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Representative images of four dasatinib-treated murine brainstem gliomas in ABC KO and ABC WT mice (10X and 40X images).

Supplemental Figure Legends

Brain distribution of Elacridar in ABC KO and ABC WT is not significantly different.

Elacridar does not significantly impact dasatinib delivery in absence of ABCG2 and ABCB1

Graph depicting fold change of Abcg2, Abcb1a, and Abcb1b transcripts of nestin-expressing brainstem progenitors, ABC KO tumor cell-lines, and ABC WT tumor cell-lines

Schematic of the survival study including a cartoon demonstrating the methodology for tumor generation

INTRODUCTION Edema is a significant cause of neuromorbidity in children and adults with brain tumors. Agents used to control this effect, such as corticosteroids, have their own associated morbidities. Sulfonylurea receptor 1 (SUR1) is a transmembrane protein that regulates the activity of ion channels in neurons, glia, and endothelial cells. SUR1 expression is upregulated in neuroinflammatory conditions. Inhibition of SUR1 with glyburide decreases edema and neuroinflammation by countering cytotoxic edema and apoptosis in rodent models of subarachnoid hemorrhage, stroke, trauma, and cerebral metastases. However, the expression of SUR1 in human brain tumors has not been elucidated. The purpose of this study was to determine SUR1 expression and cellular colocalization in a variety of human brain tumor specimens. MATERIALS AND METHODS Six glioblastoma, 12 cerebral metastases, 11 medulloblastoma, 9 supratentorial ependymoma, and 8 posterior fossa ependymoma specimens were analyzed using immunofluorescence. SUR1 expression and colocalization with blood vessels, neurons, and glial cells was analyzed and compared using ANOVA. RESULTS SUR1 expression was found in all specimens examined as a percentage of the total tissue area (mean ± SD): glioblastoma 3.9 ± 4, cerebral metastases 4.1 ± 3.1, medulloblastoma 8.2 ± 7.2, supratentorial ependymoma 9.1 ± 7, and posterior fossa ependymoma 8.1 ± 5.9. SUR1 expression was greater in supratentorial ependymoma compared to glioblastoma and metastases (p < 0.05) and greater in medulloblastoma compared to glioblastoma (p < 0.05). SUR1 colocalized most reliably with the neuronal marker, NeuN, in glioblastoma, metastases, and posterior fossa ependymoma samples (p < 0.05). SUR1 colocalized most reliably with the endothelial cell marker, CD31, in medulloblastoma samples (p < 0.05). CONCLUSION SUR1 is a putative therapeutic target to reduce neuroinflammation in adult and pediatric brain tumors. Inhibition of SUR1 may result in neuronal stabilization in glioblastoma, cerebral metastases, and posterior fossa ependymoma and reduced edema in medulloblastoma. .

Objective: Split-thickness skin graft (STSG) donor site dressings can play an integral role in reducing donor site morbidity. This study tested a novel, chitosan-based wound dressing, Opticell Ag, as an STSG donor site dressing for wounds Method: Between January and December 2016, the chitosan-based dressing was placed on participating patients' donor sites immediately following graft harvest and covered with a transparent occlusive dressing. Pain was evaluated on postoperative day one, before dressing change between days 5–7, and before and after dressing removal between days 10–14 using the Visual Analog Scale (VAS). The extent of re-epithelialisation was determined between day 10–14 and at one month, and healing quality was also evaluated at one month post-operatively using the Vancouver Scar Scale (VSS). Results: A total of 19 patients were recruited, of which 16 completed the study. Patients experienced mild-to-moderate pain in their donor sites when the chitosan-based dressing was used. Pain decreased significantly between postoperative day one and days 10–14, as well as between days 5–7 and 10–14. The mean percentage of re-epithelialisation on days 10–14 was 92% and by one month was 99%. The mean VSS at one month was 3.2±1.4. There were no statistically significant differences between patients' re-epithelialisation rates or VSS scores. There were unplanned dressing changes in four patients. No donor site infections or other adverse events were identified. Conclusion: The chitosan-based dressing tested in this study is safe, effective, and associated with reasonable pain control and acceptable healing quality. The results suggest that it is a promising STSG donor site dressing.

The treatment of burn-related wounds requires consideration of several factors, including defect size, available donor sites, exposure of critical structures, and the ultimate functional and aesthetic result of reconstruction. Although skin grafts and locoregional flaps are workhorses in burn reconstruction, they have inherent limitations that can directly impact reconstructive outcomes. Microsurgical free tissue transfer represents a viable option for the reconstruction of burn-related wounds in certain patients. Each anatomic region of the body has unique challenges that must be addressed to achieve a successful reconstruction. Therefore, the choice of free flap must be individualized to the wound and patients.

Negative pressure wound therapy (NPWT) has become a widely used treatment for acute and chronic wounds. NPWT is indicated for a variety of complex wounds, and some studies validate its use for certain aspects of burn care. Although further research is needed to explore the benefits for burns, NPWT has proven beneficial in its use as a dressing that bolsters skin grafts, promotes integration of bilaminate dermal substitutes, promotes re-epithelialization of skin graft donor sites, and potentially reduces the zone of stasis. This article reviews the literature on NPWT in burns, based on indication/application, and describes our experience with the use of modified NPWT for large burns.

