Showing papers by "Tata Memorial Hospital published in 2019"

International consensus on natural orifice specimen extraction surgery (NOSES) for colorectal cancer.

Abstract: In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.

Fluid administration for acute circulatory dysfunction using basic monitoring: narrative review and expert panel recommendations from an ESICM task force

Abstract: An international team of experts in the field of fluid resuscitation was invited by the ESICM to form a task force to systematically review the evidence concerning fluid administration using basic monitoring. The work included a particular emphasis on pre-ICU hospital settings and resource-limited settings. The work focused on four main questions: (1) What is the role of clinical assessment to guide fluid resuscitation in shock? (2) What basic monitoring is required to perform and interpret a fluid challenge? (3) What defines a fluid challenge in terms of fluid type, ranges of volume, and rate of administration? (4) What are the safety endpoints during a fluid challenge? The expert panel found insufficient evidence to provide recommendations according to the GRADE system, and was only able to make recommendations for basic interventions, based on the available evidence and expert opinion. The panel identified significant gaps in the scientific evidence on fluid administration outside the ICU (excluding the operating theater). Globally, scientific communities and health care systems should address these critical gaps in evidence through research on how basic fluid administration in resource-rich and resource-limited settings can be improved for the benefit of patients and societies worldwide.

Low-Dose vs. High-Dose Cisplatin: Lessons Learned From 59 Chemoradiotherapy Trials in Head and Neck Cancer.

Abstract: In locally advanced squamous cell carcinomas of the head and neck (LA-SCCHN), concurrent chemoradiotherapy is an integral part of multimodality management both in the adjuvant and in the definitive settings. Although de-intensification strategies have been propelled to the forefront of clinical research in human papillomavirus (HPV) positive oropharyngeal cancer, three cycles of 100 mg/m2 cisplatin given every 3 weeks concurrently with conventionally fractionated external beam radiotherapy represent a cost-effective and globally accessible treatment option for the majority of LA-SCCHN cases. Based on four large randomized trials, this regimen has become the non-surgical standard of care for cisplatin-eligible patients. Nevertheless, the outcomes in terms of efficacy, toxicity, and compliance have been rather disappointing. Therefore, there is an unmet need to find a better alternative. With limited support from randomized trials, weekly low-dose cisplatin regimens have replaced the standard high-dose schedule at some institutions. Four prospective trials exploring radiotherapy with and without weekly low-dose cisplatin have been published. Two of them were conducted in the 1980s, one of which had a negative outcome, the third study provided insufficient information on toxicity, and the fourth trial had to be prematurely terminated due to poor accrual. Moreover, the findings of two phase III trials comparing the two concurrent cisplatin regimens favored the high-dose protocol. We performed a composite meta-analysis of 59 prospective trials enrolling a total of 5,582 patients. The primary endpoint was overall survival. Reflecting different radiotherapy fractionation schemes and treatment intents, three meta-analyses were carried out, one for postoperative conventional chemoradiotherapy, one for definitive conventional chemoradiotherapy, and one for definitive altered fractionation chemoradiotherapy. In the former two settings, both high- and low-dose regimens yielded similar survival outcomes, thus, the primary objective was not met. When given concurrently with altered fractionation radiotherapy, patients treated with high-dose cisplatin had significantly longer overall survival than those who received low-dose cisplatin. In this article we provide a synthetic view of the results, discuss the issue of cumulative dose, compare two vs. three cycles of high-dose cisplatin, and present our three-step recommendations for use of the current standard of care, high-dose cisplatin, in clinical practice.

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer

Abstract: Background Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. Methods This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. Results In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). Conclusions The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer

Abstract: Background The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer. Method Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. Results/conclusion A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.

Nomograms based on preoperative multiparametric magnetic resonance imaging for prediction of molecular subgrouping in medulloblastoma: results from a radiogenomics study of 111 patients.

