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Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis in part due to the lack of early detection and screening methods. Metabolomics provides a means for noninvasive screening of tumor-associated perturbations in cellular metabolism., Methods: Urine samples of PDAC patients (n = 32), healthy age and gender-matched controls (n = 32), and patients with benign pancreatic conditions (n = 25) were examined using (1)H-NMR spectroscopy. Targeted profiling of spectra permitted quantification of 66 metabolites. Unsupervised (principal component analysis, PCA) and supervised (orthogonal partial-least squares discriminant analysis, OPLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra using SIMCA-P(+) (version 12, Umetrics, Sweden)., Results: Clear distinction between PDAC and controls was noted when using OPLS-DA. Significant differences in metabolite concentrations between cancers and controls (p < 0.001) were noted. Model parameters for both goodness of fit, and predictive capability were high (R (2) = 0.85; Q (2) = 0.59, respectively). Internal validation methods were used to confirm model validity. Sensitivity and specificity of the multivariate OPLS-DA model were summarized using a receiver operating characteristics (ROC) curve, with an area under the curve (AUROC) = 0.988, indicating strong predictive power. Preliminary analysis revealed an AUROC = 0.958 for the model of benign pancreatic disease compared with PDAC, and suggest that the cancer-associated metabolomic signature dissipates following RO resection., Conclusions: Urinary metabolomics detected distinct differences in the metabolic profiles of pancreatic cancer compared with healthy controls and benign pancreatic disease. These preliminary results suggest that metabolomic approaches may facilitate discovery of novel pancreatic cancer biomarkers.

Background: It remains uncertain whether routine preoperative breast magnetic resonance imaging (MRI) will lead to improved local outcomes after breast-conserving surgery (BCS) and radiation (RT) for invasive carcinoma. The purpose of this study was to determine whether MRI in the planning of the first lumpectomy reduces ipsilateral breast tumor recurrence (IBTR)., Methods: Using a prospective database, 472 initial lumpectomies from 463 women between 1999 and 2005 were examined. All patients had invasive cancer excised to negative margins on BCS, received RT, and were followed. IBTR rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses were performed to investigate the association between MRI for initial lumpectomies and IBTR outcomes., Results: MRI was performed before 127 (27%) lumpectomies, while 345 (73%) patients did not have a preoperative breast MRI. At median follow-up of 54 months (range 4.8-111.6 months), there was no significant difference in actuarial 8-year IBTR rates between women with preoperative MRI evaluation and women without MRI (1.8% versus 2.5%, respectively; P=0.67). After adjusting for adjuvant therapies, patient, and tumor characteristics, there continued to be no increased risk of IBTR [hazard ratio (HR) 1.7; P=0.60]. MRI visualization of tumors prior to lumpectomy did not influence the achievement of negative margins and was not associated with lower rates of re-excision (MRI: 11.8% versus no-MRI: 13.3%; P=0.50)., Conclusion: MRI evaluation of invasive carcinoma in the planning of initial lumpectomies was not associated with improved local outcomes after BCS with RT in this cohort of patients.

Background: Lumpectomy followed by radiation is standard treatment for early breast cancer. Recently, the use of partial breast intraoperative radiation (IORT) has been developed, and patients selected for IORT should not have positive margins. This study's purpose was to identify factors predicting negative margins after lumpectomy., Methods: Patient age, preoperative investigations, surgery, final pathology, and margin status were examined using a prospective database between 1999 and 2005. Univariate and multivariate logistic regression analysis were performed to identify patient and tumor factors predicting an increased rate of negative margins. The results were used to generate a patient selection algorithm., Results: The rate of positive margins at first resection was 17% in 730 lumpectomies (708 patients). Multivariate analysis revealed that older age (P = .0006), smaller tumor size (P < .0025), type of surgery (OR = 3.4 for ultrasound vs mammogram-guided wire localization, P = .003), and having a core needle biopsy (CNB) with preoperative cancer diagnosis (P < .0001) were predictive for having a negative margin. Patients older than age 50 with a preoperative CNB showing invasive cancer less that 3 cm that can be localized under ultrasound had a negative margin rate of 98% (n = 178). These patients would be ideal for consideration of IORT., Conclusions: Negative margin rates after lumpectomy are predicted by age, tumor size, preoperative investigations, and localization technique. These variables can be used to select patients for IORT with a 2.2% chance of positive margins.

Background: For patients with anal canal cancer who fail combined modality treatment (CMT), salvage surgery (SS) offers the potential for long term survival. The literature regarding SS is limited by small patient numbers and/or heterogeneous treatment protocols. We report on a large series of patients initially treated with chemoradiation at a major referral center., Methods: We identified 60 patients with persistent or recurrent anal cancer who had undergone SS; 20 were excluded. Overall and disease-free survival (OS, DFS) curves were constructed using the Kaplan Meier method. Univariate analysis was done using the Log-Rank test, and multivariable analysis using Cox proportional hazards., Results: The 40 patients (29 women, 11 men, median age 57) underwent curative intent resection. The initial procedure was multivisceral resection (n = 24), abdominoperineal resection alone (n = 14) or local excision (n = 2). Postoperative mortality was 5%. Postoperative complications were seen in 72%. Median follow-up was 18 months overall and 36 months in survivors. Median OS was 41 months; OS and disease free survival at 5 years were 39% and 30%, respectively. Recurrence was present in 21 patients at time of analysis. Failure was locoregional in 86% (18 of 21) and distant in 48% (10 of 21). Independent predictors of poor OS were male gender, Charlson Comorbidity Score and tumor size. Independent predictors of poor disease free survival were positive margins and lymphovascular invasion., Conclusion: SS for anal canal cancer was associated with significant morbidity. Long-term survival was achieved in 39% of patients. Comorbidities should guide patient selection, and R0 resection should be the goal.