Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 137
Filtrar
1.
J Oncol Pharm Pract ; 29(3): 663-668, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35112974

RESUMO

INTRODUCTION: A recent randomized trial demonstrated that sorafenib improved progression free survival (PFS) in patients with desmoid tumors despite many patients experiencing stable disease or spontaneous regression without treatment. Utilizing these trial data, we performed a cost analysis of sorafenib efficacy through two years of treatment. METHODS: Current Medicare Part D rates for sorafenib were utilized (dose 400 mg/day, cost $309/day). Annual costs per progression and objective response were calculated. Radiologic progression and response were defined using RECIST criteria. Patients with disease progression were separately analyzed in two groups: both clinical and radiologic (CAR), and radiologic alone. RESULTS: 84 previously randomized patients were analyzed (placebo: 35, sorafenib: 49). At one year, sorafenib was associated with a 43% absolute risk reduction (ARR) of CAR progression and number-needed-to-treat (NNT) of 2.3 patients/year, costing $259,406. At two years, ARR was 48% and NNT of 2.1 patients/year, costing $473,697. When evaluating only patients with RECIST defined radiologic progression, sorafenib patients experienced ARR of 13.9% with NNT 7.2 and estimated costs of $812,052 at one year. Two-year ARR was 17.5% with NNT 5.7 and estimated costs $1,285,052. Sorafenib patients experienced improved RECIST partial response rates at 1 and 2 years of 14.7% and 14.3%, with NNT 6.8 and 6.9, and costs of $766,938 and $1,556,433; respectively. CONCLUSION: For the treatment of desmoid tumors, Sorafenib led to improved PFS, but at a significant cost per patient. Favorable RECIST outcomes were less likely and costlier. Patients should be informed of possible benefits of treatment versus potential financial burden.


Assuntos
Fibromatose Agressiva , Idoso , Estados Unidos , Humanos , Sorafenibe/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Medicare , Custos e Análise de Custo , Resultado do Tratamento , Niacinamida/uso terapêutico
2.
J Surg Oncol ; 126(8): 1494-1503, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36111443

RESUMO

PURPOSE: This study sought to determine the R0 resection rate in KRAS wild-type (WT), liver-only metastatic colorectal cancer (CRC) patients initially identified as having unresectable disease who were treated with FOLFOX7 plus cetuximab. Exploratory molecular analyses were undertaken before and after treatment. METHODS: Twenty patients were enrolled. None had prior adjuvant chemotherapy. Cetuximab was added to a FOLFOX7 backbone and administered at 500 mg/m2 every 14 days with dose reductions to 400 and 300 mg/m2 in the event of toxicity. In the absence of toxicity, dose-escalations to 600, 700, and 800 mg/m2 were allowed. The mean dose of cetuximab (mg/m2 /week) throughout the study was 289 mg/m2 . Paired samples were collected for correlative studies, where feasible. RESULTS: We assessed the conversion rates from unresectable to resectable in hepatic-only, KRAS exon 2 WT mCRC. Seventeen of 20 patients undergoing chemotherapy were considered resectable by imaging criteria; R0 resection was achieved in 15/20 patients. Molecular profiling revealed heterogeneity between patients at the gene-expression, pathway signaling, and immune-profile levels. CONCLUSIONS: Although 15/20 (75%) converted to R0 resection, by 2 years, 10/15 R0 resections had recurred. Therefore, chemotherapy plus cetuximab is of limited long-term benefit in this setting. ctDNA analysis may guide additional therapy including immunotherapy.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Cetuximab/uso terapêutico , Camptotecina , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Leucovorina
3.
Oncologist ; 25(5): e798-e807, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31852811

RESUMO

BACKGROUND: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. RESULTS: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. CONCLUSION: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.


