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1.
Plast Surg (Oakv) ; 32(2): 213-219, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38681249

RESUMO

Introduction: Failure of alloplastic breast reconstruction is an uncommon occurrence that may result in abandonment of reconstructive efforts or salvage with conversion to autologous reconstruction. The purpose of this study was to identify factors that predict failure of alloplastic breast reconstruction and conversion to autologous reconstruction. Methods: A retrospective chart review was conducted of patients who underwent mastectomy and immediate alloplastic breast reconstruction between 2008 and 2019. Inclusion criteria included patients 18 years or older who underwent initial alloplastic reconstruction with a minimum of 3-year follow-up. Data collected included age, body mass index, cancer type, surgical characteristics, neo/adjuvant treatment details, and complications. Results were analyzed using Fischer's exact test, t-test, and multivariate logistic regression. Results: A total of 234 patients met inclusion criteria. Of those, 23 (9.8%) required conversion from alloplastic to autologous reconstruction. Converted patients had a mean age of 50.1 ± 8.5. The time from initial alloplastic reconstruction to conversion was 30.7 months. The most common reasons for conversion included soft tissue deficiency (48%), infection (30%), and capsular contracture (22%). Patients were converted to deep inferior epigastric perforator flap (DIEP; 52%), latissimus dorsi flap with implant (26%), and DIEP with implant (22%). Multivariate logistic regression modeling identified radiation (OR 8.4 [CI = 1.7-40.1]) and periprosthetic infection (OR 14.6 [CI = 3.4-63.8]) as predictors for conversion. Conclusions: Among patients undergoing mastectomy with immediate alloplastic breast reconstruction, those treated with radiation have 8.4 greater odds of conversion and those with a periprosthetic infection have 14.6 greater odds for conversion to an autologous reconstruction.


Introduction : L'échec d'une reconstruction mammaire alloplastique est un événement peu fréquent qui peut aboutir à un abandon des efforts de reconstruction ou à une solution de secours avec une conversion en reconstruction autologue. L'objectif de cette étude était d'identifier les facteurs prédisant l'échec de la reconstruction mammaire alloplastique et sa conversion en reconstruction autologue. Méthodes : Une étude rétrospective a été menée sur les dossiers de patientes ayant subi une mastectomie suivie d'une reconstruction mammaire alloplastique immédiate entre 2008 et 2019. Les critères d'inclusion étaient notamment des patientes âgées d'au moins 18 ans ayant subi une reconstruction alloplastique initiale avec un suivi minimum de 3 ans. La collecte de données a inclus : l'âge, l'indice de masse corporelle (IMC), le type de cancer, les caractéristiques chirurgicales, les détails sur le traitement adjuvant/néoadjuvant et les complications. Les résultats ont été analysés à l'aide du test t exact de Fischer, un test t et une analyse de régression logistique multifactorielle. Résultats : Un total de 234 patientes a satisfait les critères d'inclusion. Parmi ces patientes, 23 (9,8%) ont nécessité la conversion de la reconstruction alloplastique en reconstruction autologue. Les patientes « converties ¼ avaient un âge moyen de 50,1 ± 8,5 ans. Le délai séparant la reconstruction alloplastique initiale et la conversion était de 30,7 mois. Les motifs les plus fréquents de conversion étaient une déficience des tissus mous (48%), une infection (30%) et la formation d'une coque (22%). Les techniques de conversion utilisées étaient la technique dite DIEP ou AEIP (artère épigastrique inférieure profonde, 52%), un lambeau du grand dorsal avec implant (26%), et la technique DIEP avec implant (22%). Une modélisation d'analyse de régression logistique multifactorielle a identifié les facteurs prédictifs de conversion suivants : irradiation (rapport de cotes = 8,4 [IC = 1,7-40,1]) et l'infection périprothétique (RC = 14,6 [IC = 3,4 à 63,8]). Conclusions : Parmi les patientes subissant une mastectomie avec reconstruction mammaire alloplastique immédiate, celles qui ont reçu une radiothérapie avaient un risque de conversion 8,4 fois plus grand et les patientes ayant une infection périprothétique avaient un risque 14,6 fois plus grand de conversion en reconstruction autologue.

