Altered actin dynamics is possibly implicated in the inhibition of mechanical stimulation-induced dermal fibroblast differentiation into myofibroblasts.

The formation of hypertrophic scars and keloids is strongly associated with mechanical stimulation, and myofibroblasts are known to play a major role in abnormal scar formation. Wounds in patients with neurofibromatosis type 1 (NF1) become inconspicuous and lack the tendency to form abnormal scars. We hypothesized that there would be a unique response to mechanical stimulation and subsequent scar formation in NF1. To test this hypothesis, we investigated the molecular mechanisms of differentiation into myofibroblasts in NF1-derived fibroblasts and neurofibromin-depleted fibroblasts and examined actin dynamics, which is involved in fibroblast differentiation, with a focus on the pathway linking LIMK2/cofilin to actin dynamics. In normal fibroblasts, expression of α-smooth muscle actin (α-SMA), a marker of myofibroblasts, significantly increased after mechanical stimulation, whereas in NF1-derived and neurofibromin-depleted fibroblasts, α-SMA expression did not change. Phosphorylation of cofilin and subsequent actin polymerization did not increase in NF1-derived and neurofibromin-depleted fibroblasts after mechanical stimulation. Finally, in normal fibroblasts treated with Jasplakinolide, an actin stabilizer, α-SMA expression did not change after mechanical stimulation. Therefore, when neurofibromin was dysfunctional or depleted, subsequent actin polymerization did not occur in response to mechanical stimulation, which may have led to the unchanged expression of α-SMA. We believe this molecular pathway can be a potential therapeutic target for the treatment of abnormal scars.

Reconstruction of a Spinal Accessory Nerve Defect Using Vascularized Vastus Lateralis Motor Nerve Graft.

Massive resection of a malignant tumor of the head and neck region often requires loss of critical nerves, including the spinal accessory nerve. Recently, vascularized nerve grafts (VNGs) have been used to repair facial and other nerve defects with successful outcomes, even in cases involving factors that can inhibit nerve regeneration, such as radiotherapy. However, the effectiveness of these nerve grafts against postoperative radiotherapy has yet to be explored. We report the first successful case in reconstructing a spinal accessory nerve defect after total left parotidectomy with radical neck dissection, using a vascularized vastus lateralis motor nerve graft and an anterolateral thigh flap based on the lateral circumflex femoral system, with great shoulder function outcomes even after postoperative radiotherapy. A branch of vastus lateralis motor nerve perfused by the accompanying descending branch of lateral femoral circumflex vessel was used as a nerve graft, and was repaired in an end-to-end manner. The patient underwent postoperative radiotherapy to the area of operation. At 6-months follow-up, the patient was capable of 90 degrees lateral shoulder abduction, and at 18 months, achieved full-range shoulder abduction and reported neither functional limitations of the shoulder nor complaints of any shoulder pain (Disabilities of Arm, Shoulder, and Hand score 0). Although further study is necessary to fully understand the superiority of VNGs over postoperative radiotherapy, immediate nerve reconstruction using VNG for accessory nerve defects in patients scheduled for radiotherapy postoperation may be extremely beneficial for preserving shoulder motor function and sustaining the patient's quality of life.

Surgical Correction of Nipple Hypertrophy after Nipple-sparing Mastectomy with Breast Reconstruction.

Nipple hypertrophy is a relatively common phenomenon, particularly in the Asian patient population. The incidence and prevalence or cause of nipple hypertrophy are not well defined in the literature. As survival rates for breast cancer patients continue to improve, there is an increasing emphasis on enhancing their quality of life. Treatment options, such as lumpectomy and radiation therapy or mastectomy, now prioritize preservation of the nipple-areolar complex (NAC) through techniques like nipple-sparing mastectomy (NSM). This approach has been shown to improve patient satisfaction and quality of life. However, it is important to note that NSM is associated with certain complications, including NAC necrosis, malposition, and local recurrence of the tumor. Among those complications, nipple hypertrophy is quite rare. In this report, we present a case of nipple hypertrophy that developed after breast reconstruction, using autologous tissue. The patient, a 48-year-old woman, underwent NSM for breast cancer, and had a tissue expander placed simultaneously. Following tissue expansion, breast reconstruction with a deep inferior epigastric perforator (DIEP) flap was performed. However, during the tissue expansion phase, the patient's nipple gradually enlarged, and the protrusion became more pronounced after the DIEP flap transfer. Nipple reduction surgery was subsequently performed for both diagnostic and cosmetic purposes. We present this case along with a review of relevant literature.