Assuntos
Fluoruracila , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêutico , Qualidade de Vida , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia
4.
J Biol Chem ; 292(27): 11388-11399, 2017 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-28550085

RESUMO

Mesenchymal-to-epithelial transition (MET) and epithelial-to-mesenchymal transition (EMT) are important processes in kidney development. Failure to undergo MET during development leads to the initiation of Wilms tumor, whereas EMT contributes to the development of renal cell carcinomas (RCC). The role of calcium regulators in governing these processes is becoming evident. We demonstrated earlier that Na+/Ca2+ exchanger 1 (NCX1), a major calcium exporter in renal epithelial cells, regulates epithelial cell motility. Here, we show for the first time that NCX1 mRNA and protein expression was down-regulated in Wilms tumor and RCC. Knockdown of NCX1 in Madin-Darby canine kidney cells induced fibroblastic morphology, increased intercellular junctional distance, and induced paracellular permeability, loss of apico-basal polarity in 3D cultures, and anchorage-independent growth, accompanied by expression of mesenchymal markers. We also provide evidence that NCX1 interacts with and anchors E-cadherin to the cell surface independent of NCX1 ion transport activity. Consistent with destabilization of E-cadherin, NCX1 knockdown cells showed an increase in ß-catenin nuclear localization, enhanced transcriptional activity, and up-regulation of downstream targets of the ß-catenin signaling pathway. Taken together, knockdown of NCX1 in Madin-Darby canine kidney cells alters epithelial morphology and characteristics by destabilization of E-cadherin and induction of ß-catenin signaling.


Assuntos
Transição Epitelial-Mesenquimal , Rim/metabolismo , Transdução de Sinais , Trocador de Sódio e Cálcio/metabolismo , Animais , Caderinas/genética , Caderinas/metabolismo , Cães , Técnicas de Silenciamento de Genes , Rim/citologia , Células Madin Darby de Rim Canino , Estabilidade Proteica , Trocador de Sódio e Cálcio/genética , beta Catenina/genética , beta Catenina/metabolismo
5.
Ann Surg Oncol ; 29(13): 7939-7941, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36209327

Assuntos
Oncologistas , Humanos
6.
J Clin Oncol ; 42(13): 1520-1530, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38315963

RESUMO

PURPOSE: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects. METHODS: We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS- (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect. RESULTS: Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS-. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS- patients did not (COLOXIS- HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65). CONCLUSION: The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Fluoruracila , Leucovorina , Aprendizado de Máquina , Oxaliplatina , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Quimioterapia Adjuvante , Adulto , Ensaios Clínicos Fase III como Assunto , Estadiamento de Neoplasias
7.
Surg Oncol ; 37: 101560, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33848761

RESUMO

The gastrointestinal tract is home to diverse and abundant microorganisms, collectively referred to as the microbiome. This ecosystem typically contains trillions of microbial cells that play an important role in regulation of human health. The microbiome has been implicated in host immunity, nutrient absorption, digestion, and metabolism. In recent years, researchers have shown that alteration of the microbiome is associated with disease development, such as obesity, inflammatory bowel disease, and cancer. This review discusses the five decades of research into the human microbiome and the development of colorectal cancer - the historical context including experiments that sparked interest, the explosion of research that has occurred in the last decade, and finally the future of testing and treatment.


Assuntos
Neoplasias Colorretais/etiologia , Microbioma Gastrointestinal/fisiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos
8.
Am J Surg ; 222(5): 983-988, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33933208

RESUMO

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are rare sarcomas with 5000 new cases arising in the United States each year. Despite their low incidence, general surgeons should be familiar with GISTs since a quarter of these neoplasms are encountered incidentally. METHODS: A retrospective medical records review was conducted to create a database of all GISTs resected from January 2005 to May 2019. We isolated patients who had incidental discovery of GISTs intraoperatively or within final pathology. Characteristics of patient (Age, gender), index procedure (malignant vs. benign, elective vs. emergent) and tumor (location, size and mitotic rate) were analyzed. RESULTS: A total 48 patients were incidentally discovered to have a GIST excised during index operation. The mean age of these patients was 62 years, with 27 females and 21 males. The primary location of tumors in descending frequency was stomach (30), small bowel (15), colon/rectum (2) and esophagus (1). The average size of all tumors was 1.2 cm, with the average size of the stomach, small bowel, colon/rectum and esophagus at 0.9 cm, 1.7 cm, 0.9 cm and 0.3 cm respectively. Mitotic rate was less than 5 mitosis per 50 HPF in 96% of patients. Incidental tumors were identified during both bariatric (13) and non-bariatric stomach surgery (8), colorectal surgery (14), hernia repair (4), ampullary/pancreatic surgery (5), esophageal surgery (2) liver surgery (1) and uterine surgery (1). Most incidental-GISTs were identified during elective surgery (81%, 39). Finally, 15 of the tumors were identified during surgery for other malignancies. CONCLUSIONS: One quarter (25%) of the GISTs encountered at our academic community cancer center over a 15-year period were discovered incidentally. These tumors had less malignant characteristics overall and were likely cured with surgical resection.


