Richard J Bold

University of California, Davis, Davis, California, United States

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Publications (167)637.1 Total impact

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    ABSTRACT: Surgical morbidity and mortality (M&M) for patients with disseminated malignancy (DMa) is high, and some have questioned the role of surgery. Therefore, we sought to characterize temporal trends in M&M among DMa patients, hypothesizing that surgical intervention would remain prevalent. We queried the American College of Surgeons National Surgical Quality Improvement Program from 2006-2010. Excluding patients undergoing a primary hepatic operation, we identified 21,755 patients with DMa. Parametric and/or nonparametric statistics and logistic regression were used to evaluate temporal trends and predictors of M&M. The prevalence of surgical intervention for DMa declined slightly over the time period, from 1.9%-1.6% of all procedures (P < 0.01). Among DMa patients, the most frequent operations performed were bowel resection, other gastrointestinal procedures, and multivisceral resections, these all showed small statistically significant decreases over time (P < 0.01). The rate of emergency operations also decreased (P < 0.01). In contrast, the rate of preoperative independent functional status rose, whereas the rate of preoperative weight loss and sepsis decreased (P < 0.01). Rates of 30-d morbidity (33.7 versus 26.6%), serious morbidity (19.8 versus 14.2%), and mortality (10.4 versus 9.3%) all decreased over the study period (P < 0.05). Multivariate analysis identified standard predictors (e.g., impaired functional status, preoperative weight loss, preoperative sepsis, and hypoalbuminemia) of worse 30-d M&M. Thirty-day morbidity, serious morbidity, and mortality have decreased incrementally for patients with DMa undergoing surgical intervention, but surgical intervention remains prevalent. These data further highlight the importance of careful patient selection and goal-directed therapy in patients with incurable malignancy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Journal of Surgical Research 03/2015; DOI:10.1016/j.jss.2015.03.063 · 2.12 Impact Factor
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    ABSTRACT: Background Pancreatic ductal adenocarcinoma has proven to be one of the most chemo-resistant among all solid organ malignancies. Several mechanisms of resistance have been described, though few reports of strategies to overcome this chemo-resistance have been successful in restoring sensitivity to the primary chemotherapy (gemcitabine) and enter the clinical treatment arena.Methods We examined the ability of cellular arginine depletion through treatment with PEG-ADI to alter in vitro and in vivo cytotoxicity of gemcitabine. The effect on levels of key regulators of gemcitabine efficacy (e.g. RRM2, hENT1, and dCK) were examined.ResultsCombination of PEG-ADI and gemcitabine substantially increases growth arrest, leading to increased tumor response in vivo. PEG-ADI is a strong inhibitor of the gemcitabine-induced overexpression of ribonucleotide reductase subunit M2 (RRM2) levels both in vivo and in vitro, which is associated with gemcitabine resistance. This mechanism is through the abrogation of the gemcitabine-mediated inhibitory effect on E2F-1 function, a transcriptional repressor of RRM2.Conclusion The ability to alter gemcitabine resistance in a targeted manner by inducing metabolic stress holds great promise in the treatment of advanced pancreatic cancer.
    Journal of Experimental & Clinical Cancer Research 12/2014; 33(1):102. DOI:10.1186/PREACCEPT-8245834981349245 · 3.27 Impact Factor
  • Erin G. Brown, Robert J. Canter, Richard J. Bold
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    ABSTRACT: Background and Objectives Serial levels of CA 19-9 are correlated with treatment response and survival; however, little is known about CA 19-9 kinetics in the absence of therapy. We hypothesize that preoperative CA 19-9 kinetics predict rate of resectability as well as survival.Methods Retrospective review of 72 patients with radiographically resectable pancreatic adenocarcinoma with two pre-operative CA 19-9 levels prior to planned pancreaticoduodenectomy. Primary outcome measures were resectability and overall survival.ResultsForty-seven out of 72 patients (65%) had resectable disease. Unresectable patients had higher absolute change in CA 19-9 than patients with resectable disease (97 U/ml vs. −34 U/ml) as well as higher rate of change (4 U/ml/day vs. −1 U/ml/day). Receiver operating characteristic curves identified predictive thresholds for absolute (≥50 U/ml) and rate of CA 19-9 change (≥1 U/ml/day) that accurately identified unresectable patients. Survival analysis revealed that a change in CA 19-9 <50 U/ml and a rate of change <1 U/ml/day predicted improved survival (P = 0.04, P = 0.02); however, for patients with resectable disease, CA 19-9 changes did not predict survival.Conclusions Preoperative kinetics of CA 19-9 predict resectable disease for pancreatic cancer. These variables also predict overall survival; however, these do not predict survival for those with resectable disease. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 10/2014; 111(3). DOI:10.1002/jso.23812 · 2.84 Impact Factor
