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BACKGROUND: Neoadjuvant tyrosine kinase inhibitor (TKI) therapy has reduced tumor burden and improved survival in both primary and recurrent gastrointestinal stromal tumors (GISTs). However, no clear guidelines exist on optimal patient selection for neoadjuvant therapy (NAT). Our aim was to analyze factors and outcomes associated with the therapeutic sequence of TKI therapy before and/or after surgery for gastric GISTs. METHODS: We performed a retrospective study of patients surgically treated for a gastric GIST utilizing the 2006-2018 National Cancer Database. We examined demographic, clinical, and pathological characteristics associated with NAT versus adjuvant therapy (AT) using logistic regression. RESULTS: Of the 3732 patients, 20.4% received NAT and 79.6% had AT. Among patients receiving therapy, NAT significantly increased over our study period (12% to 30.7%). A majority of the AT group received a partial gastrectomy (77.9%) compared with the NAT group who received more near-total/total gastrectomy or gastrectomy with en bloc resection (p < 0.001). In a multivariable model, patients were more likely to receive NAT when insured (private, aOR: 2.37, 95% CI: 1.31-4.29), treated at an academic/research program (aOR: 1.83, 95% CI: 1.49-2.56), had tumors located in the proximal stomach (aOR: 1.40, 95% CI: 1.06-1.86), tumor size > 10 cm (aOR: 1.88, 95% CI: 1.41-2.51), and received near-total/total gastrectomy (aOR: 1.81, 95% CI: 1.42-2.29). There were no differences in outcomes. CONCLUSION: NAT for gastric GIST has increased in utilization. NAT was used in patients with larger tumors and who underwent more extensive resection. Despite these factors, outcomes were similar to patients receiving only AT. More studies are required to determine the therapeutic sequence for gastric GISTs.
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Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/cirugía , Terapia Neoadyuvante , Estudios Retrospectivos , Recurrencia Local de Neoplasia/cirugía , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , GastrectomíaRESUMEN
BACKGROUND: It is unknown whether rural patients with operable breast cancer do worse than urban patients in Louisiana. We performed an analysis of breast cancer based on rural versus urban residencies and evaluate factors associated with worse survival. METHODS: Data on women diagnosed with stages I to III breast cancer from 2004 to 2016 were obtained from the Louisiana Tumor Registry. Overall survival and cancer-specific survival were compared between rural and urban residencies by sociodemographic, clinical-pathologic, and treatment variables. Kaplan-Meier method and the log-rank test were used to compare the survival curves. Cox regression model was used to assess independent factors associated with overall survival and cancer-specific survival. RESULTS: Of the 27,780 patients, 2,441 patients (8.7%) resided in rural areas. Compared with urban patients, rural patients tended to be older, underinsured, more impoverished, less likely to be treated at an American College of Surgeons accredited institution, and more likely to be treated at a low-volume center (P < .005 each). For stages I and II diseases, there was a statistically significant difference in overall survival favoring urban regions, but no difference in cancer-specific survival. For stage III disease, there was no difference in either overall survival or cancer-specific survival between the 2 cohorts. Overall survival and cancer-specific survival curves for the entire cohort were not different at the 5-year mark, but become statistically significant with greater time; although rural patients had a lower long-term overall survival (P = .0001) and cancer-specific survival (P = .049) compared with urban patients, the rural-urban differences in overall survival and cancer-specific survival were no longer different after adjusting for other covariates, indicating the observed differences in univariate analysis were attributable to sociodemographic, clinicpathologic, and treatment factors. CONCLUSION: Despite rural patients with operable breast cancer having an overall lesser overall survival and cancer-specific survival than their urban counterpart, rural residence itself was not an independent predictor of outcome. In fact, particular socioeconomic factors increased the risk of death among patients residing in rural areas. Additional analysis at the patient-level is needed to understand the interactions between rurality and breast cancer outcomes in Louisiana.