Advancements in surgical wound treatment have led to skin substitutes and bioscaffolds as temporary and permanent coverage for burn wounds. Skin substitutes are used to improve wound coverage and restore the functional and aesthetic qualities of skin, and help to prevent wound infection and maintain a moist wound healing environment. Although allografts are preferred when autografts are not possible, high costs and limited availability have led to the use of xenografts and the development of skin substitutes and bioscaffolds. Despite constant evolution in the development of these skin substitutes and bioscaffolds, no single product stands out as the gold standard.

Background:Although data from other surgical disciplines do not support the use of prolonged postoperative prophylactic antibiotics, implant-based breast reconstruction is one area of plastic surgery where this may be warranted. The purpose of this study was to review the literature on antibiotic pr

PURPOSE Perforator flaps have become a preferred method of breast reconstruction but can consume considerable resources. We examined the impact of a Six Sigma program on microsurgical breast reconstruction at an academic medical center. METHODS Using methods developed by Motorola and General Electric, we applied critical pathway planning, workflow analysis, lean manufacturing, continuous quality improvement, and defect reduction to microsurgical breast reconstruction. Primary goals were to decrease preoperative-to-cut time and total operative time, through reduced variability and improved efficiency. Secondary goals were to reduce length of stay, complications, and reoperation. The project was divided into 3 phases: (1) Pre-Six Sigma (24 months), (2) Six Sigma (10 months), (3) and Post-Six Sigma (24 months). These periods (baseline, intervention, control) were compared by Student t test and χ analysis. RESULTS Over a 5-year period, 112 patients underwent 168 perforator flaps for breast reconstructions, by experienced microsurgeons. Total operative time decreased from 714 to 607 minutes (P < 0.01), across the study period, with the greatest drop occurring in unilateral cases, from 672 to 498 minutes (P < 0.01). Length of stay decreased from 6.3 to 5.2 days (P = 0.01). Overall complication rates (35.9% vs 30%, not significant) and take-back rates (20.5% vs 23.9%, not significant) remained similar over the 5-year period. Physician revenue/minute increased from US $6.28 to US $7.59, whereas hospital revenue/minute increased from US $21.84 to US $25.11. CONCLUSIONS A Six Sigma program in microsurgical breast reconstruction was associated with better operational and financial outcomes. These incremental gains were maintained over the course of the study, suggesting that these benefits were due, in part, to process improvements. However, continued reductions in total operative time and length of stay, well after the intervention period, support the possibility that "learning curve" phenomenon may have contributed to the improvement in these outcomes.

PURPOSE Various simulation models for microsurgery have been developed to overcome the limitations of Halstedian training on real patients. We wanted to assess the status of microsurgery simulation in plastic surgery residency programs in the United States. METHODS Data were analyzed from responses to a survey sent to all plastic surgery program directors in the United States, asking for type of simulation, quality of facilities, utilization by trainees, evaluation of trainee sessions, and perception of the relevance of simulation. RESULTS The survey response rate was 50%. Of all programs, 69% provide microsurgical simulation and 75% of these have a laboratory with microscope and 52% provide live animal models. Half share facilities with other departments. The quality of facilities is rated as good or great in 89%. Trainee utilization is once every 3 to 6 months in 82% of programs. Only in 11% is utilization monthly. Formal evaluation of simulation sessions is provided by 41% of programs. All program directors agree simulation is relevant to competence in microsurgery, 60% agree simulation should be mandatory, and 43% require trainees to complete a formal microsurgery course prior to live surgery. DISCUSSION There seems to be consensus that microsurgical simulation improves competence, and the majority of program directors agree it should be mandatory. Developing and implementing standardized simulation modules and assessment tools for trainees across the nation as part of a comprehensive competency-based training program for microsurgery is an important patient safety initiative that should be considered. Organizing with other departments to share facilities may improve their quality and hence utilization.

Wound management and soft-tissue repair can vary depending on the location. The head and neck, chest and back, arm and forearm, hand, abdomen, gluteal area and perineum, thigh, knee, lower leg, and foot all have different local options and preferred free flaps to use for reconstruction. Secondary reconstruction requires a detailed analysis of all aspects of the wound including any scars, soft tissue and/or skin deficits, functional defects, contour defects, complex or composite defects, and/or unstable previous wound coverage. Careful monitoring of both the patient and reconstruction is necessary in the postoperative period to ensure long-term success. This review contains 2 figures and 17 references. Key Words: free tissue transfer, pedicle flaps, soft-tissue coverage, wound closure, wound healing, wound management, wound reconstruction, tissue flaps

