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PURPOSE: Development of appropriate reimbursement models for breast reconstruction in the United States requires an understanding of relevant economic trends. The purpose of this study is to evaluate longitudinal patterns in Medicare reimbursement for frequently performed breast reconstruction procedures between 2000 and 2019. METHODS: Reimbursement data for 15 commonly performed breast reconstruction procedures were analyzed using the Centers for Medicare & Medicaid Services Physician Fee Schedule Look-Up Tool for each Current Procedural Terminology code. By utilizing changes to the US consumer price index, monetary data were adjusted for inflation to 2019 US dollars. Inflation-adjusted trends were used to calculate average annual and total percentage changes in reimbursement over time. RESULTS: From 2000 to 2019, average adjusted reimbursement for all procedures fell by 13.32%. All procedures demonstrated a negative adjusted reimbursement rate other than immediate insertion of breast prosthesis, which increased by 55.37%. The largest mean decrease was observed in breast reconstruction with other technique (-28.63%), followed by single pedicle transverse rectus abdominis myocutaneous flap (-26.02%), single pedicle transverse rectus abdominis myocutaneous flap with microvascular anastomosis (-23.33%), latissimus dorsi flap (-19.65%), and free flap reconstruction (-19.36%). CONCLUSIONS: There has been a steady yet substantial decline in Medicare reimbursement for the majority of breast reconstruction procedures over the last 20 years. Given increasing medical costs and the financial uncertainty of the US health care system, an understanding of Medicare reimbursement trends is vital for policymakers, administrators, and physicians to develop agreeable reimbursement models that facilitate growth and economic vitality of breast reconstruction in the United States.
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Mamoplastia , Retalho Miocutâneo , Médicos , Idoso , Humanos , Reembolso de Seguro de Saúde , Mamoplastia/métodos , Medicare , Estados UnidosRESUMO
BACKGROUND: Same-day discharge after mastectomy is a recently described treatment approach. Limited data exist investigating whether same-day discharge can be successfully implemented in patients undergoing mastectomy with immediate implant-based breast reconstruction (IBR). METHODS: Patients having mastectomy with IBR from 2013 to 2019 were reviewed. Enhanced recovery with same-day discharge was implemented in 2017. Patient characteristics, oncologic treatments, surgical techniques, and 90-day postoperative complications and reoperations were analyzed comparing enhanced recovery patients with historical controls. RESULTS: A total of 363 patients underwent nipple-sparing (214, 59%) or skin-sparing (149, 41%) mastectomy with 1-stage (270, 74%) or tissue expander (93, 26%) IBR. Enhanced recovery was used for 151 patients, with 79 of these patients (52%) discharged same-day. Overall, enhanced recovery patients experienced a significantly lower rate of 90-day complications (21% vs 41%, P < 0.001), including hematoma (3% vs 11%, P = 0.002), mastectomy flap necrosis (7% vs 15%, P = 0.02), seroma (1% vs 9%, P < 0.001), and wound breakdown (3% vs 9%, P = 0.05). Postoperative complication rates did not significantly differ among enhanced recovery patients discharged same day. Postoperative admissions significantly decreased after enhanced recovery implementation (100% to 48%, P < 0.001), and admitted enhanced recovery patients experienced a lower length of stay (1.2 vs 1.8, P < 0.001). Enhanced recovery patients experienced a lower incidence of ≥1 unplanned reoperation (22% vs 33%, P = 0.01); overall average unplanned and total reoperations did not significantly differ between groups. CONCLUSIONS: In conjunction with enhanced recovery practices, same-day discharge after mastectomy with IBR is a safe and feasible treatment approach.
