The increasing challenge of never smokers with adenocarcinoma lung: Need to look beyond tobacco exposure.

BACKGROUND: Lung cancer continues to remain as one of the leading causes of morbidity and mortality worldwide, despite the decreasing trends in smoking prevalence worldwide. An earlier study from the authors' institute reported the increasing trends of "Nonsmoking associated lung cancers." MATERIALS AND METHODS: All consecutive histologically confirmed patients with lung cancer who presented to the outpatient department over a year (November 2014-October 2015) were included in this current prospective study. RESULTS: Seven hundred and thirteen patients presented with clinicoradiologically suspicious findings of lung cancer in the said period. A pathological confirmation of lung cancer could be ascertained in 495 patients, and this cohort was further analyzed. The mean age of presentation was 57.76 years; the male to female ratio was approximately 2.5:1. Interestingly, 55.35% of the patients were nonsmokers. Adenocarcinoma (63%) was the predominant histology. Never smokers, both among men (P = 0.02) and women (P = 0.001), presented more frequently with adenocarcinoma histology. Further, 84.9% (45/53) of rural and 76.1% (19/25) of urban women who were never smokers reported exposure to indoor air pollution (secondhand smoke/fuel used for cooking purposes) which was significantly associated with adenocarcinoma histology. CONCLUSION: Our study confirmed our initial observation of the changing epidemiology of lung cancer in the Indian subcontinent, paralleling the global trends of rise in adenocarcinoma. Lung cancer in never smokers outnumbering that among smokers was another interesting observation. The take-home message for both the clinicians as well as the policymakers is to study factors beyond tobacco exposure to understand the direction of the current lung cancer epidemic.

Role and relevance of BRAF mutations in risk stratifying patients of papillary thyroid cancers along with a review of literature.

INTRODUCTION: Molecular markers are increasingly being explored as a potential diagnostic and prognostic tool in patients with well-differentiated thyroid cancers and B-type Raf kinase (BRAF) V600E mutation has received a wide attention in this regard. Many clinical studies have demonstrated an association of BRAF V600E mutation with aggressive clinicopathologic characteristics and high tumor recurrence and mortality in patients with papillary thyroid cancers. Papillary thyroid cancers has been abbreviated and PTCs. AIM: The present single center study aims to assess the biological behavior of conventional papillary thyroid cancers. (PTC) with somatic BRAF V600E mutation. MATERIALS AND METHODS: Patients who were managed for well differentiated thyroid cancers during 2005-2006 were included in the study. BRAF V600E mutation analysis was done by real time polymerase chain reaction after extracting genomic DNA from the representative archived formalin fixed paraffin embedded tumor tissue. RESULTS: Of the 79 patients of well-differentiated thyroid cancers included in the study, 31% harbored BRAF V600E mutation; the mutation prevalence was 39.6% in the cohort of conventional PTCs. Our study emphatically states that BRAF V600E mutation status is a significant predictor of adverse outcomes in patients with conventional PTCs. CONCLUSION: Our study further suggests a possible risk-stratified approach using age, BRAF V600E mutation status, and extrathyroidal spread, and this approach can be used to personalize the management of patients with conventional PTCs. The result of our study adds to the growing consensus that BRAF V600E mutational status should be analyzed in correlation with other molecular and clinicopathological prognostic factors for a better risk stratification.

Atezolizumab: A novel PD-L1 inhibitor in cancer therapy with a focus in bladder and non-small cell lung cancers.

In recent years, immunotherapy has come to the forefront as a major development in cancer treatment. Evasion of the immune system by tumor cells has been identified as one of the hallmarks of cancer and multiple therapies have been developed to counter this process. Programmed cell death 1 ligand 1 (PD-L1), a ligand to programmed cell death protein 1 (PD-1), is expressed by many cancer cells and the binding of PD-L1 to PD-1 results in the suppression of T-cell-mediated immune response against cancer cells. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1, thereby enhancing T-cell activity against tumor cells. Atezolizumab has been shown to be well tolerated with no dose-limiting toxicities in phase I trials. Atezolizumab was approved by the U.S. Food and Drug Administration in 2016 for the treatment of platinum-resistant metastatic non-small cell lung cancer (NSCLC) and urothelial cancer based on phase II and preliminary phase III studies that have shown significant improvement in objective response rate and median overall survival. There are 117 ongoing clinical trials of atezolizumab currently. Given its efficacy in NSCLC and urothelial carcinoma, atezolizumab holds much potential in the future of cancer therapeutics.