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    ABSTRACT: Objectives: To evaluate readmission rates and associated factors to identify potentially preventable readmissions. Background: The decision to penalize hospitals for readmissions is compelling health care systems to develop processes to minimize readmissions. Research to identify preventable readmissions is critical to achieve these goals. Methods: We performed a retrospective review of University HealthSystem Consortium database for cancer patients hospitalized from January 2010 to September 2013. Outcome measures were 7-, 14-, and 30-day readmission rates and readmission diagnoses. Hospital and disease characteristics were evaluated to evaluate relationships with readmission. Results: A total of 2,517,886 patients were hospitalized for cancer treatment. Readmission rates at 7, 14, and 30 days were 2.2%, 3.7%, and 5.6%, respectively. Despite concern that premature hospital discharge may be associated with increased readmissions, a shorter initial length of stay predicted lower readmission rates. Furthermore, high-volume centers and designated cancer centers had higher readmission rates. Evaluating institutional data (N = 2517 patients) demonstrated that factors associated with higher readmission rates include discharge from a medical service, site of malignancy, and emergency primary admission. When examining readmission within 7 days for surgical services, the most common readmission diagnoses were infectious causes (46.3%), nausea/vomiting/dehydration (26.8%), and pain (6.1%). Conclusions: A minority of patients after hospitalization for cancer-related therapy are readmitted with potentially preventable conditions such as nausea, vomiting, dehydration, and pain. However, most factors associated with readmission cannot be modified. In addition, high-volume centers and designated cancer centers have higher readmission rates, which may indicate that readmission rates may not be an appropriate marker for quality improvement.
    Annals of Surgery 10/2014; 260(4):583-591. DOI:10.1097/SLA.0000000000000923 · 7.19 Impact Factor
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    ABSTRACT: Purpose Practice patterns vary with the planning and delivery of post mastectomy radiation therapy (PMRT). Our investigation examines practice patterns in the use of chest wall bolus and a boost among the Athena Breast Health Network (“Athena”). Methods Athena is a collaboration among the five University of California Medical Centers that aims to integrate clinical care and research [1]. From February 2011 to June 2011, all physicians specializing in the multidisciplinary treatment of breast cancer were invited to take a web-based practice patterns survey. Sixty-two of the 239 questions focused on radiation therapy practice environment, decision making processes, and treatment management, including the use of a bolus or boost in PMRT. Results Ninety-two percent of the radiation oncologists specializing in breast cancer completed the survey. All of the responders use a material to increase the surface dose to the chest wall during PMRT. Materials used included brass mesh, commercial bolus, and custom designed wax bolus. Fifty percent used tissue equivalent superflab bolus. Fifty-five percent of the respondents routinely use a boost to the chest wall in PMRT. Eighteen percent give a boost depending on the margin status, and 3/11 (27%) do not use a boost. Conclusions Our investigation documents practice pattern variation for the use of a PMRT boost and the use of chest wall bolus among the University of California breast cancer radiation oncologists. Further understanding of the practice pattern variation will help guide clinicians in our cancer centers to a more uniform approach in the delivery of PMRT.
    Clinical Breast Cancer 08/2014; 15(1). DOI:10.1016/j.clbc.2014.07.005 · 2.63 Impact Factor
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    ABSTRACT: Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone-associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments.
