Globally, patients who smoke cigarettes account for an estimated 60 million of the approximately 310 million operations performed annually.1 Compared with nonsmokers, smokers are at an increased risk for surgical complications (odds ratio = 1.2–1.6).2 In addition to the severe economic consequences,3 cigarette smoke decreases tissue oxygenation and aerobic metabolism, thereby impairing healing.4 Smokers have higher rates of wound infection and impaired wound healing, as well as other postoperative complications,5-14 including postoperative pulmonary complications and prolonged mechanical ventilation.15,16 These data are particularly relevant in patients undergoing pulmonary resection for suspicious nodules or proven malignancy.
Smoking cessation around the time of an operation can improve oxidative bacterial-killing mechanisms and inflammatory cell migration,17,18 as well as reduce the risk of surgical site infections.4,19 Short-term smoking abstinence improves oxygen availability to the vital organs,19,20 and prolonged smoking abstinence decreases the risk of pulmonary complications.21 This risk is time-related in that the longer the patient abstains from smoking prior to surgery, the lower the risk.15,19
Helping smokers kick the habit
Most smokers agree that quitting can be difficult, but many indicate that they want to quit eventually. Although counseling and medication are effective when used alone, U.S. Public Health Service guidelines indicate that a combination of both treatments is a more effective approach.1 Consequently, many large institutions have incorporated a tobacco dependence referral program into their oncology service. Nonetheless, many lung cancer patients continue to smoke preoperatively. A diagnosis of cancer and preparing for surgery within a short timespan are both stressful events. This life-changing information can be a critical teachable moment, when patients truly internalize the importance of changing their habits, accelerate their motivation to quit, and rapidly push themselves through the stages of change.4 Alternatively, many patients believe that smoking will help them cope with this stress and therefore experience even greater difficulty or reluctance to quit. Knowing that smoking may increase complications in the short term, and pose ongoing health risks in the long term, may help shift the balance favorably toward smoking cessation.
The Alliance A211401 study was designed to determine how surgeons can improve smoking cessation rates in conjunction with preparing a patient for lung nodule resection and whether smoking cessation can be sustained postoperatively.
The first question is how much intervention, in the form of counseling and medication, is needed. Evidence has shown that major surgery for a smoking-related illness provides a significant and effective teachable moment.22 Telephone quitlines have been determined to be cost-effective and empowering to patients, in addition to being more convenient than face-to-face counseling, and have demonstrated real-world effectiveness.23 Quitlines are a free way for patients to talk to a specialist about smoking cessation. Quitlines can also be used to help patients remain smoke-free. The effectiveness increases if the health care professional initiates the connection between the patient and the telephone counselor.24 Although we know that some exceptional first-line medications are available for smoking cessation,25-28 some cancer patients may respond poorly to these drugs or simply may prefer not to add to their growing list of medications.
Is pharmacotherapy absolutely needed, or can messaging and telephone counseling be enough support to stop smoking? Does timing of smoking cessation matter? The ideal time for smoking cessation prior to surgery varies in the literature from one to 12 weeks, but does that mean that if you see a patient today who smokes and the operation is scheduled to be performed in two weeks, smoking cessation will be pointless? Absolutely not. Smoking cessation at any time is beneficial, but how beneficial in terms of reducing complications and improving quality of life? Especially with a cancer diagnosis, time from smoking cessation to surgical resection cannot be delayed for an excessive period of time. The Alliance A211401 study will address these questions.
Opportunities to participate
All participating patients will be advised to stop smoking by their surgical team and will be proactively connected to the National Cancer Institute’s (NCI) smoking quitline (1-877-44U-QUIT). Patients will be randomized to either placebo or varenicline, also known as Chantix (see study schema, Figure 1). The study will evaluate the relationship between smoking cessation, postoperative complications, and duration of smoking cessation before surgery.
Figure 1. A211401 schema
In this study, surgery should be performed at least 10 days after randomization to trials and within 12 weeks of randomization. The accrual goal is 626 patients who have lung cancer surgery and are followed for 24 weeks after the operation. The primary outcome will be the rate of surgical complications, as identified using American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) data. Secondary outcomes include quality of life, postoperative care (length of hospital and high dependency unit stay), and rates of smoking abstinence. All patients will have the option of enrolling in the correlative genetic study. Alliance A211401 is now recruiting participants. Refer to the study protocol for complete information on the trial design, treatment plan, and patient eligibility. For questions, contact Ivana T. Croghan, PhD, by e-mail at firstname.lastname@example.org, phone at 800-845-7853, or fax at 507-255-0742; or Rachel Wills at email@example.com or 773-702-9814.
- Nolan MB, Warner DO. Perioperative tobacco use treatments: Putting them into practice. BMJ. 2017;358:j3340.
