Abstract
Background
The possible negative effects of smoking on postoperative outcomes have not been well-studied in cancer patients.
Methods
We used the VA Surgical Quality Improvement Program (VASQIP) database for the years 2002–2008, which assesses pre-operative risk factors and post-operative outcomes for patients undergoing major surgery within the VA healthcare system.
Results
Compared to never smokers, prior smokers and current smokers with GI malignancies were significantly more likely to have surgical site infection (SSI)( Odds ratio, OR:1.25, 95%CI:1.09–1.44)(OR:1.20, 95%CI:1.05–1.38), combined pulmonary complications (CPO: pneumonia, failure to wean from ventilator, reintubation) (OR:1.60, 95%CI:1.38–1.87)(OR:1.96, 95%CI:1.68–2.29) and return to the operating room (OR:1.20, 95%CI:1.03–1.39)(OR:1.31 95%CI:1.13–1.53), respectively. Both prior and current smokers had a significantly higher mortality at 30 days (OR:1.50, 95%CI:1.19–1.89)(OR: 1.41, 95%CI:1.08–1.82) and one year (OR:1.22, 95%CI:1.08–1.38)(OR:1.62, 95%C I:1.43–1.85). Thoracic surgery patients who were current smokers were more likely to develop CPO (OR:1.62, 95%CI:1.25–2.11), and mortality within one year (OR:1.50, 95%CI:1.17–1.92) compared to non-smokers, but SSI rates were not affected by smoking status. Current smokers had a significant increase in postsurgical length of stay (overall 4.3% [p<0.001], GI 4.7% [p=0.003], thoracic 9.0% [p<0.001]) compared to prior smokers.
Conclusions
Prior and current smoking status is a significant risk factor for major postoperative complications and mortality following GI cancer and thoracic operations in veterans. Smoking cessation should be encouraged prior to all major cancer surgery in the VA population to decrease postoperative complications and length of stay.
Keywords: Smoking, Cancer, Surgery outcomes, Postoperative complications
In the United States, approximately half of adult men reported smoking cigarettes in 1965 and many of these individuals did so for over 20 years.1 The association between smoking and the increased risk of developing certain malignancies has been well-established2–3 and cigarette smoking accounts for approximately 30% of all cancer deaths in the general population.3 There is also evidence that continued smoking after malignancy diagnosis may lead to a higher recurrence rate or second primary tumor compared to non-smokers.4–5
There is conflicting evidence regarding the attributable risk of smoking on post-operative complications in patients undergoing major surgical procedures.6–9 The risk of hospital death and pulmonary complications after lung cancer resection is increased by smoking.10–11 This increased rate of complications in smokers may result in longer postoperative stay, increased health care costs and postoperative mortality compared to non-smokers.
Most solid organ based cancers are treated with surgical interventions. These are often complex procedures with associated morbidity and mortality. Cancer patients have higher prevalence of smoking and may be at higher incidence of smoking related complications.4
Postoperative medical and surgical complications have been shown to result in an omission or significant delay in the initiation of adjuvant chemotherapy in colon and rectal cancer.12–13 Delays in adjuvant chemotherapy were correlated with poorer disease-specific and overall survival in one of these studies.12 Postoperative length of stay has also been shown to independently predict adjuvant chemotherapy delay in cancer patients.12 Since smoking is a potentially modifiable preoperative risk factor for postoperative medical and surgical complications, smoking cessation interventions may decrease the risk of developing postoperative complications and length of stay and therefore improve the odds of smokers getting appropriate postoperative chemotherapy for their cancer.
Given that cancer operations are ‘time-sensitive’, quantifying the potential benefit of smoking cessation intervention is necessary information to adopt this strategy. In addition, the negative effects of smoking may not be uniform across various disease sites. While there is evidence that smokers have an increased risk of postoperative complications and possibly death in general and thoracic surgery patients, this area has not been well-studied for major gastro-intestinal surgeries.
Our study examined the effects of smoking on the rate of postoperative complications and mortality following major cancer surgery in the Veteran Affairs (VA) population, using a large national database, the VA Surgical Quality Improvement Program. Our objective was to examine whether smoking was associated with higher risk of postoperative complications and mortality after major surgery in patients with cancer, and whether this risk varies by the type of the primary tumor site.
Methods
Data source
Data for this study were obtained from the VA Surgical Quality Improvement Program (VASQIP), which assesses pre-operative risk factors, operative data, and 30-day postoperative outcomes for patients undergoing major surgery within the VA system. The VASQIP started in 1991 to analyze risk-adjusted 30-day morbidity and mortality data within the Veterans Health Administration. Of the approximately 375,000 surgical procedures in the VA yearly, 150,000 are major surgeries. The VASQIP is a prospectively collected database for patients undergoing major surgery within all VA acute care facilities. A trained surgical clinical nurse collects the data from electronic charts. On the 30th postoperative day, the nurse obtains outcome information through chart review, reports from morbidity and mortality conferences, and communication with each patient by letter or by telephone.