Assuntos
Neoplasias Gastrointestinais/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Achados Incidentais , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia/estatística & dados numéricos , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade
9.
Surg Oncol ; 37: 101319, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34103239

RESUMO

BACKGROUND: Pancreatic tumors are frequently found in a geriatric population. Given that the median age of patients with pancreatic cancer is 70 years at diagnosis and the ubiquity of CT and MRI imaging has increased the detection of pancreas masses, pancreatic surgeons often find themselves operating on patients of advanced age. This study sought to evaluate the outcomes of pancreatic resection in an octogenarian population at a single institution with a dedicated surgical oncology team. STUDY DESIGN: A retrospective chart review was performed for all patients undergoing pancreatic resection over a 13-year period at an academic community cancer center. Patient characteristics and operative outcomes were compared between patients aged 80 and older, and those younger than 80. Student t-tests, Fisher's exact test, and Kruskal-Wallis tests were used for univariate analyses. RESULTS: Over the 13-year period, a total of 48 patients of 403 undergoing pancreatic resections were aged 80 or older. Of these 48 patients, 35 underwent pancreaticoduodenectomy (Whipple) and 13 underwent distal pancreatectomy. Patient characteristics including ASA classification were similar among the two age groups. The procedures themselves were equally complicated with similar operative times, transfusion requirements, estimated blood losses, and portal vein resections. The number and severity of complications such as delayed gastric emptying and pancreatic leak were not statistically different between the two groups. Additionally, the 30-day reoperation, readmission, and mortality rates were not statistically different. Outcomes at 90-days revealed an increased rate of readmission amongst octogenarians who underwent Whipple without an increase in rates of major complications. The total number of deaths in the octogenarian group was 3 (6.2%) vs. 6 (1.7%) in the non-octogenarian group (p = 0.080). The median length of stay was similar amongst the two age groups. CONCLUSIONS: At a large-volume academic community cancer center with a dedicated surgical oncology team, highly selected octogenarians can undergo pancreatic resection safely with outcomes that do not differ significantly from their younger counterparts.


Assuntos
Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/estatística & dados numéricos , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Maryland/epidemiologia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Ann Surg Oncol ; 17(4): 959-66, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20082144

RESUMO

BACKGROUND: The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies. METHODS: All patients enrolled in NSABP adjuvant trials C-01 through C-05 with stage II and III disease who were treated with surgery or with surgery plus 5-FU/LV were examined for overall survival (OS), disease-free survival (DFS), and recurrence-free interval (RFI). Time-to-event by treatment group was examined using adjusted Kaplan-Meier estimates and multivariable Cox regression analysis. RESULTS: There were 2,966 eligible patients: 693 (23%) surgery and 2,273 (77%) surgery plus 5-FU/LV; 1,255 (42%) stage II and 1,711 (58%) stage III. Age > or =60 years [hazard ratio (HR) = 1.36, P < 0.0001], male gender (HR = 1.20, P = 0.0012), and more nodes positive or fewer nodes examined (P < 0.0001) were associated with worse survival. At 5 years, the adjusted OS was 0.62 [confidence interval (CI) = 0.60-0.63] in the surgery group and 0.76 (CI = 0.74-0.78) in the surgery plus 5-FU/LV group. Treatment with 5-FU/LV was associated with improved outcome compared with surgery: OS (HR = 0.62, P < 0.0001), DFS (HR = 0.66, P < 0.0001) and RFI (HR = 0.64, P < 0.0001). Improved OS with adjuvant treatment was seen in both stage II (HR = 0.58, 95% CI = 0.48-0.71) and stage III disease (HR = 0.65, 95% CI = 0.55-0.75). CONCLUSIONS: This analysis demonstrates that treatment of colon cancer patients with 5-FU/LV following surgery provides benefit over surgery alone and can provide anticipated survival outcomes with which to compare modern adjuvant trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Operatórios , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
11.
Surg Oncol Clin N Am ; 29(1): 23-34, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757311

RESUMO

This article reviews advances in precision medicine for colorectal carcinoma that have influenced screening and treatment, and potentially prevention. Advances in molecular techniques have made it possible for better patient selection for therapies; therefore, mutational analysis should be performed at diagnosis to guide treatment. Future efforts should focus on validating these treatments in specific subgroups and on understanding the mechanisms of resistance to therapies to enable treatment optimization, promote efficacy, and reduce treatment costs and toxicities.


