Outcomes for Physiologic Microsurgical Treatment of Secondary Lymphedema Involving the Extremity.

OBJECTIVE: The aim of this study was to examine the long-term impact of physiologic surgical options, including VLNT and LVB, on patients with secondary lymphedema of the upper or lower extremity (UEL/LEL). SUMMARY BACKGROUND DATA: VLNT and LVB have become increasingly popular in the treatment of lymphedema. However, there is a paucity of long-term data on patient outcomes after use of these techniques to treat lymphedema. METHODS: An analysis of prospectively collected data on all patients who underwent physiologic surgical treatment of secondary lymphedema over a 5.5-year period was performed. Patient demographics, surgical details, subjective reported improvements, LLIS scores, and postoperative limb volume calculations were analyzed. RESULTS: Two hundred seventy-four patients with secondary lymphedema (197 upper, 77 lower) were included in the study. More than 87% of UEL patients and 60% of LEL patients had reduction in excess limb volume postoperatively. At 3 months postoperatively, patients with UEL had a 31.1% reduction in volume difference between limbs, 33.9% at 6 months, 25.7% at 12 months, 47.4% at 24 months and 47.7% at 4 years. The reduction in limb volume difference followed a similar pattern but was overall lower for LEL patients. Greater than 86% of UEL and 75% of LEL patients also had improvement in LLIS scores postoperatively. Fifty-nine complications occurred (12.9%); flap survival was >99%. CONCLUSIONS: Patients with secondary UEL/LEL who undergo VLNT/LVB demonstrate improved functional status and reduced affected limb volumes postoperatively. Patients with UEL seem to have a more substantial reduction in limb volume differential compared to LEL patients.

Office-Based Forehead Flaps: A Safe and Reliable Reconstructive Option.

BACKGROUND: Forehead flaps are one of the workhorse flaps for nasal reconstruction, especially for large defects involving the nasal tip, ala, or multiple nasal subunits. Forehead flaps are often performed on older patients who have accompanying comorbidities and who may be at higher risk for anesthetic complications. The aim of this retrospective study was to compare the safety and success of forehead flap nasal reconstruction in 2 different clinical settings: those performed under local anesthesia in an office-based procedure room, compared with those performed in the operating room under either general anesthesia or intravenous sedation. METHODS: A retrospective chart review was performed on all patients who underwent forehead flap reconstruction between the years of 2011 and 2018 by the senior author. Patient demographics, operative details, and postoperative complications were recorded and analyzed. Patients were followed for 1 year postoperatively or until the end of the study period. Patients were excluded if they had an accompanying unrelated cosmetic procedures performed during first-stage forehead flap reconstruction. RESULTS: A total of 96 forehead flaps were performed, 35 of which (36.5%) were done in an office-based procedure room using local anesthesia only. Patient ages ranged from 45 to 92 years, with an average age of 71.9 years. The majority of flaps (n = 81, 85.3%) were divided at the second-stage procedure. There was no statistically significant difference in time elapsed between first- and second-stage procedures between groups (procedure room: 22.6 days; operating room: 23.8 days). There were 13 total postoperative complications (13.5%), but there was no statistically significant difference in complication rate between groups (office-based: 3 complications, 8.6%; operating room: 10 complications, 16.4%). CONCLUSIONS: Our data suggest that forehead flap reconstruction can be done safely with acceptable postoperative results when performed under local anesthesia in an office-based outpatient setting.

Exchange hybrid cranioplasty using particulate bone graft and demineralized bone matrix: the best of both worlds.

Reconstruction of craniofacial defects in children presents several challenges that are not encountered in the adult population. Autologous bone grafts have long been the criterion standard for repairing these defects. Recently, several new materials and techniques have expanded our arsenal of reconstructive options. In this clinical report, we describe the use of both particulate bone grafting and demineralized bone matrix together to repair craniofacial defects encountered in pediatric patients.

Risk Factors for Upper Extremity Impairment after Mastectomy: A Single Institution Retrospective Review.

