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Pancreatic Neoplasms: HELP
Articles by Oscar Joe Hines
Based on 58 articles published since 2010
(Why 58 articles?)
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Between 2010 and 2020, O. J. Hines wrote the following 58 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial A Cutoff of 2 cm Instead of 3 cm Would Detect More Malignant BD-IPMNs: Is There a Reason to Be Wary of the International Consensus Guidelines? 2016

Hines, O Joe / Stark, Alexander P. ·Department of Surgery, University of California Los Angeles, Los Angeles, CA. ·Pancreas · Pubmed #26658036.

ABSTRACT: -- No abstract --

2 Review Emerging Evidence for the Clinical Relevance of Pancreatic Cancer Exosomes. 2019

Massoumi, Roxanne L / Hines, O Joe / Eibl, Guido / King, Jonathan C. ·From the Department of Surgery, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA. ·Pancreas · Pubmed #30531240.

ABSTRACT: The last 5 years have seen a dramatic increased interest in the field of exosome biology. Although much is unknown about the role of exosomes in human health and disease, disparate scientific disciplines are recognizing the highly conserved role that exosomes play in fundamental biological processes. Recently, there have been intriguing discoveries defining the role of exosomes in cancer biology. We performed a structured review of the English-language literature using the PubMed database searching for articles relating to exosomes and pancreatic ductal adenocarcinoma (PDAC). Articles were screened for relevance and content to judge for inclusion. Evidence implicates exosomes in the pathogenesis, local progression, metastasis, immune evasion, and intercellular communication of PDAC. Basic science discoveries in exosome biology have the potential to change the clinical management of PDAC, where, despite advances in early detection, diagnosis, staging, chemotherapy, and surgery, survival rates have been stagnant for decades and PDAC remains the most deadly human gastrointestinal malignancy.

3 Review Quality of Life in Patients With Pancreatic Cancer and Their Caregivers: A Systematic Review. 2018

Bauer, Margaret R / Bright, Emma E / MacDonald, James J / Cleary, Elizabeth H / Hines, O Joe / Stanton, Annette L. · ·Pancreas · Pubmed #29521939.

ABSTRACT: Little is known about quality of life (QOL) of patients with pancreatic cancer and their caregivers compared with adults with other cancers. This systematic review summarizes the available evidence base, identifies its limitations, and recommends directions for research and clinical application. A systematic review was conducted of research on QOL in adults with pancreatic cancer and their caregivers. Quality of life was examined in the following specific domains: psychological, physical, social, sexual, spiritual, and general. Of the 7130 articles reviewed, 36 studies met criteria for inclusion. Compared with healthy adults or population norms, adults with pancreatic cancer had worse QOL across all domains. Compared with patients with other cancer types, patients with pancreatic cancer evidenced worse psychological QOL. Physical and social QOL were either similar or more compromised than in patients with other cancers. Limited data preclude conclusions about sexual, spiritual, and caregiver QOL. Patients with pancreatic cancer evidence decrements in multiple QOL domains, with particular strain on psychological well-being. Methodological limitations of available studies restrict definitive conclusions. Future research with well-defined samples, appropriate statistical analyses, and longitudinal designs is needed. Findings from this review support the merits of distress screening, integration of mental health professionals into medical teams, and attention to caregiver burden.

4 Review Obesity and Pancreatic Cancer: Overview of Epidemiology and Potential Prevention by Weight Loss. 2018

Xu, Mu / Jung, Xiaoman / Hines, O Joe / Eibl, Guido / Chen, Yijun. ·From the Department of Surgery, University of California, Los Angeles, Los Angeles, CA. ·Pancreas · Pubmed #29346216.

ABSTRACT: Currently, there are no effective preventive strategies for pancreatic cancer. Obesity has been increasingly recognized as a strong but modifiable risk factor of pancreatic cancer. In this article, we aim to review the literature regarding weight loss on prevention of pancreatic cancer. Epidemiological and laboratory studies have shown that obesity is associated with increased incidence of pancreatic cancer and potentially worse cancer outcome. Whereas the underlying pathomechanisms remain unclear, chronic inflammation, insulin resistance, and altered intestinal microbiota are all implicated in the carcinogenic effect of obesity. Weight loss, especially the durable and significant weight loss after bariatric surgery, has been shown to reduce the risks of multiple cancers and may become a good intervention for pancreatic cancer prevention.