Abstract: Background Novel biological insights have led to consensus classification of medulloblastoma into 4 distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We aimed to predict molecular subgrouping in medulloblastoma based on preoperative multiparametric magnetic resonance imaging (MRI) characteristics. Methods A set of 19 MRI features were evaluated in 111 patients with histologic diagnosis of medulloblastoma for prediction of molecular subgrouping. MRI characteristics were correlated with molecular subgroups derived from tissue samples in 111 patients (WNT = 17, SHH = 44, Group 3 = 27, and Group 4 = 23). Multinomial logistic regression of imaging parameters was performed on a training cohort (TC) of 76 patients, representing two-thirds of randomly selected patients from each of 4 molecular subgroups, to generate binary nomograms. Validation of these nomograms was performed on the remaining 35 patients as the validation cohort (VC). Results Medulloblastoma subgroups could be accurately predicted by preoperative MRI features in 74% of cases. Predictive accuracy was excellent for SHH (95%), acceptably high for Group 4 (78%), modest for Group 3 (56%) and worst for WNT (41%) subgroup medulloblastoma. SHH-specific nomogram was associated with excellent correlation between TC and VC, with area under the curve (AUC) of 0.939 and 0.991, respectively. AUC for Group 4 was acceptable at 0.851 and 0.788 in TC and VC, respectively; however, these values were consistently suboptimal in WNT and Group 3 medulloblastoma. Conclusion The predictive accuracy of MRI-based nomograms was excellent for SHH and encouraging for Group 4 medulloblastoma. Further work is needed for Group 3 and WNT-pathway medulloblastoma.

Tobacco related oral cancer.

Abstract: ### What you need to know Oral cancer accounts for over 140 000 deaths annually across the world. Over 300 000 people are diagnosed with oral cancer each year.1 The incidence of oral cancer in the United Kingdom has increased by 68% over the past 20 years.2 Most oral cancers result from tobacco smoking or using tobacco in other forms.34 In the developed world, oral cancers linked to human papillomavirus (HPV) infection are on the rise.56 Tobacco related oral cancer is an important contributor to lost productivity in developing countries from premature deaths.7 General practitioners (GPs) can play an important role in prevention and in early recognition of signs and prompt referral of patients. In this clinical update, we review the presentation of tobacco related oral cancers and provide guidance for GPs, dentists, and nurses on how to spot oral cancer and further management. Tobacco use, alcohol consumption, and poor diet together possibly explain about 90% of head and neck cancers.3 Smoking accounts for 75% of oral cancers in the United States,4 with higher risk for cancers of the larynx than for …

Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study.

Abstract: Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients’ prognosis. Methods: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. Results: AR status shows population-specific patterns of association with patients’ overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted.

Challenges in the management of septic shock: a narrative review.

Abstract: While guidelines provide important information on how to approach a patient in septic shock, "many challenges remain" for the management of these patients. In this narrative review, the panel discusses the challenges in identifying the right hemodynamic target, optimization of fluid therapy, selection of vasopressor agents, identification of patients who may benefit from inotropic agents or on the contrary beta-blockade, and use of steroids. The place for microcirculation-targeted therapy is debated as well as the use of alternative techniques (blood purification) and therapies (vitamin C). The implications of hemodynamic alterations on antibiotic doses is discussed. Finally, the specific challenges in low- and middle-income countries are addressed. Ongoing trials address some of these challenges, but many uncertainties will remain, and individualized therapies based on careful clinical assessment will continue to be essential to optimizing the care of patients with septic shock.

Outcome of uncommon EGFR mutation positive newly diagnosed advanced non-small cell lung cancer patients: a single center retrospective analysis.

Abstract: Background The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients. Patients and methods We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan-Meier method and compared between groups using log-rank test. Results Out of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8-8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4-28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1-21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2-37.0, P=0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2-41.2, P=0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations. Conclusion Uncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.

Guidelines for Antibiotic Prescription in Intensive Care Unit.

Abstract: How to cite this article: Khilnani GC, Zirpe K, Hadda V, Mehta Y, Madan K, Kulkarni A, Mohan A, Dixit S, Guleria R, Bhattacharya P. Guidelines for Antibiotic Prescription in Intensive Care Unit. Indian Journal of Critical Care Medicine 2019;23 (Suppl 1):1-63.

Phase III randomized trial comparing gefitinib to gefitinib with pemetrexed-carboplatin chemotherapy in patients with advanced untreated EGFR mutant non-small cell lung cancer (gef vs gef+C).

Abstract: 9001Background: Standard first-line therapy for EGFR mutant advanced non-small cell lung cancer (NSCLC) is an EGFR-directed oral TKI. We evaluated whether adding pemetrexed-carboplatin to oral TKI ...

Depth of invasion alone as an indication for postoperative radiotherapy in small oral squamous cell carcinomas: An International Collaborative Study.