Advanced buffer materials for indoor air CO2 control in commercial buildings.

In this study, we evaluated solid sorbents for their ability to passively control indoor CO2 concentration in buildings or rooms with cyclic occupancy (eg, offices, bedrooms). Silica supported amines were identified as suitable candidates and systematically evaluated in the removal of CO2 from indoor air by equilibrium and dynamic techniques. In particular, sorbents with various amine loadings were synthesized using tetraethylenepentamine (TEPA), poly(ethyleneimine) (PEI) and a silane coupling agent 3-aminopropyltriethoxysilane (APS). TGA analysis indicates that TEPA impregnated silica not only displays a relatively high adsorption capacity when exposed to ppm level CO2 concentrations, but also is capable of desorbing the majority of CO2 by air flow (eg, by concentration gradient). In 10 L flow-through chamber experiments, TEPA-based sorbents reduced outlet CO2 by up to 5% at 50% RH and up to 93% of CO2 adsorbed over 8 hours was desorbed within 16 hours. In 8 m3 flow-through chamber experiments, 18 g of the sorbent powder spread over a 2 m2 area removed approximately 8% of CO2 injected. By extrapolating these results to real buildings, we estimate that meaningful reductions in the CO2 can be achieved, which may help reduce energy requirements for ventilation and/or improve air quality.

Chemotherapy delivery for resected colorectal cancer liver metastases: Management and outcomes in routine clinical practice.

BACKGROUND: International guidelines recommend peri-operative chemotherapy for patients with resectable colorectal cancer liver metastases (CRCLM). Chemotherapy delivery in routine practice is not well described. METHODS: All cases of CRC who underwent resection of LM in 2002-2009 were identified using the population-based Ontario Cancer Registry. Electronic treatment records identified chemotherapy delivered within 16 weeks before or after hepatectomy. All pathology reports were reviewed to describe extent of LM. Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional hazards model and propensity score analysis were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall (OS) survival. RESULTS: We identified 1310 patients. Sixty-two percent of cases (815/1310) received peri-operative chemotherapy; 25% (200/815) pre-operative, 45% (366/815) post-operative, and 31% (249/815) pre- and post-operative. Utilization of chemotherapy increased over time from 51% in 2002 (57/112) to 73% in 2009 (157/216, p < 0.001). Fifty-four percent of patients received FOLFOX, 41% FOLFIRI, and 10% 5-FU monotherapy. Factors that were independently associated with greater utilization of post-operative chemotherapy included younger age (p < 0.001), female sex (p = 0.050), shorter disease-free interval (p = 0.006), and no prior adjuvant chemotherapy (p < 0.001). Utilization of chemotherapy varied substantially across geographic regions (from 24% to 71%, p = 0.001). Post-operative chemotherapy was associated with improved CSS (HR 0.58, 95%CI 0.44-0.76) and OS (HR 0.49, 95%CI 0.38-0.61); results were consistent in propensity score analysis. CONCLUSION: Utilization of chemotherapy for resected CRCLM in routine practice has evolved with emerging evidence. Post-operative chemotherapy is associated with improved survival in the general population.

Etanercept decreases synovial expression of tumour necrosis factor-α and lymphotoxin-α in rheumatoid arthritis.