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Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Alta do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: The purpose of this study is to evaluate how prior breast augmentation impacts rates of complications and risk for reoperation after mastectomy with concurrent breast reconstruction. METHODS: Patients undergoing nipple-sparing, skin-sparing, or simple mastectomy with implant-based reconstruction from 2008 to 2018 were identified in a prospective database. Postoperative complications and reoperations were then analyzed comparing patients with prior augmentation to patients without history of previous breast surgery. RESULTS: A total of 468 patients were identified with a median follow-up of 4 years. Of these, 72 had prior augmentation mammoplasty. These patients underwent nipple-sparing (52, 72%), skin-sparing (15, 21%), or simple (5, 7%) mastectomy with immediate direct-to-implant (46, 61%) or tissue expander (26, 35%) reconstruction. On univariate analysis, this cohort had a lower body mass index (23.3 vs 25.3, P = 0.003), a higher rate of nipple-sparing mastectomy (72% vs 54%, P = 0.01), and a higher prevalence of stage I disease (44% vs 33%, P = 0.04). Differences in age, comorbidities, reconstructive techniques, tumor size, and neoadjuvant/adjuvant therapies were not significant. Overall complication rate between patients with or without prior augmentation did not significantly differ (51% vs 50%, P = 0.83); no significant differences in rates of surgical site infection, hematoma, mastectomy skin flap/wound necrosis, nipple complications, implant loss, or capsular contracture were found. Analysis of reoperations between patients with and without prior augmentation revealed no significant differences in average number of subsequent planned, unplanned, or total reoperations. On multivariate analysis, prior breast augmentation was found to be associated with significantly increased risk for undergoing ≥1 unplanned reoperation (odds ratio, 2.28; 95% confidence interval, 1.28-4.05, P = 0.005). CONCLUSIONS: Prior augmentation mammoplasty does not significantly affect rates of postoperative complications after mastectomy with concurrent reconstruction. Although prior augmentation does not affect number of subsequent reoperations on average, it does increase the risk of experiencing 1 or more unplanned reoperation after mastectomy with reconstruction.
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Implantes de Mama , Neoplasias da Mama , Mamoplastia , Implantes de Mama/efeitos adversos , Neoplasias da Mama/cirurgia , Seguimentos , Humanos , Mamoplastia/efeitos adversos , Mastectomia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Three-dimensional (3D) nipple-areolar tattoo is a novel approach to nipple-areolar complex reconstruction for which little data exist. Our aim was to evaluate 3D nipple-areolar tattoo outcomes and investigate if patient factors, payer status, surgeries, or therapies affect tattoo utilization. METHODS: Patients pursuing skin-sparing (SSM) or attempted nipple-sparing mastectomy (NSM) with breast reconstruction from 2008 to 2019 were reviewed. Outcomes included frequency of 3D tattoo, post-procedure complications (infections, or other local adverse sequelae), and rates, indications, and timing of revisions. Patient factors, payer status, surgeries, and adjuvant therapies underwent univariate analysis comparing rates of 3D tattoo and revisions. RESULTS: A total of 191 patients were identified; median follow-up was 4 years. The majority of patients were white (165, 86%), married (146, 76%), and post-menopausal (97, 51%), with private insurance (156, 81%). Surgeries included SSM (172, 90%) or attempted NSM (19, 10%) with implant (154, 81%) or autologous reconstruction (37, 19%). Sixty-two patients (32%) underwent 3D nipple-areolar tattooing. No post-procedure complications occurred. After tattooing, 20 patients (32%) pursued revisions, the majority due to color fading (12, 60%). Average time from tattoo to completion of revisions was 5.6 months. Patients undergoing autologous reconstruction had a higher rate of 3D tattooing (p < 0.001). Adjuvant radiation led to a higher rate of revisions (p = 0.02). Patient factors, payer status, index mastectomy, and chemotherapy did not significantly affect rates of 3D tattooing or revisions. CONCLUSIONS: 3D nipple-areolar tattoo utilization is likely unaffected by