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1.
J Public Health (Oxf) ; 45(2): e266-e274, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-36321614

RESUMO

BACKGROUND: Screening options for pancreatic ductal adenocarcinoma (PDAC) are limited. New-onset type 2 diabetes (NoD) is associated with subsequent diagnosis of PDAC in observational studies and may afford an opportunity for PDAC screening. We evaluated this association using a large administrative database. METHODS: Patients were identified using claims data from the OptumLabs® Data Warehouse. Adult patients with NoD diagnosis were matched 1:3 with patients without NoD using age, sex and chronic obstructive pulmonary disease (COPD) status. The event of PDAC diagnosis was compared between cohorts using the Kaplan-Meier method. Factors associated with PDAC diagnosis were evaluated with Cox's proportional hazards modeling. RESULTS: We identified 640 421 patients with NoD and included 1 921 263 controls. At 3 years, significantly more PDAC events were identified in the NoD group vs control group (579 vs 505; P < 0.001). When controlling for patient factors, NoD was significantly associated with elevated risk of PDAC (HR 3.474, 95% CI 3.082-3.920, P < 0.001). Other factors significantly associated with PDAC diagnosis were increasing age, increasing age among Black patients, and COPD diagnosis (P ≤ 0.05). CONCLUSIONS: NoD was independently associated with subsequent diagnosis of PDAC within 3 years. Future studies should evaluate the feasibility and benefit of PDAC screening in patients with NoD.


Assuntos
Carcinoma Ductal Pancreático , Diabetes Mellitus Tipo 2 , Neoplasias Pancreáticas , Adulto , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/complicações , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/epidemiologia , Carcinoma Ductal Pancreático/complicações , Estudos Retrospectivos , Neoplasias Pancreáticas
2.
Artigo em Inglês | MEDLINE | ID: mdl-30588087

RESUMO

Axillary web syndrome (AWS) is a common condition occurring in up to 86% of patients following breast cancer surgery with ipsilateral lymphadenectomy of one or more nodes. AWS presents as a single cord or multiple thin cords in the subcutaneous tissues of the ipsilateral axilla. The cords may extend variable distances "down" the ipsilateral arm and/or chest wall. The cords frequently result in painful shoulder abduction and limited shoulder range of motion. AWS most frequently becomes symptomatic between 2 and 8 weeks postoperatively but can also develop and recur months to years after surgery. Education about and increased awareness of AWS should be promoted for patients and caregivers. Assessments for AWS should be performed on a regular basis following breast cancer surgery especially if there has been associated lymphadenectomy. Physical therapy, which consists of manual therapy, exercise, education, and other rehabilitation modalities to improve range of motion and decrease pain, is recommended in the treatment of AWS.

3.
Chem Soc Rev ; 47(10): 3737-3758, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-29748676

RESUMO

Life's diverse molecular functions are largely based on only a small number of highly conserved building blocks - the twenty canonical amino acids. These building blocks are chemically simple, but when they are organized in three-dimensional structures of tremendous complexity, new properties emerge. This review explores recent efforts in the directed discovery of functional nanoscale systems and materials based on these same amino acids, but that are not guided by copying or editing biological systems. The review summarises insights obtained using three complementary approaches of searching the sequence space to explore sequence-structure relationships for assembly, reactivity and complexation, namely: (i) strategic editing of short peptide sequences; (ii) computational approaches to predicting and comparing assembly behaviours; (iii) dynamic peptide libraries that explore the free energy landscape. These approaches give rise to guiding principles on controlling order/disorder, complexation and reactivity by peptide sequence design.