OBJECTIVES: Etanercept is an effective tumour necrosis factor (TNF)-α inhibitor drug with the unique ability to block not only TNF-α but also lymphotoxin (LT)-α, at least in vitro. We aimed to investigate the in vivo effect of etanercept on synovial expression of TNF-α and LT-α. METHOD: Synovial biopsies from 12 rheumatoid arthritis (RA) patients started on etanercept and 11 RA patients started on infliximab were obtained at baseline and 8 weeks after treatment initiation. Synovial expression of TNF-α and LT-α was evaluated by immunohistochemistry followed by computer-assisted image analysis. Differences between paired samples were analysed by the Wilcoxon test and between groups by the Mann-Whitney test. A p-value < 0.05 was considered statistically significant. RESULTS: Six out of the 12 of the patients started on etanercept achieved an American College of Rheumatology (ACR)50 response. Macroscopic evaluation of the joints during arthroscopy revealed a significant decrease of local inflammation mainly in good ACR50 responders. Synovial expression of both LT-α and TNF-α decreased but the differences did not reach statistical significance at a group level. By contrast, a significant decrease in both LT-α and TNF-α was observed when only good ACR50 responders were analysed. Despite higher levels of baseline synovial TNF-α in the good responders, neither baseline LT-α nor TNF-α could predict clinical response after 8 weeks. A decreasing trend of the synovial levels of LT-α was also observed in good responders to infliximab, but the difference did not reach statistical significance. CONCLUSIONS: Etanercept treatment modulates the synovial expression of both TNF-α and LT-α in vivo, a mechanism that might partly explain its clinical efficacy in RA.

Incomplete discoid lateral meniscus: a case report.

The variations of lateral meniscus include pathologic entities which vary in size, shape and attachment. In this manuscript, we report a case of discoid lateral meniscus which was observed in an embalmed fetal cadaver. It was an incomplete variety of the discoid meniscus and observed on the right side knee. The clinical implication of this discoid meniscus has been emphasized along with the review of literature. The morphological and embryologic details of the discoid lateral menisci are discussed.

Bilateral arterial variation in the upper extremity--an anatomical case report.

We report a case of bilateral arterial variation in the upper extremities of a male cadaver. In the left upper extremity, it was observed that the ulnar artery was arising from axillary artery. This ulnar artery was superficial throughout its course at the medial aspect of the arm and forearm. It was highly tortuous and did not have any branches either in the arm or forearm. It ended as the superficial palmar arch in the palm. However the brachial artery entered the cubital fossa and divided into radial and common interosseus arteries. In contrast, the right upper extremity was having normal brachial artery which was terminated into the ulnar and radial arteries at the cubital fossa. However, there was an accessory brachial artery present at the arm and ended at the cubital fossa. We believe that these anatomical variations are because of abnormal developmental vascular pattern in the region. In clinical practice, accurate knowledge of the arterial variations of upper extremity is of considerable importance in case of reparative surgeries and fracture management. They are of interest to the vascular and plastic surgeons.

Bone morphometry.

OBJECTIVES: To compare anatomical measurements with that of radiological measurements. BACKGROUND: The radiological measurements are commonly used in clinical practice. It is well known that the anatomical measurements are more accurate than radiological. The comparison of anatomicoradiological measurements is not reported hitherto. METHODS: One human adult cadaveric femur bone was used for the present study. It was measured both anatomically and radiologically. RESULTS: In digital X- ray measurements, the length from the upper lip of fovea capitis to the most prominent part of greater trochanter was 87.2 mms, from the upper most part of greater trochanter to the isthmus it was 147.9 mms, mediolateral width of medullary cavity at the isthmus was 8.9 mms, the mediolateral width at the distal root of lesser trochanter was 18.5 mms, anteroposterior width of medullary cavity at the isthmus was 11.5 mms, the anteroposterior width at the distal root of lesser trochanter was 16.8 mms. The same measurements were 91.2 mms, 154.6 mms, 11.8 mms, 19.7 mms, 11.9 mms and 18.5 mms when taken anatomically using the digital vernier caliper. CONCLUSION: The present study showed that in all the parameters measured the radiological values were slightly lesser than the anatomical values. Considering the variations in the values, the implants can be designed for a particular case in orthopedic surgery. We believe that this study adds an important reference in the scientific literature (Tab. 1, Fig. 2, Ref. 5).

The relevance of "Nonsmoking-associated lung cancer" in India: a single-centre experience.

