Significant Smoking History Research Articles

A Woman With Treatment-Resistant Hypertension.

Although this is not a particularly unusual or rare case of hypertension, it highlights the challenges we have as clinicians in managing such patients. The patient, a 60 year-old woman, was referred to the tertiary blood pressure clinic at Glasgow’s Western Infirmary 5 years ago by a consultant cardiologist for management of resistant hypertension. This lady has a vasculopathy with ongoing intermittent claudication and had previous bilateral superficial femoral artery occlusions on a background of hypercholesterolemia and a significant smoking history. The patient has problematic underlying ischemic heart disease, having had angina since 2001, numerous percutaneous interventions, and a 2-vessel coronary artery bypass graft. Despite this, she had a non–ST-segment–elevation myocardial infarction (MI) 2 years before presentation. Blood pressure at first visit to the clinic was 182/106 mm Hg despite numerous antihypertensive medications, including an angiotensin-converting enzyme inhibitor, calcium channel blocker, 2 different diuretics, α-blocker, and β-blocker in addition to her antianginal and secondary preventative medications (Table). Review of case notes and previous clinic documentation revealed that clinic blood pressure was elevated for at least 10 years with systolic readings ranging from 150 to 200 and diastolic between 90 and 100 mm Hg. View this table: Table. Total Daily Dose of Antihypertensive Medications: An Overview of Antihypertensive Medication at the Time of Referral to the Clinic (2010), Before RDN (2012) and Immediately After RDN (2012), and in 2015 The patient was admitted to the investigation ward for a week of workup. During this time, routine biochemistry showed normal renal function and electrolytes. Urine albumin/creatinine ratio was within the microalbuminuric range at 4.2 mg/mmol. Cardiac and mediastinal contours seemed normal on chest x-ray, and neither ECG nor echocardiogram showed significant left ventricular hypertrophy (LVH). No biochemical evidence to suggest pheochromocytoma or primary aldosteronism was found. Renal ultrasound exhibited 2 normal sized nonobstructed kidneys with no …

A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma

Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC). Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled. Afatinib alone was given daily for two weeks as lead-in and subsequently given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) every 21days as IC. Afatinib was started at a dose of 20mg daily and dose escalated using a modified Fibonacci design. After completion of IC, afatinib was discontinued and patients received concurrent cisplatin 40mg/m(2) weekly and standard radiation. Toxicity was assessed using CTCAE version 4.0. Seven of nine patients completed afatinib lead-in and IC. Five patients had partial response and two patients had stable disease after IC. Dose level 1 (afatinib 20mg) was well tolerated with one grade 3 (ALT elevation) and one grade 4 (neutropenia) toxicities. However, dose level 2 (afatinib 30mg) was not well tolerated with nine grade 3 (pneumonia, abdominal pain, diarrhea, pancytopenia, and UTI), two grade 4 (sepsis) and one grade 5 (death) toxicities. The MTD of afatinib given with carboplatin AUC 6mg/mlmin and paclitaxel 175mg/m(2) is 20mg daily. Combination of afatinib at doses higher than 20mg with carboplatin and paclitaxel should be administered with caution due to the toxicities.

KRAS-Mutant Lung Cancers in the Era of Targeted Therapy.

KRAS-mutant lung cancers account for approximately 25% of non-small cell lung carcinomas, thus representing an enormous burden of cancer worldwide. KRAS mutations are clear drivers of tumor growth and are characterized by a complex biology involving the interaction between mutant KRAS, various growth factor pathways, and tumor suppressor genes. While KRAS mutations are classically associated with a significant smoking history, they are also identified in a substantial proportion of never-smokers. These mutations are found largely in lung adenocarcinomas with solid growth patterns and tumor-infiltrating lymphocytes. A variety of tools are available for diagnosis including Sanger sequencing, multiplex mutational hotspot profiling, and next-generation sequencing. The prognostic and predictive roles of KRAS status remain controversial. It has become increasingly clear, however, that KRAS mutations drive primary resistance to EGFR tyrosine kinase inhibition. Until recently, mutant KRAS was not thought of as a clinically-targetable driver in lung cancers. With the expansion of our knowledge regarding the biology of KRAS-mutant lung cancers and the role of MEK and PI3K/mTOR inhibition, the face of targeted therapeutics for this genomic subset of patients is slowly beginning to change.

