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Figure 1.
Representative Thin Adipofascial Flap
Representative Thin Adipofascial Flap

Vascular arcade is clearly visible centrally.

Figure 2.
Postoperative Example of Near-Total Palate Reconstruction With Anterolateral Thigh Adipofascial Flap
Postoperative Example of Near-Total Palate Reconstruction With Anterolateral Thigh Adipofascial Flap

Oral mucosa has enclosed the reconstruction.

Figure 3.
Operative Example of Total Nasal Reconstruction With Anterolateral Thigh Adipofascial Flap
Operative Example of Total Nasal Reconstruction With Anterolateral Thigh Adipofascial Flap

The thin, pliable flap can easily conform to the shape of the nasal cavity.

Table.  
Patient Characteristics
Patient Characteristics
1.
Song  YG, Chen  GZ, Song  YL.  The free thigh flap: a new free flap concept based on the septocutaneous artery. Br J Plast Surg. 1984;37(2):149-159.
PubMedArticle
2.
Malhotra  K, Lian  TS, Chakradeo  V.  Vascular anatomy of anterolateral thigh flap. Laryngoscope. 2008;118(4):589-592.
PubMedArticle
3.
Hanasono  MM, Skoracki  RJ, Silva  AK, Yu  P.  Adipofascial perforator flaps for “aesthetic” head and neck reconstruction. Head Neck. 2011;33(10):1513-1519.
PubMedArticle
4.
Wang  X, Qiao  Q, Liu  Z,  et al.  Free anterolateral thigh adipofascial flap for hemifacial atrophy. Ann Plast Surg. 2005;55(6):617-622.
PubMedArticle
5.
Agostini  V, Dini  M, Mori  A, Franchi  A, Agostini  T.  Adipofascial anterolateral thigh free flap for tongue repair. Br J Plast Surg. 2003;56(6):614-618.
PubMedArticle
6.
Agostini  T, Agostini  V.  Further experience with adipofascial ALT flap for oral cavity reconstruction. J Plast Reconstr Aesthet Surg. 2008;61(10):1164-1169.
PubMedArticle
7.
Seth  R, Revenaugh  PC, Scharpf  J, Shipchandler  TZ, Fritz  MA.  Free anterolateral thigh fascia lata flap for complex nasal lining defects. JAMA Facial Plast Surg. 2013;15(1):21-28.
PubMedArticle
8.
Moloy  PJ.  Reconstruction of intermediate sized mucosal defects with the pectoralis major myofascial flap. J Otolaryngol. 1989;18(1):32-35.
PubMed
9.
Uppin  SB, Ahmad  QG, Yadav  P, Shetty  K.  Use of the submental island flap in orofacial reconstruction—a review of 20 cases. J Plast Reconstr Aesthet Surg. 2009;62(4):514-519.
PubMedArticle
10.
Nthumba  PM.  The supraclavicular artery flap: a versatile flap for neck and orofacial reconstruction. J Oral Maxillofac Surg. 2012;70(8):1997-2004.
PubMedArticle
11.
Valentini  V, Cassoni  A, Marianetti  TM, Battisti  A, Terenzi  V, Iannetti  G.  Anterolateral thigh flap for the reconstruction of head and neck defects: alternative or replacement of the radial forearm flap? J Craniofac Surg. 2008;19(4):1148-1153.
PubMedArticle
12.
Anain  SA, Yetman  RJ.  The fate of intraoral free muscle flaps: is skin necessary? Plast Reconstr Surg. 1993;91(6):1027-1031.
PubMedArticle
13.
Syme  DB, Shayan  R, Grinsell  D.  Muscle-only intra-oral mucosal defect reconstruction. J Plast Reconstr Aesthet Surg. 2012;65(12):1654-1659.
PubMedArticle
14.
Agostini  T, Agostini  V, Lazzeri  D.  Current roles of adipofascial anterolateral thigh flap in head and neck reconstructions. Head Neck. 2011;33(4):595-597.
PubMedArticle
15.
Johnson  MA, Langdon  JD.  Is skin necessary for intraoral reconstruction with myocutaneous flaps? Br J Oral Maxillofac Surg. 1990;28(5):299-301.
PubMedArticle
16.
Phillips  JG, Postlethwaite  K, Peckitt  N.  The pectoralis major muscle flap without skin in intra-oral reconstruction. Br J Oral Maxillofac Surg. 1988;26(6):479-485.
PubMedArticle
17.
Taghinia  AH, Pribaz  JJ.  Complex nasal reconstruction. Plast Reconstr Surg. 2008;121(2):15e-27e. doi:10.1097/01.prs.0000298113.56554.c3.
PubMedArticle
18.
Shaw  RJ, Batstone  MD, Blackburn  TK, Brown  JS.  The anterolateral thigh flap in head and neck reconstruction: “pearls and pitfalls.” Br J Oral Maxillofac Surg. 2010;48(1):5-10.
PubMedArticle
Original Investigation
Nov/Dec 2014