The study protocol was reviewed and approved by the local VA Research and Development Committee and the Institutional Review Board at the institutions of each co-author, as well as by the Surgical Quality Data Use Group of the Office of Patient Care Services, VA Central Office, Washington, D.C.
Patients
The original study population consisted of 502,647 patients undergoing elective surgery between years 2002–2008. Patients undergoing emergent surgery were excluded by using the emergency case variable in the data set, because the attributable risk of smoking on complications after emergent surgery would not be amendable to pre-operative smoking cessation interventions to reduce them. For patients with multiple operations in the database, we used the patient’s first operation for this study. The International Classification of Diseases (ninth edition) code (ICD-9) was used to identify patients with gastrointestinal (GI), lung, and urinary tract malignancies (Supplemental Table 1A). The Current Procedure Terminology (CPT) codes (Supplemental Table 1B) were used to identify major surgical procedures related to the ICD-9 codes, resulting in 22,391 patients with available smoking status (current, prior, never smoker). Of these 22,391 patients 1,561 were found to have more than one cancer site possibly secondary to metastatic disease, and these patients were excluded from our study. This provided us with 20,830 subjects for analysis. After excluding all cases that were coded as emergencies, we were left with 20,413 cases. All gastro-intestinal cancer patients were grouped into the GI group (n=12,432), all lung cancer patients were grouped into the thoracic surgery group (n=4490), and all urinary tract malignancies were grouped into the urology group (n=3491).
Definitions of Outcomes of Interest
Postoperative outcomes of interest were complications occurring within 30 days of the index operation, return to OR within 30 days, post-surgical length of stay, 30 day and 1 year mortality. Post-operative complications included : surgical site infection (SSI, including superficial and deep wound infections); cardiovascular, pulmonary, urinary tract and CNS complications; return to OR; and postoperative hospital length of stay. In addition, we also grouped complications into a composite pulmonary outcome (CPO: pneumonia, failure to wean from ventilator > 48 hrs or re-intubation for cardio-respiratory failure). The following complications were grouped together and called vascular complications: venous thromboembolism, stroke/cerebrovascular accident, myocardial infarction. A composite outcome was created by combining SSI, vascular and pulmonary complications.
The VASQIP data collection includes two smoking variables: current smoker (patient has smoked cigarettes in the year prior to admission for surgery); and total number of pack-years of smoking. For the purposes of this study, each patient was classified into current, prior, and never smoker. Current smoker was defined as a patient who was classified as “yes” for the current smoker variable, and had a value for pack-years of >0 or missing. Prior smoker was defined as a patient who was classified as “no” for the current smoker variable and whose value for the pack-years variable was >0. Never smoker was defined as a patient who was classified as “no” for the current smoker variable and whose value for the pack-years variable was =0 or missing. Patients who had a “yes” for current smoker, but who had pack-years =0 (an inconsistency), or who were missing the current smoker variable were excluded.
Statistical analyses
Baseline patient characteristics were compared among the three smoking groups (never, prior, and current) using chi-square tests of association for categorical variables and the one-factor analysis of variance for continuous variables. Unadjusted postoperative outcome rates were compared by smoking status using Pearson’s chi-square test of association.
For each of the dichotomous postoperative outcomes, the adjusted odds ratios for the current and prior smoking groups were compared to the never smokers as the reference group using multilevel multivariable logistic regression analysis. The association of pack years with postoperative outcomes was similarly performed for the most frequently occurring outcomes. Pack years was divided into quartiles and split by smoking status. A log-linear multilevel multivariable regression analysis modeled the association of smoking status and post-surgical length of stay. All regression analyses were adjusted for age, race/ethnicity, work RVU, surgeon specialty, ASA classification, alcohol use, and year of surgery. SSI was additionally adjusted for wound classification. Clustering of patients within hospitals was accounted for with a random effect of hospital and included in the model when statistically appropriate. Reported odds ratios represent the ratio of the odds of a postoperative outcome in prior (or current) smokers to the odds of the same event in the non-smoker group. A confidence interval which includes one implies no statistically significant difference in the odds of a given outcome between smoking groups. All analyses were performed using SAS® software, Version 9.2 (SAS Institute Inc., Cary, North Carolina).
Results
Patient characteristics of the study sample are presented in Table 1. Most of the baseline patient characteristics were statistically significantly different between the three smoking groups, although many of the differences were not clinically meaningful. Current smokers were younger, had higher pack years of smoking, had a lower prevalence of diabetes, but had higher rates of alcohol consumption, COPD, and >10% loss of body weight in the last 6 months.
Table 1.
