Incidence, Impact, and Management of Incidentalomas on Preoperative Computed Tomographic Angiograms for Breast Cancer Patients with and without Genetic Mutations.

BACKGROUND: Preoperative abdominal computed tomographic angiograms for free flap breast reconstruction improve operative safety and efficiency, but incidental findings are common and potentially affect management. In addition, the authors hypothesized that patients with genetic mutations might have a higher rate of significant findings. The authors present the largest series of computed tomographic angiogram "incidentalomas" in these two populations and an evidence-based algorithm for managing common findings. METHODS: All patients undergoing free flap breast reconstruction at Northwell Health between 2009 and 2017 were eligible. Medical history, perioperative details, and radiology reports were examined with abnormal findings recorded. Published literature was reviewed with radiologists to develop standardized guidelines for incidentaloma management. RESULTS: Of 805 patients included, 733 patients had abdominal imaging. One hundred ninety-five (27 percent) had a completely negative examination. In the remaining 538 patients, benign hepatic (22 percent) and renal (17 percent) findings were most common. Sixteen patients (2.2 percent) required additional imaging (n = 15) or procedures (n = 5). One finding was concerning for malignancy-renal cell carcinoma-which interventional radiology ablated postoperatively. Seventy-nine patients (10.8 percent) had a genetic mutation but were not found to have a statistically significant higher rate of incidentalomas. CONCLUSIONS: The authors' rate of computed tomographic angiography incidental findings (73 percent) is consistent with previous studies, but the rate requiring further intervention (2.2 percent) is lower. Incidental findings were no more common or pathologic among genetic mutation carriers. The authors also introduce an evidence-based algorithm for the management of common incidentalomas. Using these guidelines, plastic surgeons can reassure patients, regardless of mutation status, that incidentalomas are most commonly benign and have minimal impact on their surgical plan.

Evaluation of internal mammary lymph node biopsy during microsurgical breast reconstruction: An analysis of 230 consecutive patients.

INTRODUCTION: Clinical significance of internal mammary (IM) lymph node biopsy during microvascular free flap breast reconstruction remains controversial. Some microsurgeons may choose to biopsy an IM lymph node during routine IM vessel dissection. The authors reviewed the results of IM lymph node biopsy during autologous breast reconstruction. METHODS: A retrospective chart review of patients who underwent autologous breast reconstruction during a seven-year period (January 2010 to January 2017) was performed. Patient demographic data, disease staging, flap details, pathology reports, and adjuvant treatment were evaluated. RESULTS: A total of 230 patients with a mean age of 52.1 (SD 9.3) underwent IM lymph node biopsy (n = 297). Single IM lymph node was removed in 169 patients, 2 nodes were removed in 56 patients, 3 nodes in 4 patients, and 4 nodes in a single patient. Histopathologic analysis demonstrated presence of IM lymph node metastasis in 16 patients (7.0%). Thirteen patients were found to have metastatic IM lymph nodes in the setting of immediate reconstruction. Three patients were found to have metastatic IM lymph nodes in the setting of delayed. Five out of 16 patients (31.3%) had negative axillary sentinel lymph node biopsy and IM lymph nodes were the only site of nodal metastases. All five of these patients were upstaged accordingly and received adjuvant therapy based on the discussion at the multidisciplinary breast tumor conference. CONCLUSIONS: Opportunistic internal mammary lymph node sampling during autologous breast reconstruction can be performed with minimal morbidity and has significant impact on the disease staging and adjuvant treatment.

Primary Sternal Osteomyelitis: A Case Report and Review.

Primary sternal osteomyelitis (PSO) remains a rare but morbid and challenging condition. Due to the limited reports of PSO in the literature, management of this disease continues to lack consensus. We present a case report highlighting how PSO remained, in our experience, refractory to medical management, and how operative intervention provided resolution, and a review of the literature.

The Timing of Chemoprophylaxis in Autologous Microsurgical Breast Reconstruction.

