Oscar J Hines

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States

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Publications (215)913.9 Total impact

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    ABSTRACT: The 2012 Sendai Criteria recommend that patients with 3 cm or larger branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any additional "worrisome features" or "high-risk stigmata" may undergo close observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD-IPMN <2 cm. These changes have generated concern among physicians treating patients with pancreatic diseases. The purposes of this study were to (i) apply the new Sendai guidelines to our institution's surgically resected BD-IPMN and (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring high-grade dysplasia or invasive cancer.
    Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 11/2014;
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    ABSTRACT: Surgical resection is recommended for all mucinous cystic neoplasms (MCNs) of the pancreas as a result of: 1) lack of an accurate tumor marker for invasive cancer; 2) young age at diagnosis; and 3) historical studies revealing 36 per cent incidence of malignancy in resected lesions. This study compares the clinicopathologic and prognostic features of our series of resected MCNs to recent studies using the current International Association of Pancreatology (IAP) system. Thirty-eight resected MCNs were identified. Almost all patients were female (97.4%); median age at diagnosis was 53.5 years (interquartile range [IQR], 41.3 to 61.0). The majority occurred in the body/tail of the pancreas (86.8%); median size on computed tomography/magnetic resonance imaging was 5.0 cm (IQR, 3 to 8.8). Comparison of the five high-grade (HG, 13.2%) and 33 low-grade (86.8%) MCNs revealed that 1) patients were similar in age (55.0 vs 52.0 years, respectively) and 2) HG lesions were significantly larger on preoperative imaging (9.9 vs 3.5 cm) and final pathology (10.9 vs 3.5 cm). These data, taken together with five recent studies that adhere to the 2012 IAP criteria (385 total MCNs), reveal that a cutoff of less than 3 cm without mural nodules would have only missed one (0.26%) HG lesion. Surveillance of these lesions may be appropriate for some patients.
    The American surgeon 10/2014; 80(10). · 0.92 Impact Factor
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    ABSTRACT: General surgical residency continues to experience attrition. To date, work hour amendments have not changed the annual rate of attrition.
    JAMA surgery. 07/2014;
  • O Joe Hines
    Surgery 06/2014; · 3.37 Impact Factor
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    ABSTRACT: Objective To satisfy trainees’ operative competency requirements while improving feedback validity and timeliness using a mobile Web-based platform. Design The Southern Illinois University Operative Performance Rating Scale (OPRS) was embedded into a website formatted for mobile devices. From March 2013 to February 2014, faculty members were instructed to complete the OPRS form while providing verbal feedback to the operating resident at the conclusion of each procedure. Submitted data were compiled automatically within a secure Web-based spreadsheet. Conventional end-of-rotation performance (CERP) evaluations filed 2006 to 2013 and OPRS performance scores were compared by year of training using serial and independent-samples t tests. The mean CERP scores and OPRS overall resident operative performance scores were directly compared using a linear regression model. OPRS mobile site analytics were reviewed using a Web-based reporting program. Setting Large university-based general surgery residency program. Participants General Surgery faculty used the mobile Web OPRS system to rate resident performance. Residents and the program director reviewed evaluations semiannually. Results Over the study period, 18 faculty members and 37 residents logged 176 operations using the mobile OPRS system. There were 334 total OPRS website visits. Median time to complete an evaluation was 45 minutes from the end of the operation, and faculty spent an average of 134 seconds on the site to enter 1 assessment. In the 38,506 CERP evaluations reviewed, mean performance scores showed a positive linear trend of 2% change per year of training (p = 0.001). OPRS overall resident operative performance scores showed a significant linear (p = 0.001), quadratic (p = 0.001), and cubic (p = 0.003) trend of change per year of clinical training, reflecting the resident operative experience in our training program. Differences between postgraduate year-1 and postgraduate year-5 overall performance scores were greater with the OPRS (mean = 0.96, CI: 0.55-1.38) than with CERP measures (mean = 0.37, CI: 0.34-0.41). Additionally, there were consistent increases in each of the OPRS subcategories. Conclusions In contrast to CERPs, the OPRS fully satisfies the Accreditation Council for Graduate Medical Education and American Board of Surgery operative assessment requirements. The mobile Web platform provides a convenient interface, broad accessibility, automatic data compilation, and compatibility with common database and statistical software. Our mobile OPRS system encourages candid feedback dialog and generates a comprehensive review of individual and group-wide operative proficiency in real time.
