Following flap transfer to the chest, completion of the revascularization, and the dissection of recipient chest nerves, the acquired nerve gap defect varied in every dissection. The primary reason for the variability was because of the manipulation and insetting of the flap. Taking this into consideration, an interposing nerve allograft, either 5 or 7 cm in length allowed an unopposed flap rotation and flap inset in all dissections, while utilizing various ICN2-4 combinations (Fig. 6).
Breast neurotization follows the general principles of standard nerve injury repair. When possible, tensionless primary repair should be performed; however, if primary repair is not possible, then bridging materials are utilized, which may include nerve autografts, tube conduits, and processed nerve allografts.30–32
Authors have commented on being able to raise a sufficiently long intercostal nerve (ICN) branch with the abdominal flap that allows for tensionless primary repair. Indeed, an intercostal nerve up to 10–12 cm in length can be harvested, but the harvested nerve would include both sensory and motor components (Fig. 7). However, in harvesting a mixed nerve lies the crux of the issue. Once the recipient intercostal nerve begins to regenerate toward the transferred flap by the donor mixed intercostal nerve, only the sensory half of the nerve may neurotize the flap, while the remaining half of the regenerating nerve would blindly end into the clipped donor motor component. We believe this is the anatomical basis and explanation as to why there is an unexpected shortcoming in the degree of sensory recovery in the autograft-neurotized breast. Additionally, donor-site morbidity (bulge and hernias due to iatrogenic rectus muscle denervation) is also increased in these instances, particularly if the large type 2 nerve as described by Rozen et al.3,33–36 is sacrificed.
Based on our anatomical dissections, we were able to consistently dissect and extract only the sensory branch of the ICN to the abdominal flap. By dividing the nerve branch distal to the sensory-motor Y-junction, motor innervation to the rectus abdominis muscle is preserved and the risk of axonal loss via divided motor side branches is minimized. Thus, donor-site morbidity is kept to a minimum and more importantly the chance for successful flap reinnervation is increased. This technique, however, results in a rather short target nerve, that in return mandates the use of techniques to bridge the resulting nerve gap.9,37
In terms of nerve gap bridging mediums, a mixed sensory-motor autograft for aforementioned reasons may adequately bridge the gap, but have less than adequate sensory recovery and the gap length during breast neurotization far exceeds what is recommended for reconstruction with nerve conduits, which is about 6 mm.38–44 The most comprehensive review on tube conduits and allografts as an alternative to nerve autografts was performed by Safa and Buncke45 in 2016 and they found that in gaps under 6 mm, tube conduits performed well, but beyond this length the reliability declined rapidly and outcomes were significantly less consistent. In light of these findings, the favorable breast neurotization results reported by Spiegel et al.,18 who used 40 mm hollow tube conduits are rather surprising and not otherwise replicated. In contrast, processed nerve allografts are found to perform reliably in gaps up to 70 mm with the difference being attributed to the structural preservation of the nerve architecture and the presence of laminin in the nerve micro-environment of the allograft.46,47 Collectively, the current clinical data show that allografts are safe, they result in successful neurotization for reconstructed nerve gaps up to 70 mm in length, their results are comparable with nerve autograft without the associated donor-site morbidity, and their clinical results are significantly better than hollow tube conduits.39,40,46–49 For example, Salomon et al.47 examined the use of allograft to span defects ≥ 50 mm of the inferior alveolar nerve and found that 87.5% of patients had sensory recovery to S3 or greater on the Medical Research Council Classification (MRCC) scale, which has been often used as the metric for functional sensory recovery.
Several cadaveric and clinical studies have shown that the breast is normally innervated via various lateral and cutaneous branches of ICN2 through ICN6.50–55 As suggested in the literature, we believe that the ICN3, ICN4, and ICN2 are appropriate recipient nerves for the purpose of flap neurotization. Based on our experience with the cadaver dissections, its identification and dissection are both straightforward and consistent. It is also important to highlight that if dual neurotization is desired, in addition to ICN3, either the ICN2 or ICN4 are also readily available and easily identified within the same surgical field (Figs. 6, 8). Regarding muscular or nerve damage incurred by dissection, the intercostal nerves are already transected during mastectomy and with removal of the breast specimen, so no additional morbidity is incurred by using these nerve stumps. Pectoralis major muscle fibers are spread parallel to their path and do not need to be transected, thus minimizing the muscle damage. This is standard when removing rib cartilage medially and exposing mammary vessels in preparation for microvascular anastomosis.