    Proceedings of the National Academy of Sciences 08/2014; 111(39). DOI:10.1073/pnas.1404171111 · 9.81 Impact Factor
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    ABSTRACT: Background: The relationship between procedural relative value units (RVUs) for surgical procedures and other measures of surgeon effort are poorly characterized. We hypothesized that RVUs would poorly correlate with quantifiable metrics of surgeon effort. Methods: Using the 2010 American College of Surgeons - National Surgical Quality Improvement Program (NSQIP) database, we selected 11 primary current procedural terminology codes associated with high volume surgical procedures. We then identified all patients with a single reported procedural RVU who underwent nonemergent, inpatient general surgical operations. We used linear regression to correlate length of stay (LOS), operative time, overall morbidity, frequency of serious adverse events (SAEs), and mortality with RVUs. We used multivariable logistic regression using all preoperative NSQIP variables to determine other significant predictors of our outcome measures. Results: Among 14,481 patients, RVUs poorly correlated with individual LOS (R-2 = 0.05), operative time (R-2 = 0.10), and mortality (R-2 = 0.35). There was a moderate correlation between RVUs and SAEs (R-2 = 0.79) and RVUs and overall morbidity (R-2 = 0.75). However, among low-to mid-level RVU procedures (11-35) there was a poor correlation between SAEs (R-2 = 0.15), overall morbidity (R-2 = 0.05), and RVUs. On multivariable analysis, RVUs were significant predictors of operative time, LOS, and SAEs (odds ratio 1.06, 95% confidence interval: 1.05-1.07), but RVUs were not a significant predictor of mortality (odds ratio 1.02,95% confidence interval: 0.99-1.05). Conclusions: For common, index general surgery procedures, the current RVU assignments poorly correlate with certain metrics of surgeon work, while moderately correlating with others. Given the increasing emphasis on measuring and tracking surgeon productivity, more objective measures of surgeon work and productivity should be developed.
    Journal of Surgical Research 05/2014; 190(2). DOI:10.1016/j.jss.2014.05.052 · 2.12 Impact Factor
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    ABSTRACT: IMPORTANCE Changes in health care reimbursement policy have led to an era in which hospitals are motivated to improve quality of care while simultaneously reducing costs. Research demonstrating the most efficient means to target costs may have a positive effect on patient quality of life and the overburdened health care system. OBJECTIVE To evaluate the effect of hospital length of stay (LOS) and the occurrence of postoperative complications on total charges in patients undergoing elective pancreaticoduodenectomy. DESIGN, SETTING, AND PATIENTS We performed a retrospective review of 89 cases identified in an institutional database of patients who underwent elective pancreaticoduodenectomy at an academic tertiary care center from December 1, 2007, through May 31, 2012. MAIN OUTCOMES AND MEASURES Occurrence of postoperative and inpatient complications, LOS, incidence of readmission within 60 days of discharge, and hospital charges from initial postoperative hospitalization. Linear regression analysis was performed comparing LOS with hospital charges. RESULTS Thirty-four of 89 patients (38%) developed postoperative complications. Mean and median LOSs were 12 and 8 days, respectively. The LOS was significantly related to postoperative complications. Of the 34 patients who developed complications, the mean LOS was 19 days compared with 7 days for those patients not developing complications (P < .001). Only 2 of 55 patients (4%) without complications were readmitted to the hospital, whereas 13 of 34 patients (38%) with complications required readmission. Perioperative hospital charges were significantly related to LOS (R2 = 0.840, R = 0.917). For those patients without complications, linear regression demonstrated a daily hospital charge of $11 612 (R2 = 0.923, R = 0.961). However, for those patients with complications, the optimal relationship between LOS and hospital charges was exponential (R2 = 0.832). CONCLUSIONS AND RELEVANCE Prolonged LOS is associated with increased total charges, but given the exponential increase in charges, the complication itself has an effect on increased charges above and beyond that of a prolonged hospitalization. The drive to reduce LOS after pancreaticoduodenectomy has minimal effect on overall charges to the patient. Efforts should be directed instead at reducing complications because this has a much more significant effect on financial outcomes.
    05/2014; 149(7). DOI:10.1001/jamasurg.2014.151
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    ABSTRACT: Cancer is the second leading cause of death in the United States. Cancer care is a complex and complicated process involving diverse practitioners, multiple specialists, and a range of inpatient, outpatient, and home care services with numerous transitions for the patients. Cancer patients undergoing chemotherapy are at risk of unplanned emergency visits and hospitalizations and can benefit from care coordination. There are few examples of systems that fully engage patients, family and caregivers along with clinicians and other care resources to collaboratively coordinate chemotherapy. This paper reports on the development of a prototype “personal health network” (PHN) using social networking technology to support patient-centered chemotherapy care coordination in a comprehensive cancer center. Requirements for the prototype were generated by analyzing two frameworks, the cancer continuum framework and the framework for information technology in care coordination, and reviewing the literature on self-management and care coordination. The resulting requirements were implemented and reviewed with a trans-disciplinary team of clinicians and researchers. The PHN was found to fulfill the key requirements identified through the analysis of frameworks. A prototype was built rapidly and reviewed by an internal trans-disciplinary team. The refined prototype will be field tested with patients and nurse care coordinators to assess usefulness and usability in preparation for a larger scale clinical trial.
