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Pancreatic Neoplasms: HELP
Articles by Barish H. Edil
Based on 74 articles published since 2010
(Why 74 articles?)
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Between 2010 and 2020, Barish Edil wrote the following 74 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials. 2015

Paniccia, Alessandro / Merkow, Justin / Edil, Barish H / Zhu, Yuwen. ·Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. ·Chin J Cancer Res · Pubmed #26361407.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC.

2 Review Update on pancreatic neuroendocrine tumors. 2014

McKenna, Logan R / Edil, Barish H. ·Department of Surgery, University of Colorado, Academic Office One, Aurora, CO, USA. ·Gland Surg · Pubmed #25493258.

ABSTRACT: Pancreatic neuroendocrine tumors (pNETs) are relatively rare tumors comprising 1-2% of all pancreas neoplasms. In the last 10 years our understanding of this disease has increased dramatically allowing for advancements in the treatment of pNETs. Surgical excision remains the primary therapy for localized tumors and only potential for cure. New surgical techniques using laparoscopic approaches to complex pancreatic resections are a major advancement in surgical therapy and increasingly possible. With early detection being less common, most patients present with metastatic disease. Management of these patients requires multidisciplinary care combining the best of surgery, chemotherapy and other targeted therapies. In addition to surgical advances, recently, there have been significant advances in systemic therapy and targeted molecular therapy.

3 Review Vaccine therapy for pancreatic cancer. 2013

Salman, Bulent / Zhou, Donger / Jaffee, Elizabeth M / Edil, Barish H / Zheng, Lei. ·Department of Surgery; Johns Hopkins University of School of Medicine; Baltimore, MD USA ; The Sol Goldman Pancreatic Cancer Research Center; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Sidney Kimmel Comprehensive Cancer Center; Johns Hopkins University School of Medicine; Baltimore, MD USA. · Department of Oncology; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Sidney Kimmel Comprehensive Cancer Center; Johns Hopkins University School of Medicine; Baltimore, MD USA. · Department of Oncology; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Skip Viragh Pancreatic Cancer Center; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Sol Goldman Pancreatic Cancer Research Center; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Sidney Kimmel Comprehensive Cancer Center; Johns Hopkins University School of Medicine; Baltimore, MD USA. · Department of Surgery; University of Colorado; Aurora, CO USA. · Department of Surgery; Johns Hopkins University of School of Medicine; Baltimore, MD USA ; The Sol Goldman Pancreatic Cancer Research Center; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Sidney Kimmel Comprehensive Cancer Center; Johns Hopkins University School of Medicine; Baltimore, MD USA ; Department of Oncology; Johns Hopkins University School of Medicine; Baltimore, MD USA ; The Skip Viragh Pancreatic Cancer Center; Johns Hopkins University School of Medicine; Baltimore, MD USA. ·Oncoimmunology · Pubmed #24498551.

ABSTRACT: Pancreatic cancer is a lethal disease and currently available therapies have significant limitations. Pancreatic cancer is thus an ideal setting for the development of novel treatment modalities such as immunotherapy. However, relevant obstacles must be overcome for immunotherapeutic regimens against pancreatic cancer to be successful. Vaccine therapy relies on the administration of biological preparations that include an antigen that (at least ideally) is specifically expressed by malignant cells, boosting the natural ability of the immune system to react against neoplastic cells. There are a number of ways to deliver anticancer vaccines. Potent vaccines stimulate antigen presentation by dendritic cells, hence driving the expansion of antigen-specific effector and memory T cells. Unlike vaccines given as a prophylaxis against infectious diseases, anticancer vaccines require the concurrent administration of agents that interfere with the natural predisposition of tumors to drive immunosuppression. The safety and efficacy of vaccines against pancreatic cancer are nowadays being tested in early phase clinical trials.

4 Review Advancements in pancreatic neuroendocrine tumors. 2013

Sadaria, Miral R / Hruban, Ralph H / Edil, Barish H. ·Department of Surgery, University of Colorado Anschutz Medical Campus, Division of GI, Tumor and Endocrine Surgery, Academic Office One, 12631 East 17th Avenue, C311, Aurora, CO 80045, USA. ·Expert Rev Gastroenterol Hepatol · Pubmed #23899286.

ABSTRACT: Pancreatic neuroendocrine tumors (PanNETs) have increased in incidence in the USA over the last 20 years. Although PanNETs are often misconceived as being indolent tumors as they have a far more favorable prognosis over pancreatic adenocarcinoma, roughly 60-70% of patients have metastatic disease at the time of diagnosis due to presentation late in the disease process. While improvements in imaging modalities allow for early detection and better tumor localization, recent advancements in basic science, as well as surgical and medical management of PanNETs have further improved the prognosis. The mainstay of therapy for localized PanNETs is surgical intervention, which has become safer and is slowly shifting towards a more minimally invasive approach. However, the prognosis still remains relatively bleak for patients with unresectable disease. Fortunately, novel molecular targeted therapies, such as everolimus and sunitinib, have recently come into the limelight and have shown significant promise for the treatment of locally advanced and metastatic disease.

