This study reviews the outcomes of Mohs micrographic surgery using full-thickness skin grafts and composite grafts with respect to patient- and surgery-specific variables, particularly early vs delayed defect reconstruction.
Key Points
Question
Is delaying reconstruction of Mohs defects with composite grafts or full-thickness skin grafts associated with decreased risk of postoperative complications?
Findings
In this cohort study of 310 full-thickness skin graft and composite graft recipients with 320 Mohs defects, early reconstruction (defined as ≤6 days) and male sex were associated with increased risk of postoperative complications. These findings are consistent with previously published studies with regard to timing of full-thickness skin graft reconstruction.
Meaning
These findings suggest that delaying graft reconstruction can improve viability of full-thickness skin grafts and composite grafts in select patients; this strategy can be considered in patients at increased risk for developing postoperative complications, such as current smokers, patients with large defects, and patients who require use of composite grafts.
Abstract
Importance
Reconstructing Mohs defects often requires grafting in the form of full-thickness skin grafts (FTSGs) and composite grafts. These grafts can be complicated by a variable and often indeterminable survival rate. Other researchers have found that delaying FTSG reconstruction improves graft outcomes, but the optimal interval between excision and reconstruction remains unclear, and no study has examined the association between delaying composite graft reconstruction and graft survival.
Objective
To review the outcomes of Mohs micrographic surgery defect reconstruction using FTSG and composite grafts with respect to patient- and surgery-specific variables, particularly early vs delayed reconstruction.
Design, Setting, and Participants
This retrospective, single-institution cohort study assessed patients who underwent Mohs reconstructive surgery from January 1, 2012, to January 1, 2018. No patients had to be excluded for inadequate follow-up or incomplete medical records. Delayed reconstruction was defined as greater than 6 days after Mohs excision, the third quartile of the interval to reconstruction among our cohort.
Main Outcomes and Measures
Primary outcome was postoperative complications, including hematoma, infection, dehiscence, epidermolysis, and partial or full graft loss.
Results
A total of 320 defects were reconstructed with FTSG or composite grafts in 310 patients (median [range] age, 68 [21-96] years; 167 female [53.9%]) during the 6-year study period. The mean interval between the ablative and reconstructive operations was 4.73 days (range, 0-35 days). Univariate logistic regression was used to determine the significant indicators among patient and defect characteristics analyzed. A multivariate logistic regression model found delayed reconstruction to have a protective association (odds ratio, 0.52; 95% CI, 0.27-0.97; P = .046) and male sex to have a harmful association (odds ratio, 2.51; 95% CI, 1.52-4.20; P < .001) with postoperative complications.
Conclusions and Relevance
This study found that delaying reconstruction in FTSGs and composite grafts was associated with decreased rates of postoperative complications, and male sex was associated with an increased risk of postoperative complications. The findings suggest that this strategy can be considered in patients at increased risk for developing postoperative complications, such as current smokers, patients with large defects, and patients who require use of composite grafts.
Level of Evidence
3.
Introduction
Basal cell carcinoma and squamous cell carcinoma of the head and neck are typically treated with simple surgical excision and Mohs micrographic surgery (MMS).1 Resultant defects often require repair, and the reconstructing surgeon must select the most appropriate reconstructive modality for the defect, considering functional and aesthetic outcomes. Full-thickness skin grafts (FTSGs) and composite grafts are 2 reconstructive techniques frequently used to reconstruct Mohs defects. However, grafting is associated with an increased rate of necrosis compared with local and interpolated flaps because of the temporary loss of blood supply.2,3,4
The benefit of delaying placement of FTSGs has previously been described by multiple groups.3,5,6,7 These studies evaluated only FTSG reconstruction, but graft loss is an even greater risk in defects reconstructed with composite (skin and cartilage) grafts.4,8 Alterations in surgical technique and use of systemic and topical pharmacotherapy, hyperbaric oxygen, and hypothermia are techniques that improve composite graft survival, but the consequences of delaying reconstruction are still unclear.8 We hypothesized that delaying FTSG and composite graft reconstruction is associated with decreased risk of graft necrosis and other functional complications. We performed a large retrospective review using logistic regression modeling to evaluate our hypothesis.