Patient characteristics by smoking status in cancer patients, %(n) or mean (
| Overall (n=20,413) | Never Smoked (n=8,375) | Prior Smoker (n=5,096) | Current Smoker (n=6,942) | P-value | ||
|---|---|---|---|---|---|---|
| Patient Demographics | ||||||
| Male gender | Male | 97.8 (19,961) | 97.6 (8,172) | 98.6 (5,023) | 97.5 (6,766) | <0.001 |
| Race | White, Hispanic | 4.1 (842) | 5.9 (497) | 3.1 (156) | 2.7 (189) | <0.001 |
| Black | 15.1 (3,089) | 15.3 (1,282) | 11.8 (601) | 17.4 (1,206) | ||
| White, not of Hispanic origin | 63.8 (13,032) | 61.9 (5,181) | 68.0 (3,465) | 63.2 (4,386) | ||
| Unknown/Other | 16.9 (3,450) | 16.9 (1,415) | 17.2 (874) | 16.7 (1,161) | ||
| Age | Mean (S.D.) | 66.6 (10.2) | 68.8 (10.4) | 69.3 (9.3) | 62.1 (9.0) | <0.001 |
| Pack years of smoking | Mean (S.D.) | 37.9 (39.0) | 0.0 (0.0) | 49.2 (36.3) | 59.1 (34.7) | <0.001 |
|
| ||||||
| Pre Operative Status | ||||||
| Diabetes | 23.2 (4,733) | 26.9 (2,249) | 26.2 (1,333) | 16.6 (1,151) | <0.001 | |
| ETOH > 2 drink a day 2 weeks. before admission | 11.0 (2,231) | 6.0 (497) | 8.4 (429) | 18.9 (1,305) | <0.001 | |
| Chemotherapy for malignancy in last 30 days | 1.7 (343) | 1.4 (120) | 1.6 (79) | 2.1 (144) | 0.006 | |
| Congestive heart failure in 30 days before surgery | 1.6 (325) | 1.7 (139) | 2.0 (101) | 1.2 (85) | 0.004 | |
| History of severe COPD | 20.5 (4,189) | 9.7 (815) | 24.9 (1,270) | 30.3 (2,104) | <0.001 | |
| Open wound/wound infection | 1.0 (211) | 1.0 (83) | 1.0 (52) | 1.1 (76) | 0.814 | |
| > 10% loss of body weight in last 6 months | 10.4 (2,114) | 8.6 (722) | 9.9 (505) | 12.8 (887) | <0.001 | |
| Functional health status (1–3) | Independent | 94.7 (19,324) | 93.9 (7,863) | 94.5 (4,816) | 95.7 (6,645) | <0.001 |
| Partially dependent | 4.8 (972) | 5.4 (450) | 5.0 (256) | 3.8 (266) | ||
| Totally dependent | 0.6 (117) | 0.7 (62) | 0.5 (24) | 0.4 (31) | ||
| Preoperative serum albumin | Mean (S.D.) | 3.8 (0.6) | 3.8 (0.6) | 3.8 (0.5) | 3.8 (0.6) | 0.004 |
|
| ||||||
| Surgical Profile | ||||||
| ASA class | Healthy patient | 0.4 (75) | 0.6 (50) | 0.2 (12) | 0.2 (13) | <0.001 |
| Mild systemic disease | 16.9 (3,452) | 20.5 (1,720) | 13.3 (678) | 15.2 (1,054) | ||
| Severe systemic disease | 71.7 (14,639) | 68.5 (5,737) | 73.5 (3,744) | 74.3 (5,158) | ||
| Constant threat to life | 10.9 (2,234) | 10.3 (863) | 12.9 (656) | 10.3 (715) | ||
| Moribund Patient | 0.1 (13) | 0.1 (5) | 0.1 (6) | 0.0 (2) | ||
| Fiscal year (Oct 1–Sept 31) | 2002 | 16.1 (3,295) | 15.5 (1,297) | 17.4 (886) | 16.0 (1,112) | <0.001 |
| 2003 | 16.5 (3,359) | 16.4 (1,370) | 17.3 (884) | 15.9 (1,105) | ||
| 2004 | 15.4 (3,153) | 14.6 (1,223) | 17.2 (874) | 15.2 (1,056) | ||
| 2005 | 14.5 (2,964) | 13.7 (1,144) | 15.7 (798) | 14.7 (1,022) | ||
| 2006 | 13.6 (2,778) | 12.8 (1,076) | 14.6 (743) | 13.8 (959) | ||
| 2007 | 12.6 (2,569) | 11.5 (964) | 13.9 (707) | 12.9 (898) | ||
| 2008 | 11.2 (2,295) | 15.5 (1,301) | 4.0 (204) | 11.4 (790) | ||
| Wound classification | Clean | 23.7 (4,835) | 20.8 (1,743) | 24.1 (1,229) | 26.8 (1,863) | <0.001 |
| Clean/contaminated | 73.3 (14,960) | 75.7 (6,338) | 73.1 (3,726) | 70.5 (4,896) | ||
| Contaminated | 2.6 (534) | 3.1 (260) | 2.4 (123) | 2.2 (151) | ||
| Infected | 0.4 (84) | 0.4 (34) | 0.4 (18) | 0.5 (32) | ||
| Work RVU | Mean (S.D.) | 23.8 (6.2) | 23.4 (6.0) | 23.7 (6.0) | 24.5 (6.5) | <0.001 |
| Total operation time | Mean (S.D.) | 3.3 (1.8) | 3.2 (1.7) | 3.3 (1.7) | 3.4 (1.9) | <0.001 |
All postoperative outcomes differed statistically significantly by smoking status (Table 2). The unadjusted rates of complications including postoperative pneumonia, failure to wean from the ventilator, re-intubation, return to the OR, combined pulmonary complications and for the composite outcome were highest in the current smoker group. Prior smokers had the highest unadjusted rate of SSI, venous thromboembolism, stroke, myocardial infarction, renal failure, urinary tract infection, mortality rates at 30-days and 1-year as well as combined vascular complications. Mean post-operative surgical length of stay varied by almost one day between never smokers (9.8 days) and prior and current smokers (10.6–10.7 days; P<0.001).
