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1.
Surg Endosc ; 29(7): 2039-45, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25361647

RESUMO

AIM: Atrial fibrillation (AF) has been associated with higher morbidity after esophagectomy. The objective of this study is to identify the surgical risk factors associated with new-onset atrial fibrillation after esophagectomy. METHODS: After Institutional Review Board approval, a prospectively maintained database was retrospectively queried to identify patients who underwent esophagectomy between 2003 and 2013. Data variables collected include pre-operative, intra-operative, and post-operative factors. Appropriate statistical analysis is performed utilizing Sigmaplot(®) version 12.3. RESULTS: From 2003 to 2013, 245 esophagectomies were performed at our institution, of these, 192 (147 males, mean age of 62 ± 11.12 years) were included in the final analysis and 53 were excluded [25 Roux-en-Y reconstruction (including three Merendino procedures), 20 had AF before surgery, and eight with staged esophagectomy]. Of 192 esophagectomies, 160 had malignancy (138 adenocarcinoma and 22 squamous cell carcinoma) and 106 (66.25%) received neo-adjuvant therapy. Esophagectomies were performed with Ivor Lewis Mckeown approach in 78 patients [34 Minimally Invasive (MIE), 37 open, and 7 Hybrid], Ivor Lewis approach in 56 patients (31 MIE, 10 Open, 15 Hybrid) and Transhiatal approach in 58 patients (16 MIE and 42 Open). Gastric conduit was used in 185 patients and colonic conduit in seven patients. Overall 30-day or in-hospital mortality was 3.6% (7/192). Forty-five (23.4%) patients with esophagectomy developed new-onset AF. Median onset of AF was post-op day 3 (0-32). They were older (65.7 vs. 61.3, p = 0.021), with medical comorbidities (thyroid disorder, hyperlipidemia, and coronary artery disease; p < 0.05) and lower diffusion capacity on Pulmonary function test (80.16 vs. 87.74%, p = 0.02) and stayed longer in hospital (19 vs. 14 days, p < 0.001) with severe post-operative complications (Clavien score ≥ III) (69 vs. 35.3%, p < 0.001). Multiple logistic regression analysis showed transthoracic approach (OR = 3.71, CI = 1.23-11.17, p = 0.02) and thyroid disorder (OR = 6.29, CI = 1.54-25.65, p = 0.01), and severe post-op complications (OR = 3.34, CI = 1.20-9.28, p = 0.02) were significantly associated with the development of new-onset AF. CONCLUSIONS: Transthoracic approach is an independent risk factor for the development of new-onset AF after esophagectomy. New-onset AF is associated with severe post-operative complications and longer hospital stay. Minimally invasive approach does not decrease the incidence of new-onset AF.


Assuntos
Adenocarcinoma/cirurgia , Fibrilação Atrial/epidemiologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Hiperlipidemias/epidemiologia , Incidência , Laparoscopia/métodos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Análise Multivariada , Capacidade de Difusão Pulmonar , Estudos Retrospectivos , Fatores de Risco , Doenças da Glândula Tireoide/epidemiologia
2.
Methodist Debakey Cardiovasc J ; 19(1): 43-48, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37188100

RESUMO

Left ventricular assist devices (LVAD) can be utilized for heart failure patients as a bridge to transplant, bridge to destination, or bridge to recovery. Given the lack of a universally accepted consensus for assessing myocardial recovery, techniques and strategies in LVAD explantation also vary. In addition, the incidence of LVAD explantation remains relatively low, and surgical techniques of explantation continue to be areas of interest. Our approach using a felt-plug Dacron technique is an effective way to preserve left ventricular geometry and cardiac function.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Humanos , Estudos Retrospectivos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Miocárdio , Remoção de Dispositivo/métodos
3.
Breast Cancer Res ; 12(1): R12, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20149218

RESUMO

INTRODUCTION: Most breast cancers that occur in women with germline BRCA1 mutations are estrogen receptor-negative (ER-) and also typically lack expression of progesterone receptor (PR) and HER2 overexpression. We undertook a study to assess the clinical factors that predict for an estrogen receptor positive (ER+) breast cancer in BRCA1 mutation carriers and to characterize the pathologic features of these tumors. METHODS: Clinical characteristics of BRCA1 carriers with 58 ER+ and 114 ER- first invasive breast cancers were compared. Pathologic features of BRCA1 ER+ cancers were compared to those of BRCA1 ER- cancers and to age-matched ER+ sporadic cancers. RESULTS: BRCA1 carriers aged > or = 50 at diagnosis of first invasive breast cancer were more likely to have an ER+ cancer compared to those aged < 50 (57% vs 29%, P = 0.005). ER+ BRCA1 cancers were less likely than ER- BRCA1 cancers to have "BRCA-associated" features such as high mitotic activity, geographic necrosis/fibrotic focus, and pushing margins (RR 0.06, 0.22, 0.24; P < 0.001, 0.02, 0.03 respectively). When compared to sporadic ER+ cancers, ER+ BRCA1 cancers were more often of invasive ductal type (RR 2.4, P = 0.03), with a high mitotic rate (RR 5.0, P = 0.006) and absent or mild lymphocytic infiltrate (RR 10.2, P = 0.04). CONCLUSIONS: BRCA1 carriers who are older at first breast cancer diagnosis are more likely to have ER+ tumors than younger BRCA1 carriers. These ER+ cancers appear pathologically "intermediate" between ER- BRCA1 cancers and ER+ sporadic breast cancers raising the possibility that either some ER+ BRCA1 cancers are incidental or that there is a unique mechanism by which these cancers develop.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Heterozigoto , Mutação , Receptores de Estrogênio/análise , Adulto , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
4.
Breast Cancer Res ; 12(6): R95, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21080930