5 Review Pancreatic Cyst Disease: A Review. 2016

Stark, Alexander / Donahue, Timothy R / Reber, Howard A / Hines, O Joe. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California. ·JAMA · Pubmed #27139061.

ABSTRACT: IMPORTANCE: Cystic lesions of the pancreas are common and increasingly detected in the primary care setting. Some patients have a low risk for developing a malignancy and others have a high risk and need further testing and interventions. OBSERVATIONS: Pancreatic cysts may be intraductal mucinous neoplasms, mucinous cystic neoplasms, serous cystadenomas, solid pseudopapillary neoplasms, cystic variations of pancreatic neuroendocrine tumors, pancreatic ductal adenocarcinomas, or 1 of several types of nonneoplastic cysts. Mucinous (intraductal mucinous neoplasm or mucinous cystic neoplasm) lesions have malignant potential and should be distinguished from serous lesions (serous cystadenomas) that are nearly always benign. Symptomatic patients or those having high-risk features on initial imaging (eg, main pancreatic duct dilatation, a solid component, or mural nodule) require further evaluation with advanced imaging, possibly followed by surgical resection. Advanced imaging includes endoscopic ultrasound with cyst fluid analysis and cytology to confirm the type of cyst and determine the risk of malignancy. Small cysts (size <3 cm) in asymptomatic patients without any suspicious features may be observed with serial imaging because the risk for malignancy is low. CONCLUSIONS AND RELEVANCE: The management of pancreatic cysts requires risk stratification for malignant potential based on the presence or absence of symptoms and high-risk features on cross-sectional imaging. Because pancreatic cysts are becoming more frequently diagnosed, clinicians should have a systematic approach for establishing a diagnosis and determining which patients require treatment.

6 Review Early detection of sporadic pancreatic cancer: summative review. 2015

Chari, Suresh T / Kelly, Kimberly / Hollingsworth, Michael A / Thayer, Sarah P / Ahlquist, David A / Andersen, Dana K / Batra, Surinder K / Brentnall, Teresa A / Canto, Marcia / Cleeter, Deborah F / Firpo, Matthew A / Gambhir, Sanjiv Sam / Go, Vay Liang W / Hines, O Joe / Kenner, Barbara J / Klimstra, David S / Lerch, Markus M / Levy, Michael J / Maitra, Anirban / Mulvihill, Sean J / Petersen, Gloria M / Rhim, Andrew D / Simeone, Diane M / Srivastava, Sudhir / Tanaka, Masao / Vinik, Aaron I / Wong, David. ·From the *Department of Medicine, Mayo Clinic, Rochester, MN; †Department of Biomedical Engineering, University of Virginia, Charlottesville, VA; Departments of ‡Biochemistry and Molecular Biology, §Pathology and Microbiology, and ∥Surgery, Fred & Pamela Buffett Cancer Center, University of Nebraska, Omaha, NE; ¶Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD; #Division of Gastroenterology, University of Washington, Seattle, WA; **Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD; ††Sawgrass Leadership Institute, Ponte Vedra Beach, FL; ‡‡Department of Surgery, University of Utah, Salt Lake City, UT; §§Department of Radiology, Stanford University School of Medicine, Stanford; ∥∥Department of Medicine, David Geffen School of Medicine, and ¶¶General Surgery, University of California Los Angeles, Los Angeles, CA; ##Kenner Family Research Fund; ***Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; †††Department of Internal Medicine, University of Greifswald, Greifswald, Germany; ‡‡‡Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; §§§Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥∥∥Gastroenterology Division, Department of Internal Medicine and Comprehensive Cancer Center, and ¶¶¶Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, MI; ###Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD; ****Departments of Surgery and Oncology, Kyushu University, Fukuoka, Japan; ††††Department of Medicine, Eastern Virginia Medical School, Norfolk, VA; and ‡‡‡‡Division of Oral Biology and Medicine, CLA School of Dentistry, Jonnson Comprehensive Cancer Center, University of California Los Angeles, L ·Pancreas · Pubmed #25931254.