    2014 International Conference on Collaboration Technologies and Systems (CTS); 05/2014
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    ABSTRACT: Objective This study aims to estimate and test temporal differences in mental health (MH) need and service use among adult cancer survivors nationally before and after important policy recommendations for psychosocial cancer care.Methods Adults (n = 58,585) from the National Health Interview Survey, 2005 and 2010, were categorized as having (1) no chronic disease, (2) chronic disease other than cancer, (3) cancer without other chronic disease, and (4) cancer with other chronic disease. In these groups, we compared psychological distress, MH visits, and unmet need for MH services. Survey-weighted logistic regression was used to model these variables as functions of disease status and sociodemographic covariates and the interactions of disease status and survey year.ResultsWhereas the proportion of individuals with psychological distress and MH visits was significantly higher in 2010 versus 2005 for the no chronic disease group, the only group with significantly lower unmet need in 2010 versus 2005 was the cancer with other chronic disease group (5.3% vs. 3.0%, p < 0.05). In adjusted models, cancer survivors with other chronic disease had significantly lower odds of unmet need in 2010 (odds ratio 1.38; 95% confidence interval 0.85, 2.25) than in 2005 (odds ratio 3.32; 95% confidence interval 2.28, 4.83).Conclusions We find evidence of MH care quality improvement among cancer survivors between 2005 and 2010, a period that coincides with policy and clinical attention to psychosocial cancer care. These efforts may have reduced, but not eliminated, unmet need for MH services among cancer survivors. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 05/2014; 24(1). DOI:10.1002/pon.3569 · 4.04 Impact Factor
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    ABSTRACT: Background/Aim: The Akt signaling pathway mediates a potent anti-apoptotic signal in pancreatic cancer and inhibition of this pathway has become an attractive mechanism to increase the efficacy of traditional chemotherapies. Autophagy is a lysosomal catabolic pathway by which eukaryotic cells recycle macromolecules and organelles. Although autophagy may function as a survival mechanism under metabolic stress conditions, it also serves as an alternate route to programmed cell death distinct from apoptosis. In the present study, we examined the role of autophagy in Akt-mediated regulation of cell death in pancreatic cancer. Mia-PaCa-2 and PANC-1 human pancreatic cancer cell lines were used in our experiments. The small-molecule inhibitor A-443654 was used to inhibit Akt, and rapamycin was used to inhibit mTOR. Autophagy was inhibited with Chloroquine and 3-methyladenine. Autophagy was assessed by immunoblotting for light chain-3 (LC-3) processing as well as fluorescence microscopy for autophagosome formation following transfection with a LC-3/GFP construct. Cell death was determined by fluorescence-activated cell sorting (FACS) with quantitation of the sub-G0 content. Inhibition of either Akt or mTOR induced autophagy; inhibition of Akt but not of mTOR led to traditional caspase-mediated apoptosis. When autophagy was inhibited, cell death was abrogated following Akt, but not mTOR, inhibition. The Akt signaling pathway regulates both autophagy and apoptosis through divergent pathways; mTOR mediates autophagy signaling but appears to be un-involved in cell death. Autophagy appears to play a role in the regulation of cell survival by Akt, but only when proximal signaling pathways not involving mTOR are simultaneously activated.
    Anticancer research 02/2014; 34(2):631-7. · 1.87 Impact Factor
  • Journal of Surgical Research 02/2014; 186(2):683. DOI:10.1016/j.jss.2013.11.944 · 2.12 Impact Factor
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    ABSTRACT: In the modern era of esophagectomy, we hypothesized that perioperative morbidity and mortality from cervical or thoracic sites of anastomoses would not be different. We used the American College of Surgeons National Surgical Quality Improvement Program database to identify patients who underwent esophagectomy for lower esophageal or gastroesophageal (GE) junction malignancies from 2005 to 2010. Patients were categorized as having either a cervical or thoracic anastomosis based on CPT codes. There were 601 (66%) cervical and 308 (34%) thoracic anastomoses. Cervical anastomoses were associated with greater than 2 units of blood transfusion in a higher proportion of patients (10% vs. 3%, P = 0.001), and higher superficial surgical site infections (13% vs. 7%, P = 0.003). There were no difference in rates of organ/space infections (6% vs. 7%, P = 0.70), overall morbidity (38% vs. 39%, P = 0.84), or mortality (3% vs. 4%, P = 0.34). Median length of stay was similar (11.5 days cervical vs. 11 days thoracic, P = 0.89), even among patients with organ/space infections (18 days cervical vs. 21 days thoracic, P = 0.49). On multivariate analysis thoracic anastomosis was not a significant predictor of increased overall morbidity (OR 1.13: 95%CI 0.83-1.54). After esophagectomy, the site of anastomosis does not predict an increased risk of perioperative morbidity or mortality. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 12/2013; 108(7). DOI:10.1002/jso.23423 · 2.84 Impact Factor
