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1.
Plast Reconstr Surg ; 149(4): 767e-773e, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35188924

RESUMO

BACKGROUND: The revenue generated by plastic surgeons assisting other surgical services is poorly captured by hospital accounting systems, which categorize solely by attending physician of record. The financial impact of reconstructive surgery is thus systematically underestimated. The authors sought to quantify the overlooked value of plastic surgeons as consultants who facilitate complex and profitable operations. METHODS: Hospital billing data were reviewed for inpatient operations over a 3-year fiscal period (2015 to 2017). Cases in which a plastic surgeon assisted were identified. Case mix index, a measure of complexity that correlates with profit, and contribution margin, defined as revenue minus cost, were obtained for each case. RESULTS: Five hundred fifty-four cases required a reconstructive surgeon; 18,904 nonconsultation cases were identified for comparison. Average net revenue per case involving a consultation was 1.79 times greater than for control cases (p < 0.0001). Average contribution margin was 1.73 times greater (p < 0.005). The highest contribution margins stemmed from joint cases with cardiothoracic surgery and neurosurgery. Case mix index was significantly higher for consultation cases than for controls (4.5 versus 3.9; p < 0.0001). In 434 cases (78 percent), plastic surgery assisted with an integral aspect of the operation, meaning the surgery could not have been technically performed without reconstructive assistance. CONCLUSIONS: The authors' findings demonstrate that cases involving plastic surgeons have a higher profit margin than those performed by any department alone. However, this revenue is not appropriately attributed because of oversimplified financial metrics. The skill set of reconstructive surgeons is an undervalued resource for both patient care and hospital economics.


Assuntos
Procedimentos de Cirurgia Plástica , Cirurgiões , Cirurgia Plástica , Centros Médicos Acadêmicos , Consultores , Humanos
3.
Plast Reconstr Surg Glob Open ; 9(10): e3870, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34703715

RESUMO

BACKGROUND: Unilateral cleft palates have a large spectrum of variability. Key morphologic factors such as cleft width and palatal length are not represented in current classification systems. Palate length and velopharyngeal port size are clinically linked to speech outcomes, as the soft palate must close the posterior pharynx for proper phonation. This study investigates the relationship between objective preoperative measures and postoperative velopharyngeal port size, to define a reproducible severity scale. METHODS: Surgical data were prospectively collected from unilateral cleft palate patients in Morocco, Bolivia, Vietnam, and Madagascar. Key measurements were cleft width and palate width at the hard-soft palate junction, alveolar cleft width, vertical alveolar discrepancy, velopharyngeal port size. Cleft width ratio (CWR) was defined as the width of the cleft at the hard-soft junction, divided by the palate width. RESULTS: Seventy-six patients were evaluated. Thirty-one had complete clefts and average age at surgical repair was 2.9 years. Mean CWR was 0.50 ± 0.12. Palate length was increased by an average of 2.2 mm (11%) after palatoplasty. Multivariate analysis determined greater CWR and larger preoperative velopharyngeal ports were significantly correlated with a smaller percent change in palate length after palatoplasty (P < 0.01). CONCLUSIONS: A wider palatal cleft decreases the surgeon's ability to decrease velopharyngeal port size through palatoplasty. Given the ease of measurement even in low-resource settings, CWR may be a valuable tool for setting expectations for speech results, modifying surgical technique, and correlating future speech outcomes in evidence-based cleft care.