RESUMO

INTRODUCTION: The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to develop as BRCA1 carriers age, suggesting that they may be incidental and unrelated to BRCA1 deficiency. The purpose of this study was to compare the prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+ and ER- breast cancers that have occurred in BRCA1 carriers and to determine whether age at diagnosis or any pathologic features or biomarkers predict for loss of wt BRCA1 in these breast cancers. METHODS: Relative amounts of mutated and wt BRCA1 DNA were measured by quantitative polymerase chain reaction performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER- invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation was determined on all cancers in which sufficient DNA was available. Immunostains for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53 were performed on paraffin sections from tissue microarrays containing these cancers. RESULTS: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1-associated cancers (81.0% vs 88.6%, respectively; P = 0.53). One of nine cancers tested that retained wt BRCA1 demonstrated BRCA1 gene methylation. Age at diagnosis was not significantly different between first invasive ER+ BRCA1 breast cancers with and without loss of wt BRCA1 (mean age 45.2 years vs 50.1 years, respectively; P = 0.51). ER+ BRCA1 cancers that retained wt BRCA1 were significantly more likely than those that lost wt BRCA1 to have a low mitotic rate (odds ratio (OR), 5.16; 95% CI, 1.91 to ∞). BRCA1 cancers with loss of wt BRCA1 were more likely to express basal cytokeratins CK 5/6 or 14 (OR 4.7; 95% CI, 1.85 to ∞). CONCLUSIONS: We found no difference in the prevalence of loss of wt BRCA1 between ER+ and ER- invasive BRCA1-associated breast cancers. Our findings suggest that many of the newer therapies for BRCA1 breast cancers designed to exploit the BRCA1 deficiency in these cancers may also be effective in ER+ cancers that develop in this population.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Genes BRCA1 , Receptores de Estrogênio/genética , Fatores Etários , Biomarcadores Tumorais , Neoplasias da Mama/patologia , Metilação de DNA , Receptores ErbB/análise , Feminino , Humanos , Queratinas/análise , Análise em Microsséries , Mutação , Reação em Cadeia da Polimerase , Receptores de Estrogênio/análise , Proteína Supressora de Tumor p53/análise
8.
Am J Surg Pathol ; 36(10): 1483-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22613997

RESUMO

Although most breast cancers in BRCA1 mutation carriers are estrogen receptor negative (ER-) with a basal-like phenotype, up to one third are ER positive (ER+). Little is known about the characteristics of this subgroup. To address this, we compared histologic and immunophenotypic features of 60 BRCA1-related ER+ breast cancers with those of 85 BRCA1-related ER- cancers and 174 matched ER+ sporadic cancers. ER+ BRCA1-related cancers were significantly less likely than ER- BRCA1-related cancers to be of pure invasive ductal type (P<0.001) and to be of histologic grade 3 (P<0.001), and less frequently to have a high mitotic rate (P<0.001), pushing (or unknown) margins (P<0.001), a moderate/marked lymphocytic infiltrate (P=0.003), or geographic necrosis/fibrotic focus (P<0.001). In addition, ER+ BRCA1-related cancers less often expressed CK5/6 (P<0.0001), CK14 (P<0.0001), and epidermal growth factor receptor (P<0.0001) and more often expressed progesterone receptor (P<0.0001). In contrast, when compared with ER+ sporadic cancers, ER+ BRCA1-related cancers were significantly more often of invasive ductal type (P=0.005) and of histologic grade 3 (P=0.006), more frequently had a high mitotic rate (P=0.0003), and were more often CK14+ (P=0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more closely with sporadic ER+ cancers, whereas others clustered more closely with ER- BRCA1-related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1 in ER+ BRCA1-related cancers were similar to those in ER- BRCA1-related cancers but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1-related breast cancers show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers as well as some similarities to ER- BRCA1-related cancers.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/patologia , Mutação , Receptores de Estrogênio/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Análise por Conglomerados , Feminino , Fibrose , Heterozigoto , Humanos , Imunofenotipagem , Necrose , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Análise Serial de Tecidos
9.
Cancer Discov ; 2(6): 503-11, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22628410

RESUMO

BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , PTEN Fosfo-Hidrolase/genética , Proteína Supressora de Tumor p53/genética , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Mutação , PTEN Fosfo-Hidrolase/metabolismo , Proteína Supressora de Tumor p53/metabolismo
10.
Horm Mol Biol Clin Investig ; 2(1): 177-90, 2010 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25961191

RESUMO

The objective of this review was to examine data from preclinical, clinical and epidemiological studies to evaluate if testosterone (T) poses increased risk of breast cancer in women. Appraisal of the existing literature produced several lines of evidence arguing against increased breast cancer risk with T. These include: (i) Data from breast tumor cell lines treated with androgens did not corroborate the notion that T increases breast cancer risk. On the contrary, androgens appear to be protective, as they inhibit tumor cell growth. (ii) Many of the epidemiological studies claiming an association between T and breast cancer did not adjust for estrogen levels. Studies adjusted for estrogen levels reported no association between T and breast cancer. (iii) Data from clinical studies with exogenous androgen treatment of women with endocrine and sexual disorders did not show any increase in incidence of breast cancer. (iv) Women afflicted with polycystic ovary disease, who exhibit high levels of androgens do not show increased risk of breast cancer compared to the general population. (v) Female to male transsexuals, who receive supraphysiological doses of T for long time periods prior to surgical procedures, do not report increased risk of breast cancer. (vi) Finally, women with hormone responsive primary breast cancer are treated with aromatase inhibitors, which block conversion of androgens to estrogens, thus elevating androgen levels. These women do not experience increased incidence of contralateral breast cancer nor do they experience increased tumor growth. In conclusion, the evidence available strongly suggests that T does not increase breast cancer risk in women.

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