BACKGROUND: Lung cancer remains a major cause of morbidity and mortality worldwide, accounting for more deaths than any other cancer cause. AIM: The aim of this study was to analyze the clinical profile and the epidemiological trends in lung cancer patients from a single centre with an emphasis on the smoking practices. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data of 258 consecutive hospital in-patients with a proven diagnosis of lung cancer at a tertiary care oncology centre between 2003 and 2007. RESULTS: The median age of patients in our study was 56 years; the male to female ratio was approximately 3.5:1. Non-small-cell lung cancer (NSCLC) was the predominant histology in 224 patients; the histology in the remaining 34 patients was small-cell carcinoma. Within NSCLC, the most common histology was adenocarcinoma followed by squamous cell carcinoma. One hundred and two patients were never-smokers as compared to 156 patients who were ever-smokers. Among the smokers, the majority of them were found to be cigarette smokers compared to 28.2% bidi smokers. There was a very significant correlation found with adenocarcinoma among nonsmokers, and with squamous cell carcinoma among the smokers compared to non-smokers. CONCLUSIONS: Our study suggests that the epidemiology of lung cancer in India is possibly changing, with close to 40% of our lung cancer patients being nonsmokers. More importantly, our study reflects the global trend of rise in adenocarcinoma histology. These observations need to be substantiated in similar studies of larger magnitude, preferably population-based.

Clinically oriented morphometric study of medial and lateral menisci of the knee joint in adult cadavers.

PURPOSE: The objective was to analyze the peripheral and inner border lengths of the medial and lateral menisci and the distance between anterior and posterior horns. MATERIALS AND METHODS: The menisci from 23 adult knee joints (46 menisci) of the formalin fixed cadaver lower limbs were used. The peripheral and inner borer lengths of the menisci were measured with a non elastic cotton thread and the distance between the horns were measured with the vernier caliper of 0.02 mm accuracy. RESULTS: The mean peripheral lengths of the medial and lateral menisci were 99.06 +/- 11.21 and 90.25 +/- 9.36 mm respectively. The inner border lengths for the same were determined as 55.44 +/- 8.37 and 50.63 +/- 5.33 mm respectively. The distances between the anterior and posterior horns were 24.13 +/- 4.19 and 11.31 +/- 3.86 mm for the same. The peripheral length and inter horn distance of the medial meniscus was more than the lateral, the statistically significance was observed (*p<0.05). The other parameters obtained were statistically not significant. CONCLUSION: The present study had determined some important anatomical data which may be of importance to the orthopaedic literature. The findings are also enlightening for the anthropologists and clinical anatomists.

Foramina on the zygomatic bone: its clinical significance.

AIM: To study the anatomy of zygomatico-orbital, zygomatico-facial and zygomatico temporal foramina in south Indian population. MATERIALS AND METHODS: 50 dry adult skulls of south Indian origin were studied. The number of ZO, ZF and ZT were recorded on each side. The distances of these foramina to the nearest palpable bony points, infero-lateral angle of the orbit and infra-orbital foramen were measured using Vernier's calipers. RESULTS: Variable number of ZO and ZF foramina, ranging from 0 to 4 was seen. Single ZO foramen in 56% and 44%, double in 6% and 12%, absent in 38% and 44% on right and left sides were seen. Distance of ZO foramen from inferolateral angle of orbit was 9+2.51 mm and 7.8+1.74 mm on right and left side respectively. The mean distance from infraorbital foramen was 29.93+2.76 mm and 30.19+ 3.52 mm on right and left side respectively. Single ZF foramen in 40% and 42%, double in 10% and 8%, 3 in 4% on right side and 4 in 2% on left sides were seen. In the remaining 46% and 48% of bones, the ZF foramen was absent. Mean distance from inferolateral angle of orbit was 8.05+2.68 and 9.15+2.11 mm respectively on the right and left side. Mean distance from infraorbital foramen was 25.45+4.35 mm and 25.42+4 mm respectively on right and left side. CONCLUSION: The location of ZO and ZF foramen can be population specific and knowledge of its location is important during stabilization of zygomatic fractures, in endoscopic subperiosteal facelift.

Adult soft-tissue sarcomas of the head and neck.

BACKGROUND: Head and neck sarcomas are relatively rare tumors, accounting for only about 2% of all head and neck malignancies and for 4 to 10% of all soft tissue sarcomas. The rarity and more over the heterogeneity of these tumors make rigorous study of their clinical behavior difficult. AIMS: We analyzed our single center experience of adult soft tissue sarcomas of the head and neck. SETTINGS AND DESIGN: Our study included 27 patients of adult soft-tissue sarcomas of the head and neck who presented to our center between January 1996 and December 2005. MATERIALS AND METHODS: Patient characteristics, clinical features, treatment modalities, clinical course, and long-term outcomes and its determinants were analyzed. RESULTS: Surgery in the form of wide excision aimed at achieving negative margins was the main modality of treatment and adjuvant radiation was used in selected patients. The five-year disease-free survival was 64.5% and overall survival (OS) was 68%. Of the multiple potential factors analyzed, univariate analysis showed grade, margin status, and adjuvant radiation to be the important prognostic factors for the survival. The multivariate analysis however only showed margin status and adjuvant radiation to be prognostic. CONCLUSIONS: Surgery with negative margins is a key to long-term survival. Complete resection with adjuvant radiation in selected cases potentially decreases local recurrences and improves OS.

