Systematic Implementation of Effective Quality Assurance Processes for the Assessment of Radiation Target Volumes in Head and Neck Cancer.

PURPOSE: Significant heterogeneity exists in clinical quality assurance (QA) practices within radiation oncology departments, with most chart rounds lacking prospective peer-reviewed contour evaluation. This has the potential to significantly affect patient outcomes, particularly for head and neck cancers (HNC) given the large variance in target volume delineation. With this understanding, we incorporated a prospective systematic peer contour-review process into our workflow for all patients with HNC. This study aims to assess the effectiveness of implementing prospective peer review into practice for our National Cancer Institute Designated Cancer Center and to report factors associated with contour modifications. METHODS AND MATERIALS: Starting in November 2020, our department adopted a systematic QA process with real-time metrics, in which contours for all patients with HNC treated with radiation therapy were prospectively peer reviewed and graded. Contours were graded with green (unnecessary), yellow (minor), or red (major) colors based on the degree of peer-recommended modifications. Contours from November 2020 through September 2021 were included for analysis. RESULTS: Three hundred sixty contours were included. Contour grades were made up of 89.7% green, 8.9% yellow, and 1.4% red grades. Physicians with >12 months of clinical experience were less likely to have contour changes requested than those with <12 months (8.3% vs 40.9%; P < .001). Contour grades were significantly associated with physician case load, with physicians presenting more than the median number of 50 cases having significantly less modifications requested than those presenting <50 (6.7% vs 13.3%; P = .013). Physicians working with a resident or fellow were less likely to have contour changes requested than those without a trainee (5.2% vs 12.6%; P = .039). Frequency of major modification requests significantly decreased over time after adoption of prospective peer contour review, with no red grades occurring >6 months after adoption. CONCLUSIONS: This study highlights the importance of prospective peer contour-review implementation into systematic clinical QA processes for HNC. Physician experience proved to be the highest predictor of approved contours. A growth curve was demonstrated, with major modifications declining after prospective contour review implementation. Even within a high-volume academic practice with subspecialist attendings, >10% of patients had contour changes made as a direct result of prospective peer review.

MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer.

Background: MSR1 repeats are a 36-38 bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV). Patients and methods: Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer. Results: MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1 and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P = 4.80 × 10-7) and ion channel activity (P = 2.7 × 10-4). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9 and 11 copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P = 0.004; P = 0.03). In the white British population, the minor allele conferred an increased risk of 1.21-3.51 times for all non-familial disease, or 1.7-5.3 times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27-1.56; P =0.009). Conclusions: MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.

Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1.

This corrects the article DOI: 10.1038/onc.2016.383.

Post-adenoidectomy quality of life in children with refractory chronic rhinosinusitis.

OBJECTIVE: This study aimed to evaluate post-adenoidectomy quality of life in children with refractory chronic rhinosinusitis. METHODS: A prospective interventional study of children aged 4-12 years with chronic refractory rhinosinusitis was conducted. A total of 60 children completed follow up. Nasal endoscopy and non-contrast computed tomography of the paranasal sinuses were performed, and both symptoms and their effects on patient quality of life pre- and post-adenoidectomy were evaluated. RESULTS: The most frequent symptoms were nasal obstruction, cough, fever and fatigue, which were experienced by 100 per cent, 90 per cent, 85 per cent and 81.7 per cent of children, respectively. Nasal endoscopy showed oedema and discharge were present in all children. A statistically significant post-operative improvement in sinus and nasal quality of life was seen in 53 children (88.3 per cent). CONCLUSION: Adenoidectomy is a simple, first-line surgical procedure for managing paediatric chronic rhinosinusitis refractory to maximal medical therapy and leads to an improved quality of life.

Role of honey after tonsillectomy: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Honey reduced post-tonsillectomy pain, but its effects on awakening at night, inflammation and healing of the tonsillar fossa were controversial. OBJECTIVES: This systematic review and meta-analysis of randomised controlled trials (RCTs) evaluated the effect of oral honey on pain, consumption of painkillers, awakening at night, healing of tonsillar fossa and adverse effects in children after tonsillectomy. METHODS: A search of MEDLINE, EMBASE, Scopus, CINAHL and Cochrane Collaboration Library databases was performed without any restriction of publication year. The end date of search was 30 June 2016. The search was supplemented by search from Google, hand search of cross-references of selected articles and reviews, and contacting the authors of different studies. The inclusion criteria were RCTs comparing the effect of honey with control on different outcomes, in children after tonsillectomy. RESULTS: Our search generated 64 studies, and eight RCTs met our inclusion criteria. The methodological quality of RCTs was poor. Compared to control, honey significantly decreased postoperative pain from day 1 to day 7 (P = 0.05 to <0.0001); consumption of painkillers from days 1 to 5 (P = 0.03 to 0.003) and on day 10 (P = 0.002); and number of awakening at night due to pain on days 2 and 4 after tonsillectomy (P = 0.0001, 0.004). The healing of tonsillar fossa was significantly greater with honey compared to control on days 3-4 (P = 0.02) and days ≥9 (P = 0.01) after tonsillectomy. The adverse effects were not significantly different between honey and control groups. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) of the evidence for different outcomes varied from 'low' to 'very low'. CONCLUSIONS: Honey improved pain, requirement of painkillers and awakening at night due to pain in children after tonsillectomy. There was little improvement in healing of tonsillar fossa. The GRADE of the evidence varied from 'low' to 'very low'. A good-quality, placebo-controlled RCT of different doses and durations of administration of honey is required to evaluate its clear efficacy and safety in children after tonsillectomy.

