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PurposeBreast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC). The high TNBC prevalence (>25%) in India remains a challenge in clinical management. Association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. These studies are however predominantly representative of western population. Therefore, we investigated germline profiles of multi-institutional cohort of TNBC patients in IndiaMethodsUsing a multi-gene NGS (next-generation sequencing) panel of 26 ACMG recommended genes associated with inherited cancers.ResultsIn our study cohort of 193 TNBC patients, we identified 57 pathogenic mutations of which BRCA1 (71.93%) and BRCA2 (14.03%) were most commonly mutated. Additionally, 8 pathogenic mutations were identified in non-BRCA genes associated with the HR pathway. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. Comparison of allele-frequency with the global databases like TCGA (The Cancer Genome Atlas), gnomAD and Genome Asia 100K indicated that the novel mutations were unique. Furthermore, we identified 48 variants of uncertain significance (VUS) (24.9%).ConclusionsOur study confirms the major proportion of mutations in BRCA1/2 genes in TNBCs in India. Interestingly, a higher proportion of VUS were found in the non-BRCA genes compared to BRCA1/2 emphasizing the need for functional studies of the non-BRCA genes. Additionally, large scale studies are also warranted to elucidate the landscape of germline mutations relevant to the Indian population and their probable clinical implications.

Breast cancer incidence is on the rise in India as in rest of the world. While the advances in overall cancer care are at par, the surgical interventions have not been changing at the same pace in India, as in the rest of the developed world. Partly, this is due to the relatively more advanced state of cancer at detection and partly due to lack of awareness resulting in apprehension and slow acceptance of de-escalation of surgical interventions by the treating surgeons, and the beneficiaries, the patients. The article looks at the current scenario, available evidence on the practices and pitfalls with possible solutions for advancing surgical care of breast cancer in India.

The report evaluates the effect of coronavirus disease (COVID-19) pandemic on breast cancer treatment and management at a single-surgeon cancer care unit in one of the hotspots of COVID-19 in India. In response to the pandemic, the adjustments were made in the clinical practice to accommodate social distancing. Patient consultations were done over phone call or in-clinic visit with prior appointment to reduce the risk of exposure to COVID-19. Total number of patients that were treated at the clinic and the essential surgeries performed during the pandemic phases are summarized in the report. The methodology adopted here for care and management of the cancer patients can serve as a guiding principle for cancer care units in the country.

BackgroundPrecise prediction of residual tumour size following neoadjuvant systemic therapy for breast cancer is crucial in assessing response and surgical decision making. Our study is aimed at assessing the performance of conventional imaging modalities like ultrasound and mammography in predicting the residual tumour size after neoadjuvant systemic therapy and in evaluating the impact of imaging on the surgical outcomes.MethodsWe retrospectively compared the tumour size measured by ultrasonography and mammography and the residual tumour size on final histopathology in 109 patients. Concordance was defined as a size difference within 25% of the histopathology size. We also looked at the distribution of concordance between different T status and molecular subtypes, accuracy of USG in predicting pathological complete response and axillary lymph nodal metastasis and also surgical outcomes in the discordant cases.ResultsThe concordance rates of mammography and ultrasonography were 68.2% and 52.3% respectively without statistically significant difference between the two modalities (p = 0.081). Combination of both the modalities had a concordance rate of 57.8%. Ultrasonography had accuracy of 81.7% for predicting pathological complete response and 79.8% for predicting axillary nodal metastasis. We did not identify any influence of histologic subtype on the associations between preoperative measurements and pathology size or the accuracy for detecting pathological complete response (p values 0.43 and 0.46 respectively). In 12 cases, the radiology-pathology discordance could have led to large excision volume surgeries. In the overall cohort, recurrence free survival and overall survival rates at median follow up of 19.1 month were 87.2% and 95.4% respectively.ConclusionsUltrasound and mammography showed moderate concordance with pathology for estimation of the residual tumour size without any significant difference in the performance between the two. Despite the moderate concordance, surgical outcomes were fairly well managed in the discordant cases with the oncoplastic surgical techniques. Our study highlights the usefulness of the cheaper and widely available conventional imaging modalities in the developing countries where the cost of treatment is to be contained.