Methods
Study Design
We performed a retrospective medical record review from January 1, 2012, through January 1, 2018, at a single academic medical center. Participants in this study were patients of the senior authors (S.S.P. and J.J.C.). All patients had a minimum of 1 week of follow-up after their reconstruction. There were no patients who had to be excluded because of inadequate follow-up or incomplete medical records. All patients who undergo MMS at our institution (University of Virginia Health System) sign a consent form approved by the University of Virginia Institutional Review Board for Health Sciences Research for data and photograph entry into our previously published database. Institutional review board approval extends to all research using this database.4,9 Data were deidentified; however, our research database has facial photographs, which by definition is an identifier. This study did not require looking at the photographs but only the outcomes as described in the medical record regarding graft take or complications.
Data Collection
Patient characteristics included in our database were age, sex, smoking status, history of diabetes, use of anticoagulant or antiplatelet therapies, and history of radiotherapy to the head and neck. Perioperative characteristics include the date of MMS, date of reconstruction, defect characteristics, and reconstructive details. Composite location defects were defined as defects that involved more than 1 facial unit. Reconstructive techniques used for each defect were recorded, including local flaps, interpolated flaps, FTSGs, cartilage grafts, composite grafts, and combined reconstruction. Post-MMS wound care was not standardized because of the many MMS surgeons who refer patients to our practice.
Main Outcome Measures
The primary outcome measure was postoperative functional complications; aesthetic outcomes were not assessed in this study. Specific complications included hematoma, infection, dehiscence, epidermal sloughing (epidermolysis), and graft necrosis. Hematoma was defined by clinical examination and included as a complication whether an intervention was required or whether it resolved with observation alone. Infection was defined clinically and treated with antibiotics with or without surgical intervention. Partial graft loss was defined clinically by loss of any portion of the graft, including even a small section of epidermolysis that progressed to a scab; even if the area healed with wound care (as most did), it was counted as partial necrosis. Complete graft loss was defined clinically as greater than 90% loss of the graft. Dehiscence was defined as any separation at the suture line.
Statistical Analysis
Statistical analysis was performed using the R statistical computing language (R Foundation for Statistical Computing). A level of significance of P < .05 was established for all statistical tests. Descriptive statistics of the patient and defect characteristics were calculated, and the Pearson χ2 test and 2-tailed paired t test were used to evaluate differences in categorical and continuous variables, respectively, between groups. Univariate logistic regression models determining postoperative complications were constructed from possible variables. A multivariable logistic regression model was constructed from those univariate variables with a P < .20 and other clinically relevant variables.
Results
A total of 320 defects in 310 patients (median [range] age, 68 [21-96] years; 167 female [53.9%]) were reconstructed using FTSGs or composite grafts during the study period. A total of 252 defects were reconstructed with FTSGs and 71 with composite skin grafts. Patient and defect characteristics are summarized in Table 1. Of the patients included in the study, 57 (18.4%) were current smokers and 77 (24.8%) were receiving antiplatelet therapy. Defect locations are summarized in Table 1. Nasal defects were the most common in our population, and nearly 10% were composite defects. The overall number of complications was 107 (33.4%), and the most common complication was partial graft loss (most of which was temporary epidermolysis), comprising 87 (27.2%) of all procedures (Table 2). The mean interval between MMS and reconstruction was shorter in the group experiencing postoperative complications (3.49 vs 5.36 days, P = .009).
Table 1. Patient and Defect Characteristics.
| Characteristic | Findinga |
|---|---|
| Patient Characteristics (N = 310) | |
| Age, y | |
| Mean (SD) | 67.24 (12.9) |
| Median (range) | 68 (21-96) |
| Sex | |
| Male | 143 (46.1) |
| Female | 167 (53.9) |
| Current smoker | 57 (18.4) |
| Diabetes mellitus | 36 (11.6) |
| Prior radiotherapy to head and neck | 3 (<0.01) |
| Anticoagulation therapy | 19 (6.1) |
| Antiplatelet therapy | 77 (24.8) |
| Defect Characteristics (N = 320) | |
| Location | |
| Nose | 227 (70.9) |
| Forehead | 13 (4.1) |
| Scalp | 23 (7.2) |
| Cheek | 25 (7.8) |
| Lip | 7 (2.2) |
| Eyelid | 5 (1.6) |
| Ear | 20 (6.3) |
| Composite | 37 (11.6) |
| Interval to reconstruction, d | |
| Mean (IQR) | 4.7 (1-6) |
| Median (range) | 1 (0-35) |
| FTSG | 252 (78.8) |
| Composite graft | 71 (22.2) |
| Defect area, mean (median) [range], cm2 | 2.83 (6.67) [0.1-91] |
Abbreviations: FTSG, full-thickness skin graft; IQR, interquartile range.