"Hydrogen-generating Si-based agent improves fat graft survival in rats".

BACKGROUND: Regulating excessive inflammation and oxidative stress in fat grafting may improve retention rates. Hydrogen effectively combats oxidative stress and inflammation and reportedly inhibits ischemia-reperfusion injury in various organs. Unfortunately, with conventional methods of hydrogen administration, incorporating hydrogen continuously into the body over a long period of time is difficult. We hypothesized that a Silicon (Si)-based agent we recently developed would aid in fat grafting as it can generate large amounts of hydrogen continuously in the body. METHODS: Fat grafting was performed on the backs of rats fed either a normal or 1.0 wt% Si-based agent-containing diet. To investigate synergistic effects with adipose-derived stromal cells (ASCs), which improve retention rates of fat grafting, fat grafting with ASCs (1.0×10 5/400 mg fat) was also performed in each rat. Postoperative retention rates of grafted fat over time, inflammatory indices, apoptosis and oxidative stress markers, histological findings, and expression levels of inflammation-related cytokines and growth factors were compared between the four groups. RESULTS: Intake of Si-based agent and addition of ASCs significantly reduced inflammatory indices, oxidative stress, and apoptosis of grafted fat, and improved long-term retention rates, histological parameters, and grafted fat quality. Under our experimental conditions, intake of the Si-based agent and addition of ASCs yielded comparable improvements in fat graft retention. Combining the two enhanced these effects even further. CONCLUSION: Oral administration of the hydrogen-generating Si-based agent may improve grafted fat retention by regulating the inflammatory response and oxidative stress in grafted fat. CLINICAL RELEVANCE STATEMENT: This study demonstrates improved grafted fat retention rates using a Si-based agent. This Si-based agent has the potential to expand the range of therapeutic indications of hydrogen-based therapy to conditions for which hydrogen has yet to be found effective, such as fat grafting.

Total breast reconstruction with a fat-augmented latissimus dorsi flap: A comparative study between muscle and myocutaneous flaps.

The fat-augmented latissimus dorsi myocutaneous flap can overcome the volume insufficiency of latissimus dorsi flaps by immediate fat grafting into the flap. When breast skin supplementation is unnecessary, latissimus dorsi flaps can be harvested as a muscle flap to avoid an additional back incision. Here, we compared the efficacy of fat-augmented latissimus dorsi myocutaneous and muscle flaps in total breast reconstruction. We retrospectively reviewed 94 cases of unilateral total breast reconstruction using fat-augmented latissimus dorsi flaps (muscle: 40, myocutaneous: 54) at our hospital from September 2017 to March 2022. The muscle flap group had a significantly shorter operative time than the myocutaneous flap group (p < 0.0001). Mastectomy specimen weight did not differ between the 2 groups, but total flap weight in the muscle flap group was significantly lower (p < 0.0001). Conversely, total fat graft volume, fat graft volume to the latissimus dorsi flap, and fat graft volume to the pectoralis major muscle were significantly greater in the muscle flap group (p < 0.0001, p < 0.0001, and p = 0.02, respectively). The percentage of cases requiring additional fat grafting was significantly higher in the muscle flap group, but postoperative esthetic evaluation did not significantly differ between the 2 groups. Both groups scored high on each BREAST-Q item, but the muscle flap group scored significantly higher for "Satisfaction with Back." Although the frequency of additional fat grafting was higher than with fat-augmented latissimus dorsi myocutaneous flaps, total breast reconstruction with fat-augmented latissimus dorsi muscle flaps is a viable technique with a short operative time and high patient satisfaction.

Stretching Promotes Wound Contraction Through Enhanced Expression of Endothelin Receptor B and TRPC3 in Fibroblasts.

