Key Points
Question
Is smoking associated with an increased risk of acute and long-term postoperative complications after Mohs reconstruction with a flap or graft?
Findings
In this case-control study of 1008 patients undergoing Mohs reconstruction repaired by flap or graft, both current and former smoking were associated with an increased risk of acute complications. However, there was not a similar association between smoking status and long-term complications.
Meaning
This study suggests that smoking is an important lifestyle factor to consider for preoperative planning; these results may allow the surgeon to better quantify the magnitude of risk.
Abstract
Importance
Smoking, a common lifestyle trait, is considered by many surgeons to be a major risk factor for postoperative complications. However, in the literature on local reconstruction, the association between smoking and the rate of postoperative complications after cutaneous tissue transfer is not well characterized.
Objective
To study the outcomes of flaps and grafts used in Mohs micrographic surgery reconstruction with respect to smoking status and patient-specific and surgery-specific variables.
Design, Setting, and Participants
This retrospective case-control study was conducted at a single tertiary referral center among 1008 patients who underwent Mohs reconstruction repaired by flap or graft between July 1, 2012, and June 30, 2016, and were selected via consecutive sampling. Cases with incomplete records or those in which a single flap or graft was used to repair multiple defects were excluded. Data analysis was performed from September 2017 to January 2018.
Main Outcomes and Measures
Postoperative acute and long-term complications. Acute complications included postsurgical infection, dehiscence, hematoma, uncontrolled bleeding, and tissue necrosis that required medical counseling or intervention. Long-term complications included functional or cosmetic outcomes that prompted the patient to request or the surgeon to offer additional intervention.
Results
Of the 1008 patients included in the study (396 women and 612 men), the median (SD) age was 70 (12) years (range, 21-90 years). A total of 128 patients (12.7%) were current smokers, 385 (38.2%) were former smokers, and 495 (49.1%) were never smokers. On multivariate logistic regression, current smoking (odds ratio [OR], 9.58; 95% CI, 3.63-25.3), former smoking (OR, 3.64; 95% CI, 1.41-9.38), larger defect size (OR, 2.25; 95% CI, 1.58-3.20), and the use of free cartilage graft (OR, 8.19; 95% CI, 2.02-33.1) were associated with increased risks of acute complications. For long-term complications, central face location (OR, 25.4; 95% CI, 6.16-106.5), use of interpolation flap or flap-graft combination (OR, 3.49; 95% CI, 1.81-6.74), larger flap size (OR, 1.42; 95% CI, 1.09-1.87), and basal cell carcinomas or other basaloid tumors (OR, 3.43; 95% CI, 1.03-11.5) were associated with an increased risk, whereas increased age (OR, 0.66 per 10-year interval; 95% CI, 0.54-0.80) was associated with decreased risk.
Conclusions and Relevance
This study suggests that both current and former smokers are at increased risk for acute postsurgical complications but that smoking status is not associated with long-term complications. These findings may allow the surgeon to better quantify the magnitude of risk and provide helpful information for patient counseling.
Level of Evidence
3.
This case-control study examines the outcomes of flaps and grafts used in Mohs micrographic surgery reconstruction with respect to smoking status and patient-specific and surgery-specific variables.