2.
Ann Plast Surg ; 91(4): 428-432, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37713149

RESUMO

AIMS: As a result of COVID-19, there have been restrictions on surgical interventions across Canada. Immediate breast reconstruction (IBR), while an essential component of cancer care, is classified as elective surgery and therefore has been restricted in access over the course of the pandemic. The purpose of this study was to compare wait times for breast cancer patients undergoing surgical intervention for IBR before and since the COVID-19 pandemic. METHODS: This was a retrospective cross-sectional study of consecutive patients who underwent IBR between July 2018 and October 2021 by 5 plastic surgeons at a single Canadian health center. Wait times to consultation and surgical intervention between pre- and post-COVID cohorts were analyzed. RESULTS: A total of 161 patients met inclusion criteria. For ablative surgery, there was no difference in wait times to surgical oncology consultation (14.0 ± 12.3 vs 14.0 ± 11.0 days, P = 0.991) and surgical intervention with IBR (41.0 ± 49.8 vs 35.0 ± 58.0 days, P = 0.621) between the pre- and post-COVID cohorts. For breast reconstruction, while time to consultation with plastic surgery (12.5 ± 14.8 vs 11.0 ± 12.8 days, P = 0.775) remained unchanged, usage of autologous techniques was reduced [n = 13 (16%) vs n = 2 (2%), P = 0.006], and time to second-stage alloplastic reconstruction increased (230 ± 102 vs 325 ± 224 days, P = 0.044) post-COVID. CONCLUSIONS: Swift adoption of evidence driven protocols has resulted in comparable wait times for breast cancer ablative procedures. However, utilization of autologous techniques and wait times to second-stage reconstructions have increased.


Assuntos
Neoplasias da Mama , COVID-19 , Mamoplastia , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , Estudos Transversais , Estudos Retrospectivos , Canadá/epidemiologia , Neoplasias da Mama/cirurgia
3.
Aesthet Surg J ; 42(12): 1408-1413, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-35709374

RESUMO

BACKGROUND: The recall of Allergan Biocell (Irvine, CA) devices due to the association between anaplastic large cell lymphoma (ALCL) and macrotextured breast implants means that plastic surgeons are faced with the challenge of caring for patients with these implants in situ. Cosmetic and reconstructive surgeons have been contacting affected patients to encourage them to follow up and discuss the most appropriate risk-reduction strategies. OBJECTIVES: The aim of this study was to evaluate patient concerns about the risk of breast implant-associated ALCL (BIA-ALCL) and to compare management differences between cosmetic and reconstructive patients. METHODS: A retrospective review was performed of 432 patients with macrotextured implants who presented to clinic after being contacted (121 reconstructive and 311 cosmetic). These records were analyzed for their presenting concerns, surgery wait times, and management plans. Statistical analysis was performed to compare the cohorts, and odds ratios (ORs) were computed to determine the association between patient concerns and their choice of management. RESULTS: After consultation, 59.5% of the reconstructive cohort and 49.5% of the cosmetic cohort scheduled implant removal or exchange. The reconstructive population had a higher rate of ALCL concern (62.7%); however, both cohorts had a significant OR, demonstrating an expressed fear of ALCL likely contributed to their subsequent clinical management (OR cosmetic, 1.66; OR reconstructive, 2.17). CONCLUSIONS: Although the risk of ALCL appears to be more concerning to the reconstructive population, both cohorts were equally motivated to have their implants removed. Informing patients about their ALCL risk is crucial to ensure a patient-supported risk reduction plan.


Assuntos
Implante Mamário , Implantes de Mama , Neoplasias da Mama , Linfoma Anaplásico de Células Grandes , Cirurgia Plástica , Humanos , Feminino , Implantes de Mama/efeitos adversos , Linfoma Anaplásico de Células Grandes/epidemiologia , Linfoma Anaplásico de Células Grandes/etiologia , Linfoma Anaplásico de Células Grandes/patologia , Implante Mamário/efeitos adversos , Remoção de Dispositivo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Neoplasias da Mama/cirurgia
4.
Can J Surg ; 64(4): E377-E380, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296592

RESUMO

Summary: The COVID-19 pandemic has caused unprecedented challenges in health care, threatening access and delivery of medical services across all sectors. Patients with breast cancer desiring breast reconstruction require timely interdisciplinary care; resource limitations threaten access to this elective reconstructive element of cancer care. An expert panel was convened to identify challenges, recommend preliminary solutions, and identify important future directions in anticipation of prolonged restrictions. This paper presents consensus recommendations for care of breast cancer reconstruction patients during the pandemic based on expert opinion from the BC Breast Reconstruction Network.