Anterolateral Thigh Adipofascial Flap in Mucosal Reconstruction

Author Affiliations
  • 1Head and Neck Institute, Department of Otolaryngology–Head and Neck Surgery, Cleveland Clinic, Cleveland, Ohio
JAMA Facial Plast Surg. 2014;16(6):395-399. doi:10.1001/jamafacial.2014.447
Abstract

Importance  This study describes a reliable technique for mucosal reconstruction of large defects using components of a common free flap technique.

Objective  To review the harvest technique and the varied scenarios in which the anterolateral thigh adipofascial flap (ALTAF) can be used for mucosal restoration in oral cavity and nasal reconstruction.

Design, Setting, and Participants  A retrospective review of the medical records of 51 consecutive patients was conducted. The patients had undergone ALTAF head and neck reconstruction between January 2009 and June 2013. Each case was reviewed, and flap survival and goal-oriented results were evaluated.

Results  Thirty patients met the inclusion criteria and were included in the analysis. The mean patient age was 60.6 years. Reconstruction sites included the tongue, palate, gingiva, floor of the mouth, and nasal mucosa. All mucosal reconstructions maintained function and form of replaced and preserved tissues. One patient (3%) experienced flap failure that was reconstructed with a contralateral adipofascial flap with excellent outcome. Three patients (10%) required minor flap revisions. There were no other complications.

Conclusions and Relevance  The ALTAF is a versatile flap easily harvested for use in several types of mucosal reconstructions.

Level of Evidence  4.

Introduction

Large mucosal defects can be challenging to the reconstructive surgeon. Throughout the oral and nasal cavities, the mucosa is a thin, compliant, and functional membrane providing properties necessary for mastication, food bolus control, speech, and nasal airway patency. The unique properties and limited supply of mucosa are fundamental difficulties in reconstruction of large defects. With larger mucosal defects, complicated closures, or irradiated fields, microvascular-free tissue transfer often is indicated to ensure vascularized coverage.

The anterolateral thigh (ALT) flap has recently become a “workhorse” of head and neck reconstruction. Since its description as a musculocutaneous free flap by Song et al in 1984,1 the ALT has been adopted for a number of indications. The flap is reliably vascularized by several perforators off of the descending or transverse branch of the lateral circumflex femoral artery. Although predominantly musculocutaneous, all of these perforators traverse the fascia overlying the vastus lateralis (fascia lata) as well as the subcutaneous fat before terminating in the subdermal plexus.2 Consequently, the ALT flap can be harvested without skin and without inclusion of muscle surrounding the perforators, resulting in a thin, pliable, ALT adipofascial free flap (ALTAF).

To date, there have been few case series and case reports36 describing the use of ALTAF in the head and neck. We now have several years of experience with this flap for mucosal reconstruction and have used it for oral cavity reconstruction, including palate, gingival, tongue, and buccal mucosa reconstruction. We also have used the flap in nasal lining reconstruction.7 In this article, we review the straightforward harvest of the ALTAF and highlight our experience with the versatile indications and some contraindications for use of this flap.

Methods

All patients undergoing free tissue transfer at the Cleveland Clinic, Cleveland, Ohio, between January 1, 2009, and June 30, 2013, were reviewed, and those undergoing ALTAF for mucosal reconstruction were included in the study. The Cleveland Clinic institutional review board approved this research and waived the need for informed consent.

