Spectroscopic insight into breast cancer: profiling small extracellular vesicles lipids via infrared spectroscopy for diagnostic precision.

Breast cancer, a leading cause of female mortality due to delayed detection owing to asymptomatic nature and limited early diagnostic tools, was investigated using a multi-modal approach. Plasma-derived small EVs from breast cancer patients (BrCa, n = 74) and healthy controls (HC, n = 30) were analyzed. Small EVs (n = 104), isolated through chemical precipitation, underwent characterization via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Validation involved antibody-based tests (TSG101, CD9, CD81, CD63). Infrared spectra of small EVs were obtained, revealing significant differences in lipid acyl chains, particularly in the C-H stretching of CH3. The study focused on the lipid region (3050-2900 cm-1), identifying peaks (3015 cm-1, 2960 cm-1, 2929 cm-1) as distinctive lipid characteristics. Spectroscopic lipid-to-lipid ratios [(I3015/I2929), (I2960/I2929)] emerged as prominent breast cancer markers. Exploration of protein, nucleic acid, and carbohydrate ratios indicated variations in alpha helices, asymmetric C-H stretching vibrations, and C-O stretching at 1033 cm-1. Principal component analysis (PCA) successfully differentiated BrCa and HC small EVs, and heatmap analysis and receiver operating characteristic (ROC) curve evaluations underscored the discriminatory power of lipid ratios. Notably, (I2960/I2929) exhibited 100% sensitivity and specificity, highlighting its potential as a robust BrCa sEV marker for breast cancer detection.

Borderline tumours of ovary and fertility preservation-Outcomes from a tertiary care center in India.

OBJECTIVE: Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. METHODS: A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. RESULTS: Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. CONCLUSION: FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Fruit Quality Assessment of Novel Hybrid Pummelo × Sweet Orange and Its Molecular Characterization Using Acidity Specific Markers.

Research background: There is considerable diversity in newly developed pummelo × sweet orange citrus hybrids. Most hybrids showed lower peel thickness and high juice yield but there is a lack of information on fruit quality parameters and molecular characterization. Therefore, the aim of the current study is to determine the content of antioxidants and properties of the fresh juice of 24 new pummelo × sweet orange citrus hybrids (Citrus maxima [Burm. f.] Osbeck × Citrus sinensis [L.] Osbeck) and the parental genotypes along with molecular characteristics determined using acidity specific markers. Experimental approach: The correlation and estimate of inheritance of the fruit juice properties: ascorbic acid, total phenol, total flavonoid, total antioxidant, total soluble solid and sugar contents, pH, titratable acidity, along with sensory evaluation was performed. Molecular characterization of these hybrids was carried out using de novo generated acidity specific simple sequence repeat (SSR) markers. Results and conclusions: The main constituents of the fruit juice of pummelo × sweet orange hybrids were observed in the range of w(ascorbic acid)=40.00-58.13 mg/100 g, total phenols expressed as gallic acid equivalents w(GAE)=40.67-107.33 mg/100 g, total antioxidants expressed as Trolox equivalents b(Trolox)=2.03-5.49 µmol/g, total flavonoids expressed as quercetin equivalents w(QE)=23.67-59.33 mg/100 g, along with other properties: total soluble solids=7.33-11.33 %, w(total sugar)=2.10-5.76 %, w(reducing sugar)=1.69-2.78 %, w(non-reducing sugar)=0.39-3.17 % and titratable acidity 1.00-2.11 %. The above parameters differed significantly in the fruit juice of the evaluated pummelo × sweet orange hybrids. Considering these parameters, the hybrids SCSH 17-9, SCSH 13-13, SCSH 11-15 and SCSH 3-15 had superior antioxidant properties in terms of these parameters. A higher heritability (≥80 %) was also observed for all juice properties. Molecular characterization of pummelo × sweet orange hybrids showed that >50 % of the hybrids were grouped with medium acidity parents. Both molecular and biochemical parameter-based clustering showed that interspecific hybrids exhibit transgressive segregation with increased antioxidants that help alleviate the health problems. Novelty and scientific contribution: These newly developed pummelo × sweet orange citrus hybrids are a valuable source of high-quality antioxidants for a healthy diet. The identification of trait markers that enable selection at the seedling stage is of great benefit to citrus breeders, as the characteristic features of a mature tree are not yet visible at the juvenile stage.