    Journal of Surgical Education 01/2014; · 1.63 Impact Factor
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    ABSTRACT: IMPORTANCE Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. OBJECTIVE To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. MAIN OUTCOMES AND MEASURES Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. RESULTS All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P = .007) and HP treatment response (hazard ratio, 9.0; P = .009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P = .05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P = .04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P = .01) in tumor cells and microRNA-21 expression in the stroma (P = .05), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P = .004). CONCLUSIONS AND RELEVANCE Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.
    JAMA surgery. 12/2013;
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    ABSTRACT: The objective of this study was to summarize all clinical studies evaluating the prognostic role of gemcitabine (GEM) metabolic genes in pancreaticobiliary (PB) cancer patients receiving GEM therapy in the neoadjuvant, adjuvant, or palliative settings. Meta-analyses were performed to calculate the pooled hazard ratios for each gene by each clinical outcome (overall survival [OS], disease-free survival [DFS], and progression-free survival) using a random-effects approach. The search strategy identified 16 eligible studies, composed of 632 PB patients total, with moderate quality. Compared with low expression, pooled hazard ratios for OS of hENT1, dCK, RRM1, RRM2, and DPD were 0.37 (95% confidence interval [CI], 0.28-0.47), 0.40 (95% CI, 0.20-0.80), 2.21 (95% CI, 1.12-4.36), 2.13 (95% CI, 1.00-4.52), and 1.91 (95% CI, 1.16-3.17), respectively. A similar trend was observed for each of these biomarkers in DFS and progression-free survival prognostication. Subgroup analyses for hENT1 showed a comparable survival correlation in the adjuvant and palliative settings. High expression of hENT1 in PB cancer patients receiving GEM-based adjuvant therapy is associated with improved OS and DFS and may be the best examined prognostic marker to date. Evidence for other biomarkers is limited by a small number of publications investigating these markers.
    Pancreas 11/2013; 42(8):1303-10. · 2.95 Impact Factor
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    ABSTRACT: The optimal surgical management of small nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) remains controversial. We sought to identify (1) clinicopathologic factors associated with survival in NF-PNETs and (2) preoperative tumor characteristics that can be used to determine which lesions require resection and lymph node (LN) harvest. The records of all 116 patients who underwent resection for NF-PNETs between 1989 and 2012 were reviewed retrospectively. Preoperative factors, operative data, pathology, surgical morbidity, and survival were analyzed. The overall 5- and 10-year survival rates were 83.9 and 72.8 %, respectively. Negative LNs (p = 0.005), G1 or G2 histology (p = 0.033), and age <60 years (p = 0.002) correlated with better survival on multivariate analysis. The 10-year survival rate was 86.6 % for LN-negative patients (n = 73) and 34.1 % for LN-positive patients (n = 32). Tumor size ≥2 cm on preoperative imaging predicted nodal positivity with a sensitivity of 93.8 %. Positive LNs were found in 38.5 % of tumors ≥2 cm compared to only 7.4 % of tumors <2 cm. LN status, a marker of systemic disease, was a highly significant predictor of survival in this series. Tumor size on preoperative imaging was predictive of nodal disease. Thus, it is reasonable to consider parenchyma-sparing resection or even close observation for NF-PNETs <2 cm.