4.
Plast Reconstr Surg Glob Open ; 9(5): e3627, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34036031

RESUMO

Although oncologic surgery is deemed urgent during the COVID-19 pandemic, clinical guidelines in reconstructive surgery have been unclear. Utilizing propensity-matched pre-pandemic data and our institutional experience during the crisis, we aimed to assess the safety of immediate device reconstruction following mastectomy to aid in decision-making during the pandemic. METHODS: Women undergoing mastectomy only and mastectomy with immediate breast reconstruction (IBR) with tissue expander or permanent implant from the 2007-2013 ACS-NSQIP datasets were included. Multivariate analysis of independent variables was used to form propensity-matched cohorts. Incidence of 30-day major postoperative bleeding and hospital length of stay were compared. RESULTS: In total, 13,580 mastectomy only patients and 11,636 IBR patients were identified. Factors that were found to be associated with IBR included age (P = 0.022), BMI (P < 0.001), race (P = 0.010), diabetes (P = 0.007), chronic steroid use (P = 0.003), pulmonary disease (P = 0.004), cardiovascular disease (P < 0.001), disseminated cancer (P = 0.001), chemotherapy before surgery (P = 0.016), low hematocrit (P < 0.001), and total operative time (P < 0.001). After propensity matching, immediate device reconstruction following mastectomy was not found to be associated with greater risk of postoperative bleeding (1.4% versus 1.0%, P = 0.334) or increased length of stay (1.5 ± 2.9 versus 1.5 ± 3.5 days, P = 0.576). CONCLUSIONS: Immediate device reconstruction does not elevate morbidity in terms of postoperative bleeding or does not increase the length of hospital exposure. Tissue expander or implant reconstruction can be safely performed immediately following mastectomy during the COVID-19 pandemic. Further, our institutional experience during the pandemic indicates that select patients can continue to safely undergo ambulatory mastectomy with device placement.

5.
J Surg Oncol ; 123(5): 1215-1231, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33621375

RESUMO

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.


Assuntos
Neoplasias da Mama/cirurgia , Mama/inervação , Mamoplastia/métodos , Regeneração Nervosa , Transferência de Nervo/métodos , Sensação/fisiologia , Feminino , Humanos , Transplante Autólogo
6.
Plast Reconstr Surg Glob Open ; 9(1): e3392, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33564601

RESUMO

BACKGROUND: Prepectoral implant-based breast reconstruction provides an alternative to submuscular reconstruction, but the increased acellular dermal matrix (ADM) required has the potential to lead to increased costs and decreased supply of this limited-resource material. We present a method for prepectoral reconstruction utilizing skin-graft meshing techniques to increase the surface area of usable ADM. METHODS: Forty-four patients underwent this technique from February 2019 to February 2020. Patient characteristics, operative details, and outcomes, including complications and patient satisfaction utilizing the BREAST-Q, were analyzed. Cost analysis relative to projected cost of nonmeshed techniques was performed. RESULTS: There were 20 unilateral and 24 bilateral procedures, for a total of 68 breast reconstructions. Mean age was 45.9 years (32-71). Mean implant volume was 485 cm3 (265-800), and one sheet of ADM was used for each breast with an average surface area of 161 cm2. Median follow-up was 350 days (212-576). Minor complications included an infection treated with oral antibiotics. Major complications included one axillary hematoma and one delayed implant loss. One patient underwent revision for asymmetry. Mean BREAST-Q score was 47.4/60. Cost ranged from $4113 to 5025 per breast, compared with the projected $9125-18250 per breast for other techniques in the literature. CONCLUSIONS: In contrast to previously described uses of ADM in prepectoral reconstruction, meshing maximizes resource utilization by expanding the coverage of a single sheet. Early findings demonstrate minimal complications and high patient satisfaction, suggesting the approach has potential to provide the benefits of prepectoral reconstruction while responsibly preserving product availability and tempering healthcare costs.

7.
Gland Surg ; 10(1): 479-486, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33634005

RESUMO

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.

8.
Plast Reconstr Surg ; 145(6): 1067e-1072e, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32459778

RESUMO

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.


Assuntos
Anormalidades Craniofaciais/cirurgia , Má Oclusão/cirurgia , Maxila/cirurgia , Osteotomia de Le Fort/métodos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Tratamento Conservador , Estudos de Viabilidade , Feminino , Humanos , Incidência , Masculino , Osteotomia de Le Fort/efeitos adversos , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
J Hand Surg Am ; 45(2): 162.e1-162.e5, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31103246

RESUMO

We present a rare case and unusual presentation of digital extensor tendon congenital hypoplasia. A 34-year-old woman presented to our clinic with the inability to extend her index, middle, and ring fingers since birth. Her tendons were reconstructed using transfer of flexor digitorum superficialis tendons from the middle and ring fingers to the extensor aponeurosis of the index, middle, and ring fingers. An acellular dermal substitute was applied in a novel way to reconstruct the extensor retinaculum and promote a successful functional outcome.