Comparison of conventional diffusion-weighted imaging, diffusion kurtosis imaging and intravoxel incoherent motion in characterization of sonographically indeterminate adnexal masses.

PURPOSE: To evaluate the role of conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) in distinguishing benign from malignant adnexal masses. METHODS: 38 patients with 45 adnexal masses were enrolled in this prospective study and assessed with multiparametric MRI, including the IVIM-DKI sequence, on a 3 T MRI system. The mean apparent diffusion coefficient (ADC) from conventional DWI, the apparent diffusion coefficient derived from DKI (Dapp), the apparent kurtosis coefficient (Kapp), true diffusion coefficient (Dt), perfusion fraction (f) and pseudo-diffusion coefficient (Dp) were measured. RESULTS: The mean ADC, Dapp, and Dt were significantly higher in benign adnexal masses than in malignant adnexal masses (p < 0.001). f and Dp were also significantly higher in benign adnexal masses, with p values of 0.026 and 0.002, respectively. Kapp was higher in malignant masses (p < 0.001). Among mean ADC, Dapp, and Dt, mean ADC had the highest area under the curve (AUC) of 0.885. However, no statistically significant differences were observed between the ROCs of various diffusion parameters. CONCLUSION: The mean ADC, Dapp, and Kapp are useful parameters in discriminating between benign and malignant adnexal masses. Dt derived from IVIM also helps in distinguishing benign and malignant adnexal masses; however, no incremental role of IVIM and DKI over ADC could be identified in our study.

Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Introduction: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. Objective: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). Materials and methods: It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020. All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. The variants were classified based on American College of Medical Genetics guidelines. Demographic and clinicopathological details were extracted from the case record files. Results: One hundred and fifty-five patients were referred to the FCC and underwent pretest counselling. A total of 99 (63.9%) patients underwent genetic testing. Among them, 62 patients (62/99 = 62.6%) had a germline variant. A pathogenic/likely pathogenic (P/LP) germline variant was identified in 41 (41.4%) of the patients who underwent testing. Additional variants of unknown significance (VUS) were identified in seven patients who also carried a P/LP variant. VUS alone was detected in 21 patients (21/99 = 21.2%). Among the P/LP pathogenic variants (PV), BRCA 1 PV were seen in 27 patients (65.8%), BRCA 2 variants in 7 patients (17.1%), ATM variants in 3 patients (7.3%) and RAD51, TP53, CHEK2 and HMMR in 1 patient each. Variants were significantly more common in patients with a family history (FH) of malignancy than those without FH (58.5% versus 29.5%; p = 0.013). Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. Conclusion: We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

Abdominal fat depots and their association with insulin resistance in patients with type 2 diabetes.