    Journal of Gastrointestinal Surgery 10/2013; · 2.36 Impact Factor
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    ABSTRACT: The association between gallbladder polyps (GBP) and gallbladder cancer (GBC) is unclear. We sought to determine the association between preoperative diagnosis of GBP on imaging and GBC. A retrospective review of patients over 9 years was conducted using International Classification of Diseases, 9th Revision codes for GBP and GBC who underwent cholecystectomy at our institution. Demographics, imaging findings, and pathology results were recorded. A total of 2416 patients underwent cholecystectomy during the study period. Twenty-seven had an operation for GBP either as a result of concern for size or symptoms. Polyp sizes were categorized as less than 1 cm, 1 to 2 cm, or 2 cm or greater. Twenty-four patients in this group (88.9%) had no evidence of high-grade dysplasia or cancer and all of these benign polyps were 2 cm or less on imaging. One patient with a 2.4-cm polyp had high-grade dysplasia, and two patients with polyps over 3 cm had adenocarcinoma. During the same period, 20 patients had an operation for GBC with two patients common to the polyp group. The group of patients with noncancerous polyps was significantly younger than the cancer group (polyps and no polyps). The cancer group was more likely to be symptomatic. Therefore, polyps over 2 cm should be removed given the risk of high-grade dysplasia and cancer above this size. Polyps less than 2 cm were not associated with high-grade dysplasia or cancer and thus surgery may not be required. Intermediate- and small-sized polyps can be monitored with serial ultrasound, especially in younger, asymptomatic patients in whom the risk of malignancy is low.
    The American surgeon 10/2013; 79(10):1005-8. · 0.92 Impact Factor
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    ABSTRACT: Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'-UTR) in regulating growth and survival through gene suppression. Deregulated miRNA expression contributes to disease progression in several cancers types, including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2) resulting in increased cancer growth and metastases. Human PaCa cell lines were used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 ± 0.06 in AsPC-1, 0.20 ± 0.05 in Capan-2 and 0.10 ± 0.02 in MIA PaCa-2. miR-143 was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with 10 μM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187 ± 18 and 152 ± 26 fold in BxPC-3 and 182 ± 7 and 136 ± 9 fold in HPAF-II. miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 ± 0.3 fold in BxPC-3 and 2.5 ± 0.2 fold in HPAF-II. COX-2 expression and cellular proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143. PGE2 levels decreased by 39.3 ± 5.0 % in BxPC-3 and 48.0 ± 3.0 % in HPAF-II transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX-2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway in regulating miR-143 expression.
    Biochemical and Biophysical Research Communications 08/2013; · 2.28 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) patients demonstrate highly variable survival within each stage of the American Joint Committee on Cancer (AJCC) staging system. We hypothesize that tumor grade is partly responsible for this variation. Recently our group developed a novel tumor, node, metastasis, grade (TNMG) classification system utilizing Surveillance Epidemiology and End Results (SEER) data in which the presence of high tumor grade results in advancement to the next higher AJCC stage. This study's objective was to validate this TNMG staging system utilizing single-institution data. All patients with PDAC who underwent resection at UCLA between 1990 and 2009 were identified. Clinicopathologic data reviewed included age, sex, node status, tumor size, grade, and stage. Grade was redefined as a dichotomous variable. The impact of grade on survival was assessed by Cox regression analysis. Disease was restaged into the TNMG system and compared to the AJCC staging system. We identified 256 patients who underwent resection for PDAC. Patients with low-grade tumors experienced a 13-month improvement in median survival compared to those with high-grade tumors. On multivariate analysis, tumor grade was the strongest predictor of survival with a hazard ratio of 2.02 (p = 0.0005). Restaging disease according to the novel TNMG staging system resulted in improved survival discrimination between stages compared to the current AJCC system. We were able to demonstrate that grade is one of the strongest independent prognostic factors in PDAC. Restaging with our novel TNMG system demonstrated improved prognostication. This system offers an effective and convenient way of adding grade to the current AJCC staging system.