Abstract: BACKGROUND We aimed to investigate whether depth of invasion (DOI) should be an independent indication for postoperative radiotherapy (PORT) in small oral squamous cell carcinomas (SCC). METHODS Retrospective analysis of DOI (<5, 5 to <10, ≥10 mm) and disease-specific survival (DSS) in a multi-institutional international cohort of 1409 patients with oral SCC ≤4 cm in size treated between 1990-2011. RESULTS In patients without other adverse factors (nodal metastases; close [<5 mm] or involved margins), there was no association between DOI and DSS, with an excellent prognosis irrespective of depth. In the absence of PORT, the 5-year disease-specific mortality was 10% with DOI ≥10 mm, 8% with DOI 5-10 mm, and 6% with DOI <5 mm (P = .169), yielding an absolute risk difference of only 4%. CONCLUSION The deterioration in prognosis with increasing DOI largely reflects an association with other adverse features. In the absence of these, depth alone should not be an indication for PORT outside a clinical trial.

Tumor induced osteomalacia in head and neck region: single center experience and systematic review

Abstract: Tumor-induced osteomalacia in the head and neck region remains a challenging diagnosis to manage. Literature pertaining to management and outcome details remains sparse. We describe two cohorts: cohort 1 included seven patients from a single center in Western India with tumors located in paranasal sinuses (n = 3), intracranial (n = 2) and maxilla (n = 2). The unique features from our series is the management of persistent disease with radiation therapy (n = 2) and peptide receptor radionuclide therapy (PRRT) (n = 1). Cohort two has 163 patients identified from 109 publications for systematic review. Paranasal sinuses, mandible, intracranial disease, maxilla and oral cavity, in descending order, are reportedly common tumor sites. Within this cohort, mean age was 46 ± 14 years at presentation with 44.1% having local symptoms. Duration of symptoms varied from 1 to 240 months. Pre-surgery mean serum phosphorus was 1.4 ± 0.4 mg/dL and median FGF-23 levels were 3.6 (IQR:1.8-6.8) times of normal upper limit of normal. Majority (97.5%) were managed primarily with surgical excision; however, primary radiotherapy (n = 2) and surgery combined with radiotherapy (n = 2) were also reported. Twenty patients had persistent disease while nine patients had recurrence, more commonly noted with intracranial and oral cavity tumors. Surgery was the most common second mode of treatment employed succeeded by radiotherapy. Four patients had metastatic disease. The most common histopathological diagnosis reported is PMT mixed connective tissue, while the newer terminology 'PMT mixed epithelial and connective tissue type' has been described in 15 patients.

Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma

Abstract: Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports linking NLRs and AIM2 to glioma pathology. NLRs are expressed by cells of innate immunity, including monocytes, macrophages, dendritic cells, endothelial cells, and neutrophils, as well as cells of the adaptive immune system. NLRs are critical regulators of major inflammation, cell death, immune and cancer-associated pathways. We used a data-driven approach to identify NLRs, AIM2 and NLR-associated gene expression and methylation patterns in low grade glioma and glioblastoma, using The Cancer Genome Atlas (TCGA) patient datasets. Since TCGA data is obtained from tumor tissue, comprising of multiple cell populations including glioma cells, endothelial cells and tumor-associated microglia/macrophages we have used multiple cell lines and human brain tissues to identify cell-specific effects. TCGA data mining showed significant differential NLR regulation and strong correlation with survival in different grades of glioma. We report differential expression and methylation of NLRs in glioma, followed by NLRP12 identification as a candidate prognostic marker for glioma progression. We found that Nlrp12 deficient microglia show increased colony formation while Nlrp12 deficient glioma cells show decreased cellular proliferation. Immunohistochemistry of human glioma tissue shows increased NLRP12 expression. Interestingly, microglia show reduced migration towards Nlrp12 deficient glioma cells.

Clinical validation of an immunohistochemistry-based CanAssist-Breast test for distant recurrence prediction in hormone receptor-positive breast cancer patients.