Lung CT Screening Reporting and Data System Speed and Accuracy Are Increased With the Use of a Semiautomated Computer Application

PurposeThe Lung CT Screening Reporting and Data System (Lung-RADS™) is an algorithm that can be used to classify lung nodules in patients with significant smoking histories. It is published in table format but can be implemented as a computer program. The aim of this study was to assess the efficiency and accuracy of the use of a computer program versus the table in categorizing lung nodules. MethodsThe Lung-RADS algorithm was implemented as a computer program. Through the use of a survey tool, respondents were asked to categorize 13 simulated lung nodules using the computer program and the Lung-RADS table as published. Data were gathered regarding time to completion, accuracy of each nodule’s categorization, users’ subjective categorization confidence, and users’ perceived efficiency using each method. ResultsThe use of a computer program to categorize lung nodules resulted in significantly increased interpretation speed (80.8 ± 37.7 vs 156 ± 105 seconds, P < .0001), lung nodule classification accuracy (99.6% vs 76.5%, P < .0001), and perceived confidence and efficiency compared with the use of the table. There were no significant differences in accuracy when comparing thoracic radiologists with the remainder of the group. ConclusionsRadiologists were both more efficient and more accurate in lung nodule categorization when using computerized decision support tools. The authors propose that other institutions use computerized implementations of Lung-RADS in the interests of both efficiency and patient outcomes through proper management. Furthermore, they suggest the ACR design future iterations of the Lung-RADS algorithm with computerized decision support in mind.

Intestinal Ischemia as the Primary Manifestation of Thromboangiitis Obliterans: A Case Report

Case presentation: A 52-year-old female presented with a significant smoking history and unexplained abdominal pain. The patient was admitted on multiple occasions and seen in the gastroenterology clinic, and underwent an extensive work-up. Laboratory data, abdominal x-ray, CT abdomen, transabdominal ultrasound, gastric emptying study, EGD, colonoscopy, and CT angiogram of the abdomen all provided no clear diagnosis. While hospitalized, the patient had an acute abdomen with free air demonstrated on CT, and subsequently underwent an exploratory laparotomy. Histology of the removed ileum displayed multiple small- and medium-sized arteries with marked medial and intimal proliferation with focal medial destruction, focal perivascular and intimal lymphocytic infiltrates and organized and recanalized thrombi. There were also organizing venous and capillary thrombi present in small-, medium-, and largesized vessels of the bowel wall and mesentery. The findings are characteristic for Buerger's disease. The patient did return to the OR on two more occasions for increased bowel ischemia, and once for right below-the-knee amputation during the hospitalization. The patient is currently being followed in the gastroenterology clinic. Literature review: Buerger's disease is a rare entity in a female over the age of forty. In our case, the initial presentation of mesenteric involvement in a female is unique. Currently there are no literature reports of a female over the age of forty having the initial presentation of Buerger's disease as abdominal pain without extremity involvement. This case study contributes to the literature by adding a rare case in a previously unidentified patient demographic. Buerger's disease should be added to the differential in similar cases. This extremely rare condition should be evaluated for young female smokers without atherosclerotic disease. However due to its nature, it is difficult to diagnose before bowel gangrene.Table 1: Diagnostic Criteria for Buerger's DiseaseTable 2: Histology CriteriaFigure 1Figure 2Figure 3

Worse Long-term Patient Survival and Higher Cancer Rates in Liver Transplant Recipients With a History of Smoking.

This study is a retrospective review of liver transplant (LT) recipients to determine the impact of tobacco exposure on 10-year survival and de novo cancer (CA) incidence. The records of 1275 consecutive LT patients were reviewed (2001 to 2011). Patients were categorized as current, previous, or never smokers (NS) at listing for LT. Additionally, smokers were stratified by pack-years of tobacco exposure. Events included patient death, cardiovascular events, and de novo cancers. Cox regression analysis was used to evaluate survival. A complete cause of death analysis is provided, as well as a detailed tumor registry. Current (n = 279) and previous smokers (n = 323) were more likely to have hepatocellular carcinoma (HCC) at transplant (25%, 29% vs 18% [NS], P < 0.001), and these 2 groups had higher HCC recurrence rates (21%, 14% vs 11% [NS], P = 0.18). De novo non-HCC CA was higher for current and previous smokers, compared to NS (18%, 16% vs 12% [NS], P = 0.05). Among those with de novo CA (n = 180), the 2 smoking groups were more likely to have non-skin CA (60%, 54% vs 27% [NS], P < 0.001). Patient survival at 10 years was worse for current smokers than the other study groups (55% vs 70%, P < 0.01). These results were largely mirrored with increased tobacco exposure. The LT outcomes are uniformly worse for patients with a history of smoking, and the risk of negative events increases with increasing tobacco use. Smokers have higher rates of HCC and recurrence, de novo cancer, and worse long-term survival. This study summarizes the clinical outcomes for 1275 LT patients over 10 years, analyzing the impact of pre transplant recipient tobacco use. There are 47% of patients with a history of smoking. Because of demonstrated higher cancer rates and decreased survival, patients with a significant smoking history should be carefully scrutinized for liver transplantation.