During the specimen dissection in our study, a 1–2 mm × 50–70 mm interposing allograft was able to easily bridge all nerve gaps between the donor flap and recipient chest nerves. It also allowed free arch of rotation for flap inset and was suitable for either single or dual neurotization. Taking this into consideration and its overall reported effectiveness in nerve reconstruction, allograft appears to offer a solution for current anatomical limitations and thus outcome limitations encountered with the neurotization of DIEP flaps. Future prospective and institutional review board–approved studies have been initiated to help clinically validate allograft effectiveness in breast neurotization. Notably there is no literature available that correlates neurotization rates with postmastectomy radiation, neoadjuvant chemotherapy, and adjuvant chemotherapy. Further research is necessary to assess the effectiveness of neurotization during these circumstances and we would currently recommend against neurotization for these scenarios, given the lack of research and risk of failure. However, a substantial portion of the target population if not the majority will not require postmastectomy radiation.56 Barring neoadjuvant or adjuvant chemotherapy, these patients would greatly benefit from neurotization. Another segment of the population that would greatly benefit is the segment undergoing prophylactic mastectomies and thus we believe at baseline there is a significant number of patients that can be helped with neurotization.
There are instances in which spontaneous reinnervation of the flap occurs; however, we believe these cases to be unpredictable exceptions and not the norm. With neurotization, the measure of sensation recovery is more significant and likely occurs under different mechanisms. Although we do not have histological confirmation currently, we believe the reinnervated axons reactivate and supply the original sensory end organs whereas spontaneous regrowth likely produces spontaneous sensation by random ingrowth into the subdermal plexus.
The primary limitation of our dissection findings and the discussed implications is that there have been no clinical studies published, which utilize the selective dissection of only the sensory component of the ICN of the abdominal flap for breast neurotization during DIEP flap reconstructions. However, we are confident that selective dissection and utilization of only the sensory component will significantly improve sensory recovery to be much closer to the sensation of the native breast. Also, we believe that the processed nerve allograft will go hand in hand with this neurotization procedure as the sensory only nerve pedicle will inherently create a nerve gap that is prohibitive of direct neurorrhaphy and bridging with a conduit. The reviewed data are compelling, and we are confident that the utilization of the sensory only component in combination with the allograft for breast neurotization will result in similar outcomes as the referenced nonbreast studies since the principles behind nerve regeneration and the mechanism of regeneration through processed nerve allograft is still the same. In DIEP flap reconstructions, selectively dissecting out and utilizing only the sensory ICN component has the potential to significantly improve sensory recovery and minimize donor-site morbidities.
Another limitation is relatively small study sample (12 hemi-dissections) to suggest appropriate statistical power of observed anatomical variations, thus necessitating prospective clinical evaluations of donor and recipient nerve diameters, their available length upon piercing flap or their distance to flap, all directly affecting the ultimate acquired nerve gap size and thus reconstructive choice. Until those prospective data are available, our data suggest surgeon should be aware of regular nerve variations, potentially affecting what nerve and what reconstructive tool to utilize.
Based on our cadaveric dissections, we provide a likely anatomical explanation as to why sensory recovery after current breast neurotization methods during a DIEP flap reconstruction has been less than optimal. The utilization of a mixed sensory and motor nerve autograft is prohibitive to maximal sensory recovery. The sensory branch of the intercostal nerve can be selectively dissected and extracted with the abdominal flap, thus allowing maximal recovery of sensation and preserving the motor branch of the intercostal nerve to the rectus abdominis muscle. Based on these implications, we envision that the integration of this principle will best be served with a processed nerve allograft that has been shown to be effective in neurotization procedures in lengths up to 7 cm. The feasibility and versatility of bridging the existing nerve gap with nerve allograft is demonstrated and the simplicity of the procedure outlined. Ongoing prospective studies are underway to investigate the functional implications of the proposed principle.
1. Zurrida S, Veronesi U. Milestones in breast cancer treatment. Breast J. 2015;21:3–12.
2. Yueh JH, Slavin SA, Adesiyun T, et al. Patient satisfaction in postmastectomy breast reconstruction: a comparative evaluation of DIEP, TRAM, latissimus flap, and implant techniques. Plast Reconstr Surg. 2010;125:1585–1595.
3. Nahabedian MY, Momen B, Galdino G, et al. Breast reconstruction with the free TRAM or DIEP flap: patient selection, choice of flap, and outcome. Plast Reconstr Surg. 2002;110:466–475; discussion 476.
4. Blondeel N, Vanderstraeten GG, Monstrey SJ, et al. The donor site morbidity of free DIEP flaps and free TRAM flaps for breast reconstruction. Br J Plast Surg. 1997;50:322–330.
5. Nahabedian MY, Tsangaris T, Momen B. Breast reconstruction with the DIEP flap or the muscle-sparing (MS-2) free TRAM flap: is there a difference? Plast Reconstr Surg 2005;115:436–444; discussion 445436.