ABSTRACT: Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

7 Review Endoscopic and operative palliation strategies for pancreatic ductal adenocarcinoma. 2015

Stark, Alexander / Hines, O Joe. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: joehines@mednet.ucla.edu. ·Semin Oncol · Pubmed #25726060.

ABSTRACT: Malignant biliary obstruction, duodenal, and gastric outlet obstruction, and tumor-related pain are the complications of unresectable pancreatic adenocarcinoma that most frequently require palliative intervention. Surgery involving biliary bypass with or without gastrojejunostomy was once the mainstay of treatment in these patients. However, advances in non-operative techniques-most notably the widespread availability of endoscopic biliary and duodenal stents-have shifted the paradigm of treatment away from traditional surgical management. Questions regarding the efficacy and durability of endoscopic stents for biliary and gastric outlet obstruction are reviewed and demonstrate high rates of therapeutic success, low rates of morbidity, and decreased cost. Surgery remains an effective treatment modality, and still produces the most durable relief in appropriately selected patients.

8 Review CXCR2: a target for pancreatic cancer treatment? 2013

Hertzer, Kathleen M / Donald, Graham W / Hines, O Joe. ·Hirshberg Translational Pancreatic Cancer Research Laboratory, David Geffen School of Medicine at UCLA, Department of Surgery , 675 Charles E Young Drive, MRL 2535, Los Angeles, CA 90095 , USA. ·Expert Opin Ther Targets · Pubmed #23425074.

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.

9 Review Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. 2011

Assifi, M Mura / Lu, Xuyang / Eibl, Guido / Reber, Howard A / Li, Gang / Hines, O Joe. ·Department of Surgery, UCLA School of Public Health, Los Angeles, CA, USA. ·Surgery · Pubmed #21878232.

ABSTRACT: BACKGROUND: Neoadjuvant treatment has proven beneficial for many gastrointestinal (GI) malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. This meta-analysis examines the best available phase II trials using neoadjuvant treatment for resectable and borderline/unresectable pancreatic adenocarcinoma. METHODS: Phase II trials were identified using a MEDLINE search, and the Cochrane Central Register of Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups: Patients with initially resectable tumors (group A), and patients with borderline/unresectable tumors (group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. RESULTS: A total of 14 phase II clinical trials including 536 patients were analyzed. After treatment, resectability was 65.8% (95% CI, 55.4-75.6%) compared with 31.6% in group B (95% CI, 14.0-52.5%). A partial response was observed in patients with borderline/unresectable tumors; 31.8 (95% CI, 24.2-39.8%) in group B and 9.5% (95% CI, 2.9-19.4%) in group A (P = .003). Progressive disease was seen in 17.0% (95% CI, 11.9-22.7) of patients in group A versus 21.8% (95% CI, 10.1-36.5%) in group B (P = .006). Median survival in resected patients was 23 months for group A and 22 months for group B. CONCLUSION: Neoadjuvant treatment seems to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors initially deemed marginal for operative intervention were able to be ultimately resected after treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.

10 Review Anti-angiogenic agents in pancreatic cancer: a review. 2011

Assifi, M Mura / Hines, O Joe. ·Department of Surgery, UCLA David Geffen School of Medicine, University of California-Los Angeles, CA 90095-6904, USA. muraassifi@gmail.com ·Anticancer Agents Med Chem · Pubmed #21521158.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer related death in the United States, with a 5-year survival of less than five percent. Since the majority of patients have locally advanced or metastatic disease at the time of diagnosis, there has been little progress made to extend survival. For over ten years, chemotherapy with gemcitabine has been standard treatment for those patients with advanced pancreatic cancer, prolonging survival by only 5-6 months. To improve upon this modest benefit, several investigations have explored other strategies aimed at curbing pancreatic cancer growth. Because pancreatic cancer has been found to have a profoundly hypoxic environment with high vascular in-growth, several agents have been developed to target the angiogenesis process. Major emphasis has been placed on anti- vascular endothelial growth factor (VEGF) models and the epidermal growth factor receptor (EGFR) signaling pathway. Over the past several years, a number of phase II and phase III trials have combined gemcitabine with these novel treatments, with the hope of prolonging survival in patients with pancreatic cancer. This review will discuss these therapies and their potential application in a clinical setting.