Primary Care Provider-Delivered Smoking Cessation Interventions and Smoking Cessation Among Participants in the National Lung Screening Trial.

The National Lung Screening Trial (NLST) found a reduction in lung cancer mortality among participants screened with low-dose computed tomography vs chest radiography. In February 2015, Medicare announced its decision to cover annual lung screening for patients with a significant smoking history. These guidelines promote smoking cessation treatment as an adjunct to screening, but the frequency and effectiveness of clinician-delivered smoking cessation interventions delivered after lung screening are unknown. To determine the association between the reported clinician-delivered 5As (ask, advise, assess, assist [talk about quitting or recommend stop-smoking medications or recommend counseling], and arrange follow-up) after lung screening and smoking behavior changes. A matched case-control study (cases were quitters and controls were continued smokers) of 3336 NLST participants who were smokers at enrollment examined participants' rates and patterns of 5A delivery after a lung screen and reported smoking cessation behaviors. Prevalence of the clinician-delivered 5As and associated smoking cessation after lung screening. Delivery of the 5As 1 year after screening were as follows: ask, 77.2%; advise, 75.6%; assess, 63.4%; assist, 56.4%; and arrange follow-up, 10.4%. Receipt of ask, advise, and assess was not significantly associated with quitting in multivariate models that adjusted for sociodemographic characteristics, medical history, screening results, nicotine dependence, and motivation to quit. Assist was associated with a 40% increase in the odds of quitting (odds ratio, 1.40; 95% CI, 1.21-1.63), and arrange was associated with a 46% increase in the odds of quitting (odds ratio, 1.46; 95% CI, 1.19-1.79). Assist and arrange follow-up delivered by primary care providers to smokers who were participating in the NLST were associated with increased quitting; less intensive interventions (ask, advise, and assess) were not. However, rates of assist and arrange follow-up were relatively low. Our findings confirm the need for and benefit of clinicians taking more active intervention steps in helping patients who undergo screening to quit smoking.

Rheumatoid arthritis-associated interstitial lung disease

Rheumatoid-associated interstitial lung disease (RA-ILD) is an important extra-articular manifestation of rheumatoid arthritis (RA), contributing to significant morbidity and mortality. Mortality is increased by 3-folds in RA-ILD patients in contrast with those without ILD. RA-ILD is frequently observed in males, and the risk of developing ILD is associated with older age at time of RA onset, male gender, and greater RA disease severity. Usual interstitial pneumonia (UIP) being the most common, with the worst prognosis. RA-ILD patients with UIP pattern tend to be older, more likely to be males, and have a more significant smoking history and worse survival. In contrast, those without the UIP pattern tend to be younger, more likely to be women, and have a less significant smoking history. This review discusses the diagnosis and therapeutic option in the management of RA-ILD.

Integration of lung cancer screening into practice is lacking.

Integration of lung cancer screening into practice is lacking.

Combined Intrathoracic and Subcutaneous Splenosis Discovered 51 Years after Abdominal Trauma.

Splenosis is a rare condition that results from the autotransplantation of splenic parenchyma into unexpected locations such as the abdomen or subcutaneous tissue. In the presence of coexisting injury to the diaphragm intrathoracic transplantation can occur emerging as single or multiple pleural-based masses. This occurs after traumatic rupture of the spleen and is usually asymptomatic, only to be discovered incidentally on routine thoracic or abdominal imaging. To our knowledge this is the third documented case of combined intrathoracic and subcutaneous splenosis found in English literature. This occurred in a 71-year-old male involved in a motor vehicle accident at age 19 requiring urgent splenectomy. He has a significant cigarette smoking history and was referred to our hospital for further evaluation of an abnormality seen on shoulder X-ray.