BACKGROUND: Patients undergoing autologous breast reconstruction are at high risk of perioperative venous thromboembolic events. The efficacy of chemoprophylaxis in decreasing venous thromboembolic events is well established, but the timing of chemoprophylaxis remains controversial. The authors compare the incidence of bleeding following preoperative versus postoperative initiation of chemoprophylaxis in microvascular breast reconstruction. METHODS: A retrospective chart review was performed from August of 2010 to July of 2016. Initiation of chemoprophylaxis changed from postoperative to preoperative in 2013, dividing subjects into two groups. Patient demographics, comorbidities, and complications were reviewed. RESULTS: A total of 196 patients (311 flaps) were included in the study. A total of 105 patients (166 flaps) received preoperative enoxaparin (40 mg) and 91 patients (145 flaps) received postoperative chemoprophylaxis. A total of five patients required hematoma evacuation (2.6 percent). Of these, one hematoma (1 percent) occurred in the preoperative chemoprophylaxis group. Seven patients received blood transfusions: three in the preoperative group and four in the postoperative group (2.9 percent versus 4.4 percent; p = 0.419). There was a total of one flap failure, and there were no documented venous thromboembolic events in any of the groups. CONCLUSIONS: This study demonstrates that preoperative chemoprophylaxis can be used safely in patients undergoing microvascular breast reconstruction. The higher rate of bleeding in the postoperative group may be related to the onset of action of enoxaparin of 4 to 6 hours, which allows for intraoperative hemostasis in the preoperative group and possibly potentiating postoperative oozing when administered postoperatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Breast Tissue Expanders with Magnetic Ports: Clinical Experience at 1.5 T.

BACKGROUND: The purpose of this study was to evaluate breast tissue expanders with magnetic ports for safety in patients undergoing abdominal/pelvic magnetic resonance angiography before autologous breast reconstruction. METHODS: Magnetic resonance angiography of the abdomen and pelvis at 1.5 T was performed in 71 patients in prone position with tissue expanders with magnetic ports labeled "MR Unsafe" from July of 2012 to May of 2014. Patients were monitored during magnetic resonance angiography for tissue expander-related symptoms, and the chest wall tissue adjacent to the tissue expander was examined for injury at the time of tissue expander removal for breast reconstruction. Retrospective review of these patients' clinical records was performed. T2-weighted fast spin echo, steady-state free precession and gadolinium-enhanced spoiled gradient echo sequences were assessed for image artifacts. RESULTS: No patient had tissue expander or magnetic port migration during the magnetic resonance examination and none reported pain during scanning. On tissue expander removal (71 patients, 112 implants), the surgeons reported no evidence of tissue damage, and there were no operative complications at those sites of breast reconstruction. CONCLUSION: Magnetic resonance angiography of the abdomen and pelvis in patients with certain breast tissue expanders containing magnetic ports can be performed safely at 1.5 T for pre-autologous flap breast reconstruction perforator vessel mapping. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Chairs and chiefs of plastic surgery: is it an insider job?

PURPOSE: There is no more important decision an academic Plastic Surgery Department or Division can make than naming a chair or chief. Externally recruited leadership brings fresh perspectives and connections. Critics, however, argue that they lack the in-depth knowledge of the institution's culture and history that may be needed to succeed. The ability and skill of an internal candidate is already known and can increase the odds of that person's success in the leadership position. Finally, external recruitment can be a more costly process. Ultimately, the decision is really a litmus test for a Plastic Surgery program. The authors aim to evaluate factors influencing ascent in Plastic Surgery leadership, including training history, internal promotion, and external recruiting. METHODS: All Plastic Surgery residency programs accredited by the Accreditation Council for Graduate Medical Education were noted (n = 71). Academic departmental chairs or divisional chiefs of these residency programs were identified at the time of study design (October 1, 2011). For each chair or chief, gender, training history, and faculty appointment immediately prior to the current leadership position was recorded. RESULTS: There were 71 academic chairs or chiefs of Plastic Surgery residency programs at the time of data collection. The majority (62%) had done fellowship training following Plastic Surgery residency. Fellowships included hand (43%), craniofacial (29%), microsurgery (18%), and other types (10%). The majority (73%) of leaders were internal hires (P < 0.01), having faculty appointments at their institutions prior to promotion. However, only a fraction (22%) of these internal hires had done Plastic Surgery residency or fellowship training at that institution (P < 0.01). External recruits consisted of 27% of all 71 academic hires (P < 0.01). CONCLUSIONS: Many factors influence the decision to recruit leadership from internally or to hire an external candidate. These include the time to fill the position, program culture, candidate experience, and cost. These results support that the insider/outsider hire decision is ultimately one of duality. That dichotomy is achieved with an emphasis on internal promotion, but always with an eye towards the advantages of bringing in external talent as a valuable contribution to increase organizational success.

