Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Nasal Construction in Congenital Arhinia Due to Novel SMCHD1 Gene Variant.

Arhinia, or congenital absence of the nose, is an exceedingly rare anomaly caused by pathogenic variants in the gene SMCHD1 . Arhinia exhibits unique reconstructive challenges, as the midface is deficient in skeletal and soft tissue structures. The authors present 2 related patients with arhinia who harbor a novel SMCHD1 gene variant and illustrate their surgical midface and nasal construction. Targeted sequencing was carried out on DNA samples from the 2 affected patients, 1 anosmic and 1 healthy parent, to identify variants in exons 3 to 13 of SMCHD1 . The affected patients and anosmic parent were found to have a novel SMCHD1 gene variant p.E473V. A staged surgical approach was applied. First, both patients underwent a LeFort II osteotomy and distraction osteogenesis to improve the projection of the midfacial segment, followed by tissue expansion of the forehead, and nasal construction with a forehead flap that was placed over a costochondral framework derived from rib cartilage. The novel gene variant could guide future investigations on genetic pathways and molecular processes that underly the physiological and pathologic development of the nose. Further investigations on the variable expressivity ranging from anosmia to arhinia could improve clinical genetic screens for risk stratification of individuals with anosmia on passing on arhinia to their children. Due to the exceptional rarity and complexity of congenital arhinia, most surgical approaches are developed on a single-case basis. This case series, albeit limited to 2 cases, is the largest pedigree of such cases in the literature. It highlights key principles of a staged approach to nasal construction in arhinia and discusses nuances and improvements learned between both patients. It subsequently offers an optimized guide to this surgical strategy.

Triangular Fossa Graft for Philtral Reconstruction After Facial Burns: A 34-Year Experience.

BACKGROUND: Upper lip burns and skin grafts used for the resulting deformities all contract, leading to distortion of regional tissues and producing a flattened upper lip devoid of normal anatomic landmarks. Absence of the philtral contour draws attention to the upper lip and can accentuate other reconstructive inadequacies. Philtral restoration requires a 3-dimensional reconstruction capable of resisting contractile forces to restore and maintain normal relationships between the upper and lower lips. METHODS: This was a 34-year retrospective review of a single surgeon's experience using a composite triangular fossa graft from the ear for philtral reconstruction. Ten patients were identified and analyzed using records of follow-up examinations, long-term clinical evaluations, and photographic documentation. RESULTS: Five males and 5 females were identified with 2- to 34-year follow-up. Age at operation ranged from 14 to 52 years. Percent total body surface area ranged from less than 1% to greater than 90%. Previous upper lip grafts prior to the auricular graft included 5 full-thickness skin grafts and 5 split-thickness skin grafts. No significant complications were noted. All patients were satisfied with the end aesthetic result and donor site morbidity. CONCLUSIONS: A triangular fossa composite graft restores and preserves the philtral dimple and corrects the obvious visible deformity of a featureless upper lip. Addition of tissue loosens the lip transversely, and the cartilage component provides a consistent and predictable upper lip position. This results in improved projection, a concave shape to the upper lip, and a better relationship with the lower lip. Restoration of this anatomic landmark creates a more normal-appearing upper lip and helps to minimize the negative impact of other abnormalities in this vitally important area. The overall improvement in total facial appearance can be profound.

Antegrade Foreheadplasty: A Novel Surgical Approach for Upper Eyelid Contracture Deformities in Pediatric Patients.

The intricate and delicate structure of the periorbital region, particularly in pediatric patients, presents challenges to eyelid reconstruction. Much like the more common lower eyelid ectropion, upper eyelid ectropion can result from lack of tissue, scar contracture, or over-resection as in blepharoplasty. In burns and trauma, the cause of cicatricial ectropion is typically direct scar contracture from injuries to the eyelid. However, in some cases, extrinsic wounds involving contracture to the forehead or eyebrow can result in upper eyelid cicatricial ectropion. Direct reconstruction and skin grafting of the eyelid present complex challenges, especially in the acute inflammatory phase of traumatic injury and burn care. Furthermore, in many of these cases the periorbital and lamellae anatomy is preserved, but rather severely displaced due to scar contracture forces. The authors discuss our experience with treatment of extrinsic upper eyelid cicatricial ectropion in a series of 4 pediatric patients with burns or trauma to the forehead and periorbital regions. In all 4 cases, the antegrade foreheadplasty procedure helped to provide globe coverage, while avoiding skin matching difficulties and the intrinsic risks of operating on the eyelid during the acute phase of recovery. There is currently very limited data for the use of this technique to correct such defects. With this study, the authors hope to establish the antegrade foreheadplasty as a reconstructive option for a select patient population.