Data are presented as number (percentage) of patients unless otherwise indicated.
Table 2. Types of Postoperative Complications.
| Complication | No. (%) of Procedures (N = 320) |
|---|---|
| All complications | 107 (33.4) |
| Hematoma | 6 (1.9) |
| Infection | 4 (1.3) |
| Dehiscence | 3 (0.9) |
| Epidermolysis | 14 (4.4) |
| Partial graft necrosis | 87 (27.2) |
| Complete graft necrosis | 10 (3.1) |
For composite graft and FTSG reconstruction, the interval between ablative and reconstructive surgery had a positively skewed distribution with a median of 1 day, a mean of 4.7 days, and a range of 0 to 35 days (Figure). Early and delayed reconstructions were defined by a cutoff at the third quartile of 6 days (early reconstruction defined as ≤6 days and delayed reconstruction as >6 days). The baseline characteristics of the patients and defects were compared between those who received early vs delayed reconstruction. The only statistically significant difference was the proportion of complications; the complication rate was 36.4% in the early group vs 22.9% in the delayed group (P = .03) (Table 3).
Figure. Number of Defects and Distribution of Complications at Different Intervals to Graft Reconstruction.
Table 3. Comparison of the Baseline Characteristics of Defects Reconstructed Early vs Late.
| Characteristic | Interval, da | P Value | |
|---|---|---|---|
| ≤6 (n = 250) | >6 (n = 70) | ||
| Male | 120 (48.0) | 27 (38.6) | .16 |
| Female | 130 (52.0) | 43 (61.4) | |
| Nonsmoker | 199 (79.6) | 62 (88.6) | .09 |
| Current smoker | 51 (20.4) | 8 (11.4) | |
| No diabetes | 220 (88.0) | 62 (88.6) | .90 |
| Diabetes | 30 (12.0) | 8 (11.4) | |
| No anticoagulant use | 233 (93.2) | 66 (92.3) | .75 |
| Anticoagulant use | 17 (6.8) | 4 (5.7) | |
| No antiplatelet use | 193 (77.2) | 47 (67.1) | .09 |
| Antiplatelet use | 57 (22.8) | 23 (32.9) | |
| No prior radiotherapy | 247 (98.8) | 70 (100) | .36 |
| Prior radiotherapy | 3 (1.2) | 0 | |
| No FTSG | 48 (19.2) | 20 (28.6) | .09 |
| FTSG | 202 (80.8) | 50 (71.4) | |
| No composite graft | 199 (79.6) | 50 (71.4) | .15 |
| Composite graft | 51 (20.4) | 20 (28.6) | |
| No complication | 159 (63.6) | 54 (77.1) | .03 |
| Complication | 91 (36.4) | 16 (22.9) | |
| Location of defect | |||
| Nose | 178 (71.2) | 49 (70.0) | .56 |
| Forehead | 11 (4.4) | 2 (2.9) | |
| Scalp | 19 (7.6) | 4 (5.7) | |
| Cheek | 18 (7.2) | 7 (1.0) | |
| Lip | 7 (2.8) | 0 | |
| Eyelid | 3 (1.2) | 2 (2.9) | |
| Ear | 14 (5.6) | 6 (8.9) | |
| Area, mean, cm2 | 6.9 | 5.8 | .32 |
| Age, mean, y | 67.4 | 67.5 | .96 |
Abbreviation: FTSG, full-thickness skin graft.
Data are presented as number (percentage) of patients unless otherwise indicated.
On univariate analysis, male sex, early reconstruction, and increasing defect size were statistically significant variables associated with an increased risk of postoperative complications. A multivariable logistic regression model was constructed with all variables with P < .20 on univariable analysis and additional clinically relevant variables, including age, current smoking status, and composite location.4,10,11 The statistically significant variables in the multivariable regression model were male sex and delayed reconstruction (Table 4). Delayed reconstruction had a protective association (odds ratio, 0.52; 95% CI, 0.27-0.97; P = .046), and male sex had a harmful association (odds ratio, 2.51; 95% CI, 1.52-4.20; P < .001).
