Publications by authors named "Jajini Varghese"

Recent advances in neoadjuvant systemic therapy (NST) have significantly improved pathologic complete response rates in early breast cancer, challenging the role of axillary lymph node dissection in nose-positive patients. Targeted axillary dissection (TAD) integrates marked lymph node biopsy (MLNB) and tracer-guided sentinel lymph node biopsy (SLNB). The introduction of new wire-free localisation markers (LMs) has streamlined TAD and increased its adoption.

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Recent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST.

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Cancer epigenetic mechanisms support the acquisition of hallmark characteristics during oncogenesis. EZH2 - an important histone methyltransferase that writes histone H3 lysine 27 trimethylation marks - is known to be dysregulated in cancer cells. However, the interactions between EZH2 and miRNAs that form a complex network of cross-talk and reciprocal regulation that enable cancer cells to acquire hallmark characteristics have been relatively poorly appreciated.

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Objectives: Breast reconstructive surgery is often performed following breast cancer treatment to restore the natural appearance of the breast. Despite various research performed in this field, there is a discrepancy between the research question that is considered crucial jointly by patients, carers and healthcare professionals and the research performed. The Breast Reconstruction Priority Setting Partnership was formed to determine the top research priorities in all aspects of breast reconstructive surgery.

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Increased breast density is a risk factor for breast cancer and can mask cancer on mammography. This survey attempts to understand clinician views regarding breast density notification in the United Kingdom. Two separate breast density surveys were distributed to radiologists and breast surgeons between May 2019 and May 2020.

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Cancer has traditionally been hailed a genetic disease, dictated by successive genetic aberrations which alter gene expression. Yet, recent advances in molecular sequencing technologies, enabling the characterisation of cancer patient phenotypes on a large scale, have highlighted epigenetic changes as a hallmark of cancer. Epigenetic modifications, including DNA methylation and demethylation and histone modifications, have been found to play a key role in the pathogenesis of a wide variety of cancers through the regulation of chromatin state, gene expression and other nuclear events.

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Background: The impact of neoadjuvant chemotherapy (NACT) on surgical outcomes following immediate breast reconstruction (IBR) remains unclear. While it is generally considered safe practice to perform an IBR post NACT, reported complication rates in published data are highly variable with the majority of studies including fewer than 50 patients in the NACT and IBR arm. To evaluate this further, we conducted a systematic review and meta-analysis on the effect of NACT on autologous and implant based immediate breast reconstructions.

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Oro-facial fibrosis presents a significant disease burden in patients with systemic sclerosis, but there remains no established treatment modality. Autologous fat grafting is a minimally invasive surgical procedure that is now increasingly recognised for its regenerative capacity, propagating an expansion of heterogeneous indications beyond volume restoration, including fibrotic diseases such as systemic sclerosis. We present a 42-year-old woman with oro-facial involvement of systemic sclerosis leading to severe limitation in mouth opening and closure, with marked retraction of the lower lip and gingival display.

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Three-dimensional (3D) photography provides a promising means of breast volumetry. Sources of error using a single-captured surface to calculate breast volume include inaccurate designation of breast boundaries and prediction of the invisible chest wall generated by computer software. An alternative approach is to measure differential volume using subtraction of 2 captured surfaces.

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Fat hypertrophy is a less commonly known complication of autologous fat transfer. We present a 32-year-old female with left hemifacial atrophy associated with systemic sclerosis, who was treated with 7 fat transfer procedures to correct the facial asymmetry. A total of 236.

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The last two decades have seen significant advances within the field of adipose stromal cell transfers, with novel clinical applications being published every few months. This article gives a brief historical overview of the development of stem cell biology and fat grafting.

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Background: The applications for fat grafting have increased recently, within both regenerative and reconstructive surgery. Although fat harvesting, processing and injection techniques have been extensively studied and standardised, this has not had a big impact on the variability of outcome following fat grafting. This suggests a possible larger role of patient characteristics on adipocyte and adipose-derived stem cell (ADSC) viability and function.

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Background: Individual differences in breast size are a conspicuous feature of variation in human females and have been associated with fecundity and advantage in selection of mates. To identify common variants that are associated with breast size, we conducted a large-scale genotyping association meta-analysis in 7169 women of European descent across three independent sample collections with digital or screen film mammograms.

Methods: The samples consisted of the Swedish KARMA, LIBRO-1 and SASBAC studies genotyped on iCOGS, a custom illumina iSelect genotyping array comprising of 211 155 single nucleotide polymorphisms (SNPs) designed for replication and fine mapping of common and rare variants with relevance to breast, ovary and prostate cancer.

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Background: Mammographic breast density and endogenous sex-hormone levels are both strong risk factors for breast cancer. This study investigated whether there is evidence for a shared genetic basis between these risk factors.

Methods: Using data on 1,286 women from 617 families, we estimated the heritabilities of serum estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels and of three measures of breast density (dense area, nondense area, and percentage density).

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Percent mammographic density adjusted for age and body mass index (BMI) is one of the strongest risk factors for breast cancer and has a heritable component that remains largely unidentified. We performed a three-stage genome-wide association study (GWAS) of percent mammographic density to identify novel genetic loci associated with this trait. In stage 1, we combined three GWASs of percent density comprised of 1241 women from studies at the Mayo Clinic and identified the top 48 loci (99 single nucleotide polymorphisms).

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Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures.

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Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer.

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High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)).

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Genome-wide association studies (GWAS) have led to the identification of more than 100 common, low-penetrance loci for cancer. At these loci, common genetic variants are associated with moderate increases in risk, typically <1.5-fold.

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