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Neoplasias de la Mama/mortalidad , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Incidencia , Louisiana/epidemiología , Pacientes no Asegurados , Persona de Mediana Edad , Pobreza , Determinantes Sociales de la Salud , Factores Socioeconómicos , Adulto JovenRESUMEN
BACKGROUND: SOX9, a progenitor cell marker, is important for pancreatic ductal development. Our goal was to examine SOX9 expression differences in intraductal papillary mucinous neoplasms (IPMNs) and ductal adenocarcinoma (PDAC) compared with benign pancreatic duct (BP). METHODS: SOX9 expression was evaluated by immunohistochemistry performed on 93 specimens: 37 BP, 24 low grade (LG) IPMN, 12 high grade (HG) IPMN, and 20 PDAC. A linear mixed-effects model was used to compare the percentage of cells expressing SOX9 by specimen type. A separate linear mixed-effects model evaluated differences in SOX9 expression by staining intensity in pancreatic epithelial cells. RESULTS: Nuclear SOX9 expression was detected in the epithelial cells of 98% HG IPMN, 93% LG IPMN, 83% PDAC, and 60% BP. Compared with BP, SOX9 was expressed from a significantly greater percentage of cells in LG IMPN, HG IMPN, and PDAC (p < 0.001 for each). BP and PDAC showed greater variability in SOX9 expression in epithelial cells compared with IPMNs which showed strong, homogenous SOX9 expression in almost all cells. Compared with BP, both LG and HG IPMN showed significantly greater SOX9 expression (p < 0.001 for each), but there was no significant difference in SOX9 expression between LG and HG IPMN (p > 0.05). PDAC had significantly higher expression of SOX9 compared with BP but significantly lower SOX9 expression compared with LG or HG IPMN (p < 0.001 for each). CONCLUSIONS: IPMNs demonstrated the highest expression levels of SOX9. SOX9 expression in BP and PDAC demonstrated much more heterogeneity compared with the strong, uniform expression in IPMN.
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Adenocarcinoma Mucinoso/patología , Carcinoma Ductal Pancreático/patología , Carcinoma Papilar/patología , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Lesiones Precancerosas/patología , Factor de Transcripción SOX9/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Papilar/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos/metabolismo , Neoplasias Pancreáticas/metabolismo , Lesiones Precancerosas/metabolismo , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Although internal mammary chain (IMC) metastases are an independent predictor of prognosis, collecting IMC sentinel nodes (SN) remains controversial. We sought to determine predictors for IMC nodal positivity and the role positive IMC-SNs have on changing staging and management. METHODS: We reviewed a prospectively collected database (1997-2012) to identify patients who had IMC drainage detected on lymphoscintigraphy and underwent biopsy. Chi square tests and logistic regression models were used to determine trends and factors associated with IMC node positivity. RESULTS: A total of 122 patients with cTis-T2cN0M0 breast cancer underwent IMC-SN biopsy. Mean age of the cohort was 53 years, and mean tumor size was 2.0 cm. Identification of IMC nodes was successful in 100% of the cases. There were no complications. Sentinel nodes mapped to the IMC alone in 14 of 122 (11%) patients. Overall, 26% of patients were node positive, with 12 of 122 (10%) patients having a positive IMC-SN. In patients with a positive axilla, IMC-SN was positive in 33% of patients, whereas in patients with a negative axilla, IMC-SN was positive in 3% of cases (P < 0.001). The number of positive axillary nodes was the only independent predictor of IMC positivity (1-3 positive axillary nodes odds ratio 16.9, 95% CI 3.1-91.1; ≥4 positive axillary nodes odds ratio 45.0, 95% CI 4.0-500.7). IMC-SN positivity led to a more advanced nodal category in all patients and more accurate staging in 4 of 12 (33%) patients. CONCLUSIONS: IMC-SN biopsy is predictable and safe. Identification of IMC metastases though IMC-SN biopsy has the potential to alter the stage and adjuvant therapy of breast cancer patients.
