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1.
J Plast Reconstr Aesthet Surg ; 90: 266-272, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38401198

RESUMO

BACKGROUND: Sternotomy wound complications are more frequent after orthotopic heart transplantation (OHT) compared to other cardiac surgeries, primarily due to additional risk factors, including immunosuppression. Flap closure often becomes necessary for definitive treatment, although there is a scarcity of data on the outcomes of sternal wound reconstruction in this specific population. METHODS: A retrospective analysis was conducted on 604 sternal wound reconstructions performed by a single surgeon between 1996 and 2023. Inclusion criteria comprised patients who underwent OHT as their primary cardiac procedure. Surgical interventions involved sternal hardware removal, debridement, and muscle flap closure. RESULTS: The study included 66 patients, with culture-positive wound infection being the most common indication for reconstruction (51.5%). The median duration between transplantation and sternal wound reconstruction was 25 days. Bilateral pectoralis major myocutaneous advancement flaps (n = 63), rectus abdominis flaps (n = 2), or pectoralis major turnover flaps (n = 1) were used. Intraoperative wound cultures revealed positivity in 48 patients (72.7%), with Staphylococcus epidermidis being the most frequently cultured organism (25.0%). The overall complication rate was 31.8%, and two patient deaths were related to sternal wounds, resulting from multiorgan failure following septic shock. The majority of the patients reported excellent long-term functional and esthetic outcomes. CONCLUSIONS: Sternal wounds following OHT pose a significant morbidity risk. Our strategy focuses on immediate and aggressive antibiotic therapy, thorough debridement, and definitive closure with bilateral pectoralis myocutaneous advancement flaps. This approach has demonstrated complication and mortality rates comparable to the general cardiac surgery population, as well as excellent functional and esthetic results.


Assuntos
Transplante de Coração , Retalho Miocutâneo , Humanos , Desbridamento/métodos , Transplante de Coração/efeitos adversos , Músculos Peitorais/cirurgia , Estudos Retrospectivos , Esternotomia/efeitos adversos , Esterno/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Resultado do Tratamento
2.
Ann Plast Surg ; 90(6S Suppl 5): S521-S525, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36752500

RESUMO

BACKGROUND: Sternal wound infection (SWI) and dehiscence after median sternotomy for cardiac surgery remain challenging clinical problems with high morbidity. Bilateral pectoralis major myocutaneous flaps are excellent for most sternal wounds but do not reach deeper mediastinal recesses. The omental flap may be a useful adjunct for addressing these deeper mediastinal infections. METHODS: Records of 598 sternal wound reconstructions performed by a single surgeon (J.A.A.) from 1996 to 2022 were reviewed. At the time of surgery, patients underwent sternal hardware removal, debridement, and closure with bilateral pectoralis major myocutaneous flaps. Pedicled omental flaps were also mobilized when additional vascularized tissue was required within the deeper mediastinum. RESULTS: Complete data were available for 559 sternal wound reconstructions performed by the senior author during this period. Bilateral pectoralis and omental flaps were mobilized in 17 of 559 (3.04%) patients. Common indications for initial cardiac surgery included repair or replacement of diseased aortic roots (9/17; 52.94%), aortic valves (8/17; 47.06%), and mitral valves (6/17; 35.29). Mean American Society of Anesthesiologists score was 3.56. Preoperative morbidity included culture-positive wound infection (12/17; 70.59%), dehiscence (15/17; 88.24%), wound drainage (11/17; 64.71%), and inability to close the chest after the original sternotomy because of hemodynamic instability (6/17; 35.29%). Intraoperative deep mediastinal or bone cultures were positive in 8 of 17 (47.06%) patients. Postoperative complications included partial dehiscence (2/17; 11.76%), skin edge necrosis (1/17; 5.88%), seroma (1/17; 5.88%), abdominal hernia (1/17; 5.88%), and recurrent infection (2/17; 11.76%). Three patients (17.65%) died within 30 days of the reconstruction surgery. CONCLUSIONS: Patients undergoing combined pectoralis major and omental flap closure frequently had a history of aortic root and valve disease, and other significant preoperative morbidities. However, postoperative complication rates after combined flap closure were relatively low. Combined pectoralis major and omental flap reconstruction thus appears to be an effective intervention in patients with sternal wounds extending into the deep mediastinum.


