Insights on preliminary outcomes of a prospective study examining innervation of deep inferior epigastric perforator flaps in autologous breast reconstruction

Breast reconstruction has witnessed tremendous advancements over the years with autologous reconstruction becoming the gold standard treatment option, offering patients the most natural and durable results with superior long-term patient satisfaction (1-3). To further improve on patient reported outcomes and patient quality of life, the concept of neurotization and creating a sensate breast has grown in popularity since its first description decades earlier (4,5). The present study aims to present the preliminary data of a double-blind, prospective randomized study examining the outcomes of creating a sensate breast in women undergoing breast reconstruction with a free autologous deep inferior epigastric perforator (DIEP) flap (6). The authors report their outcomes with 29 non-innervated breasts and 39 innervated breasts and demonstrate improved sensation to light touch and superior protective sensation in the innervated breasts at 24-month follow-up.

Overall, the authors should be congratulated for the study design as there is rarely level one evidence guiding practices in plastic and reconstructive surgery. As such, whether the results are positive or negative, this work will help guide practice and patient counseling regarding restoration of breast sensation in autologous reconstruction. Further, the authors should be applauded for performing rigorous objective preoperative and postoperative sensory testing, with Semmes-Weinstein monofilaments, a Pressure Specified Sensory Device, and a thermostimulator.

While the preliminary results seem promising, there are significant limitations in the current report that the definitive results from the final study potentially will address. Despite the randomization, the small sample size has significant differences in the two patient populations which raises concerns for the preliminary findings. Nerve regeneration is typically superior in younger patients, and the innervated cohort was significantly younger compared to the non-innervated group (7-9). This introduces a selection bias despite the randomization as those who underwent reinnervation were the most likely to have successful nerve regeneration. Similarly, the non-innervated cohort had a higher incidence of radiation which again is a significant factor that could influence or impair nerve regeneration (10,11). Again, there is a selection bias as the patients who are the most likely to have the best outcomes underwent the reinnervation procedure since they were younger and did not receive radiation (12). Thus, while the preliminary is promising, the final study will hopefully have two equivalent cohorts to truly validate their preliminary findings.

Aside from the patient age as well as the adjuvant radiation, the innervated cohort were also more likely to undergo prophylactic mastectomies versus a therapeutic mastectomy. Consequently, the innervated group were also more likely to undergo immediate reconstruction rather than delayed reconstruction (13). While a therapeutic and prophylactic mastectomy should be performed in an identical fashion, in reality, the pattern and the perfusion of the mastectomy skin and tissue can be drastically different between two breasts and almost certainly different between the two cohorts. This suggests that the recovery of sensation could also be different. Since regions 1–4 are on the mastectomy skin flaps (except for the delayed reconstructions) which were again more common in the innervated cohort, the sensory recovery of those regions is directly related to the quality of the mastectomy skin flaps (14). The larger skin island required in delayed flaps could also influence rates of reinnervation and ultimate degree of reinnervation of the entire flap. The authors do note a significant improvement in tactile thresholds at the center of the flap in innervated compared to non-innervated flaps which represents a direct comparison of flap skin to flap skin and demonstrates the superiority of reinnervation. Perhaps a standardized area of flap skin paddle could be pre-determined and marked with a standardized template so the area could be directly compared in all patients. In this way, the periphery of large skin paddles is not compared to native breast skin. Reporting the area of the skin paddle in the final analysis may add more information about these differences between the patient groups and aid in the interpretation of the results. The authors do suggest a subgroup analysis will be performed in the final study, which could not be performed at this stage due to the small group size. In addition, some bias is introduced in this interim report since only patients who completed the 24-month follow-up were included rather than the entire randomized population in that time frame, which amounts to 41 of the 118 total patients in the study during the specified time frame. The final results of the trial, with increased group size, may address some of these concerns.

Interestingly, the authors employed a direct coaptation technique between the recipient nerve which is likely isolated in the region of the recipient internal mammary vessels used for the microvascular anastomosis and a cutaneous sensory nerve of the DIEP flap. The ability to consistently perform direct coaptation between one of the cutaneous nerves in the abdomen close to the lateral row perforators and the anterior cutaneous branch of the intercostal nerves near the recipient internal mammary vessels can be challenging (15). This may not always be possible without excessive dissection into the rectus muscle, which could compromise motor function and increase the donor site morbidity. In the present study, three patients randomized to the innervation group were unable to have the nerve reconstruction due to inadequate length. This is in contrast to other current techniques where other microsurgeons have used either a nerve conduit or a nerve allograft to create a sensate which represents another area of potential research in the space of breast reinnervation (16,17).

Another consideration is the recipient nerves which can be used for the innervation. The authors used the anterior intercostal nerves which are often readily dissected during the recipient vessel dissection. However, others have reported dissecting the fourth intercostal nerve to serve as the recipient nerve. Whether the anterior intercostal nerve in the third interspace is more effective or appropriate compared to the fourth lateral intercostal nerve is also an area that warrants further investigation, but the majority of studies do not demonstrate any significant difference in long-term outcomes (18). Nonetheless, regardless of the recipient nerve, numerous studies have demonstrated directly coapting two nerves together should improve sensation or shorten the duration to recovery of sensation (19-23).

While not utilized in the present study, the costs associated with the use of nerve allografts cannot be discounted, and the authors should be commended for designing a study obviating the need and costs of nerve allografts which is quite rare with only one other high impact study reported in the recent literature (24). The majority of studies investigating the concept of breast flap neurotization use an allograft where often the investigators are often paid consultants of companies that manufacture the allografts (15-17,25). Further analysis beyond the sensory outcomes could include analysis of added operative time to complete the nerve dissections and neurotization to determine if these reinnervation procedures are warranted. The authors conclude the findings demonstrated in their interim analysis will translate into a tangible clinical improvement for patients, as patients show improvement from loss of protective sensation to diminished protective sensation. However, the most critical aspect will be whether this objective improvement in sensory metrics will truly have a meaningful impact on patients and their quality of life. We expect that the final study will also report on the patient reported outcomes and patient quality of life. There is no question, the readership will be eagerly awaiting the final outcomes of this prospective study.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-475/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-475/coif). E.I.C. reports having received honoraria as a speaker for the MusculoTransplant Foundation and was the recipient of the American Society of Reconstructive Microsurgery Godina Traveling Fellowship and the American College of Surgeons Traveling Fellowship. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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