Assuntos
Cirurgia Colorretal/normas , Genômica/métodos , Neoplasias/cirurgia , Seleção de Pacientes , Medicina de Precisão/tendências , Humanos , Neoplasias/patologia , Medicina de Precisão/métodos
12.
Am Surg ; 86(12): 1728-1735, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870029

RESUMO

BACKGROUND: A randomized controlled trial of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting. METHODS: Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed. RESULTS: Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts (P < .001) and softer glands (P = .04). For all pancreatectomies, there was no difference in POPF rates (odds ratio [OR] 0.84; 95% CI 0.60-1.16, P = .29). Patients undergoing distal pancreatectomy (OR 0.70; 95% CI 0.30-1.63, P = .41) had similar rates of POPF versus pancreaticoduodenectomy (PD) patients who experienced a lower incidence of POPF (OR 0.60; 95% CI 0.42-0.86, P = .006).Mortality rates and LOS were similar. Readmission rates were decreased with pasireotide (OR 0.61; 95% CI 0.44-0.85). CONCLUSIONS: Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD, and decreased readmission rates. Further prospective, randomized studies are warranted.


Assuntos
Hormônios/uso terapêutico , Fístula Pancreática/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Somatostatina/análogos & derivados , Humanos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Somatostatina/uso terapêutico
13.
Am Surg ; 86(5): 429-436, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684027

RESUMO

BACKGROUND: A randomized controlled trial (RCT) of routine administration of pasireotide demonstrated decreased incidence of clinically significant postoperative pancreatic fistula (POPF). Recent studies have not replicated these results. A meta-analysis was performed to evaluate its efficacy in this setting. METHODS: Prospective trials utilizing pasireotide prophylactically after pancreatectomy were reviewed. The primary outcome was clinically significant POPF. Secondary outcomes included length of stay (LOS), readmission rates, and mortality. Study heterogeneity was assessed. RESULTS: Five studies totaling 1571 patients were identified. There was no difference in age, sex, or cancer rates. Pasireotide patients had smaller pancreatic ducts (P ≤.001) and softer glands (P = .04). For all pancreatectomies, there was no difference in POPF rates (OR 0.84; 95% CI 0.60-1.16, P = .29). Patients undergoing distal pancreatectomy (OR 0.70; 95% CI 0.30-1.63, P = .41) had similar rates of POPF versus pancreaticoduodenectomy (PD) patients that experienced a lower incidence of POPF (OR 0.60; 95% CI 0.42-0.86, P = .006). Mortality rates and LOS were similar. Readmission rates were decreased with pasireotide (OR 0.61; 95% CI 0.44-0.85). CONCLUSIONS: Routine administration of pasireotide did not decrease POPF rates for all pancreatectomies, but was associated with lower rates for PD and decreased readmission rates. Further prospective, randomized studies are warranted.


Assuntos
Pancreatectomia , Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia , Complicações Pós-Operatórias/prevenção & controle , Somatostatina/análogos & derivados , Humanos , Somatostatina/uso terapêutico
14.
Biomacromolecules ; 10(8): 2019-32, 2009 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-19624098