Microsurgery of the upper extremity.

In the past 50 years, hand surgeons have made considerable contributions to microsurgery. The unique demands of complex upper extremity care have driven many of the technical and scientific advances of this discipline, including functional muscle transfers, nerve transfers, and composite tissue allotransplantation. The purpose of this article was to review the current applications of microsurgery to the upper extremity.

A novel mouse model of cutaneous radiation injury.

BACKGROUND: Radiation therapy is a cornerstone of oncologic treatment. Skin tolerance is often the limiting factor in radiotherapy. To study these issues and create modalities for intervention, the authors developed a novel murine model of cutaneous radiation injury. METHODS: The dorsal skin was isolated using a low-pressure clamp and irradiated. Mice were followed for 8 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy specimens were taken and examined histologically. Tensiometry was performed and Young's modulus calculated. RESULTS: High-dose radiation isolated to dorsal skin causes progressive changes in skin perfusion, resulting in dermal thickening, fibrosis, persistent alopecia, and sometimes ulceration. There is increased dermal Smad3 expression, and decreased elasticity and bursting strength. CONCLUSIONS: This model of cutaneous radiation injury delivers reproducible localized effects, mimicking the injury pattern seen in human subjects. This technique can be used to study radiation-induced injury to evaluate preventative and therapeutic strategies for these clinical issues.

The respective roles of plastic and orthopedic surgery in limb salvage.

The evolution of techniques in plastic surgery and orthopedic surgery over the past few decades has enabled a great level of success in limb salvage. Limb salvage can now be achieved when faced with trauma, tumor, sepsis, or vascular disease. In fact, "What can be salvaged?" is now a less common debate among clinicians than "What should be salvaged?" Often discussions among surgeons from various subspecialties, including orthopedics, plastics, trauma, and vascular surgery, are characterized by how each of them can perform their respective part of the salvage operation, be it bony fixation, revascularization, or soft-tissue coverage, but none of them is certain whether it should be attempted. What is needed in these clinical situations is an interdisciplinary team approach led by individual or groups of clinicians who are familiar not only with their own subspecialized skills but also with those of their colleagues and the outcomes associated with integrated efforts at limb salvage. The concept of orthoplastic surgery is based on such an idea, where the combined skills and techniques of the orthopedic surgeon and reconstructive microsurgeon are used in concert to direct efforts toward limb salvage or decide against it when it is not indicated. This article presents a review of the roles of the two subspecialties and how an orthoplastic team can function with the current techniques to improve outcomes in limb salvage surgery.

Low-dose radiation augments vasculogenesis signaling through HIF-1-dependent and -independent SDF-1 induction.

The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1α mRNA and abolition of HIF-1α protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1α induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis.

Cutaneous low-dose radiation increases tissue vascularity through upregulation of angiogenic and vasculogenic pathways.

BACKGROUND/AIMS: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. METHODS: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. RESULTS: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. CONCLUSION: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally.

Exertional compartment syndrome of the thigh: a rare diagnosis and literature review.

Exercise-induced acute compartment syndrome of the thigh is an uncommon entity. We present a rare case of bilateral exercise-induced three-compartment syndrome of the thighs that required fasciotomies. The objective of this study was to understand the history, physical examination, signs, symptoms, pathophysiology, diagnosis, and treatment of compartment syndrome and rhabdomyolysis. A 42-year-old man presented to the Emergency Department (ED) complaining of worsening pain and swelling in both thighs 45 h after performing a lower extremity exercise regimen. The patient's thighs were tender and swollen, but there was no ecchymosis or evidence of trauma. Admitting serum creatinine kinase (CK) was 106,289 U/L. Treatment for rhabdomyolysis was initiated. The next day, he complained of escalating bilateral thigh pain. Repeat serum CK was 346,580 U/L. The patient was diagnosed with bilateral thigh compartment syndrome and immediately taken to the operating room for fasciotomies. Postoperatively, the patient's symptoms improved rapidly and his serum CK quickly returned to normal. His incisions were closed and he returned to normal activities of daily living. Because exercise-induced compartment syndrome is an extremely rare diagnosis with a high risk of poor outcome, this article serves to emphasize the importance of considering this diagnosis during the work-up of patients presenting to the ED with rhabdomyolysis.

Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells.

Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20 Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1-3/5-8) increased 3-13-fold after 5 or 20 Gy IR. 20 Gy induced a marked increase (1.6-4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48 h after 5 and 20 Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5 Gy IR. Whereas 5 Gy markedly decreased intrinsic cell apoptosis (0 Gy=16%+/-3.6 vs. 5 Gy=4.5%+/-0.3), 20 Gy increased it (21.4%+/-1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20 Gy) radiation doses. Cell migration improved significantly following 5 Gy, but not 20 Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile.

A murine model for studying diffusely injected human fat.

BACKGROUND: The study of human autologous fat grafting has been primarily anecdotal. In this study, the authors aim to develop a murine model that recapitulates human fat grafting to study the fate of injected fat and the cell populations contained within. METHODS: The authors' method of fat harvesting and refinement has been described previously. The authors injected nude and tie2/lacZ mice with 2 ml of human lipoaspirate placed on the dorsal surface in a multipass, fan-like pattern. Fatty tissue was injected in small volumes of approximately 1/30 ml per withdrawal. The dorsal skin and associated fat was excised at various time points. Sections were stained with hematoxylin and eosin and cytochrome c oxidase IV. Transgenic tie2/lacZ samples were stained with X-galactosidase. At the 8-week time point, volumetric analysis was performed. RESULTS: Volumetric analysis at the 8-week time point showed 82 percent persistence of the original volume. Gross analysis showed it to be healthy, nonfibrotic, and vascularized. Hematoxylin and eosin analysis showed minimal inflammatory or capsular reaction, with viable adipocytes. Fat grafted areas were vascularized with multiple blood vessels. Cytochrome c oxidase IV human-specific stain and beta-galactosidase expression revealed these vessels to be of human origin. CONCLUSIONS: The authors have developed a murine model with which to study the fate of injected lipoaspirate. There is a high level of persistence of the grafted human fat, with minimal inflammatory reaction. The fat is viable and vascularized, demonstrating human-derived vessels in a mouse model. This model provides a platform for studying the populations of progenitor cells known to reside in lipoaspirate.

Hedgehog signaling is essential for normal wound healing.

The hedgehog family of morphogens (sonic [Shh], Indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. Although recent work implicates Shh in postnatal tissue repair and development, conclusive evidence is lacking. Here, we demonstrated the importance of Shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the Shh signaling cascade, on tissue repair. Using a murine-splinted excisional wound model, which attenuates wound contraction in this loose-skinned rodent, we established that, by all measures (wound closure, epithelialization, granulation formation, vascularity, and proliferation), wound healing was profoundly impaired when Shh signaling was disrupted. Because embryonic disruption of Shh is associated with distinct phenotypic defects, our findings invite investigation of the potential role of Shh signaling under postnatal conditions associated with disregulated wound healing.

Gustilo grade IIIB tibial fractures requiring microvascular free flaps: external fixation versus intramedullary rod fixation.