Stromal PTEN inhibits the expansion of mammary epithelial stem cells through Jagged-1.

Fibroblasts within the mammary tumor microenvironment are active participants in carcinogenesis mediating both tumor initiation and progression. Our group has previously demonstrated that genetic loss of phosphatase and tensin homolog (PTEN) in mammary fibroblasts induces an oncogenic secretome that remodels the extracellular milieu accelerating ErbB2-driven mammary tumor progression. While these prior studies highlighted a tumor suppressive role for stromal PTEN, how the adjacent normal epithelium transforms in response to PTEN loss was not previously addressed. To identify these early events, we have evaluated both phenotypic and genetic changes within the pre-neoplastic mammary epithelium of mice with and without stromal PTEN expression. We report that fibroblast-specific PTEN deletion greatly restricts mammary ductal elongation and induces aberrant alveolar side-branching. These mice concomitantly exhibit an expansion of the mammary epithelial stem cell (MaSC) enriched basal/myoepithelial population and an increase in in vitro stem cell activity. Further analysis revealed that NOTCH signaling, specifically through NOTCH3, is diminished in these cells. Mechanistically, JAGGED-1, a transmembrane ligand for the NOTCH receptor, is downregulated in the PTEN-null fibroblasts leading to a loss in the paracrine activation of NOTCH signaling from the surrounding stroma. Reintroduction of JAGGED-1 expression within the PTEN-null fibroblasts was sufficient to abrogate the observed increase in colony forming activity implying a direct role for stromal JAGGED-1 in regulation of MaSC properties. Importantly, breast cancer patients whose tumors express both low stromal JAG1 and low stromal PTEN exhibit a shorter time to recurrence than those whose tumors express low levels of either alone suggesting similar stromal signaling in advanced disease. Combined, these results unveil a novel stromal PTEN-to-JAGGED-1 axis in maintaining the MaSC niche, and subsequently inhibiting breast cancer initiation and disease progression.

Role of mometasone furoate aqueous nasal spray for management of adenoidal hypertrophy in children.

OBJECTIVES: To study the role of mometasone furoate aqueous nasal spray for the management of adenoidal hypertrophy in children with more than 50 per cent obstruction, and to assess its impact on change in quality of life. METHODS: A prospective, randomised, double-blind, interventional placebo-controlled study was conducted. A total of 100 children aged 2-12 years completed treatment and follow up. The symptoms and degree of obstruction were evaluated by nasopharyngoscopy conducted pre-treatment and 24 weeks post-treatment. Subjects received mometasone furoate nasal spray at a daily dose of 200 µg for 8 weeks, followed by a dose of 200 µg on alternate days for 16 weeks. RESULTS were compared with those of a matched control group who were given saline nasal spray. RESULTS: With mometasone treatment, there was an 89.8 per cent reduction in clinical symptom score, and the degree of obstruction dropped from 87 to 72 per cent (p < 0.0001). A statistically significant change in quality of life scores was seen in patients treated with the mometasone nasal spray (score change of 37.47) as compared with those given saline nasal spray (score change of 11.25) (p = 0.0001). CONCLUSION: Mometasone nasal spray appears to be effective in treating children with obstructive adenoids.

A study of changing trends of prevalence and genotypic distribution of hepatitis C virus among high risk groups in North India.