RESUMO

Invasive epithelial tumors form from cells that are released from their natural basement membrane and form 3-D structures that interact with each other and with the microenvironment of the stromal tissues around the tumor, which often contains collagen. Cancer cells, growing as monolayers on tissue culture plastic, do not reflect many of the properties of whole tumors. This shortcoming limits their ability to serve as models for testing of pharmacologically active compounds, including those that are being tested as antineoplastics. This work seeks to create new 3-D cellular materials possessing properties similar to those in native tissues surrounding cancers, specifically electrospun micro- and nanofibrous collagen scaffolds that support tumor growth in 3-D. We hypothesize that a 3-D culture system will provide a better replica of tumor growth in a native environment and, thus, better report the bioactivity of antineoplastic agents. In addition, we optimized conditions and identified physical characteristics that support growth of the highly invasive, prostate cancer bone metastatic cell line C4-2B on these matrices for use in anticancer drug studies. The effects of matrix porosity, fiber diameter, elasticity, and surface roughness on growth of cancer cells were evaluated. Data indicates that while cells attach and grow well on both nano- and microfibrous electrospun membranes, the microfibrous membrane represented a better approximation of the tumor microenvironment. It was also observed that C4-2B nonadherent cells migrated through the depth of two electrospun membranes and formed colonies resembling tumors on day 3. An apoptosis study revealed that cells on electrospun substrates were more resistant to both antineoplastic agents, docetaxel (DOC), and camptothecin (CAM) compared to the cells grown on standard collagen-coated tissue culture polystyrene (TCP). Growth, survival, and apoptosis were measured, as well as the differences in the apoptotic capabilities, of the two above-mentioned compounds compared to known clinical performance. We conclude that 3-D electrospun membranes are amenable to high throughput screening for cancer cell susceptibility and combination killing (Banerjee, S.; Hussain, M.; Wang, Z.; Saliganan, A.; Che, M.; Bonfil, D.; Cher, M.; Sarkar, F.H. Cancer Research, 2007, 67 (8), 3818-26).


Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Colágeno/química , Matriz Extracelular/química , Membranas Artificiais , Modelos Anatômicos , Neoplasias da Próstata/tratamento farmacológico , Apoptose/efeitos dos fármacos , Materiais Biomiméticos , Neoplasias Ósseas/secundário , Técnicas de Cultura de Células , Humanos , Masculino , Microscopia de Força Atômica , Microesferas , Neoplasias da Próstata/patologia , Engenharia Tecidual , Células Tumorais Cultivadas
16.
Cancer Res ; 67(20): 9762-70, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17942906

RESUMO

Regulation of the MYC oncogene remains unclear. Using 10058-F4, a compound that inhibits MYC-MAX transcription factor, MYC protein and gene expression were down-regulated in Namalwa cells, a Burkitt lymphoma. Compound 10058-F4 decreased MYC mRNA (45%), MYC protein (50%), and cell growth (32%). MYC-MAX transcription factor was disrupted 24 h after treatment, resulting in transcriptional inhibition of target genes. Because microRNAs (miRNA) disrupt mRNA translation, let-7a, let-7b, and mir-98 were selected using bioinformatics for targeting MYC. Inhibition of MYC-MAX transcription factor with 10058-F4 increased levels of members of the let-7 family. In inhibited cells at 24 h, let-7a, let-7b, and mir-98 were induced 4.9-, 1.3-, and 2.4-fold, respectively, whereas mir-17-5p decreased 0.23-fold. These results were duplicated using microRNA multianalyte suspension array technology. Regulation of MYC mRNA by let-7a was confirmed by transfections with pre-let-7a. Overexpression of let-7a (190%) decreased Myc mRNA (70%) and protein (75%). Down-regulation of Myc protein and mRNA using siRNA MYC also elevated let-7a miRNA and decreased Myc gene expression. Inverse coordinate regulation of let-7a and mir-17-5p versus Myc mRNA by 10058-F4, pre-let-7a, or siRNA MYC suggested that both miRNAs are Myc-regulated. This supports previous results in lung and colon cancer where decreased levels of the let-7 family resulted in increased tumorigenicity. Here, pre-let-7a transfections led to down-regulation of expression of MYC and its target genes and antiproliferation in lymphoma cells. These findings with let-7a add to the complexity of MYC regulation and suggest that dysregulation of these miRNAs participates in the genesis and maintenance of the lymphoma phenotype in Burkitt lymphoma cells and other MYC-dysregulated cancers.


Assuntos
Linfoma de Burkitt/genética , Linfoma de Burkitt/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Fatores de Transcrição de Zíper de Leucina Básica/antagonistas & inibidores , Fatores de Transcrição de Zíper de Leucina Básica/biossíntese , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linfoma de Burkitt/metabolismo , Processos de Crescimento Celular/genética , Regulação para Baixo , Inativação Gênica , Genes myc , Humanos , MicroRNAs/biossíntese , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Ratos
17.
Am J Surg ; 218(2): 349-354, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30389119