Assuntos
Neoplasias da Mama/cirurgia , COVID-19/epidemiologia , Mamoplastia , Seleção de Pacientes , Algoritmos , Atitude do Pessoal de Saúde , COVID-19/prevenção & controle , Canadá , Consenso , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Triagem
5.
Curr Oncol ; 28(1): 702-715, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33504079

RESUMO

Breast cancer susceptibility gene (BRCA) mutation carriers have an increased risk of breast cancer. Mitigation of this risk can be achieved via surveillance or prophylactic mastectomy with or without breast reconstruction. Those that choose surgery expect to reduce their chance of developing cancer. The purpose of this study was to determine the incidence of patients developing breast cancer prior to surgery and to identify modifiable contributing factors within the patient journey. This is a historical cohort study of all BRCA mutation carriers identified through the British Columbia Cancer Hereditary Cancer Program between 2000 and 2012. Patients were divided into two groups: surveillance (S) and prophylactic mastectomy with immediate breast reconstruction (PM/IBR). The incidence of cancer, time to PM/IBR and patient journeys were analyzed. A total of 333 women were identified. The time to surgery from mutation disclosure was a median of 31 (5.3, 75.7) months. During this period, 6% of patients developed breast cancer compared with a 14% incidence of breast cancer in patients choosing surveillance. The majority of time to surgery was attributed to the period between mutation disclosure and the decision to proceed with surgery. Strategies to facilitate decision-making as well as wait list prioritization and dedicated operative time should be targeted to this population to decrease the number of women developing an interval cancer prior to surgery.


Assuntos
Neoplasias da Mama , Mamoplastia , Mastectomia Profilática , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Mastectomia
7.
Ann Surg Oncol ; 26(5): 1276-1283, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30756328

RESUMO

BACKGROUND: Despite benefits in quality of life, patient satisfaction, overall healthcare costs, and number of surgeries, historically fewer than 30% of patients undergo immediate breast reconstruction following mastectomy for breast cancer. A paucity of qualified oncologic and plastic surgeons coupled with inefficient use of operating room (OR) resources presents challenges in offering immediate breast reconstruction in a timely manner. To address these challenges, an immediate reconstruction swing room (IRSW) program was developed. METHODS: IRSW scheduling leverages two concurrently running ORs, with the surgical oncologist and plastic surgeon moving between rooms to complete 2-4 combined mastectomy cases with immediate reconstruction, in addition to 1-2 independent cases, each operative day. The final year of traditional booking was compared with IRSW scheduling to assess wait times and reconstruction rates. RESULTS: Comparing the 2 years, fewer surgical breast cases were performed with IRSW scheduling (1250 vs. 1178), however the overall number of oncology cases increased from 735 (59%) to 857 (73%). The number of immediate reconstructions performed increased from 75 to 139 (p < 0.0001), which reflects a mean of 1.2 IR cases versus 2.9 combined cases in IRSW. Overall, this facilitated an increase in the rate of immediate reconstruction following therapeutic mastectomy from 35 to 49% (p = 0.0004) and decreased wait times from core biopsy to surgery from 70 to 52 days (p < 0.0001). CONCLUSIONS: A multidisciplinary model with optimized scheduling has the potential to improve resource utilization and access to breast cancer care.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Mamoplastia/estatística & dados numéricos , Mastectomia/métodos , Planejamento de Assistência ao Paciente/normas , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Salas Cirúrgicas , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Listas de Espera
8.
Plast Reconstr Surg ; 140(1): 94e-108e, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28654611

RESUMO

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the different advances that have resulted in improved outcomes in implant-based reconstruction. 2. Gain knowledge about specific techniques that have evolved rapidly in recent years and how to implement these. 3. Gain an understanding of controversies associated with alloplastic reconstruction. 4. Recognize undesirable outcomes in implant-based breast reconstruction and understand strategies for correction. SUMMARY: There have been multiple advances in implant-based breast reconstruction. Many of these have resulted in improvements in patient outcomes and care. Understanding new techniques and technologies ensures competence in providing care for the alloplastic breast reconstruction patient. This article was prepared to accompany practice-based assessment with ongoing surgical education for the Maintenance of Certification for the American Board of Plastic Surgery. It is structured to outline the care of the patient with the postmastectomy breast deformity.