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Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Carcinoma Intraductal no Infiltrante/secundario , Carcinoma Lobular/secundario , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/cirugía , Drenaje , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Linfocintigrafia , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , RadiofármacosRESUMEN
BACKGROUND: Malignant phyllodes tumors of the breast have traditionally been treated with surgical excision. Recently, the use of adjuvant radiotherapy has been advocated to reduce the risk of local recurrence; however, this recommendation is controversial in the absence of consistent outcome data. We hypothesize that there has been a trend toward increased utilization of adjuvant radiotherapy for malignant phyllodes tumors despite its uncertain effect on outcomes. METHODS: Using the National Cancer Data Base, predictors of radiotherapy utilization were examined for women with malignant phyllodes from 1998 to 2009. Kaplan-Meier and Cox regression models were generated to determine the effect of radiotherapy on local recurrence (LR), disease-free survival (DFS), and overall survival (OS). RESULTS: Of the 3,120 patients with malignant phyllodes, 57 % underwent breast conservation surgery and 42 % underwent mastectomy. Overall, 14.3 % of women received adjuvant radiotherapy. Utilization of radiotherapy doubled over the study period (9.5 % in 1998-1999 vs. 19.5 % in 2008-2009, p < 0.001). Women were significantly more likely to receive radiotherapy if they were diagnosed later in the study, were age 50-59 years old, had tumors >10 cm, or had lymph nodes removed. For the 1,774 patients with available recurrence data, overall recurrence was 14.1 %, and LR was 5.9 %. In adjusted models, adjuvant radiotherapy reduced LR (aHR 0.43, 95 % CI 0.19-0.95) but did not impact DFS or OS after 53 months' median follow-up. CONCLUSIONS: Utilization of adjuvant radiotherapy for malignant phyllodes doubled from 1998 to 2009. Radiotherapy significantly reduced LR but had no effect on DFS or OS.
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Neoplasias de la Mama/radioterapia , Mastectomía , Recurrencia Local de Neoplasia/radioterapia , Tumor Filoide/radioterapia , Radioterapia/estadística & datos numéricos , Adulto , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Tumor Filoide/mortalidad , Tumor Filoide/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Adipokines in the tumor microenvironment may contribute to cancer growth. We hypothesized that peritumoral fat can be a source of lipid-derived energy for tumors by increasing adipose triglyceride lipase (ATGL)-mediated lipolysis and down-regulating a negative regulator of adipogenesis, pigment epithelium-derived factor (PEDF). METHODS: In a pilot study, tissue from mastectomies (n = 19) was collected from sites both adjacent (peritumoral) and distant to the tumor for comparison of ATGL, PEDF, and leptin expression levels using immunohistochemistry. Statistical analysis was performed by Student's t test to determine significance. RESULTS: Mean tumor size was 2.4 cm, and 10 (59 %) patients had tumor-positive nodes. Mean body mass index (BMI) was 28.1 kg/m(2). ATGL expression was significantly increased in obese patients (BMI ≥ 30 kg/m(2)) compared with the nonobese group (P < 0.04). Leptin expression was increased in the peritumoral stroma of obese patients compared with distant sites (P = 0.03). Peritumoral PEDF and the leptin/PEDF ratio were significantly affected by tumor size and node status. Tumors ≥ 2 cm had lower peritumoral stromal expression of PEDF than tumors <2 cm (P = 0.01). In node-positive cases, expression of PEDF was significantly decreased in the peritumoral stroma compared with node-negative cases (1.22 vs. 1.80, P < 0.04). The leptin/PEDF ratio was markedly elevated in the peritumoral region of node-positive cases versus node-negative cases (2.17 vs. 1.18, P < 0.001). CONCLUSIONS: Peritumoral expression of adipokines was altered in both obesity and more advanced breast tumors, suggesting a role for adipokines in enhancing tumor growth. Future studies should focus on the use of adipokines as biomarkers.
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Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Ácidos Grasos/metabolismo , Obesidad/metabolismo , Tejido Adiposo/patología , Adulto , Índice de Masa Corporal , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/secundario , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/secundario , Carcinoma Lobular/metabolismo , Carcinoma Lobular/secundario , Proliferación Celular , Proteínas del Ojo/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Leptina/metabolismo , Lipasa/metabolismo , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Crecimiento Nervioso/metabolismo , Obesidad/patología , Proyectos Piloto , Pronóstico , Serpinas/metabolismo , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
RATIONALE: Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. METHODS: We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent. RESULTS: Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. CONCLUSION: Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.