Table 2.
Post operative outcomes by smoking status in cancer patient
| Overall (n=20,413) | Never Smoked (n=8,375) | Prior Smoker (n=5,096) | Current Smoker (n=6,942) | P-value | |
|---|---|---|---|---|---|
| Post Operative Outcomes | |||||
| Surgical site infection | 8.9 (1,824) | 8.9 (744) | 9.8 (498) | 8.4 (582) | 0.030 |
| Venous thromboembolism | 1.3 (263) | 1.3 (110) | 1.7 (89) | 0.9 (64) | <0.001 |
| Stroke/cerebrovascular accident | 0.5 (106) | 0.4 (37) | 0.8 (39) | 0.4 (30) | 0.019 |
| Myocardial infarction | 0.9 (178) | 0.8 (68) | 1.2 (63) | 0.7 (47) | 0.004 |
| Renal failure | 2.1 (436) | 2.0 (170) | 2.8 (144) | 1.8 (122) | <0.001 |
| Urinary tract infection | 3.9 (799) | 4.1 (340) | 4.7 (238) | 3.2 (221) | <0.001 |
| Pneumonia | 7.3 (1,497) | 4.9 (409) | 8.2 (417) | 9.7 (671) | <0.001 |
| Failure to wean | 5.1 (1,048) | 3.4 (282) | 5.7 (293) | 6.8 (473) | <0.001 |
| Re-intubation | 5.8 (1,183) | 3.8 (322) | 6.4 (328) | 7.7 (533) | <0.001 |
| 30-day mortality | 3.4 (698) | 2.9 (242) | 4.6 (236) | 3.2 (220) | <0.001 |
| 1-year mortality* | 16.1 (3,292) | 13.5 (1,127) | 18.5 (941) | 17.7 (1,224) | <0.001 |
| Pulmonary complication (CPO) | 11.1 (2,272) | 7.8 (651) | 12.5 (638) | 14.2 (983) | <0.001 |
| Vascular complication | 1.4 (277) | 1.2 (103) | 2.0 (100) | 1.1 (74) | <0.001 |
| Composite outcome | 19.1 (3,901) | 16.0 (1,343) | 21.2 (1,078) | 21.3 (1,480) | <0.001 |
| Return to OR | 9.4 (1,929) | 8.1 (680) | 9.8 (498) | 10.8 (751) | <0.001 |
| Length of Post-op Surgical Stay, mean (SD) | 10.3 (10.7) | 9.8 (10.5) | 10.7 (11.0) | 10.6 (10.8) | <0.001 |
| excluding those with 30-day mortality | 10.3 (10.8) | 9.8 (10.5) | 10.7 (11.1) | 10.6 (10.9) | <0.001 |
Results are presented as column-% (n) unless specified otherwise. For patients with 30-day mortality it is unknown whether death occurred prior to hospital discharge.
Table 3a presents adjusted odds ratios for selected postoperative outcomes comparing the current and prior smokers to the never smokers by cancer sites (GI, thoracic, and urologic), followed by direct comparison of current smokers to prior smokers, using prior smokers as a reference group (Table 3b). Percent of patients who were current or prior smokers differed by cancer site: GI cancer (51%), thoracic cancer (84%), and urologic cancer (57%).
Table 3.