Introduction. Breast conserving surgery (BCS) followed by radiation therapy (RT) has become the preferred alternative to mastectomy for patients with early stage breast cancer (BC). Randomized trials have confirmed equivalent locoregional control and overall survival for BCS and mastectomy. Extreme Oncoplasty (EO) extends the indications of BCS for patients who would otherwise require mastectomy, ensuring better aesthetic outcomes and oncological safety. Methods. BC patients with multifocal/multicentric (MF/MC) tumors, extensive DCIS, or large tumor >50mm underwent EO at our breast unit. Therapeutic reduction mammaplasty (TRM) with wise pattern preoperative markings and dual pedicle technique involving parenchymal rearrangement was used for oncoplastic reconstructions in majority of the cases followed by RT. Patient reported outcome measures (PROMs) were assessed using the validated Breast-Q questionnaire. Results. Of the 39 patients in the study, 36 had unilateral and 3 had bilateral BC. Mean age was 47.2 years. Median tumor size was 75mm. 17 (43.6%) patients received NACT; none achieved a complete clinical response. 28 (71.8%) patients were administered to adjuvant chemotherapy. 33(84.6%) patients received RT to the breast with a median dose of 50Gy in 28 fractions and a boost dose of 10Gy in 5 fractions to the tumor bed. No major complications or local recurrences were observed. Excellent Breast-Q scores were observed in patients undergoing EO after 12 months of follow-up. Conclusion. EO followed by RT results in acceptable local-regional control, low rate of complications, and high patient satisfaction. In selected patients, EO could provide a safe alternative for breast conservation surgery instead of mastectomy.

Male Breast Cancer (BC) is relatively rarer, accounting for less than 1% of cancers in men. MBC is hereditary in nature and mainly attributed toBRCA1/2germline mutations. Accordingly, National Comprehensive Cancer Network (NCCN) guidelines advise genetic counselling and testing for all cases of MBCs and their unaffected family members. In this report, we present an uncommon case of male patient primarily diagnosed with pancreatic cancer who later developed asynchronous bilateral hormone positive breast cancer. We describe the genetic screening and clinical management protocol for the proband and family members. Genetic testing with next generation sequencing by uses of a multi-gene germline mutation panel revealed a likely pathogenicBRCA2variant (c.8754G>A, p.E2918E). Subsequently, 34 members of the extended family of the proband were tested for theBRCA2variant by Sanger sequencing. 6 of the family members were identified as carriers of thisBRCA2variant. Of these, three presented with hereditary breast cancer and 3 were unaffected healthy carriers.In silicoanalysis for mechanistic insights in underlying pathogenicity revealed that the silentBRCA2mutation is a spliceogenic variant that is likely to create an aberrant mRNA transcript via alternative splicing ofBRCA2gene. Our study demonstrates the clinical relevance of this silentBRCA2mutation and emphasizes the need for further experimental studies to elucidate its functional role in breast cancer pathology.