Introduction
Smoking is a common lifestyle trait that is considered by many reconstructive surgeons to be a major risk factor for postoperative complications. There is a plethora of evidence in the literature demonstrating the negative association of smoking with the physiology and molecular biology of wound healing. Smoking can cause reduced tissue perfusion as well as carbon monoxide–induced and hydrogen cyanide–induced hypoxia.1 Moreover, smoking-induced oxidative stress can impair endothelial function and stunt the local immune response.2,3 These mechanisms are thought to increase the rate of flap necrosis4,5 and surgical site infection.6,7 The association between smoking and the risk of acute postsurgical complications is well documented across various surgical specialties.8,9,10,11,12
Nevertheless, the effect of smoking in the specific setting of cutaneous tissue transfer is not well characterized in the literature describing outcomes after Mohs reconstruction.13 There are some relevant studies on otolaryngology, plastic surgery, and breast reconstruction.14,15,16 However, the clinical scenarios and patient populations in these studies are often quite different from those encountered after Mohs reconstruction. From our review of the dermatologic surgery literature, only a single retrospective case-control study pertains to this specific topic; that study examined only flap or graft necrosis and a small subset of complications and did not control for other risk factors.4 A well-designed 2018 study examining the association between delayed repair timing and the rate of acute complications after Mohs reconstruction suggested that smoking status, along with primary defect size and type of reconstruction, may be potential risk factors.17 Other studies on the perioperative risk factors of Mohs reconstruction either had limited scope18,19 or failed to include smoking as a covariate.19,20
There are even fewer studies that address the association between smoking and the long-term outcomes of Mohs reconstruction despite many interesting and relevant findings in the basic science literature. Smoking has been shown to suppress transforming growth factor beta signaling21,22 as well as hinder collagen production and extracellular matrix remodeling.23,24,25,26 Therefore, we hoped to examine whether these mechanisms would lead to a detectable clinical difference in the rate of long-term complications.
In this study, we hypothesized that smoking is associated with increased rates of acute and long-term complications after Mohs reconstruction with a flap or a graft. In our statistical analysis, we also examined other potential risk factors including age, sex, history of diabetes, status of systemic immunosuppression, use of blood thinners, tumor type and location, and defect and repair size as well as the type of flap or graft used.
Method
Design and Data Collection
This retrospective, single-center, case-control study was conducted from July 1, 2012, to June 30, 2016. Patients were included if they underwent Mohs micrographic surgery and the resulting defect was repaired with a flap or a graft at our Mohs micrographic surgery unit, which was staffed by 2 Mohs surgeons (I.A.M.). We did not include cases in which a single flap or graft was used to repair multiple defects. An additional 43 cases were excluded because of incomplete information in the medical record. A deidentified data table was constructed to collect patient age, sex, smoking status at the time of the surgery, history of diabetes, status of systemic immunosuppression, use of blood thinners, tumor type, tumor location, defect size, repair size, and the type of flap or graft used. The trial protocol was reviewed and approved by the Saint Louis University Institutional Review Board for academic year 2017-2018. Because this was a retrospective study, the need for informed consent from the participants was waived by the Saint Louis University Institutional Review Board.
Smoking status at the time of surgery was classified as never, former, or current smoker. Documented blood thinners included aspirin, other prescription antiplatelet agents, warfarin sodium, other prescription anticoagulants, and over-the-counter supplements, such as fish oil and vitamin E. Tumor types were categorized into basal cell carcinomas (BCCs) or other basaloid tumors, in situ squamous cell carcinomas, and squamous cell carcinomas or other aggressive tumors. Other basaloid tumors included trichoblastoma and “basaloid neoplasm”; other aggressive tumors included proliferating pilar cyst, sebaceous carcinomas, mucinous carcinomas, eccrine carcinomas, and dermatofibrosarcoma protuberans. Locations were classified as central face (nose, periocular skin, and perioral skin), peripheral face (forehead, lateral face, jaw, and chin), ear, and scalp and other nonfacial skin. Repair techniques included local flaps (advancement, transposition, rotation, and island pedicle), full-thickness skin grafts, interpolation flaps, free cartilage grafts, and flap-graft combinations.
Main Outcome Measures
In our practice, all patients whose repair was performed with flaps were requested to follow up at least once before the 3-month mark. All patients whose repair was performed with grafts were asked to return for suture removal and an additional follow-up at the 2-week mark along with a follow-up visit at least once before the 3-month mark. Patients were not excluded on the basis of follow-up status—all patients with completed surgical cases were included in our final analysis in the same manner as an intention-to-treat analysis. The primary outcome measures were postoperative acute complications and long-term complications. Acute complications were defined as any postsurgical infection, dehiscence, hematoma, uncontrolled bleeding, and tissue necrosis that required medical counseling or intervention. Long-term complications were defined as any postsurgical functional defect or unsatisfactory cosmesis that prompted the patient to request an additional procedural intervention or the surgeon to offer it. Such procedural interventions included intralesional corticosteroid injections, dermabrasion or laser resurfacing, and surgical revisions.
