Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Correlation of density of microvessels and myofibroblasts with the aggressiveness of central giant cell granulomas of jaws: A preliminary study.

Objectives: Central giant cell granuloma (CGCG) is a fairly common lesion involving the jaw bones. CGCG can show relatively innocuous biological behaviour or it may show clinicoradiological features suggestive of aggressive biological behaviour. To date, there are no histological parameters which can be used to predict the behaviour of these lesions. This study was conducted to assess the utility of parameters of angiogenesis, i.e., total vascular area (TVA), mean vascular area (MVA) and microvessel density (MVD), and density of myofibroblasts in aggressive and non-aggressive CGCGs. Materials and Methods: The study was undertaken as a retrospective study. A total of 20 previously diagnosed cases (10 non-aggressive and 10 aggressive) of CGCGs were included in the study. The sections were subjected to immunohistochemistry using the markers CD34 and α-SMA. For the assessment of vascular parameters, image J software was used. The density of myofibroblasts was determined in each case ranging from score-1 to 4, using the criteria given by Sridhara et al. The correlation between mean values of vascular parameters and density of myofibroblasts with aggressiveness of CGCG was assessed using Mann-Whitney U test. Results: The result of Mann-Whitney U test suggested that the differences between the values of TVA (P < 0.001), MVA (P < 0.003) and density of myofibroblasts, i.e., SMA mean (P < 0.001) and SMA score (P < 0.001), in two groups are statistically significant. The formula for the assessment of aggressiveness was obtained using discriminant analysis. Conclusions: Angiogenesis and density of myofibroblasts significantly differ in aggressive and non-aggressive cases of CGCGs. The aggressiveness of CGCG case can be predicted using the obtained formula by entering the values of vascular parameters and myofibroblasts.

Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Neutrophil: Lymphocyte ratio and oral squamous cell carcinoma: A preliminary study.

INTRODUCTION/BACKGROUND: It is well-established that host response plays a vital role in the determination of biological behavior of tumors. Inflammatory response against tumors has been a focus of research in recent years. There has been extensive research regarding inflammatory reaction in oral squamous cell carcinoma (OSCC) in tissue specimens. However, there is no much data regarding systemic inflammatory response in OSCC. It was recently reported that an elevated neutrophil:lymphocyte ratio (NLR) may correlate with aggressive biological behavior in various malignancies including head-and-neck tumors. Thus, the study was undertaken with the aim of evaluation of NLR in peripheral blood of patients suffering from OSCC. MATERIALS AND METHODS: The research was a prospective, case-control study. Hundred patients suffering from OSCC and 100 healthy individuals were included in the study, after obtaining informed consent. NLR was determined from the differential leukocyte count obtained from complete blood count in each case. Comparison of NLR was made among two groups. RESULTS: The mean value of absolute neutrophil count was found to be significantly higher in OSCC cases than in controls (P < 0.01). The mean value of NLR in OSCC was found to be 2.84, and in controls, it was 1.95. This difference was found to be statistically significant (P < 0.001). CONCLUSION: NLR and other hematological parameters may serve as surrogate marker for potential aggressive behavior of OSCC and may help in prognostic prediction of these cases.

Quantitative assessment of tumor-associated tissue eosinophilia and mast cells in tumor proper and lymph nodes of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease. Further research proves that there are several biologically important factors in tumor tissue and LNs which promote or defend LNM. While it is proposed that tumor-associated tissue eosinophils (TATE) and mast cells (MCs) have "immuno-protective" effect, this remains unproven and various researchers have conflicting opinion. Aim: The aim is to determine the presence of TATE and MCs in OSCC and to evaluate if any association exists between them and LNM. Study Design: It is a comparative retrospective study between two groups including 35 OSCC cases positive and 35 negative for LNM. Materials and Methodology: Quantification of cells was done by counting total number of cells in 10 high-power fields under ×40 objective lens using "zigzag" method and dividing it by total number of fields. Eosinophils stained bright red with carbol chromotrope and MCs purple-violet with toluidine blue. Statistics: Independent t-test and Pearson's correlation were done using STATA IC 0.2 software. The level of significance was at 5%. Comparison of eosinophil and MC infiltration was done based on gender, metastatic, nonmetastatic LN and in tumor proper. Results and Conclusion: Our study showed weak positive correlation between mean eosinophils count in tumor and LNs which implies a definite association between the microenvironment of tumor, its progression and LNM. There was a significant association between MC density and decreased LNM also. We conclude that an increased number of immunological cells (TATE and MCs) are a favorable prognostic indicator in OSCC. There is evidence of reduction in LNM with increasing density of these immunological cells. Recognition of TATE and MCs as integral to tumor biology opens an avenue for novel approaches to cancer therapies.