The Cancer Genome Atlas (TCGA) is a landmark cancer genomics program that molecularly characterized over 20,000 primary cancer and matched normal samples spanning 33 cancer types. On similar lines, the establishment of an ‘Indian Cancer Genomics Atlas (ICGA)’ has been initiated in 2019–2020 by a consortium of key stakeholders in India led by Council for Scientific and Industrial Research (CSIR), Government of India and several reputed governmental agencies, cancer hospitals, academic institutions, and private sector partners. In parallel, Bangladesh Medical Research Council (BMRC) has announced the launch of ‘Bangladesh Cancer Genome Atlas (BCGA) project with support from the ICGA teams. Teams from United States - National Cancer Institute (NCI) office of TCGA and Centre for Global Oncology, Institute of Cancer Research, London, United Kingdom are interested in extending their collaborations to these large-scale initiatives by acting as knowledge partners. With this background, an online version of the 2nd TCGA conference and workshop in India was organised with the theme of ‘Towards Team Science for Multi-omics Studies in South Asia’ on December 3–5, 2020. Over 1,500 delegates comprising of onco-clinicians, basic researchers, bioinformaticians, geneticists, translational researchers, big-data and machine-learning scientists, bioethicists and regulatory experts from across the globe attended the event. The conference agenda focused on the vision, design and plans of the ICGA project with regards to common standard operating protocols (SOPs), operations, logistics, bioethics, policy and governance models. More importantly, conference sessions were planned around the central theme of building a culture of team science for undertaking mega-cancer research projects in India and neighbouring countries. Experts from the globe deliberated on the latest technical aspects of data/biospecimen/multi-omics studies and applications of Precision Oncology in clinical cancer management.

As the COVID-19 pandemic is progressing, the therapeutic gaps in conventional management have highlighted the need for the integration of traditional knowledge systems with modern medicine. Ayurvedic medicines, especially Ashwagandha (Withania somnifera (L.) Dunal, WS), may be beneficial in the management of COVID-19. WS is a widely prescribed Ayurvedic botanical known as an immunomodulatory, antiviral, anti-inflammatory, and adaptogenic agent. The chemical profile and pharmacological activities of WS have been extensively reported. Several clinical studies have reported its safety for use in humans. This review presents a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discusses its potential for prophylaxis and management of COVID-19. We have collated the data from studies on WS that focused on viral infections (HIV, HSV, H1N1 influenza, etc.) and noncommunicable diseases (hypertension, diabetes, cancer, etc.). The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities. Using these trends, the review presents a triangulation of Ayurveda wisdom, pharmacological properties, and COVID-19 pathophysiology ranging from viral entry to end-stage acute respiratory distress syndrome (ARDS). The review proposes WS as a potential therapeutic adjuvant for various stages of COVID-19 management. WS may also have beneficial effects on comorbidities associated with the COVID-19. However, systematic studies are needed to realize the potential of WS for improving clinical outcome of patients with COVID-19.

BackgroundBreast reconstruction with an autologous lower dermal sling (ALDS) is an established one-stage procedure in patients with moderate to large ptotic breasts. However, this technique is difficult to perform in small and non/minimally ptotic breasts. We describe our experiences from a single institution about a novel Advanced Autologous Lower Dermal Sling (A-ALDS) technique for reconstruction in small breasts.MethodsWe performed one stage nipple/skin sparing mastectomies in 61 patients with immediate reconstruction either by conventional immediate breast reconstruction surgery or A-ALDS technique.ResultsMean age of study patients was 46.9 years. We observed significantly better cosmetic score and lower immediate complication rate vis-a-vis skin necrosis, implant loss with the A-ALDS technique (i.e., nil versus 3 in Conventional Immediate Breast Reconstruction Surgery - IBRS). 40 patients completed 12 months follow-up. The PROMs-Patient Reported Outcomes Measures (Breast-Q) revealed good to excellent scores for satisfaction with breast, cosmetic outcome and psychosocial well-being in patients operated with both these techniques. However, sexual well-being was significantly better in the A-ALDS group.ConclusionThe A-ALDS is a novel, cost-effective and safe technique for immediate one stage implant-based reconstruction for small breasts. It provides a dermal barrier flap and hence, ensures less complications, excellent cosmetic results and patient satisfaction.

