History Of Heavy Smoking Research Articles

The Effect of Anesthetic Technique on Cardiac Troponin-T and Systemic Inflammatory Response after Major Abdominal Cancer Surgery

Objectives: this study aims at assessment of acute inflammatory response; measured by high sensitivity C-reactive protein (hs-CRP), and myocardial injury; measured by serum cardiac troponin-T (Tn-T) in patients undergoing elective major abdominal cancer surgery with general anaesthesia or combined general and lumbar epidural anesthesia. Methods: The study included 60 ischemic patients undergoing elective major abdominal cancer surgery with risk factor(s) like(history of myocardial infraction, diabetes, hypertension, obesity or heavy smoking)randomly assigned into 2 groups; 30 patients each to receive general anesthesia (G1) or combined general and epidural anesthesia (G2). Pain severity, time to first request of rescue analgesic, analgesic consumption, hemodynamics and side effects were recorded in first 72 hrs postoperative. Serum Tn-T and hs-CRP, ECG were assessed peroperatively and 1,2,3 days postoperativly also 12-lead ECGs were recorded before and 1,2,3 days after surgery. Results: The mean VAS scores were significantly reduced in G2 allover time in comparison to G1 (p 0.03ng/ml. Regarding ECGs changes there were 2 patients (6.6%) in G1 and one patient (3.3%) in G2 showed new ischemic changes postoperatively in the form of depressed ST segment >1mm. Conclusion: The use of LEA with general anesthesia in high risk patients with ischemic heart disease undergoing major non-cardiac surgery is associated with less perioperative acute inflammatory response, less post-operative pain and can reduce the perioperative myocardial damage.

Cerebral Phaeohyphomycosis in a Patient with Neurosarcoidosis on Chronic Steroid Therapy Secondary to Recreational Marijuana Usage

Cerebral phaeohyphomycosis is often a fatal disease that typically takes a hematogenous spread after inhalation or accidental skin inoculation of pathogens. We present a patient with a history of heavy marijuana smoking while being on chronic steroid therapy for treatment of neurosarcoidosis who was found to have multiple brain abscesses from Curvularia sp. This is a ubiquitous soil-dwelling dematiaceous fungus that is generally thought to affect solely plants, but there is increasing evidence in the literature of it affecting humans and animals. We review the radiographic findings of neurosarcoidosis and cerebral phaeohyphomycosis as well as the pathophysiology of dematiaceous fungi infections.

Impact of smoking cessation on the risk of subarachnoid haemorrhage: a nationwide multicentre case control study

Background and purposeSubarachnoid haemorrhage (SAH) is the most devastating cerebrovascular disease. Cigarette smoking is one of the established risk factors for SAH, but the risk of SAH has not been...

MiRNAs expression profiling to distinguish lung squamous-cell carcinoma from adenocarcinoma subtypes

We investigated whether miRNA expression profiles can distinguish and predict outcome of non-small-cell lung carcinoma (NSCLC) patients with different histological subtypes. High-throughput microarray was used to measure miRNA expression levels in six NSCLC samples. Subsequently, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify findings in an independent set of 54 squamous-cell lung carcinomas (SCC), 51 lung adenocarcinomas (AD), and paired adjacent non-neoplastic lung tissue. We showed that, compared to adjacent non-neoplastic lung tissues, the expressions of miR-125a-5p and let-7e were decreased in AD and SCC samples, while increased expressions of miR-93, miR-205, and miR-221 were observed in SCC samples. In addition, miR-205 expression was significantly higher in SCC patients with lymph node metastasis. Lower let-7e expression was associated with lymph node metastasis, >3 cm tumor size, and differentiation of the NSCLC AD subtype. High levels of miR-100 expression also correlated with the AD subtype in current smokers. Moreover, induction of miR-93 and miR-205 expressions and reduction of let-7e were strongly associated with shorter overall survival in SCC patients, whereas AD patient survival was only associated with reduced let-7e. We identified differential expression profiles of miRNAs in AD and SCC. More importantly, in addition to morphology and immunocytochemistry approaches, we report that miR-93, miR-205, miR-221, and let-7e may represent novel biomarkers for differential diagnosis and prognosis of certain NSCLC subtypes or be new targets of histology-specific treatments. Furthermore, our results suggest a strong correlation between high expression of miR-100 and AD patients with history of heavy smoking.