PURPOSE: Hepatitis C virus (HCV) has emerged as a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. There is a great variability in HCV's geographical presence, transmission routes, genotypic distribution etc., in studied populations. We undertook this study in a North Indian hospital on patients of chronic liver disease to observe any emerging trend in risk groups, transmission patterns, genotypic distribution of the virus in this geographical region and its correlation with viral load. MATERIALS AND METHODS: There were 54 anti-HCV positive patients including 31 HCV Ribonucleic acid (RNA) positive patients were included in the study. HCV genotyping was carried out by restriction fragment length polymorphism (RFLP) followed by direct sequencing of the core region. Viral load estimation was carried out by Taqman real time polymerase chain reaction system. RESULTS: In 45/54 (83.3%) anti-HCV positive patients, iatrogenic procedures were responsible for transmission with blood transfusion alone responsible in 36/54 (67%). Genotype 3 was observed to be the commonest type found in all risk groups followed by type 1 and 2. Subtype 3b (35.5%) was found more prevalent than subtype 3a. A higher frequency of subtype 1b (19.4%) was also seen. Genotype 1 was associated with a significantly higher viral load compared to genotypes 3 and 2. No significant difference was observed in the biochemical profile among the three genotypes except for the levels of the enzyme, aspartate aminotransferase (AST). CONCLUSIONS: Iatrogenic procedures, especially contaminated blood transfusion etc., still contributes significantly to the pool of HCV infection. Genotype 3 is the predominant genotype in North India, though the subtype distribution within genotype 3 may be changing. The association of severe liver disease is significantly more with genotype 1 as evidenced by higher viral load and deranged AST levels.

Lymphangioma circumscriptum of the tongue in children: successful treatment using intralesional bleomycin.

Lymphangioma circumscriptum is an uncommon congenital skin disorder occurring commonly in limbs and genitals, and is extremely rare in tongue. Although complete surgical excision is the most widely used treatment, more conservative procedures such as sclerotherapy are being increasingly used for treatment of lymphangiomas. We present a series of two cases of lymphangioma circumscriptum of tongue which were treated successfully with intralesional bleomycin injection.

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

Outcome of endoscopic sinus surgery in patients with symptomatic chronic rhinosinusitis with minimal changes on computerised tomography.

This study was designed to assess the efficacy of functional endoscopic sinus surgery (FESS) in chronic rhinosinusitis (CRS) patients with minimal radiological findings, and based on one centre, prospective randomized controlled study, conducted in the Department of Otorhinolaryngology, Lady Hardinge Medical College, New Delhi. All the CRS out-patients (>18 years) refractory to 3 weeks of medical therapy were radiologically evaluated with computerised tomographic scan (CT) of nose and paranasal sinuses. These patients were grouped based on CT scoring (Lund Mackay staging system): group A (CT score 0-6) and group B (CT score 7-24); with 35 patients in each group. All the patients underwent FESS using Messerklinger technique. Symptom scoring of all the patients was done using visual analog scale preoperatively and postoperatively at 1-, 3-, 6- and 12-month follow-up. CRS patients with minimal evidence of disease on CT showed statistically significant improvement in symptom scores after FESS. There was no significant difference noted in the overall symptom score improvement as well as for improvement in specific symptoms in both the groups. Further, there was no correlation between the pre-operative symptoms and CT scores. A good subjective outcome in terms of symptom improvement can be obtained with FESS in patients with CRS with minimal evidence of disease on CT.

Rhinoentomophthoromycosis due to Conidiobolus coronatus. A case report and an overview of the disease in India.

Rhinoentomophthoromycosis due to Conidiobolus coronatus is a rare, chronic, granulomatous disease, occurring mainly in tropical Africa, South and Central America and south-east Asia, including India. We report a case of rhinoentomophthoromycosis in a 30-year-old male farmer, a resident of Gorakhpur city in Uttar Pradesh, which was diagnosed by histopathology and isolation C. coronatus in culture. The patient presented with a swollen nose with obstruction that had progressed slowly over one year. His nasal swelling was bilateral, diffuse, mildly tender, erythematous, non-pitting, with mucosal crusting and hypertrophy of inferior turbinates but no regional lympha-denopathy. A contrast-enhanced computed tomography (CECT) scan revealed bilateral pan-sinusitis with nasoethmoid polyposis. Culture of tissue from the nasal biopsy on Sabouraud glucose agar yielded multiple colonies of a mold with satellite smaller colonies at periphery. The isolate demonstrated the macroscopic and microscopic morphologic characteristics of C. coronatus. Its identity was further confirmed by direct DNA sequencing of internal transcribed spacer (ITS) and D1/D2 regions of rDNA. Haemotoxylin and eosin stained tissue sections of the skin biopsy revealed irregular epidermal acanthosis, marked inflammatory and granulomatous reaction with sparse, non-septate hyphae. The patient was treated successfully with a combination therapy of oral saturated potassium iodide solution, itraconazole, and intravenous infusion of amphotericin B. An overview of rhinoentomophthoromycosis cases reported to-date in India is presented.