250 words Background A breast cancer biobank with retrospectively collected patient data and FFPE tissue samples was established in 2018 at Prashanti Cancer Care Mission, Pune, India. It runs a cancer care clinic with support from a single surgeon's breast cancer practice. The clinical data and tissue sample collection is undertaken with appropriate patient consent following ethical approval and guidelines. Methods The biobank holds clinical history, diagnostic reports, treatment and follow-up information along with FFPE tumor tissue specimens, adjacent normal and, in few cases, contralateral normal breast tissue. Detailed family history and germline mutational profiles of eligible and consenting patients and their relatives are also deposited in the biobank. Results Here, we report the first audit of the biobank. A total number of 994 patients with breast disease have deposited consented clinical records in the biobank. The majority of the records (80%, n = 799) are of patients with infiltrating ductal carcinoma (IDC). Of 799 IDC patients, 434 (55%) have deposited tumor tissue in the biobank with consent. In addition, germline mutation profiles of 84 patients and their family members are deposited. Follow-up information is available for 85% of the 434 IDC patients with an average follow-up of 3 years. Conclusion The biobank has aided the initiation of translational research at our center in collaboration with eminent institutes like IISER Pune and SJRI Bangalore to evaluate profiles of breast cancer in an Indian cohort. The biobank will be a valuable resource to the breast cancer research community, especially to understand South Asian profiles of breast cancer.

Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer associated with poor prognosis. The high TNBC prevalence (>25%) in India as compared to the western population (10-15%) remains to be a challenge in clinical management. The association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. However, these studies are predominantly from germline profiling of TNBCs representative of western population. Therefore, we aimed to investigate the germline profiles of breast cancer patients in India using a multi-institutional TNBC cohort based on ACMG consensus multi-gene NGS panel. Of 193 TNBC patients, we identified 57 pathogenic mutations (diagnostic yield = 29.53%) from various genes of which BRCA1 (41/57, 71.93%) and BRCA2 (8/57, 14.03%) were most commonly mutated. We observed a high prevalence of BRCA1 mutations (41/193, 21.24%) and BRCA2 mutations (8/193, 4.14%) in our cohort as compared to published literature. Additionally, 8 pathogenic mutations were also reported in non-BRCA cancer pre-disposing genes associated with the HR pathway like ATM, CHEK2, PALB2. 10 novel mutations were identified in 3 genes namely BRCA1, BRCA2 and PALB2. The most common type of mutations was found to be frame-shift which may cause protein truncation and loss of function. Furthermore, we identified 48 variants of unknown significance (24.9%) of which about 7% were in the BRCA1/2 genes. Data mining from global databases like TCGA, Genome Asia indicated that the novel mutations were unique to the Indian population compared to the germline profiles of different ethnicities. Our study confirms the major contribution of BRCA1/2 genes in TNBCs as reported in the literature. A high percentage of the women were found to be associated with young age onset which may be attributed to BRCA mutations. We have also assessed the association of clinicopathological parameters such as tumor grade, stage, recurrence to the germline mutational status. Our analysis shows significant association of germline mutational status with family history thus underlin the importance of multi-gene panel testing as recommended by NCCN guidelines. Moreover, our results also emphasize the need for designing/implementing guidelines specific to Indian population. In summary our results indicate that Indian TNBCs have a high prevalence of BRCA1/2 mutations. Large scale studies in future are warranted to validate these preliminary findings. Citation Format: Chaitanyanand Koppiker, Ashwini Bapat, Siddharth Gahlaut, Naveen Luke, Jisha John, Rupa Mishra, Aishwarya Konnur, Namrata Namewar, Ruhi Reddy, Shaheen Shaikh, Rituja Banale, Smeeta Nare, Laleh Busheri, Asha Reddy, Ashraf Mannan, Sabarinathan Radhakrishnan, Selvi Radhakrishna, Santosh Dixit. Germline mutational profiling of TNBCs in an Indian cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB561.