All flaps were harvested as perforator-based flaps. A small fusiform skin paddle was centered over a thigh perforator after identification using handheld Doppler guidance. Medial dissection was accomplished initially to the rectus femoris muscle, where a subfascial dissection was then performed to identify fasciocutaneous or musculocutaneous perforators. Meticulous dissection was then performed along the perforators retrograde to branches of the lateral circumflex femoral artery. The small skin paddle based around one of the dominant perforators was retained during harvest to allow for easy manipulation and orientation of the flap. The perforator locations were noted on the fascia to ensure correct orientation, and the fascial edges were marked using silk sutures to again ensure correct orientation during inset (Figure 1). Perforator dissection of any musculocutaneous branches was accomplished using bipolar electrocautery and sharp dissection with meticulous attention to hemostasis. Before pedicle division, the skin paddle was removed and the flap was cut to size. Harvests were carried out in a 2-team approach while the recipient bed and vessels were prepared to limit operative and flap ischemia time.

Flap selection was based on defect location, size, shape, and necessary components. Adipofascial flaps were generally chosen for moderate to large oral cavity defects in which the underlying bony structure was maintained or an otherwise thin flap was needed. Cases of total nasal lining reconstruction were generally chosen for ALTAF flaps.

Demographic and surgical characteristics as well as operative and postoperative complications were recorded. Mucosalization was noted by clinical observation during routine postoperative follow-up. Functional factors, when appropriate, were included in the data collection.

Results

Fifty-one ALTAF flaps were identified during the study period, and 31 (61%) were performed specifically for mucosal reconstruction. The mean patient age was 60.6 years (range, 28-78 years), and demographic characteristics were similar among patients (Table). The study group comprised 16 men (53%) and 14 women (47%); the mean length of follow-up was 13.2 months (range, 1-43 months). The mean hospital length of stay was 4.6 days (range, 1-9 days). The flaps were performed for several indications, the most common being malignant neoplasms (15 [50%]) followed by exposed alveolar coverage secondary to radiotherapy or osteoradionecrosis (10 [33%]) and benign neoplasms (5 [17%]). Nineteen patients (63%) underwent radiotherapy, either prior to reconstruction or immediately following. The subsites included the nasal mucosa (11 patients [37%]), gingiva (10 [33%]), palate (4 [13%]), composite floor of the mouth (FOM) and tongue (3 [10%]), mobile tongue (1 [3%]), and FOM (1 [3%]). Overall flap size ranged from 70 to 200 cm2. Recipient vessel selection included the facial artery and vein in most cases (22 [73%]). The superficial temporal vessels (4 [13%]), angular vessels (3 [10%]), and superior thyroid vessels (1 [3%]) were selected as recipient vessels for microvascular anastomosis. There was only 1 flap failure (3%), and there were no instances of partial flap failure, wound breakdown, or need for operative microvascular revision.

All donor sites were closed primarily, and there were no donor site complications. Three patients (10%) required late revision to correct tethering of the mobile tongue resulting from postoperative scarring.

Discussion

Larger defects involving specific subsites of the oral and nasal cavities may be beyond the reconstructive ability of local or regional flaps. Areas such as the gingiva, palate, tongue, buccal mucosa, and nasal lining have limited reconstructive options because of poor local tissue availability and the specific shape and functional requirements of the subsite. Reconstructive attempts also can be limited by the heterogeneic function of various areas of the mucosa and underlying soft tissue. For example, the palate and gingival mucosa are thick and participate in masticatory function; buccal mucosa is thinner and more compliant. Even modest defects may prove to be too complicated to reconstruct with local tissues.

For larger defects, locoregional and regional flaps, such as the pectoralis major, submental island, and supraclavicular flap, have been described.810 Cutaneous free tissue transfer, including the radial forearm and ALT, have been used in the past for mucosal reconstruction. However, the included cutaneous portion is nonsecretory, hair bearing, and poorly compliant, making it less than ideal for the functionality required of the oral and nasal cavities. Furthermore, the radial forearm flap (RFF) donor site can have a higher rate of complications, such as tendon adhesion, poor sensory distribution, skin graft failure, and poor hand circulation.11 The RFF also leaves a conspicuous scar even with the arms at repose, which is undesirable for many patients. Anain and Yetman12 first reported the use of free muscle flaps for oral reconstruction to mitigate the potential drawbacks of a skin paddle, and Syme et al13 published a series of 37 patients who received muscle-only reconstructions. However, myogenous and myofascial flap use is limited owing to the flap bulk and unpredictable contraction.12 Agostini et al5 first reported a case of tongue reconstruction in 2003 and followed in 2008 and 2011 with further reports6,14 detailing their initial experience in oral cavity reconstructions using the ALTAF.