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Adenocarcinoma/genética , Adenocarcinoma/secundario , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Pulmón/patología , MicroARNs/genética , Adenocarcinoma/mortalidad , Progresión de la Enfermedad , Humanos , Pulmón/metabolismo , Neoplasias Pulmonares/mortalidad , MicroARNs/metabolismo , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To correlate microscopic margin status with survival and local control in a large cohort of patients from a high-volume pancreatic cancer center. DESIGN: Retrospective database review. A uniform procedure for margin analysis was used with 4-color inking (neck, portal vein groove, uncinate, and posterior pancreatic margin) by the surgeon in the operating room. SETTING: A tertiary care hospital. PATIENTS: We reviewed patients who underwent pancreaticoduodenectomy between September 1, 1997, and December 31, 2008, from a prospective, institutional database. MAIN OUTCOME MEASURES: Using Cox regression models, we identified pathologic characteristics associated with local recurrence (LR) after controlling for potential confounding variables. Overall and LR-free survival curves were generated by the Kaplan-Meier method. RESULTS: Of 285 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma, 97 (34.0%) had 1 or more positive microscopic margins (uncinate, 16.5%; portal vein groove, 8.8%; neck, 7.7%; and posterior, 10.5%). A total of 198 patients (69.5%) recurred, with the first site of failure being LR only in 47 (23.7%), local plus distant recurrence in 42 (21.2%), and distant recurrence only in 109 (55.1%). Patients with LR only were significantly more likely to have lymph node involvement (adjusted hazard ratio, 2.66; 95% CI, 1.25-5.63) or a positive posterior margin (adjusted hazard ratio, 4.27; 95% CI, 2.07-8.81). Patients with a positive posterior margin had significantly poorer LR-free survival with (P < .001) or without (P = .01) lymph node involvement. CONCLUSIONS: When systematically assessed, the incidence of positive microscopic margins is high. Positive posterior margins and lymph node involvement were each independently and significantly associated with LR.
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Adenocarcinoma/patología , Adenocarcinoma/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Adenocarcinoma/mortalidad , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Neoplasias Pancreáticas/mortalidad , Pancreaticoduodenectomía/métodos , Insuficiencia del TratamientoRESUMEN
We present a patient who developed an acute superior mesenteric artery (SMA) syndrome following pneumonectomy. Although rarely described, a majority of cases develop insidiously from a gradual loss of retroperitoneal fat in the setting of malnourishment. A postoperative presentation is atypical, however procedures that narrow the aortomesenteric angle have been associated with the development of SMA syndrome. This case illustrates an important anatomic relationship that thoracic surgeons performing lung resection surgery should be aware of in order to avoid predisposing patients to SMA syndrome.
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Neumonectomía/efectos adversos , Síndrome de la Arteria Mesentérica Superior/etiología , Enfermedad Aguda , Adulto , Femenino , Humanos , Síndrome de la Arteria Mesentérica Superior/terapia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Clostridial myonecrosis is an uncommon, highly lethal necrotizing soft tissue infection. The source may be occult at the time of clinical presentation. In cases caused by Clostridium septicum, there is an association with colorectal malignant disease, suggesting that underlying colonic pathology frequently is the source of the infection. METHODS: Case report and literature review. CASE REPORT: A 37-year old man with acquired immunodeficiency syndrome, end-stage renal disease, and C. difficile colitis presented to the Emergency Department (ED) with a primary complaint of abdominal pain and incidental right forearm pain. While undergoing evaluation in the ED, he developed progressive erythema, edema, and emergence of bullae over his right forearm. After rapid imaging of his abdomen, he underwent guillotine amputation of his right upper extremity because of extensive myonecrosis and total abdominal colectomy secondary to right colonic necrosis and C. difficile colitis. Blood cultures were positive for C. septicum. Microscopic examination of both the necrotic colon and the right forearm musculature demonstrated invasion of gram-positive bacilli throughout. CONCLUSIONS: Myonecrosis caused by C. septicum frequently occurs in the presence of colonic pathology, typically malignant disease. This case report illustrates the development of this pathological process in an immunosuppressed patient who did not have colon cancer, but rather colonic mucosal inflammation produced by C. difficile.
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Infecciones por Clostridium/complicaciones , Clostridium septicum , Colon/patología , Músculo Esquelético/patología , Infecciones de los Tejidos Blandos/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Adulto , Amputación Quirúrgica/métodos , Colectomía/métodos , Colon/cirugía , Enterocolitis Seudomembranosa/cirugía , Humanos , Masculino , Músculo Esquelético/cirugía , Necrosis/patología , Necrosis/cirugíaRESUMEN
BACKGROUND: Male breast cancer accounts for less than 1% of all breast cancers, yet males have a worse prognosis than females with breast cancer. METHODS: Using the 1988-2003 Surveillance, Epidemiology, and End Results Program data, we conducted a retrospective, population-based cohort study to investigate stage-specific differences in breast cancer-specific and all-cause mortality between males and females. We calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) using Cox regression models to compare breast cancer-specific and all-cause mortality by stage between males and females, controlling for potential confounding variables. RESULTS: There were 246,059 patients with a first, single, primary breast cancer [1,541 (0.6%) male; 244,518 (99.4%) female]. Compared with females, males were more likely to be older, Black, married, diagnosed at more advanced stages, and treated with mastectomy (each P < 0.001). Males also were more likely to have lower grade and estrogen/progesterone receptor-positive tumors (each P < 0.001). After controlling for confounders, males were more likely to die from their breast cancer when compared with females, only if diagnosed with stage I disease (aHR 1.72, CI 1.15-2.61). For all-cause mortality, males were more likely than females to die at each stage of disease except stage IV. CONCLUSIONS: Although all-cause mortality was higher for men than women at all stages of nonmetastatic breast cancer, higher male breast cancer-specific mortality was attributed to poorer survival in stage I disease. However, this statistical difference is unlikely to be clinically relevant and attributable to in-stage migration.