Assuntos
Mediastino , Lesões dos Tecidos Moles , Humanos , Mediastino/cirurgia , Músculos Peitorais/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Estudos Retrospectivos , Retalhos Cirúrgicos , Esternotomia/efeitos adversos , Esterno/cirurgia , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/etiologia , Desbridamento , Lesões dos Tecidos Moles/etiologia
3.
Ann Plast Surg ; 88(3 Suppl 3): S205-S208, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35513321

RESUMO

INTRODUCTION: Acellular dermal matrix (ADM) is frequently used during prepectoral tissue expander-based breast reconstruction. However, there has been a paucity of literature describing the experience of prepectoral reconstruction without the accompanying use of ADM. We seek to highlight our institutional experience with immediate prepectoral tissue expander placement without the use of ADM in breast reconstruction. METHODS: A retrospective, single-institution review of patient records was performed to identify all patients who underwent either skin sparing or nipple-sparing mastectomy with immediate tissue expander placement without the use of ADM. Demographics including age, body mass index, comorbidities, history of smoking or steroid use, perioperative radiation or chemotherapy, intraoperative details, and complication profiles during the tissue expander stage were retrospectively collected and analyzed. At the time of tissue expander placement, all mastectomy flaps were evaluated clinically and with indocyanine green laser angiography. Postoperative outcomes were tracked. RESULTS: Between 2017 and 2020, 63 patients (for a total of 108 breasts) underwent either skin sparing (16%) or nipple-sparing mastectomy (84%) with immediate prepectoral tissue expander without ADM placement. Fourteen percent of breasts developed postoperative cellulitis, 19% of breasts developed skin compromise, and 5% required a postoperative revisional procedure that did not result in immediate expander explant. There was a 13% (n = 14 breasts) explant rate occurring at a mean time of 74 days. Of those breasts that developed skin compromise, 45% went on to require eventual explant. Patients in the study were followed for an average of 6.3 months. CONCLUSIONS: Immediate prepectoral breast reconstruction using tissue expanders without ADM offers a viable alternative to established reconstructive paradigms. The major complication rate for prepectoral reconstruction without the use of ADM (17%) was found to be comparable with our historical subpectoral tissue expander reconstruction with ADM use. Tissue expander explant rates were also comparable between the prepectoral without ADM (13%) and the subpectoral with ADM cohorts. These preliminary data suggest that immediate breast reconstruction with tissue expander placement without accompanying ADM is viable alternative in the breast reconstructive algorithm.


Assuntos
Derme Acelular , Implante Mamário , Implantes de Mama , Neoplasias da Mama , Mamoplastia , Implante Mamário/métodos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/etiologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/métodos , Estudos Retrospectivos
4.
Ann Plast Surg ; 88(3 Suppl 3): S229-S234, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35513325

RESUMO

In 2019, the plastic surgery residency match changed their method for inviting students to interview. Instead of offering interview invitations and scheduling interviews on a first come, first served basis, all plastic surgery residency programs sent out secured interview spots on the same day. This universal offer date was intended to remove student worry that surrounded not scheduling an interview fast enough, as well as cause students to more carefully select which interview invitations to accept, increasing the likelihood that residency programs could interview only those students most interested in matching at their institutions. The effect of universal offer date was studied through analysis of available National Residency Match Program data, with a focus on the mean number of contiguous programs students ranked to match, as well as the mean number of applicants who residency programs ranked to fill each available position. Historical trends in plastic surgery match, trends in the match in other competitive surgical subspecialties, and applicant qualifications were also analyzed. In breaking with the general trend among all surgical subspecialties toward ranking more applicants per residency position, in 2020, fewer plastic surgery applicants were ranked by residency programs per available position, suggesting a more effective interview process and match. Matched applicant qualifications remained excellent across the period studied.