One factor that can contribute to the development of hypertrophic scar contracture is mechanical stress. Mechanical cyclic stretch stimuli enhance the secretion of endothelin-1 (ET-1) from keratinocyte. Cyclical stretching of fibroblasts also increases the expression level of the transient receptor potential ion channel (TRPC3), which is known to couple with the endothelin receptor and induce intracellular Ca2+ signaling via the calcineurin/nuclear factor of activated T cells (NFAT) pathway. The aim of this study was to investigate the relationship between keratinocytes and fibroblasts when they are stretched. Methods: The conditioned medium from stretched keratinocyte was added to the fibroblast populated collagen lattice. Then, we analyzed the levels of endothelin receptor in the human hypertrophic scar tissue and stretched fibroblasts. To address the function of TRPC3, we have used an overexpression system with the collagen lattice. Finally, the TRPC3 overexpressing fibroblasts were transplanted to mouse dorsal skin, and the rate of skin wound contraction was assessed. Results: Conditioned medium from stretched keratinocytes increased the rate of contraction of fibroblast populated collagen lattice. In human hypertrophic scar and stretched fibroblasts, endothelin receptor type B was increased. Cyclic stretching of TRPC3 overexpressing fibroblasts activated NFATc4, and stretched human fibroblasts showed more activation of NFATc4 in response to ET-1. The wound treated with TRPC3 overexpressing fibroblasts showed more contraction than control wound. Conclusion: These findings suggest that cyclical stretching of wounds have an effect on both keratinocytes and fibroblasts, where keratinocytes secret more ET-1, and fibroblasts develop more sensitivity to ET-1 by expressing more endothelin receptors and TRPC3.

Lymphaticovenular Anastomosis for Lymphorrhea after Expander-based Breast Reconstruction: A Case Report.

Refractory axillary lymphorrhea is a postoperative complication of breast cancer with no established standard treatment. Recently, lymphaticovenular anastomosis (LVA) was used to treat not only lymphedema but also lymphorrhea and lymphocele in the inguinal and pelvic regions. However, only a few reports have been published on the treatment of axillary lymphatic leakage with LVA. This report presents a case of successful treatment of refractory axillary lymphorrhea after breast cancer surgery with LVA. A 68-year-old woman underwent nipple-sparing mastectomy for right breast cancer, axillary lymph node dissection, and immediate subpectoral tissue expander placement. Postoperatively, the patient developed refractory lymphorrhea and subsequent seroma around the tissue expander, and underwent postmastectomy radiation therapy and frequent percutaneous aspiration of the seroma. However, lymphatic leakage persisted, and surgical treatment was planned. Preoperative lymphoscintigraphy showed lymphatic outflow from the right axilla to the space around the tissue expander. There was no dermal backflow in the upper extremities. To reduce lymphatic flow into the axilla, LVA was performed at two sites in the right upper arm. The lymphatic vessels used for anastomosis were 0.35 mm and 0.50 mm in diameter, and each was anastomosed to the vein in an end-to-end fashion. The axillary lymphatic leakage stopped shortly after the operation, and there were no postoperative complications. LVA may be a safe and simple option for the treatment of axillary lymphorrhea.

Recent advances in surgical techniques for breast reconstruction.

Although the number of patients with breast cancer continues to rise worldwide, survival rates for these patients have significantly improved. As a result, breast cancer survivors are living longer, and quality of life after treatment is of increasing importance. Breast reconstruction is an important component that affects quality of life after breast cancer surgery. With the development of silicone gel implants in the 1960s, autologous tissue transfer in the 1970s, and tissue expanders in the 1980s, breast reconstruction has advanced over the decades. Furthermore, the advent of perforator flaps and introduction of fat grafting have rendered breast reconstruction a less invasive and more versatile procedure. This review provides an overview of recent advances in breast reconstruction techniques.

Head and Neck Reconstruction With 2-Stage External Pectoralis Major Myocutaneous Flap Transfer.