Table 4. Univariate and Multivariate Logistic Regression Model Variables.
| Variable | Univariate Model | Multivariate Model | |||
|---|---|---|---|---|---|
| Coefficient | P Value | Coefficient | OR (95% CI) | P Value | |
| Age | 0.0071 | .45 | −0.0055 | 0.10 (0.98-1.01) | .60 |
| Male sex | 1.0241 | <.001 | 0.9217 | 2.51 (1.52-4.20) | <.001 |
| Smoking | 0.1174 | .70 | −0.0812 | 0.92 (0.48-1.74) | .80 |
| Antiplatelet therapy | 0.4543 | .09 | 0.5290 | 1.70 (0.96-3.01) | .07 |
| Interval >6 d | −0.6584 | .04 | −0.6529 | 0.52 (0.27-0.97) | .046 |
| Size of defect | 0.0293 | .02 | 0.0200 | 1.02 (0.10-1.05) | .12 |
| Composite location | 0.2180 | .55 | −0.0573 | 0.94 (0.44-1.98) | .88 |
| Diabetes mellitus | 0.2978 | .40 | NA | NA | NA |
| Anticoagulant therapy | −0.0050 | .99 | NA | NA | NA |
| Skin graft | −0.1868 | .51 | NA | NA | NA |
| Composite graft | 0.2595 | .35 | NA | NA | NA |
Abbreviations: NA, not applicable; OR, odds ratio.
Discussion
The reconstructive surgeon must decide whether to perform reconstruction in an immediate or delayed manner when repairing Mohs defects. We hypothesized that delaying graft-specific reconstruction would be associated with a decreased risk of graft loss and other postoperative complications, and our regression analyses supported this hypothesis. In patients receiving a composite graft or FSTG, those who underwent delayed reconstruction had 0.52 times lesser odds of experiencing postoperative complications than those who underwent reconstruction early. In addition, male sex was associated with an increased risk of developing postoperative complications. Similar findings have been demonstrated in previous studies5,6,7,8 on early vs delayed FTSG surgery, although to our knowledge, this is the first study to describe patients receiving composite grafts.
One of the earliest studies looking at delayed FTSG reconstruction was performed by Thibault and Bennett.5 They also found that delaying reconstruction (2-8 days) was a protective factor and that male sex was associated with increased rates of graft necrosis. Robinson and Dillig6 prospectively studied the effect of delaying FTSG reconstruction by 12 to 14 days and found the delayed group had improved wound healing, aesthetic results, and functional outcomes in defects that involved the ala and nasal tip. They noted the development of granulation tissue at the time of reconstruction, which they hypothesized led to improved outcomes in the delayed group. In other studies on both graft and flap reconstruction of Mohs defects delayed more than 2 days, one study4 found no increased risk in postoperative complications and another11 demonstrated a harmful effect of delaying reconstruction.
Immediately after graft placement, the graft depends on plasmatic imbibition—uptake of fluid and nutrients from the adjacent wound bed. Delaying graft placement allows the development of granulation tissue within the wound bed with its associated vascular ingrowth, which is especially important because electrocautery is frequently used in MMS and tissue that appears to be viable may in fact be condemned because of adjacent cautery burn. Improved vascular wound beds lead to a shortened ischemic period, which can last 48 hours after graft placement before capillary ingrowth occurs, also known as inosculation.3,7 After ablative surgery, Gruber et al3 noted an evolution of the wound bed. At 5 to 7 days postoperatively, there was still residual wound necrosis from electrocautery, whereas by 12 to 14 days after excision, significant granulation tissue has formed. We believe that this improved vascular wound bed reduces graft necrosis, which comprised most of the complications encountered in our study. Other proposed theories as to why delaying graft reconstruction is associated with decreases in complications include decreased risk of bleeding and decreased depth of the wound bed.6,7
The reason why men were found to have increased risk of postoperative complications in our study and the one performed by Thibault and Bennett5 is not immediately clear. Thibault and Bennett5 proposed that higher sebaceous gland density in men could explain the higher rates of graft necrosis. Men also have increased skin thickness, which may affect graft take.5,12 Although not accounted for in our data, the senior surgeons note that patients, regardless of sex, with thicker sebaceous skin routinely have more graft complications. In addition to needing to leave a thicker graft to match the surrounding skin, it is possible that the higher bacterial load in the sebaceous glands contributes to graft failure.