Table 3a. Comparison of current and prior smokers, using never smokers as a reference group. Table 3b Direct comparison of current smokers to prior smokers, using prior smokers as a reference group
| Table 3a
| |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer Site |
Smoking Status |
Surgical Site Infection |
Pneumonia | Failure to wean | Reintubation | Combined Pulmonary outcome |
Return to OR | 30-day Mortality | 1-year Mortality |
|
GI n=12,432 |
Never (49%) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Prior (25%) | 1.25 (1.09, 1.44) | 1.52 (1.26, 1.84) | 1.58 (1.28, 1.97) | 1.66 (1.35, 2.04) | 1.60 (1.38, 1.87) | 1.20 (1.03, 1.39) | 1.50 (1.19, 1.89) | 1.22 (1.08, 1.38) | |
| Current (26%) | 1.20 (1.05, 1.38) | 1.98 (1.64, 2.40) | 2.21 (1.79, 2.73) | 2.15 (1.75, 2.65) | 1.96 (1.68, 2.29) | 1.31 (1.13, 1.53) | 1.41 (1.08, 1.82) | 1.62 (1.43, 1.85) | |
|
| |||||||||
|
Thoracic n=4490 |
Never (16%) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Prior (29%) | 0.69 (0.38, 1.26) | 1.05 (0.76, 1.44) | 1.15 (0.76, 1.74) | 1.11 (0.77, 1.60) | 1.08 (0.81, 1.42) | 0.97 (0.68, 1.39) | 1.43 (0.88, 2.34) | 1.19 (0.92, 1.54) | |
| Current (55%) | 0.93 (0.54, 1.60) | 1.51 (1.12, 2.03) | 1.64 (1.11, 2.40) | 1.72 (1.22, 2.42) | 1.62 (1.25, 2.11) | 1.30 (0.94, 1.81) | 1.30 (0.79, 2.13) | 1.50 (1.17, 1.92) | |
|
| |||||||||
|
Urology n=3491 |
Never (43%) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Prior (21%) | 1.18 (0.70, 1.99) | 1.48 (0.90, 2.45) | 1.48 (0.81, 2.71) | 1.09 (0.63, 1.86) | 1.26 (0.85, 1.86) | 1.69 (1.15, 2.49) | 1.26 (0.68, 2.34) | 1.04 (0.77, 1.41) | |
| Current (36%) | 1.23 (0.78, 1.93) | 1.97 (1.23, 3.15) | 1.37 (0.75, 2.48) | 1.27 (0.77, 2.10) | 1.57 (1.09, 2.27) | 1.44 (1.00, 2.07) | 1.16 (0.62, 2.17) | 1.19 (0.90, 1.58) | |
| Table 3b
| |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer Site |
Smoking Status |
Surgical Site Infection |
Pneumonia | Failure to wean | Reintubation | Combined Pulmonary outcome |
Return to OR | 30-day Mortality | 1-year Mortality |
|
GI n=12,432 |
Never (49%) | 0.80 (0.70, 0.91) | 0.66 (0.54, 0.79) | 0.63 (0.51, 0.78) | 0.60 (0.49, 0.74) | 0.62 (0.53, 0.73) | 0.84 (0.72, 0.97) | 0.67 (0.53, 0.84) | 0.82 (0.72, 0.93) |
| Prior (25%) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| Current (26%) | 0.96 (0.82, 1.11) | 1.30 (1.07, 1.59) | 1.40 (1.12, 1.74) | 1.30 (1.05, 1.60) | 1.22 (1.04, 1.44) | 1.10 (0.93, 1.30) | 0.94 (0.72, 1.23) | 1.33 (1.16, 1.53) | |
|
| |||||||||
|
Thoracic n=4490 |
Never (16%) | 1.44 (0.79, 2.62) | 0.95 (0.69, 1.31) | 0.87 (0.57, 1.31) | 0.90 (0.62, 1.30) | 0.93 (0.70, 1.23) | 1.03 (0.72, 1.47) | 0.70 (0.43, 1.14) | 0.84 (0.65, 1.09) |
| Prior (29%) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| Current (55%) | 1.34 (0.83, 2.18) | 1.44 (1.15, 1.81) | 1.42 (1.06, 1.90) | 1.55 (1.19, 2.01) | 1.51 (1.23, 1.85) | 1.34 (1.03, 1.74) | 0.91 (0.64, 1.30) | 1.26 (1.05, 1.52) | |
|
| |||||||||
|
Urology n=3491 |
Never (43%) | 0.85 (0.50, 1.43) | 0.67 (0.41, 1.12) | 0.68 (0.37, 1.24) | 0.92 (0.54, 1.58) | 0.79 (0.54, 1.17) | 0.59 (0.40, 0.87) | 0.79 (0.43, 1.47) | 0.96 (0.71, 1.30) |
| Prior (21%) | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| Current (36%) | 1.04 (0.62, 1.75) | 1.33 (0.80, 2.20) | 0.92 (0.50, 1.71) | 1.17 (0.67, 2.04) | 1.25 (0.84, 1.86) | 0.85 (0.58, 1.25) | 0.92 (0.46, 1.81) | 1.14 (0.83, 1.57) | |
Current = Current smoker within one year, Prior = Non-current smoker with >0 recorded pack-years of smoking, Never = Non-current smoker with 0 or missing recorded pack-years of smoking Adjusted for fixed effects of age, race/ethnicity, work RVU, surgeon specialty, ASA classification, alcohol use, and year. SSI additionally adjusted for wound class. Models include a random effect for hospital when possible.