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    ABSTRACT: There is little information about the use of text messaging (texting) devices among resident and faculty physicians for patient-related care (PRC). To determine the prevalence, frequency, purpose, and concerns regarding texting among resident and attending surgeons and to identify factors associated with PRC texting. E-mail survey. University medical center and its affiliated hospitals. Surgery resident and attending staff. Prevalence, frequency, purpose, and concerns regarding patient-related care text messaging. Overall, 73 (65%) surveyed physicians responded, including 45 resident (66%) and 28 attending surgeons (62%). All respondents owned a texting device. Majority of surgery residents (88%) and attendings (71%) texted residents, whereas only 59% of residents and 65% of attendings texted other faculty. Most resident to resident text occurred at a frequency of 3-5 times/d (43%) compared with most attending to resident texts, which occurred 1-2 times/d (33%). Most resident to attending (25%) and attending to attending (30%) texts occurred 1-2 times/d. Among those that texted, PRC was the most frequently reported purpose for resident to resident (46%), resident to attending (64%), attending to resident (82%), and attending to other attending staff (60%) texting. Texting was the most preferred method to communicate about routine PRC (47% of residents vs 44% of attendings). Age (OR: 0.86, 95% CI: 0.79-0.95; p = 0.003), but not sex, specialty/clinical rotation, academic rank, or postgraduate year (PGY) level predicted PRC texting. Most resident and attending staff surveyed utilize texting, mostly for PRC. Texting was preferred for communicating routine PRC information. Our data may facilitate the development of guidelines for the appropriate use of PRC texting.
    Journal of Surgical Education 11/2013; 70(6):826-834. DOI:10.1016/j.jsurg.2012.05.003 · 1.39 Impact Factor
  • Clinical Breast Cancer 10/2013; DOI:10.1016/j.clbc.2013.08.010 · 2.63 Impact Factor
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    ABSTRACT: We sought to characterize the extent of extremity soft tissue tumor (ESTT) resections among surgical specialties, hypothesizing that substantial variation exists in the number of ESTT resections performed by specialty. We queried the UHC-AAMC database for data from 85 institutions for years 2007-2009. We abstracted data on total number of musculoskeletal (MSK) procedures, number of subcutaneous (SQ), deep, and malignant ESTT resections, and anatomic site of resection. Data were available for 4,682 practitioners including the following specialties: general surgery (GS, N = 2,195), plastic surgery (PS, N = 792), surgical oncology (SO, N = 533), general orthopedics (GO, N = 1,079), and orthopedic oncology (OO, N = 83). The mean number of all MSK procedures performed per year was 19.0 ± 2.3 GS, 179.6 ± 3.0 PS, 32.4 ± 6.2 SO, 798.6 ± 115.4 GO, and 482.9 ± 6.5 OO (P = 0.001). SQ ESTT resections per year were similar among specialties (1.7 ± 0.3 GS, 2.7 ± 0.3 PS, 2.4 ± 0.4 SO, 1.7 ± 0.5 GO, 4.7 ± 0.2 OO), while deep and malignant resections were more likely performed by OO (combined deep and malignant: 0.9 ± 0.1 GS, 2.0 ± 0.4 PS, 9.9 ± 0.6 SO, 5.8 ± 0.3 GO, and 63.6 ± 8.1 OO, P = 0.001). Adjusting for number of physicians in the database, of the total deep and malignant ESTT resections, 9.4% were performed by GS, 7.7% by PS, 26.0% by SO, 30.8% by GO, and 26.0% by OO. Nearly 50% of deep and malignant ESTT resections are performed by non-oncology-designated surgeons. Approximately 17% are performed by practitioners who complete an average of one to two of these procedures per year. These findings may have significant implications for quality of care in soft tissue tumor surgery. J. Surg. Oncol. 2013; 108:142-147. © 2013 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 09/2013; 108(3):142-7. DOI:10.1002/jso.23372 · 2.84 Impact Factor
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    Richard J Bold
    Annals of Surgical Oncology 04/2013; DOI:10.1245/s10434-012-2820-6 · 3.94 Impact Factor