Assuntos
Implante Mamário/métodos , Medicina Baseada em Evidências , Mamoplastia/métodos , Derme Acelular , Tecido Adiposo/transplante , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Fatores de Tempo , Alicerces Teciduais
9.
Plast Reconstr Surg ; 139(1): 204e-229e, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28027256

RESUMO

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Gain an understanding of the different methods of autologous reconstruction available. 2. Understand the timing of autologous breast reconstruction and the impact of adjuvant and neoadjuvant treatments. 3 Understand the factors necessary for a comprehensive patient assessment. 4. Gain knowledge of patient factors that will affect autologous reconstruction and potential contraindications. 5. Summarize the patient-reported and clinical outcomes of autologous breast reconstruction. SUMMARY: This article was prepared to accompany practice-based assessment with ongoing surgical education for the Maintenance of Certification for the American Board of Plastic Surgery. It is structured to outline the care of the patient with the postmastectomy breast deformity.


Assuntos
Mamoplastia/métodos , Adulto , Idoso , Autoenxertos , Medicina Baseada em Evidências , Feminino , Humanos , Pessoa de Meia-Idade , Reoperação , Retalhos Cirúrgicos
10.
Plast Reconstr Surg ; 135(6): 1530-1539, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26017589

RESUMO

BACKGROUND: Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo. METHODS: This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing. RESULTS: The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)]. CONCLUSIONS: In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Nitroglicerina/uso terapêutico , Retalhos Cirúrgicos/patologia , Administração Tópica , Adulto , Idoso , Neoplasias da Mama/patologia , Colúmbia Britânica , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Mamoplastia/efeitos adversos , Pessoa de Meia-Idade , Necrose/tratamento farmacológico , Necrose/patologia , Pomadas/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/patologia , Valores de Referência , Medição de Risco , Retalhos Cirúrgicos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
Plast Reconstr Surg ; 134(1): 1e-10e, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25028850

RESUMO

BACKGROUND: An increasing number of women who undergo immediate two-stage tissue expander/implant breast reconstruction will require postmastectomy radiation therapy. An important variable is the timing of radiotherapy relative to surgery. The authors report their experience treating a large consecutive series of patients who underwent postmastectomy radiation therapy to the tissue expander before exchange for a permanent implant. METHODS: Patients who had their tissue expander irradiated before implant exchange were identified. Complications, capsular contracture, revision surgery, and autologous salvage rates of irradiated patients were compared with a control group of nonirradiated patients. RESULTS: Immediate two-stage tissue expander/implant reconstruction was initiated in 604 patients, with 113 irradiated breasts meeting inclusion criteria. Three hundred thirty-nine nonirradiated breasts constituted the control group. There was a 4.2 increased odds of major complications in the irradiated group, after adjusting for plastic surgeon, age, body mass index, smoking, chemotherapy, and cancerous breast (OR, 4.2; p=0.001). The grade III and IV capsular contracture rate was significantly higher in the irradiated group compared with the control group (21.7 percent versus 10 percent; p<0.008). The revision rate in the control group was higher compared with the irradiated group (30.2 percent versus 20.9 percent; p<0.001). CONCLUSIONS: Postmastectomy irradiation to the tissue expander is associated with high complications; however, these patients have an acceptable capsular contracture rate that compares favorably with other implant-based radiotherapy algorithms. Revision rates were less than expected in irradiated breasts. This study suggests that immediate tissue expander/implant reconstruction is a reasonable surgical option in the setting of postmastectomy radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Implante Mamário/métodos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Cuidados Pós-Operatórios , Expansão de Tecido/métodos , Adulto , Idoso , Colúmbia Britânica , Protocolos Clínicos , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Universidades , Adulto Jovem
12.
Plast Reconstr Surg ; 133(6): 738e-747e, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24867734