BACKGROUND: Asian-Indians show thin fat phenotype, characterized by predominantly central deposition of excess fat. The roles of abdominal subcutaneous fat (SAT), intra-peritoneal adipose tissue, and fat depots surrounding the vital organs (IPAT-SV) and liver fat in insulin resistance (IR), type-2 diabetes (T2D) and metabolic syndrome (MetS) in this population are sparsely investigated. AIMS AND OBJECTIVES: Assessment of liver fat, SAT and IPAT-SV by MRI in subjects with T2D and MetS; and to investigate its correlation with IR, specifically according to different quartiles of HOMA-IR. METHODS: Eighty T2D and the equal number of age sex-matched normal glucose tolerant controls participated in this study. Abdominal SAT, IPAT-SV and liver fat were measured using MRI. IR was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). RESULTS: T2D and MetS subjects have higher quantity liver fat and IPAT-SV fat than controls (P = 9 x 10-4 and 4 x 10-4 for T2D and 10-4 and 9 x 10-3 for MetS subjects respectively). MetS subjects also have higher SAT fat mass (P = 0.012), but not the BMI adjusted SAT fat mass (P = 0.48). Higher quartiles of HOMA-IR were associated with higher BMI, W:H ratio, waist circumference, and higher liver fat mass (ANOVA Test P = 0.020, 0.030, 2 x 10-6 and 3 x 10-3 respectively with F-values 3.35, 3.04, 8.82, 4.47 respectively). In T2D and MetS subjects, HOMA-IR showed a moderately strong correlation with liver fat (r = 0.467, P < 3 x 10-5 and r = 0.493, P < 10-7), but not with SAT fat and IPAT-SV. However, in MetS subjects IPAT-SV fat mass showed borderline correlation with IR (r = 0.241, P < 0.05), but not with the BMI adjusted IPAT-SV fat mass (r = 0.13, P = 0.26). In non-T2D and non-MetS subjects, no such correlation was seen. On analyzing the correlation between the three abdominal adipose compartment fat masses and IR according to its severity, the correlation with liver fat mass becomes stronger with increasing quartiles of HOMA-IR, and the strongest correlation is seen in the highest quartile (r = 0.59, P < 10-3). On the other hand, SAT fat mass tended to show an inverse relation with IR with borderline negative correlation in the highest quartile (r = -0.284, P < 0.05). IPAT-SV fat mass did not show any statistically significant correlation with HOMA-IR, but in the highest quartile it showed borderline, but statistically insignificant positive correlation (P = 0.07). CONCLUSION: In individuals suffering from T2D and MetS, IR shows a trend towards positive and borderline negative correlation with liver fat and SAT fat masses respectively. The positive trend with liver fat tends to become stronger with increasing quartile of IR. Therefore, these findings support the theory that possibly exhaustion of protective compartment's capacity to store excess fat results in its pathological deposition in liver as ectopic fat.

Whole exome sequencing identifies novel variants of PIK3CA and validation of hotspot mutation by droplet digital PCR in breast cancer among Indian population.

BACKGROUND: Breast cancer (BC) is the most common malignancy with very high incidence and relatively high mortality in women. The PIK3CA gene plays a pivotal role in the pathogenicity of breast cancer. Despite this, the mutational status of all exons except exons 9 and 20 still remains unknown. METHODS: This study uses the whole exome sequencing (WES) based approach to identify somatic PIK3CA mutations in Indian BC cohorts. The resultant hotspot mutations were validated by droplet digital PCR (ddPCR). Further, molecular dynamics (MD) simulation was applied to elucidate the conformational and functional effects of hotspot position on PIK3CA protein. RESULTS: In our cohort, PIK3CA showed a 44.4% somatic mutation rate and was among the top mutated genes. The mutations of PIK3CA were confined in Exons 5, 9, 11, 18, and 20, whereas the maximum number of mutations lies within exons 9 and 20. A total of 9 variants were found in our study, of which 2 were novel mutations observed on exons 9 (p.H554L) and 11 (p.S629P). However, H1047R was the hotspot mutation at exon 20 (20%). In tumor tissues, there was a considerable difference between copy number of wild-type and H1047R mutant was detected by ddPCR. Significant structural and conformational changes were observed during MD simulation, induced due to point mutation at H1047R/L position. CONCLUSIONS: The current study provides a comprehensive view of novel as well as reported single nucleotide variants (SNVs) in PIK3CA gene associated with Indian breast cancer cases. The mutation status of H1047R/L could serve as a prognostic value in terms of selecting targeted therapy in BC.

Bilateral Breast Cancer: Clinical Profile and Management.

There is paucity of literature regarding the demography, histopathology, management, and outcomes of bilateral breast cancer (BBC). We present our experience of treating 127 BBC with multimodality management. An audit of prospectively maintained computerized breast cancer database of the department of surgical oncology at a tertiary care center was performed. Demography, clinical profile, molecular sub-types, treatment patterns, and outcomes were analyzed. A total 127 patients presented with BBC between 1992 and 2019. Ninety-four had metachronous (MBBC) and 33 had synchronous breast cancer (SBBC). Most contralateral breast cancer (CBC) patients had early-stage breast cancer in comparison to the index side cancer (37% vs 32%). Ninety-four patients underwent bilateral mastectomy and only 18 patients underwent bilateral breast conservation. Seventy-one patients undergoing BCS and surgery for LABC were given postoperative radiotherapy. All patients received adjuvant chemo- and/or hormonal therapy both for index and CBC based on the stage and hormone receptor status. Thirty-three percent of patients had either locoregional or distant relapse. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of the entire cohort were 86.6% and 68.4% respectively. There was no difference in the OS and DFS between SBBC and MBBC. The incidence of BBC is expected to increase with effective diagnostic and therapeutic interventions and improving survival. Patients require individualized treatment planning in a multidisciplinary treatment setting.