Penis Transplantation: First US Experience.

OBJECTIVE: We describe the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND: Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 penis transplants have been performed worldwide. METHODS: After institutional review board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by a multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After appropriate donor identification and recipient induction with antithymocyte globulin, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a donor skin pedicle as the composite allograft. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS: Intraoperative, the allograft had excellent capillary refill and strong Doppler signals after revascularization. Operative reinterventions on postoperative days (PODs) 2 and 13 were required for hematoma evacuation and skin eschar debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff I), progressed by POD 32 (Banff III), and required a repeat course of methylprednisolone and antithymocyte globulin. At 7 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. CONCLUSIONS: We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our successful penile transplantation pilot experience represents a proof of concept for an evolution in reconstructive transplantation.

Ellipsoid Smooth Muscle Tumor of the Lower Eyelid: An Exploration of Its Possible Origin.

Ocular adnexal smooth muscle masses/neoplasms are extremely rare. Such lesions are comparatively more common in the conjunctiva than in the orbit and are most unusual in the eyelid. A 58-year-old woman slowly developed over 4 months a firm, movable sausage-shaped lesion in the deep lateral half of the right lower eyelid. The lesion ran parallel to and above the orbital rim. At surgery, the lesion was located between the orbicularis muscle and the inferior orbital septum. The term ellipsoid is used descriptively and does not imply any particular biologic behavior. Immunohistochemical evaluation revealed smooth muscle actin and desmin positivity. Due to the ubiquity of small blood vessels and the absence of smooth muscle bundles in the potential space between the orbicularis striated muscle and the inferior orbital septum, venular smooth muscle emerges as a highly likely source for the lesion.

Proof-of-Concept Studies for Marker-Based Ultrasound Doppler Analysis of Microvascular Anastomoses in a Modified Large Animal Model.

Background Despite attempts to solve the problem of flap monitoring, assessing the patency of vascular anastomoses postoperatively remains challenging. In addition, experimental data suggest that near-total vessel occlusion is necessary to produce significant changes in clinical appearance or monitoring devices. We sought to develop an ultrasound-based system that would provide definitive data on anastomotic function. Methods A system was developed consisting of a resorbable marker made from poly-lactic-co-glycolic acid (PLGA) implanted during the time of surgery coupled with ultrasound software to detect the anastomotic site and perform Doppler flow analysis. Surgical procedures consisting of microvascular free tissue transfer or femoral vessel cutdown were performed followed by marker placement, closure, and ultrasound monitoring. Transient vascular occlusion was produced via vessel-loop constriction. Permanent thrombosis was induced via an Arduino-controlled system applying current to the vessel intima. Results Four surgeries (one femoral vessel cutdown and three microvascular tissue transfer) were successfully performed in Yorkshire swine. The markers were readily visualized under ultrasound and provided a bounding area for Doppler analysis as well as orientation guidance. Transient spasm and partial occlusion were detected based on changes in Doppler data, while complete occlusion was evident as the total loss of color Doppler. Conclusion In this preliminary report, we have conceptualized and developed a novel system that enables the real-time visualization of vascular pedicle flow at the bedside using Doppler ultrasound and a surgically implanted marker. In a large animal model, use of the system allowed identification of the anastomosis, flow analysis, and real-time detection of flow loss.

Microsurgical Reconstruction of Complex Scalp Defects: An Appraisal of Flap Selection and the Timing of Complications.