Assuntos
Nanoestruturas/química , Nanotecnologia , Peptídeos/química , Sequência de Aminoácidos , Simulação de Dinâmica Molecular , Estrutura Molecular , Tamanho da Partícula , Termodinâmica
4.
Br J Surg ; 105(2): e121-e130, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29341149

RESUMO

BACKGROUND: Modern advances in genetic sequencing techniques have allowed for increased availability of genetic testing for hereditary cancer syndromes. Consequently, more people are being identified as mutation carriers and becoming aware of their increased risk of malignancy. Testing is commonplace for many inheritable cancer syndromes, and with that comes the knowledge of being a gene carrier for some patients. With increased risk of malignancy, many guidelines recommend that gene carriers partake in risk reduction strategies, including risk-reducing surgery for some syndromes. This review explores the quality-of-life consequences of genetic testing and risk-reducing surgery. METHODS: A narrative review of PubMed/MEDLINE was performed, focusing on the health-related quality-of-life implications of surgery for hereditary breast and ovarian cancer, familial adenomatous polyposis and hereditary diffuse gastric cancer. RESULTS: Risk-reducing surgery almost uniformly decreases cancer anxiety and affects patients' quality of life. CONCLUSION: Although the overwhelming quality-of-life implications of surgery are neutral to positive, risk-reducing surgery is irreversible and can be associated with short- and long-term side-effects.


Assuntos
Testes Genéticos/métodos , Síndromes Neoplásicas Hereditárias/genética , Qualidade de Vida/psicologia , Predisposição Genética para Doença , Humanos , Síndromes Neoplásicas Hereditárias/psicologia , Síndromes Neoplásicas Hereditárias/cirurgia , Comportamento de Redução do Risco , Oncologia Cirúrgica/métodos
5.
Org Biomol Chem ; 15(31): 6541-6547, 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28745772

RESUMO

There is significant interest in the use of unmodified self-assembling peptides as building blocks for functional, supramolecular biomaterials. Recently, dynamic peptide libraries (DPLs) have been proposed to select self-assembling materials from dynamically exchanging mixtures of dipeptide inputs in the presence of a nonspecific protease enzyme, where peptide sequences are selected and amplified based on their self-assembling tendencies. It was shown that the results of the DPL of mixed sequences (e.g. starting from a mixture of dileucine, L2, and diphenylalanine, F2) did not give the same outcome as the separate L2 and F2 libraries (which give rise to the formation of F6 and L6), implying that interactions between these sequences could disrupt the self-assembly. In this study, coarse grained molecular dynamics (CG-MD) simulations are used to understand the DPL results for F2, L2 and mixed libraries. CG-MD simulations demonstrate that interactions between precursors can cause the low formation yield of hexapeptides in the mixtures of dipeptides and show that this ability to disrupt is influenced by the concentration of the different species in the DPL. The disrupting self-assembly effect between the species in the DPL is an important effect to take into account in dynamic combinatorial chemistry as it affects the possible discovery of new materials. This work shows that combined computational and experimental screening can be used complementarily and in combination providing a powerful means to discover new supramolecular peptide nanostructures.


Assuntos
Nanoestruturas/química , Biblioteca de Peptídeos , Peptídeos/química , Simulação de Dinâmica Molecular
6.
Soft Matter ; 12(40): 8307-8315, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27722469

RESUMO

Despite progress, a fundamental understanding of the relationships between the molecular structure and self-assembly configuration of Fmoc-dipeptides is still in its infancy. In this work, we provide a combined experimental and computational approach that makes use of free energy equilibration of a number of related Fmoc-dipeptides to arrive at an atomistic model of Fmoc-threonine-phenylalanine-amide (Fmoc-TF-NH2) which forms twisted fibres. By using dynamic peptide libraries where closely related dipeptide sequences are dynamically exchanged to eventually favour the formation of the thermodynamically most stable configuration, the relative importance of C-terminus modifications (amide versus methyl ester) and contributions of aliphatic versus aromatic amino acids (phenylalanine F vs. leucine L) is determined (F > L and NH2 > OMe). The approach enables a comparative interpretation of spectroscopic data, which can then be used to aid the construction of the atomistic model of the most stable structure (Fmoc-TF-NH2). The comparison of the relative stabilities of the models using molecular dynamic simulations and the correlation with experimental data using dynamic peptide libraries and a range of spectroscopy methods (FTIR, CD, fluorescence) allow for the determination of the nanostructure with atomistic resolution. The final model obtained through this process is able to reproduce the experimentally observed formation of intertwining fibres for Fmoc-TF-NH2, providing information of the interactions involved in the hierarchical supramolecular self-assembly. The developed methodology and approach should be of general use for the characterization of supramolecular structures.