BACKGROUND: In head and neck surgery cases where skin is severely scarred or adhered to surrounding tissue, reconstruction can be difficult to perform using microsurgical tissue or conventional pedicled pectoralis major myocutaneous flap (PMMF) transfer given the risks, which include damage to major vessels when manipulating scarred skin. For such cases, we perform a 2-stage external PMMF transfer, whereby the PMMF is directly sutured to the defect over the neck skin (without manipulation the hardened skin), and the flap division is then performed secondarily. METHODS: A total of 30 patients who had histories of radiotherapy (60-70 Gy) and prior neck dissection received the 2-stage external PMMF transfer procedure. Indications for the flaps included pharyngeal fistula closure in 12 patients, reconstruction for mandibular necrosis after radiotherapy in 8 patients, salvage surgery for partial or total necrosis of the free flap in 4 patients, and simultaneous reconstruction after tumor excision in 6 patients. Two patients underwent a second external PMMF transfer from the contralateral side because of postoperative complications, yielding a total of 32 flap transfers. RESULTS: Twenty-nine flaps showed complete flap survival, whereas 3 had partial necrosis. Other complications, despite complete flap survival, included large fistulas requiring additional surgery for fistula closure (1 patient) and small fistulas that were closed without requiring reoperation (7 patients). CONCLUSIONS: External PMMF transfer offers a safe, simple, and effective option in cases where free flap surgery is considered difficult or the risks associated with neck manipulation are high.

Squamous Cell Carcinoma of the Scalp Arising in a Site of Synthetic Hair Grafts.

Synthetic hair implantation was developed in the 1970s and initially gained popularity until major cutaneous complications, such as facial swelling, severe dermatitis, recurrent cellulitis, and cicatricial alopecia, became an issue. In particular, the procedure has been suggested to have a possible causal relationship with squamous cell carcinoma (SCC). This article describes the third reported case in the English literature of SCC arising in a site of synthetic hair grafts. The patient was an 80-year-old man with a prominent verrucous tumor in the parietal region; he had undergone synthetic hair implantation for the past 28 years. The pathological diagnosis of SCC was made by dermal punch biopsy, and computed tomography images revealed cranial osteolytic changes, with possible direct dural tumor invasion. Extensive resection of the tumor and reconstruction were performed following downsizing radiotherapy. The protruding tumor was excised with the adjacent portion of the parietal bone. Several synthetic hair grafts were found stuck in the cranium. The defect area was reconstructed with a synthetic bone material and a free latissimus dorsi muscle flap with skin graft. The pathological examination revealed well-differentiated SCC surrounded by numerous synthetic hair grafts inducing inflammatory cell infiltration and severe cicatrizing fibrous changes. The postoperative course was uneventful, and no recurrence or metastasis was observed at 9 months postoperatively.

Bipedicled SIEA Flap with Deep Inferior Epigastric Artery and Vein Grafts for Breast Reconstruction.

A superficial inferior epigastric artery (SIEA) flap can be an alternative to a deep inferior epigastric artery perforator (DIEAP) flap in cases where SIEAs are relatively well developed. Although an SIEA flap is less invasive than a DIEAP flap, the pedicles of the former are anatomically shorter, making it more difficult to choose recipient vessels when bilateral SIEAs are necessary. A 45-year-old female diagnosed with cancer of the left breast underwent mastectomy (specimen weight: 750 g) and immediate two-stage breast reconstruction using a free abdominal flap with bilateral pedicles was planned. Preoperative computed tomographic angiography showed that the bilateral DIEAPs in the flap were less than one millimeter in diameter, whereas the bilateral SIEAs were well developed enough for us to opt for a double-pedicled stacked SIEA flap. After the double-pedicled SIEA flap was elevated, folded, and temporarily placed in the subcutaneous pocket, the pedicle length on one side was found to be insufficient. Therefore, portions of the right composite deep inferior epigastric artery (DIEA) and vein (DIEV) grafts (roughly 7 cm) were collected from a short fasciotomy and anastomosed to the peripheral ends of the right SIEA and SIEV, respectively. Following this, the left SIEA and SIEV were antegradely anastomosed to the internal mammary artery and vein (IMA/IMV), while the DIEA/DIEV grafts were retrogradely anastomosed to the IMA/IMV, respectively. We recommend the proactive use of this method, as pedicle extension using the DIEA/DIEV grafts enables a higher degree of freedom in unilateral breast reconstruction using bilateral SIEA flaps.

Moisturization of the Surgical Field during Cancer Resection Reduces Perioperative Complications in Reconstruction Surgery.