Unveiling the Significance of FGF8 Overexpression in Orchestrating the Progression of Ovarian Cancer.

The asymptomatic nature, high rate of disease recurrence, and resistance to platinum-based chemotherapy highlight the need to identify and characterize novel target molecules for ovarian cancer. Fibroblast growth factor 8 (FGF8) aids in the development and metastasis of ovarian cancer; however, its definite role is not clear. We employed ELISA and IHC to examine the expression of FGF8 in the saliva and tissue samples of epithelial ovarian cancer (EOC) patients and controls. Furthermore, various cell assays were conducted to determine how FGF8 silencing influences ovarian cancer cell survival, adhesion, migration, and invasion to learn more about the functions of FGF8. In saliva samples, from controls through low-grade to high-grade EOC, a stepped overexpression of FGF8 was observed. Similar expression trends were seen in tissue samples, both at protein and mRNA levels. FGF8 gene silencing in SKOV3 cells adversely affected various cell properties essential for cancer cell survival and metastasis. A substantial reduction was observed in the cell survival, cell adhesion to the extracellular matrix, migration, and adhesion properties of SKOV3 cells, suggesting that FGF8 plays a crucial role in the development of EOC. Conclusively, this study suggests a pro-metastatic function of FGF8 in EOC.

Expression of DKK1 in Endometrial Endometrioid Carcinoma and Its Correlation with Wnt/ß-catenin Signalling Pathway.

Objectives: Endometrial cancer is the most prevalent form of cancer affecting female reproductive organs. The most common histologic type, endometrioid carcinoma, accounts for 75-80% of all endometrial cancer cases. Studies on DKK1 expression profiles and their inhibitory role in the Wnt signalling pathway in the genesis and development of endometrial carcinoma are scarce. This study aimed to investigate DKK1 expression in endometrial carcinoma and its correlation with the Wnt/ß-catenin pathway. Methods: A total of 160 formalin-fixed paraffin-embedded samples were included in this study (50 cases of endometrial atypical hyperplasia, 50 cases of endometrioid endometrial carcinoma, 30 cases of proliferative endometrium and 30 cases of secretory endometrium). The expression patterns of DKK1, E-cadherin, ß-catenin and c-Myc in endometrial atypical hyperplasia and carcinoma were investigated and compared with that of proliferative and secretory endometrium. Immunohistochemistry and analysis were performed from July 2018 to June 2020. Results: A decreasing pattern of immunopositivity for DKK1, E-cadherin and ß-catenin from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma was found. Increasing c-Myc immunopositivity was noted from proliferative/secretory endometrium to endometrial atypical hyperplasia and endometrioid carcinoma. Moreover, decreasing DKK1 immunopositivity was well correlated with E-cadherin, ß-catenin and c-Myc immunopositivity. Conclusion: Decreasing DKK1 positivity from benign endometrium to endometrioid carcinoma suggests a negative regulatory function of DKK1 in endometrioid carcinoma. DKK1 is downregulated in the Wnt signalling pathway in endometrioid endometrial carcinoma. Therefore, DKK1 is promising as a biomarker for screening endometrioid carcinoma. Future studies should examine the reactivation of the DKK1 gene, which may be a valuable strategy for antagonising the Wnt signalling pathway.

Evaluation of cervical cancer screening during pregnancy in India: Human papillomavirus testing can change the paradigm.