6. Allen RJ. DIEP versus TRAM for breast reconstruction. Plast Reconstr Surg. 2003;111:2478.
7. Zhong T, Lao A, Werstein MS, et al. High-frequency ultrasound: a useful tool for evaluating the abdominal wall following free TRAM and DIEP flap surgery. Plast Reconstr Surg. 2006;117:1113–1120.
8. Chen CM, Halvorson EG, Disa JJ, et al. Immediate postoperative complications in DIEP versus free/muscle-sparing TRAM flaps. Plast Reconstr Surg. 2007;120:1477–1482.
9. Rozen WM, Ashton MW, Murray AC, et al. Avoiding denervation of rectus abdominis in DIEP flap harvest: the importance of medial row perforators. Plast Reconstr Surg. 2008;122:710–716.
10. Temple CL, Ross DC, Kim S, et al. Sensibility following innervated free TRAM flap for breast reconstruction: Part II. Innervation improves patient-rated quality of life. Plast Reconstr Surg. 2009;124:1419–1425.
11. Rabin R. After mastectomies, an unexpected blow: numb new breasts. The New York Times. January 29, 2017.
12. Lehmann C, Gumener R, Montandon D. Sensibility and cutaneous reinnervation after breast reconstruction with musculocutaneous flaps. Ann Plast Surg. 1991;26:325–327.
13. Liew S, Hunt J, Pennington D. Sensory recovery following free TRAM flap breast reconstruction. Br J Plast Surg. 1996;49:210–213.
14. Place MJ, Song T, Hardesty RA, et al. Sensory reinnervation of autologous tissue TRAM flaps after breast reconstruction. Ann Plast Surg. 1997;38:19–22.
15. Blondeel PN, Demuynck M, Mete D, et al. Sensory nerve repair in perforator flaps for autologous breast reconstruction: sensational or senseless? Br J Plast Surg. 1999;52:37–44.
16. Temple CL, Tse R, Bettger-Hahn M, et al. Sensibility following innervated free TRAM flap for breast reconstruction. Plast Reconstr Surg. 2006;117:2119–2127; discussion 2128.
17. Shaw WW, Orringer JS, Ko CY, et al. The spontaneous return of sensibility in breasts reconstructed with autologous tissues. Plast Reconstr Surg. 1997;99:394–399.
18. Spiegel AJ, Menn ZK, Eldor L, et al. Breast reinnervation: DIEP neurotization using the third anterior intercostal nerve. Plast Reconstr Surg Glob Open. 2013;1:e72.
19. Slezak S, McGibbon B, Dellon AL. The sensational transverse rectus abdominis musculocutaneous (TRAM) flap: return of sensibility after TRAM breast reconstruction. Ann Plast Surg. 1992;28:210–217.
20. Mahajan AL, Chapman TW, Mandalia MR, et al. Sun burn as a consequence of resting reading glasses on a reconstructed breast. J Plast Reconstr Aesthet Surg. 2010;63:e170.
21. Enajat M, Rozen WM, Audolfsson T, et al. Thermal injuries in the insensate deep inferior epigastric artery perforator flap: case series and literature review on mechanisms of injury. Microsurgery. 2009;29:214–217.
22. Kay AR, McGeorge D. Susceptibility of the insensate reconstructed breast to burn injury. Plast Reconstr Surg. 1997;99:927.
23. Gowaily K, Ellabban MG, Iqbal A, et al. Hot water bottle burn to reconstructed breast. Burns. 2004;30:873–874.
24. Nahabedian MY, McGibbon BM. Thermal injuries in autogenous tissue breast reconstruction. Br J Plast Surg. 1998;51:599–602.
25. Pusic AL, Klassen AF, Scott AM, et al. Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q. Plast Reconstr Surg. 2009;124:345–353.
26. Tindholdt TT, Tønseth KA. Spontaneous reinnervation of deep inferior epigastric artery perforator flaps after secondary breast reconstruction. Scand J Plast Reconstr Surg Hand Surg. 2008;42:28–31.
27. Santanelli F, Longo B, Angelini M, et al. Prospective computerized analyses of sensibility in breast reconstruction with non-reinnervated DIEP flap. Plast Reconstr Surg. 2011;127:1790–1795.
28. Stromps JP, Bozkurt A, Grieb G, et al. Spontaneous reinnervation of deep inferior epigastric perforator flaps after delayed breast reconstruction. J Reconstr Microsurg. 2016;32:169–177.
29. Beugels J, Cornelissen AJM, Spiegel AJ, et al. Sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions: a systematic review. J Plast Reconstr Aesthet Surg. 2017;70:1229–1241.
30. Lundborg G. A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance. J Hand Surg Am. 2000;25:391–414.
31. Brooks DN, Weber RV, Chao JD, et al. Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery. 2012;32:1–14.
32. Zuniga JR. Sensory outcomes after reconstruction of lingual and inferior alveolar nerve discontinuities using processed nerve allograft–a case series. J Oral Maxillofac Surg. 2015;73:734–744.