Concordance of driver mutations in primary and matched metastasis from patients with non-small cell lung cancer (NSCLC) using next-generation sequencing (NGS).

7529 Background: Progress in treating NSCLC continues to be limited by high recurrence rates after definitive treatment of localized disease and frequent presentation with metastatic disease. In these pts, diagnostic samples are often limited in size and may be inadequate for genotyping necessary in this disease. In applying genomic profiling to aid treatment planning for patients with metastatic NSCLC, it is critical to determine whether archived primary tumor adequately reflects the genomic spectrum of the patient’s metastatic disease or whether biopsy of a metastatic site is required. We undertook this study using NGS technology to characterize paired primary-metastatic biopsy genomic profiles. Methods: Primary and matched metastatic tumor pairs plus adjacent normal tissue from 15 pts with NSCLC (adenocarcinoma 9/squamous 4/large cell 2) and heavy smoking history were analyzed using a targeted NGS assay in a CLIA laboratory (Foundation Medicine). Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 778X with 99% of bases covered >100X. Results: Among the 30 tumors, 373 somatic alterations were identified; 96 were known NSCLC drivers including: TP53 (14 pts), KRAS (4 pts), SOX2 (4 pts), STK11 (2 pts), CDKN2A (2 pts) and SMARCA4 (2 pts) in full agreement with their respective histological type. In all cases (15/15), primary and metastatic tumors from the same patient demonstrated 90% driver mutation concordance (74/82, 95 % CI, 82-95%). For other mutations, the majority of which are likely passengers, the 69% (201/291) concordance rate was significantly lower (p< .001).The total number of alterations between primaries (190) and metastases (183) was remarkably similar. Conclusions: These results suggest that genomic profiles of primary tumor can identify the key somatic alterations present in matched NSCLC metastases and therefore is a suitable specimen for clinical decision making in the majority of cases. Our data does not support the routine need for a new biopsy upon recurrence since variability in mutational status is low.

ALK and MET genes in advanced lung adenocarcinomas: The Lung Cancer Mutation Consortium experience.

7589 Background: The Lung Cancer Mutation Consortium (LCMC) consisting of 14 US Cancer Centers was established to evaluate a panel of molecular mutations in advanced lung adenocarcinoma. ALK gene fusions and MET gene amplification were assessed by FISH in CLIA certified laboratories. Methods: Molecular tests were performed in stage IIIB or IV lung adenocarcinoma. To date, FISH assays have been completed in 901 patients for ALK (ALK break-apart, Abbott Molecular) and in 654 patients for MET (in house/Abbott Molecular reagents). ALK+ specimens were defined by split 3’ALK/5’ALK signals (gap >2 signal diameters) or single 3’ALK signals in >15% of tumor cells. MET gene amplification (MET+) was defined by ratio mean MET/mean CEP7 ≥2. Results: The ALK+ patient subset (N=75, 8.3%) compared to the ALK- had significantly lower age at diagnosis (52 vs. 60, p<0.001) and less frequent heavy smoking history (61% never-smokers among ALK+ vs. 31% among ALK-, p<0.001; pack-year for current/former smokers 17 vs. 40, p=0.003). Liver metastases were significantly more frequent among ALK+ than ALK- (23% vs.10%, p=0.004); no difference was detected in bone, brain and adrenal gland metastases. MET+ (N=29, 4.4%) was significantly associated with female sex (72% female among MET+ vs. 39% among MET-, p<0.001) and marginally more frequent in patients with adrenal metastasis; no difference was detected for age at diagnosis and smoking history. Follow-up on 73 ALK+ patients indicated that 56% received crizotinib as targeted therapy. Response was unknown in 8% and unreportable in 22% patients enrolled in ongoing randomized trials. Among patients with evaluable response, complete response, partial response, stable disease, and progressive disease were found respectively in 3%, 66%, 28%, and 3%. Conclusions: The LCMC successfully tested ALK and MET FISH in a large number of lung adenocarcinomas. It was demonstrated that directing positive patients to specific interventions is feasible, and that grouping of testing and trials within consortia may maximise relevant trial accrual in rare molecular subtypes. Supported by NCI-GO award. Submitted on behalf of the LCMC.

