PubMed Health⌕ Search

Biomedical subjects

Rebekah R White

Publications and source records attributed to Rebekah R White.

11 recordsLinked to original sources
PubMed2006

Evaluation of preoperative therapy for pancreatic cancer using a prognostic nomogram.

BACKGROUND: Theoretical benefits of preoperative chemoradiation therapy (preop CRT) for pancreatic cancer include improved efficacy, resectability, and patient selection. The goal of this study was to evaluate the applicability of a nomogram, which was developed for patients undergoing resection without preop CRT and which incorporates several post-resection pathological factors, to a population of patients who received preop CRT prior to resection. METHODS: From 1994 to 2004, 82 patients with biopsy-proven, radiographically localized adenocarcinoma of the pancreatic head underwent preop CRT followed by pancreaticoduodenectomy (PD); 50 concurrent patients underwent PD without preop CRT. Mean nomogram-predicted disease-specific survival (DSS) rates were compared with observed DSS rates from the time of resection. RESULTS: Despite having more locally advanced tumors on initial staging (21 vs. 8%; P < .05), patients who received preop CRT had smaller resected tumors (mean 2.3 vs. 3.1 cm; P < .01), were less likely to have T3 tumors (54 vs. 80%, P < .01), were less likely to have positive lymph nodes (29 vs. 58%, P < .01), and had fewer positive lymph nodes (mean .4 vs. 1.9, P < .01), all factors that imply treatment effect and favorably impact on nomogram-predicted DSS. Observed DSS was similar to predicted DSS in both groups. CONCLUSIONS: The similarity in observed and predicted DSS following resection in patients who received preop CRT suggests that the effects of preop CRT-whether treatment, selection, or no effect-are reflected by the nomogram. The ability of the nomogram to evaluate the effects of preop CRT on survival is limited by the potential effects of preop CRT on factors within the nomogram.

Adenocarcinoma↗
PubMed2006

Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy.

BACKGROUND: Neoadjuvant chemoradiotherapy (neo-CRT) is being used with increasing frequency for periampullary tumors, but how it alters the complication rate of pancreaticoduodenectomy (PD) is unclear. METHODS: A retrospective analysis was conducted of 79 patients with periampullary malignancies who received 5-fluorouracil-based neo-CRT followed by PD. RESULTS: There was no difference in mortality between PD after neo-CRT (3.8%) and conventional PD for either malignant (4.5%) or benign (2.2%) disease. Focusing only on patients with malignancy, the neo-CRT group had a significantly lower pancreatic leak rate than the conventional group (10% vs. 43%; P < .001). Intra-abdominal abscesses were less common in the neo-CRT group (8.8% vs. 21%; P = .019), and there was one (1.2%) amylase-rich abscess in neo-CRT group, compared with eight (12%) in the conventional group. In addition, two patients in the conventional group died of leak-associated sepsis, compared with none in the neo-CRT group. Multivariate analysis revealed that neoadjuvant chemoradiation (odds ratio, .15) was the most significant factor associated with a reduced risk of pancreatic leak. CONCLUSIONS: Neo-CRT does not increase the mortality or morbidity of PD. In contrast, neo-CRT was associated with a marked reduction in the incidence of pancreatic leak, as well as leak-associated morbidity and mortality.

Adult↗
PubMed2005

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. METHODS: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods. RESULTS: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation. CONCLUSIONS: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Adenocarcinoma↗
PubMed2004

Antidote-mediated control of an anticoagulant aptamer in vivo.

Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.

Animals↗
PubMed2004

RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins.

We studied the RNA aptamer Toggle-25/thrombin interaction during inhibition by antithrombin (AT), heparin cofactor II (HCII) and protein C inhibitor (PCI). Thrombin inhibition was reduced 3-fold by Toggle-25 for AT and HCII, but it was slightly enhanced for PCI. In the presence of glycosaminoglycans, AT and PCI had significantly reduced thrombin inhibition with Toggle-25, but it was only reduced 3-fold for HCII. This suggested that the primary effect of aptamer binding was through the heparin-binding site of thrombin, anion-binding exosite-2 (exosite-2). We localized the Toggle-25 binding site to Arg 98, Glu 169, Lys 174, Asp 175, Arg 245, and Lys 248 of exosite-2. We conclude that a RNA aptamer to thrombin exosite-2 might provide an effective clinical reagent to control heparin's anticoagulant action.

Anions↗
PubMed2004

Neoadjuvant therapy for pancreatic cancer: the Duke experience.