Assuntos
Dipeptídeos/química , Fluorenos/química , Simulação de Dinâmica Molecular , Estrutura Molecular , Nanoestruturas
7.
Phys Chem Chem Phys ; 18(6): 4659-67, 2016 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-26794129

RESUMO

Aromatic peptide amphiphiles are known to self-assemble into nanostructures but the molecular level structure and the mechanism of formation of these nanostructures is not yet understood in detail. Molecular dynamic simulations using the CHARMM force field have been applied to a wide variety of peptide-based systems to obtain molecular level details of processes that are inaccessible with experimental techniques. However, this force field does not include parameters for the aromatic moieties which dictate the self-assembly of these systems. The standard CHARMM force field parameterization protocol uses hydrophilic interactions for the non-bonding parameters evaluation. However, to effectively reproduce the self-assembling behaviour of these molecules, the balance between the hydrophilic and hydrophobic nature of the molecule is essential. In this work, a modified parameterization protocol for the CHARMM force field for these aromatic moieties is presented. This protocol is applied for the specific case of the Fmoc moiety. The resulting set of parameters satisfies the conformational and interactions analysis and is able to reproduce experimental results such as the Fmoc-S-OMe water/octanol partition free energy and the self-assembly of Fmoc-S-OH and Fmoc-Y-OH into spherical micelles and fibres, respectively, while also providing detailed information on the mechanism of these processes. The effectiveness of the parameters for the Fmoc moiety validates the protocol as a robust approach to paramterise this class of compounds.


Assuntos
Peptídeos/química , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Nanoestruturas , Teoria Quântica
8.
Chem Sci ; 7(8): 5160-5170, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30155166

RESUMO

Infrared surface enhanced Raman scattering (SERS) is an attractive technique for the in situ detection of nanoprobes in biological samples due to the greater depth of penetration and reduced interference compared to SERS in the visible region. A key challenge is to understand the surface layer formed in suspension when a specific label is added to the SERS substrate in aqueous suspension. SERS taken at different wavelengths, theoretical calculations, and surface-selective sum frequency generation vibrational spectroscopy (SFG-VS) were used to define the surface orientation and manner of attachment of a new class of infrared SERS labels with a thiopyrylium core and four pendant 2-selenophenyl rings. Hollow gold nanospheres (HGNs) were used as the enhancing substrate and two distinct types of SERS spectra were obtained. With excitation close to resonance with both the near infrared electronic transition in the label (max 826 nm) and the plasmon resonance maximum (690 nm), surface enhanced resonance Raman scattering (SERRS) was obtained. SERRS indicates that the major axis of the core is near to perpendicular to the surface plane and SFG-VS obtained from a dried gold film gave a similar orientation with the major axis at an angle 64-85° from the surface plane. Longer excitation wavelengths give SERS with little or no molecular resonance contribution and new vibrations appeared with significant displacements between the thiopyrylium core and the pendant selenophene rings. Analysis using calculated spectra with one or two rings rotated indicates that two rings on one end are rotated towards the metal surface to give an arrangement of two selenium and one sulphur atoms directly facing the gold structure. The spectra, together with a space filled model, indicate that the molecule is strongly adsorbed to the surface through the selenium and sulphur atoms in an arrangement which will facilitate layer formation.

9.
Org Biomol Chem ; 12(22): 3598-603, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24756541

RESUMO

The use of alternative solvents in the iridium-catalysed hydrogen isotope exchange reaction with developing phosphine/NHC Ir(I) complexes has identified reaction media which are more widely applicable and industrially acceptable than the commonly employed chlorinated solvent, dichloromethane. Deuterium incorporation into a variety of substrates has proceeded to deliver high levels of labelling (and regioselectivity) in the presence of low catalyst loadings and over short reaction times. The preparative outputs have been complemented by DFT studies to explore ligand orientation, as well as solvent and substrate binding energies within the catalyst system.