    Annals of Surgical Oncology 08/2013; · 4.12 Impact Factor
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    ABSTRACT: There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, e.g. weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a diet high in fats and calories (HFCD; ~4,535 kcal/kg; 40% of calories from fats) or control diet (CD; ~3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared to control animals, mice fed the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of IGF-1. The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T-cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results demonstrate that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity as well as to evaluate dietary- and chemo-preventive strategies targeting obesity-associated pancreatic cancer development.
    Cancer Prevention Research 08/2013; · 4.89 Impact Factor
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    ABSTRACT: Anti-apoptotic Bcl-2 family proteins have been reported to play an important role in apoptotic cell death of human malignancies. The aim of this study was to delineate the mechanism of anti-apoptotic Bcl-2 family proteins in pancreatic cancer (PaCa) cell survival. We first analyzed the endogenous expression and subcellular localization of anti-apoptotic Bcl-2 family proteins in six PaCa cell lines by Western blot. To delineate the functional role of Bcl-2 family proteins, siRNA-mediated knock-down of protein expression was used. Apoptosis was measured by Cell Death ELISA and Hoechst 33258 staining. In the results, the expression of anti-apoptotic Bcl-2 family proteins varied between PaCa cell lines. Mcl-1 knock-down resulted in marked cleavage of PARP and induction of apoptosis. Down-regulation of Bcl-2 or Bcl-xL had a much weaker effect. Simultaneous knock-down of Bcl-xL and Mcl-1 strongly induced apoptosis, but simultaneous knock-down of Bcl-xL/Bcl-2 or Mcl-1/Bcl-2 had no additive effect. The apoptosis-inducing effect of simultaneous knock-down of Bcl-xL and Mcl-1 was associated with translocation of Bax from the cytosol to the mitochondrial membrane, cytochrome c release, and caspase activation. These results demonstrated that Bcl-xL and Mcl-1 play an important role in pancreatic cancer cell survival. Targeting both Bcl-xL and Mcl-1 may be intriguing therapeutic strategy in PaCa.
    Biochimica et Biophysica Acta 08/2013; · 4.66 Impact Factor
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    ABSTRACT: INTRODUCTION: The Joint Commission Surgical Care Improvement Project (SCIP) includes performance measures aimed at reducing surgical site infections (SSI). One measure defines approved perioperative antibiotics for general operative procedures. However, there may be a subset of procedures not adequately covered with the use of approved antibiotics. We hypothesized that piperacillin-tazobactam is a more appropriate perioperative antibiotic for pancreaticoduodenectomy (PD). METHODS: In collaboration with hospital epidemiology and the Division of Infectious Diseases, we retrospectively reviewed records of 34 patients undergoing PD between March and May 2008 who received SCIP-approved perioperative antibiotics and calculated the SSI rate. After changing our perioperative antibiotic to piperacillin-tazobactam, we prospectively reviewed PDs performed between June 2008 and March 2009 and compared the SSI rates before and after the change. RESULTS: For 34 patients from March through May 2008, the SSI rate for PD was 32.4 per 100 cases. Common organisms from wound cultures were Enterobacter and Enterococcus (50.0% and 41.7%, respectively), and these were cefoxitin resistant. From June 2008 through March 2009, 106 PDs were performed. During this period, the SSI rate was 6.6 per 100 surgeries, 80% lower than during March through May 2008 (relative risk, 0.204; 95% confidence interval [CI], 0.086-0.485; P = .0004). CONCLUSION: Use of piperacillin-tazobactam as a perioperative antibiotic in PD may reduce SSI compared with the use of SCIP-approved antibiotics. Continued evaluation of SCIP performance measures in relationship to patient outcomes is integral to sustained quality improvement.