Background: Patients with breast cancer treated with mastectomy are more likely to develop upper extremity dysfunction compared with those treated with breast-conserving therapy. This study aimed to identify cancer and treatment characteristics that may be risk factors for development of upper extremity dysfunction in patients treated with mastectomy. Methods: The authors performed a retrospective chart review of patients at the University of Chicago who were treated with a unilateral or bilateral mastectomy from 2010 to 2020 and developed upper extremity dysfunction based on International Classification of Disease-10 codes. Patients were analyzed by side of body (left or right). Patient demographics and treatment characteristics were extracted from the electronic medical record. Results: In total, 259 patients met criteria and were included in our study. A total of 396 upper extremities were recorded as experiencing dysfunction and were analyzed. Mean age was 60 years (range = 28-96), and mean body mass index was 28.4 (SD = 7.5). An estimated 54% of patients underwent breast reconstruction. After multivariable analysis, chronic upper extremity pain was found to be associated with ipsilateral radiotherapy (P < 0.001) and ipsilateral in situ cancer (0.041). Limited range of motion was found to be associated with ipsilateral invasive cancer (P = 0.01), any ipsilateral mastectomy surgery (P < 0.001), and ipsilateral radiotherapy (P = 0.03). Musculoskeletal dysfunction was found to be associated with no ipsilateral modified radical mastectomy (P = 0.033). No oncological or treatment characteristics were found to be associated with decreased strength or adhesive capsulitis. Furthermore, breast reconstruction (implant or autologous tissue based) was not associated with upper extremity dysfunction. Conclusion: Breast cancer characteristics and treatment modalities may predispose patients treated with mastectomy to developing types of upper extremity dysfunction.

Health Disparities in Patients Seeking Physiological Surgical Treatment for Lymphedema.

BACKGROUND: Previous studies have demonstrated racial disparities in breast cancer treatment and secondary lymphedema. However, no studies have yet examined the effects of race and socioeconomic status on physiological surgical treatment for lymphedema. The authors aimed to evaluate whether disparities exist within patients seeking physiological surgical lymphedema treatment. METHODS: A retrospective review was performed of patients presenting for physiological surgical treatment of lymphedema from 2013 to 2019. Data on demographics, medical history, socioeconomic factors, lymphedema, and treatments were collected. RESULTS: A total of 789 patients (712 women and 77 men) seeking physiological surgical treatment of lymphedema were selected. Their mean age was 54.4 ± 13.4 years. A total of 620 patients (78.5%) self-reported as White, 120 (15.2%) as Black, 17 (2.2%) as Asian, five (0.6%) as Hispanic, and eight (2.4%) as multiracial. A total of 566 patients (71.7%) met criteria for surgical candidacy. White race was associated with increased rates of surgical candidacy compared with Black race (46.6% versus 77.2%; P < 0.0001). Compared with White patients, Black patients presented with a longer symptom duration (11.07 versus 6.99 years; P < 0.001), had a higher body mass index (mean, 34.5 versus 28.1; P < 1 × 10 -10 ), had a higher International Society of Lymphology stage ( P < 0.05), and were less likely to have maximized medical treatment for lymphedema (30.8% versus 55.4%; P < 0.01). CONCLUSIONS: This study demonstrates racial disparities in patients seeking physiological surgical treatment for lymphedema. Black patients present later with more severe disease, receive less nonsurgical treatment before consultation, and are less likely to meet criteria for physiological surgery. Improved patient and provider education on lymphedema and appropriate diagnosis and nonsurgical treatment is of primary importance to address this disparity.

Physical and Functional Outcomes of Simultaneous Vascularized Lymph Node Transplant and Lymphovenous Bypass in the Treatment of Lymphedema.

BACKGROUND: The authors analyze the outcomes of simultaneous vascularized lymph node transplant and lymphovenous bypass for treatment of primary and secondary lymphedema. To the best of their knowledge, this is the largest study to date with long-term outcome data of this novel approach. METHODS: Three hundred twenty-eight patients who underwent physiologic surgical treatment over a 5.5-year period were evaluated using a prospective database and chart review. Preoperative characteristics, operative details, and postoperative outcomes (volume difference change, Lymphedema Life Impact Scale score) were assessed. Statistical analysis including multivariate regression was performed. RESULTS: Two hundred twenty patients (67.1 percent) underwent simultaneous vascularized lymph node transplant and lymphovenous bypass. Mean body mass index was 26.9 ± 4.7 kg/m 2 . Ninety-two patients (41.8 percent) had lymphedema of the lower extremity, 121 (55.0 percent) had upper extremity involvement, and seven had lymphedema of upper and lower extremities (3.2 percent). Average duration of lymphedema was 95.4 ± 103.6 months. Thirty patients (13.6 percent) had primary lymphedema and 190 patients (86.4 percent) had secondary lymphedema. The majority improved and experienced volume reduction of an average 21.4 percent at 1 year ( p < 0.0001), 36.2 percent at 2 years ( p < 0.0001), 25.5 percent at 3 years ( p = 0.1), and 19.6 percent at 4 years. Median Lymphedema Life Impact Scale scores were 7.0 points lower ( p < 0.0001) at 3 months and improved progressively over time to 27.5 points lower at 3 years postoperatively ( p < 0.005). CONCLUSIONS: Simultaneous vascularized lymph node transplant and lymphovenous bypass is an appropriate and effective approach for both early and advanced stages of primary and secondary lymphedema, with significant objective and subjective improvements. Volume reduction in the affected limb was observed at all time points postoperatively, with significant improvement in Lymphedema Life Impact Scale scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Four-Quadrant Approach Squared: Ethical Analysis of Living Donation in Vascularized Composite Allotransplantation.