Compared to never smokers, prior smokers and current smokers with GI malignancies were significantly more likely to have surgical site infection (SSI), pneumonia, failure to wean from ventilator, reintubation, CPO and return to the OR. Both prior smokers and current smokers had a significantly higher mortality at 30 days and one year. (Table 3a) Direct comparison of current and prior smokers showed significantly higher rate of pneumonia, failure to wean from the ventilator, reintubation rates, CPO and one year mortality favoring prior smokers within the GI group. (Table 3b)
Compared to never smokers, current smokers in the thoracic group were more likely to develop pneumonia, failure to wean from ventilator, reintubation, and CPO. SSI rates did not differ by smoking status. (Table 3a) Current smokers also had significantly higher mortality rates at one year. Direct comparison of current to prior smokers showed a higher rate of pneumonia, failure to wean form the ventilator, reintubation rate, CPO, return to OR and one year mortality favoring the prior smokers within the thoracic group (Table 3b).
Compared to never smokers, urology cancer patients who were current smokers had increased probability of pneumonia, CPO and return to OR. The probability of returning to OR was also elevated in prior smokers in the urology group. (Table 3a) Direct comparison of current to prior smokers showed no significant differences within the urology group (Table 3b).
For all cancer sites combined, prior smokers did not show a significantly different length of stay compared with never smokers in the adjusted model. Current smokers had a significant increase in their length of stay for combined cancer sites compared with never smokers (5.9%: p<0.001) and for GI and thoracic individually (GI 7.5% [p<0.001], thoracic 8.2% [p=0.003]). Direct comparison of current to prior smokers showed similar findings of those between current and never smokers (overall 4.3% [p<0.001], GI 4.7% [p=0.003], thoracic 9.0% [p<0.001]).
Table 4 presents postoperative complications analyzed by pack year of smoking in current and prior smokers. The number of pack years smoked showed no significant correlation with postoperative outcome in current or prior smokers.
Table 4.
Effect of pack years on postoperative outcomes
| Postoperative Outcome | Never Smoked | Prior Smokers (pack years) | Current Smokers (pack years) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| 1–20 | 21–40 | 41–60 | > 60 | 1–20 | 21–40 | 41–60 | > 60 | ||
| Surgical Site Infection | 1.00 | 1.22 (0.43, 3.50) | 1.18 (0.41, 3.39) | 1.63 (0.56, 4.73) | 1.04 (0.36, 2.96) | 0.72 (0.31, 1.68) | 1.27 (0.29, 5.64) | 0.28 (0.04, 2.07) | 1.07 (0.32, 3.53) |
| Combined Pulmonary outcome | 1.00 | 0.90 (0.21, 3.79) | 1.24 (0.37, 4.12) | 1.38 (0.41, 4.63) | 1.17 (0.40, 3.47) | 1.12 (0.51, 2.47) | 0.77 (0.10, 6.10) | 1.61 (0.54, 4.74) | 1.76 (0.65, 4.76) |
| 1-year Mortality | 1.00 | 2.07 (0.92, 4.68) | 1.15 (0.44, 3.03) | 0.60 (0.18, 2.00) | 0.26 (0.06, 1.10) | 1.14 (0.64, 2.06) | 0.77 (0.17, 3.47) | 1.39 (0.56, 3.47) | 0.95 (0.36, 2.53) |
Discussion
To our knowledge, this is the largest study to date examining smoking related postoperative complications in patients with cancer. We analyzed postoperative complications and mortality in three common cancer groups (GI, thoracic and urologic) undergoing cancer surgeries stratified by smoking status (current, prior, never) in over 20,000 VA patients. GI cancer patients had elevated risk of SSI, pneumonia, failure to wean from ventilator, reintubation, CPO, return to OR, postoperative length of stay, 30-day and one-year mortality in both current and prior smokers when comparing these groups to never smokers. Direct comparison of current to prior smokers showed that current smokers had a higher rate of pneumonia, failure to wean form the ventilator, reintubation rate, CPO and one-year mortality. The thoracic cancer group had an elevated risk of pulmonary complications, length of stay and one-year mortality for current smokers only. Direct comparison of current to prior smokers showed a persistently higher rate of pneumonia, failure to wean, reintubation, CPO, return to OR and one year mortality. Urology cancer patients had higher risk of pneumonia, CPO and return to OR in current smokers. Direct comparison of current to prior smokers showed no significant rate of postoperative complications in this group of patients.