Assuntos
Dedos , Tendões , Adulto , Aponeurose , Feminino , Dedos/cirurgia , Humanos , Ligamentos , Tendões/cirurgia , Punho
10.
J Reconstr Microsurg ; 35(9): 662-668, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31302902

RESUMO

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 < 0.0001). Filled programs ranked a greater number of applicants per position, mean = 8.5 (1.8%), compared to partially filled, mean = 4.6 (2.6%), and unfilled mean = 3.6 (3.4%), programs (p = 0.0014). In 2015, 55.0% of programs matched their first or second choice compared to 30.4% of programs in 2018, mean = 43.0 (10.1%). 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.


Assuntos
Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Microcirurgia/educação , Seleção de Pessoal , Adulto , Feminino , Humanos , Internato e Residência , Masculino , São Francisco , Estados Unidos
11.
12.
Aesthet Surg J ; 39(9): NP370-NP376, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30329011

RESUMO

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.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/psicologia , Mamilos/cirurgia , Preferência do Paciente/estatística & dados numéricos , Satisfação do Paciente , Adolescente , Adulto , Crowdsourcing/estatística & dados numéricos , Estética , Feminino , Humanos , Masculino , Mamoplastia/métodos , Mastectomia/efeitos adversos , Preferência do Paciente/psicologia , Estudos Retrospectivos , Inquéritos e Questionários/estatística & dados numéricos , Adulto Jovem
13.
Ann Plast Surg ; 81(6): e12-e19, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30074525

RESUMO

BACKGROUND: Pilonidal 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 techniques and outcomes of PD surgery, to better guide decision making. METHODS: A literature review using directed search terms was performed to identify studies addressing PD management, in accordance with the PRISMA guidelines. Data on techniques, outcomes, and complications were collected. RESULTS: Open healing remains the most widely used treatment method and achieves reliable outcomes at the expense of prolonged wound healing, between 21 and 71 days. Asymmetric closure reduces healing time to 10 to 23 days and produces significantly fewer recurrences relative to midline closure (P < 0.05). Outcomes are similar between various asymmetric techniques; the Bascom cleft lift, Karydakis flap, and Limberg transposition are commonly used approaches which all demonstrate recurrence rates under 6%. Deroofing is associated with a significantly lower rate of complications than any closure procedure at 1.4% (P < 0.05), with recurrence in only 1% to 10% of patients, and represents a favorable treatment alternative. CONCLUSIONS: Despite the heterogeneous nature of studies on PD, certain techniques have been consistently shown to optimize postoperative outcomes. Deroofing sinuses and allowing secondary healing results in low rates of recurrence with minimal morbidity. When closure is preferred, off-midline flaps provide more effective coverage than midline repair. Treatment recommendations should be guided by individualized patient preferences and be grounded in high-quality data.


Assuntos
Seio Pilonidal/cirurgia , Humanos , Técnicas de Fechamento de Ferimentos , Cicatrização
14.
Aesthet Surg J ; 38(8): 861-869, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-29365056

RESUMO

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.


Assuntos
Contorno Corporal/métodos , Nádegas/cirurgia , Estética , Lipectomia/métodos , Coxa da Perna/anatomia & histologia , Tecido Adiposo/transplante , Adulto , Idoso , Nádegas/anatomia & histologia , Crowdsourcing/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários/estatística & dados numéricos , Coxa da Perna/cirurgia , Adulto Jovem
15.
Plast Reconstr Surg Glob Open ; 6(11): e2002, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30881800