- Weiser TG, Regenbogen SE, Thompson KD, et al. An estimation of the global volume of surgery: A modelling strategy based on available data. Lancet. 2008;372(9633):139-144.
- Warner DO, Borah BJ, Moriarty J, Schroeder DR, Shi Y, Shah ND. Smoking status and health care costs in the perioperative period: A population-based study. JAMA Surg. 2014;149(3):259-266.
- Sorensen LT. Wound healing and infection in surgery. The clinical impact of smoking and smoking cessation: A systematic review and meta-analysis. Arch Surg. 2012;147(4):373-383.
- Sorensen LT. Wound healing and infection in surgery: The pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: A systematic review. Ann Surg. 2012;255(6):1069-1079.
- Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: Systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569.
- Garces YI, Hays JT. Tobacco dependence: Why should an oncologist care? J Clin Oncol. 2003;21(9):1884-1886.
- Theiss SM, Boden SD, Hair G, Titus L, Morone MA, Ugbo J. The effect of nicotine on gene expression during spine fusion. Spine (Phila Pa 1976). 2000;25(20):2588-2594.
- Scolaro JA, Schenker ML, Yannascoli S, Baldwin K, Mehta S, Ahn J. Cigarette smoking increases complications following fracture. J Bone Joint Surg Am. 2014;96(8):674-681.
- Rejali M, Rejali AR, Zhang L, Yang S. Effects of nicotine on the cardiovascular system. Vasc Dis Prev. 2005;2(2):135-144.
- Middlekauff HR, Park J, Moheimani RS. Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: Mechanisms and implications for cardiovascular risk. J Am Coll Cardiol. 2014;64(16):1740-1750.
- Saetta M, Turato G, Baraldo S, et al. Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation. Am J Respir Crit Care Med. 2000;161:1016-1021.
- Dhillon NK, Murphy WJ, Filla MB, Crespo AJ, Latham HA, O’Brien-Ladner A. Down modulation of IFN-gamma signaling in alveolar macrophages isolated from smokers. Toxicol Appl Pharmacol. 2009;237(1):22-28.
- Garey KW, Neuhauser MM, Robbins RA, Danziger LH, Rubinstein I. Markers of inflammation in exhaled breath condensate of young healthy smokers. Chest. 2004;125(1):22-26.
- Yousefzadeh A, Chung F, Wong DT, Warner DO, Wong J. Smoking cessation: The role of the anesthesiologist. Anesth Analg. 2016;122(5):1311-1320.
- Hawn MT, Houston TK, Campagna EJ, et al. The attributable risk of smoking on surgical complications. Ann Surg. 2011;254(6):914-920.
- Sorensen LT, Toft B, Rygaard J, Ladelund S, Teisner B, Gottrup F. Smoking attenuates wound inflammation and proliferation while smoking cessation restores inflammation but not proliferation. Wound Repair Regen. 2010;18(2):186-192.
- Sorensen LT, Nielsen HB, Kharazmi A, Gottrup F. Effect of smoking and abstention on oxidative burst and reactivity of neutrophils and monocytes. Surgery. 2004;136(5):1047-1053.
- Wong J, Lam DP, Abrishami A, Chan MT, Chung F. Short-term preoperative smoking cessation and postoperative complications: A systematic review and meta-analysis. Can J Anaesth. 2012;59(3):268-279.
- Myers K, Hajek P, Hinds C, McRobbie H. Stopping smoking shortly before surgery and postoperative complications: A systematic review and meta-analysis. Arch Intern Med. 2011;171(11):983-989.
- Bluman LG, Mosca L, Newman N, Simon DG. Preoperative smoking habits and postoperative pulmonary complications. Chest. 1998;113(4):883-889.
- Shi Y, Warner DO. Surgery as a teachable moment for smoking cessation. Anesthesiology. 2010;112(1):102-107.
- Warner DO, Klesges RC, Dale LC, et al. Telephone quitlines to help surgical patients quit smoking patient and provider attitudes. Am J Prev Med. 2008;35(6 Suppl):S486-493.
- Stead LF, Hartmann-Boyce J, Perera R, Lancaster T. Telephone counselling for smoking cessation. Cochrane Database Syst Rev. 2013;8:CD002850.
- Rinker B. The evils of nicotine: An evidence-based guide to smoking and plastic surgery. Ann Plast Surg. 2013;70(5):599-605.
- Rennard SI, Daughton DM. Smoking cessation. Clin Chest Med. 2014;35(1):165-176.
- De Hoyos A, Southard C, DeCamp MM. Perioperative smoking cessation. Thorac Surg Clin. 2012;22(1):1-12.
- Cahill K, Stevens S, Lancaster T. Pharmacological treatments for smoking cessation. JAMA. 2014;311(2):193-194.