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    ABSTRACT: BACKGROUND DATA: Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established. AIMS: To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases. METHODS: 84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors. RESULTS: Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm(2) was an independent predictor for NSLN metastases and extranodal disease. CONCLUSION: Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 03/2013; 39(6). DOI:10.1016/j.ejso.2013.02.017 · 2.89 Impact Factor
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    ABSTRACT: Autophagy is an intracellular recycling mechanism that helps cells to survive against environmental stress and nutritional starvation. We have recently shown that prostate cancers undergo metabolic stress and caspase-independent cell death following exposure to arginine deiminase (ADI, an enzyme that degrades arginine in tissue). The aims of our current investigation into the application of ADI as a novel cancer therapy are to identify the components mediating tumor cell death, and to determine the role of autophagy (stimulated by ADI and/or rapamycin) on cell death. Using advanced fluorescence microscopy techniques including 3D deconvolution and superresolution structured-illumination microscopy (SIM), we show that prostate tumor cells that are killed after exposure to ADI for extended periods, exhibit a morphology that is distinct from caspase-dependent apoptosis; and that autophagosomes forming as a result of ADI stimulation contain DAPI-stained nuclear material. Fluorescence imaging (as well as cryo-electron microscopy) show a breakdown of both the inner and outer nuclear membranes at the interface between the cell nucleus and aggregated autophagolysosomes. Finally, the addition of N-acetyl cysteine (or NAC, a scavenger for reactive oxygen species) effectively abolishes the appearance of autophagolysosomes containing nuclear material. We hope to continue this research to understand the processes that govern the survival or death of these tumor cells, in order to develop methods to improve the efficacy of cancer pharmacotherapy.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2013; DOI:10.1117/12.2004759 · 0.20 Impact Factor
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    ABSTRACT: BACKGROUND: There are conflicting data regarding improvements in postoperative outcomes with perioperative epidural analgesia. We sought to examine the effect of perioperative epidural analgesia vs. intravenous narcotic analgesia on perioperative outcomes including pain control, morbidity, and mortality in patients undergoing gastric and pancreatic resections. METHODS: We evaluated 169 patients from 2007 to 2011 who underwent open gastric and pancreatic resections for malignancy at a university medical center. Emergency, traumatic, pediatric, enucleations, and disseminated cancer cases were excluded. Clinicopathologic data were reviewed among epidural (E) and non-epidural (NE) patients for their association with perioperative endpoints. RESULTS: One hundred twenty patients (71 %) received an epidural and 49 (29 %) did not. There were no significant differences (P > 0.05) in mean pain scores at each of the four days (days 0-3) among the E (3.2 ± 2.7, 3.2 ± 2.3, 2.3 ± 1.9, and 2.1 ± 1.9, respectively) and NE patients (3.7 ± 2.7, 3.4 ± 1.9, 2.9 ± 2.1, and 2.4 ± 1.9, respectively). Within each of the E and NE patient groups, there were significant differences (P < 0.0001) in mean pain scores from day 0 to day 3 (P < 0.0001). Of the E patients, 69 % also received intravenous patient-controlled analgesia (PCA). Ileus (13 % E vs. 8 % NE), pneumonia (12 % E vs. 8 % NE), venous thromboembolism (6 % E vs. 4 % NE), length of stay [11.0 ± 12.1 (8, 4-107) E vs. 12.2 ± 10.7 (7, 3-54) NE], overall morbidity (36 % E vs. 39 % NE), and mortality (4 % E vs. 2 % NE) were not significantly different. CONCLUSIONS: Routine use of epidurals in this group of patients does not appear to be superior to PCA.
    Journal of Gastrointestinal Surgery 01/2013; 17(4). DOI:10.1007/s11605-013-2142-4 · 2.39 Impact Factor

Publication Stats

3k Citations
637.10 Total Impact Points

Institutions

  • 1993–2014
    • University of California, Davis
      • • Division of Surgical Oncology
      • • Department of Surgery
      Davis, California, United States
  • 1998–2013
    • California State University, Sacramento
      Sacramento, California, United States
    • University of Houston
      Houston, Texas, United States
  • 2012
    • Moffitt Cancer Center
      Tampa, Florida, United States
  • 1997–2002
    • University of Texas MD Anderson Cancer Center
      • • Department of Cancer Biology
      • • Department of Surgical Oncology
      Houston, TX, United States
  • 1993–1998
    • University of Texas Medical Branch at Galveston
      • Department of Surgery
      Galveston, TX, United States
  • 1994–1996
    • Oakland University
      Рочестер, Michigan, United States
    • Texas A&M University - Galveston
      Galveston, Texas, United States