Harvesting the ALTAF flap as an adipofascial perforator flap allows the same straightforward, low-morbidity harvest of the traditional ALT flap combined with a thin, pliable flap. The harvest technique is not adversely affected in patients with a large amount of subcutaneous adipose tissue. The ALT provides the additional advantages of an inconspicuous donor site and potentially lower morbidity compared with other sites, such as the RFF. The ALTAF retains size and volume and may require less subsequent debulking, deepithelialization, and depilation procedures than flaps, retaining a cutaneous component.

Mucosalization of intraoral cutaneous flaps is variable, and patients often are left with a nonsecretory island of skin within a dynamic mucosal surface. This finding can create difficulties with food and mucus clearance that can subsequently affect eating, speech, and nasal airflow. Prior studies8,15,16 with nonepithelialized free flaps demonstrated mucosalization when the flaps were placed intraorally. Agostini et al5 observed robust mucosalization within 45 days of adipofascial flap inset, and biopsy results of the surface revealed a squamous epithelial lining with stromal nerve structures.

Subsites

Tongue reconstruction with the ALTAF yields a pleasing postoperative result with exceptional color match, bulk, and mobility of the neomucosa. We have also had good results with FOM reconstructions that do not contain a mobile tongue component. In these cases, the flap allows for a moist FOM that does not collect food and provides a thin base for tongue articulation. Tongue and FOM composite defects were initially attempted with this flap, but 3 patients had synechial formation between the 2 components, limiting articulation and requiring surgical revision. The formation was particularly evident when 2 constantly opposed surfaces were reconstructed (eg, the ventral tongue and anterior FOM). Consequently, in cases of 2 opposing mucosal surfaces, we caution against use of the ALTAF.

Subsites of the oral cavity that require a thin, broad coverage are ideal for ALTAF reconstruction. Buccal inset, similar to the FOM, allows for a quickly mucosalized surface that will minimally trap food and secretions—this is particularly useful for defects that extend to the alveolus and FOM. However, given the sensitivity of patients to scar contracture in the buccal region, we are also cautious about allowing extensive buccal defects to secondarily mucosalize, and we still prefer RFF in this setting. Gingival mucosal coverings without bony discontinuity, as in cases of marginal mandibulectomy and osteoradionecrosis debridement, are ideal scenarios for this flap. To date, we have performed 8 reconstructions for osteoradionecrosis debridement, and no patients have required revision or experienced exacerbations of their osteoradionecrosis. The thin nature of the flap allows quick return to presurgical masticatory function without revisions that may be necessary with the use of a cutaneous flap.

The palate presents a unique subsite that is thin and mucosalized on both the intraoral and intranasal surfaces. The hard palate is necessarily rigid for food bolus control and speech articulation; the soft palate is compliant and dynamic to participate in nasopharyngeal closure. The fascial component of the ALTAF can be secured to the periosteum of the alveolus to provide a thin, firm reconstruction with limited contracture and rapid mucosalization potential (Figure 2). For palate reconstruction with a pure ALTAF, we recommend that ALTAF be considered with preservation of bony alveolar arch structures. Certainly, if there is significant bone resected, an osseus flap may be more suitable. Another contraindication for ALTAF reconstruction in the palate is if the defect involves a significant portion of the soft palate. Without the ability to secure the posterior edge of the flap, nasopharyngeal patency and competence are unpredictable. In these instances, either a thinned ALT cutaneous perforator or radial forearm free flap is preferred.

Reconstruction of the nasal lining continues to be a unique challenge with the limitations of intranasal access and volume, large surface area of reconstruction, and poor functionality without respiratory epithelium. Taghinia and Pribaz17 recommended the RFF for nasal lining reconstruction. However, the RFF is again limited owing to the presence of keratinizing squamous epithelium, which can cause nasal dryness and crusting postoperatively.17 In addition, the RFF is limited by its greater thickness and poor pliability compared with native mucosa or even the ALTAF. The fascia lata component of the ALTAF allows it to be securely suspended from facial skeletal or nasal grafting components (Figure 3).