Background: Intraoperative tissue desiccation is a risk factor for infection and wound necrosis. We hypothesized that maintaining a moist environment in the surgical field would reduce perioperative complications in free flap reconstruction for head and neck cancer surgery. Methods: A total of 331 patients who underwent free flap reconstruction after head and neck cancer surgery from January 2013 to December 2017 at Osaka International Cancer Institute were included in the study. We classified patients into two groups: those in whom saline was sprayed only during reconstruction (control group: 162 patients) and those in whom saline was sprayed in the surgical field intermittently during cancer resection and reconstruction (moisturized group: 169 patients). We compared perioperative complications, including intraoperative arterial anastomotic thrombosis, between the two groups. Other candidate risk factors for intraoperative arterial thrombosis that were assessed included a history of preoperative irradiation, history of neck surgery, advanced age, and flap type. Results: Rates of abscess formation and intraoperative arterial thrombosis were significantly lower in the moisturized group than in the control group (6.5% versus 12.7%, P < 0.05 and 3.0% versus 11.1%, P < 0.01, respectively). Binomial logistic regression analysis revealed that, in addition to no moisturization during cancer resection, advanced age and jejunal flap use were significant risk factors for intraoperative arterial thrombosis. Conclusions: Moisturization of the surgical field during cancer resection reduced the rate of perioperative complications in free flap reconstruction. Although simple, preventing desiccation of the surgical field by spraying saline solution intermittently had significant benefits on postoperative complications.

Hydrogen-generating Si-based agent protects against skin flap ischemia-reperfusion injury in rats.

Hydrogen is effective against ischemia-reperfusion (I/R) injury in skin flaps. However, the difficulty of continuously administering a sufficient amount of hydrogen using conventional methods has been an issue in the clinical application of hydrogen-based therapy. An Si-based agent administered orally was previously shown to continuously generate a large amount of hydrogen in the intestinal environment. In this study, we assessed the effect of the Si-based agent on the inhibition of I/R injury in skin flaps using a rat model. In the I/R groups, the vascular pedicle of the abdominal skin flap was occluded for three hours followed by reperfusion. In the I/R + Si group, the Si-based agent was administered perioperatively. After reperfusion, flap survival rate, blood flow, oxidative stress markers, inflammatory markers/findings, and degree of apoptosis were evaluated. Flap survival rate was significantly higher, and histological inflammation, apoptotic cells, oxidative stress markers, and levels of inflammatory cytokine mRNA and protein expression were significantly lower, in the I/R + Si group compared to the I/R group. The Si-based agent suppressed oxidative stress, apoptosis, and inflammatory reactions resulting from I/R injury, thereby contributing to improvements in skin flap survival.

Successful separation of male pygopagus with anal canal and urethral reconstruction: a case report.

BACKGROUND: Pygopagus is a type of conjoined twin binding at the buttocks. Some cases of pygopagus involve the fusion of the gastrointestinal tract, urinary tract, and spinal cord. Few cases of male pygopagus have been reported; however, the prognosis after separation is unclear. Herein, we report a case of male pygopagus in which successful separation was performed with the reconstruction of the anal canal. CASE PRESENTATION: Twins with male pygopagus were born at 35 weeks by cesarean section. They shared a common anus, penis, and scrotum with four testes. The infants had normal defecation and urination after birth. The separation surgery was scheduled when they were 5 months. Two distinct anesthesia teams and four surgical teams (neurosurgery, pediatric urology, plastic surgery, and pediatric surgery) were involved in the multidisciplinary approach. After separating the spinal cord, we found that the anal canal and sphincter muscle complex were fused near the anal aperture, and we separated them. The fused penis and testis were separated and reconstructed using the same incisional line as the other separation, and the reconstructions of the anal canals with the sphincter muscle complex were completed. Both patients had an uneventful postoperative course. At 2 years of age, they could walk and defecate independently. In addition, they voided spontaneously without urinary incontinence at the time of 3 years and 11 months. CONCLUSIONS: Separation of the spinal cord with anal canal and urethral reconstruction is important for male pygopagus patients as it allows them to preserve their independent function.

Selective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain.