Assuntos
Química Orgânica/métodos , Medição da Troca de Deutério/métodos , Hidrogênio/química , Irídio/química , Anilidas/química , Catálise , Conformação Molecular , Niclosamida/química , Solventes/química
10.
Br J Surg ; 97(5): 707-13, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20235085

RESUMO

BACKGROUND: Evolving evidence suggests that, in selected patients with tumour category 1 (T1) extremity soft tissue sarcoma (ESTS), surgery alone offers satisfactory results without decreasing survival. This study assessed the effect of sarcoma treatments on survival outcomes of T1 ESTS in a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results database, 1618 patients with primary ESTS underwent limb-sparing surgery. Multivariable analysis was used to assess the impact of radiotherapy on overall survival (OS) and sarcoma-specific survival (SSS), adjusting for co-variables. RESULTS: Some 803 patients (49.6 per cent) underwent surgery alone for T1 ESTS. Radiotherapy in patients with low- and high-grade tumours did not result in any significant difference in OS or SSS. When stratified by grade, multivariable analysis showed that adjuvant radiotherapy was not an independent predictor of SSS (hazard ratio (HR) 1.05; P = 0.906) or OS (HR 0.89; P = 0.695) in low-grade tumours. Neither was radiotherapy a significant predictor of SSS (HR 0.87; P = 0.608) or OS (HR 0.67; P = 0.071) in high-grade tumours. CONCLUSION: This population-based appraisal validated previous evidence supporting a role for surgery alone in the treatment of T1 ESTS. Future policies should be tailored to offer patients minimal yet effective therapy, rather than maximum tolerated therapy.


Assuntos
Extremidades , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia Adjuvante , Sarcoma/mortalidade , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/radioterapia , Adulto Jovem
11.
Magn Reson Med ; 61(5): 1232-7, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19235916

RESUMO

We report initial results with single voxel spectroscopy (SVS) using diffusion weighting and localization by adiabatic selective refocusing (LASER) in breast tumors to measure the apparent diffusion coefficient of water (ADCw). This is a quick (30 s) and relatively easy method to implement compared with image-based diffusion measurements, and is insensitive to lipid signal contamination. The ADCw and concentration of total choline containing compounds [tCho] were evaluated for associations with each other and final pathologic diagnosis in 25 subjects. The average (+/- SD) ADCw in benign and malignant lesions was 1.96 +/- 0.47 mm(2)/s and 1.26 +/- 0.29 x 10(-3) mm(2)/s, respectively, P< 0.001. Receiver operating characteristic curve analysis showed an area under the curve of 0.92. Analysis of the single voxel (SV) ADCw and [tCho] showed significant correlation with a R(2) of 0.56, P< 0.001. Compared with more commonly used image-based methods of measuring water ADC, SV-ADCw is faster, more robust, insensitive to fat, and potentially easier to implement on standard clinical systems.


Assuntos
Algoritmos , Água Corporal , Neoplasias da Mama/química , Neoplasias da Mama/diagnóstico , Espectroscopia de Ressonância Magnética/métodos , Água/análise , Adulto , Difusão , Estudos de Viabilidade , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
12.
Minerva Ginecol ; 57(3): 293-303, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16166937