RESUMO

BACKGROUND: Direct-to-implant single-stage immediate breast reconstruction using acellular dermal matrix is a cost-effective alternative to two-stage expander-implant reconstruction. The purpose of this study was to identify predictors of direct-to-implant single-stage immediate breast reconstruction failure, defined as need for early (≤6 months) revision surgery. METHODS: The authors conducted a retrospective cohort study of all patients with direct-to-implant single-stage immediate breast reconstruction in 2010 and 2011 at three University of British Columbia hospitals. Data were compared between successful and failed single-stage reconstructions. Predictors of failure were identified using multivariate logistic regression. Patient demographics and complications were compared to a random sample of control patients with two-stage alloplastic reconstruction without acellular dermal matrix. RESULTS: Of 164 breasts that underwent direct-to-implant single-stage immediate breast reconstruction, 52 (31.7 percent) required early revision. Increasing breast cup size was the only significant predictor of early revision compared with bra size A (OR for bra size B, 4.86; C, 4.96; D, 6.01; p < 0.05). Prophylactic mastectomies showed a trend toward successful single stage (OR, 0.47; p = 0.061), whereas smoking history trended toward failure (OR, 1.79; p = 0.065). Mastectomy flap necrosis was significantly higher in direct-to-implant single-stage immediate reconstruction cases compared to two-stage controls. CONCLUSIONS: Direct-to-implant breast reconstruction can be reliably performed in a single stage in patients with small breast size. Increasing breast cup size confers a higher chance of early revision. A two-stage approach may be more cost-effective in larger breasted patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Assuntos
Derme Acelular , Implante Mamário/métodos , Adulto , Idoso , Implante Mamário/efeitos adversos , Feminino , Humanos , Contratura Capsular em Implantes/epidemiologia , Modelos Logísticos , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
14.
J Plast Reconstr Aesthet Surg ; 65(10): 1390-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22652292

RESUMO

INTRODUCTION: We have previously shown 28.6% of re-excisions for margin-positive cutaneous SCC to yield residual tumour (positive re-excision). Original tumour diameter and thickness conferred significant risks for positive re-excision. We now report a 5-year prospective follow-up of our re-excision cohort. RESULTS: Of 676 consecutive SCC patients, 84 underwent wider-excision for positive margins. 79 of these patients completed a mean of 28 months follow-up. Overall, 9/79 (11%) of this re-excision cohort experienced locoregional recurrence, all within 2 years of primary resection. Of the positive re-excisions, 29% experienced recurrence, vs 5% in those with negative re-excisions. Logistic-regression analysis revealed positive re-excision to predict recurrence (P<0.05, RR 10.1), independent from tumour-grade, anatomical site, size, and delay to re-excision. CONCLUSION: Factors associated with residual tumour on re-excision are similar to characteristics of high-risk SCCs; larger tumours in particular are more likely to persist and may benefit from wider excision-margins at original resection. Positive re-excision is newly identified as a significant risk for locoregional recurrence, whilst negative re-excision is associated with a return to a low-risk prognosis, for all tumours. Our findings thus support the treatment of cutaneous SCC through to completion. We also recommend re-excision where narrow or close margins are reported. Patients with a positive re-excision should be considered at high risk for recurrence, requiring extended follow-up.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Neoplasias Cutâneas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/mortalidade , Prognóstico , Estudos Prospectivos , Reoperação/métodos , Medição de Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Resultado do Tratamento , Reino Unido
17.
J Thorac Cardiovasc Surg ; 137(4): 853-61, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19327508