COVID-19 patients show heterogeneity in clinical presentation and outcomes that makes pandemic control and strategy difficult; optimizing management requires a systems biology approach of understanding the disease. Here we sought to potentially understand and infer complex disease progression, immune regulation, and symptoms in patients infected with coronaviruses (35 SARS-CoV and 3 SARS-CoV-2 patients and 57 samples) at two different disease progression stages. Further, we compared coronavirus data with healthy individuals (n = 16) and patients with other infections (n = 144; all publicly available data). We applied inferential statistics (the COVID-engine platform) to RNA profiles (from limited number of samples) derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, a subset of integrated blood-based gene profiles (signatures) distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalization) from recovering-like patients. These signatures also hierarchically represented multiple (at the system level) parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle observations included PBMC-based increases in cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage showed significantly enhanced TNF, IFN-γ, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, our analysis revealed overlapping genes associated with potential comorbidities (associated diabetes) and disease-like conditions (associated with thromboembolism, pneumonia, lung disease, and septicemia). Overall, our COVID-engine inferential statistics platform and study involving PBMC-based RNA profiling may help understand complex and variable system-wide responses displayed by coronavirus-infected patients with further validation.

COVID-19 patients show significant clinical heterogeneity in presentation and outcomes that makes pandemic control and strategy difficult; optimising management requires a systems biology approach of understanding the disease. Here we sought to understand and infer complex system-wide changes in patients infected with coronaviruses (SARS-CoV and SARS-CoV-2; n=38 and 57 samples) at two different disease stages compared with healthy individuals (n=16) and patients with other infections (n=144). We applied inferential statistics/machine-learning approaches (the COVID-engine platform) to RNA profiles derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, an integrated blood-based gene signatures distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalisation) from recovering-like patients. These signatures also hierarchically represented systems-level parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle confirmatory observations included PBMC-associated increases in ACE2, cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage had significantly enhanced TNF, IFN-g, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, PBMC-derived surrogate-based approach revealed overlapping genes associated with comorbidities (associated diabetes), and disease-like symptoms (associated with thromboembolism, pneumonia, lung disease and septicaemia). Overall, our study involving PBMC-based RNA profiling may further help understand complex and variable systems-wide responses displayed by coronavirus-infected patients.

Immediate breast reconstruction surgery (IBRS) with a sub-pectoral placement of implant improves quality of life of patients undergoing a mastectomy. Implant-based IBRS with autologous lower dermal sling (ALDS) procedure provides an effective surgical alternative to acellular dermal matrices. However, the influence of this procedure on radiation therapy (RT) outcomes remains unclear. This study aims at investigating post-surgery complications after 1 year in patients who have undergone IBRS-ALDS and RT. In this single-institution retrospective study, 78 implant-based IBRS patients with data available for a minimum of 1-year follow-up were stratified into group A (n = 40; IBRS) and group B (n = 38; IBRS + RT). Based on the use of ALDS procedure, group A patients were further stratified into sub-groups A1 (conventional IBRS; n = 21) and A2 (ALDS-IBRS; n = 19). Similarly, group B patients were sub-stratified into sub-groups B1 (conventional IBRS + RT; n = 18) and B2 (ALDS-IBRS + RT; n = 20). Clinical assessment and patient-reported outcome measures (PROMs) after 1-year post-surgery were conducted using Baker classification and BREAST-Q questionnaire, respectively. Patients in sub-group B1 exhibited higher percentages of overall major complications (41.6%) when compared to sub-group B2 (8.2%). Capsular contracture (12.5%) and reconstruction failure (20.8%) rates were higher for sub-group B1 vis-a-vis sub-group B2. Superior breast reconstruction outcomes with psycho-social well-being were observed in group B patients in comparison to group A (p