age, marriage, menopause, or payer status. Radiotherapy and color fading can lead to more revisions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Neoplasias da Mama , Mamoplastia , Tatuagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/efeitos adversos , Mastectomia , Mamilos/cirurgia , Satisfação do Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: A chimerically configured gracilis and profunda artery perforator (PAP) flap is highly prevalent based on recent computed tomography (CT)-imaging data. The purpose of this study is to further characterize the vascular anatomy of this novel flap configuration and determine the feasibility of flap dissection. METHODS: To characterize flap arterial anatomy, lower extremity CT angiograms performed from 2011 to 2018 were retrospectively reviewed. To characterize venous anatomy and determine the feasibility of flap harvest, the lower extremities of cadavers were evaluated. RESULTS: A total of 974 lower extremity CT angiograms and 32 cadavers were included for the assessment. Of the 974 CT angiograms, majority (966, 99%) were bilateral studies, yielding a total of 1,940 lower extremities (right-lower-extremity = 970 and left-lower-extremity = 970) for radiographic evaluation. On CT angiography, a chimerically configured gracilis and PAP flap was found in 51% of patients (n = 494/974). By laterality, chimeric anatomy was present in 26% of right lower extremities (n = 254/970) and 25% of left lower extremities (n = 240/970); bilateral chimeric anatomy was found in 12% (n = 112/966) of patients. Average length of the common arterial pedicle feeding both gracilis and PAP flap perforasomes was 31.1 ± 16.5 mm (range = 2.0-95.0 mm) with an average diameter of 2.8 ± 0.7 mm (range = 1.3-8.8 mm).A total of 15 cadavers exhibited chimeric anatomy with intact, conjoined arteries and veins allowing for anatomical tracing from the profunda femoris to the distal branches within the tissues of the medial thigh. Dissection and isolation of the common pedicle and distal vessels was feasible with minimal disruption of adjacent tissues. Chimeric flap venous anatomy was favorable, with vena commitante adjacent to the common pedicle in all specimens. CONCLUSION: Dissection of a chimeric medial thigh flap consisting of both gracilis and PAP flap tissues is feasible in a cadaveric model. The vascular anatomy of this potential flap appears suitable for future utilization in a clinical setting.
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Retalho Perfurante , Angiografia , Cadáver , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/cirurgia , Humanos , Estudos Retrospectivos , Coxa da Perna/diagnóstico por imagemRESUMO
BACKGROUND: Pressure ulceration, pyogenic arthritis, and hip heterotopic ossification are complications encountered in spinal cord injury patients. The Girdlestone procedure has been established as an effective treatment modality for hip pathology in this population and is particularly efficacious when a muscle flap is used to fill the femoral resection defect. We previously reported its use as a 3-stage procedure. Through time, experience was gained, and consequently, our technique has evolved to a 1-stage procedure. METHODS: A retrospective analysis of all spinal cord injury patients who had undergone Girdlestone arthroplasty or excision of heterotopic ossification by the pressure ulcer management team at Rancho Los Amigos National Rehabilitation Center between 1991 and 2005 was performed. A description of our management, operative protocol, outcome, and complication is given. RESULTS: Over 15 years (between 1991 and 2005), 295 patients underwent 330 procedures. Hips were operated for infection, heterotopic ossification, pressure ulceration, dislocation, femoral head necrosis, or fracture or a combination of the above. Twenty-five cases (7.6%) required surgical revision for wound breakdown in the immediate postoperative period. Average follow-up was 40.3 months; 43.6% of patients developed recurrence of ulceration requiring surgery. The average time until recurrence was 27.3 months. CONCLUSIONS: The Girdlestone arthroplasty is an effective modality to treat hip infection, ankylosis, heterotopic ossification, dislocation, or other pathology associated with the spinal cord injury patient. Long-term follow-up of a large patient population reveals the efficacy of the procedure in preventing recurrence and improving patient quality of life.