Principles of initial wound management include adequate debridement, bacterial contamination assessment, nutritional optimization, and moist wound healing versus the use of negative-pressure wound therapy. The main goals of coverage procedures are to achieve a healed wound and avoid infection. Aside from allowing to heal by secondary intention, options for wound closure include primary closure, skin grafting, local flaps, and free flaps. Each wound should be evaluated on an individual basis to determine which method of coverage is most appropriate. This review contains 13 figures, 2 tables, and 22 references. Key Words: free tissue transfer, pedicle flaps, soft-tissue coverage, wound closure, wound healing, wound management, wound reconstruction, tissue flaps

Background/Aims: We performed a morphometric analysis of Chiari I malformations to look for predictors of cervical syrinx formation. Methods: Eighteen patients with Chiari I malformation and associated cervical syrinx and 16 patients with Chiari I malformation without associated cervical syrinx were included in the study. Chiari I size was obtained from the radiology report; foramen magnum diameter, cerebellar volume, posterior fossa volume and intracranial volume were calculated using OsiriX software, and average measurements were compared between the two groups. Results and Conclusion: Patients with Chiari I with syrinx had an average tonsillar descent of 13.03 ± 5.31 mm compared to 9.25 ± 3.31 mm in the Chiari I without syrinx group (p < 0.05). Patients with Chiari I and syrinx also showed increased cerebellar crowding with a higher cerebellar volume to posterior fossa volume ratio; however, this difference was not significant (0.83 vs. 0.81; p = 0.1872). No difference between groups was found in posterior fossa volume, intracranial volume and foramen magnum diameter. Therefore, only Chiari I size based on the extent of tonsillar herniation was found to be a determinant of cervical syrinx formation.

Negative-pressure wound therapy (NPWT) has become a widely used and well-described treatment for acute and chronic wounds. The authors discuss advantages of XL-NPWT for large burns, infection prevention, promoting re-epithelialization, and fluid management. The techniques are described such as the “total body wrap” or “sandwich” technique, in which affected areas are sandwiched between large polyurethane dressings and silver-impregnated nonadherent foam that is applied to both recipient and donor sites, as well as over any intervening intact skin or burn wound. Although relatively new, XL-NPWT has proven to be safe and effective in treating burns ≥15% TBSA.

Supplemental Digital Content is available in the text., Background: The incidence of bilateral mastectomies is increasing along with the rates of breast reconstructions. A substantial number of patients will present with abdominal scars after Cesarean section, laparoscopy, laparotomy, and so on. The aim of this study was to evaluate the impact of prior abdominal scars on complication rates in abdominal bilateral free flap breast reconstruction. Methods: All consecutive patients with autologous free flap breast reconstruction between 2007 and 2014 were eligible. The relevant demographic and clinical data were prospectively collected into a study-specific database. Complications and reoperations were prospectively registered after postoperative outpatient visits. Results: Overall, 493 patients underwent abdominally based breast reconstruction during the study period: unilateral (n = 250; 50.7%) or bilateral (n = 243; 49.3%). In the bilateral group, the abdominal scar locations were Pfannenstiel (n = 73; 30.1%), midline (n = 16; 6.6%), lower oblique (n = 17; 7.0%), upper oblique (n = 5; 2.1%), and laparoscopic (n = 69; 28.4%). Four (1.7%) flap failures (including 1 converted to a pedicled transverse rectus abdominis flap) were registered, all occurring in patients from the scar group: 3 with Pfannenstiel incision and 1 patient with prior laparoscopy. Pfannenstiel scar was associated with higher risk of hematoma at the recipient site when compared with no scar group (13.7% versus 2.2%; P = 0.006). Partial flap necrosis, infection, and seroma occurred in 14 (5.9%), 8 (3.4%), and 5 (2.1%) patients, respectively, and no differences between the scar groups were identified. Conclusion: Surgical outcomes of bilateral reconstructions in patients with abdominal scars are generally comparable with ones in patients without prior surgery; however, some problems have been identified. These procedures might have some intraoperative considerations and often require increased operative times. Apart from the traditional preoperative computed tomography angiography, intraoperative imaging (e.g., fluorescence angiography) may be advocated in patients with abdominal scars.

The technique of three-dimensional (3D) nipple-areola complex (NAC) tattooing is a significant advance in obtaining improved esthetic results for women undergoing breast reconstruction. The application of 3D techniques or “realism” in tattoo artistry has significant potential to improve the esthetic outcomes of reconstructive surgery. Traditional coloring techniques for NAC tattooing ignore the artistic principles of light and shadow to create depth on a two-dimensional surface. The method presented in this article is essentially the inverse of traditional technique and results in a more realistic and 3D reconstruction that can appear better than surgical methods. When combined with surgical nipple reconstruction in appropriate patients, excellent results can be achieved. Overall, plastic surgeons have just begun to explore the possible applications of medical tattoos in plastic surgery that may allow us to enhance the esthetic results of not only breast reconstruction but other areas alike.