Ethnopharmacological relevance Withania somnifera (L.) Dunal (WS) is one of the moststudied Rasayana botanicals used in Ayurveda practice for its immunomodulatory, anti-aging, adaptogenic, and rejuvenating effects. The botanical is being used for various clinical indications, including cancer. Several studies exploring molecular mechanisms of WS suggest its possible role in improving clinical outcomes in cancer management. Therefore, research on WS may offer new insights in rational development of therapeutic adjuvants for cancer. Aim of this review The review aims at providing a detailed analysis of in silico, in vitro, in vivo, and clinical studies related to WS and cancer. It suggests possible role of WS in regulating molecular mechanisms associated with carcinogenesis. The review discusses potential of WS in cancer management in terms of cancer prevention, anti-cancer activity, and enhancing efficacy of cancer therapeutics. Material and methods The present narrative review offers a critical analysis of published literature on WS studies in cancer. The reported studies were analysed in the context of pathophysiology of cancer, commonly referred as ‘cancer hallmarks’. The review attempts to bridge Ayurveda knowledge with biological insights into molecular mechanisms of cancer. Results Critical analysisof the published literature suggests an anti-cancer potential of WS with a key role in cancer prevention. The possible mechanisms for these effects are associated with the modulation of apoptotic, proliferative, and metastatic markers in cancer. WS can attenuate inflammatory responses and enzymes involved in invasion and metastatic progression of cancer.The properties of WS are likely to be mediated through withanolides, which may activate tumor suppressor proteins to restrict proliferation of cancer cells. Withanolides also regulate the genomic instability, and energy metabolism of cancer cells. The reported studies indicate the need for deeper understanding of molecular mechanisms of WS in inhibiting angiogenesis and promoting immunosurveillance. Additionally, WS can augment efficacy and safety of cancer therapeutics. Conclusion The experimentally-supported evidence of immunomodulatory, anti-cancer, adaptogenic, and regenerative attributes of WS suggest its therapeutic adjuvant potential in cancer management. The adjuvant properties of withanolides can modulate multidrug resistance and reverse chemotherapy-induced myelosuppression. These mechanisms need to be further explored in systematically designed translational and clinical studies that will pave the way for integration of WS as a therapeutic adjuvant in cancer management.

Primary angiosarcoma of the breast is a rare (0.04% of all malignant breast tumors) and potentially life-threatening disease. Given its variable and non-specific clinical, radiological and pathological presentation, accurate diagnosis is a challenge. Primary angiosarcoma of the breast predominantly occurs in younger patients and it is often overlooked and misdiagnosed at radiology and pathology. To ensure that this aggressive malignancy is not overlooked, radiologists need to be aware of the fact that such tumors may present with non-specific imaging features. We report a case of a 32-year-old female with primary angiosarcoma of the breast presenting with non-specific imaging features. It was initially interpreted as a capillary cavernous hemangioma at histopathology following an ultrasound-guided biopsy. This eventually turned out to be angiosarcoma after a second histopathology opinion was sought in light of the radiology-pathology discordance.

Purpose Breast cancer is the most common cancer in India, affecting all socio-economic strata. Despite its growing global acceptance, Breast Oncoplasty Surgery (BOS) remains nascent in India, necessitating local context-specific innovative delivery models for clinicians and the general public. Here, we present experiences from Orchids Breast Health Clinic (OBHC; Pune, India) with the implementation of BOS clinical services, training, and research and community outreach. Methods OBHC, a dedicated breast unit, has established the first dedicated BOS clinic in India, conducted hands-on training workshops for trainee surgeons, developed an MCh degree program in breast oncoplasty with the University of East Anglia (Norwich, United Kingdom), undertaken BOS research in Indian patients, and created outreach programs to popularize BOS. Results A cost-effective one surgeon–dual role concept wherein the same surgeon performs onco- and plastic surgery and one-stage implant-based breast reconstruction has been adopted. Since 2013, BOS cases included BCS (n = 440), breast reconstruction (n = 210), and therapeutic mammoplasty (n = 135). The unavailability of acellular dermal matrices has prompted the innovation of a surgical technique, termed Advanced Autologous Dermal Sling, which uses vascularized local tissue as implant cover. Significant improvement in postsurgery outcomes and protection against radiation complications has been observed. BOS hospitalization costs have been reduced by 50% thereby, which has led to high rates of acceptance (80%) of BOS in patients at OBHC. Young breast surgeons from across India and South Asian Association for Regional Cooperation countries have enrolled in the MCh degree program, which involves an embedded curriculum with online didactic modules and hands-on training workshops in Pune, India. Longitudinal follow-up after 1, 3, and 5 years postsurgery in the study cohorts is undertaken for post-BOS outcomes using clinical assessment (Bakers scale) and patient-reported outcomes measures (BREAST-Q questionnaire). Multiple research projects are undergoing peer-review before publication. To increase awareness of BOS among Indian women, community awareness campaigns with the theme of Losing Is Not an Option are underway via public talks, symposia, marathon, and op-eds in electronic and print media. Conclusion The OBHC model of Affordable Excellence in BOS, developed in the Indian context, can be extrapolated to benefit patients with breast cancer from other low- and middle-income countries. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . No COIs from the authors.