Background The World Health Organization's call for elimination of cervical cancer envisages 70% screening coverage of women aged 35 and 45 years by an effective test. In India, this target seems unrealistic as awareness and access to cancer prevention services are poor. However, the institutional delivery rate is now >80%. We evaluated the acceptability and feasibility of human papillomavirus (HPV) testing and its role in screening during pregnancy. Methods This observational study recruited 275 pregnant women aged >25 years between 12 and 34 weeks of gestation for screening by cytology and HPV testing. Colposcopy was advised if either test was positive. Acceptability and feasibility were assessed by a questionnaire. Results Cytology and HPV reports were available for 269 subjects. The median age was 28 years and median parity was two. Only 98 (36.4%) had heard about carcinoma cervix. Awareness improved with education (p < 0.001). On cytology, only 4 (1.5%) were abnormal (atypical squamous cells of undetermined significance 3; low-grade squamous intraepithelial lesion 1). The prevalence of high-risk HPV infection was 8.2% (22/269). On colposcopy, all had the Swede score <5. No high-grade cervical intraepithelial neoplasia or carcinoma was detected. Pre-procedure, 183 (68.0%) subjects expressed apprehension, post-procedure 114 (42.4%) of them had realized that their apprehensions were unfounded. Women found screening to be more uncomfortable after 28 weeks of gestation (n=26/68; 38.2%; p<0.001). Physicians found the cervix more difficult to visualize after 20 weeks of gestation (p<0.001). Conclusions HPV screening at 16-20 weeks of pregnancy is acceptable, feasible, and can greatly improve screening coverage in resource-limited settings. Pregnancy is a good opportunity to improve awareness of the screening programmes.

Combination of 3PO analog PFK15 and siPFKL efficiently suppresses the migration, colony formation ability, and PFK-1 activity of triple-negative breast cancers by reducing the glycolysis.

Among all the subtypes of breast cancer, triple-negative breast cancer (TNBC) has been associated with the worst prognosis. Recently, for many solid tumors (including breast cancer) metabolic reprogramming has appeared as a cancer cell hallmark, and the elevated glycolytic pathway has been linked to their aggressive phenotype. In the present study, we evaluated the prognostic and therapeutic relevance of PFKFB3 (6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase) in TNBCs. Prognostic significance of PFKFB3 expression was evaluated in overall breast cancers as well as in TNBCs. PFKFB3 inhibitor (3PO potent analogue i.e., PFK15) cytotoxicity in TNBC cell lines (MDA-MB-231 and MDA-MB-468) was analyzed using an MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cancer cell physiological characteristics like clonogenicity and migration were also investigated after PFK15 treatment. As fructose-2,6-bisphosphate (F-2,6-BP), has been associated with increased PFK-1 activity, the effect of PFKFB3 inhibition by PFK15 was investigated on two major isoforms of phosphofructokinase-1 (PFK-1) in breast cancer, that is, phosphofructokinase-platelet type (PFKP) and phosphofructokinase-liver type (PFKL) (relevant to breast cancer). For PFKL inhibition, the siRNA approach was used. PFKFB3 expression was significantly correlated with inferior overall survival in breast cancer patients including TNBCs. PFK15 treatment in TNBC cells (i.e., MDA-MB-231 and MDA-MB-468) resulted in a decreased PFKP expression, thereby leading to reduced colony formation ability, migration rate, and extracellular lactate levels. However, to our surprise PFK15 treatment in both TNBC cells also resulted in elevated PFKL levels. Our results demonstrated that the combinatorial inhibition of PFK15 with siPFKL was more effective in TNBC cells, as it led to a decrease in colony formation ability, migration rate, extracellular lactate levels, and PFK-1 activity when compared with individual treatments. Using bona fide PFKFB3 inhibitor, that is, AZ67, we further show that AZ67 treatment to TNBC cells has no effect either on the expression of PFKP and PFKL, or on the lactate production. In summary, our present in vitro study demonstrated that 3PO derived PFK15 mechanism of action is totally different from AZ67 in TNBC cells. However, we advocate that the PFK15-mediated inhibition (along with PFKL) on the TNBCs migration, colony formation, and PFK-1 activity can be further explored for the therapeutic advantage of TNBC patients.

Minimally Invasive Parathyroidectomy as the Surgical Management of Single Parathyroid Adenomas: A Tertiary Care Experience.