Higher Levels of Circulating Fibrocytes Are Associated with Lower Oxygen Saturation in Adults with Sickle Cell Disease

Background: In patients with sickle cell disease (SCD), tissue injury due to vaso-occlusion can result in fibrosis and organ dysfunction. Fibrocytes are circulating bone marrow-derived cells that can home to damaged organs, differentiate into fibroblasts and myofibroblasts and contribute to scarring. Fibrocytes have been implicated in the pathogenesis of pulmonary fibrosis in several animal models, including a mouse model of SCD. A preliminary study of patients with SCD suggests that the concentration of circulating fibrocytes is increased compared to controls. To build upon these findings, we tested the hypothesis that in adults with SCD higher levels of fibrocytes are associated with measures of lung disease.Methods: In a prospective cohort study of steady state adults with SCD, peripheral blood fibrocytes were measured and subjects underwent a pulmonary assessment that included pulmonary function tests, resting pulse oximetry, a 6-minute walk test, 2-D echocardiography, and high-resolution chest CT. A control group of healthy, African Americans also provided fibrocyte measurements and had pulmonary function testing. Fibrocytes were identified as collagen-1+ CD45+ cells using quantitative flow cytometry. For statistical analyses, fibrocyte values were log-transformed. Continuous and dichotomous variables were tested with Pearson’s correlation and Mann-Whitney U, respectively.Results: The cohort was comprised of 47 adults with SCD and 19 healthy African American controls. Sixty percent of the SCD subjects were HbSS or HbS-β-thalassemia0. Mean age (SD) of SCD cases was 35 years (±11) and 70% were female. Twenty-seven percent of SCD cases had asthma and 41% had a significant smoking history. Sixty-four percent of SCD cases had ground glass opacities on CT of the lung, 34% had bronchiectasis and 20% had evidence of pulmonary fibrosis. Compared to controls, patients with SCD had lower forced expiratory volume in 1 second (p<0.001), forced vital capacity (p<0.001), and pre- and post-bronchodilator 25-75% forced expiratory flow (FEF25-75%) (p=0.006). Fibrocyte levels also trended higher in patients with SCD compared to controls (median 1.2 x 106 vs. 8.5 x 105, p=0.07). Within patients with SCD, most fibrocytes expressed the chemokine receptor CXCR4 and smaller subsets expressed CCR2 or CCR7. Increased levels of fibrocytes in patients with SCD were associated with lower oxygen saturation (p=0.01) and higher reticulocyte counts (p=0.01). Lower oxygen saturation and higher reticulocyte counts were also associated with each other, independent of fibrocytes (p=0.007). Fibrocytes expressing CXCR4, a chemokine that mediates homing to the lungs, were associated with lower post-bronchodilator FEF25-75% (p=0.04). There was no association between fibrocyte levels and other measures of pulmonary function testing, degree of fibrosis on high-resolution CT, or abnormalities on 2-D echocardiogram or 6-minute walk.Conclusion: In adults with SCD, higher fibrocyte levels were associated with lower resting oxygen saturation and FEF25-75%, a measure of lung obstruction. Significant lung pathology was observed in a high percentage of SCD patients. The associations between fibrocyte levels, hypoxia and a measure of pulmonary dysfunction suggest that fibrocytes contribute to this lung disease. Higher reticulocyte counts in patients with increased fibrocytes may be due to the association of both reticulocyte count and fibrocyte level with hypoxia. Ongoing longitudinal studies may better define the relationship between fibrocytes and evolving lung disease. If additional evidence is found in these longitudinal studies, fibrocytes could be a therapeutic target to prevent chronic pulmonary disease in adults with SCD. DisclosuresField:NKTT: Consultancy, Research Funding. Strieter:Novartis: Employment.