Influence of Cigarette Smoking on Survival and Tumor Invasiveness in Clinical Stage IA Lung Adenocarcinoma

The objective of this study was to investigate the association between cigarette smoking, cancer survival, and pathological features of clinical stage IA lung adenocarcinoma. Between August 1992 and December 2007, 1,070 consecutive patients with clinical stage IA lung adenocarcinoma underwent complete resection with systematic lymph node dissection. Univariate analysis by log-rank tests was performed to determine unfavorable prognostic factors, and the Cox proportional hazards regression model was used to identify the potential independent predictors. The overall 5-year survival rate of patients with greater than 20 pack-years (PY>20) was 71%, significantly lower than patients with 20 or less pack-years (PY≤20; 86%; p<0.001). Postoperative pathological prognostic factors, including moderate or poor histologic differentiation, lymphatic permeation, intratumoral vascular invasion, visceral pleural invasion, and lymph node metastasis, were detected more often in patients with greater than 20 PY. Sixty-five percent of the patients in this study had pathological stage IA tumors, and their overall 5-year survival rates with 20 or less PY and greater than 20 PY were 97% and 86%, respectively (p<0.001). In patients with clinical stage IA adenocarcinoma, a history of heavy smoking was associated with poor outcomes and was a statistically significant predictor of histologic tumor invasion.

The challenge of breathlessness in the detection of pulmonary hypertension

Acute or chronic shortness of breath (dyspnoea) is a common reason for patients to consult their primary care physicians. However, appropriate diagnosis and deciding whether or when to refer the patient to specialist care can be a challenge. Dyspnoea has been defined as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity” [1]; however, patients may use a variety of descriptions for their symptoms, such as “my chest feels tight” or “I cannot get enough air” [2]. A patient's perception of their symptoms will also vary depending on their context, such as whether they occur on physical exertion or at rest, and on whether symptoms have come on acutely or developed gradually over time. Individuals with chronic dyspnoea are often limited in their activities, with resulting impairment in physical functioning and quality of life [1]. Dyspnoea can be a symptom of a variety of underlying conditions. These include cardiac conditions (such as myocardial infarction, arrhythmias or valvular disease), pulmonary conditions (such as asthma, chronic obstructive pulmonary disease (COPD), pneumonia, pulmonary embolism or lung malignancy), or a range of other causes (such as panic attacks, thyroid disease, anaemia or obesity) [1–3]. In many cases, dyspnoea may be due to multifactorial causes [4]. For some patients, the probable cause of dyspnoea may be obvious, such as exacerbation of known asthma, COPD or heart failure, but for others, particularly younger previously healthy individuals, a thorough diagnostic evaluation to establish the underlying cause is required. A full clinical history and physical examination provide the first clues to the diagnosis of dyspnoea. For example, intermittent breathlessness with triggering factors may suggest asthma, while a history of heavy tobacco smoking and a productive cough may suggest COPD …

Migrating Tumor

Migrating Tumor

Gefitinib for a Poor Performance Status Patient with Squamous Cell Carcinoma of the Lung Harboring &lt;i&gt;EGFR&lt;/i&gt; Mutation

Recent reports have shown gefitinib, epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) induced marked improvement in ECOG performance status (PS) as first-line therapy in EGFR mutation-positive patients with extremely poor PS. EGFR mutations frequently occur in east-Asian, female, non-smoking, adenocarcinoma patients, however they are occasionally detected in patients with non-adenocarcinomas or with a heavy smoking history. We describe a case in which EGFR mutation was detected in a male, current smoker, squamous cell carcinoma (SCC) patient with PS 4, who showed a marked response to the first-line gefitinib therapy. EGFR mutational analysis is recommended even for SCC patients especially in east-Asian populations.