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Artroplastia/métodos , Articulação do Quadril/cirurgia , Ossificação Heterotópica/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Úlcera por Pressão/cirurgia , Traumatismos da Medula Espinal/complicações , Retalhos Cirúrgicos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/etiologia , Úlcera por Pressão/etiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Every year, nearly 1.2 million people are affected by nonmelanoma skin cancers (NMSCs) in the United States. Most published data focus on comparing the efficacy of Mohs micrographic surgery (MMS) versus traditional surgical excision (TSE) for NMSCs in H-zone lesions of the face. There is paucity of data regarding the 2 treatments in other areas such as the non-H-zone areas of the face, the trunk, and extremities. Our study focused on the efficacy of the 2 treatments in areas of the body where the skin was not of premium. METHOD: A retrospective chart review was performed of patients with NMSCs treated with TSE at the West Los Angeles Veterans Affairs Hospital between 2000 and 2008. Patients with at least a 3-year follow-up were selected for the study. Institutional review board approval was obtained before commencement of the study. Age, sex, and race-matched patients were selected in the MMS group. Data collected included demographic data, tumor characteristics, surgical treatment, reconstructions, recurrence rates, complications, and follow-up course. Data were analyzed using SigmaStat 3.5. RESULTS: A total of 588 patients were treated for NMSCs at our institute between 2000 and 2008, of which 289 patients had non-H-zone, extremity, and trunk lesions. The follow-up period for these patients was at least 3 years. Average age of this group was 67.1 (11.4) with 89.9% being males. Age, sex, and race-matched group of 200 patients treated with MMS for NMSCs were randomly chosen from the same time range. Average size of lesions was 17.4 (16.9) mm in the TSE group and 1.1 (0.4) mm in the MMS group (P < 0.05). Primary reconstruction was performed in non-premium areas (ie, non-H-zone areas of the face, the trunk, and extremities) in 98.7% patients in the TSE group and 61.5% patients in the MMS group (P < 0.05). Secondary reconstructive rate was 1.3% in TSE compared to 37.5% in MMS. Overall recurrence rate was 4.8% (compared to 3% with MMS). Of the 29 patients who had recurrences within the TSE group, 27 were H-zone lesions and 2 were non-H-zone lesions. DISCUSSION: One of the primary goals of NMSC management is to treat the lesion with adequate oncologic margins, while preserving maximal function and cosmesis. Our data look at the non-premium areas to quantify the clinical efficacy of TSE versus MMS. The size of lesions treated by TSE was significantly larger than those treated by MMS in all areas of the body. The primary closure rates were significantly higher and secondary procedure rates significantly lower in the TSE group compared to the MMS group, in non-premium areas. Our data suggest that patients with NMSCs may be more effectively treated with TSE than MMS in non-premium areas of the body. Additional studies are ongoing, including economic modeling and cost analysis.
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Cirurgia de Mohs , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Idoso , Procedimentos Cirúrgicos Dermatológicos , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
Pressure ulcers in spinal cord injury represent a challenging problem for patients, their caregivers, and their physicians. They often lead to recurrent hospitalizations, multiple surgeries, and potentially devastating complications. They present a significant cost to the healthcare system, they require a multidisciplinary team approach to manage well, and outcomes directly depend on patients' education, prevention, and compliance with conservative and surgical protocols. With so many factors involved in the successful treatment of pressure ulcers, an update on their comprehensive management in spinal cord injury is warranted. Current concepts of local wound care, surgical options, as well as future trends from the latest wound healing research are reviewed to aid medical professionals in treating patients with this difficult problem.