11 Clinical Trial Pancreatic cancer patients with lymph node involvement by direct tumor extension have similar survival to those with node-negative disease. 2015

Williams, Jennifer L / Nguyen, Andrew H / Rochefort, Matthew / Muthusamy, V Raman / Wainberg, Zev A / Dawson, David W / Tomlinson, James S / Hines, O Joe / Reber, Howard A / Donahue, Timothy R. ·Department of Surgery, Harbor-UCLA Medical Center, Torrance, California. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California. · Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California. · Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California. · Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, California. ·J Surg Oncol · Pubmed #26303811.

ABSTRACT: BACKGROUND: Lymph node (LN) involvement is a well-known poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). However, there have been conflicting results on the significance of the mechanism of LN involvement, "direct" tumor invasion versus "metastatic," disease on patient survival. METHODS: Clinicopathologic records from all patients who underwent resection for PDAC from 1990 to 2014 at a single-institution were reviewed. RESULTS: Of the 385 total patients, there was tumor invasion outside of the pancreas in 289 (75.1%) patients. Overall, 239 (62.1%) had node-positive disease: 220 (92.0%) by "metastatic" involvement, 14 (5.9%) by "direct" tumor extension, and five (2.1%) by a mix of "metastatic" and "direct". There were no significant differences in clinicopathologic factors associated with PDAC survival between "metastatic" and "direct" LN patients. The median overall survival for the whole cohort was 31.1 months. Compared to overall survival in patients with LN-negative disease (median 40.7 months), those with LNs involved by "metastatic" spread was significantly shorter (median 25.7 months, P < 0.001), yet "direct" LN extension was similar (median 48.1 months, P = 0.719). CONCLUSIONS: The mechanism of LN involvement affects PDAC prognosis. Patients with LNs involved by direct extension have similar survival to those with node-negative disease.

12 Article The New American Joint Committee on Cancer TNM Staging System for Pancreatic Cancer-Balancing Usefulness With Prognostication. 2018

Court, Colin M / Hines, O Joe. ·Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles. ·JAMA Surg · Pubmed #30285059.

ABSTRACT: -- No abstract --

13 Article Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice. 2018

Xu, Mu / Chang, Hui-Hua / Jung, Xiaoman / Moro, Aune / Chou, Caroline Ei Ne / King, Jonathan / Hines, O Joe / Sinnett-Smith, James / Rozengurt, Enrique / Eibl, Guido. ·Departments of Surgery, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, CHS 72-236, Los Angeles, CA, 90095, USA. · CURE: Digestive Diseases Research Center, University of California at Los Angeles, Los Angeles, USA. · Departments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. · Departments of Surgery, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, CHS 72-236, Los Angeles, CA, 90095, USA. GEibl@mednet.ucla.edu. · CURE: Digestive Diseases Research Center, University of California at Los Angeles, Los Angeles, USA. GEibl@mednet.ucla.edu. ·BMC Cancer · Pubmed #30086728.

ABSTRACT: BACKGROUND: Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC. METHODS: KC;Hsl RESULTS: Compared to KC;Hsl CONCLUSIONS: HSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.

14 Article Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis. 2018

Isacoff, William H / Reber, Howard A / Bedford, Rudolph / Hoos, William / Rahib, Lola / Upfill-Brown, Alexander / Donahue, Timothy / Hines, O Joe. ·Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), 1301 20th Street, Suite 280, Santa Monica, CA, 90404, USA. whisacoff@earthlink.net. · Department of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA. · Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), 1301 20th Street, Suite 280, Santa Monica, CA, 90404, USA. · Pancreatic Action Network, Manhattan Beach, CA, USA. ·Target Oncol · Pubmed #29882102.

ABSTRACT: BACKGROUND: Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic. OBJECTIVE: In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy. PATIENTS AND METHODS: Since July of 2008, we have treated 65 patients with 5FU (180 mg/m RESULTS: The median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy. CONCLUSIONS: This non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective.

15 Article Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model. 2018

Chang, Hui-Hua / Moro, Aune / Chou, Caroline Ei Ne / Dawson, David W / French, Samuel / Schmidt, Andrea I / Sinnett-Smith, James / Hao, Fang / Hines, O Joe / Eibl, Guido / Rozengurt, Enrique. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg, Freiburg, Germany. · Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. GEibl@mednet.ucla.edu. ·Sci Rep · Pubmed #29651002.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the Kras

16 Article Incidence of pancreatic cancer is dramatically increased by a high fat, high calorie diet in KrasG12D mice. 2017

Chang, Hui-Hua / Moro, Aune / Takakura, Kazuki / Su, Hsin-Yuan / Mo, Allen / Nakanishi, Masako / Waldron, Richard T / French, Samuel W / Dawson, David W / Hines, O Joe / Li, Gang / Go, Vay Liang W / Sinnett-Smith, James / Pandol, Stephen J / Lugea, Aurelia / Gukovskaya, Anna S / Duff, Michael O / Rosenberg, Daniel W / Rozengurt, Enrique / Eibl, Guido. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. · Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. · Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States of America. · Pancreatic Research Group, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America. · Center for Molecular Oncology, UCONN Health, Farmington, CT, United States of America. · Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, United States of America. · Southern California Research Center for ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States of America. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America. · Department of Biostatistics, School of Public Health at UCLA, Los Angeles, CA, United States of America. · Department of Genetics and Genome Sciences, UCONN Health, Farmington, CT, United States of America. ·PLoS One · Pubmed #28886117.

ABSTRACT: Epidemiologic data has linked obesity to a higher risk of pancreatic cancer, but the underlying mechanisms are poorly understood. To allow for detailed mechanistic studies in a relevant model mimicking diet-induced obesity and pancreatic cancer, a high-fat, high-calorie diet (HFCD) was given to P48+/Cre;LSL-KRASG12D (KC) mice carrying a pancreas-specific oncogenic Kras mutation. The mice were randomly allocated to a HFCD or control diet (CD). Cohorts were sacrificed at 3, 6, and 9 months and tissues were harvested for further analysis. Compared to CD-fed mice, HFCD-fed animals gained significantly more weight. Importantly, the cancer incidence was remarkably increased in HFCD-fed KC mice, particularly in male KC mice. In addition, KC mice fed the HFCD showed more extensive inflammation and fibrosis, and more advanced PanIN lesions in the pancreas, compared to age-matched CD-fed animals. Interestingly, we found that the HFCD reduced autophagic flux in PanIN lesions in KC mice. Further, exome sequencing of isolated murine PanIN lesions identified numerous genetic variants unique to the HFCD. These data underscore the role of sustained inflammation and dysregulated autophagy in diet-induced pancreatic cancer development and suggest that diet-induced genetic alterations may contribute to this process. Our findings provide a better understanding of the mechanisms underlying the obesity-cancer link in males and females, and will facilitate the development of interventions targeting obesity-associated pancreatic cancer.

17 Article Direct growth-inhibitory effects of prostaglandin E2 in pancreatic cancer cells in vitro through an EP4/PKA-mediated mechanism. 2017

Schmidt, Andrea / Sinnett-Smith, James / Young, Steven / Chang, Hui-Hua / Hines, O Joe / Dawson, David W / Rozengurt, Enrique / Eibl, Guido. ·Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA; Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg, Freiburg, Germany. · Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: GEibl@mednet.ucla.edu. ·Surgery · Pubmed #28222855.

ABSTRACT: BACKGROUND: There is strong evidence linking inflammation and the development of pancreatic ductal adenocarcinoma. Cyclooxygenase-2 (COX-2) and COX-2-derived PGE METHODS: Human pancreatic ductal adenocarcinoma cell lines, Panc-1 and MIA PaCa-2, were treated with PGE RESULTS: PGE CONCLUSION: Our study provides evidence that PGE

18 Article Reply. 2017

Hines, O Joe. ·Department of Surgery David Geffen School of Medicine at UCLA Los Angeles, CA joehines@mednet.ucla.edu. ·Pancreas · Pubmed #27977630.

ABSTRACT: -- No abstract --

19 Article Assessment of a Revised Management Strategy for Patients With Intraductal Papillary Mucinous Neoplasms Involving the Main Pancreatic Duct. 2017

Sugimoto, Motokazu / Elliott, Irmina A / Nguyen, Andrew H / Kim, Stephen / Muthusamy, V Raman / Watson, Rabindra / Hines, O Joe / Dawson, David W / Reber, Howard A / Donahue, Timothy R. ·Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA). · Division of Digestive Diseases, David Geffen School of Medicine at UCLA. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA. ·JAMA Surg · Pubmed #27829085.

ABSTRACT: Importance: According to the 2012 International Consensus Guidelines, the diagnostic criterion of intraductal papillary mucinous neoplasms (IPMNs) involving the main duct (MD IPMNs) or the main and branch ducts (mixed IPMNs) of the pancreatic system is a main pancreatic duct (MPD) diameter of 5.0 mm or greater on computed tomography (CT) or magnetic resonance imaging (MRI). However, surgical resection is recommended for patients with an MPD diameter of 10.0 mm or greater, which is characterized as a high-risk stigma. An MPD diameter of 5.0 to 9.0 mm is not an indication for immediate resection. Objectives: To determine an appropriate cutoff (ie, one with high sensitivity and negative predictive value) of the MPD diameter on CT or MRI as a prognostic factor for malignant disease and to propose a new management algorithm for patients with MD or mixed IPMNs. Design, Setting, and Participants: This retrospective cohort study included 103 patients who underwent surgical resection for a preoperative diagnosis of MD or mixed IPMN and in whom IPMN was confirmed by surgical pathologic findings at a single institution from July 1, 1996, to December 31, 2015. Main Outcomes and Measures: Malignant disease was defined as high-grade dysplasia or invasive adenocarcinoma on results of surgical pathologic evaluation. An appropriate MPD diameter on preoperative CT or MRI to predict malignant disease was determined using a receiver operating characteristic curve analysis. The prognostic value of the new management algorithm that incorporated the new MPD diameter cutoff was evaluated. Results: Among the 103 patients undergoing resection for an MD or mixed IPMN (59 men [57.3%]; 44 women [42.7%]; median [range] age, 71 [48-86] years), 64 (62.1%) had malignant disease. Diagnostic accuracy for malignant neoplasms was highest at an MPD diameter cutoff of 7.2 mm (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.81). An MPD diameter of 7.2 mm or greater was also an independent prognostic factor for malignant neoplasms (odds ratio, 12.76; 95% CI, 2.43-66.88; P = .003) on logistic regression analysis after controlling for preoperative variables. The new management algorithm, which included an MPD diameter of 7.2 mm or greater as one of the high-risk stigmata, had a higher sensitivity (100%), negative predictive value (100%), and accuracy (66%) for malignant disease than the 2012 version of the International Consensus Guidelines (95%, 57%, and 63%, respectively). Conclusions and Relevance: In this single-center, retrospective analysis, an MPD diameter of 7.2 mm was identified as an optimal cutoff for a prognostic factor for malignant disease in MD or mixed IPMN. These data support lowering the accepted criteria for MPD diameter when selecting patients for resection vs surveillance so as not to overlook cancer in IPMN.

20 Article Polyglycolic Acid Mesh in Distal Pancreatectomy: A Tool for Preventing Postoperative Pancreatic Fistula? 2017

Juo, Yen-Yi / Hines, O Joe. ·Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles. ·JAMA Surg · Pubmed #27784043.

ABSTRACT: -- No abstract --

21 Article Association of Histopathologic Phenotype of Periampullary Adenocarcinomas With Survival. 2017

Williams, Jennifer L / Chan, Carmen K / Toste, Paul A / Elliott, Irmina A / Vasquez, Charles R / Sunjaya, Dharma B / Swanson, Eric A / Koo, Jamie / Hines, O Joe / Reber, Howard A / Dawson, David W / Donahue, Timothy R. ·Department of Surgery, Harbor-UCLA Medical Center, Los Angeles, California2Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles. · Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles. · Department of Pathology, University of Utah, Salt Lake City. · Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles. · Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles6Department of Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. ·JAMA Surg · Pubmed #27732711.

ABSTRACT: Importance: Patients with periampullary adenocarcinomas have widely variable survival. These cancers are traditionally categorized by their anatomic location of origin, namely, the duodenum, ampulla, distal common bile duct (CBD), or head of the pancreas. However, they can be alternatively subdivided histopathologically into intestinal or pancreaticobiliary (PB) types, which may more accurately estimate prognosis. Objectives: To identify factors associated with survival in patients with periampullary adenocarcinomas and to compare survival between those having intestinal-type or PB-type cancers originating from the duodenum, ampulla, or distal CBD with those having pancreatic ductal adenocarcinoma (PDAC). Design, Setting, and Participants: This study was a retrospective analysis of medical records in a prospectively maintained database. Three pathologists separately evaluated histopathologic phenotypes at a university-based tertiary referral center. Study participants were all patients (N = 510) who underwent pancreatoduodenectomy for adenocarcinoma between January 1995 and December 2014. Main Outcome and Measure: Overall survival. Results: This study identified 510 patients (mean [SD] age, 66.1 [10.9] years; 245 female [48%]) who underwent pancreatoduodenectomy for adenocarcinomas: 13 duodenal, 110 ampullary, 43 distal CBD, and 344 PDAC. The median overall survival was 61.2 (interquartile range [IQR], 22.0-111.0), 70.4 (IQR, 26.7-147.7), 40.6 (IQR, 15.2-59.6), and 31.4 (IQR, 17.3-86.3) months for patients with cancers of the duodenum, ampulla, distal CBD, or pancreas, respectively (P = .01), indicating a significant difference between the 4 tumor anatomic locations. Most duodenal (61.5% [8 of 13]) and ampullary (51.8% [57 of 110]) cancers were intestinal type, and most distal CBD tumors were PB type (86.0% [37 of 43]). Those with intestinal-type duodenal, ampullary, or distal CBD adenocarcinomas had longer median overall survival than those with PB type (71.7 vs 33.3 months, P = .02) or PDAC (31.4 months, P = .003). There was no survival difference between PB-type cancers and PDAC (33.3 vs 31.4 months, P = .66). On multivariable analysis, histologic grade (hazard ratio [HR], 1.98; 95% CI, 1.56-2.52; P < .001), histopathologic phenotype (HR, 1.75; 95% CI, 1.16-2.64; P = .008), and nodal status (HR, 1.45; 95% CI, 1.12-1.87; P = .05) were significantly associated with survival, while anatomic location was not. Conclusions and Relevance: Histopathologic phenotype is a better prognosticator of survival in patients with periampullary adenocarcinomas than tumor anatomic location. Those with PB-type duodenal, ampullary, or distal CBD adenocarcinomas have survival similar to those with PDAC.

22 Article Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer. 2016

Ankeny, J S / Court, C M / Hou, S / Li, Q / Song, M / Wu, D / Chen, J F / Lee, T / Lin, M / Sho, S / Rochefort, M M / Girgis, M D / Yao, J / Wainberg, Z A / Muthusamy, V R / Watson, R R / Donahue, T R / Hines, O J / Reber, H A / Graeber, T G / Tseng, H R / Tomlinson, J S. ·Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA. · Veteran's Health Administration, Greater Los Angeles, Department of Surgery, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA. · Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA. · California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA 90095, USA. · UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA. · Department of Hematology/Oncology, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA. · Department of Gastroenterology, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA. ·Br J Cancer · Pubmed #27300108.

ABSTRACT: BACKGROUND: Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation. METHODS: Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC. RESULTS: We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ⩾3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001). CONCLUSION: CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.

23 Article CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer. 2016

Williams, Jennifer L / Kadera, Brian E / Nguyen, Andrew H / Muthusamy, V Raman / Wainberg, Zev A / Hines, O Joe / Reber, Howard A / Donahue, Timothy R. ·Department of Surgery, Harbor-UCLA Medical Center, Torrance, CA, 90502, USA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. · Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. tdonahue@mednet.ucla.edu. · Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 72-215 CHS, Box 956904, Los Angeles, CA, 90095, USA. tdonahue@mednet.ucla.edu. ·J Gastrointest Surg · Pubmed #27114246.

ABSTRACT: BACKGROUND: Compared to the widely adopted 2-4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival. METHODS: Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992-2014 were reviewed. RESULTS: After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P = 0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P = 0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P = 0.930). CONCLUSIONS: Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.