NOS1AP variant associated with incidence of type 2 diabetes in calcium channel blocker users in the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: To validate the reported association between rs10494366 in NOS1AP (the gene encoding nitric oxide synthase-1 adaptor protein) and the incidence of type 2 diabetes in calcium channel blocker (CCB) users and to identify additional NOS1AP variants associated with type 2 diabetes risk. METHODS: Data from 9 years of follow-up in 9,221 middle-aged white and 2,724 African-American adults free of diabetes at baseline from the Atherosclerosis Risk in Communities study were analysed. Nineteen NOS1AP variants were examined for associations with incident diabetes and fasting glucose levels stratified by baseline CCB use. RESULTS: Prevalence of CCB use at baseline was 2.7% (n = 247) in whites and 2.3% (n = 72) in African-Americans. Among white CCB users, the G allele of rs10494366 was associated with lower diabetes incidence (HR 0.57, 95% CI 0.35-0.92, p = 0.016). The association was marginally significant after adjusting for age, sex, obesity, smoking, alcohol use, physical activity, hypertension, heart rate and electrocardiographic QT interval (HR 0.63, 95% CI 0.38-1.04, p = 0.052). rs10494366 was associated with lower average fasting glucose during follow-up (p = 0.037). No other variants were associated with diabetes risk in CCB users after multiple-testing correction. No associations were observed between any NOS1AP variant and diabetes development in non-CCB users. NOS1AP variants were not associated with diabetes risk in either African-American CCB users or non-CCB users. CONCLUSIONS/INTERPRETATION: We have independently replicated the association between rs10494366 in NOS1AP and incident diabetes among white CCB users. Further exploration of NOS1AP variants and type 2 diabetes and functional studies of NOS1AP in type 2 diabetes pathology is warranted.

Lipoma of the deep lobe of parotid gland - a case report and review of literature.

Lipoma of deep lobe of parotid gland is a rare clinical entity. Less than 10 cases have been reported in the literature in our knowledge. Because of their rarity, they are not often considered in the differential diagnosis of parotid tumors. A case of 45-year-old man with an unusually large deep lobe lipoma of parotid gland is presented in this article which was surgically managed by total conservative parotidectmy. The clinical picture, radiological and histopathological features of this entity is being discussed here. Review of literature of this clinical situation has been presented in the present article.

Electron emission from a semiconductor quantum ring under normally incident radiation.

In this paper we investigate the current density due to electrons emitted during normal irradiation of a toroidal quantum ring of a strongly degenerate wide-gap semiconductor. The computed results show that the current density increases in a step-like manner with increase in the incident photon energy. Increased current density can be obtained by reducing the dimensions of the ring. The threshold energy for photoemission becomes an oscillatory function of the cross-sectional radius, and can be used as an important tool for monitoring parameters such as the cross-sectional radius and doping density. The threshold energy is, however, independent of the circumference of the ring.

IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women.

Elevated levels of the inflammatory cytokine IL-6 are associated with the development of disability, frailty, and mortality in older adults. These outcomes are likely mediated through inflammatory activity that alters hormones, skeletal muscle, and the immune system. Polymorphic variants in the IL-6 gene influence IL-6 expression. We hypothesized that IL-6 alleles associate with increased serum of IL-6, decreased muscle strength, and frailty, and tested this in the Women's Health and Aging cohorts. We genotyped 463 participants age 70-79, and identified three common IL-6 haplotype blocks for the Caucasian (n=363) and African American (n=100) subsets. Using linear and logistic regression, and adjusting for age, BMI, race, and osteoarthritis, we identified no significant or clinically meaningful relationship between any single IL-6 single nucleotide polymorphism (SNP) or any IL-6 haplotype and serum IL-6 level, grip, knee, or hip strength, or frailty. Given that the promoter SNP (rs1800795) has been reported to influence IL-6 levels and health outcomes, we performed a similar association study in the In Chianti population (n=266) and confirmed lack of association. These results suggest that IL-6 gene variation may not be an important factor in the determination of elevated IL-6 levels and related phenotypes found in older women.

Ear, nose and throat manifestations in pediatric chronic renal failure patients undergoing peritoneal dialysis.

Ear, Nose and Throat manifestations have been frequently observed in patients with chronic renal failure. Many factors viz. ototoxic drugs, associated conditions of renal failure such as electrolyte imbalance, alteration in blood urea etc. have been implicated for these manifestations. The present study has been conducted to evaluate ear, nose and throat manifestations in thirty pediatric patients (age group 4-16 year) of chronic renal failure undergoing peritoneal dialysis. Probable patho-physiology and treatment of ENT manifestations has been discussed. The remarkable findings in all these cases were the high blood urea level. Most of these manifestations were markedly improved by correction of the renal functions and ideal therapeutic measures.

Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10.

PURPOSE: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.