SUMMARY: Vascularized composite allotransplantation has become a widely accepted method for reconstruction or restoration of body parts, and the various ethical dilemmas that accompany vascularized composite allotransplantation have been widely discussed. As advancements in immunosuppression and tolerance continue to be made, the concept of living donor vascularized composite allotransplantation will likely become a popular option of the "reconstructive elevator." In this article, the authors discuss the various ethical implications of living donor vascularized composite allotransplantation.

Advances in surgical treatment of lymphedema.

An estimated 250 million people worldwide suffer from lymphedema. In the past, the firstline option for treatment was nonsurgical management, either in the form of compression garments or wrapping, or comprehensive decongestive therapy, with debulking surgery reserved for the more advanced cases. However, with improvements in microsurgical techniques and imaging modalities, surgical intervention is increasingly being utilized. This review highlights recent advancements in the surgical treatment of lymphedema, specifically focusing on improvements in imaging, surgical techniques, and prevention of lymphedema.

Post-Breast Surgery Pain Syndrome: Shifting a Surgical Paradigm.

Post-mastectomy pain syndrome and the less well-described post-breast surgery pain syndrome are long-term neuropathic pain conditions that may affect more than 50% of patients after mastectomy and breast surgery. While the etiology, risk factors, and management have been reviewed in our literature, we offer here a focused outline that will gear the plastic surgeon with tools to lead a multidisciplinary, algorithmic approach to the care of patients with post-mastectomy pain syndrome/post-breast surgery pain syndrome. After reading this article, we hope the reader will have improved awareness of post-mastectomy pain syndrome/post-breast surgery pain syndrome, and thus be able to incorporate appropriate treatments and preventative steps into their primary surgical routine.

Urban Frostbite: Strategies for Limb Salvage.

Under ideal circumstances, severely frostbitten extremities are rapidly rewarmed and treated with thrombolytic therapy within 6 to 24 hours. In an "inner city," urban environment, most patients who suffer frostbite injuries present in a delayed fashion, sustain repeated injuries further complicated by psychological issues or intoxication, and are rarely ideal candidates for thrombolytic therapy within the prescribed timeframe. We describe our experience with the treatment of urban frostbite injuries. A retrospective review of patients with cold injuries sustained between November 2013 and March 2014 treated at a verified burn center in an urban setting was performed. Fifty-three patients were treated (42 males, 11 females). Average patient age was 41.8 years (range 2-84 years). No patients met criteria for thrombolytic therapy due to multiple freeze-thaw cycles or presentation greater than 24 hours after rewarming. Deep frostbite was seen in 10 patients. Of these patients, nine underwent debridement, resulting in partial limb amputations at levels guided by Tri-phasic technetium (Tc-99m) bone scans. Wound closure and limb-length salvage was then achieved by: free flap coverage (n = 2), local flaps (n = 8), split-thickness skin grafting (n = 22), and secondary intention healing (n = 6). While tissue plasminogen activator has been successful in reducing the need for digital amputation following frostbite injuries, in our experience, this treatment modality is not applicable to the urban patient population who often present late and after cycles of reinjury. Therefore, our approach focused on salvaging limb length with durable coverage, as the injuries were unable to be reversed.

Wide excision and healing by secondary intent for the surgical treatment of hidradenitis suppurativa: A single-center experience.