RESUMO

OBJECTIVE: We sought to identify changes in four-and-a-half LIM-protein 2 levels and location in human cardiomyocytes during the transition from compensated aortic stenosis to left ventricular failure. We also sought to characterize four-and-a-half LIM-protein 2 binding with the metabolic enzymes phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform during this transition and their consequential subcellular localization in failing human ventricles. METHODS: Left ventricular biopsy specimens from selected patients undergoing aortic valve replacement for aortic stenosis were allocated to one of 2 groups: (1) nondilated with preserved left ventricular function (nonfailing group, n = 16) and (2) grossly dilated with poor left ventricular function (failing group, n = 15). These were compared with a control group of unused donor hearts (n = 6). Protein levels and subcellular localization were determined by means of Western blotting and immunofluorescence. Four-and-a-half LIM-protein 2 binding to adenylate kinase, creatine kinase M isoform, or phosphofructokinase 2 was studied by means of coimmunoprecipitation. Phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform activities were assayed in protein extractions. RESULTS: Four-and-a-half LIM-protein 2 levels were preserved in nonfailing hypertrophied hearts but reduced by 53% in failing hearts. The pattern of four-and-a-half LIM-protein 2 staining was disrupted in failing hearts: four-and-a-half LIM-protein 2 was lost from the sarcomere but present in the perinuclear Golgi apparatus complex. Phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform coimmunoprecipitated in vitro and colocalized with four-and-a-half LIM-protein 2 in both hypertrophied and failing hearts. Phosphofructokinase 2 and adenylate kinase activities were reduced to 77% and 58% of normal values in compensated aortic stenosis, with phosphofructokinase 2 activity decreased further to 56% of normal value in failing hearts, but creatine kinase activity remained unchanged. CONCLUSIONS: Altered four-and-a-half LIM-protein 2 expression in heart failure is associated with disruption of the normal subcellular localization of phosphofructokinase 2, adenylate kinase, and creatine kinase M isoform and reduced activity of phosphofructokinase 2 and adenylate kinase, which might have important consequences for myocardial energy metabolism in heart failure.


Assuntos
Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/fisiopatologia , Proteínas de Homeodomínio/biossíntese , Proteínas Musculares/biossíntese , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/biossíntese , Adulto , Idoso , Estenose da Valva Aórtica/fisiopatologia , Feminino , Humanos , Proteínas com Homeodomínio LIM , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/enzimologia
18.
J Thorac Cardiovasc Surg ; 136(3): 709-16, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18805276

RESUMO

OBJECTIVE: We identified changes in Jumonji (JARID2) expression in failing human hearts and determined its effects on expressions of atrial natriuretic factor (ANF), myosin light chain 2a (MLC2A), and alpha myosin heavy chain (MHCA), genes associated with both human heart failure and the fetal gene program. METHODS: Left ventricular outflow tract cardiac biopsy samples were taken from 31 patients with aortic valvular stenosis. Hearts were grouped according to left ventricular size and function: nonfailing hearts (undilated with good function) and failing hearts (dilated with poor function). Protein levels were determined by Western blotting, and messenger RNA transcript levels by ratiometric reverse transcriptase-polymerase chain reaction. Luciferase assays in HL-2 cells were used to assess effects of Jarid2 on Anf, Mlc2a, and Mhca transcriptions. Chromatin immunoprecipitation was used to detect interaction of JARID2 with specific target-gene promoters. RESULTS: JARID2 and MHCA expressions were reduced in failing hearts, whereas MLC2A and ANF were increased. In HL-2 cell culture, Jarid2 suppressed Anf and Mlc2a but enhanced Mhca. Jarid2 expression was reduced by cyclic mechanical stress, with concomitant increased Anf and Mlc2a and decreased Mhca expressions, reproducing the expression profile found in decompensated human pressure overload. CONCLUSION: Jumonji expression is reduced by mechanical stress in human heart failure from aortic stenosis. JARID2 regulates ANF, MLC2A, and MHCA transcription and contributes to reexpression of the fetal gene program in decompensated aortic stenosis. JARID2 appears important in transcriptional regulation of fetal genes and may emerge as a diagnostic marker for left ventricular decompensation in aortic stenosis.


Assuntos
Fator Natriurético Atrial/análise , Miosinas Cardíacas/análise , Insuficiência Cardíaca/genética , Cadeias Leves de Miosina/análise , Proteínas do Tecido Nervoso/genética , Transcrição Gênica/fisiologia , Miosinas Ventriculares/análise , Animais , Estenose da Valva Aórtica/complicações , Western Blotting , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Camundongos , Pessoa de Meia-Idade , Complexo Repressor Polycomb 2 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Mecânico , Fatores de Transcrição/análise
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