Diagnosis of pulmonary thromboemboli by tongue examination: an example for integration of Traditional Chinese Medicine and modern medicine

Phlegm in traditional Chinese medicine (TCM) is a sign for various problems caused by disturbance in fluid metabolism. We describe an example of using TCM concepts in combination with modern medicine investigations to diagnose pulmonary thrombo-emboli. A 71-year-old man with previous history of chronic obstructive pulmonary disease, heavy smoking and thrombosis in left leg vessels presented with signs and symptoms of lung infection. He was initially considered to be treated for pneumonia. Despite anticoagulant therapy his INR (international normalized ratio) was lower than expected. In addition on tongue examination we found a sign in TCM: dark reddish purple tongue with a thick greasy coat. Based on this clue we suspected that “blood stasis” could be the probable underlying cause for this condition. This primary diagnosis was confirmed by investigations including computed tomography-scan and doppler ultrasound. This sign helped us to think that thrombosis could be the possible cause for changes of tongue.

Selective Epithelial Ischemia of Transferred Free Jejunum After Late Loss of Its Vascular Pedicle

Free flaps are considered to revascularize from the surrounding tissue and survive without their original pedicle flow after a certain period postoperatively. We report 2 patients who developed mucosal ischemia of the transferred jejunum by ligation of its vascular pedicle 10 and 25 months after microvascular free jejunal transfer. Both patients had a history of heavy smoking, and had undergone definitive radiotherapy and previous surgery to the recipient bed. Both were treated conservatively; however, a stenotic change of the transferred jejunum remained in 1 patient. If poorly revascularized flaps, such as jejunal flaps, were transferred to the irradiated and scarred recipient bed, revascularization might never reach completion. If pedicle division is required in such cases, reanastomosis of the pedicle would be ideal regardless of the time after the transfer.

Árangur lungnasmækkunaraðgerða við langvinnri lungnaþembu á Íslandi

Lung volume reduction surgery (LVRS) can benefit patients with severe emphysema. The aim of this study was to evaluate the outcome of LVRS performed in Iceland. A prospective study of 16 consecutive patients who underwent bilateral LVRS through median sternotomy between January 1996 and December 2008. All patients had disabling dyspnea, lung hyperinflation, and emphysema with upper lobe predominance. Preoperatively all patients underwent pulmonary rehabilitation. Spirometry, lung volumes, arterial blood gases and exercise capacity were measured before and after surgery. Mean follow-up time was 8.7 years. Mean age was 59.2 ± 5.9 years. All patients had a history of heavy smoking. There was no perioperative mortality and survival was 100%, 93%, and 63% at 1, 5, and 10 years, respectively. The forced expiratory volume in 1 second (FEV1) and the forced vital capacity (FVC) improved significantly after surgery by 35% (p<0.001) and 14% (p<0.05), respectively. The total lung capacity, residual volume and partial pressure of CO2 also showed statistically significant improvements but exercise capacity, O2 consumption and diffusing capacity of the lung for CO did not change. Prolonged air leak (≥ 7 days) was the most common complication (n=7). Five patients required reoperation, most commonly for sternal dehiscence (n=4). In this small prospective study, FEV1 and FVC increased and lung volumes and PaCO2 improved after LVRS. Long term survival was satisfactory although complications such as reoperations for sternal dehiscence were common and hospital stay therefore often prolonged.

The Impact of Heavy Smoking on Anastomotic Leakage and Stricture After Low Anterior Resection in Rectal Cancer Patients

Anastomotic complications after low anterior resection are associated with perianastomotic ischemia. Smoking is one of the main causes of microvascular disease that is correlated with tissue ischemia. The purpose of the present study was to assess the impact of smoking on anastomotic complications after low anterior resection in rectal cancer patients. Between January 2005 and December 2008, 412 patients underwent low anterior resection for rectal cancers by a single surgeon at Seoul National University Hospital. Excluded from this series were 197 patients with postoperative radiation therapy, cancers that were located above 10 cm from the anal verge, or lack of medical records, and the remaining 215 patients were included for analysis. Significant variables in the univariate analysis were subsequently subject to multivariate analysis for identification of risk factors for complications. The rate of anastomotic complications was 10.7% (23 of 215 patients). Univariate analysis showed that male gender, body mass index higher than 25 kg/m(2), smoking history, smoking amount, type of operation, and presence of a protective stoma were associated with anastomotic complications. In multivariate analysis, a history of heavy smoking was a significant risk factor for anastomotic complications. A history of heavy smoking (more than 40 pack-years) is an independently significant risk factor for anastomotic complications after low anterior resection in rectal cancer patients.