These findings support the need for considering smoking cessation interventions even in “time-sensitive” operations for GI cancers and thoracic cases, where current smoking status was shown to have significantly elevated risk adjusted complication rates and mortality, following major cancer operations in the VA population. Since current smokers had a persistently elevated risk of pulmonary complications compared to never smokers as well as prior smokers, even short term smoking cessation programs may improve cancer surgery outcomes and could lower medical costs by decreasing postoperative complications and length of post-surgical hospital stay. In addition, decreasing postoperative complications, return to OR and post-surgical length of stay, via smoking cessation interventions may decrease the risk of delaying or completely omitting appropriate postoperative chemotherapy in selected patients.
Cheung et al.12 examined the etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer using the SEER database. They found that while advanced age and African-American race contribute to adjuvant chemotherapy delays, postoperative recovery is the most important factor. In addition, increase in the length of postoperative hospital stay independently predicted delay in adjuvant chemotherapy as well. Hendren et al13 also examined surgical complications and their association with omission of chemotherapy for Stage III colorectal cancer. Adjuvant chemotherapy was omitted in 46% of patient with complications, compared to 31% of patients without complications (P<0.001). Having a complication was independently associated with omission of chemotherapy in multivariable analysis in their study. They concluded that implementation of quality improvement measures that effectively reduce perioperative complications may also provide a long-term cancer survival benefit. Delay in initiation of adjuvant chemotherapy was shown to be associated with inferior survival in patients with early stage breast cancer as well.14
The negative effects of smoking on perioperative outcomes have been studied in the thoracic surgery literature.10–11 Smoking is a predictor of prolonged length of stay after lobectomy for lung cancer. Wright et al. conducted a large study using the Society of Thoracic Surgeons database showing that smoking significantly and independently contributed to adverse postoperative events in lung cancer patients. These adverse perioperative events impair quality of life, delay return to work and other regular everyday activities, increase cost of health care and raise the risk of death. Sorensen8 performed a large study examining risk factors for tissue and wound complications in GI surgery. Independent predictors of perioperative complications were smoking, comorbidities and perioperative blood loss. However, the overwhelming majority of patients in this study had benign disease (85%) with over 40% of these operations having been performed for hernias.
There are several difficulties in trying to implement smoking cessation prior to major cancer operations. The optimal time for smoking cessation is debatable15–18. Smoking cessation for more than 4 weeks has been reported to demonstrate benefits, at least in wound healing.15 Most cancer cases need to be done within a few weeks after diagnosis for fears of disease spreading and lesions becoming inoperable. Notable exceptions could be locally advanced esophageal and rectal tumors, where the current standard of care is neoadjuvant chemoradiation. However, these patients make up only a small minority of most general surgery/surgical oncology practices. In addition, coordinating a smoking cessation program with neoadjuvant chemotherapy could be challenging, especially in a patient population with significant social issues. On the other hand, an accurate staging and preoperative medical clearance following cancer diagnosis in mostly middle aged or elderly patients usually takes some time, giving a window of opportunity to intervene. Furthermore, pre-operative smoking cessation interventions may indirectly improve cancer surgery outcomes, including time to adjuvant therapy via decreasing post-surgical complications, return to OR and surgical length of stay. Future studies should examine the relationship between smoking related complications and delay of adjuvant chemotherapy.
Our study has several limitations. This is a retrospective review of a prospectively collected multi-institutional database from multiple VA medical centers across the US. The majority of our patients are upper middle-age or elderly males, so our results may not be directly applicable to the private sector with younger patients and more females. We also had a higher than average rate of smokers; for instance, only 17% of our patients were never-smokers in the thoracic surgery group. There might be the chance for some misclassification in our smoking status groups, due to missing data for number of pack-years of smoking. In addition, there is evidence from prior studies that there is a poor correlation between self-reporting and actual smoking status4, further contributing to the chance of misclassification of actual smoking status in our study.
In summary, we found that smoking has significantly increased the risk of postoperative complications in patients undergoing major cancer surgery in the VA. In addition to showing significantly elevated rates of postoperative complications and mortality when comparing current and prior smokers to non-smokers, undergoing elective GI and thoracic operations, we also showed a significantly elevated rate of postoperative complications and death when directly comparing current to prior smokers with GI cancers and thoracic malignancies. Based on these results, we recommend considering smoking cessation interventions prior to all major cancer operations in the VA population to decrease postoperative complication rates, mortality and surgical length of stay.
Supplementary Material
Synopsis.
Prior and current smoking significantly increases the risk of postoperative pulmonary complications, return to the operating room within 30 days, length of stay and mortality after major cancer surgery in the VA population. Short-term smoking cessation interventions may be helpful in decreasing these risks.
Acknowledgments
Sources of support: VA Health Services Research and Development IAB 06-038-2
Footnotes
Financial disclosures: J.A.S. has received speaker honoraria from Abbott; research and travel grants from Allergan, Takeda, Savient, Wyeth and Amgen; and consultant fees from Savient, URL Pharmaceuticals and Novartis.