Cancer-specific cell surface antigens are ideal therapeutic targets for monoclonal antibody (mAb)-based therapy. Here, we report that multiple myeloma (MM), an incurable hematological malignancy, can be specifically targeted by an mAb that recognizes a ubiquitously present protein, CD98 heavy chain (hc) (also known as SLC3A2). We screened more than 10,000 mAb clones raised against MM cells and identified R8H283, an mAb that bound MM cells but not normal hematopoietic or nonhematopoietic cells. R8H283 specifically recognized CD98hc. R8H283 did not react with monomers of CD98hc; instead, it bound CD98hc in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on MM cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not react with them. The glycoforms of CD98hc present on normal leukocytes were distinct from those present on MM cells, which may explain the lack of R8H283 reactivity to normal leukocytes. R8H283 exerted anti-MM effects without damaging normal hematopoietic cells. These findings suggested that R8H283 is a candidate for mAb-based therapies for MM. In addition, our findings showed that a cancer-specific conformational epitope in a ubiquitous protein, which cannot be identified by transcriptome or proteome analyses, can be found by extensive screening of primary human tumor samples.

Effects of Temporary and Permanent Muscle Denervation on Fat Graft Retention in the Latissimus Dorsi Muscle: An Experimental Study in Rats.

BACKGROUND: In breast reconstruction with a latissimus dorsi flap, immediate fat grafting is useful for increasing flap volume. However, factors such as latissimus dorsi muscle atrophy and fat graft retention affect the volume of the reconstructed breast, and reports are inconsistent regarding treatment of the thoracodorsal nerve. This study examined how thoracodorsal nerve treatment affects the rates of latissimus dorsi flap preservation and fat graft retention using a rat model. METHODS: Fat harvested from the inguinal region was grafted to the latissimus dorsi muscle elevated as a pedicled muscle flap on the experimental side and to the intact LD muscle on the contralateral side (control). Rats were divided into intact thoracodorsal nerve (Ni), temporary denervation (Ntd), and permanent denervation (Npd) groups (n = 8 each). Fat retention and muscle preservation rates were determined, and histological changes were analyzed postoperatively. RESULTS: Fat retention rates did not significantly differ between the Ni and Ntd groups. Only the Npd group showed a significant decrease in fat retention rate relative to the control side (p < 0.01). The quality of the grafted fat as reflected by histological parameters was significantly lower, and the viable adipocyte area and muscle fiber preservation rate significantly decreased, in the Npd group compared to the other groups. CONCLUSIONS: Permanent thoracodorsal nerve denervation resulted in severe muscle atrophy and a significantly decreased fat retention rate. Temporary denervation had no significant benefit, suggesting that preserving the thoracodorsal nerve may be desirable for achieving sufficient volume in latissimus dorsi flap breast reconstruction with immediate fat grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sensory Reinnervation With Subcutaneously Embedded Innervated Flaps: An Experimental Study in Rats.

BACKGROUND: In breast reconstruction, both aesthetic outcomes and sensory function are important for postoperative quality of life. Innervated flaps are useful in reconstruction after conventional mastectomy (CM), which leaves a large portion of the skin paddle exposed on the body surface. However, whether they are also useful in skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) remains unclear. This study aimed to examine the usefulness of innervated flaps in restoring sensation after SSM and NSM using a rat model. METHODS: Dorsal cutaneous nerves of rats were entirely eliminated except for the medial branch of the dorsal cutaneous nerve of thoracic segment 13, resulting in an innervated field surrounded by a denervated field. The innervated field was elevated as an innervated island flap and then subcutaneously embedded, with the skin paddle deepithelialized entirely (NSM group, n = 5) or except at the center (SSM group, n = 6). In the control model (CM group, n = 5), the flap was sutured back into its original position. Postoperative changes in the mechanonociceptive field were evaluated using the cutaneous trunci muscle reflex test. Immunohistochemical evaluation of regenerated nerves in the new mechanonociceptive field was performed at postoperative week 12. RESULTS: In the SSM and CM groups, the mechanonociceptive field expanded around the skin paddle. In the NSM group, a new mechanonociceptive field appeared at postoperative week 4 and expanded thereafter. Areas of the mechanonociceptive field at postoperative week 12 did not differ significantly between the SSM and NSM groups, but were significantly smaller compared with the CM group and comparable to original flap areas. Histologically, S100- and PGP9.5-positive nerve fibers were observed in the dermis of the new mechanonociceptive field and subcutaneous flap tissue. CONCLUSIONS: Subcutaneously embedded innervated island flaps induced nerve regeneration and sensory reinnervation of the denervated skin, suggesting that innervated flaps may also be useful in reconstruction post-SSM/NSM.