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Guias como Assunto , Úlcera por Pressão , Traumatismos da Medula Espinal/complicações , Humanos , Úlcera por Pressão/terapiaRESUMO
Background: The potential for opioid prescription medication addiction and abuse has been a growing concern in healthcare. It is not uncommon for hand surgery patients to be overprescribed opioid medication for postoperative pain management. The objective of this study was to characterize changes in opioid prescription practices of hand surgeons treating Medicare Part D patients from 2013 to 2019. Methods: A retrospective analysis of Medicare Part D prescriber data from 2013 to 2019 was conducted. This database provides information on drugs paid for under the Medicare Part D Prescription Drug Program. For each prescriber and medication, the dataset includes the total number of prescriptions dispensed (original prescriptions and number of refills), and total medication cost. Results: In 2013, the 10 most common medications prescribed totaled 114,409 prescriptions, with 89,701 (78.4%) opioid prescriptions. In 2019, the 10 most common medications prescribed totaled 164,955 prescriptions, with 109,665 (66.5%) opioid prescriptions. Although total opioid prescriptions dropped, there was a 22% increase in the total number of prescriptions written. The two most common medications prescribed, hydrocodone-acetaminophen and oxycodone-acetaminophen, totaled 75,796 in 2013, compared with 76,518 in 2019. The overall number of prescriptions for nonsteroidal anti-inflammatory drugs increased by 157%, and the percentage of total opioids prescribed declined by 7.9%. Conclusions: The increase in total opioid prescriptions from 2013 to 2019 by hand surgeons in the Medicare Part D Prescription Drug Program lags behind the recommended shift to nonopioid pain management. The reasons for the overall rise in prescriptions deserve further exploration.
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Pressure injuries (PIs) are a spectrum of localized tissue destruction that develops most often at a bony prominence. PIs are the result of a combination of extrinsic (eg, pressure, shear, friction, and moisture) and intrinsic (nutritional status, spasticity, decreased sensation, and vascular disease) factors. Given their complex etiology, management of PIs requires a multidisciplinary approach from a team of health care professionals. After addressing both extrinsic and intrinsic factors, local wound care is generally recommended for stages 1 to 2 PIs and surgical intervention for stages 3 to 4.
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Úlcera por Pressão , Pessoal de Saúde , Humanos , Estado Nutricional , Úlcera por Pressão/etiologia , Úlcera por Pressão/terapiaRESUMO
BACKGROUND: Limited data exist outlining reoperations after direct-to-implant (DTI), tissue expander (TE) and autologous free-flap breast reconstruction. METHODS: Patients undergoing mastectomy with reconstruction from 2008 to 18 were reviewed. Patient factors, surgical techniques, planned, unplanned, and total reoperations were analyzed. RESULTS: Among 544 total patients, the majority underwent DTI (294, 54%) or TE (176, 32%); 74 (14%) received autologous free-flaps. Majority of DTI patients (55%) underwent subsequent reoperations. Compared to autologous tissue, DTI had less patients undergo additional surgery (76% vs. 55%, P = 0.001). Incidence of total unplanned reoperations did not significantly differ between reconstructive groups. The rate of unplanned reoperations due to complications was lowest for DTI (39%) when compared to TE (48%) and autologous (55%, P = 0.015). Compared to TE, DTI carried a lower risk for ≥2 total reoperations (OR = 0.21, 95% CI 0.13-0.33, P < 0.001). CONCLUSIONS: Seldom "one and done," additional surgery after DTI remains significant.
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Implantes de Mama , Neoplasias da Mama , Mamoplastia , Implantes de Mama/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/métodos , Complicações Pós-Operatórias/etiologia , Reoperação/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The effect of postoperative sensation on quality-of-life (QoL) following nipple-sparing mastectomy (NSM) with implant-based reconstruction is not well described. We evaluated the impact of breast and nipple sensation on patient QoL by using BREAST-Q. METHODS: Patients undergoing NSM with implant reconstruction from 2008 to 2020 were mailed a survey to characterize their postoperative breast and nipple sensation. BREAST-Q metrics were compared between totally numb patients and those with sensation. RESULTS: A total of 349 patients were included. Overall, 131 (38%) responded; response rates regarding breast and nipple sensation were 36% (N = 124/349) and 34% (N = 117/349). Median time from surgery to survey completion was 6 years. The majority had bilateral procedures (101, 77%), including direct-to-implant (99, 76%) and tissue expander (32, 24%) reconstruction. Regarding breast sensation, the majority of patients reported their reconstructed breasts as totally numb (47, 38%) or much less sensation than before surgery (59, 48%). Regarding nipple sensation, the majority of patients reported their nipples were totally numb (67, 57%) or had much less sensation than before surgery (37, 32%). Total numbness of reconstructed breasts resulted in a significantly lower chest physical well-being (mean score: 73.5 vs. 81.2, respectively, P = 0.048). Total numbness of postoperative nipple(s) resulted in significantly lower chest physical (mean score: 74.8 vs. 85.2, respectively, P = 0.007), psychosocial (mean score 77.4 vs. 84.4, respectively, P = 0.041), and sexual well-being (mean score: 55.7 vs. 68.3, respectively, P = 0.002). CONCLUSIONS: Long-term breast and nipple sensation are significantly diminished after NSM with implant reconstruction. Patients with preserved sensation experience better physical, psychosocial, and sexual well-being.