Assuntos
Internato e Residência , Cirurgia Plástica , Humanos , Cirurgia Plástica/educação
5.
Plast Reconstr Surg ; 146(6): 1382-1390, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33234975

RESUMO

BACKGROUND: Surgical dehiscence can occur after lower extremity orthopedic procedures. Underlying vascular aberrancy and localized ischemia contribute to chronic wound development requiring advanced techniques such as free tissue transfer. Localized vascular abnormality is an underrecognized contributing factor to such dehiscence. The authors reviewed their lower extremity free tissue transfer experience in this population to analyze the incidence of arterial abnormality and outcomes. METHODS: The authors conducted a retrospective review of 64 lower extremity free tissue transfers performed for chronic wounds after orthopedic procedures from 2011 to 2018. The primary outcome was major arterial abnormality as identified on angiography. Secondary outcomes were flap success, limb salvage, and ambulation status. RESULTS: The median age was 58 years, and 44 were men (69 percent). Comorbidities included osteomyelitis (77 percent), diabetes (39 percent), and peripheral vascular disease (17 percent). The incidence of arterial abnormality on angiography was 47 percent. Defect location correlated with angiosome of arterial abnormality in 53 percent. The flap success rate was 92 percent. Limb salvage and ambulation rates were 89 and 89 percent, respectively, at an average follow-up of 17.6 months. Men demonstrated an increased rate of limb salvage (p = 0.026). Diabetes (p = 0.012), arterial abnormality (p = 0.044), and arterial flap complication (p = 0.010) correlated with amputation. CONCLUSIONS: The high incidence of arterial abnormality in this population highlights the importance of expedient multidisciplinary care, including vascular and plastic surgery. Diagnostic angiography is important for identifying major arterial abnormality and the need for free tissue transfer for definitive coverage.


Assuntos
Arteriopatias Oclusivas/epidemiologia , Retalhos de Tecido Biológico/transplante , Procedimentos Ortopédicos/efeitos adversos , Deiscência da Ferida Operatória/cirurgia , Idoso , Amputação Cirúrgica/estatística & dados numéricos , Angiografia/estatística & dados numéricos , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/cirurgia , Artérias/diagnóstico por imagem , Artérias/cirurgia , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Salvamento de Membro/estatística & dados numéricos , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/epidemiologia , Estudos Retrospectivos , Deiscência da Ferida Operatória/etiologia
6.
Plast Reconstr Surg ; 145(1): 164e-171e, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881626

RESUMO

BACKGROUND: Although venous thrombosis is a leading cause of flap failure, the majority of lower extremity free flap planning is centered on arterial system evaluation. Preoperative identification of relevant abnormality in lower extremity venous systems by means of duplex ultrasound may aid in the diagnosis of clinically important abnormality that could affect lower extremity flap outcomes. METHODS: Between November of 2014 and August of 2017, 57 patients underwent preoperative lower extremity venous duplex imaging and free tissue transfer for lower extremity wounds. A retrospective review was performed to describe lower extremity venous pathologic findings, relevant patient demographic data, comorbid conditions, and outcomes. Discovery of venous abnormality helped guide recipient vein selection. RESULTS: Fifty-seven consecutive patients underwent 59 free flap operations to treat chronic lower extremity wounds. Venous duplex ultrasonography detected venous insufficiency (defined as >0.5 second of reflux) in 23 patients (39.0 percent), including 16 (27.2 percent) with deep thigh reflux, six (10.2 percent) with superficial calf reflux, and four (6.78 percent) with deep calf reflux. Deep venous thrombosis was found in four patients (6.78 percent) and treated with anticoagulation. The flap success rate was 98.3 percent. Five patients (8.47 percent) progressed to amputation. At a mean follow-up time of 15.1 ± 9.51 months (range, 1.67 to 35.2 months), 53 patients (89.8 percent) were able to continue community ambulation. CONCLUSIONS: Lower extremity venous duplex testing before free tissue transfer may be useful for optimizing flap recipient vessel selection and for detecting potentially unknown venous abnormality. Development of free flap planning protocols incorporating preoperative vascular imaging is important to achieving good functional outcomes in this comorbid patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.