    Surgery 05/2013; · 3.37 Impact Factor
  • Pancreatology 03/2013; 13(2):e3–e4. · 2.04 Impact Factor
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    ABSTRACT: Introduction: Pancreatic cancer, a leading cause of cancer deaths worldwide, is very aggressive and has minimally effective treatment options. For those who have no surgical options, medical treatments are limited. The chemokine receptor CXCR2 has become the subject of much interest recently because of multiple studies indicating its involvement in cancer and inflammatory conditions. Research now indicates that CXCR2 and its ligands are intimately involved in tumor regulation and growth and that inhibition of its function shows promising results in multiple cancer types, including pancreatic cancer. Areas covered: In this study, the authors review basic molecular and structural details of CXCR2, as well as the known functions of CXCR2 and several of its ligands in inflammation and cancer biology with specific attention to pancreatic cancer. Then the future possibilities and questions remaining for pharmacological intervention against CXCR2 in pancreatic cancer are explored. Expert opinion: Many current inhibitory strategies already exist for targeting CXCR2 in vitro as well as in vivo. Clinically speaking, CXCR2 is an exciting potential target for pancreatic cancer; however, CXCR2 is functionally important for multiple processes and therapeutic options would benefit from further work toward understanding of these roles as well as structural and target specificity.
    Expert Opinion on Therapeutic Targets 02/2013; · 4.90 Impact Factor
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    ABSTRACT: The association between gallbladder polyps (GBP) and gallbladder cancer (GBC) is unclear. We sought to determine the association between preoperative diagnosis of GBP on imaging and GBC. A retrospective review of patients over 9 years was conducted using International Classification of Diseases, 9th Revision codes for GBP and GBC who underwent cholecystectomy at our institution. Demographics, imaging findings, and pathology results were recorded. A total of 2416 patients underwent cholecystectomy during the study period. Twenty-seven had an operation for GBP either as a result of concern for size or symptoms. Polyp sizes were categorized as less than 1 cm, 1 to 2 cm, or 2 cm or greater. Twenty-four patients in this group (88.9%) had no evidence of high-grade dysplasia or cancer and all of these benign polyps were 2 cm or less on imaging. One patient with a 2.4-cm polyp had high-grade dysplasia, and two patients with polyps over 3 cm had adenocarcinoma. During the same period, 20 patients had an operation for GBC with two patients common to the polyp group. The group of patients with noncancerous polyps was significantly younger than the cancer group (polyps and no polyps). The cancer group was more likely to be symptomatic. Therefore, polyps over 2 cm should be removed given the risk of high-grade dysplasia and cancer above this size. Polyps less than 2 cm were not associated with high-grade dysplasia or cancer and thus surgery may not be required. Intermediate- and small-sized polyps can be monitored with serial ultrasound, especially in younger, asymptomatic patients in whom the risk of malignancy is low.
    The American surgeon 01/2013; 79(10):1005-1008. · 0.92 Impact Factor
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    ABSTRACT: To describe the development of a cadaver-based educational program and report our residents' assessment of the new program. An anatomy-based educational program was developed using fresh frozen cadavers to teach surgical anatomy and operative skills to general surgery (GS) trainees. Residents were asked to complete a voluntary, anonymous survey evaluating perceptions of the program (6 questions formulated on a 5-point Likert scale) and comparing cadaver sessions to other types of learning (4 rank order questions). Large university teaching hospital. Medical students, residents, and faculty members were participants in the cadaver programs. Only GS residents were asked to complete the survey. Since its implementation, 150 residents of all levels participated in 13 sessions. A total of 40 surveys were returned for a response rate of 89%. Overall, respondents held a positive view of the cadaver sessions and believed them to be useful for learning anatomy (94% agree or strongly agree), learning the steps of an operation (76% agree or strongly agree), and increasing confidence in doing an operation (53% agree or strongly agree). Trainees wanted to have more sessions (87% agree or strongly agree), and believed they would spend free time in the cadaver laboratory (58% agree or strongly agree). Compared with other learning modalities, cadaver sessions were ranked first for learning surgical anatomy, followed by textbooks, simulators, web sites, animate laboratories, and lectures. Respondents also ranked cadaver sessions first for increasing confidence in performing a procedure and for learning the steps of an operation. Cost of cadavers represented the major expense of the program. Fresh cadaver dissections represent a solution to the challenges of efficient, safe, and effective general surgery education. Residents have a positive attitude toward these teaching sessions and found them to be more effective than other learning modalities.