References
- 1.Fontham ETH, Thun MJ, Ward E, Balch AJ, Delancey JOL, Samet JM. American Cancer Society perspectives on environmental factors and cancer. CA Cancer J Clin. 2009;59:343–351. doi: 10.3322/caac.20041. [DOI] [PubMed] [Google Scholar]
- 2.Brennan JA, Boyle JO, Koch, et al. Association between cigarette smoking and mutation of the p53 gene in squamous-cell carcionoma of the head and neck. N Engl J Med. 1995;332:712–717. doi: 10.1056/NEJM199503163321104. [DOI] [PubMed] [Google Scholar]
- 3.Hanna LM, Jacobs EJ, Thun MJ. The association between cigarette smoking and risk of colorectal cancer in a large prospective cohort form the United States. Cancer Epidemiol Biomarkers Prev. 2009;18(12):3362–3367. doi: 10.1158/1055-9965.EPI-09-0661. [DOI] [PubMed] [Google Scholar]
- 4.Wein RO. Preoperative smoking cessation. Arch Otolarungol Head Neck Surg. 2009;135(6):597–601. doi: 10.1001/archoto.2009.33. [DOI] [PubMed] [Google Scholar]
- 5.Schwartz LH, Ozsahin M, Zhang GN, et al. Synchronous and metachronous head and neck carcinomas. Cancer. 1994;74(7):1933–1938. doi: 10.1002/1097-0142(19941001)74:7<1933::aid-cncr2820740718>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- 6.Lotfi CJ, Cavalcanti RC, Silva AMC, et al. Risk factors for surgical-site infection in head and neck surgery. Otolaryngol Head Neck Surg. 2008;138:74–80. doi: 10.1016/j.otohns.2007.09.018. [DOI] [PubMed] [Google Scholar]
- 7.Sorensen LT, Horby J, Friis, Pilsgaard B, Jorgensen T. Smoking as a risk factor for wound healing and infection in breast cancer surgery. Eur J Surg Onc. 2002;28:815–820. doi: 10.1053/ejso.2002.1308. [DOI] [PubMed] [Google Scholar]
- 8.Sorensen LT, Hemmingsen U, Kallahave F, et al. Risk factors for tissue and wound complications in gastrointestinal surgery. Ann Surg. 2005;241:654–658. doi: 10.1097/01.sla.0000157131.84130.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Fawcett A, Shembekar J, Church JS, et al. Smoking, hypertension and colonic anastomotic healing; a combined clinical and histopathological study. Gut. 1996;38:714–718. doi: 10.1136/gut.38.5.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Mason DP, Subramanian S, Nowicki ER, et al. Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database Study. Ann Thorc Surg. 2009;88:362–371. doi: 10.1016/j.athoracsur.2009.04.035. [DOI] [PubMed] [Google Scholar]
- 11.Wright CD, Gaissert HA, Grab JD, O’Brien SM, Peterson ED, Allen MS. Predictors of prolonged length of stay after lobectomy for lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk-adjustment model. Ann Thorac Surg. 2008;85:1857–1865. doi: 10.1016/j.athoracsur.2008.03.024. [DOI] [PubMed] [Google Scholar]
- 12.Cheung WY, Neville BA, Earle CC. Etiology in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer. Dis Colon Rectum. 2009;52:1054–1064. doi: 10.1007/DCR.0b013e3181a51173. [DOI] [PubMed] [Google Scholar]
- 13.Hendren S, Birkmeyer JD, Yin H, Banerjee M, Sonnenday C, Morris MM. Surgical complications are associated with omission of chemotherapy for Stage III colorectal cancer. Dis Colon Rectum. 2010;53:1587–1593. doi: 10.1007/DCR.0b013e3181f2f202. [DOI] [PubMed] [Google Scholar]
- 14.Lorisch C, Paltiel C, Gelmon K, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006;24:4888–4894. doi: 10.1200/JCO.2005.01.6089. [DOI] [PubMed] [Google Scholar]
- 15.Sorensen LT, Karlsmark T, Gottrup F. Abstinence from smoking reduces incisional wound infection: a randomized control trial. Ann Surg. 2003;238:1–5. doi: 10.1097/01.SLA.0000074980.39700.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Moller AM, Villebro N, Pedersen T, Tonnesen H. Effect of preoperative smoking intervention on postoperative complications: a randomized clinical trial. Lancet. 2002;359:114–117. doi: 10.1016/S0140-6736(02)07369-5. [DOI] [PubMed] [Google Scholar]
- 17.Kuri M, Nakagawa M, Tanaka H, Hasuo S, Kishi Y. Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery. Anesthesiology. 2005;102:892–896. doi: 10.1097/00000542-200505000-00005. [DOI] [PubMed] [Google Scholar]
- 18.Nakagawa M, Tanaka H, Tsukuma H, Kishi Y. Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery. Chest. 2001;120:705–710. doi: 10.1378/chest.120.3.705. [DOI] [PubMed] [Google Scholar]
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