocol, an upfront nephrectomy (unilateral resectable tumors) and preoperative chemotherapy (large/unresectable Stage I-III) were followed. The records were reviewed for demographics, stage, preoperative chemotherapy, predictive factors, and outcome. Survival curves were plotted by the Kaplan-Meier method, and analysis was performed using the SPSS software version 16. Results: One hundred and fifty-six children were included, median age was 4.1 years, with a male predominance. The most common stages of the presentation were II (40.4%) and III (34.6%). An upfront surgery was done in 27.6%, while remaining received preoperative chemotherapy. The median follow-up was 22 months, and the events included relapse in 46 (29.48%) and death in 54 (34.61%). The mean survival time was 45.7 (95% confidence interval [CI], 41.08-50.30). The 2-year overall survival was 65.38% (95% CI, 59-73), and the 2-year event-free survival was 36% (95% CI, 32-41). On comparison of the impact of preoperative chemotherapy, the survival estimates in Stages I-III and relapse rate were statistically similar, tumor size reduced significantly, and tumor spill was significantly lower (P < 0.05). Conclusion: WT is associated with late presentation, sub-optimal survival, and higher relapse in our setting associated with practice gaps related to the management including practice violations.

Incorporating Tumor Biology to Predict Hepatocellular Carcinoma Recurrence in Patients Undergoing Living Donor Liver Transplantation Using Expanded Selection Criteria.

Conventional selection criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are based on tumour size/number only, and do not consider vital surrogates of tumor biology such as alpha-fetoprotein (AFP) and tumor [18 F]fluorodeoxyglucose positron emission tomography ([18 F]FDG PET) avidity. We analyzed survival outcomes, and predictors of HCC recurrence in 405 patients with cirrhosis and HCC (HCC-cirr) who underwent living donor LT (LDLT) using our expanded selection criteria: no extrahepatic disease or major vascular invasion, irrespective of tumor size/number. Fifty-one percent patients had tumours beyond Milan, and 43% beyond the University of California San Francisco [UCSF] criteria. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64% and 70%, respectively. Three preoperatively available factors predicted recurrence: pre-LT AFP ≥100 ng/mL (P = 0.005; hazard ratio [HR], 2.190), tumor burden beyond the UCSF criteria (P = 0.001; HR, 2.640), and [18 F]FDG PET avidity (P = 0.004; HR, 2.442). A prognostic model based on the number and combination of the aforementioned preoperative risk factors was developed using a competing-risk RFS model. Three risk groups were identified: low (none or a single risk factor present, 9.3% recurrence), moderate (AFP ≥100 ng/mL and [18 F]FDG PET avidity, or beyond UCSF tumor and [18 F]FDG PET avidity, 25% recurrence), and high (AFP ≥100 ng/mL and beyond UCSF, or presence of all 3 risk factors, 46% recurrence). Acceptable long-term outcomes were achieved using our expanded selection criteria. Our prognostic model to predict recurrence based on preoperative biological and morphological factors could guide pretransplant management (downstaging versus upfront LDLT) with the aim of reducing post-LDLT recurrence.

Validation of gene expression profiles of candidate genes using low density array in peripheral blood of tobacco consuming head and neck cancer patients and auto/taxi drivers with preneoplastic lesions.

TaqMan Low-Density Array (TLDA) based Real-Time PCR (RT-PCR) of selected genes showed increased expression of polycyclic aromatic hydrocarbons (PAHs) metabolizing cytochrome P450s (CYPs), glutathione S-transferases (GSTs) and associated transcription factors in biopsy and peripheral blood samples isolated from head and neck squamous cell carcinoma (HNSCC) patients when compared to the controls. The genes involved in DNA repair, signal transduction pathway, EMT pathway, apoptosis, and cell adhesion/motility were found to be altered in both peripheral blood and biopsy samples of HNSCC patients. Transcription profiles in blood isolated from auto/taxi drivers, with pre-neoplastic lesions and history of tobacco use, also showed similar alterations. The present TLDA data thus demonstrates that low-density array of selected genes in peripheral blood has the potential to be used as a surrogate for providing insight into cancer progression pathways and possibly as an early biomarker for monitoring tobacco induced HNSCC.