Correlation of Clinical and Dosimetric Parameters With Radiographic Lung Injury Following Stereotactic Body Radiotherapy

Radiographic changes occur in over half of patients treated with stereotactic body radiotherapy (SBRT) to the lung, correlating histopathologically with injury. We quantified radiographic density changes (ie, fibrosis) at 3, 6, and 12 months and investigated the relationship between these volumes and clinical and dosimetric parameters. The study population consisted of patients treated with SBRT to the lung for stage I primary lung cancers (n = 39) or oligometastatic lesions (n = 17). Fractionation schemes included 3 fractions of 12, 14, or 18 gray (Gy) and 4 fractions of 12 or 12.5 Gy prescribed to cover 95% of the planning target volume (PTV). Planning computed tomography (CT) scans were rigidly registered to follow-up CT scans obtained at intervals of 3, 6, and 12 months. Fibrotic volumes were contoured on the follow-up scans. Associations between the volume of fibrosis and clinical and dosimetric parameters were investigated using univariate linear regression. Scans were available for 65 and 47 lesions at 6 and 12 months, respectively. Age, years since quitting smoking, and GOLD Global Initiative for Chronic Obstructive Lung Disease score were significantly associated with increasing volume of fibrosis (P < .05). Total dose, dose per fraction, PTV, and volumetric parameters (V0-V55) were also significantly associated with increasing volumes of fibrosis (P < .01). For dosimetric parameters, the effect was largest for V55. Age, significant smoking history, and GOLD score were significantly associated with increasing volumes of fibrosis following SBRT. In a multivariate model adjusted for age and smoking history, V10 through V50 and PTV size remained significant predictors of fibrotic volume. Further, there is a strong dose-response relationship between the volume of lung exposed to a certain dose and the fibrotic volume. The predominant kinetic patterns of fibrosis demonstrate peaking fibrotic volumes at 6 and 12 months. These results provide insight for expectations of fibrosis after SBRT.

Lung Donor Availability and Implications For Pediatric Candidates Aged 9-11 Years.

Lungs are allocated differently to pediatric candidates aged 0-11 and >12 years in the US. In 2013, US policy was modified to allow a pathway to increased access to lungs from older donors for candidates aged 0-11. However, size considerations limit the number of donors suitable for young candidates. We aimed to estimate the proportion of potential lung donors to which candidates aged 9-11 (i.e., those closest to the age 12 cutoff) could gain increased access. We determined the acceptable donor height range for candidates aged 9-11 by examining current height restrictions for candidates listed 2008-2012, and considered donors with height 105-165 cm potentially acceptable. We excluded potential donors with positive hepatitis B or C status or significant smoking history (>20 pack-years), current smokers, and CDC high-risk donors. We limited potential donors to those for whom at least one lung match run was performed (not necessarily resulting in a transplant); if a match run is not performed, the organ cannot be made available to any candidate. Candidates aged 9-11 are given first priority for offers from donors aged <12 and can access offers from donors aged >12 only after they have been turned down by candidates aged >12. By affording candidates aged 9-11 earlier access to donors aged ≥12, the number of potential donors approximately doubles by including all donors age <18 and nearly doubles again by including all donors age <25 (Table 1).Table 1: Estimates of Donor Availability for Pediatric Candidates Aged 9-11 YearsThis analysis demonstrates the potential increase in the overall donor pool for pediatric transplant candidates aged 9-11 if the allocation algorithm eliminates the 12-year age restriction on donor distribution. However, we recognize that not all donors will be suitable for any specific candidate.

English

The epidemiologic evidence linking COPD and cardiovascular morbidity and mortality is strong. Even after adjustments for traditional cardiovascular risk factors such as serum total cholesterol hypertension, obesity and smoking, patients with COPD have a two- to threefold increase in the risk of cardiovascular events including death. Age >60 yrs., Male sex, Significant Smoking History, T2 Diabetes Mellitus, Body Mass Index >30 Kg/M2, Left Ventricular Hypertrophy have a statistically significant correlation to cardiovascular mortality & morbidity. Significant relations were demonstrated between the treatment that patient requires for stability & cardiovascular morbidity & mortality in Central India.

Does Phosphodiesterase Inhibition Lessen Facial Flap Necrosis in Tobacco Cigarette Users?

Tobacco cigarette smoking remains a serious risk factor for necrosis of local facial skin flaps. To date, no pharmacological therapies exist for cigarette smoke-induced impairment of skin flap tissue survival. Accumulating evidence suggest that phosphodiesterase-5 (PDE-5) inhibitor therapy may counteract the negative effects of cigarette smoke on flap survival. Here, we evaluate skin flap survival in a series of consecutive tobacco cigarette users treated with the PDE-5 inhibitor, sildenafil, who underwent local flap facial reconstruction. We included 11 patients (5 females; median age: 64) with a significant smoking history. Seventeen facial flaps were performed for 14 defects. All patients received sildenafil in the postoperative setting. One complication of necrosis of the flap distal margin was encountered. Follow-up was available for all patients. Our results demonstrate that facial reconstruction in tobacco cigarette smokers can be performed with improved success and that sildenafil therapy may mitigate the deleterious effects of smoking on flap survival.