Abstract: CanAssist-Breast (CAB) is an immunohistochemistry (IHC)-based prognostic test for early-stage Hormone Receptor (HR+)-positive breast cancer patients. CAB uses a Support Vector Machine (SVM) trained algorithm which utilizes expression levels of five biomarkers (CD44, ABCC4, ABCC11, N-Cadherin, and Pan-Cadherin) and three clinical parameters such as tumor size, grade, and node status as inputs to generate a risk score and categorizes patients as low- or high-risk for distant recurrence within 5 years of diagnosis. In this study, we present clinical validation of CAB. CAB was validated using a retrospective cohort of 857 patients. All patients were treated either with endocrine therapy or chemoendocrine therapy. Risk categorization by CAB was analyzed by calculating Distant Metastasis-Free Survival (DMFS) and recurrence rates using Kaplan-Meier survival curves. Multivariate analysis was performed to calculate Hazard ratios (HR) for CAB high-risk vs low-risk patients. The results showed that Distant Metastasis-Free Survival (DMFS) was significantly different (P-0.002) between low- (DMFS: 95%) and high-risk (DMFS: 80%) categories in the endocrine therapy treated alone subgroup (n = 195) as well as in the total cohort (n = 857, low-risk DMFS: 95%, high-risk DMFS: 84%, P 74% of high Ki-67 and IHC4 score intermediate-risk zone patients into low-risk category. Overall the data suggest that CAB can effectively predict risk of distant recurrence with clear dichotomous high- or low-risk categorization.

Holistic support coupled with prospective tracking reduces abandonment in childhood cancers: A report from India.

Abstract: Background High cure rates of over 80% in childhood cancers reported from high-income countries (HICs) are not replicated in low- and middle-income countries (LMICs). Treatment abandonment (TxA) is an important reason for this poorer outcome. We assessed the effect of a holistic support group approach coupled with prospective tracking on TxA in children with cancer in a limited-resources environment. Methods In 2010, all existing nongovernmental organizations (NGOs) working with childhood cancer at our hospital were brought together to form a pediatric cancer foundation with the aim of providing holistic support to the patient and family, including financial, psychosocial, lodging, educational, and bereavement support. Simultaneously, prospective tracking of all children with a Time-Responsive Electronic Abandonment Tracking (TREAT) system was also established. The impact of these measures on TxA over the 2009-2016 period was compared using the log-rank test. Results The annual rate of abandonment reduced from 20% in 2009 to 10.4% in 2010 and 5.2% in 2011. It has been consistently between 3% and 6% from 2012 to 2016 (P -0.04). TxA after the initiation of treatment dropped from 9% in 2009 to 1% in 2016 (P -0.02), while refusal to initiate treatment dropped from 11% to 2.7% (P -0.23) over the same period. Conclusions A holistic support group consisting of the hospital team, as well as existing NGOs and governmental organizations, along with a systematic and prospective tracking system significantly reduced abandonment in a resource-constrained setting. This cost-effective holistic support group may be applicable in other LMICs with similar healthcare systems.

Extranodal extension in resected oral cavity squamous cell carcinoma: more to it than meets the eye.

Abstract: Objective/hypothesis Extranodal extension (ENE) is an independent prognosticator in head-neck Squamous cell carcinoma (SCC). All patients with ENE, however, do not behave the same, and there is a need for further risk stratification. This study evaluates the prognostic significance of various grades of ENE and the number of nodes with ENE on overall survival (OS) in oral cavity SCC (OCSCC). Study design Retrospective cohort study. Methods Ninety-four patients with node-positive OCSCC treated with primary surgery and appropriate adjuvant therapy during the year 2011 were evaluated. Surgical histopathology slides of all patients were reviewed, and ENE was graded according to the grading system proposed by Lewis Jr et al. RESULTS: On univariate analysis, lymph node density (LND) greater than or equal to 0.12 (P = 0.013), the presence of ENE in more than two nodes (P = 0.006), and ENE grade 3 through 4 (P = 0.035) were associated with worse (OS). Conventional prognostic factors such as tumor (T) stage, nodal (N) stage, stage grouping, depth of invasion, and pattern of invasion did not have a significant impact on OS. On multivariate analysis, the presence of ENE in more than two nodes (P = 0.018) independently predicted a worse OS. Extranodal extension grade 3 through 4 showed a trend toward significance (P = 0.08). A combination of LND greater than or equal to 0.12, ENE grade 3 through 4, and ENE in more than two lymph nodes conferred the poorest prognosis (3-year OS: 18%; P = 0.000). Conclusion In patients with ENE and advanced nodal disease, T stage, N stage, stage group, depth, and pattern of invasion lose their impact on OS. In patients with ENE, nodal characteristics such as LND, the number of nodes with ENE, and grade of ENE serve as important prognosticators and aid in further risk stratification. Level of evidence 4 Laryngoscope, 129:1130-1136, 2019.