33. Meek MF, Coert JH, Robinson PH. Poor results after nerve grafting in the upper extremity: Quo vadis? Microsurgery. 2005;25:396–402.
34. IJpma FF, Nicolai JP, Meek MF. Sural nerve donor-site morbidity: thirty-four years of follow-up. Ann Plast Surg. 2006;57:391–395.
35. Rozen WM, Ashton MW, Kiil BJ, et al. Avoiding denervation of rectus abdominis in DIEP flap harvest II: an intraoperative assessment of the nerves to rectus. Plast Reconstr Surg. 2008;122:1321–1325.
36. Rozen WM, Tran TM, Ashton MW, et al. Refining the course of the thoracolumbar nerves: a new understanding of the innervation of the anterior abdominal wall. Clin Anat. 2008;21:325–333.
37. Wolford LM, Rodrigues DB. Autogenous grafts/allografts/conduits for bridging peripheral trigeminal nerve gaps. Atlas Oral Maxillofac Surg Clin North Am. 2011;19:91–107.
38. Lohmeyer JA, Kern Y, Schmauss D, et al. Prospective clinical study on digital nerve repair with collagen nerve conduits and review of literature. J Reconstr Microsurg. 2014;30:227–234.
39. Means KR Jr, Rinker BD, Higgins JP, et al. A multicenter, prospective, randomized, pilot study of outcomes for digital nerve repair in the hand using hollow conduit compared with processed allograft nerve. Hand (N Y). 2016;11:144–151.
40. Agnew SP, Dumanian GA. Technical use of synthetic conduits for nerve repair. J Hand Surg Am. 2010;35:838–841.
41. Mackinnon SE, Dellon AL. A study of nerve regeneration across synthetic (Maxon) and biologic (collagen) nerve conduits for nerve gaps up to 5 cm in the primate. J Reconstr Microsurg. 1990;6:117–121.
42. Boeckstyns ME, Sørensen AI, Viñeta JF, et al. Collagen conduit versus microsurgical neurorrhaphy: 2-year follow-up of a prospective, blinded clinical and electrophysiological multicenter randomized, controlled trial. J Hand Surg Am. 2013;38:2405–2411.
43. Moore AM, Wagner IJ, Fox IK. Principles of nerve repair in complex wounds of the upper extremity. Semin Plast Surg. 2015;29:40–47.
44. Ducic I, Fu R, Iorio ML. Innovative treatment of peripheral nerve injuries: combined reconstructive concepts. Ann Plast Surg. 2012;68:180–187.
45. Safa B, Buncke G. Autograft substitutes: conduits and processed nerve allografts. Hand Clin. 2016;32:127–140.
46. Zuniga JR, Williams F, Petrisor D. A case-and-control, multisite, positive controlled, prospective study of the safety and effectiveness of immediate inferior alveolar nerve processed nerve allograft reconstruction with ablation of the mandible for benign pathology. J Oral Maxillofac Surg. 2017;75:2669–2681.
47. Salomon D, Miloro M, Kolokythas A. Outcomes of immediate allograft reconstruction of long-span defects of the inferior alveolar nerve. J Oral Maxillofac Surg. 2016;74:2507–2514.
48. Whitlock EL, Tuffaha SH, Luciano JP, et al. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve. 2009;39:787–799.
49. Guo Y, Chen G, Tian G, et al. Sensory recovery following decellularized nerve allograft transplantation for digital nerve repair. J Plast Surg Hand Surg. 2013;47:451–453.
50. Ducic I, Larson EE. Outcomes of surgical treatment for chronic postoperative breast and abdominal pain attributed to the intercostal nerve. J Am Coll Surg. 2006;203:304–310.
51. Ducic I, Seiboth LA, Iorio ML. Chronic postoperative breast pain: danger zones for nerve injuries. Plast Reconstr Surg. 2011;127: 41–46.
52. Ducic I, Larson E. Managment of chronic postoperative breast pain. In: Surgery of the Breast: Principles and Art. 2011: 3rd ed. 947–951.
53. Ducic I, Zakaria HM, Felder JM 3rd, et al. Nerve injuries in aesthetic breast surgery: systematic review and treatment options. Aesthet Surg J. 2014;34:841–856.
54. Sarhadi NS, Shaw Dunn J, Lee FD, et al. An anatomical study of the nerve supply of the breast, including the nipple and areola. Br J Plast Surg. 1996;49:156–164.
55. Schlenz I, Kuzbari R, Gruber H, et al. The sensitivity of the nipple-areola complex: an anatomic study. Plast Reconstr Surg. 2000;105:905–909.
56. Recht A, Comen EA, Fine RE, et al. Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. Pract.Radiat.Oncol. 2016; 6:e219–e234.