The advantages of neoadjuvant (preoperative) chemoradiation therapy for pancreatic cancer include the assurance that all resected patients receive multimodality therapy; the opportunity for patients with occult metastatic disease to manifest themselves; and the potential to improve resectability. Since 1994, Duke University Medical Center has treated over 180 patients with localized pancreatic cancer using neoadjuvant 5-fluorouracil (5FU)-based chemoradiation therapy (CRT). Approximately 20% of patients demonstrate distant disease progression during CRT and avoid the morbidity of laparotomy. Almost 20% of locally advanced tumors on initial-staging CT can be resected following CRT. Patients who have successfully undergone resection have experienced favorable survival with an estimated 5-year survival rate of 36%. This article reviews the authors' experience and the lessons learned from it.

Adult↗
PubMed2003

Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.

Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangiogenic growth factors. To investigate the specific role of Ang2 in the adult vasculature, we generated a nuclease-resistant RNA aptamer that binds and inhibits Ang2 but not the related Tie2 agonist, angiopoietin-1. Local delivery of this aptamer but not a partially scrambled mutant aptamer inhibited basic fibroblast growth factor-mediated neovascularization in the rat corneal micropocket angiogenesis assay. These in vivo data directly demonstrate that a specific inhibitor of Ang2 can act as an antiangiogenic agent.

Angiogenesis Inducing Agents↗
PubMed2003

Thin melanomas: predictive lethal characteristics from a 30-year clinical experience.

OBJECTIVE: To guide treatment and clinical follow-up by defining the natural history of thin melanomas and identifying negative prognostic characteristics that may delineate high-risk patients. SUMMARY BACKGROUND DATA: In following > 10,000 patients with cutaneous melanoma over the past 30 years, our institution has observed nodal or metastatic disease in approximately 15% of patients with a thin (<1 mm) primary lesion. METHODS: A database query of patients with cutaneous melanoma returned 1158 patients with primary lesion < or = 1 mm thick and who received their initial treatment at a single institution. Median follow-up was 11 years (range, 1 to 34 years). Patient and melanoma characteristics as well as outcomes were recorded and statistically analyzed. RESULTS: 6.6% of patients had nodal or distant disease at presentation. Over time, an additional 9.4% developed metastases, including nodal and distal recurrences. Overall incidence of advanced disease was 15.3%. Univariate analysis identified male gender (P = 0.01), advanced age (>45 years; P = 0.05), and Breslow thickness (>0.75 mm; P = 0.008) as significant negative prognostic characteristics. Of patients with these 3 high-risk characteristics, 19.7% developed advanced disease (likelihood ratio 6.3; P = 0.007 versus nonhigh-risk patients). This group had more than twice the incidence of nodal recurrences. Patients with recurrence had significantly decreased 10-year survival (82% versus 45%; P < 0.0001). Surprisingly, neither ulceration nor Clark level predicted advanced disease. CONCLUSIONS: Thin melanomas are potentially lethal lesions. Long-term follow-up identified a high-risk population of older males with tumors between 0.75 mm and 1.0 mm whose risk of recurrent disease approaches 20%. Traditionally accepted negative prognostic factors such as ulceration and discordant Clark levels are not predictive for metastasis in this population. Given the poor prognosis associated with recurrent disease, we recommend close clinical evaluation and follow-up to maximize accurate staging and therapeutic options.

Disease-Free Survival↗
PubMed2002

Long-term survival in 2,505 patients with melanoma with regional lymph node metastasis.

OBJECTIVE: To examine the long-term outcomes of patients with melanoma metastatic to regional lymph nodes. SUMMARY BACKGROUND DATA: Regional lymph node metastasis is a major determinant of outcome for patients with melanoma, and the presence of regional lymph node metastasis has been commonly used as an indication for systemic, often intensive, adjuvant therapy. However, the risk of recurrence varies greatly within this heterogeneous group of patients. METHODS: Database review identified 2,505 patients, referred to the Duke University Melanoma Clinic between 1970 and 1998, with histologic confirmation of regional lymph node metastasis before clinical evidence of distant metastasis and with documentation of full lymph node dissection. Recurrence and survival after lymph node dissection were analyzed. RESULTS: Estimated overall survival rates at 5, 10, 15, and 20 years were 43%, 35%, 28%, and 23%, respectively. This population included 792 actual 5-year survivors, 350 10-year survivors, and 137 15-year survivors. The number of positive lymph nodes was the most powerful predictor of both overall survival and recurrence-free survival; 5-year overall survival rates ranged from 53% for one positive node to 25% for greater than four nodes. Primary tumor ulceration and thickness were also powerful predictors of both overall and recurrence-free survival in multivariate analyses. The most common site of first recurrence after lymph node dissection was distant (44% of all patients). CONCLUSIONS: Patients with regional lymph node metastasis can enjoy significant long-term survival after lymph node dissection. Therefore, aggressive surgical therapy of regional lymph node metastases is warranted, and each individual's risk of recurrence should be weighed against the potential risks of adjuvant therapy.

Adult↗