Epidermal growth factor receptor-mutated non-small-cell lung cancer: A primer on contemporary management

Abstract: Non-small-cell lung cancer (NSCLC) constitutes 85% of patients diagnosed with lung cancer. In metastatic cases, its treatment classically consists of systemic cytotoxic chemotherapy, which resulted in a median overall survival of 7.9 months. However, over the last decade, improved understanding of driver mutations, especially identification of epidermal growth factor receptor (EGFR) mutation, has changed the treatment landscape of these patients. Our understanding of EGFR mutations has improved tremendously, and we now have three generations of EGFR tyrosine kinase inhibitors, have identified secondary resistance mutations, and have developed agents targeting these resistance mutations, making precision medicine a reality. We review these developments and try to propose an optimal approach toward the management of these patients with EGFR-mutated NSCLC.

Testing and interpreting assumptions of COX regression analysis

Abstract: The COX regression analysis is like any statistical test that is based on multiple assumptions. This is a guide for how to test the assumptions and how to interpret the results.

Compliance with point-of-sale tobacco control policies and student tobacco use in Mumbai, India

Abstract: Background We measured how student tobacco use and psychological risk factors (intention to use and perceived ease of access to tobacco products) were associated with tobacco vendor compliance with India’s Cigarettes and Other Tobacco Products Act provisions regulating the point-of-sale (POS) environment. Methods We conducted a population-based cross-sectional survey of high school students (n=1373) and tobacco vendors (n=436) in school-adjacent communities (n=26) in Mumbai, India. We used in-class self-administered questionnaires of high school students, face-to-face interviews with tobacco vendors and compliance checks of tobacco POS environments. Logistic regression models with adjustments for clustering were used to measure associations between student tobacco use, psychological risk factors and tobacco POS compliance. Results Compliance with POS laws was low overall and was associated with lower risk of student current tobacco use (OR 0.48, 95% CI 0.26 to 0.91) and current smokeless tobacco use (OR 0.40, 95% CI 0.21 to 0.77), when controlling for student-level and community-level tobacco use risk factors. Compliance was not associated with student intention to use tobacco (OR 0.50; 95% CI 0.21 to 1.18) and perceived ease of access to tobacco (OR 0.73; 95% CI 0.53 to 1.00). Conclusions Improving vendor compliance with tobacco POS laws may reduce student tobacco use. Future studies should test strategies to improve compliance with tobacco POS laws, particularly in low-income and middle-income country settings like urban India.

ISNO consensus guidelines for practical adaptation of the WHO 2016 classification of adult diffuse gliomas

Abstract: Introduction: Recent advances in the molecular biology of adult diffuse gliomas have brought about a paradigm shift in their diagnostic criteria, as witnessed in the World Health Organization (WHO) 2016 guidelines for central nervous system tumors. It is now mandatory to perform several molecular tests to reach a definitive integrated diagnosis in most of the cases. This comes with additional cost and higher turnaround time, which is not always affordable in developing countries like India. In addition, the non-uniform distribution of advanced research and diagnostic testing centers adds to the difficulty. Methods: The Indian Society of Neuro-oncology (ISNO) multidisciplinary expert panel consisting of neuropathologists, neurosurgeons, and radiation/medical oncologists convened to prepare the national consensus guidelines for approach to diagnosis of adult diffuse gliomas. Results: Algorithms for arriving at an integrated diagnosis of adult diffuse gliomas predominantly using immunohistochemistry and with minimum possible additional molecular testing were agreed upon, thus addressing the problems of cost, accessibility, and turnaround time. Mandatory and optional tests were proposed for each case scenario. Conclusion: This document represents the consensus of the various neuro-oncology disciplines involved in diagnosis and management of patients with adult diffuse gliomas. The article reflects a practical adaptation of the WHO recommendations to suit a resource constrained setup.

Downregulation of miR-204 expression defines a highly aggressive subset of Group 3/Group 4 medulloblastomas