RESUMO

BACKGROUND: Sacral pathology requiring partial or total sacrectomy is rare, and reconstructing the ensuing defects requires careful decision-making to minimize morbidity. The purpose of this study was to review the experience of a single institution with reconstructing large sacral defects, to identify risk factors for suboptimal outcomes. METHODS: A retrospective chart review was conducted of all patients who underwent sacrectomy over a 10-year period. Univariate analysis of differences in risk factors between patients with and without various postoperative complications was performed. Multivariate logistic regression was used to identify predictive variables. RESULTS: Twenty-eight patients were identified. The most common diagnosis leading to sacrectomy was chordoma (39%). Total sacrectomy was performed on 4 patients, whereas 24 patients underwent partial resection. Reconstructive modalities included 15 gluteal advancement flaps, 4 pedicled rectus abdominis myocutaneous flaps, and 9 paraspinous muscle or other flap types. There was an overall complication rate of 57.1% (n = 12) and a 28.6% (n = 8) incidence of major complications. There were significantly more flap-related complications in patients who underwent total sacrectomy (P = 0.02). Large defect size resulted in significantly more unplanned returns to the operating room (P < 0.01). CONCLUSION: Consistent with other published series', the overall complication rate exceeded 50%. Defect volume and sacrectomy type were the strongest predictors of postoperative complications and return to the operating room, while reconstructive strategy showed limited power to predict patient outcomes. We recommend that patients anticipated to have large sacral defects should be appropriately counseled regarding the incidence of wound complications, regardless of reconstructive approach.

16.
J Clin Invest ; 127(5): 1826-1838, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28394259

RESUMO

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-ß 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.


Assuntos
Células da Medula Óssea , Glioma , Células Mieloides , Neovascularização Patológica , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Linhagem Celular Tumoral , Glioma/irrigação sanguínea , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Proteína 2 Inibidora de Diferenciação/genética , Proteína 2 Inibidora de Diferenciação/metabolismo , Camundongos , Camundongos Transgênicos , Células Mieloides/metabolismo , Células Mieloides/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
17.
Clin Cancer Res ; 23(12): 3109-3119, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28039266

RESUMO

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.


Assuntos
Astrocitoma/tratamento farmacológico , Janus Quinase 1/genética , Neovascularização Patológica/tratamento farmacológico , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Animais , Astrocitoma/sangue , Astrocitoma/genética , Astrocitoma/patologia , Antígeno CD11b/antagonistas & inibidores , Antígeno CD11b/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Janus Quinase 1/antagonistas & inibidores , Masculino , Camundongos , Células Mieloides/efeitos dos fármacos , Células Mieloides/patologia , Neovascularização Patológica/patologia , Microambiente Tumoral/efeitos dos fármacos
18.
J Neurosurg ; 123(1): 23-30, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25859807

RESUMO

OBJECT: While most meningiomas are benign, 1%-3% display anaplastic features, with little current understanding regarding the molecular mechanisms underlying their formation. In a large single-center cohort, the authors tested the hypothesis that two distinct subtypes of anaplastic meningiomas, those that arise de novo and those that progress from lower grade tumors, exist and exhibit different clinical behavior. METHODS: Pathology reports and clinical data of 37 patients treated between 1999 and 2012 for anaplastic meningioma at Memorial Sloan-Kettering Cancer Center (MSKCC) were retrospectively reviewed. Patients were divided into those whose tumors arose de novo and those whose tumors progressed from previously documented benign or atypical meningiomas. RESULTS: Overall, the median age at diagnosis was 59 years and 57% of patients were female. Most patients (38%) underwent 2 craniotomies (range 1-5 surgeries) aimed at gross-total resection (GTR; 59%), which afforded better survival when compared with subtotal resection according to Kaplan-Meier estimates (median overall survival [OS] 3.2 vs 1.3 years, respectively; p = 0.04, log-rank test). Twenty-three patients (62%) presented with apparently de novo anaplastic meningiomas. Compared with patients whose tumors had progressed from a lower grade, those patients with de novo tumors were significantly more likely to be female (70% vs 36%, respectively; p = 0.04), experience better survival (median OS 3.0 vs 2.4 years, respectively; p = 0.03, log-rank test), and harbor cerebral hemispheric as opposed to skull base tumors (91% vs 43%, respectively; p = 0.002). CONCLUSIONS: Based on this single-center experience at MSKCC, anaplastic meningiomas, similar to glial tumors, can arise de novo or progress from lower grade tumors. These tumor groups appear to have distinct clinical behavior. De novo tumors may well be molecularly distinct, which is under further investigation. Aggressive GTR appears to confer an OS advantage in patients with anaplastic meningioma, and this is likely independent of tumor progression status. Similarly, those patients with de novo tumors experience a survival advantage likely independent of extent of resection.


Assuntos
Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/cirurgia , Meningioma/mortalidade , Meningioma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Craniotomia/métodos , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/classificação , Meningioma/classificação , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
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