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Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/mortalidad , Carcinoma Intraductal no Infiltrante/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Carcinoma Intraductal no Infiltrante/epidemiología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
An important mechanism by which pancreatic cancer avoids antitumor immunity is by recruiting regulatory T cells (Tregs) to the tumor microenvironment. Recent studies suggest that suppressor Tregs and effector Th17 cells share a common lineage and differentiate based on the presence of certain cytokines in the microenvironment. Because IL-6 in the presence of TGF-ß has been shown to inhibit Treg development and induce Th17 cells, we hypothesized that altering the tumor cytokine environment could induce Th17 and reverse tumor-associated immune suppression. Pan02 murine pancreatic tumor cells that secrete TGF-ß were transduced with the gene encoding IL-6. C57BL/6 mice were injected s.c. with wild-type (WT), empty vector (EV), or IL-6-transduced Pan02 cells (IL-6 Pan02) to investigate the impact of IL-6 secretion in the tumor microenvironment. Mice bearing IL-6 Pan02 tumors demonstrated significant delay in tumor growth and better overall median survival compared with mice bearing WT or EV Pan02 tumors. Immunohistochemical analysis demonstrated an increase in Th17 cells (CD4(+)IL-23R(+) cells and CD4(+)IL-17(+) cells) in tumors of the IL-6 Pan02 group compared with WT or EV Pan02 tumors. The upregulation of IL-17-secreting CD4(+) tumor-infiltrating lymphocytes was substantiated at the cellular level by flow cytometry and ELISPOT assay and mRNA level for retinoic acid-related orphan receptor γt and IL-23R by RT-PCR. Thus, the addition of IL-6 to the tumor microenvironment skews the balance toward Th17 cells in a murine model of pancreatic cancer. The delayed tumor growth and improved survival suggests that induction of Th17 in the tumor microenvironment produces an antitumor effect.
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Linfocitos T CD4-Positivos/inmunología , Interleucina-17/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Pancreáticas/inmunología , Subgrupos de Linfocitos T/inmunología , Animales , Linfocitos T CD4-Positivos/metabolismo , Línea Celular Tumoral , Separación Celular , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Humanos , Inmunohistoquímica , Interleucina-17/biosíntesis , Interleucina-6/inmunología , Interleucina-6/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Subgrupos de Linfocitos T/metabolismo , Transducción GenéticaRESUMEN
OBJECTIVE: To determine the safety and efficacy of saline-linked surface radiofrequency ablation (SLSRFA) in a clinical setting. SUMMARY BACKGROUND DATA: We have previously identified safe and effective parameters for use of SLSRFA in a porcine model. METHODS: An initial study was conducted to determine if parameters defined in the porcine model were safe and effective in human livers. In 16 patients undergoing liver resection, normal areas of liver were treated with SLSRFA using various power/diameter combinations (10 W/1 cm; 15 W/2 cm; 45 W/4 cm) for 9 minutes with and without inflow occlusion. In a second study, superficial hepatic colorectal cancer (CRC) metastases were treated at 45 W/4 cm for 9 minutes without inflow occlusion in 11 patients. Ablation depth was measured and samples were examined for cell viability by nicotine adenine dinucleotide stain. This study was registered in the ClinicalTrials.gov database and has the following ID number, NCT00869843. RESULTS: Ablation depth in normal liver varied from 3 to 20 mm. Depth was significantly dependent on power, lesion size, and inflow occlusion. Nicotine adenine dinucleotide stains showed total cell necrosis to the full depth of ablation. In the second study, large hepatic CRC metastases showed total cell necrosis to a mean depth of 12 mm. Two tumors less than 7 mm in depth showed complete necrosis. Metastases were more susceptible to SLSRFA than normal liver. CONCLUSION: SLSRFA completely and safely ablates normal liver to a depth of at least 4 mm at 45 W/4 cm treatment parameters. Remarkably, it is even more effective in ablating metastatic CRC. SLSRFA is an effective tool for extending resection margins and for ablating superficial small tumors or superficial parts of large tumors.