Statistical Analysis
Statistical analyses were performed using IBM SPSS Statistics, version 25 (IBM Corp). For continuous variables, univariate analyses were performed using discriminant analysis with analysis of variance. For categorical variables, univariate analyses were performed using Pearson χ2 test by default except for cases better suited for the Fisher exact test owing to a small expected number of observations less than 5. All variables with P < .20 on univariate analysis and smoking status were included in the first iteration of multivariate logistic regression. To avoid overfitting of the regression model,27 only covariates with P < .05 from the first iteration were used to perform the second iteration of multivariate logistic regression. All P values were 2-sided, and statistical significance was defined as P < .05. Data analysis was performed from September 2017 to January 2018.
Results
A total of 1008 patients met all inclusion criteria. All patient demographics and clinical characteristics were compiled into Table 1. The median (SD) age was 70 (12) years (range, 21-90 years), and there were 612 men and 396 women. A total of 128 patients (12.7%) were current smokers, 385 (38.2%) were former smokers, and 495 (49.1%) were never smokers. In all, 170 patients (16.9%) had a history of diabetes and 19 (1.9%) were immunosuppressed. For antiplatelet medications, 410 patients (40.7%) were taking aspirin and 67 (6.6%) were taking a prescription antiplatelet agent other than aspirin. For anticoagulant medications, 55 patients (5.5%) were taking warfarin and 14 (1.4%) were taking a prescription anticoagulant other than warfarin. A total of 66 patients (6.6%) were taking an over-the-counter blood thinner.
Table 1. Univariate Analysis Covariates and Primary Outcomes.
| Characteristic | Acute Complication, Valuea | P Value | Long-term Complication, Valuea | P Value |
|---|---|---|---|---|
| Age, median (SD), y | ||||
| No complication | 69.3 (12.2) | .61b | 69.8 (12.0) | <.001b,c |
| With complication | 68.3 (14.4) | 62.6 (13.8) | ||
| Defect size, mean (SD), cm2 | ||||
| No complication | 3.5 (5.4) | <.001b,c | 3.7 (5.6) | .38b |
| With complication | 6.8 (6.3) | 3.1 (3.2) | ||
| Flap size, mean (SD), cm2 | ||||
| No complication | 12.4 (14.1) | <.001b,c | 12.5 (14.6) | .08b,c |
| With complication | 20.9 (24.3) | 15.6 (16.0) | ||
| Sex | ||||
| Male | 32/612 (5.2) | .02c,d | 35/612 (5.7) | .01c,d |
| Female | 9/396 (2.3) | 40/396 (10.1) | ||
| Smoking status | ||||
| Never | 6/495 (1.2) | <.001c,d | 40/495 (8.1) | .33d |
| Former | 18/385 (4.7) | 23/385 (6.0) | ||
| Current | 17/128 (13.3) | 12/128 (9.4) | ||
| Tumor type | ||||
| SCCIS | 1/60 (1.7) | .77e | 1/60 (1.7) | .001c,e |
| BCC or basaloid | 35/820 (4.3) | 72/820 (8.8) | ||
| SCC or other | 5/128 (3.9) | 2/128 (1.6) | ||
| Location | ||||
| Peripheral face | 7/169 (4.1) | .10c,e | 2/169 (1.2) | <.001c,e |
| Central face | 23/627 (3.7) | 73/627 (11.6) | ||
| Ear | 5/157 (3.2) | 0/157 | ||
| Scalp and other | 6/55 (10.9) | 0/55 | ||
| Repair type | ||||
| Local flap | 25/751 (3.3) | .008c,e | 48/751 (6.4) | <.001c,e |
| FTSG | 7/166 (4.2) | 8/166 (4.8) | ||
| Interpolation or combined flap or graft | 6/78 (7.7) | 18/78 (23.1) | ||
| Free cartilage graft | 3/13 (23.1) | 1/13 (7.7) | ||
| Antiplatelet agent | ||||
| None | 21/531 (4.0) | .03c,e | 42/531 (7.9) | .67e |
| Aspirin | 13/410 (3.2) | 30/410 (7.3) | ||
| Other | 7/67 (10.4) | 3/67 (4.5) | ||