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Neoplasias da Mama , Mamoplastia , Mastectomia Subcutânea , Neoplasias da Mama/cirurgia , Feminino , Humanos , Hipestesia , Mamoplastia/métodos , Mastectomia/métodos , Mastectomia Subcutânea/métodos , Mamilos/fisiologia , Mamilos/cirurgia , Satisfação do Paciente , Qualidade de Vida , Estudos Retrospectivos , SensaçãoRESUMO
Seroma is a common complication of body-contouring surgery. Current literature focuses on prevention or initial management of seroma formation; however, no definitive evidence exists to guide management of chronic or recurrent seromas. We describe a case of a recurrent abdominal wall seroma following abdominoplasty. The seroma was present for 8 years despite employing multiple treatment modalities. After presentation to our clinic, the patient was taken to the operating room, where the seroma pseudocapsule was excised, progressive tension sutures were utilized, and drains were placed. To date, there has been no recurrence of the seroma. We propose that chronicity, recurrence, and persistence of seroma are indications for surgical intervention.
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Pyoderma gangrenosum (PG) is a diagnosis of exclusion worsened by surgical debridement. This report presents two atypical manifestations of PG in the reconstructed breast, whereby the disease is only confined to the irradiated chest wall tissue bed, sparing the abdominal donor sites and the contralateral reconstructed breast.
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BACKGROUND: Ramifications of postoperative complications on long-term survival after mastectomy are uncertain. METHODS: Overall complications (Clavien-Dindo Grades I-IIIB) and wound complications were analyzed using the Kaplan-Meier method for impact on 5-year overall (OS) and disease-free survival (DFS). RESULTS: A total of 378 patients underwent mastectomy alone (157, 41%) or mastectomy with reconstruction (221, 59%) for Stage I-III disease with a median follow-up of 5 years. Postoperative complications occurred in 186 patients (49%), requiring non-surgical (I/II = 83, 22%) or surgical (IIIa/IIIb = 103, 27%) management. Wound complications occurred in 140 patients (37%). Reconstruction was associated with a higher rate of complication (P < 0.001). Postoperative complications after mastectomy (with or without reconstruction) did not significantly affect OS or DFS. Wound complications also showed no significant effect on OS or DFS following mastectomy alone, or mastectomy with reconstruction. CONCLUSIONS: Postoperative complications after mastectomy, with or without reconstruction, bear no significant impact on 5-year survival.
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Neoplasias da Mama/cirurgia , Mamoplastia , Mastectomia , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Objective: The descending genicular artery provides the dominant pedicle for the medial femoral condyle and medial femoral trochlear free flaps. Variations of the flap include using a skin paddle for monitoring, a vastus medialis muscle component, and the medial superior geniculate artery for the pedicle. We present a case of a 49-year-old man with a distal tibial fracture from a motor vehicle accident complicated by chronic osteomyelitis, poor soft tissue envelope, and tibial nonunion. Methods: The composite lower extremity defect was reconstructed with a chimeric myo-osseous variant of the medial femoral condyle free flap since no perforator was available to the skin and there was a large amount of dead space. Results: At 9 months postoperatively, there was successful tibial union, adequate coverage of the defect, and a return to unassisted ambulation. Conclusions: The chimeric myo-osseous variant of the medial femoral condyle free flap adds to the versatility of this flap and has application in reconstructing defects of bone that also require soft tissue coverage.