Assuntos
Rejeição de Enxerto/prevenção & controle , Traumatismos da Perna/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Insuficiência Venosa/diagnóstico , Trombose Venosa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/transplante , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Humanos , Incidência , Perna (Membro)/irrigação sanguínea , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Ultrassonografia Doppler Dupla , Veias/diagnóstico por imagem , Insuficiência Venosa/complicações , Insuficiência Venosa/epidemiologia , Trombose Venosa/complicações , Trombose Venosa/epidemiologia , Adulto Jovem
7.
Wounds ; 31(11): 272-278, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31730509

RESUMO

INTRODUCTION: Tissue ischemia resulting from arterial insufficiency is a major factor affecting lower extremity wound healing in patients with peripheral arterial disease (PAD). Accelerated wound closure with split-thickness skin grafting (STSG) provides a durable barrier to infection and can prevent limb loss. Published STSG outcomes data are minimal in the post endovascular intervention population. OBJECTIVE: In this study, the authors examine factors predictive of STSG healing in patients with PAD following vascular intervention, including the effect of non-inline flow via arterial-arterial and non-arterial collateralization. MATERIALS AND METHODS: Patients with PAD and wounds of the foot and ankle who underwent STSG between January 2014 and December 2016 were retrospectively reviewed. All patients received angiographic evaluation and endovascular or open revascularization where necessary. Effects of extremity revascularizations, STSG percent take, and amputation rate were evaluated. RESULTS: Thirty-five patients with 47 wounds underwent STSG. There were 21 men and 14 women with a mean age of 64 ± 13 years. Revascularization was required in 23 patients (25 extremities) before STSG, with balloon angioplasty for tibial artery lesions as the most common revascularization. Patent pedal arch was present in 8 patients; 35 patients had an absent or incomplete pedal arch. Patients with a fully patent pedal arch healed at a significantly higher rate than those with an absent or incomplete pedal arch at 1 month (62.5% vs. 17.1%, P ⟨ .05). At 90-day follow-up, 9 of 35 (25.7%) patients with 9 of 47 (19.1%) wounds were lost to follow-up, leaving 18 of 38 (47.37%) wounds healed and 20 (52.63%) still open. Ultimately, 36 of 47 (76.60%) wounds healed and 6 major amputations in 6 patients were required at a mean 502 ± 342 days follow-up. CONCLUSIONS: These results suggest the importance of arterial-arterial connections such as the pedal arch to the healing potential of foot and ankle wounds after STSG in this high-risk patient population.


Assuntos
Tornozelo/patologia , Pé/patologia , Isquemia/fisiopatologia , Doença Arterial Periférica/fisiopatologia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Cicatrização/fisiologia , Idoso , Angiografia , Angioplastia com Balão , Tornozelo/irrigação sanguínea , Desbridamento/métodos , Procedimentos Endovasculares/métodos , Feminino , Pé/irrigação sanguínea , Sobrevivência de Enxerto/fisiologia , Humanos , Isquemia/cirurgia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
J Vasc Surg Cases Innov Tech ; 5(4): 435-437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31660467

RESUMO

Negative pressure wound therapy with intermittent instillation, especially with the addition of antibiotics in the case of infection, is a versatile treatment modality for the closure of wounds and can be used both primarily after débridement and secondarily after failure of muscle flap coverage. We present a case in which negative pressure wound therapy with intermittent instillation of rifampin was used to successfully close a groin wound secondary to an infected prosthetic vascular graft that initially failed to close with a muscle flap. Consideration of this approach to wound closure and graft salvage is important because of the seriousness and relatively common incidence of prosthetic vascular graft infection after infrainguinal arterial bypass revascularization.