RESUMO

Sentinel lymph node (SLN) biopsy has replaced routine axillary lymph node dissection (ALND) for most breast cancer patients with clinically normal lymph nodes. The morbidity (lymphedema, arm numbness) of SLN biopsy is significantly less than ALND. The use of alternative injection sites (skin or subareolar) yields high SLN identification rates and may shorten the learning curve associated with standard peritumoral injection. The dual-agent (radiocolloid plus blue dye) technique is recommended to decrease false-negative rates, especially when surgeons are just learning how to perform SLN biopsy. Regardless of the technique employed, SLN identification rates should be > 95% with a false-negative rate of < 5%. Using serial sectioning and immunohistochemistry, SLN micrometastases can be identified in 10% to 20% of node-negative patients. However, the clinical significance of micrometastases is not known. Axillary recurrence is rare for patients without SLN metastases who do not undergo further axillary surgery. Outside a clinical trial, ALND is recommended for most patients with SLN metastases, except for cases with SLN metastases < 0.2 mm detected by immunohistochemistry alone. The indications for SLN biopsy have expanded and include breast cancer patients with multifocal/multicentric disease and large tumors, and male breast cancer. Although minimally invasive internal mammary SLN biopsy is feasible, the usefulness of this procedure is not established.


Assuntos
Neoplasias da Mama/patologia , Estadiamento de Neoplasias/métodos , Biópsia de Linfonodo Sentinela/métodos , Axila , Feminino , Humanos
13.
Med Sci Sports Exerc ; 33(11): 1876-81, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11689738

RESUMO

PURPOSE: To assess the effects of creatine monohydrate on isometric force-time curve parameters of sedentary college males aged 18-25 yr. METHODS: This double-blind study randomly assigned subjects to either a treatment (with creatine (Cr)) group (N = 11) or placebo group (P) (N = 8). The Cr group received 20 g x d(-1) of Cr for the first 5 d, in 5-g doses, four times daily (loading period) followed by a 5-g x d(-1) dose for the next 5 d (maintenance phase) and then no Cr ingestion for 7 d (washout period). Each 5-g dose was mixed with 250 mL of Gatorade. The P group received a placebo (cornstarch) following the exact same dosage regimen and protocol as the Cr group. All subjects were sedentary and had not used any nutritional supplements for 6 months before the study. Measurements of isometric force production of four muscle groups (elbow flexors and extensors; knee flexors and extensors) were characterized by a number of force-time parameters including strength (MF), time to maximal force (TMF), rate of force development (MRFD), and intermittent endurance (total impulse (TI) and percent force decrement (PFD)). Testing was done at pretreatment, after the 10-d loading and maintenance phases, and after the washout phase. RESULTS: Repeated measures ANOVA indicated no significant group effect for any muscle group concerning the maximal strength parameters and only two significant time effects for the knee flexors during MF and MRFD. Similarly, there were no significant group effects for any muscle group during the endurance trials; however, there was a significant time effect concerning TI for each muscle group tested. CONCLUSION: Our findings indicate that oral supplementation with creatine monohydrate in untrained males does not positively influence isometric strength but may enhance intermittent isometric muscular endurance.


Assuntos
Creatina/farmacologia , Contração Isométrica/efeitos dos fármacos , Músculo Esquelético/fisiologia , Adolescente , Adulto , Água Corporal/efeitos dos fármacos , Suplementos Nutricionais , Cotovelo/fisiologia , Humanos , Joelho/fisiologia , Estilo de Vida , Masculino , Resistência Física/efeitos dos fármacos , Valores de Referência
14.
Am J Surg ; 182(4): 307-11, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11720660

RESUMO

BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.


Assuntos
Neoplasias da Mama/patologia , Linfa/fisiologia , Axila , Mama/patologia , Reações Falso-Negativas , Feminino , Humanos , Linfonodos/fisiopatologia , Metástase Linfática , Pessoa de Meia-Idade , Estudos Prospectivos , Vigilância de Evento Sentinela
15.
Ann Surg ; 234(3): 292-9; discussion 299-300, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11524582

RESUMO

OBJECTIVE: To determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. METHODS: Analysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. RESULTS: A total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.