Aim: The purpose of this review was to evaluate the effectiveness of photodynamic therapy (PDT) for periodontitis. This review also elucidates application of photodynamic therapy for noninvasive management of periodontitis without leading to bacterial resistance. Background: Periodontal diseases are one of the major causes of tooth loss in adults and are considered primarily an anaerobic bacterial infections caused by the so-called red complex species. Bacteria present in a biofilm community, enzymes, endotoxins, and other cytotoxic factors lead to tissue destruction and initiate chronic inflammation. Since many years pioneers have been working to provide logical and cost-effective therapy for management of periodontitis. Periodontal researchers have found that PDT is advantageous to suppress anaerobic bacteria. Clinical Significance: Applications of PDT in dentistry are growing rapidly. PDT application has an adjunctive benefit besides mechanical treatment at sites with difficult access. Necessity for flap surgery may be reduced, patient comfort may increase, and treatment time may decrease. The application of photosensitizing dyes and their excitation by visible light enables effective killing of periodonto-pathogens. The introduction of laser along with photosensitizers has brought a revolutionary change. Conclusion: The application of photodynamic therapy in management of periodontal diseases is very valuable. The therapy should be combined with nonsurgical periodontal therapy. Proper clinical application of photodynamic therapy can and will help patients who are systemically compromised and cannot undergo surgical therapy.

Activation of the pregnane X receptor (PXR) mediates the induction of several drug transporters and -metabolizing enzymes. In vitro studies have reported that several of these genes are induced after exposure to the hepatocarcinogen, 2-acetylaminofluorene (2-AAF). Thus, we hypothesized that PXR may play a role in the in vivo induction of gene expression by 2-AAF. We examined the expression of the drug-metabolizing enzymes CYP1A2 and CYP3A11 and the drug transporters breast cancer resistance protein (BCRP), MRP2, and OATP2. Wild-type (PXR+/+) and PXR-null (PXR–/–) C57BL/6 mice were injected daily for 7 days with 150 or 300 mg/kg 2-AAF suspended in corn oil (i.p.), whereas the control group received corn oil vehicle. Levels of mRNA isolated from liver were measured by reverse transcription-polymerase chain reaction and normalized to β-actin. Treatment of PXR+/+ mice resulted in a dose-dependent 2- to 4-fold induction ( p < 0.001) of MRP2, OATP2, BCRP, CYP3A11, and CYP1A2, but no induction was observed in PXR–/– mice. Induction of PXR mRNA was observed in the 2-AAF-treated PXR+/+ mice. Furthermore, a dose-dependent increase in CYP3A4 promoter construct activity was observed in HepG2 cells cotransfected with human or rat PXR, indicating that 2-AAF does indeed activate PXR. These results suggest that PXR is responsible for 2-AAF-mediated induction of drug efflux transporters and biotransformation enzymes in the liver. Moreover, novel findings demonstrate that PXR plays a role in regulation of the drug efflux transporter, BCRP, in mice.