| Warfarin or DOAC | ||||
| None | 37/939 (3.9) | .42e | 73/939 (7.8) | .54e |
| Warfarin | 3/55 (5.5) | 2/55 (3.6) | ||
| Other | 1/14 (7.1) | 0/14 | ||
| Other anticoagulant agent | ||||
| No | 37/942 (3.9) | .34e | 71/942 (7.5) | .81e |
| Yes | 4/66 (6.1) | 4/66 (6.1) | ||
| Diabetes | ||||
| No | 37/838 (4.4) | .22d | 61/838 (7.3) | .67d |
| Yes | 4/170 (2.4) | 14/170 (8.2) | ||
| Immunosuppression | ||||
| No | 40/989 (4.0) | .55e | 75/989 (7.6) | .39e |
| Yes | 1/19 (5.3) | 0/19 |
Abbreviations: BCC, basal cell carcinoma; DOAC, direct oral anticoagulant; FTSG, full-thickness skin graft; SCC, squamous cell carcinoma; SCCIS, squamous cell carcinoma in situ.
Data are presented as number/total number (percentage) of patients unless otherwise indicated.
Derived using discriminant analysis with analysis of variance.
Statistically significant.
Derived using Pearson χ2 test.
Derived using Fisher exact test.
For tumor types, 820 tumors (81.3%) were BCCs or other basaloid tumors, 128 (12.7%) were squamous cell carcinomas or other aggressive tumors, and 60 (6.0%) were in situ squamous cell carcinomas (Table 1). There were no melanoma cases in our Mohs log during the study period because head and neck melanomas were removed via geometric staged excision. For tumor locations, 627 (62.2%) were on the central face, 169 (16.8%) on the lateral face, 157 (15.6%) on the ear, and 55 (5.5%) on the scalp or other locations. The mean (SD) defect size was 3.6 (5.5) cm2 (range, 0.18-110 cm2), and the mean (SD) flap or graft size was 12.7 (14.7) cm2 (range, 0.25-240 cm2). For repairs, a local flap was used in 751 cases (74.5%), a full-thickness skin graft in 166 cases (16.5%), an interpolation flap or a flap-graft combination in 78 cases (7.7%), and a free cartilage graft in 13 cases (1.3%).
The overall rate of acute complications was 4.1% (n = 41). This included 19 cases of infection, 10 of flap or graft necrosis (1.0%), 10 of wound dehiscence, and 6 of hematoma or uncontrolled bleeding (numbers total more than 41 because some patients experienced more than 1 acute complication). The overall rate of long-term complications was 7.4% (n = 75). Of these, 38 cases required only intralesional corticosteroid injections, 26 required dermabrasion or laser resurfacing, 6 required surgical revision, and the patients in 5 cases declined scar resurfacing.
On univariate analysis, the rate of acute complications was found to be significantly associated with defect size, flap size, sex, smoking status, repair type, and antiplatelet use (Table 1). Tumor size also met the inclusion criteria for the first iteration of multivariate analysis. Because there is a proportional association between defect size and flap size, only defect size was included in the multivariate analysis because of its smaller P value on univariate analysis and its known association with the risk of acute complications.17 After 2 iterations of multivariate logistic regression (Table 2), current smoking (odds ratio [OR], 9.58; 95% CI, 3.63-25.3), former smoking (OR, 3.64; 95% CI, 1.41-9.38), larger defect size (OR, 2.25; 95% CI, 1.58-3.20), and the use of free cartilage graft (OR, 8.19; 95% CI, 2.02-33.1) were found to be associated with an increased rate of acute complications. This multivariate model provided excellent predictive value within our data set, with an area under the receiving operating characteristic curve of 0.81 (95% CI, 0.74-0.88).