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Ablación por Catéter/métodos , Neoplasias Colorrectales/patología , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Animales , Humanos , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Modelos Animales , Cloruro de Sodio/administración & dosificación , Porcinos , Resultado del TratamientoRESUMEN
BACKGROUND: We investigated differences in breast cancer mortality between younger (younger than 40 years of age) and older (40 years of age and older) women by stage at diagnosis to identify patient and tumor characteristics accounting for disparities. STUDY DESIGN: We conducted a retrospective study of women diagnosed with breast cancer in the 1988 to 2003 Surveillance, Epidemiology, and End Results Program data. Multivariate Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals to compare overall and stage-specific breast cancer mortality in women younger than 40 years old and women 40 years and older, controlling for potential confounding variables identified in univariate tests. RESULTS: Of 243,012 breast cancer patients, 6.4% were younger than 40 years old, and 93.6% were 40 years of age or older. Compared with older women, younger women were more likely to be African American, single, diagnosed at later stages, and treated by mastectomy. Younger women had tumors that were more likely to be higher grade, larger size, estrogen receptor/progesterone receptor-negative, and lymph-node positive (p < 0.001). Younger women were more likely to die from breast cancer compared with older women (crude HR = 1.39; CI, 1.34 to 1.45). Controlling for confounders, younger women were more likely to die compared with older women if diagnosed with stage I (aHR = 1.44; CI, 1.27 to 1.64) or stage II (aHR = 1.09; CI, 1.03 to 1.15) disease and less likely to die if diagnosed with stage IV disease (aHR = 0.85; CI, 0.76 to 0.95). CONCLUSIONS: Higher breast cancer mortality in younger women was attributed to poorer outcomes with early-stage disease. Additional studies should focus on specific tumor biology contributing to the increased mortality of younger women with early-stage breast cancer.
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Neoplasias de la Mama/mortalidad , Causas de Muerte , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Estudios de Cohortes , Intervalos de Confianza , Supervivencia sin Enfermedad , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Black women often present with advanced-stage breast cancer compared with White women, which may result in the observed higher mortality among Black women. Age-related factors (e.g., comorbidity) also affect mortality. Whether racial disparities in mortality are evident within age and/or stage groups has not been reported, and risk factors for greater mortality among Black women are not well defined. METHODS: Using the 1988-2003 Surveillance, Epidemiology, and End Results Program data, we conducted a retrospective, population-based cohort study to compare overall and stage-specific breast-cancer mortality between Black and White women within each age (<40, 40-49, 50-64, and 65+) and stage (stage 0-IV and unstaged) group at diagnosis. Cox regression models calculated unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CI), the latter controlling for potential confounders of the relationship between race and survival. RESULTS: In the 1988-2003 Surveillance, Epidemiology, and End Results data, 20,424 Black and 204,506 White women were diagnosed with first primary breast cancer. In unadjusted models, Black women were more likely than White women to die from breast cancer (HR: 1.90; 95% CI: 1.83-1.96) and from all causes (HR: 1.52; 95% CI: 1.48-1.55) during follow-up. In models stratified by age and stage, Black women were at increased risk of breast-cancer-specific mortality within each stage group among women <65 y. CONCLUSION: Racial disparities in breast-cancer-specific mortality were predominantly observed within each stage at diagnosis among women <65 y old. This greater mortality risk for Black women was largely not observed among women >or=65 y of age.