9.
Plast Reconstr Surg ; 144(4): 693e-699e, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568319

RESUMO

Fatigue is inevitable at all stages of a surgical career. The sustained high degree of concentration required for surgery is complicated by long surgeon working hours and sleep deprivation, which force surgeons to learn to manage and mitigate the effects of physical and mental fatigue on their performance. Extensive evidence exists detailing the potentially dangerous effects of surgeon fatigue on patient safety, but few reports exist offering a comprehensive strategy to mitigate the effects of fatigue on clinical performance. To promote improved detection and mitigation of fatigue among surgeons, the authors have highlighted several deliberate fatigue-management techniques that they have found to be particularly effective in their own experiences. These techniques include proper planning to maximize team efficiency, and the use of scheduled and unscheduled intraoperative breaks for mental and physical rest and regeneration. The decision to take a much-needed break is often neglected because of concerns about prolonging the duration of an operation; with proper self-awareness of fatigue and brief mental checks during natural intraoperative slowdowns, however, the surgeon can quickly assess the need for a much-needed moment of recovery. The authors hope surgeons will find the fatigue-mitigation strategies presented here to be helpful in promoting both their own wellness and the safety and wellness of their patients.


Assuntos
Fadiga/prevenção & controle , Cirurgia Geral , Doenças Profissionais/prevenção & controle , Humanos
11.
Ann Plast Surg ; 82(2): 180-183, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30557182

RESUMO

Vascularized osteocutaneous free flaps have seen increasing use in foot and ankle surgery for the repair of bony defects secondary to chronic nonunion, osteomyelitis, and fractures. One example is the Medial Femoral Condyle (MFC) Flap. The utility of the MFC flap for the repair of a bony defect in a diabetic patient, however, has yet to be explored. We report the long-term results of a case describing the use of an MFC flap to reconstruct an osseous defect resulting from first metatarsophalangeal joint resection in a diabetic patient.


Assuntos
Artropatia Neurogênica/cirurgia , Neuropatias Diabéticas/cirurgia , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica/métodos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
12.
Plast Reconstr Surg ; 143(2): 604-613, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30531626

RESUMO

BACKGROUND: In patients with lower extremity wounds, free tissue transfer is often the last option before amputation, making it crucial to optimize preoperative planning to prevent flap breakdown. No consensus exists regarding preoperative vascular workup before lower extremity free tissue transfer. In this study, the authors analyzed the utility of using arteriography for lower extremity free flap planning. METHODS: A retrospective review was performed of 57 patients who underwent lower extremity arteriography and 59 free flap operations for lower extremity wounds between November of 2014 and August of 2017. Findings were used to guide flap recipient vessel selection. Arterial abnormality was addressed by means of endovascular intervention, where appropriate. Encountered abnormality was described and patient demographics, comorbidities, and outcomes were analyzed for correlation with abnormal angiographic studies. RESULTS: Angiographic abnormalities were observed in 40 patients (67.8 percent), including 23 (57.5 percent) with stenosis/occlusion, 20 (50.0 percent) with atretic/nonvisualized vessels, and 11 (27.5 percent) requiring endovascular intervention. Stenosis/occlusion was detected in nine patients (15.3 percent) with no previously known arterial disease, leading to a new diagnosis of peripheral vascular disease. The flap survival rate was 98.3 percent, six patients (10.2 percent) ultimately progressed to amputation, and 53 patients (89.8 percent) were able to continue community ambulation at a mean follow-up time of 15.1 ± 9.51 months (range, 1.67 to 35.2 months). After arteriography, two patients (3.39 percent) suffered contrast-induced acute kidney injury. No other complications were noted. CONCLUSION: Preoperative lower extremity arteriography aids in the diagnosis of peripheral vascular disease, allows for timely endovascular intervention, and allows for optimal flap recipient vessel selection with a low complication rate. CLINICAL QUESTION/LEVEL OF EVIDENC: Diagnostic, IV.