Abstract: Genome-wide expression profiling studies have identified four core molecular subgroups of medulloblastoma: WNT, SHH, Group 3 and Group 4. Molecular markers are necessary for accurate risk stratification in the non-WNT subgroups due to the underlying heterogeneity in genetic alterations and overall survival. MiR-204 expression was evaluated in molecularly classified 260 medulloblastomas from an Indian cohort and in 763 medulloblastomas from the MAGIC cohort, SickKids, Canada. Low expression of miR-204 in the Group 3 / Group 4 tumors identify a highly aggressive subset of tumors having poor overall survival, in the two independent cohorts of medulloblastomas. Downregulation of miR-204 expression correlates with poor survival within the Group 4 as well indicating it as a valuable risk-stratification marker in the subgroup. Restoration of miR-204 expression in multiple medulloblastoma cell lines was found to inhibit their anchorage-independent growth, invasion potential and tumorigenicity. IGF2R was identified as a novel target of miR-204. MiR-204 expression resulted in downregulation of both M6PR and IGF2R that transport lysosomal proteases from the Golgi apparatus to the lysosomes. Consistent with this finding, miR-204 expression resulted in reduction in the levels of the lysosomal proteases in medulloblastoma cells. MiR-204 expression also resulted in inhibition of autophagy that is known to be dependent on the lysosomal degradation pathway and LC3B, a known miR-204 target. Treatment with HDAC inhibitors resulted in upregulation of miR-204 expression in medulloblastoma cells, suggesting therapeutic role for these inhibitors in the treatment of medulloblastomas. In summary, miR-204 is not only a valuable risk stratification marker in the combined cohort of Group 3 / Group 4 medulloblastomas as well as in the Group 4 itself, that has paucity of good prognostication markers, but also has therapeutic potential as indicated by its tumor suppressive effect on medulloblastoma cells.

Analysis of 50 cases of solid pseudopapillary tumor of pancreas: Aggressive surgical resection provides excellent outcomes.

Abstract: Introduction This study reports the clinicopathological characteristics and the perioperative and long-term treatment outcomes after aggressive surgical resection in solid pseudopapillary tumor (SPT) of the pancreas performed at a high volume center for pancreatic surgery in India. Materials and methods We analyzed a prospectively maintained database of the patients operated for SPT at Tata Memorial Hospital, India over a period of 11 years from February 2007 to February 2018. Results Fifty consecutive patients operated for SPT, during the study period were included. The median age at presentation was 24 years. Majority of the patients (43/50) were female (86%). Disease was predominantly localized in the head and uncinate process of pancreas (66%). Median tumor size was 7.7 cm (Range 1.6–15 cm). Tumor extent was radiologically defined as borderline resectable or locally advanced in 48% (n = 24) patients. Forty-six major pancreatic resections were performed, which included 10 (21%) vascular resections, 2 synchronous liver metastasectomies, 1 multi visceral resection and 5 total pancreaticosplenectomies. Five of these resections were reoperations in patients deemed inoperable on exploration at other centers. R0 resection was achieved in 47 patients (98%). Postoperative major morbidity was 19% and there was no mortality. At a median follow-up of 29 months (Range, 1–121 months), all patients were alive without any recurrence. Conclusion Aggressive complete surgical resection of SPT achieves excellent long-term survival. Surgery, especially for large and borderline resectable tumors, can be potentially complex and should be performed at high-volume centers to provide the best chance of cure.

The Continuing Evolution of Molecular Functional Imaging in Clinical Oncology: The Road to Precision Medicine and Radiogenomics (Part II)

Abstract: An Online First version of this article was made available online at http://link.springer.com/journal/40291/onlineFirst/page/1 on 01 Nov 2018. An error was subsequently identified in the article, and the following correction should be noted.

Raman exfoliative cytology for prognosis prediction in oral cancers: A proof of concept study.

Abstract: Oral cancer is associated with high rates of recurrence, attributable to field cancerization. Early detection of advanced field changes that can potentially progress to carcinoma can facilitate timely intervention and can lead to improved prognosis. Previous in vivo studies have successfully detected advanced field effects in oral cancers. Raman exfoliative cytology has previously shown to differentiate normal, oral pre-cancer and cancers. The present study explores Raman-exfoliative-cytology-based detection of field effects. Exfoliated cells were collected from tumor (n = 16) and contralateral-normal appearing mucosa (n = 16) of oral cancer patients, and healthy tobacco habitues (n = 20). After spectral acquisition, specimens were Pap-stained for cytological evaluation. Data analysis, by Principal Component Analysis and Principal Component-Linear Discriminant Analysis, indicate several spectral-misclassifications between contralateral normal and tumor, which were investigated and correlated with spectral, cytological and clinical outcomes. A qualitative analysis by grouping patients with number of misclassifications with tumor (Group 1: 0, Group 2: 1 and Group 3: >1) was explored. Group 3 with highest misclassifications showed spectral and cytological similarity to tumor group - one patient was a case of early inoperable residual disease, despite clear margins on histopathology. Thus, these misclassifications could be indicative of cancer field changes, and can prospectively help to identify patients susceptible to recurrences .