We found on univariate testing that male sex, defect size, and early reconstruction were associated with an increased risk of developing postoperative complications. On univariate analysis, age, current smoking status, composite location, history of diabetes, and anticoagulant medication use were not associated with an increased risk of postoperative complications. These variables were chosen because they have previously been reported by others to affect postoperative outcomes. Smoking has been found in several studies4,10,13 to be associated with increased complications in Mohs defect reconstruction. However, a large prospective study14 found no increased risk of necrosis after cutaneous surgery in smokers vs nonsmokers. Although there is mixed evidence on whether smoking is associated with increased risk of postoperative complications, smoking cessation is highly encouraged because of the known negative association it has with wound healing.15 In a previous study,4 which evaluated all Mohs defect reconstruction modalities, smoking was associated with increased risk of postoperative complications. In that study,4 the rate of smoking was 20.5% in 591 patients, whereas in our current study, the prevalence was slightly lower at 18.4% of 310 patients. The larger sample size and higher prevalence may have made the association of smoking with postoperative outcomes easier to detect in prior models.
Anticoagulant or antiplatelet medication use was not significantly associated with adverse outcomes, a finding that is consistent with previously published studies.4,16,17 A history of diabetes mellitus was also not associated with postoperative complications. Although diabetes is associated with adverse outcomes in head and neck free flap reconstruction, this was not true in prior studies4,11,18 that examined the association of diabetes with MMS defect reconstruction.
Future studies would require establishing the optimal period for improved graft outcomes based on other measures of graft success, such as aesthetic outcomes and wound contraction, which are especially important in the nasal valve area. In these future studies, detailed wound bed assessments at consultation and just before reconstruction could determine the correlation of granulation tissue formation and the adequacy of wound care with postoperative complications. Assessments of sebaceous gland density and donor skin thickness could help identify possible explanations for differences in outcomes between sexes.
Delaying reconstruction may provide another means to improve the outcomes of FTSGs and composite grafts. From our findings, discussing the potential benefit of delayed wound grafting may be presented to patients while taking into account their willingness to care for an open wound and surgery scheduling needs. This counseling is most important in a select group of patients at increased risk for postoperative complications, such as current smokers, patients with large defects, and patients with defects in which a composite graft will be used for reconstruction.
Strengths and Limitations
The strengths of our study include our large patient population and the inclusion of composite grafts in our cohort for analysis, which has not been done before this study.4,11 The postoperative graft recipient site care and postoperative evaluation were also standardized between the 2 senior authors (S.S.P. and J.J.C.).
The retrospective nature of this study was a limitation because we relied on the documentation available in the electronic medical record. The distribution of time to delay was nonparametric; therefore, we could accurately evaluate time to delay as a linear variable. Given the nonparametric distribution, we followed the statistical practice of picking the third quartile as a binary variable (before/after). Thus, we could not directly compare the days of delay with other studies3,6 that found 12 to 14 days of delay (and also the preferred minimum delay time by J.J.C.) or pick a statistically strongest day beyond which delay confers the most protection using a receiver operating characteristic curve. Patients were also referred from multiple Mohs surgeon practices, where postoperative care was not standardized.
The largest component of our complications was partial graft necrosis (87 of 107 complications), most of which was epidermolysis (Table 2). Because grafts with epidermolysis typically heal well without any long-term adverse events, it could be argued that measuring epidermolysis as a complication is not clinically sensible. However, as an indicator of graft health and viability, epidermolysis is important to observe and gives a measure to compare grafting techniques because total graft loss occurs at such a low event rate (10 total losses of 320 grafts) that comparison becomes statistically difficult.
Conclusions
It is important to counsel patients regarding patient-specific and perioperative factors that may improve graft survival. In this study, we found that early reconstruction and male sex were associated with increased rates of postoperative complications in FTSG and composite graft recipients. It may be particularly important to consider graft delay as a method of improving graft viability even in composite graft recipients or those with risk factors for adverse outcomes, such as smokers. Further study is needed into the direct association between wound bed granulation tissue with graft success. Prospective study is also needed to confirm our findings and those by prior groups.