Influence of smoking history on imaging characteristics among patients with human papillomavirus-positive oropharyngeal cancer: a blinded matched-pair analysis.

Human papillomavirus (HPV)-positive oropharyngeal cancers represent a distinct clinical entity with more favorable prognosis than do HPV-negative oropharyngeal cancers. However, among patients with HPV-positive oropharyngeal carcinomas, those with a significant smoking history have a much worse prognosis. Recently, imaging characteristics of oropharyngeal cancers were identified as markers of poor prognosis. The purpose of this study was to determine whether nodal imaging characteristics differ between smokers and never/light smokers with HPV-positive oropharyngeal cancer. A review of 130 pretreatment computed tomographic examinations of HPV-positive oropharyngeal cancers in smokers (>10 pack-years) and never/light smokers (10 pack-years) matched for T stage and tumor subsite was performed, with the reviewing radiologist blinded to the HPV status, smoking history, and clinical stage. Additionally 24 pretreatment computed tomographic examinations of patients with HPV-negative oropharyngeal cancers were also reviewed in a blinded fashion. Imaging characteristics of metastatic nodal disease were compared using the testing (Fisher exact testing where appropriate) and McNemar testing for the matched-pair analysis. As expected, those with HPV-positive oropharyngeal cancer were more likely to be younger, male, non-Hispanic white, never/former smokers, and never drinkers than were those with HPV-negative oropharyngeal cancer. Furthermore, the HPV-positive oropharyngeal cancers were more likely to be in the tonsil, smaller T category, higher N category, poorly differentiated, than were the HPV-negative oropharyngeal cancers. However, among the HPV-positive oropharyngeal cancers, we could identify no obvious difference in the pretreatment imaging characteristics of paired smokers and never/light smokers. Among the patients with HPV-positive oropharyngeal cancer, no imaging characteristics were identified to correlate with the critical prognostic feature smoking status. Cystic and necrotic nodal metastases, as described previously, were more common among the patients with HPV-positive than those with HPV-negative oropharyngeal cancers. Although cystic nodal metastases were more common among the never/light smokers with HPV-positive oropharyngeal cancer than among smokers with HPV-positive oropharyngeal cancer, however, because these results did not reach statistical significance, we concluded that the imaging results cannot serve as a surrogate for an HPV-driven phenotype.

THE EFFECT OF SMOKING ON ANASTOMOTIC STRICTURE RATES FOLLOWING OESOPHAGECTOMY

IntroductionAnastomotic stricture following oesophagectomy causes a significant morbidity and often necessitates repeated dilation or even revision surgery. Smoking has been identified as a cause of microvascular disease associated with ischaemia.Aims/BackgroundPreviously...

Abstract 4785: A pilot study of the association and prevalence of the human papillomavirus (HPV) in non-small cell lung cancer (NSCLC).