Reconstruction of the ascending portion of the mandible, including the angle, ramus, and condyle, can be a challenging surgical problem. Many treatment options are available, but no single procedure has been able to restore long-term form and function in every case. Currently, autologous nonvascularized bone grafts are the most common treatment, with the costochondral graft as the historic leader. Nonvascularized grafts can often restore vertical height and normal function but may face the challenge of long-term durability secondary to bone resorption. Emerging techniques in microvascular surgery may offer an alternative approach with the benefits of resistance to resorption and infection by maintaining a viable blood supply to the graft. Vascularized grafts may thus be used to full advantage in cases where prior surgery, scarring, disrupted vasculature, or radiation damage may compromise the long-term surgical success of a nonvascularized graft. This article reviews the literature and summarizes key points regarding nonvascularized and vascularized treatment modalities for reconstruction of the ascending mandible. In addition, we present the use of the femoral medial epicondyle free flap based on the descending genicular vascular pedicle as a novel reconstruction of the ascending portion of the mandible with minimal donor-site morbidity. Knowledge of all available options will aid the surgeon in achieving the optimal reconstruction for their patient and improve long-term outcomes.

The 2013 Boston Marathon bombings resulted in a large and unexpected influx of patients requiring acute multidisciplinary surgical care. The authors describe the surgical management experience of these patients at Brigham & Women's Hospital and Brigham & Women's Faulkner Hospital, with a particular focus on the important role played by reconstructive plastic surgery. The authors suggest that this experience illustrates the value of reconstructive plastic surgery in the treatment of these patients specifically and of trauma patients in general, and argue for the increasing importance of promoting our identity as a specialty.

Fat necrosis (FN) is a common complication of autologous breast reconstruction, yet no classification system exists to describe it. We sought to develop and validate a tool for meaningful reporting, comparison of techniques, and treatment planning. Our hypothesis was that a valid classification system would demonstrate higher grades of FN for pedicled transverse rectus abdominus myocutaneous (pTRAM) flaps as compared to free flaps (FF).A classification system for FN was developed: grade I, radiologic evidence only; grade II, palpable but not visible FN; grade III, palpable and visible FN; and grade IV, symptomatic FN. For validation, we applied this system to patients who had undergone pTRAM flaps from 2002 to 2006 and FF from 2006 to 2010 at our institution.We performed 93 pTRAM flaps in 69 patients and 102 FF in 69 patients. One patient had grade I FN and was observed. Of the 29 patients with grade II FN, 48% were observed, 17% had biopsy, and 35% underwent debridement. Of the 9 patients with grade III FN, 11% underwent biopsy and 89% had debridement. All patients with grade IV FN underwent debridement. The distribution of FN differed between pTRAM and FF. The mean FN grade for patients undergoing pTRAM was 1.4 versus 0.4 for those undergoing FF (P0.05). Fat necrosis requiring reoperation was more frequent in the pTRAM group (23.7% vs 5.9%, P0.05).Our validation study confirmed that FN grade was associated with the need for surgery and was higher for pedicled flaps as compared to FFs. As it is similar to the Baker grading system for capsular contracture, this classification system is familiar to all plastic surgeons. It is simple, easy to remember, clinically oriented, and could be readily incorporated into outcome studies of autologous breast reconstruction.

Background Implant-based breast reconstruction with an acellular dermal matrix is one of the most common procedures performed by plastic surgeons. Although numerous matrices are available, there is little literature comparing them. This study compares the rates of complications between two commonly used products: AlloDerm (human cadaveric) and SurgiMend (fetal bovine) acellular dermal matrices. Methods A retrospective review of a single center's 6-year experience was performed for consecutive, immediate breast reconstructions with acellular dermal matrix from 2009 to 2014. The authors compared demographics and surgical characteristics between patients receiving AlloDerm versus SurgiMend. Multivariate logistic regression was used to determine any association between type of matrix and surgical complications and to identify other clinical predictors for complications. Results A total of 640 patients underwent 952 reconstructions using AlloDerm [578 breasts (61 percent)] or SurgiMend [374 breasts (39 percent)]. The average follow-up was 587 days. Multivariate analysis revealed that type of matrix was not an independent risk factor for the development of complications. However, smoking, age, radiotherapy, and initial tissue expander fill volume were associated with increased risk of postoperative complications. Conclusions Both AlloDerm and SurgiMend acellular dermal matrices demonstrate similar rates of major complications when used in immediate implant-based breast reconstruction. In contrast, preoperative radiation therapy, smoking, increasing age, and initial tissue expander fill volume are independent risk factors for postoperative complications. Reconstructive surgeons should take these findings into consideration when performing implant-based breast reconstruction with a dermal matrix.