As noted, the variety of defects within the oral and nasal cavities provides unique challenges to the reconstructive surgeon. These challenges can be overcome by proper flap selection and technical execution.

Technical Considerations

The ALTAF harvest is technically similar to the ALT flap harvest with several important additional considerations. When initially harvesting, we prefer to include a small strip of skin centered on the more robust Doppler signals. This skin can be discarded later or used as a skin graft for flap coverage as needed. The skin strip allows easy manipulation and orientation of the flap during harvest; fat and fascia alone can be difficult to manipulate without trauma.

The flap is harvested as a perforator flap, which is done to minimize reconstructive bulk and potential postoperative contracture. Meticulous dissection and judicious use of bipolar electrocautery are important during this stage to minimize potential bleeding sites before inset. Because the thin perforators are harvested with the pedicle, clear orientation should be maintained so that kinking or twisting during inset and pedicle tunneling can be avoided. Some authors18 advocate marking the perforator to avoid this potentially disastrous complication. We have not found this to be necessary; however, we believe that it is helpful to note the perforator entry site into the fascia to adequately center the flap during shaping. Marking of the fascial edges with sutures immediately after making cuts also aids in flap inset because once the flap is harvested, locating the exact edges on a thin, pliable flap can be challenging after it has been removed from the leg. Before ligating the pedicle, the skin and subcutaneous fat can be removed to the desired flap thickness. A thin layer of suprafascial fat should be maintained to avoid interruption of the fascial plexus that runs on the superficial surface of the fascia lata (Figure 1).

Primary shaping also should be done before removal from the donor site because the perforators are most easily noted at this stage and hemostasis as well as flap blood flow can be ensured. Although it is unclear what size of fascia contains enough arterial and venous flow to support flap transfer, at least 2 cm of fascia circumferentially around the perforators should be preserved. In addition, when shaping the flap, one should remember that the fascia lata is minimally distensible and take care to precisely fit the flap to the reconstructive site. As with any flaps lacking a cutaneous component, contracture is possible, and Hanasono et al3 recommended a 10% volume overcorrection when harvesting flaps in anticipation of radiation-induced atrophy. We agree that there may be a certain degree of contracture of the flap, especially if the patient is to undergo radiotherapy. However, this is negligible when the fascia lata is firmly inset to rigid structures such as bone, cartilage, or periosteum.

We experienced 4 flap-related complications. The only instance of total flap loss involved a flap for osteoradionecrosis coverage; a late failure was observed at 2 weeks. The cause of this failure is unclear, but it was suspected to involve a late microvascular thrombosis because the flap was viable up to 1 week postoperatively. The microvascular anastomosis was accomplished at the distal facial vessels just below the mandibular border in an area directly in the prior radiation field. In this case, the vessels may have been suboptimal for reliable anastomosis. The patient underwent revision with an ALTAF anastomosed to the ipsilateral superficial temporal vessels without incident. Three patients required operative revision after radiotherapy contraction when tethering was noted to affect their articulation and oromotor function. These revisions included 2 composite lateral FOM and mobile tongue defects and 1 ventral tongue and anterior FOM defect reconstruction. These observations led us to reconsider use of the ALTAF when 2 opposing mucosal surfaces are encountered.

Conclusions

The ALTAF can be reliably harvested as a thin, pliable, and variable area free flap with minimal donor site morbidity. This flap is ideal for mucosal reconstruction and should be considered for select oral cavity and nasal lining reconstructions.

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Article Information

Accepted for Publication: April 7, 2014.

Corresponding Author: Michael A. Fritz, MD, Head and Neck Institute, Department of Otolaryngology–Head and Neck Surgery, Cleveland Clinic, 9500 Euclid Ave, Desk A71, Cleveland, OH 44195 (fritzm1@ccf.org).

Published Online: August 14, 2014. doi:10.1001/jamafacial.2014.447.

Author Contributions: Drs Revenaugh and Fritz had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: Revenaugh.

Drafting of the manuscript: Revenaugh.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Revenaugh, Haffey.

Administrative, technical, or material support: All authors.

Study supervision: Haffey, Seth, Fritz.

Conflict of Interest Disclosures: None reported.