Abstract Introduction: Given its potent oncogenic properties, the prevalence of HPV, and the proximity of the bronchial epithelia to the oral cavity we hypothesized that HPV infection may have a role in the causality of NSCLC in patients without a significant smoking history. In Asia, studies report rates of HPV infection in NSCLC tumors as high as 80%. The expression of p16 in head and neck cancer is a reliable surrogate for HPV, and its presence portends a good prognosis. The goal of our study was to analyze archival lung tissue for the presence of p16 expression and HPV infection among never smokers or &amp;lt; 10 pack year smoking patients with NSCLC. Methods: Surgical specimens from never/light smokers was identified in the Fox Chase Cancer Center Biosample Repository. A tissue microarray was constructed for immunohistochemistry analysis on the quantitative platform, AQUA, for p16. DNA was also extracted from archival tissue for assessment of p16 status. Real-time PCR and reverse hybridization (INNO-LiPA) was utilized to detect evidence of HPV genes in tumor samples. In order to determine if the viral genome was episomal or integrated, PCR to determine E2:E6 ratios were employed. The association of p16 expression and HPV infection was assessed. Study results: Available tissue included 36 NSCLC surgical specimens from never/light smokers (1995-2009). Patient characteristics were: 28 female, age range: 47-84, Histology: adenocarcinoma (31, 86%), adenosquamous (3, 8%), and squamous (2, 6%). TNM Stage: T1 (5, 14%), T2 (27, 75%), T3 (1, 3%), T4 (1, 3%), N0 (18, 50%), N1 (8, 22%), N2 (8, 22%), N3 (1, 3%), M1 (2, 5.5%). The p16 AQUA score range: 91-7733. A natural cut point occurred at 3000 with 25 low (p16-) and 8 high (p16+) expressers. AQUA score correlated with standard IHC H score (p=0.0005). There was no significant relationship between p16 level and gender, T or N stage. p16+ was associated with a trend towards inferior survival (HR 2.18, p=0.157). Evidence of HPV 16 and 18 viral DNA, as measured by real-time PCR and reverse hybridization (INNO-LiPA) was detected in 4 samples; 16 (2, 5.5%), 18 (2, 5.5%). Additional high risk oncogenic HPV viruses which were also detected included HPV 35, 52 and 53. Based on the calculation of HPV 16 E2:E6 ratios, both specimens (1 male, 1 female) with evidence of HPV16 infection also had evidence of genome integration of HPV16 DNA. There was no association between HPV infection and p16 expression. Conclusions: In our series of NSCLC among never or light smokers, the rate of HPV 16 viral infection and integration was 5.5%. Notably, all HPV 16 infected tumors had integrated genomes; a novel finding among NSCLC tumors in the Western population. In our small series, p16+ status was not associated with HPV infection. Future study of the potential role of HPV in the pathogenesis of NSCLC warrants exploration, including an assessment of genomic integration of additional strains of high risk HPV DNA. Citation Format: Ranee Mehra, Brian Egleston, Donghua Yang, Walter Scott, Hossein Borghaei, Camille Ragin. A pilot study of the association and prevalence of the human papillomavirus (HPV) in non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4785. doi:10.1158/1538-7445.AM2013-4785

Can lungs be taken for transplantation from donors with a significant smoking history?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Can lungs be taken for transplantation from donors with a significant smoking history?’. Five papers were found using the reported search that represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. These studies compared the outcome and survival between patients who receive lungs from smokers with those receiving non-smoker lungs. None of these studies were randomized controlled trials. They retrospectively analysed a cohort of patients undergoing lung transplantation for the past 10 years. These studies showed worse outcomes in the early postoperative period, such as longer intensive care unit stay, longer ventilation time and higher early postoperative mortality, with lungs harvested from smokers. Two studies also demonstrated a worse long-term outcome in recipients of lungs from smokers, whereas the other two showed worse results during the early postoperative period only. These latter two studies reported similar survival rates after 3 months and up to 3 years in recipients receiving smoker vs non-smoker lungs. One study, however, showed a better 5-year survival with smoker lungs compared with non-smokers, although in this study, lungs from heavy smokers showed the worse outcome. Despite the difference in long-term results and outcome reported by these authors, all of these studies unanimously indicate that lungs from smokers should not be rejected, as survival in these patients receiving smoker lungs is still significantly higher in 3 and 5 years compared with that in those who remain on the transplant waiting list. In conclusion, the current evidence in the literature suggests that lungs from smokers can be used for transplantation. Patients should, however, be fully informed of the risks involved with these lungs and the worse outcome compared with those receiving non-smoker lungs.

Pelvic Mass 21 Years after Total Hip Arthroplasty

Background. Long-term urologic complications after total hip arthroplasty are rare, and reports in the urologic literature are scant. We present a recent case and review the relevant literature. Case. A 77-year-old man was referred to the urology clinic for a single episode of gross painless hematuria, abnormal urine cytology, and pelvic mass. He had a significant smoking history. Surgical history included right total hip arthroplasty 21 years prior. Results. Pelvic ultrasound revealed a large mass abutting the right bladder wall. Subsequent computed tomography indicated that the mass was extrinsic to the bladder. Results of computed tomography-guided biopsy of the mass were consistent with foreign body granuloma. Surveillance imaging confirmed no growth or progression, and intervention was deferred. Conclusion. Long-term complications of total hip arthroplasty may present with signs and symptoms of urologic disease. Reports in the urologic literature are rare.