The aim of our study is to assess the feasibility, safety and adequacy of focused parathyroidectomy for single parathyroid adenoma accurately localized preoperatively by ultrasound neck and Tc99m sestamibi scan. The study was conducted in the department of Otorhinolaryngology of SMS Medical College and Hospital, Jaipur on 116 patients of primary hyperparathyroidism who underwent minimally invasive parathyroidectomy (MIP) for single gland adenoma localized by USG neck and tc99m sestamibi scans. S. Calcium and S. PTH followed up on day 1, 6th week and 6th month. Outcomes were determined on the basis of cure rate, duration of hospitalization, complication rates and disease persistence/recurrence rate. 82 (70.68%) females and 34 (29.31%) males belonging to the age group of 21-67 years (43.02 ± 14) formed the basis of our study. Skeletal (73.27%) and renal (62.93%) were the most common presentations. Accuracy of USG and sestamibi accurately was 93.10% and 96.55% respectively with combined accuracy of 100%. Preoperative serum calcium levels of 10.7-16.03 mg/dl (13.09 ± 2.11) and serum PTH 127-2196 pg/ml (846.57 ± 776.55) were observed. Cure rate of MIP was 99.13%. No permanent complications seen. MIP can be used as the surgical procedure of choice for PHPT caused by single gland adenoma aided by USG and sestamibi scan. The cure rates are equivalent to the bilateral neck exploration (> 95%) with minimal morbidity and complications. Hence, it is a more feasible, safe and effective treatment option.

Primary leiomyosarcoma of the vulva - a rare occurrence.

Vulval tumours are rare, representing merely 4% of all gynaecological neoplasms. 98% of vulvar lesions are benign, and only 2% are malignant. Of all vulvar malignancies, while squamous cell carcinoma is the most common malignancy, leiomyosarcomas of the vulva are extremely rare. Usually these tumours have nonspecific clinical manifestations, often leading to misdiagnoses of Bartholin cysts or abscesses. We describe a case of a 47-year-old woman who presented with a nonspecific painless swelling in the left vulva for 2 months which was diagnosed as leiomyosarcoma of the vulva on biopsy as well as resection.

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver but is rare in the paediatric age group; thus, it may be misdiagnosed as the more common tumour, hepatoblastoma. Management varies in both these tumours, and pathological diagnosis thus plays an important role for definitive therapy. Only a few case reports available in the literature have described the cytological characteristics of paediatric HCC. The present study was thus planned to evaluate the cytomorphological features of paediatric HCC. METHODS: Cases diagnosed with HCC on ultrasound-guided fine needle aspiration cytology over a period of 14 years were retrieved. The cases were evaluated for detailed cytological features including cellularity, architecture, sinusoidal wrapping, trabecular thickness, necrosis, anisonucleosis, chromatin, nucleoli, nuclear contours, bi- or multinucleation, intranuclear and intracytoplasmic inclusions, naked nuclei, extra-medullary haematopoiesis, monomorphism, and nuclear overlapping. RESULTS: Twelve cases of HCC were included in the study. The median age at diagnosis was 10 years. Serum alpha-fetoprotein level was raised in most of them. Five of the 12 cases were characterised as moderately differentiated, three as poorly differentiated, two as well differentiated, and two as the fibrolamellar type of HCC. Cytohistological correlation was performed in seven cases. CONCLUSIONS: Ultrasound-guided fine needle aspiration serves as a useful tool to diagnose paediatric HCC and differentiate it from other primary hepatic malignancies, especially hepatoblastoma which closely mimics HCC in this age group, as serum alpha protein levels and imaging findings are unable to distinguish these two tumours.

Evaluation of Dual Dye Technique for Sentinel Lymph Node Biopsy in Breast Cancer: Two-Arm Open-Label Parallel Design Non-Inferiority Randomized Controlled Trial.

INTRODUCTION: Radioisotope and blue dye are standard agents for performing sentinel lymph node (SLN) biopsy in breast cancer. The paucity of nuclear medicine facility poses logistic challenge. This study evaluated performance of radioisotope & methylene blue (MB) with indocyanine green (ICG) and MB for SLNB. PATIENTS AND METHODS: This randomized controlled trial was conducted from December 2019 to July 2022 comparing SLN identification proportions of radioisotope-blue dye [Group A] with dual dye (MB + ICG; Group B]. Secondary objective included time required and cost effectiveness of performing SLNB. Sample size of 70 (35 in each arm) was calculated. Upfront operable node negative early breast cancer was included in the study. Clinico-demographic data, number & type of SLN, time taken were noted. Cost analysis was done including the equipment, manpower & consumables. Chi-square/Fisher exact test was used to compare proportion between two groups. p value of less than 0.05 was considered to represent statistical significance. RESULTS: Seventy patients randomized to either group were similar in clinico-demographic and tumor characteristics. SLN identification rate (IR) was 91.43% in group A and 100% in group B. Overall IR of MB, radioisotope and ICG were 91.43%, 91.43% and 100%, respectively. Mean number of SLNs identified were 3 in group A and 4 in group B. Median time required for SLNB was 12 min and 14 min in either group, respectively. Cost of performing SLNB was higher in Group B. CONCLUSION: SLNB using dual dye is non-inferior to radioisotope-blue dye in upfront operable early breast cancer. Trial registration number Clinical Trial registry India CTRI/2020/02/023503.