BACKGROUND: The purposes of this study were to report a 7-year experience of microvascular reconstruction of scalp defects, compare flap type and outcomes, and evaluate the implications of short and long term complications. METHODS: Following institutional review board approval, a single surgeon's patients requiring microvascular scalp reconstruction were retrospectively reviewed from 2005 to 2011. Flap choice, complications, and outcomes were statistically analyzed. RESULTS: Nineteen patients met inclusion criteria (10 male and 9 female) with a mean age of 60.2 ± 21.4 years (range, 23-90 years). All free tissue transfers (n = 20) achieved 100% soft tissue coverage. Mean size calvarial defect was 106.6 ± 67.2 cm(2) (range, 35-285 cm(2)), with 11 requiring cranioplasty. Free flaps included the following: 13 anteriolateral thigh, 5 ulnar, 1 latissimus dorsi, and 1 thoracodorsal artery perforator. Mean flap size was 154.1 ± 87.3 cm(2) (range, 42-336 cm(2)). Early complications (<30 days following surgery) occurred in 21.1% of patients and late complications (>30 days following surgery) in 52.6% of patients. Patients with an early complication were 2 times more likely to develop a late complication (relative risk, 2.1) but did not reach statistical significance. Late complications were more likely to require surgical intervention, 84.2% versus 60% of early complications (P = 0.079). CONCLUSIONS: Microvascular free tissue transfer is the mainstay of complex scalp defects but carries a high likelihood of future reoperations. Early complications are less concerning than late complications, as the need for future surgical intervention is associated with late complications. There is lack of evidence to support a superior flap choice.

Revisiting the anatomic relationship of the marginal mandibular nerve and the posterior facial vein: a cadaveric study.

In preparation for the donor and recipient facial vascularized composite allotransplant (VCA), the marginal mandibular nerve branch should be identified and co-apted to the recipient's nerve to allow for re-innervation. We describe a method to identify the marginal mandibular branch of the facial nerve in facial VCA donors and recipients. Through cadaver dissections, the posterior facial vein was traced posteriorly to identify the marginal mandibular branch of the facial nerve. In cases where we were unable to use this relationship, we found the posterior facial venous system to be diminutive. This technique is useful for finding the marginal mandibular branch when dissecting anterograde to the parotid gland.

Comparison of free fibular flaps with reamer-irrigator-aspirator bone grafts for the reconstruction of critical-sized mandibular defects.

OBJECTIVE: Vascularized bone flaps are currently indicated for reconstructing mandibular defects 6 cm or larger. This technique can result in donor-site morbidity and requires microsurgery. To explore alternative methods of mandibular reconstruction, we sought to compare bone graft obtained with the reamer-irrigator-aspirator (RIA) device with the free fibula (FF) flap for the reconstruction of a critical-sized mandibular defect. METHODS: Sixteen 3-month-old Yorkshire pigs underwent 6-cm full-thickness resection of the left mandible. For the FF group (n = 8), an osseous FF flap was raised from the left leg and placed into the defect. For the RIA group (n = 8), a RIA Instrument Set was used on the ipsilateral femur to ream the femoral canal and harvest RIA putty. This putty containing medullary bone marrow contents and cortical bone was packed into the defect. At the study end point, volumetric, biomechanical, and histologic analyses were performed. RESULTS: Operative times were significantly shorter in the RIA group (RIA,126 [30] min; FF, 346 [50] min; P < 0.05). Biomechanical testing of reconstructed sites showed no significant difference in maximum fracture loads between both groups (RIA, 468 [97] N; FF, 689 [262] N; P = 0.11). Mean (SD) volume ratio of bone growth at the reconstructed sites was comparable between both groups (RIA, 71% [4.5%]; FF, 72% [3.3%]; P = 0.60). Equal bone quality was confirmed histologically. CONCLUSIONS: The RIA technique significantly reduces operative time and provides bone of equal strength and histologic quality to FF flap reconstruction in a large animal model. The RIA method may represent an efficient technique for the reconstruction of craniomaxillofacial defects.

Reconstruction of porcine critical-sized mandibular defects with free fibular flaps: the development of a craniomaxillofacial surgery model.

Vascularized bone flaps are the well-known standards of care for reconstruction of segmental mandibular defects ≥ 6 cm. We developed a large animal critical-sized mandibular defect model in which osseous free fibula flaps were used for reconstruction.In this study a total of eight 3-month-old Yorkshire pigs underwent 6 cm full-thickness resection of the left hemimandible. An osseous free fibula flap from the left leg was harvested and contoured to the mandibular defect. Bone placement and plate position was confirmed with fluoroscopy. Animals were followed with serial radiographs and clinical evaluations.Free fibulas were transferred successfully in all eight animals. The average operative time was 346 minutes, and the average flap ischemia time was 86 minutes. The average volume ratio of reconstructed hemimandibles to nonoperated control hemimandibles was 0.72 ± 0.33. The average maximum fracture load was 689 ± 262 N, and the average ratio of biomechanical fracture load for these samples compared with contralateral control hemimandibles was 0.88 ± 0.25.It is concluded that the porcine osseous free fibula flaps can be reliably harvested and viably transferred to critical-sized posterior mandibular defects with acceptable long-term results. The described microsurgical large animal model is acceptable for use in craniomaxillofacial experimentation.