Background Topical vasodilators are frequently used during free tissue transfer to prevent and treat vasospasm and microvascular thrombosis. A variety of agents have been studied and are available, yet most microsurgeons select an agent based on anecdotal evidence or personal training. Our aim was to review the literature on topical vasodilators so microsurgeons can make more informed decisions about which agent to use. Methods A systemic review of the literature was performed on PubMed, EMBASE, and Google Scholar using keywords “topical vasodilator,” “antispasmodic,” “vasospasm,” “free flaps,” and “microsurgery.” Studies were included if they provided a comparative quantitative assessment of topical vasodilators and were written in English. In vitro, in vivo, and clinical studies were included. Results A total of 15 studies were identified and included in our analysis. The three most common classes of topical vasodilator include local anesthetics, phosphodiesterase inhibitors, and calcium channel blockers (CCBs). Of the most commonly used topical vasodilators, CCBs (nifedipine and verapamil) were most effective followed by papaverine and lidocaine. Conclusion The most effective topical vasodilators appear to be CCBs including nifedipine, nicardipine, and verapamil. Evidence suggests that these agents are more effective than papaverine and lidocaine solutions that are commonly used. Future research should directly compare individual CCBs to assess the most effective agent. Studies to date have focused on vessels other than those used by microsurgeons, and therefore further studies specific to these vessels are warranted.

The free fibula is the flap of choice for reconstructing most segmental mandibular defects resulting from head and neck resections. The use of miniplates or reconstruction bars for fixation has been described in the literature. We wanted to compare outcomes between the 2 methods of fixation in head and neck cancer patients.An IRB approved retrospective review of 25 consecutive patients undergoing free fibula flap reconstruction of the mandible for head and neck cancer over a period of 5 years was performed. Patient demographics, risk factors, number of fibula osteotomies, defect length, and clinical outcomes were noted. Fourteen patients were reconstructed with miniplates and 12 with reconstruction bars. The choice of plate fixation was determined by the individual reconstructive surgeon. Wound complications requiring surgery and hardware removal rate were recorded.Average follow-up was 27 months. There was no significant difference with regard to age (P = 0.67), sex (P = 0.77), smoking (P = 0.63), neoadjuvant radiation (P = 0.47), number of osteotomies (P = 0.99), or defect length (P = 0.95) between the 2 groups. Of the 4 patients requiring hardware removal for infection or persistent symptoms, all were in the miniplate group (P = 0.05). Other clinical outcomes, such as hematoma, wound dehiscence, infection, fistula formation, and osteoradionecrosis were comparable between the 2 groups without significant differences. The overall complication rate was similar as well (P = 0.25).Different from other reports in the literature, we show that miniplate use resulted in more hardware removal for infection or persistent symptoms, and this was statistically significant while controlling for patient demographics, risk factors, number of osteotomies, and defect length. Much like other reports in the literature, however, there is no statistically significant difference in overall complication rates, and all other specific complications, when using miniplates versus reconstruction bars. The decision to use miniplates versus reconstruction bars remains a clinical one. In our experience, for 0 to 1 osteotomy, a reconstruction bar suffices. For multiple osteotomies, however, miniplates allow for more customization.

Introduction Few educational programs exist for medical students that address professionalism in surgery, even though this core competency is required for graduate medical education and maintenance of board certification. Lapses in professional behavior occur commonly in surgical disciplines, with a negative effect on the operative team and patient care. Therefore, education regarding professionalism should begin early in the surgeon's formative process, to improve behavior. The goal of this project was to enhance the attitudes and knowledge of medical students regarding professionalism, to help them understand the role of professionalism in a surgical practice. Methods We implemented a 4-h seminar, spread out as 1-h sessions over the course of their month-long rotation, for 4th-year medical students serving as acting interns (AIs) in General Surgery, a surgical subspecialty, Obstetrics/Gynecology, or Anesthesia. Teaching methods included lecture, small group discussion, case studies, and journal club. Topics included Cognitive/Ethical Basis of Professionalism, Behavioral/Social Components of Professionalism, Managing Yourself, and Leading While You Work. We assessed attitudes about professionalism with a pre-course survey and tracked effect on learning and behavior with a post-course questionnaire. We asked AIs to rate the egregiousness of 30 scenarios involving potential lapses in professionalism. Results A total of 104 AIs (mean age, 26.5 y; male to female ratio, 1.6:1) participated in our course on professionalism in surgery. Up to 17.8% of the AIs had an alternate career before coming to medical school. Distribution of intended careers was: General Surgery, 27.4%; surgical subspecialties, 46.6%; Obstetrics/Gynecology, 13.7%; and Anesthesia, 12.3%. Acting interns ranked professionalism as the third most important of the six core competencies, after clinical skills and medical knowledge, but only slightly ahead of communication. Most AIs believed that professionalism could be taught and learned, and that the largest obstacle was not enough time in the curriculum. The most effective reported teaching methods were mentoring and modeling; lecture and journal club were the effective. Regarding attitudes toward professionalism, the most egregious examples of misconduct were substance abuse, illegal billing, boundary issues, sexual harassment, and lying about patient data, whereas the least egregious examples were receiving textbooks or honoraria from drug companies, advertising, self-prescribing for family members, and exceeding work-hour restrictions. The most important attributes of the professional were integrity and honesty, whereas the least valued were autonomy and altruism. The AIs reported that the course significantly improved their ability to define professionalism, identify attributes of the professional, understand the importance of professionalism, and integrate these concepts into practice (all P Conclusions Although medical students interested in surgery may already have well-formed attitudes and sophisticated knowledge about professionalism, this core competency can still be taught to and learned by trainees pursuing a surgical career.