24 Article Long-term survival in patients with pancreatic ductal adenocarcinoma. 2016

Stark, Alexander P / Sacks, Greg D / Rochefort, Matthew M / Donahue, Timothy R / Reber, Howard A / Tomlinson, James S / Dawson, David W / Eibl, Guido / Hines, O Joe. ·Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA. · Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; Department of Surgery, Greater Los Angeles VA Healthcare System, Los Angeles, CA. · Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA. · Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA. Electronic address: joehines@mednet.ucla.edu. ·Surgery · Pubmed #26847803.

ABSTRACT: BACKGROUND: Long-term survival (LTS) is uncommon for patients with pancreatic ductal adenocarcinoma (PDAC). We sought to identify factors that predict 10-year, LTS after resection of PDAC. METHODS: We identified all patients with PDAC who underwent resection at UCLA after 1990 and included all patients eligible for observed LTS (1/1/1990-12/31/2004). An independent pathologist reconfirmed the diagnosis of PDAC in patients with LTS. Logistic regression was used to predict LTS on the basis of patient and tumor characteristics. RESULTS: Of 173 included patients, 53% were male, median age at diagnosis was 66 years, and median survival was 23 months. The rate of observed LTS was 12.1% (n = 21). Age, sex, number of lymph nodes evaluated, margin status, lymphovascular invasion, and adjuvant chemotherapy and radiation were not associated with LTS. The following were associated with LTS on bivariate analysis: low AJCC stage (Ia, Ib, IIa) (P = .034), negative lymph node status (P = .034), low grade (well-, moderately-differentiated) (P = .001), and absence of perineural invasion (P = .019). Only low grade (odds ratio 7.17, P = .012) and absent perineural invasion (odds ratio 3.28, P = .036) were independently associated with increased odds of LTS. Our multivariate model demonstrated good discriminatory power for LTS, as indicated by a c-statistic of 0.7856. CONCLUSION: Absence of perineural invasion and low tumor grade were associated with greater likelihood of LTS. Understanding the tumor biology of LTS may provide critical insight into a disease that is typically marked by aggressive behavior and limited survival.

25 Article Robust Early Inflammation of the Peripancreatic Visceral Adipose Tissue During Diet-Induced Obesity in the KrasG12D Model of Pancreatic Cancer. 2016

Hertzer, Kathleen M / Xu, Mu / Moro, Aune / Dawson, David W / Du, Lin / Li, Gang / Chang, Hui-Hua / Stark, Alexander P / Jung, Xiaoman / Hines, Oscar Joe / Eibl, Guido. ·From the Departments of *Surgery and †Pathology and Laboratory Medicine,David Geffen School of Medicine at UCLA, Los Angeles, CA; and ‡Department of Biostatistics, Fielding School of Public Health at UCLA, Los Angeles, CA. ·Pancreas · Pubmed #26495779.

ABSTRACT: OBJECTIVES: Obesity increases the incidence of multiple types of cancer. Our previous work has shown that a high-fat, high-calorie diet (HFCD) leads to visceral obesity, pancreatic inflammation, and accelerated pancreatic neoplasia in KrasG12D (KC) mice. In this study, we aimed to investigate the effects of an HFCD on visceral adipose inflammation with emphasis on potential differences between distinct visceral adipose depots. METHODS: We examined the weight and visceral obesity in both wild-type and KC mice on either control diet (CD) or HFCD. After 3 months, mice were killed for histological examination. Multiplex assays were also performed to obtain cytokine profiles between different adipose depots. RESULTS: Both wild-type and KC mice on an HFCD exhibited significantly increased inflammation in the visceral adipose tissue, particularly in the peripancreatic fat (PPF), compared with animals on a CD. This was associated with significantly increased inflammation in the pancreas. Cytokine profiles were different between visceral adipose depots and between mice on the HFCD and CD. CONCLUSIONS: Our results clearly demonstrate that an HFCD leads to obesity and inflammation in the visceral adipose tissue, particularly the PPF. These data suggest that obesity-associated inflammation in PPF may accelerate pancreatic neoplasia in KC mice.

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