Bilateral anomaly of rectus capitis posterior muscles in the suboccipital triangle and its clinical implication.

Rectus capitis posterior muscles are located in the suboccipital triangle and function in extension and lateral rotation of the head and neck. There are two of these muscles on each side: the rectus capitis posterior major and the rectus capitis posterior minor. In the present case we observed bilateral double rectus capitis posterior major muscle and bilateral absence of rectus capitis posterior minor muscle. The additional rectus capitis posterior major may put more strain to the spine of the axis and mean time the bilateral absence of rectus capitis posterior minor muscles will result in muscular in coordination in the suboccipital region while balancing the head. The present variation should be considered in the aetiology of cervicogenic headache.

Prediction of postoperative pulmonary reserve in lung resection patients.

UNLABELLED: We performed Ventilation/Perfusion scans for patients planned for thoracotomy with resection of the primary or metastatic lung tumors. We predicted the post-operative FEV1 (Forced Expiratory Volume in first second) using Differential Lung Analysis software. METHODS: 34 patients were evaluated with Ventilation/Perfusion (V/Q) scans. Ventilation scan was performed with Tc-99m DTPA Aerosol and Perfusion Scan with Tc99m MAA, on 2 different days. The numbers of counts in anterior and posterior views of V/Q scans were calculated individually. Anterior and posterior arithmetical mean was calculated and post-operative FEV1 was predicted with the use of Differential Lung Analysis software. In most of the patients, the counts in the ventilation scan were lower and they were related to preoperative FEV1. Depending on the volume of lung resection, i.e. Upper, Middle and Lower zones or Total Pneumonectomy, FEV1 was calculated. Whenever FEV1 was >0.8 (L), the patient was taken up for resection (and if there were no other risk factors, such as cardiac complications, chronic obstructive pulmonary diseases, and any other pathological conditions involving the contralateral lung). RESULTS: Most of the 34 patients were taken up for lung resection based on our FEV1 predictions. In 7 patients, repeat spirometry (i.e. pulmonary function test) was done at varying intervals after surgical procedures and the variation between preoperative FEV(1) and postoperative FEV(1) was only ±15%, at the most. CONCLUSION: Postoperative FEV(1) based on V/Q scan and pulmonary function tests helped us to proceed with lung resection after assessment of the pulmonary reserve.

Morphometric analysis of clavicle in nepalese population.

BACKGROUND: Determining the sex of deceased is easy when a complete skeleton is available for examination. On the whole, the bones are heavier, larger and markings of muscular attachments are more pronounced in the male than in the female. OBJECTIVE: The purpose of this study was attempted to evolve an easily applied formula to enable the assessment of sex in an unknown clavicles and to know about comparative differences between the right and left clavicles, from certain metrical parameters. METHODS: The study was an observational, cross-sectional and descriptive in nature. The present study was conducted on 257 adult clavicles out of which, 135 were of the right side and 122 of left side. The maximum length of the clavicle (in mm) was taken. RESULTS: The length of the right clavicles varies from 108 mm to 178 mm with an average of 143.21 mm ± 11.13 mm S.D. The length of the left clavicles varies from 111 mm to 181 mm with an average 145.53 mm ± 11.04 mm S.D. It has been observed that the left clavicle was longer than the right clavicle by 2.32 mm. There was no such single character which can determine the sex of all clavicles. Depending on the length alone, the sex can be decided in 13.33% male and 4.44% female right clavicles and 16.39% male and 9.83% female bones if the left clavicle is considered. CONCLUSION: The left clavicle was longer than the right clavicle. The determination of sex from the clavicle has a great medico legal significance to the toxicologists. It also helps the anthropologists in their study of evolution of mankind and migration of races.