Previous Presentation: This study was presented as a poster at the American Academy of Facial Plastic and Reconstructive Surgery fall meeting; September 6, 2012; Washington, DC.

References
1.
Song  YG, Chen  GZ, Song  YL.  The free thigh flap: a new free flap concept based on the septocutaneous artery. Br J Plast Surg. 1984;37(2):149-159.
PubMedArticle
2.
Malhotra  K, Lian  TS, Chakradeo  V.  Vascular anatomy of anterolateral thigh flap. Laryngoscope. 2008;118(4):589-592.
PubMedArticle
3.
Hanasono  MM, Skoracki  RJ, Silva  AK, Yu  P.  Adipofascial perforator flaps for “aesthetic” head and neck reconstruction. Head Neck. 2011;33(10):1513-1519.
PubMedArticle
4.
Wang  X, Qiao  Q, Liu  Z,  et al.  Free anterolateral thigh adipofascial flap for hemifacial atrophy. Ann Plast Surg. 2005;55(6):617-622.
PubMedArticle
5.
Agostini  V, Dini  M, Mori  A, Franchi  A, Agostini  T.  Adipofascial anterolateral thigh free flap for tongue repair. Br J Plast Surg. 2003;56(6):614-618.
PubMedArticle
6.
Agostini  T, Agostini  V.  Further experience with adipofascial ALT flap for oral cavity reconstruction. J Plast Reconstr Aesthet Surg. 2008;61(10):1164-1169.
PubMedArticle
7.
Seth  R, Revenaugh  PC, Scharpf  J, Shipchandler  TZ, Fritz  MA.  Free anterolateral thigh fascia lata flap for complex nasal lining defects. JAMA Facial Plast Surg. 2013;15(1):21-28.
PubMedArticle
8.
Moloy  PJ.  Reconstruction of intermediate sized mucosal defects with the pectoralis major myofascial flap. J Otolaryngol. 1989;18(1):32-35.
PubMed
9.
Uppin  SB, Ahmad  QG, Yadav  P, Shetty  K.  Use of the submental island flap in orofacial reconstruction—a review of 20 cases. J Plast Reconstr Aesthet Surg. 2009;62(4):514-519.
PubMedArticle
10.
Nthumba  PM.  The supraclavicular artery flap: a versatile flap for neck and orofacial reconstruction. J Oral Maxillofac Surg. 2012;70(8):1997-2004.
PubMedArticle
11.
Valentini  V, Cassoni  A, Marianetti  TM, Battisti  A, Terenzi  V, Iannetti  G.  Anterolateral thigh flap for the reconstruction of head and neck defects: alternative or replacement of the radial forearm flap? J Craniofac Surg. 2008;19(4):1148-1153.
PubMedArticle
12.
Anain  SA, Yetman  RJ.  The fate of intraoral free muscle flaps: is skin necessary? Plast Reconstr Surg. 1993;91(6):1027-1031.
PubMedArticle
13.
Syme  DB, Shayan  R, Grinsell  D.  Muscle-only intra-oral mucosal defect reconstruction. J Plast Reconstr Aesthet Surg. 2012;65(12):1654-1659.
PubMedArticle
14.
Agostini  T, Agostini  V, Lazzeri  D.  Current roles of adipofascial anterolateral thigh flap in head and neck reconstructions. Head Neck. 2011;33(4):595-597.
PubMedArticle
15.
Johnson  MA, Langdon  JD.  Is skin necessary for intraoral reconstruction with myocutaneous flaps? Br J Oral Maxillofac Surg. 1990;28(5):299-301.
PubMedArticle
16.
Phillips  JG, Postlethwaite  K, Peckitt  N.  The pectoralis major muscle flap without skin in intra-oral reconstruction. Br J Oral Maxillofac Surg. 1988;26(6):479-485.
PubMedArticle
17.
Taghinia  AH, Pribaz  JJ.  Complex nasal reconstruction. Plast Reconstr Surg. 2008;121(2):15e-27e. doi:10.1097/01.prs.0000298113.56554.c3.
PubMedArticle
18.
Shaw  RJ, Batstone  MD, Blackburn  TK, Brown  JS.  The anterolateral thigh flap in head and neck reconstruction: “pearls and pitfalls.” Br J Oral Maxillofac Surg. 2010;48(1):5-10.
PubMedArticle
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