Combined Pulmonary Fibrosis and Emphysema Syndrome in a Patient Age 28 Years with Severe Systemic Sclerosis: Figure 1.

To the Editor: Combined pulmonary fibrosis and emphysema (CPFE) has recently been defined as a distinct syndrome occurring in adult heavy smokers in their sixties and characterized by dyspnea, crackles at lung auscultation, and diagnostic imaging features on high resolution computed tomography (HRCT) of the chest1. Spirometry is often normal or subnormal due to the opposite compensatory effects of pulmonary fibrosis (usually resulting in restrictive lung disease) and of emphysema (usually resulting in obstructive lung disease)1. CPFE has been reported in a series of patients with connective tissue disease (CTD) as a novel hitherto unrecognized pulmonary manifestation2. We describe a “radical” case of CPFE in a young woman with severe systemic sclerosis (SSc) yet with no history of heavy smoking. A 28-year-old woman, an ex-smoker of tobacco (less than 5 pack-years over 10 years) and ex-smoker of cannabis (1 joint per week for 5 years), presented with mild dyspnea. She had no significant environmental or occupational exposure. Limited cutaneous … Address correspondence to Dr. Cottin; E-mail: vincent.cottin{at}chu-lyon.fr

Extraosseus Uptake of F-18 Fluoride in the Primary Malignancy and Cerebral Metastasis in a Case of Non–Small-Cell Lung Cancer

A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study.

Better Evidence about Screening for Lung Cancer

In October 2010, the National Cancer Institute (NCI) announced that patients who were randomly assigned to screening with low-dose computed tomography (CT) had fewer deaths from lung cancer than did patients randomly assigned to screening with chest radiography. The first report of the NCI-sponsored National Lung Screening Trial (NLST) in a peer-reviewed medical journal appears in this issue of the Journal.1 Eligible participants were between 55 and 74 years of age and had a history of heavy smoking. They were screened once a year for 3 years and were then followed for 3.5 additional years with no screening. At . . .

Successful Bronchoscopic Cryorecanalization in a Case of Endobronchial Lipoma

Endobronchial lipomas are rare benign tumors; less than 150 cases have been reported so far. Bronchial occlusion usually leads to a misdiagnosis of asthma/COPD or malignancy. We report the case of a 67-year-old man with a history of heavy smoking (100 pack years), dyspnea on exertion, cough, and malaise who was treated for pneumonia for three weeks. Due to nonresolving atelectasis of the superior segment of the right lower lobe, a malignant endobronchial tumor was suspected. Rigid bronchoscopy with cryorecanalization led to both the definite histopathological diagnosis of endobronchial lipoma and the reopening of an endoluminal airway obstruction during one procedure.

Advances in the Treatment of Peripheral Vascular Disease in Diabetes and Reduction of Major Amputations