Assuntos
Neoplasias da Mama/patologia , Competência Clínica/normas , Biópsia de Linfonodo Sentinela , Reações Falso-Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
16.
J Am Coll Surg ; 192(6): 684-9; discussion 689-91, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11400961

RESUMO

BACKGROUND: Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS: A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeon's previous experience, and type of operation were not significant. CONCLUSIONS: The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Biópsia de Linfonodo Sentinela/normas , Neoplasias da Mama/cirurgia , Distribuição de Qui-Quadrado , Coloides , Corantes , Reações Falso-Negativas , Feminino , Humanos , Modelos Logísticos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/normas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Radioisótopos , Compostos Radiofarmacêuticos , Fatores de Risco
17.
Am Surg ; 67(6): 522-6; discussion 527-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11409798

RESUMO

Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.


Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Reações Falso-Negativas , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Palpação
18.
Arch Surg ; 136(5): 563-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11343548

RESUMO

BACKGROUND: Sentinel lymph node (SLN) biopsy is a minimally invasive procedure that provides accurate nodal staging information. The need for completion axillary dissection after finding a positive SLN for breast cancer has been questioned. HYPOTHESIS: The presence of nonsentinel node (NSN) metastases in the axillary dissection specimen correlates with tumor size, the number of SLNs removed, and the number of positive SLNs. DESIGN: Prospective, multi-institutional study. PARTICIPANTS AND METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a nationwide study involving 148 surgeons. All patients underwent SLN biopsy, followed by level I/II axillary dissection. All SLNs were evaluated histologically at a minimum of 2-mm intervals. Immunohistochemical analysis using antibodies for cytokeratin was performed at the discretion of each participating institution. All NSNs were evaluated by routine histologic examination. RESULTS: An SLN was identified in 1268 (90%) of 1415 patients. Increasing tumor size was significantly correlated with increasing likelihood of positive NSNs: T1a, 14%; T1b, 22%; T1c, 30%; T2, 45%; and T3, 57% (P =.002, chi(2) test). The presence of positive NSNs was not significantly associated with the number of SLNs removed. Patients with more than 1 positive SLN were more likely to have positive NSNs than those with only 1 positive SLN (50% vs 32%; P<.001, chi(2) test). Increasing tumor size and the presence of multiple positive SLNs were also associated with the presence 4 or more positive axillary nodes. Multivariate analysis confirmed that tumor size and the number of positive SLNs were independent factors predicting the presence of positive NSNs. CONCLUSIONS: The likelihood of positive NSNs correlates with increasing tumor size and the presence of multiple positive SLNs. However, even patients with small primary tumors have a substantial risk of residual axillary nodal disease after SLN biopsy. These data will be helpful in counseling patients regarding the need for completion axillary dissection after a positive SLN is identified.


Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Axila , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Valor Preditivo dos Testes , Estudos Prospectivos
19.
Ann Surg ; 233(5): 676-87, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11360892

RESUMO

OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.


Assuntos
Neoplasias da Mama/patologia , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Humanos , Injeções Intradérmicas , Injeções Intralesionais , Pessoa de Meia-Idade
20.
Cancer Pract ; 9(2): 92-6, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11879284

RESUMO

PURPOSE: This article reviews the current literature on lymphatic mapping and sentinel lymph node dissection (SLND) for breast cancer and presents educational information for patients who are considering undergoing this procedure. OVERVIEW: Lymphatic mapping with SLND has been tested widely in patients with breast cancer, primarily in the context of clinical trials. Research studies have found a high degree of accuracy, with the sentinel lymph node (SLN) predicting the status of the axillary node basin. The ability of the surgeon to identify the SLN and the accuracy of the technique correlate with the number of procedures conducted. With the increase in the number of patients having lymphatic mapping and SLND for breast cancer who may not be part of a clinical trial, there is a need for educational materials to help clinicians teach patients about the procedure. CLINICAL IMPLICATIONS: Because of the complexity of the information, patients need both written and verbal information to decide whether to undergo an SLND. In the setting of a clinical trial, patient education materials add to the informed consent document. As the use of SLND for breast cancer becomes more common, the need for clear, concise, informative patient education materials is even more imperative.


Assuntos
Neoplasias da Mama/patologia , Metástase Linfática , Educação de Pacientes como Assunto/métodos , Biópsia de Linfonodo Sentinela , Feminino , Humanos
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