BACKGROUND: This study reviewed a single center's 14-year experience with surgical treatment of chronic, severe hidradenitis suppurativa (HS) through wide excision technique and healing by secondary intention. METHODS: All patients who underwent wide excision of HS between 2000 and 2014 and allowed to heal by secondary intention were included. Wound care consisted of topical antimicrobials and hydrotherapy. Physical therapy was initiated for joint contracture prevention. Patients were followed until complete wound closure. RESULTS: Seventeen patients underwent 23 separate surgical encounters, five with excision of multiple areas. Seventeen excisional procedures were conducted on the upper half of the body (axillary, breast) and 11 on the lower half (inguinal, perineum, perianus, and abdomen). Two patients developed HS recurrence adjacent to the surgical site (one requiring reexcision and the other treated with topical therapy), whereas two developed HS flares at distant nonsurgical sites managed medically. The mean follow-up was 1.02 years with a median of 6 months ranging from 1.2 months to 5.25 years. Complete wound healing ranged from 8 weeks to 16 months, with limited range of motion (ROM) in two patients. CONCLUSIONS: Attempts at removing all tissue affected by HS through wide surgical excision are the mainstay intervention for achieving complete local cure, particularly in the most severe cases of the disease. Our experience with wide excision of disease and healing by secondary intent demonstrated clinically satisfactory functional and excellent aesthetic results in multiple anatomic areas and even for large defects. This healing modality requires strict adherence to the wound healing protocol, which is often tolerated only by patients who have endured symptoms of severe HS for an extended length of time.

Osteoprotegerin deficiency results in disruption of posterofrontal suture closure in mice: implications in nonsyndromic craniosynostosis.

BACKGROUND: Little is known about the role of osteoclasts in cranial suture fusion. Osteoclasts are predominantly regulated by receptor activator of nuclear factor kappa B and receptor activator of nuclear factor kappa B ligand, both of which lead to osteoclast differentiation, activation, and survival; and osteoprotegerin, a soluble inhibitor of receptor activator of nuclear factor kappa B. The authors' work examines the role of osteoprotegerin in this process using knockout technology. METHODS: Wild-type, osteoprotegerin-heterozygous, and osteoprotegerin-knockout mice were imaged by serial micro-computed tomography at 3, 5, 7, 9, and 16 weeks. Suture density measurements and craniometric analysis were performed at these same time points. Posterofrontal sutures were harvested from mice after the week-16 time point and analyzed by means of histochemistry. RESULTS: Micro-computed tomographic analysis of the posterofrontal suture revealed reduced suture fusion in osteoprotegerin-knockout mice compared with wild-type and heterozygous littermates. Osteoprotegerin deficiency resulted in a statistically significant decrease in suture bone density in knockout mice. There was no reduction in the density of non-suture-containing calvarial bone between wild-type and osteoprotegerin-knockout mice. Histochemistry of suture sections supported these micro-computed tomographic findings. Finally, osteoprotegerin-knockout mice had reduced anteroposterior skull distance at all time points and an increased interorbital distance at the week-16 time point. CONCLUSION: The authors' data suggest that perturbations in the expression of osteoprotegerin and subsequent changes in osteoclastogenesis lead to alterations in murine cranial and posterofrontal suture morphology.

Molecular basis of cranial suture biology and disease: Osteoblastic and osteoclastic perspectives.

The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures. Here, the borders of the calvarial bones and neighboring tissues above and below, function as a complex. Through coordinated remodeling efforts of bone deposition and resorption, the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain's demands for expansion. However, when this delicate balance is disturbed, a number of pathologic conditions ensue; and if left uncorrected, may result in visual and neurocognitive impairments. A prime example includes craniosynostosis, or premature fusion of one or more cranial and/or facial suture(s). At the present time, the only therapeutic measure for craniosynostosis is surgical correction by cranial vault reconstruction. However, elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture fusion. Such deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture defects. In this review, we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components: dura mater, osteoblastic related molecular pathways and osteoclastic related molecular pathways.

Prelaminated fascia lata free flap for large nasal septal defect reconstruction.

Nasal septal defects can be challenging to repair, given their location, size, and the unique, tri-layered structure of the septum, which includes a thin piece of cartilage positioned between mucosal layers. The report herein presents a case of a 47 year-old woman with a large symptomatic nasal septal perforation, despite saline irrigations and ointment. Placement of a septal button or a traditional surgical approach was not considered because of the extremely large nature of the perforation. We describe the use of a tri-layered fascia lata flap prelaminated with buccal mucosa grafts to successfully repair this complicated defect. Subsequent follow-up visits showed complete repair of the defect and patent nasal passages, without the need for any debulking procedures. Based on these results, we conclude that a prelaminated fascia lata flap is a good reconstructive option for large, complex nasal septal defects, bringing thin, healthy mucosalized tissue to the defect and minimizing future surgical procedures.