    Journal of Surgical Education 11/2012; 69(6):693-8. · 1.07 Impact Factor
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    ABSTRACT: Management of infected pancreatic necrosis (IPN) has for decades been based on early operative débridement. This approach is associated with mortality rates as high as 58 per cent. Recently, the care of these patients has evolved and emphasizes delayed operation and early intervention with percutaneous drainage. In 2002, we began to incorporate these new principles for the treatment of IPN and herein characterize the recent UCLA experience with management of IPN. A retrospective review of patients with IPN treated at UCLA between 2002 and 2011 was conducted. Mean patient age was 53.4 years. Mean Ranson's score was 3.3 ± 2.3 and average number of concurrent comorbidities 3.2 ± 2.5. All patients were treated with intravenous antibiotics. Thirteen of 18 patients (72.2%) had percutaneous drainage catheters placed (mean 1.1 drains per patient). Two patients were treated with percutaneous drainage alone. Sixteen of 18 (88.9%) eventually underwent surgical débridement. Of the operative patients, mean time from diagnosis to surgery was 28.4 days. The mortality in this group was 16.7 per cent. In conclusion, antibiotics and percutaneous drainage is an acceptable and possibly preferable initial therapeutic strategy for patients with IPN. Delayed operation and early intervention with percutaneous drainage appears to improve mortality for these patients.
    The American surgeon 10/2012; 78(10):1151-5. · 0.92 Impact Factor
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    ABSTRACT: Tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) activates β-adrenergic receptor (β-AR) signaling through Src/focal adhesion kinases (FAKs)/mitogen-activated protein kinase to modulate proliferation, migration, and survival. Apigenin (4', 5, 7-trihydroxyflavone) is reported to attenuate proliferation and migration of cancer cells. This study was designed to determine the effects of apigenin on NNK-induced procarcinogenesis using human pancreatic cancer cells BxPC-3 and MIA PaCa-2, which express β-AR. Proliferation and migration were assessed by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and scratch assays. β-AR, FAK/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) expression and activation were assessed by Western blotting and real-time polymerase chain reaction. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone caused a dose- and time-dependent increase in BxPC-3 and MIA PaCa-2 cell proliferation that was inhibited by propranolol or apigenin. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone also stimulated a time-dependent increase in FAK and ERK activation that was suppressed by propranolol or apigenin. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-enhanced gap closure at 24 hours was prevented by either propranolol or apigenin. Apigenin suppressed the effects of NNK on pancreatic cancer cell proliferation and migration that are mediated through the β-AR and its downstream signals FAK and ERK activation. These findings suggest a therapeutic role for this natural phytochemical in attenuating the procarcinogenic effects of NNK on pancreatic cancer proliferation and migration.
    Pancreas 08/2012; 41(8):1306-15. · 2.95 Impact Factor

Publication Stats

3k Citations
913.90 Total Impact Points

Institutions

  • 2014
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2008–2013
    • VA Greater Los Angeles Healthcare System
      Los Angeles, California, United States
  • 1994–2013
    • University of California, Los Angeles
      • • Department of Surgery
      • • Division of General Surgery
      • • Department of Medicine
      Los Angeles, CA, United States
  • 2011
    • County of Los Angeles Public Health
      Los Angeles, California, United States
  • 2010
    • John Wayne Cancer Institute
      Santa Monica, California, United States
  • 2006–2010
    • University of Southern California
      • • Department of Surgery
      • • Department of Medicine
      Los Angeles, California, United States
  • 2009
    • Technische Universität München
      München, Bavaria, Germany
  • 2002–2008
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2005–2007
    • Universität Heidelberg
      • Institute of Pathology (Mannheim)
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1996–2007
    • Children's Hospital Los Angeles
      • Department of Surgery
      Los Angeles, California, United States
  • 2003
    • Heidelberg University
      Tiffin, Ohio, United States