In recent years, life expectancy has increased in many societies consequent to better health conditions. Although the trends of decreasing mortality rates from ischemic heart disease and stroke have continued into the 21st century, both causes continue to be the biggest killers in the Western societies. No change is predicted in the foreseeable future and consequently both these conditions contribute significantly to the burden of disease. 1 Diabetes is considered a cardiovascular disease equivalent and with diabetes patients share the benefits of the improved approach to the treatment of cardiovascular disease. However, because of the longer life span and disease duration, other chronic complications such as peripheral arterial disease (PAD) may well become more evident. In a recent survey, PAD was present in 21% of newly diagnosed type 2 diabetic patients 2 and in about 50% of the patients admitted to a diabetic foot clinic on account of a new foot ulcer. It is interesting to emphasize that half of those patients had concomitant peripheral neuropathy. 3 Neuropathy can mask the classic PAD symptoms as claudication, thereby delaying a diagnosis. On the other hand, the presence of PAD may limit the use of total contact cast that is considered the “gold standard” treatment for neuropathic ulcerations. PAD alone is responsible for the increased risk of lower limb amputation observed in patients with diabetes. 4,5 In type 1 diabetes, the overall 25-year cumulative incidence of lower extremity amputation (LEA) is 10.1%. History of heavy smoking, high HbA1c, presence of hypertension are all factors related to PAD and major determinants associated with LEA. 6 In addition, major complex gender differences exist in diabetes-related LEA: Men are more likely to undergo LEA. 7 The presence of a foot infection increases the risk of LEA. A multidisciplinary approach to diabetic foot problems is mandatory to reduce the frequency of LEA, particularly when PAD is complicated by the presence of infected foot ulcers. 8 Today significantly better outcomes are expected for patients with diabetes affected by critical limb ischemia (CLI) based on improved technical options in peripheral revascularization, new options in antibiotic therapy, and aggressive wound debridement and wound care. Until recently, open peripheral arterial bypass has been the firstline surgical treatment option for PAD. Although open bypass is associated with successful results, the invasive nature of the surgery can limit optimal overall outcome. Endovascular procedure is less invasive; however, it reaches similar limb salvage rates in patients with CLI, 9 with the added benefits of fewer wound complications and a shorter hospital stay. As expected, endovascular therapy is increasingly being considered as a first-line treatment option in carefully selected PAD diabetic patients. With the widespread adoption of endovascular therapy, there has been a profound shift in practice patterns for lower extremity PAD. In the past decade, there has been a consistent increase in the number of patients treated by peripheral transluminal angioplasty because of CLI. 10 Hong et al 10 reported that in the general population the average annual number of endovascular interventions is increased by 78% while there is a concomitant decrease in open bypass by 20%. The same authors found that the trends in amputation were consistent with the increase in endovascular therapy. The number of major amputations (ankle to above-the-knee level) decreased by 21% and the number of minor amputations, defined as involving the toe and forefoot, showed a moderate decrease of 5%. Although better outcomes for CLI have been observed in the general population, the LEA observed in patients with diabetes are reportedly reduced, unchanged, or even increased. A recent survey conducted in England reported that the number and incidence of amputations decreased in the aging nondiabetic population whereas the overall population

Early adulthood obesity, cumulative smoking, and esophageal cancer survival.

1546 Background: Obesity and smoking have been associated with worsening outcomes of several cancer types. However, little is known about the combined impact of early adulthood obesity (decades prior to diagnosis) and smoking on mortality of esophageal cancer (EC). Methods: We analyzed data from a cohort of 345 patients with EC from Boston, USA enrolled from 1999 to 2004. Associations between early adulthood body mass index (EABMI) (not at time of diagnosis) and smoking and overall survival (OS) were assessed using Cox proportional hazard models, adjusted for age, stage, performance status. Results: EABMI was independently associated with worse OS (HRadj=1.04; 95% CI, 1.01-1.07; p=0.009; continuous variable (CV)). When patients were evaluated in quartiles, the highest quartile of EABMI (>26.9) had the worst survival (HRadj=1.52; 1.1-2.1; p=0.01). In contrast, BMI 1 year prior to diagnosis had no association with OS. Cumulative smoking also independently conferred worse OS (HRadj=1.01; 1.00-1.01; p=0.005; CV); when evaluated using quintiles, OS was worst in the heaviest smoking quintile (>85 pack-years) (HRadj=1.60; 95% CI, 1.1-2.3; p=0.007). Compared with the lowest weight patients (during their early adulthood years) who were never smokers, HRadj for mortality increased progressively with increasing quintiles of both smoking and quartiles of EABMI. In joint effects analysis, within the highest BMI quartile (>26.9), the HRadj rose from 0.4 (0.1-1.5; lowest smoking quintile, consisting of lifetime never-smokers) through 1.8 (0.8-3.9; highest smoking quintile of >56 pack-years). Likewise, within the highest smoking quintile (>56 pack-years), the HRadj rose from 1.0 (0.4-2.3; lowest BMI quartile of <21) through to 1.8 (0.8-3.9; highest BMI quartile >26.9). Conclusions: Among EC patients, elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk. The combination of obesity and smoking is related to an especially higher mortality risk. These differences may reflect differences in obesity- or smoking-related comorbidities, but may also be due to biologic differences arising from different, adiposity-related carcinogenic pathways.