This study evaluates how the transition from pedicled transverse rectus abdominis myocutaneous (pTRAM) to perforator flaps at an academic center has affected outcome and reimbursement.In 2006, our practice transitioned to almost exclusively perforator flaps for breast reconstruction. This study retrospectively compares pTRAM flaps performed from 2002 to 2006 (group 1) with perforator flaps from 2006 to 2010 (group 2). Operative time, complications, and reimbursement were compared between the 2 groups.We performed 93 pTRAM flaps in 69 patients in group 1 and 102 perforator flaps in 69 patients in group 2. Operative time was shorter in group 1 for unilateral breast reconstruction (399 vs. 543 minutes, P = 0.0001), but no significant difference was noted for bilateral cases (547 vs. 658 minutes, P = 0.1). Fat necrosis requiring reoperation (23.7% vs. 5.9%, P = 0.0004) and partial flap necrosis (20.6% vs. 7.2%, P = 0.045) were more frequent in group 1. There was a higher frequency of abdominal hernia (8.8% vs. 1.6%, P = 0.2) but fewer hematomas (1.5% vs. 10%, P = 0.06) in group 1, although statistical significance was not reached between the 2 groups. Mean adjusted payment per case was $3658.67 for group 1 versus $5256.48 for group 2 (P = 0.004), whereas payment per minute was $9.25 for group 1 versus $9.13 for group 2 (P = 0.9). Perforator flaps appear to be as profitable as pTRAM flaps with lower morbidity.The transition from pTRAM to perforator flap can be done successfully with appropriate resources and support. The development of a perforator flap practice represents an opportunity cost in optimizing patient care and should be an option to patients seeking breast reconstruction.

Purpose Because of the anatomic variability of the deep inferior epigastric artery, preoperative CT angiography (pCTA) has gained popularity for planning abdominal perforator flap breast reconstruction. This study evaluates how pCTA has affected preoperative planning, operative time, and outcome. Methods We performed a retrospective study of abdominal free flap breast reconstruction at our institution over a 4-year period, with pCTA performed routinely after the first year. Operative time and outcomes were compared between procedures with and without pCTA. Incidental findings were recorded. Results Between 2006 and 2010, 102 abdominal perforator flap surgeries were performed on 69 patients; of whom, 51 patients had pCTA and 18 did not. pCTA changed preoperative planning in 50% of cases by identifying the best perforator in unilateral cases or perforators with long intramuscular course. Preoperative plan based on pCTA corresponded to operative procedures in 89% of cases. The sensitivity and positive predictive value of pCTA to localize perforators were 79% and 92%, respectively. Operative time was significantly reduced with pCTA for both unilateral (636 vs. 496 minutes, P = 0.017) and bilateral cases (746 vs. 629 minutes, P = 0.05). Rates of fat necrosis, partial flap necrosis, and complete flap loss were comparable between the 2 groups. Incidentalomas were found in 36% of patients. Conclusions pCTA appears to reduce operative time by minimizing time spent identifying perforators, assisting in side selection for unilateral reconstruction, and optimizing planning when a long intramuscular course is identified. The effect of a learning curve cannot be excluded and is the chief limitation of this study.

Traditional coloring techniques for nipple-areola tattooing ignore the artistic principles of light and shadow to create depth on a two-dimensional surface. The method presented in this article is essentially the inverse of traditional technique and results in a more realistic and three-dimensional reconstruction that can appear better than surgical methods. The application of three-dimensional techniques or "realism" in tattoo artistry has significant potential to improve the aesthetic outcomes of reconstructive surgery.

SUMMARY The method of abdominal hernia repair known as components separation, described by Ramirez et al. in 1990, has enjoyed widespread popularity because of the sound anatomical principles it uses and most importantly the clinical success of the procedure. Although the authors who described this technique made no proprietary claims and did not discuss the history of abdominal hernia repair, they have certainly been credited with the development of this procedure. With this article, the author hopes to place components separation in historical perspective, and give credit to Donald Herron Young, who published the concept of external oblique relaxing incisions for repair of epigastric hernias in 1961. Born in Canada, Young studied and worked as a surgeon in England for most of his life. A biographical sketch is included.

Dasatinib is a multikinase inhibitor in clinical trials for glioma, and thus far has failed to demonstrate significant efficacy. We investigated whether the ABC efflux transporters ABCG2 and ABCB1 expressed in the blood–brain barrier (BBB), are limiting the efficacy of dasatinib in the treatment of glioma using genetic and pharmacologic approaches. We utilized a genetic brainstem glioma mouse model driven by platelet-derived growth factor-B and p53 loss using abcg2/abcb1 wild-type (ABC WT) or abcg2/abcb1 knockout mice (ABC KO). First, we observed that brainstem glioma tumor latency is significantly prolonged in ABC KO versus ABC WT mice (median survival of 47 vs. 34 days). Dasatinib treatment nearly doubles the survival of brainstem glioma-bearing ABC KO mice (44 vs. 80 days). Elacridar, an ABCG2 and ABCB1 inhibitor, significantly increases the efficacy of dasatinib in brainstem glioma-bearing ABC WT mice (42 vs. 59 days). Pharmacokinetic analysis demonstrates that dasatinib delivery into the normal brain, but not into the tumor core, is significantly increased in ABC KO mice compared with ABC WT mice. Surprisingly, elacridar did not significantly increase dasatinib delivery into the normal brain or the tumor core of ABC WT mice. Next, we demonstrate that the tight junctions of the BBB of this model are compromised as assessed by tissue permeability to Texas Red dextran. Finally, elacridar increases the cytotoxicity of dasatinib independent of ABCG2 and ABCB1 expression in vitro. In conclusion, elacridar improves the efficacy of dasatinib in a brainstem glioma model without significantly increasing its delivery to the tumor core. Mol Cancer Ther; 15(5); 819–29. ©2016 AACR.

Objective Negative pressure has been employed in various aspects of burn care and the aim of this study was to evaluate the evidence for each of those uses. Methods The PubMed and Cochrane CENTRAL databases were queried for articles in the following areas: negative pressure as a dressing for acute burns, intermediate treatment prior to skin grafting, bolster for skin autografts, dressing for integration of dermal substitutes, dressing for skin graft donor sites, and integrated dressing in large burns. Results Fifteen studies met our inclusion criteria. One study showed negative pressure wound therapy improved perfusion in acute partial-thickness burns, 8 out of 9 studies showed benefits when used as a skin graft bolster dressing, 1 out of 2 studies showed improved rate of revascularization when used over dermal substitutes, and 1 study showed increased rate of re-epithelialization when used over skin graft donor sites. Conclusions Negative pressure can improve autograft take when used as a bolster dressing. There is limited data to suggest that it may also improve the rate of revascularization of dermal substitutes and promote re-epithelialization of skin graft donor sites. Other uses suggested by studies that did not meet our inclusion criteria include improving vascularity in acute partial-thickness burns and as an integrated dressing for the management of large burns. Further studies are warranted for most clinical applications to establish negative pressure as an effective adjunct in burn wound care.

Background The deep inferior epigastric perforator (DIEP) flap is a major advance in breast reconstruction, but many surgeons are reluctant to use it because of concerns about a higher flap loss rate when compared with free/muscle-sparing transverse rectus abdominis myocutaneous (TRAM) flaps. Previous studies, however, have not statistically analyzed the relationship of patient characteristics to outcome. This study evaluates the authors' institutional experience with immediate postoperative complications following DIEP and free/muscle-sparing TRAM flaps. Methods Results of 200 consecutive free/muscle-sparing TRAM and DIEP flaps performed by two surgeons at a single institution between 2003 and 2005 were reviewed using a prospectively maintained database. The incidence of flap complications was compared. Patient demographics, procedure type, diagnosis, adjuvant treatment, and complications were recorded. Outcome variables included total and partial flap loss, infection, seroma, hematoma, wound-healing problems, fat necrosis, and mastectomy flap necrosis. Results One hundred forty-three patients were treated with 159 free/muscle-sparing TRAM flaps and 41 DIEP flaps. The demographics of the two groups were statistically similar. No statistically significant differences were noted in total or partial flap loss. Conclusions In the authors' series, the use of the DIEP flap did not result in more postoperative flap-related complications when compared with the free/muscle-sparing TRAM flap. Furthermore, no patient characteristics were statistically associated with a more successful result. The authors conclude that in patients whose anatomy reveals perforators of adequate size, the DIEP flap is a safe and reliable procedure for breast reconstruction.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.

More than 1.3 million cases of cancer will be diagnosed in 2006 in the United States alone, and 90% of patients with advanced cancer will experience significant, life-altering cancer-induced pain. Bone cancer pain is the most common pain in patients with advanced cancer as most common tumors including breast, prostate, and lung have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, pain and anemia, which reduce the survival and quality of life of the patient. Currently, the factors that drive cancer pain are poorly understood; however, several recently introduced models of cancer pain are not only providing insight into the mechanisms that drive bone cancer pain but are guiding the development of novel mechanism-based therapies to treat the pain and skeletal remodeling that accompanies metatstatic bone cancer. As analgesics can also influence disease progression, findings from these studies may lead to therapies that have the potential to improve the quality of life and survival of patients with skeletal malignancies.

Although a variety of techniques for upper blepharoplasty have been described, few studies illustrate and clinically evaluate a system for marking incisions. Presented is a 10-year experience using a specific method for marking upper blepharoplasty incisions that consistently yielded excellent esthetic results. All upper blepharoplasties performed by the senior author between April, 1994 and April, 2004 were reviewed. Markings were designed to end the medial incision 6 mm from the angular vein, end the lateral incision 12 mm from the palpebral fissure, and to extend the incisions superiorly at 45 degrees. Over 10 years, 476 patients underwent cosmetic upper blepharoplasty. There were 22 (4.6%) revisions. Eighteen (3.8%) were performed in clinic using CO 2 laser, and 4 (0.8%) patients required surgical revision. Patient satisfaction was high, and no scars were visible outside the brow. Excellent outcomes can be expected using this simple, reproducible, and widely applicable system for marking upper blepharoplasty incisions.

Pain from pancreatitis or pancreatic cancer can be both chronic and severe although little is known about the mechanisms that generate and maintain this pain. To define the peripheral sensory and sympathetic fibers involved in transmitting and modulating pancreatic pain, immunohistochemistry and confocal microscopy were used to examine the sensory and sympathetic innervation of the head, body and tail of the normal mouse pancreas. Myelinated sensory fibers were labeled with an antibody raised against 200 kD neurofilament H (clone RT97), thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and post-ganglionic sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase (TH). RT97, CGRP, and TH immunoreactive fibers were present in parenchyma of the head, body and tail of the pancreas with the relative density of both RT97 and CGRP expressing fibers being head>body>tail, whereas for TH, a relatively even distribution was observed. In all three regions of the pancreas, RT97 fibers were associated mainly with large blood vessels, the CGRP fibers were associated with the large- and medium-sized blood vessels and the TH were associated with the large- and medium-sized blood vessels as well as capillaries. In addition to this extensive set of sensory and sympathetic nerve fibers that terminate in the pancreas, there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that expressed RT97 or CGRP and were associated with the superior mesenteric plexus. These data suggest the pancreas receives a significant sensory and sympathetic innervation. Understanding the factors and disease states that sensitize and/or directly excite the nerve fibers that terminate in the pancreas as well as those that are en passant may aid in the development of therapies that more effectively modulate the pain that frequently accompanies diseases of the pancreas, such as pancreatitis and pancreatic cancer.

Diffuse intrinsic pontine gliomas (DIPGs) represent a particularly lethal type of pediatric brain cancer with no effective therapeutic options. Our laboratory has previously reported the development of genetically engineered DIPG mouse models using the RCAS/tv-a system, including a model driven by PDGF-B, H3.3K27M, and p53 loss. These models can serve as a platform in which to test novel therapeutics prior to the initiation of human clinical trials. In this study, an in vitro high-throughput drug screen as part of the DIPG preclinical consortium using cell-lines derived from our DIPG models identified BMS-754807 as a drug of interest in DIPG. BMS-754807 is a potent and reversible small molecule multi-kinase inhibitor with many targets including IGF-1R, IR, MET, TRKA, TRKB, AURKA, AURKB. In vitro evaluation showed significant cytotoxic effects with an IC50 of 0.13 μM, significant inhibition of proliferation at a concentration of 1.5 μM, as well as inhibition of AKT activation. Interestingly, IGF-1R signaling was absent in serum-free cultures from the PDGF-B; H3.3K27M; p53 deficient model suggesting that the antitumor activity of BMS-754807 in this model is independent of IGF-1R. In vivo, systemic administration of BMS-754807 to DIPG-bearing mice did not prolong survival. Pharmacokinetic analysis demonstrated that tumor tissue drug concentrations of BMS-754807 were well below the identified IC50, suggesting that inadequate drug delivery may limit in vivo efficacy. In summary, an unbiased in vitro drug screen identified BMS-754807 as a potential therapeutic agent in DIPG, but BMS-754807 treatment in vivo by systemic delivery did not significantly prolong survival of DIPG-bearing mice.

Objective The use of negative-pressure-wound-therapy (NPWT) is associated with improved outcomes in smaller burns. We report our experience using extra-large (XL) NPWT dressings to treat ≥15% total body surface area (TBSA) burned and describe our technique and early outcomes. We also provide NPWT exudate volume for predictive fluid resuscitation in these critically ill patients. Methods We retrospectively reviewed patients treated with XL-NPWT from 2012 to 2014. Following excision/grafting, graft and donor sites were sealed with a layered NPWT dressing. We documented wound size, dressing size, NPWT outputs, graft take, wound infections, and length of stay (LOS). Mean NPWT exudate volume per %TBSA per day was calculated. Results Twelve burn patients (mean TBSA burned 30%, range 15-60%) were treated with XL-NPWT (dressing TBSA burned and skin graft donor sites range 17-44%). Average graft take was 97%. No wound infections occurred. Two patients had burns ≥50% TBSA and their LOS was reduced compared to ABA averages. XL-NPWT outputs peaked at day 1 after grafting followed by a steady decline until dressings were removed. Average XL-NPWT dressing output during the first 5 days was 101±66mL/%BSA covered per day. 2 patients developed acute kidney injury. Conclusion The use of XL-NPWT to treat extensive burns is feasible with attention to application technique. NPWT dressings appear to improve graft take, and to decrease risk of infection, LOS, and pain and anxiety associated with wound care. Measured fluid losses can improve patient care in future applications of NPWT to large burn wounds.