Table 2. Multivariate Logistic Regression of Eligible Covariates for Acute Complications.
| Acute Complication | Iteration 1 | Iteration 2 | ||
|---|---|---|---|---|
| OR (95% CI) | P Value | OR (95% CI) | P Value | |
| Former smoker | 3.15 (1.19-8.33) | .02 | 3.64 (1.41-9.38) | .007 |
| Current smoker | 9.12 (3.40-24.4) | <.001 | 9.58 (3.63-25.3) | <.001 |
| Defect size (Ln)a | 2.10 (1.46-3.03) | <.001 | 2.25 (1.58-3.20) | <.001 |
| Free cartilage graft | 7.04 (1.67-29.6) | .008 | 8.19 (2.02-33.1) | .003 |
| Other antiplatelet | 2.2 (0.85-5.6) | .11 | NA | NA |
| Location | 1.7 (0.63-4.6) | .30 | NA | NA |
| Male sex | 1.4 (0.64-3.2) | .38 | NA | NA |
Abbreviations: Ln, natural log–transformed; NA, not applicable; OR, odds ratio.
Natural log transformation was performed to normalize the sample distribution into a bell curve.
On univariate analysis, the rate of long-term complications was found to be significantly associated with tumor location, repair type, flap size, age, tumor type, and sex (Table 1). As the primary variable of interest, smoking status was also included in the first iteration of multivariate analysis. After 2 iterations of multivariate logistic regression (Table 3), central face location (OR, 25.4; 95% CI, 6.16-106.5), use of an interpolation flap or a flap-graft combination (OR, 3.49; 95% CI, 1.81-6.74), larger flap size (OR, 1.42; 95% CI, 1.09-1.87), and BCCs or other basaloid tumors (OR, 3.43; 95% CI, 1.03-11.5) were found to be associated with an increased rate of long-term complications. Older age (OR, 0.66; 95% CI, 0.54-0.80) was associated with a decreased rate of long-term complications. This multivariate model also provided excellent predictive value within our data set, with an area under the receiving operating characteristic curve of 0.83 (95% CI, 0.78-0.86).
Table 3. Multivariate Logistic Regression of Eligible Covariates for Long-term Complications.
| Long-term Complication | Iteration 1 | Iteration 2 | ||
|---|---|---|---|---|
| OR (95% CI) | P Value | OR (95% CI) | P Value | |
| Former smoker | 0.88 (0.49-1.6) | .65 | NA | NA |
| Current smoker | 0.94 (0.44-2.0) | .88 | NA | NA |
| Central face location | 24.7 (5.94-103.1) | <.001 | 25.4 (6.16-106.5) | <.001 |
| Interpolation or combined flap-graft | 3.44 (1.77-6.68) | <.001 | 3.49 (1.81-6.74) | <.001 |
| Older age, per each 10-y increase | 0.67 (0.55-0.81) | <.001 | 0.66 (0.54-0.80) | <.001 |
| Larger flap or graft size (Ln)a | 1.44 (1.03-1.90) | .01 | 1.42 (1.09-1.87) | .01 |
| BCC or other basaloid tumor | 3.54 (1.05-11.9) | .04 | 3.43 (1.03-11.5) | .045 |
| Female sex | 1.2 (0.73-2.1) | .43 | NA | NA |
Abbreviations: BCC, basal cell carcinoma; Ln, natural log–transformed; NA, not applicable; OR, odds ratio.
Natural log transformation was performed to normalize the sample distribution into a bell curve.
Discussion
In this retrospective case-control study, we found that smoking is significantly associated with acute complications after cutaneous tissue transfer in Mohs reconstruction. Our finding is consistent with previous literature across various specialties.8,9,10,11,12,15 Similarly, the risk associated with larger defect size is consistent with findings of previous studies in the breast reconstruction literature14 and the microvascular surgery literature.28 With regard to the risk associated with free cartilage graft, the empirical evidence in the literature is scarce. Nevertheless, considering that this advanced repair technique sometimes requires blind dissection and often leaves a partial wound to be healed by secondary intent, the associated risk is not entirely surprising.