RESUMO

BACKGROUND: We sought to evaluate the post-operative outcomes of patients undergoing pancreaticoduodenectomy at a high volume academic community cancer center. METHODS: A retrospective review was performed of patients undergoing pancreaticoduodenectomy over a 10-year period. RESULTS: Over 10 years, 213 patients underwent pancreaticoduodenectomy. Median age was 66y. Most patients had significant comorbidities (median ASA = 3) and were overweight (median BMI = 27). Median operative time and blood loss were 253 min and 500 ml, respectively. 160 (75%) out of 213 patients had a malignant lesion on final pathology. 121 (76%) out of 160 had R0 resection. Median lymph nodes harvested was 13. Overall incidence of DGE was 31% (67/213), with clinically significant DGE in 15% (32/213). Pancreatic leak rate was 18% (37/213), with clinically significant leaks in 10% (21/213). Median length of stay was 8 days. Grade 3/4 morbidity rate was 21% (44/206), and 30-day mortality was 2% (5/213). CONCLUSIONS: At a high volume academic community cancer center, pancreaticoduodenectomy can be performed with excellent outcomes on par with any academic center or university hospital.


Assuntos
Neoplasias Duodenais/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/estatística & dados numéricos , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Centros Comunitários de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos , Adulto Jovem
19.
Ann Surg Oncol ; 15(9): 2363-71, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18470568

RESUMO

INTRODUCTION: The Society of Surgical Oncology (SSO) created a task force to address the issue of surgical outcomes as it pertains to clinical practice. A survey of its members was conducted to determine which domains of "outcomes" are important and relevant to surgical oncologists. METHODS: Participation of 1,929 SSO members was solicited via e-mail; 1,881 messages were successfully delivered. The survey instrument was administered via a web-based portal. The questionnaire was comprised of three parts: demographic information; rating scales to assess interest, involvement, and knowledge in the various domains of surgical outcomes; and questions to elicit preferences and opinions on current topics in the field of surgical outcomes. RESULTS: There was an overall response rate of 30% (570 of 1,881). Respondents were representative of the general membership with respect to demographics acquired in self-reported profiles. Most members valued the clinical application of evidence-based medicine, adoption of new technologies, and quality monitoring of cancer care as particularly important areas in outcomes research. SSO members also rated quality improvement measures as important. However, there is uncertainty whether current efforts to enforce quality indicators by third party payers or with public accountability would be helpful. CONCLUSION: Overall, this survey successfully delineated beliefs and views of the SSO members with regard to areas of particular interest in surgical outcomes, including improving the quality of cancer care. These findings have implications for planning future agendas for outcomes and health service research and in guiding national policy efforts on behalf of all SSO members.


Assuntos
Inquéritos Epidemiológicos , Oncologia/estatística & dados numéricos , Neoplasias/cirurgia , Padrões de Prática Médica , Sociedades Médicas/estatística & dados numéricos , Institutos de Câncer , Pesquisa sobre Serviços de Saúde , Humanos , Projetos de Pesquisa , Inquéritos e Questionários , Resultado do Tratamento
20.
Ann Surg Oncol ; 15(11): 3058-64, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18712451

RESUMO

INTRODUCTION: The multidisciplinary approach to cancer care has been established through a statewide videoconferencing network to discuss prospective patient management issues. To our knowledge this is the first report of a statewide community cancer center videoconferencing network in the USA. METHODS: Four of seven American College of Surgeons Commission on Cancer community hospitals in the state of Delaware agreed to participate in a statewide videoconferencing network. Through information technology all centers can communicate pathology and radiology results via visualization methodology. Information is shared on a weekly basis with discussion of treatment decisions and diagnostic procedures. The videoconferencing occurs over a 60-min period. RESULTS: All cases have been prospectively presented. The videoconferencing has led to an increase in National Cancer Institute (NCI) treatment and cancer control clinical trials accrual. American Society of Clinical Oncology (ASCO) guidelines and the National Comprehensive Cancer Center Network (NCCN) guidelines have been followed in 92% of case presentations as recommended by the videoconference participants. Physician and support personnel do not have to travel to any of the centers since technology allows communication amongst all participants through their own community cancer centers. CONCLUSION: A statewide community cancer center videoconferencing network has resulted in high compliance with ASCO and NCCN guidelines and improvement in accrual to NCI Clinical trials.


Assuntos
Institutos de Câncer/organização & administração , Serviços de Saúde Comunitária/organização & administração , Neoplasias/terapia , Comunicação por Videoconferência/estatística & dados numéricos , Humanos , National Cancer Institute (U.S.) , Neoplasias/prevenção & controle , Estudos Prospectivos , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA