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Supplemental Figure 1. CD11b+ myeloid cells in glioma correlate to tumor grade. Supplemental Figure 2. Schematic depicted for bone marrow transplant of RCAS tumor bearing animals. Supplemental Figure 3. Analysis of tumor sections for necrosis and microvascular proliferation. Supplemental Figure 4. AZD1480 impairs phosphorylation of Stat3 but has no effect in vitro and IDH status

Purpose: While the tumor microenvironment has been known to play an integral role in tumor progression, the function of nonresident bone marrow–derived cells (BMDC) remains to be determined in neurologic tumors. Here we identified the contribution of BMDC recruitment in mediating malignant transformation from low- to high-grade gliomas.Experimental Design: We analyzed human blood and tumor samples from patients with low- and high-grade gliomas. A spontaneous platelet-derived growth factor (PDGF) murine glioma model (RCAS) was utilized to recapitulate human disease progression. Levels of CD11b+/GR1+ BMDCs were analyzed at discrete stages of tumor progression. Using bone marrow transplantation, we determined the unique influence of BMDCs in the transition from low- to high-grade glioma. The functional role of these BMDCs was then examined using a JAK 1/2 inhibitor (AZD1480).Results: CD11b+ myeloid cells were significantly increased during tumor progression in peripheral blood and tumors of glioma patients. Increases in CD11b+/GR1+ cells were observed in murine peripheral blood, bone marrow, and tumors during low-grade to high-grade transformation. Transient blockade of CD11b+ cell expansion using a JAK 1/2 Inhibitor (AZD1480) impaired mobilization of these cells and was associated with a reduction in tumor volume, maintenance of a low-grade tumor phenotype, and prolongation in survival.Conclusions: We demonstrate that impaired recruitment of CD11b+ myeloid cells with a JAK1/2 inhibitor inhibits glioma progression in vivo and prolongs survival in a murine glioma model. Clin Cancer Res; 23(12); 3109–19. ©2016 AACR.

As the sophistication of microsurgical breast reconstruction continues to evolve, plastic surgeons are focusing on techniques to improve functional and psychosocial outcomes for patients, including breast sensation. Interest in neurotization of breast flaps, among both patients and surgeons, has grown significantly in recent years. This study aimed to review the outcomes of neurotization across autologous flap reconstructions, to provide a comprehensive analysis of the efficacy of this technique in improving postoperative sensory recovery.

Breast reconstruction is an important part of the cancer treatment paradigm and the psychosocial benefits are well described in the literature. Notably, breast reconstruction restores both the functional and emotional losses patients experience due to tumor resection. Post-cancer quality of life is an important benchmark of successful treatment; therefore, breast reconstruction is an essential component that should be offered whenever possible. Over time, reconstructive techniques and outcomes have improved dramatically resulting in better patient safety and decreased operative morbidity. When counseling a patient for surgery, the provider must consider all aspects of a patient’s health. Ideally, breast cancer patients should be physically, emotionally, and oncologically appropriate candidates for reconstruction. However, in concerted effort to provide opportunities for as many patients as possible, the definition of who is a good candidate for reconstruction has evolved to include higher risk patients. These patients include those with advanced age, nicotine use, obesity, and significant ptosis. With improvements in surgical procedures and perioperative care, this population may also benefit from restorative surgery. However, the exact risk of complications and necessary counseling has gone largely undefined in this population. This article examines particular “high-risk” groups that may be challenging for extirpative and reconstructive surgeons and offers current guidelines for practice.

BACKGROUND Midface hypoplasia dramatically affects the normative facial cascade. Simultaneous Le Fort III and Le Fort I procedures (Le Fort III/I) provide a powerful tool for achieving significant midface advancement. This study presents the authors' approach for addressing midface hypoplasia in the setting of class III malocclusion using Le Fort III/I advancement. METHODS This was an institutional review board-approved retrospective review of patients who underwent Le Fort III/I advancement at the authors' institution from 2009 to 2019. Demographic, surgical, and postoperative data were recorded. The authors' operative technique and surgical pearls are described. RESULTS Twenty-five patients met inclusion criteria, 15 male patients (60 percent) and 10 female patients (40 percent). Patient age ranged from 14.9 to 21.6 years. Diagnoses included Crouzon syndrome, nonsyndromic developmental skeletal dysplasia, cleft lip/palate, Klippel-Feil syndrome, Apert syndrome, Van den Ende-Gupta syndrome, and Pfeiffer syndrome. Le Fort III advancements averaged 6.18 ± 1.38 mm and Le Fort I advancements averaged 6.70 ± 2.48 mm. Thirteen patients underwent simultaneous bilateral sagittal split osteotomy with average movement of 5.85 ± 1.21 mm. Average follow-up was 1.3 ± 1.0 years. One patient experienced intraoperative cerebrospinal fluid leak that resolved with expectant management. Three patients experienced major complications (12 percent) postoperatively necessitating repeated orthognathic operations. Ten patients experienced minor complications (40 percent). Average length of stay was 10 days, with all patients achieving improvement of their facial profile. CONCLUSIONS The authors' experience reaffirms the relative safety of simultaneous Le Fort III/I advancement. This technique should be considered in select patients with global midface retrusion and class III malocclusion. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, IV.

BackgroundPilonidal disease (PD) is a recalcitrant condition associated with significant morbidity. It affects 26 in 100,000 individuals; however, there is no consensus on optimal surgical treatment, and up to half of patients struggle with recurrence. This review appraises the current literature on

Background Breast reconstruction outcomes have traditionally been measured by evaluating the opinions of patients and surgeons. Objectives Our goal was to assess the views of the general public. Methods A survey was designed and distributed through a crowdsourcing website called Amazon Mechanical Turk. Questions assessed participant demographics, personal experience with breast reconstruction, perceptions on breast reconstruction, and opinions regarding aesthetics results. Responses were analyzed using chi-square test. Results A total of 992 responses were collected. Most participants were female (56.1%), white (32.1%), aged 30 to 39 years (40.4%), and had a bachelor’s degree (42.0%). A total of 44.2% had personal experience with breast reconstruction and 25.8% with nipple reconstruction. Several aesthetic and reconstructive factors were significantly favored over others across sex, ethnicity, age group, education level, and personal experience with breast reconstruction. For instance, women were more likely to prefer reconstructed nipples (P < 0.0001), view a breast without a nipple as complete (P = 0.024) and place less importance on nipple shape (P = 0.002). Additionally, those who personally experienced nipple reconstruction were willing to undergo more procedures for a complete nipple-areola complex (P < 0.0001), to increase aesthetic results (P = 0.018), and to increase chances of nipple survival (P = 0.002). Conclusions Crowdsourcing can be useful in plastic surgery and has helped identify several key findings. The importance of the nipple in reconstruction has been validated; almost three-quarters of respondents did not view a breast without a nipple as complete. The aesthetic preferences seem to support bilateral nipple-sparing reconstruction when possible. Most importantly, the respondents helped elucidate key differences in perception of aesthetic outcomes.

Purpose: While the tumor microenvironment has been known to play an integral role in tumor progression, the function of nonresident bone marrow–derived cells (BMDC) remains to be determined in neurologic tumors. Here we identified the contribution of BMDC recruitment in mediating malignant transformation from low- to high-grade gliomas. Experimental Design: We analyzed human blood and tumor samples from patients with low- and high-grade gliomas. A spontaneous platelet-derived growth factor (PDGF) murine glioma model (RCAS) was utilized to recapitulate human disease progression. Levels of CD11b+/GR1+ BMDCs were analyzed at discrete stages of tumor progression. Using bone marrow transplantation, we determined the unique influence of BMDCs in the transition from low- to high-grade glioma. The functional role of these BMDCs was then examined using a JAK 1/2 inhibitor (AZD1480). Results: CD11b+ myeloid cells were significantly increased during tumor progression in peripheral blood and tumors of glioma patients. Increases in CD11b+/GR1+ cells were observed in murine peripheral blood, bone marrow, and tumors during low-grade to high-grade transformation. Transient blockade of CD11b+ cell expansion using a JAK 1/2 Inhibitor (AZD1480) impaired mobilization of these cells and was associated with a reduction in tumor volume, maintenance of a low-grade tumor phenotype, and prolongation in survival. Conclusions: We demonstrate that impaired recruitment of CD11b+ myeloid cells with a JAK1/2 inhibitor inhibits glioma progression in vivo and prolongs survival in a murine glioma model. Clin Cancer Res; 23(12); 3109–19. ©2016 AACR.

Background There has been no peer-reviewed published data analyzing the microsurgery match since it was established. The aim of this study is to present and analyze match data to inform residents and programs regarding outcomes. Methods Anonymized data were requested from the San Francisco Match, which was plotted and analyzed utilizing Pearson's Chi-square, unpaired t-test, and one-way analysis of variance (ANOVA). Results Match data was obtained from the years 2014 to 2018. The match rate decreased from 84.6% in 2015 to 67.3% in 2018, mean = 73.7 (8.29%), and (p = 0.01735). The position fill rate fluctuated from 82.9% in 2014 to 90.0% in 2016, mean = 86.5 (3.0%). In 2014 and 2015, 66.7% of applicants matched their first or second choice compared to 48.0% in 2018, mean = 58.7 (8.3%), (p =.04785). Matched applicants ranked mean = 6.6 (1.4%) programs versus 3.4 (1.3) for unmatched, (p Conclusion The application process for microsurgery has become more competitive. Matched applicants rank more programs than do unmatched. Fully filled programs rank more applicants per position than do unfilled or partially filled. Applicants and programs are increasingly less likely to match their top choices.

Background As the popularity of aesthetic gluteoplasty continues to grow, there is renewed focus on defining the ideal buttocks. However, the literature lacks studies characterizing an ideal thigh, despite the impact of thigh contour on overall gluteal aesthetic. Objectives The authors performed the first population analysis of the characteristics of perception of attractive thighs, to identify a role for fat grafting of the thigh in gluteoplasty. Methods Survey images were digitally modified to create thighs of varying widths and angles relative to fixed buttocks. Thigh-to-buttock ratios and the buttock-thigh junction were studied. Data were stratified and analyzed according to age, gender, and ethnicity of the respondents. Amazon Mechanical Turk was used as a novel crowdsourcing platform for surveying aesthetic preferences. Results A total of 1034 responses were included of whom 54.4% were male, and 45.6% were female. All age groups and ethnicities were represented. Overall, 43.8% of respondents preferred the widest buttock-thick junction angle on posterior view. There was no clear preference between larger or smaller thigh-to-hip ratios on lateral view. Conclusions Characteristics of the ideal thigh include wider thighs with greater horizontal projection, creating a more natural contour from the augmented buttock. These findings represent a paradigm shift from the traditionally assumed preference for slender thighs. Plastic surgeons should carefully consider thigh anatomy in their gluteal augmentation patients, as simultaneous thigh augmentation may lead to a more aesthetically pleasing outcome. Further research is needed into best practices and techniques to attain ideal thigh proportions.

Tumors are capable of coopting hematopoietic cells to create a suitable microenvironment to support malignant growth. Here, we have demonstrated that upregulation of kinase insert domain receptor (KDR), also known as VEGFR2, in a myeloid cell sublineage is necessary for malignant progression of gliomas in transgenic murine models and is associated with high-grade tumors in patients. KDR expression increased in myeloid cells as myeloid-derived suppressor cells (MDSCs) accumulated, which was associated with the transformation and progression of low-grade fibrillary astrocytoma to high-grade anaplastic gliomas. KDR deficiency in murine BM-derived cells (BMDCs) suppressed the differentiation of myeloid lineages and reduced granulocytic/monocytic populations. The depletion of myeloid-derived KDR compromised its proangiogenic function, which inhibited the angiogenic switch necessary for malignant progression of low-grade to high-grade tumors. We also identified inhibitor of DNA binding protein 2 (ID2) as a key upstream regulator of KDR activation during myeloid differentiation. Deficiency of ID2 in BMDCs led to downregulation of KDR, suppression of proangiogenic myeloid cells, and prevention of low-grade to high-grade transition. Tumor-secreted TGF-β and granulocyte-macrophage CSF (GM-CSF) enhanced the KDR/ID2 signaling axis in BMDCs. Our results suggest that modulation of KDR/ID2 signaling may restrict tumor-associated myeloid cells and could potentially be a therapeutic strategy for preventing transformation of premalignant gliomas. This study was supported by the Department of Defense Con- gressionally Directed Medical Research Programs (DOD CDMRP, CA120318 to Y. Huang), Elizabeth’s Hope (J. Greenfield), the Starr Foundation, the Paduano Foundation, the Champalimaud Foun- dation, the Malcolm Hewitt Wiener Foundation, the POETIC Foundation, the Sohn Foundation, the Hartwell Foundation, and the Children’s Cancer and Blood Foundation (all to D. Lyden). Address correspondence to: David Lyden, Department of Pediatrics, Weill Medical Medicine, 413 E. 69th Street, Box 284, New York, New York 10021, USA. Phone: 646.962.6238; E-mail: dcl2001@med.cornell.edu. Or to: Jeffrey P. Greenfield, Department of Neurological Surgery, Weill Cornell Medicine, 525 E 68th Street, Box 99, New York, New York 10065, USA. Phone: 212.746.2363; E-mail: jpgreenf@med.cornell.edu. HP’s present address is: Microenvironment and Metastasis Group, Department of Molecular Oncology, Spanish National Cancer Research Center (CNIO), Madrid, Spain. Sí

INTRODUCTION: Low grade gliomas lack neovascularization when compared to their high grade counterparts. Bone marrow-derived cells (BMDCs) are recruited to the tumor site and mediate the angiogenic switch during malignant transformation. This process ultimately supports the exponential growth kinetics displayed by high grade tumors that often exhibit aberrant vasculature. In order to elucidate the functional consequence of impairing BMDCs, in particular myeloid-derived suppressor cells (MDSC), we employed JAK 1/2 inhibitors. JAK 1/2 inhibition prior to the angiogenic switch in low grade glial tumors resulted in reduced neo-vascularization (CD31) and cellular proliferation (Ki67+). To conclusively prove impaired MDSC recruitment, we pursued a series of bone marrow transplant studies to demonstrate the effect of interrogated JAK 1/2 signaling on GFP+ BMDCs recruitment to the tumor core and periphery. METHODS: A spontaneous, transgenic PDGF-driven murine glioma model was utilized to recapitulate low-grade to high-grade progression. Tumor bearing animals were lethally irradiated (10Gy) at 2 weeks old and transplanted with age appropriate bone marrow from GFP donor mice. After a 4 week bone marrow reconstitution, the animals were treated with JAK1/2 inhibitors via oral gavage for 4 weeks. Immunofluorescence was used to characterize the impact on GFP+ BMDC recruitment at the tumor site. Flow cytometry was then used to quantify GFP+ BMDCs at the tumor site and periphery (blood and bone marrow). RESULTS: The number of GFP + BMDCs recruited to the tumor core is markedly reduced in post-transplant JAK treated animals. These animals demonstrate a significant survival advantage and exhibit delayed transformation on MRI and histologically, consistent with our previous findings. Flow cytometry and immunofluorescence demonstrates impaired Cd11b + /GR1+ mobilization in the bone marrow, peripheral blood and at the tumor core. CONCLUSION: The utility of GFP+ bone marrow transplant model system proves that JAK 1/2 Inhibition plays a direct role in impairment of MDSC infiltration.