Machine Learning Model Based on Insulin Resistance Metagenes Underpins Genetic Basis of Type 2 Diabetes.

Insulin resistance (IR) is considered the precursor and the key pathophysiological mechanism of type 2 diabetes (T2D) and metabolic syndrome (MetS). However, the pathways that IR shares with T2D are not clearly understood. Meta-analysis of multiple DNA microarray datasets could provide a robust set of metagenes identified across multiple studies. These metagenes would likely include a subset of genes (key metagenes) shared by both IR and T2D, and possibly responsible for the transition between them. In this study, we attempted to find these key metagenes using a feature selection method, LASSO, and then used the expression profiles of these genes to train five machine learning models: LASSO, SVM, XGBoost, Random Forest, and ANN. Among them, ANN performed well, with an area under the curve (AUC) > 95%. It also demonstrated fairly good performance in differentiating diabetics from normal glucose tolerant (NGT) persons in the test dataset, with 73% accuracy across 64 human adipose tissue samples. Furthermore, these core metagenes were also enriched in diabetes-associated terms and were found in previous genome-wide association studies of T2D and its associated glycemic traits HOMA-IR and HOMA-B. Therefore, this metagenome deserves further investigation with regard to the cardinal molecular pathological defects/pathways underlying both IR and T2D.

Imaging features of accessory cavitated uterine mass (ACUM): a peculiar yet correctable cause of dysmenorrhea.

Accessory cavitated uterine mass (ACUM) is a rare form of developmental mullerian anomaly which causes chronic pelvic pain, dysmenorrhea and infertility in young females. It is a non-communicating, accessory cavity within an otherwise normal uterus, lined by functional endometrium and surrounded by myometrium-like smooth muscle cells which imparts it uterus-like appearance. USG and MRI are the imaging modalities which help in reaching the diagnosis. Knowledge of this entity and awareness of its imaging features can help diagnose this often underdiagnosed and surgically correctable cause of dysmenorrhea.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Central nervous system metastasis from epithelial ovarian cancer- predictors of outcome.

Management of central nervous system (CNS) metastases from epithelial ovarian cancer (EOC) is an unmet need. We analyzed data on 41 such patients to evaluate predictors of outcome. Between January, 2010 and December 2020, among 1028 patients with EOC treated at our institute 41 (3.98%) developed CNS metastasis. Median age of patients was 48 years, ranging from 22 to 75 years. Primary outcome measure was progression free survival (PFS). Overall survival (OS), and analysis of prognostic factors were secondary outcome measures. An intention to treat analysis was done. We also performed review the literature (n=2253) as regards to clinicopathological and radiological features, treatment received, survival outcomes and prognostic factors. Median time from diagnosis of EOC to CNS metastasis was 27 months (range: 0 to 101 months). 33(80.5%) patients had FIGO stage III-IV at baseline and serous carcinoma (75.6%) was common pathology subtype. Thirteen (31.7%) patients had isolated CNS metastasis and 28 (68.3%) had intra-abdominal disease in addition. Nineteen (46.3%) patients achieved complete response post treatment with surgery, radiation and chemotherapy. Median PFS and OS from the time of CNS metastasis is 12 (range:1 to 51) months and 33 (range: 1 to 71) months, respectively. Absence of extracranial disease and lower serum CA-125 at diagnosis of CNS metastasis were predictive of superior PFS and OS on multivariate analysis. CNS metastasis is a late event in EOC, post multiple lines of treatment. Patients with disease limited to brain and treated with surgical resection and chemoradiation have best outcome.