References
- 1.Thissen MR, Neumann MH, Schouten LJ. A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol. 1999;135(10):1177-1183. doi: 10.1001/archderm.135.10.1177 [DOI] [PubMed] [Google Scholar]
- 2.Rogers-Vizena CR, Lalonde DH, Menick FJ, Bentz ML. Surgical treatment and reconstruction of nonmelanoma facial skin cancers. Plast Reconstr Surg. 2015;135(5):895e-908e. doi: 10.1097/PRS.0000000000001146 [DOI] [PubMed] [Google Scholar]
- 3.Gruber PJ, Walen S, Massa ST, Maher IA. Using grafts and granulation to improve nasal repair. Facial Plast Surg. 2017;33(1):20-26. doi: 10.1055/s-0036-1597948 [DOI] [PubMed] [Google Scholar]
- 4.Miller MQ, David AP, McLean JE, Park SS, Christophel J. Association of Mohs reconstructive surgery timing with postoperative complications. JAMA Facial Plast Surg. 2017;;20(2):122-127. doi: 10.1001/jamafacial.2017.1154 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Thibault MJ, Bennett RG. Success of delayed full-thickness skin grafts after Mohs micrographic surgery. J Am Acad Dermatol. 1995;32(6):1004-1009. doi: 10.1016/0190-9622(95)91340-8 [DOI] [PubMed] [Google Scholar]
- 6.Robinson JK, Dillig G. The advantages of delayed nasal full-thickness skin grafting after Mohs micrographic surgery. Dermatol Surg. 2002;28(9):845-851. doi: 10.1097/00042728-200209000-00013 [DOI] [PubMed] [Google Scholar]
- 7.Lewis R, Lang PG Jr. Delayed full-thickness skin grafts revisited. Dermatol Surg. 2003;29(11):1113-1117. [DOI] [PubMed] [Google Scholar]
- 8.Harbison JM, Kriet JD, Humphrey CD. Improving outcomes for composite grafts in nasal reconstruction. Curr Opin Otolaryngol Head Neck Surg. 2012;20(4):267-273. doi: 10.1097/MOO.0b013e328355b1f2 [DOI] [PubMed] [Google Scholar]
- 9.Miller MQ, Rikhi SR, Park SS, Christophel JJ. An innovative photographic database for cutaneous facial defects. Laryngoscope. 2016;126(11):2451-2455. doi: 10.1002/lary.25917 [DOI] [PubMed] [Google Scholar]
- 10.Goldminz D, Bennett RG. Cigarette smoking and flap and full-thickness graft necrosis. Arch Dermatol. 1991;127(7):1012-1015. doi: 10.1001/archderm.1991.01680060086009 [DOI] [PubMed] [Google Scholar]
- 11.Patel SA, Liu JJ, Murakami CS, Berg D, Akkina SR, Bhrany AD. Complication rates in delayed reconstruction of the head and neck after Mohs micrographic surgery. JAMA Facial Plast Surg. 2016;18(5):340-346. doi: 10.1001/jamafacial.2016.0363 [DOI] [PubMed] [Google Scholar]
- 12.Dao H Jr, Kazin RA. Gender differences in skin: a review of the literature. Gend Med. 2007;4(4):308-328. doi: 10.1016/S1550-8579(07)80061-1 [DOI] [PubMed] [Google Scholar]
- 13.Woodard CR, Park SS. Reconstruction of nasal defects 1.5 cm or smaller. Arch Facial Plast Surg. 2011;13(2):97-102. doi: 10.1001/archfacial.2011.6 [DOI] [PubMed] [Google Scholar]
- 14.Dixon AJ, Dixon MP, Dixon JB, Del Mar CB. Prospective study of skin surgery in smokers vs. nonsmokers. Br J Dermatol. 2009;160(2):365-367. doi: 10.1111/j.1365-2133.2008.08846.x [DOI] [PubMed] [Google Scholar]
- 15.Silverstein P. Smoking and wound healing. Am J Med. 1992;93(1A):22S-24S. doi: 10.1016/0002-9343(92)90623-J [DOI] [PubMed] [Google Scholar]
- 16.Otley CC, Fewkes JL, Frank W, Olbricht SM. Complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs. Arch Dermatol. 1996;132(2):161-166. doi: 10.1001/archderm.1996.03890260063009 [DOI] [PubMed] [Google Scholar]
- 17.Kraft CT, Bellile E, Baker SR, Kim JC, Moyer JS. Anticoagulant complications in facial plastic and reconstructive surgery. JAMA Facial Plast Surg. 2015;17(2):103-107. doi: 10.1001/jamafacial.2014.1147 [DOI] [PubMed] [Google Scholar]
- 18.Valentini V, Cassoni A, Marianetti TM, et al. Diabetes as main risk factor in head and neck reconstructive surgery with free flaps. J Craniofac Surg. 2008;19(4):1080-1084. doi: 10.1097/SCS.0b013e3181763531 [DOI] [PubMed] [Google Scholar]