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Hand transplantation requires precise preoperative planning and surgical execution. Coordinating a transplant team-including surgeons, anesthesiologists, nurses, and supporting staff-is a time-sensitive challenge when a donor-recipient match is confirmed. International human limb transplantation occurs when the recipient and donor are in separate countries. The authors describe the logistics behind the first transatlantic adult bilateral hand transplantation, which, to date, required the highest level of coordination and timing. The authors' experience serves as a proof of concept that international limb transplantation or salvage is possible when the complex logistics of such an endeavor are carefully anticipated.
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Transplante de Mão/métodos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Feminino , França , Humanos , Obtenção de Tecidos e Órgãos/organização & administração , Estados UnidosRESUMO
Inhibition of angiogenesis is currently perceived as one of the promising strategies in the treatment of cancer. The antiangiogenic property of thalidomide has inspired a second wave of research on this teratogenic drug. Previous studies from our group and others demonstrated that metabolites of thalidomide are responsible for the drug's pharmacological actions. On the basis of the structures of these metabolites, we synthesized 118 thalidomide analogues. Preliminary screening selected 7 of these 118 analogues for more extensive testing in the current study. In the rat aortic ring assay, all 4 analogues in the N-substituted class and 2 of the 3 analogues in the tetrafluorinated class significantly inhibited microvessel outgrowth at 12.5-200 microM. Thalidomide failed to block angiogenesis at similar concentrations. Subsequently, the effects of these analogues on human umbilical vein endothelial cell proliferation and tube formation were determined. Those analogues showing antiangiogenicity in the rat aortic ring assay also demonstrated antiproliferative action in human umbilical vein endothelial cells. Cell proliferation was not affected by thalidomide. Interestingly, all 7 analogues as well as thalidomide suppressed tube formation. Two tetrafluorinated analogues consistently showed the highest potency and efficacy in all three assays. The in vivo toxicity of representative analogues from each class was also evaluated. Taken together, our results support the further development and evaluation of novel thalidomide analogues as antiangiogenic agents.
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Inibidores da Angiogênese/farmacologia , Talidomida/análogos & derivados , Talidomida/farmacologia , Adenocarcinoma/patologia , Androgênios , Animais , Aorta/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Masculino , Estrutura Molecular , Neoplasias Hormônio-Dependentes/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Neoplasias da Próstata/patologia , Ratos , Relação Estrutura-Atividade , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
PURPOSE: Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis, which exerts direct effects on vascular endothelial cells, including endothelial cell proliferation and survival, tubulogenesis, and vascular permeability. In this study, we examined whether Neovastat, a naturally occurring multifunctional antiangiogenic drug, could inhibit the endothelial cell response to VEGF stimulation. RESULTS: We demonstrated that Neovastat was able to block the VEGF-dependent microvessel sprouting from Matrigel-embedded rat aortic rings, and it also blocked the VEGF-induced endothelial cell tubulogenesis in vitro. In vivo studies showed that Neovastat was able to specifically inhibit VEGF-induced plasma extravasation in numerous tissues, including pancreas and skin. The mechanism of action of Neovastat on VEGF-mediated effects was also evaluated at the molecular level. Neovastat was shown to compete against the binding of VEGF to its receptor in endothelial cells and significantly inhibited the VEGF-dependent tyrosine phosphorylation of VEGF receptor-2, whereas it had no significant effect on VEGF receptor-1 activity. Moreover, the inhibition of receptor phosphorylation was correlated with a marked decrease in the ability of VEGF to induce pERK activation. Neovastat does not compete against the binding of basic fibroblast growth factor, indicating a preferential inhibitory effect on the VEGF receptor. CONCLUSIONS: Because Neovastat was shown previously to inhibit metalloproteinase activities, these results suggest that Neovastat is able to target multiple steps in tumor neovascularization, further emphasizing its use as a pleiotropic, multifunctional antiangiogenic drug.