BACKGROUND: Gustilo IIIB fractures involve high-energy tibial fractures for which there is inadequate soft tissue coverage. In addition to orthopedic fixation, these injuries require soft tissue reconstruction, often in the form of a microvascular free flap. Although the majority of orthopedic literature favorably compares intramedullary rod fixation to external fixation in open tibial fractures, these studies have not focused on the role of either method of fixation in relation to the soft tissue reconstruction. METHODS: Because we had noted numerous complications after providing free-flap coverage over intramedullary rodded fractures, we sought to investigate whether there were differences in outcomes between free flap-covered lower-extremity fractures which were fixated by external fixation versus intramedullary rods. A retrospective chart review was performed on all patients in our institution who had lower-extremity free flaps for coverage of Gustilo IIIB fractures from 1995-2005 in relation to the type of bony fixation. RESULTS: Of the 38 patients studied, 18 underwent external fixation of the tibial fracture, and 20 had intramedullary rodding. Overall flap survival was 95%, with 1 failure in each group. However, the intramedullary rod group had higher incidences of wound infection, osteomyelitis, and bony nonunion (25%, 25%, and 40%, respectively) than the external fixation group (6%, 11%, 17%, respectively). CONCLUSIONS: For Gustilo IIIB fractures that require free-flap coverage, the added bony and soft tissue manipulation required for intramedullary rodding may disrupt the surrounding blood supply and lead to higher rates of complications that threaten the overall success of the reconstruction. Plastic and orthopedic surgeons should discuss the optimal method of bony fixation for complex tibial fractures when a free flap will likely be needed for soft tissue coverage. This integrated team approach may help minimize complications.

Mechanical strain alters gene expression in an in vitro model of hypertrophic scarring.

Fibroblasts represent a highly mechanoresponsive cell type known to play key roles in normal and pathologic processes such as wound healing, joint contracture, and hypertrophic scarring. In this study, we used a novel fibroblast-populated collagen lattice (FPCL) isometric tension model, allowing us to apply graded biaxial loads to dermal fibroblasts in a 3-dimensional matrix. Cell morphology demonstrated dose-dependent transition from round cells lacking stress fibers in nonloaded lattices to a broad, elongated morphology with prominent actin stress fibers in 800-mg-loaded lattices. Using quantitative real-time RT-PCR, a dose dependent induction of both collagen-1 and collagen-3 mRNA up to 2.8- and 3-fold, respectively, as well as a 2.5-fold induction of MMP-1 (collagenase) over unloaded FPCLs was observed. Quantitative expression of the proapoptotic gene Bax was down-regulated over 4-fold in mechanically strained FPCLs. These results suggest that mechanical strain up-regulates matrix remodeling genes and down-regulates normal cellular apoptosis, resulting in more cells, each of which produces more matrix. This "double burden" may underlie the pathophysiology of hypertrophic scars and other fibrotic processes in vivo.

Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia.

Although it is known that systemic diseases such as diabetes result in impaired wound healing, the mechanism for this impairment is not understood. Because fibroblasts are essential for wound repair, we compared the in vitro behavior of fibroblasts cultured from diabetic, leptin receptor-deficient (db/db) mice with wild-type fibroblasts from mice of the same genetic background in processes important during tissue repair. Adult diabetic mouse fibroblast migration exhibited a 75% reduction in migration compared to normal fibroblasts (P < 0.001) and was not significantly stimulated by hypoxia (1% O(2)), whereas wild-type fibroblast migration was up-regulated nearly twofold in hypoxic conditions (P < 0.05). Diabetic fibroblasts produced twice the amount of pro-matrix metalloproteinase-9 as normal fibroblasts, as measured by both gelatin zymography and enzyme-linked immunosorbent assay (P < 0.05). Adult diabetic fibroblasts exhibited a sevenfold impairment in vascular endothelial growth factor (VEGF) production (4.5 +/- 1.3 pg/ml versus 34.8 +/- 3.3 pg/ml, P < 0.001) compared to wild-type fibroblasts. Moreover, wild-type fibroblast production of VEGF increased threefold in response to hypoxia, whereas diabetic fibroblast production of VEGF was not up-regulated in hypoxic conditions (P < 0.001). To address the question whether these differences resulted from chronic hyperglycemia or absence of the leptin receptor, fibroblasts were harvested from newborn db/db mice before the onset of diabetes (4 to 5 weeks old). These fibroblasts showed no impairments in VEGF production under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. Markers of cellular viability including proliferation and senescence were not significantly different between diabetic and wild-type fibroblasts. We conclude that, in vitro, diabetic fibroblasts show selective impairments in discrete cellular processes critical for tissue repair including cellular migration, VEGF production, and the response to hypoxia. The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic, leptin receptor-deficient db/db mice. These observations support a role for fibroblast dysfunction in the impaired wound healing observed in human diabetics, and also suggest a mechanism for the poor clinical outcomes that occur after ischemic injury in diabetic patients.