Breast Cancer (BC) treatment leads to mutilation and destruction of breast shape with negative effects on body image and self-esteem.One of the main goals of reconstructive and oncoplastic breast surgery is to satisfy patients and improve their quality of life (QoL).Therefore, it is important to assess the patient experience post-surgery by means of patient-reported outcome measures (PROMs) that focus on the patient’s perception of the surgery and surgical care, as well as psychosocial well-being and physical functioning. The objective of the current study was to identify predictors of patient satisfaction such as breast appearance including implant type in a selective sample of women who underwent breast reconstruction surgery using implants. Participants in this prospective study were women, (age 26–75 years) that were newly diagnosed with breast carcinoma. All consecutive patients who underwent breast reconstruction between January 2013 and October 2014 were asked to complete the BREAST-Q questionnaire 1 year after surgery. 120 patients underwent unilateral breast reconstruction using implant. While 38 patients underwent reconstruction with opposite breast reduction symmertization, 27 patients underwent therapeutic mammoplasty. The response rate for BREAST-Q questionnaire completion was 98 % with 147 out of 150 study participants completed the questionnaire. From the data collected from 147 patients, the responses could be distributed into 4 distinct groups based on the reconstruction outcomes namely “very much satisfied” (93 %) or “definitely and mostly satisfied” (94 %) or “satisfied” with the outcome (88 %) or “definitely agree on having reconstruction rather than the alternative of having no breast “(91 %).The results showed significant improvement in all four areas that were evaluated after surgery namely satisfaction with the appearance of the breasts, psychosocial, sexual and physical well-being. While the reconstruction surgery had an overall positive impact on quality of life it was observed that in patients that did not undergo breast reconstruction psychological issues related to sexuality were observed. Many newly diagnosed BC patients do not opt for these new surgical procedures due to psychological trauma or lack of information. Based on these observations, we propose that Breast Cancer Management protocols should also include additional counselling support for the newly diagnosed BC patients on the option of breast reconstruction along with conventional medical treatment counselling by the Oncosurgeon.

Aim While literature demonstrates that the optimum accuracy is obtained with the custom trays, the use of stock trays for elastomeric impressions appears to be popular in general practice. The aim of the study was to evaluate the effect of thickness of impression material on the dimensional accuracy of impressions made from monophasic polyvinylsiloxane impression material. This study also studies the dimensional stability of the impressions poured at different time intervals. Materials and methods A metal model simulating two abutment teeth was fabricated along with reference lines inscribed on them. Custom impression trays were fabricated with spacer thickness of 2, 4 and 6 mm. impressions were made using monophasic polyvinyl siloxane impression material. The impressions were poured and stone models were obtained. The dimensional accuracy of the impressions were determined indirectly by measuring the dimensional changes of the recovered stone models. The dimensional stability was also evaluated by pouring the impressions at time intervals of 1 hour, 24 hours and 7 days. The obtained data was statistically analyzed. Results The results of the study indicated that the impressions made from 2 and 4 mm tray space produced more accurate stone models when compared to 6 mm tray space. There was no significant deviation in the mesiodistal and buccolingual dimensions when impressions were made using impression trays with 2, 4 and 6 mm tray spacers. There was a significant decrease in interabutment distance (p = 0.001) and height of the abutment (p = 0.024) when impressions were made using impression trays with a tray space of 6 mm. There were no significant differences found among the stone models obtained from 1 hour, 24 hours and 1 week pour times. Conclusion The mesiodistal and buccolingual dimensions of the abutments were not affected by the variations in thickness of impression material. There was a decrease in the height of the abutment which was clinically not significant. As the thickness of the impression material increased, the interabutment space decreased, which is a factor of concern when impressions are made for fixed partial dentures. Clinical significance When monophasic polyvinylsiloxane is used as the impression material, stock trays can be used for making impressions for individual castings. How to cite this article Rajapur A, Dixit S, Hoshing C, Raikar S. The Influence of Tray Space and Repeat Pours on the Accuracy of Monophasic Polyvinylsiloxane Impression. J Contemp Dent Pract 2012;13(6):824-829.