Compared with previous studies that usually categorized patients into smokers and nonsmokers, our study is unique in that it classified former smokers into a distinct group. This group also had an increased risk of acute complications compared with never smokers (OR, 3.64). This finding may explain why the OR associated with current smokers in our study (OR, 9.58) is much higher than the ORs of 2.5 to 3.6 typically found in other studies.4,17,29 The group of never smokers may serve as a better baseline than the group of nonsmokers, which includes both never smokers and former smokers. The increased risk of acute complications in former smokers may also suggest that impairment of early wound healing persists even after smoking cessation. If this finding were true, it may help explain why smoking cessation has poor efficacy in reducing postoperative complications.30
Even if smoking cessation were efficacious as some studies advocate,31 few patients tend to adhere to this recommendation. In a 2003 study, when patients were asked to stop smoking 2 weeks before and 2 weeks after an operation, only 14.7% stopped before the surgery and 41.2% stopped after the surgery.32 An alternative solution may be to offer patients a high-dose antioxidant, such as vitamin C, which can counteract some of the negative effects caused by smoking-induced oxidative stress, such as impaired endothelial function and stunted local immune response.3 In the cardiovascular and orthopedics literature, vitamin C has been shown to improve vascular perfusion33,34,35 and augment antibacterial defense.36
With regard to long-term outcomes, this study did not find smoking to be a significant risk factor. This finding is consistent with those of laser resurfacing studies in the cosmetic literature.37,38 Perhaps the molecular changes induced by smoking were not enough to cause quantifiable clinical complications, or there may be negative confounding factors yet to be uncovered. On the topic of long-term outcomes after reconstructive surgery, the literature contains few quantitative studies that rely on objective data. An important reason for this occurrence may be that postsurgical cosmesis—a large part of overall long-term outcomes—is extremely difficult to quantify objectively, and large discrepancies often exist between patient perception and physician assessment.39 Our study may be one of the earliest attempts to measure long-term postsurgical outcomes by quantifying it as the proportion of patients who requested or were offered a corrective measure.
In this study, we found that central face location, the use of an interpolated flap or a flap-graft combination, larger flap size, and BCC or basaloid tumor type were significant risk factors for long-term complications; we found increased age to be a protective factor. The central face may be a critical area because of the amount of muscle movements and its importance in defining facial symmetry.40,41 The risk associated with larger and more complicated types of repair is not surprising because such repairs often involve long scar lines and complex tension vectors. We are unable to offer a convincing explanation for the risk associated with BCCs or other basaloid tumors other than that transforming growth factor beta signaling may be an important molecular pathway for both scar formation42 and BCC tumorigenesis.43 The protective effect associated with age may be a result of different patient perceptions and expectations, as a 2016 study observed a similar trend in self-reported scar cosmesis scores after thyroid and parathyroid surgery.44
Limitations
Being a case-control study, our study was limited by its retrospective nature and the quality of its data source. Our study relied solely on the documentations in patient medical records, and neither the data collectors nor the documenting physicians were blinded to the patients’ exposures or interventions. If we had photographs for all patients at matching time points, the photographs might have provided more objective outcome measures. Furthermore, despite taking into consideration a large array of variables, it is possible to miss important unforeseeable confounders in similar retrospective studies. Therefore, a high-quality prospective study using either smoking cessation or a high-dose antioxidant as the intervention could provide valuable insights. Last, as a single-center study, the derived results may be less generalizable despite the large sample size.
Conclusions
Our study findings suggest that both current and former smokers were at increased risk for acute postsurgical complications after Mohs reconstruction with a flap or graft. Other risk factors associated with acute complications were larger defect size and the use of a cartilage graft. However, smoking status was not associated with long-term complications. The risk factors associated with long-term complications were central face location, younger age, the use of interpolated flap or flap-graft combination, larger flap size, and BCC or basaloid tumor. These findings may allow the surgeon to better quantify the magnitude of risk and provide helpful information for patient counseling.
References
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