Pediatric Postburn Ear Reconstruction of Significant Cartilage Defects.

The external ear is a vulnerable appendage susceptible to trauma. Repairing and recreating its intricate architecture presents a formidable challenge after burn injury, especially when scar tissue, impaired vasculature, and damage to cartilage all influence reconstructive options. The authors share their institutional experience and provide a guide for reconstruction of significant postburn auricular cartilage defects. A retrospective review was conducted on 54 patients (61 ears) aged 0-21 years old admitted to a specialized pediatric burn hospital between January 2004 and January 2021 for postburn ear cartilage reconstruction. Conchal cartilage grafting was performed in 9 patients (9 ears) with an average age of 14.0 ± 5.1 years, requiring an average of 2.0 ± 1.0 procedures that resulted in one case of infection. A total of 21 patients (24 ears) with an average age of 15.1 ± 4.5 years underwent a conchal transposition flap, requiring an average of 1.8 ± 0.4 procedures that resulted in no major complications. A total of 20 patients (23 ears) with an average age of 12.0 ± 5.3 years underwent porous polyethylene implantation, requiring an average of 3.5 ± 1.5 operations that resulted in 3 complications. Costal cartilage grafting was performed in 4 patients (5 ears) with an average age of 13.2 ± 5.3 years, requiring an average of 3.2 ± 2.2 operations that resulted in one case of infection. Postburn ear cartilage defects necessitate an individualized approach tailored to a patient's reconstructive goals. In addition to defect size and location, factors such as reconstructive course duration, complication potential, and anticipated aesthetic results should be discussed with the patient.

Evaluation of liposomal bupivacaine infiltration at reconstructive skin graft donor sites in adolescent and young adult burn patients: A retrospective analysis.

BACKGROUND: Postoperative pain at skin graft donor sites is frequently undertreated in burn patients, which can impair reconstructive outcomes and result in harmful psychological consequences. We find a critical need to explore and promote non-opioid, multimodal analgesics. Donor site infiltration of the local anesthetic liposomal bupivacaine in adolescent and young adult burn patients has not been previously investigated. Therefore, the goal of this study was to evaluate intraoperative liposomal bupivacaine infiltration for postoperative donor site pain control in adolescent and young adult burn patients undergoing reconstructive skin graft procedures. METHODS: This retrospective analysis included patients aged 14-25 years, who underwent at least two reconstructive skin graft procedures, one that received donor site infiltration of the standard treatment (bupivacaine hydrochloride) and one that received donor site infiltration of liposomal bupivacaine. The final sample included 30 patients with a total of 44 liposomal bupivacaine cases and 53 standard treatment cases analyzed. RESULTS: In the authors' five-year experience, the use of liposomal bupivacaine compared to standard treatment was associated with statistically significant decreases in 0-4 h postoperative pain scores (mean 1.4/10 versus 2.3/10, p = 0.04) and 0-24 h postoperative pain scores (mean 1.7/10 versus 2.4/10, p = 0.02). Neither analgesic was associated with adverse events. Differences in length of stay and inpatient postoperative opioid usage were not regarded as significant. CONCLUSION: In this retrospective analysis, the authors report the first results that suggest intraoperative liposomal bupivacaine donor site infiltration may be associated with statistically improved patient outcomes in adolescent and young adult burn patients. However, the reported differences are most likely not clinically significant, establishing the necessity for further evaluation of using liposomal bupivacaine in this unique patient population.

Inflammatory and infectious complications of laser therapy in treatment of hypertrophic burn scars: Correlations in literature review & case reports.