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Neoplasias de la Mama/etnología , Neoplasias de la Mama/mortalidad , Disparidades en el Estado de Salud , Adulto , Factores de Edad , Anciano , Población Negra , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Grupos Raciales , Estudios Retrospectivos , Factores de Riesgo , Programa de VERF , Análisis de Supervivencia , Estados Unidos/epidemiología , Población BlancaRESUMEN
Surgery is the cornerstone of treatment for women with nonmetastatic breast cancer. In contrast, standard treatment for patients with Stage IV disease includes chemotherapy and radiation, with surgery usually reserved for local tumor-related complications. Little is known about the predictive factors associated with primary tumor resection for Stage IV breast cancer. We conducted a retrospective, population-based, case-control study using the 1988-2003 Surveillance Epidemiology and End Results (SEER) data. Using multiple logistic regression, we identified patient and tumor characteristics from among SEER region, age at diagnosis, year of diagnosis, marital status, race, Hispanic ethnicity, tumor grade, and size that were associated with surgical resection of the primary breast tumor (compared with no surgical resection) among women with stage IV breast cancer. Adjusted odds ratios and 95% confidence intervals are reported. Of 10,017 patients, 4,836 (48%) underwent surgical resection of the primary breast tumor. Patients in the Northeast and Midwest and patients presenting with two or more primary breast tumors were more likely to have surgical resection. Patients who were older, diagnosed after 1992, unmarried, black, and whose tumors were >5 cm, inflammatory, of unknown size, indeterminate grade, or unknown progesterone status were less likely to have had surgical resection of the primary tumor. Several patient and tumor characteristics were significantly associated with surgical resection of the primary breast tumor in Stage IV disease. Further study of the surgery decision-making process is recommended.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Niño , Etnicidad , Femenino , Humanos , Inflamación/patología , Estado Civil , Persona de Mediana Edad , Estadificación de Neoplasias , Grupos Raciales , Receptores de Progesterona/análisis , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Primary treatments for stage IV breast cancer are chemotherapy and radiation, with surgery usually reserved for tumor-related complications. We sought to determine whether surgical removal of the primary tumor provides a survival advantage for women with metastatic breast cancer. METHODS: We conducted a retrospective, population-based cohort study by using the 1988-2003 Surveillance, Epidemiology, and End Results (SEER) program data. By use of multivariate Cox regression models, overall survival in women with stage IV disease was compared between women who underwent surgical excision of their breast tumor with women who did not, controlling for potential confounding demographic, tumor- and treatment-related variables, and propensity scores (accounting for variables associated with the likelihood of having surgery). RESULTS: Of 9734 SEER patients with stage IV breast cancer, 47% underwent breast cancer surgery and 53% did not. Median survival was longer for women who had surgery than for women who did not, both among women who were alive at the end of the study period (36.00 vs. 21.00 months; P < .001) and among women who had died during follow-up (18.00 vs. 7.00 months; P < .001). After controlling for potential confounding variables and propensity scores, patients who underwent surgery were less likely to die during the study period compared with women who did not undergo surgery (adjusted hazard ratio, .63, 95% confidence interval, .60-.66). CONCLUSIONS: Analysis of the 1988-2003 SEER data indicated that extirpation of the primary breast tumor in patients with stage IV disease was associated with a marked reduction in risk of dying after controlling for variables associated with survival.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Programa de VERF , Neoplasias de la Mama/diagnóstico , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Schizophrenia, many believe, reflects an enhanced vulnerability to psychological stress. Controlled exposure to stressors, however, has produced inconclusive results, particularly with regards to neurohormones. Some of the variability may be attributable to the nature and psychological significance of the stimulus and failure to control physiologic confounds. In addition, it is possible that the heterogeneity of schizophrenia is an important factor. In a carefully designed study and in a controlled setting, we measured the neuroendocrine response of eight polydipsic hyponatremic (PHS), seven polydipsic normonatremic (PNS), and nine nonpolydipsic normonatremic (NNS) (ie normal water balance) schizophrenic in-patients as well as 12 healthy controls (HC) to two different stressors: one of which appears to influence neuroendocrine secretion through its psychological (cold pressor) and the other (upright posture) through its systemic actions. Subjects in the three psychiatric groups were stabilized and acclimated to the research setting, and all received saline to normalize plasma osmolality. Following the cold pressor, plasma adrenocorticotropin and cortisol levels showed a more prolonged rise in PHS patients relative to PNS patients. NNS patients, in contrast, exhibited blunted responses relative to both of the polydipsic groups and the HC. Peak vasopressin responses were also greater in PHS and blunted in NNS patients. Responses to the postural stimulus were similar across patient groups. These findings provide a mechanism for life threatening water intoxication in schizophrenia; help to reconcile conflicting findings of stress responsiveness in schizophrenia; and potentially identify a discrete patient subset with enhanced vulnerability to psychological stress.