Postoperative pathologic assessment of surgical margins in oral cancer: A contemporary review.

Adequacy of resection margins is of utmost importance for decisions regarding postoperative treatment and prediction of prognosis in patients with oral squamous cell carcinoma. However, there are differences in opinions about various basic concepts of surgical margins in oral and maxillofacial pathology. Fundamental issues such as concepts of positive or negative surgical margins and impact of epithelial dysplasia at margin require clarification to standardize the practice of postoperative margin surveillance. The issue of postresection tissue shrinkage must be considered and addressed while reporting the status of surgical margin. The current status of "molecular assessment" of resection margins is far from mature and it may expand the horizons of postoperative margin surveillance in future. The present review summarizes the fundamental concepts and methods involved in postoperative assessment of surgical margins in oral and maxillofacial pathology. This will help in understating the rationale of current approach for the assessment of resection margins. Understanding the limitations of the existing approach will also help to improve our practice of postoperative margin surveillance.

Quantitative assessment of tumor-associated tissue eosinophilia and mast cells in tumor proper and lymph nodes of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection, and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease. Further research proves that there are several biologically important factors in tumor tissue and LNs which promote or defend LNM. While it is proposed that tumor-associated tissue eosinophils (TATE) and mast cells (MCs) have "immuno-protective" effect, this remains unproven and various researchers have conflicting opinion. AIM: The aim is to determine the presence of TATE and MCs in OSCC and to evaluate if any association exists between them and LNM. STUDY DESIGN: It is a comparative-retrospective study between 2 groups including 35 OSCC cases positive and 35 negative for LNM. MATERIALS AND METHODOLOGY: Quantification of cells was done by counting total number of cells in 10 high-power fields under ×40 objective lens using "zigzag" method and dividing it by total number of fields. Eosinophils stained bright red with carbol chromotrope and MCs purple-violet with toluidine blue. STATISTICS: Independent t-test and Pearson's correlation were done using STATA IC 0.2 software. Level of significance was at 5%. Comparison of eosinophil and MC infiltration was done based on gender, metastatic, nonmetastatic LN, and in tumor proper. RESULTS AND CONCLUSION: This study showed weak positive correlation between mean eosinophils count in tumor and LNs. Recognition of TATE and MCs as integral to tumor biology opens an avenue for novel approaches to cancer therapies. We conclude that an increased number of immunological cells are a favorable prognostic indicator in OSCC.

Cutaneous horn: A mask to underlying malignancy.

Cutaneous horns (cornu cutaneum) are uncommon lesions consisting of keratotic material resembling that of an animal horn. It is a conical- or cylindrical-shaped excessive hyperkeratosis of variable size ranging from few millimeters to several centimeters with a variable in size and shape, such as cylindrical, conical, pointed, transversely or longitudinally corrugated, or curved like a ram's horn. The lesions typically occur in sun-exposed areas, particularly the face, ear, nose, forearms and dorsum of hands. Even though 60% of the cutaneous horns are benign in nature, the possibility of skin cancer should always be kept in mind. The clinical diagnosis includes various benign and malignant lesions at its base. Lesions associated with cutaneous horn are keratosis, sebaceous molluscum, verruca, trichilemmal, Bowen's disease, epidermoid carcinoma, malignant melanoma and basal cell carcinoma. Herewith, we report a case of cutaneous horn on the upper lip vermillion masking the underlying malignancy at its base.

Plunging Ranula Occurring Without its Oral Counterpart: A Case Report.

A ranula is a lesion that arises from mucin spillage from the sublingual or submandibular gland ducts, beneath the mucosa of the oral floor. A plunging or cervical ranula dissects the mylohyoid muscle and appears as a submandibular swelling. Rarely, a plunging ranula is encountered without its oral counterpart. Here, we report a rare case of a plunging ranula that occurred without its oral counterpart in a 11-year-old male patient. We have also discussed the pathogenesis and treatment options for the ranula.

Oxaliplatin-induced lung fibrosis.

Oxaliplatin has been approved for use as an adjuvant treatment in stage III colorectal carcinoma by the US-FDA. The majority of toxicity caused by this drug is manageable. However, rare, isolated cases of pulmonary fibrosis induced by this drug have been reported in literature. We report one such case of rapidly evolving pulmonary fibrosis following treatment with oxaliplatin.