INTRODUCTION: Hypertrophic burn scars contribute to morbidity through secondary symptoms of pain, pruritus, and scar contracture. Traditional treatment methods are now augmented by the use of monochromatic light therapies, which are generally accepted as safe and effective. However, little literature is available regarding the complications of laser treatments of hypertrophic burn scars and even less regarding inflammatory and infectious complications. METHODS: A literature search using PubMed was performed to identify literature pertaining to infectious and inflammatory complications of cutaneous laser treatments. Additionally, we reviewed cases of inflammatory and infectious complications occurring at our institution after laser treatment of hypertrophic burn scars. RESULTS: We identified 1 publication related to complications of laser therapy in the treatment of burn scars. In this series of 163 laser sessions, the reported incidence of adverse events was 25.1%, of which 6 cases 3.7% were related to inflammatory and infectious processes. In the 391 laser sessions performed at our institution (December, 2015 and July, 2016) 9 cases of inflammatory and infectious complications were noted yielding an incidence of 2.3%. Cases included 3 each of cellulitis, Systemic Inflammatory Response Syndrome (SIRS), and complicated SIRS. CONCLUSION: We found the most common inflammatory complication was SIRS with MSSA positive wound cultures. Three cases underwent hospitalization along with fluids and vasopressors, despite negative blood cultures. In light of the high prevalence of MSSA in the natural skin flora and negative blood cultures, the inability to establish a true source of infection lead to declaring these cases "complicated SIRS" and not sepsis. Correlative factors that may have led to complications reported in our cases were: preoperative evidence of infection, no preoperative antibiotics administered, no postoperative antibiotic dressings, combined procedures, and large treatment areas. The true mechanism of inflammatory and infectious complication is yet to be determined, but we postulate that these factors place a greater challenge on an already burdened immune system. Determining whether this is a true causal mechanism, leading to an aggravated inflammatory response, benefits from further investigation. APPLICABILITY OF RESEARCH TO PRACTICE: We urge institutions preforming such procedures to advise patients on preoperative wound preparation. We recommend that each individual with a preexisting history of infection and/or preoperative culture evidence of infection receive antibiotics, particularly when undergoing combined procedures or procedures involving higher surface areas. Although complications are rare, the benefits of these precautionary measures outweigh the risks when it comes to prevention and management.

Experience of outreach in a resource-constrained environment: 10 years of outcomes in burn care.

OBJECTIVE: The objective of this work was to describe an efficient and sustainable outreach model in a resource-constrained environment, with a multifaceted approach focusing on national policy change, telemedicine, injury prevention, education and treatment of burns. SUMMARY BACKGROUND DATA: Burn injury constitutes a significant portion of morbidity and mortality worldwide, particularly in children, and in low- and middle-income countries. METHODS: We reviewed the impact of ten-years of a burn outreach program. Our focus was on clinical data on burn care within one region of Ukraine. We assessed knowledge of burn prevention/first aid utilizing a large survey, analyzed clinical data from our outreach clinic and telemedicine program, and analyzed data within a newly created burn repository within Ukraine. RESULTS: A national burn prevention policy has been implemented through our efforts along with a burn prevention program. Educational efforts have led to improvements of major complication rates (wound infection [7% vs. 16%], pneumonia [2.4% vs. 0.3%], sepsis [1.6% vs. 0.6%], UTI [2% vs. 0.6%], and cellulitis [11% vs. 3.4%]), respiratory support of acutely ill patients [1.3% vs. 0.4%], and blood transfusion triggers. CONCLUSIONS: Broadly, our model could be an example of building sustainable outreach programs in resource-constrained environments. Through collaboration with local healthcare providers, we have developed and implemented an outreach program in a resource-constrained environment.

Latissimus dorsi free flap phalloplasty: a systematic review.

A phalloplasty is a complex genital reconstruction procedure of creating a neophallus. Several techniques to create a neophallus are described, based on different vascularized flaps, and each of them has its advantages and drawbacks. The aim of this study is to present musculocutaneous latissimus dorsi (MLD) flap as a viable option for total phalloplasty, with an interest in clinical outcomes and complications. A comprehensive literature review of all available reports about MLD flap phalloplasty was made. The following keywords were used on PubMed: latissimus dorsi musculocutaneous/myocutaneous free flap and phalloplasty. Research criteria revealed five articles and the results of 182 patients were analyzed. A total number of the patients, indications, operative technique, follow-up period, postoperative results, and complications were presented. In conclusion, MLD free flap presents a good choice for phalloplasty providing sufficient amount of tissue for safe implantation of penile prosthesis and successful penetrative sexual intercourse. The erogenous sensitivity is preserved with clitoris or glans penis incorporated into the base of the neophallus, and voiding in a standing position is achievable after urethral reconstruction. The main drawback is the lack of tactile sensation of the neophallus and the significant advantage is a well-concealed donor site.