Distinct effects of platelet-rich plasma and BMP13 on rotator cuff tendon injury healing in a rat model.

BACKGROUND: Although platelet-rich plasma (PRP) is used clinically to augment tendon healing, bone morphogenetic protein-13 (BMP13) may provide a better therapeutic avenue to improve early tendon healing and repair. HYPOTHESIS: Exogenous expression of BMP13 in tenocytes will up-regulate genes involved in tendon healing. Direct delivery of adenovirus-mediated BMP13 (AdBMP13) into the injured rat supraspinatus tendon will increase biomechanical properties. STUDY DESIGN: Controlled laboratory study. METHODS: Exogenous expression of BMP13 and the major growth factors in PRP (transforming growth factor-ß1 [TGF-ß1], vascular endothelial growth factor-A [VEGF-A], and platelet-derived growth factor-BB [PDGF-BB]) was accomplished by using recombinant adenoviral vectors. The expression of tendon- and matrix-associated genes in growth factor-treated tenocytes was analyzed by use of semiquantitative reverse-transcription polymerase chain reaction. A total of 32 rats with supraspinatus defect were divided into 4 groups and injected with adenovirus-containing green fluorescent protein (AdGFP; negative control), PRP, AdBMP13, or PRP+AdBMP13. All rats were sacrificed at 2 weeks after surgery, and tendons were harvested for biomechanical testing and histologic analysis. RESULTS: BMP13 up-regulated type III collagen expression compared with AdGFP control and PRP growth factors (P < .01). BMP13 and PRP growth factors each up-regulated fibronectin expression (P < .01). There was an increase in stress to failure in each of the 3 treatment groups (P < .05 for PRP; P < .01 for AdBMP13 or PRP+AdBMP13) compared with AdGFP control. AdBMP13 demonstrated higher stress to failure than did the PRPs (P < .01). The addition of PRP did not increase the BMP13-enhanced stress to failure or stiffness. The biomechanical results were further supported by histologic analysis of the retrieved samples. CONCLUSION: Exogenous expression of BMP13 enhances tendon healing more effectively than PRP as assessed by tendon- and matrix-associated gene expression, biomechanical testing, and histologic analysis. CLINICAL RELEVANCE: While PRP is used in the clinical setting, BMP13 may be explored as a superior biofactor to improve rotator cuff tendon healing and reduce the incidence of retears.

Mechanical Leeching with Venocutaneous Fistula and Monitoring with Near-infrared Spectroscopy.

SUMMARY: The report herein describes the use of a venocutaneous fistula with angiocatheter attachment and near-infrared spectroscopy device to correct venous congestion of a vertical upper gracilis free flap used for breast reconstruction. This method of mechanical leeching was precisely controlled through monitoring trends in the tissue oxygen saturation levels of the flap, allowing venous congestion to be relieved before it became clinically apparent.

BMP signaling in mesenchymal stem cell differentiation and bone formation.

Bone morphogenetic proteins (BMPs) are members of the TGF-ß superfamily and have diverse functions during development and organogenesis. BMPs play a major role in skeletal development and bone formation, and disruptions in BMP signaling cause a variety of skeletal and extraskeletal anomalies. Several knockout models have provided insight into the mechanisms responsible for these phenotypes. Proper bone formation requires the differentiation of osteoblasts from mesenchymal stem cell (MSC) precursors, a process mediated in part by BMP signaling. Multiple BMPs, including BMP2, BMP6, BMP7 and BMP9, promote osteoblastic differentiation of MSCs both in vitro and in vivo. BMP9 is one of the most osteogenic BMPs yet is a poorly characterized member of the BMP family. Several studies demonstrate that the mechanisms controlling BMP9-mediated osteogenesis differ from other osteogenic BMPs, but little is known about these specific mechanisms. Several pathways critical to BMP9-mediated osteogenesis are also important in the differentiation of other cell lineages, including adipocytes and chondrocytes. BMP9 has also demonstrated translational promise in spinal fusion and bone fracture repair. This review will summarize our current knowledge of BMP-mediated osteogenesis, with a focus on BMP9, by presenting recently completed work which may help us to further elucidate these pathways.