Assuntos
Angiografia , Pé Diabético/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Extremidade Inferior/cirurgia , Doenças Vasculares Periféricas/diagnóstico por imagem , Procedimentos de Cirurgia Plástica , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Pé Diabético/complicações , Feminino , Seguimentos , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/complicações , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Resultado do Tratamento
13.
J Surg Oncol ; 118(5): 840-844, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30114332

RESUMO

There is a growing body of evidence to suggest that surgeon posture while operating contributes to cervical musculoskeletal strain, discomfort, and chronic pain. Microsurgeons may be particularly susceptible to this risk due to persistent neck flexion, long periods of static posture, and the use of heavy, high-power loupe magnification. Several techniques are thus presented that may help in obviating the cervicospinal repercussions of performing microsurgery.


Assuntos
Ergonomia , Microcirurgia , Dor Musculoesquelética/prevenção & controle , Doenças Profissionais/prevenção & controle , Postura , Cirurgiões , Fenômenos Biomecânicos/fisiologia , Vértebras Cervicais/fisiologia , Equipamentos e Provisões , Humanos , Microcirurgia/efeitos adversos , Microcirurgia/instrumentação , Fadiga Muscular , Dor Musculoesquelética/etiologia , Doenças Profissionais/etiologia , Duração da Cirurgia
16.
Plast Reconstr Surg Glob Open ; 6(12): e2005, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30656107

RESUMO

Human acellular dermal matrix (ADM) can augment prepectoral prosthetic-based direct-to-implant breast reconstruction by providing an additional soft-tissue layer between breast implant and skin, as well as to reinforce the inframammary fold and breast pocket. Utilizing ADM in this way has helped reduce rates of implant rippling, capsular contracture, and implant extrusion. Difficulty in securing ADM-wrapped implants has caused many surgeons to improvise techniques for secure implantation. Here, we describe a simple technique for creating suture tabs within the ADM for efficient fixation of the ADM-implant construct to the chest wall.

17.
Sarcoma ; 2017: 8685638, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29138631

RESUMO

BACKGROUND: Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. METHODS: We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). RESULTS: 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. CONCLUSIONS: This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

18.
Pediatr Blood Cancer ; 62(10): 1709-16, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25907661

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder that predisposes affected individuals to formation of benign neurofibromas, peripheral nerve tumors that can be associated with significant morbidity. Loss of the NF1 Ras-GAP protein causes increased Ras-GTP, and we previously found that inhibiting MEK signaling downstream of Ras can shrink established neurofibromas in a genetically engineered murine model. PROCEDURES: We studied effects of MEK inhibition using 1.5 mg/kg/day PD-0325901 prior to neurofibroma onset in the Nf1 (flox/flox); Dhh-Cre mouse model. We also treated mice with established tumors at 0.5 and 1.5 mg/kg/day doses of PD-0325901. We monitored tumor volumes using MRI and volumetric measurements, and measured pharmacokinetic and pharmacodynamic endpoints. RESULTS: Early administration significantly delayed neurofibroma development as compared to vehicle controls. When treatment was discontinued neurofibromas grew, but no rebound effect was observed and neurofibromas remained significantly smaller than controls. Low dose treatment of mice with PD-0325901 resulted in neurofibroma shrinkage equivalent to that observed at higher doses. Tumor cell proliferation decreased, although less than at higher doses with drug. Tumor blood vessels per area correlated with tumor shrinkage. CONCLUSIONS: Neurofibroma development was not prevented by MEK inhibition, beginning at 1 month of age, but tumor size was controlled by early treatment. Moreover, treatment with PD-0325901 at very low doses may shrink neurofibromas while minimizing toxicity. These studies highlight how genetically engineered mouse models can guide clinical trial design.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Difenilamina/análogos & derivados , Inibidores Enzimáticos/farmacologia , MAP Quinase Quinase Quinases/antagonistas & inibidores , Neurofibromatose 1/patologia , Animais , Difenilamina/farmacologia , Modelos Animais de Doenças , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica
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