5 Review Vaccines for pancreatic cancer. 2012

Soares, Kevin C / Zheng, Lei / Edil, Barish / Jaffee, Elizabeth M. ·The Sidney Kimmel Cancer Center, Skip Viragh Clinical Pancreatic Cancer Center, Aurora, CO, USA. ·Cancer J · Pubmed #23187853.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) remains a highly lethal disease; new therapeutic modalities are urgently needed. A number of immunotherapies tested in preclinical models have shown promise. Early-phase clinical trials have demonstrated evidence of immune activation that in some cases correlates with clinical response. Moreover, recent evidence delineates the intricate role of inflammation in PDA, even at its earliest stages. Pancreatic ductal adenocarcinoma is thus ripe for immunotherapy; however, significant challenges remain before success can be realized. Future studies will need to focus on the discovery of novel PDA antigens and the identification of the multiple immune suppressive pathways within the PDA tumor microenvironment that inhibit an effective PDA-targeted immune response. Technologies are now available to rapidly advance discovery. Rapid translation of new discoveries into scientifically driven clinical trials testing combinations of immune agents will likely continue to shift the procarcinogenic tumor environment toward the most potent anticancer response.

6 Review The current management of pancreatic neuroendocrine tumors. 2012

Ellison, Trevor A / Edil, Barish H. ·Department of Surgery, The Johns Hopkins Hospital, 1550 Orleans Street, CRB II, Room 506, Baltimore, MD 21287, USA. ·Adv Surg · Pubmed #22873046.

ABSTRACT: PanNETs constitute a rare and heterogeneous group of pancreatic neoplasms whose overall prognosis is better than the more common pancreatic adenocarcinoma. Although surgery is the only treatment that provides a cure, many adjuvant therapies have been explored with some new, exciting, targeted therapies just approved for PanNETs. With growing interest in this type of neoplasm, an increasing number of clinical trials and natural history studies should shed light on the best management for these patients.

7 Review Laparoscopic distal pancreatectomy is associated with significantly less overall morbidity compared to the open technique: a systematic review and meta-analysis. 2012

Venkat, Raghunandan / Edil, Barish H / Schulick, Richard D / Lidor, Anne O / Makary, Martin A / Wolfgang, Christopher L. ·Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. ·Ann Surg · Pubmed #22511003.

ABSTRACT: OBJECTIVE: To compare laparoscopic distal pancreatectomy (LDP) versus open distal pancreatectomy (ODP) by using meta-analytical techniques. BACKGROUND: LDP is increasingly performed as an alternative approach for distal pancreatectomy in selected patients. Multiple studies have tried to assess the safety and efficacy of LDP compared with ODP. METHODS: A systematic review of the literature was performed to identify studies comparing LDP and ODP. Intraoperative outcomes, postoperative recovery, oncologic safety, and postoperative complications were evaluated. Meta-analysis was performed using a random-effects model. RESULTS: Eighteen studies matched the selection criteria, including 1814 patients (43% laparoscopic, 57% open). LDP had lower blood loss by 355 mL (P < 0.001) and hospital length of stay by 4.0 days (P < 0.001). Overall complications were significantly lower in the laparoscopic group (33.9% vs 44.2%; odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.57-0.95), as was surgical site infection (2.9% vs 8.1%; OR = 0.45, 95% CI 0.24-0.82). There was no difference in operative time, margin positivity, incidence of postoperative pancreatic fistula, and mortality. CONCLUSIONS: LDP has lower blood loss and reduced length of hospital stay. There was a lower risk of overall postoperative complications and wound infection, without a substantial increase in the operative time. Although a thorough evaluation of oncological outcomes was not possible, the rate of margin positivity was comparable to the open technique. The improved complication profile of LDP, taken together with the lack of compromise of margin status, suggests that this technique is a reasonable approach in selected cancer patients.

8 Review Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy. 2012

de Wilde, Roeland F / Edil, Barish H / Hruban, Ralph H / Maitra, Anirban. ·The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins University School of Medicine, 1550 Orleans Street Baltimore, MD 21231, USA. ·Nat Rev Gastroenterol Hepatol · Pubmed #22310917.

ABSTRACT: Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ∼1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ∼65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance.

9 Review Neuroendocrine pancreatic tumors: guidelines for management and update. 2012

Burns, William R / Edil, Barish H. ·Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD 21287, USA. wburnsi1@jhmi.edu ·Curr Treat Options Oncol · Pubmed #22198808.

ABSTRACT: Pancreatic neuroendocrine tumors (PanNETs) are a diverse group of rare neoplasms. Commonly referred to as islet cell tumors, PanNETs are classified as functional or nonfunctional depending on their production of specific pancreatic endocrine hormones (e.g. insulin, gastrin, glucagon, and others) and association with the resultant clinical syndromes. While most PanNETs are sporadic, syndromic patients, in particular those with multiple endocrine neoplasia type 1 (MEN-1) and von Hippel Lindau (VHL), are at increased risk of developing these tumors. Recent investigations of patients with sporadic and syndromic PanNETs have elucidated critical pathways in tumor development, such as mammalian target of rapamycin (mTOR) signaling and its downstream growth factors such as vascular endothelial growth factor (VEGF). Prognosis ranges from favorable for localized, low-grade neoplasms to poor for advanced, high-grade tumors. Regardless of the stage at presentation, surgery is the first-line therapy for patients with disease amenable to surgical resection. We favor formal pancreatectomy with conventional lymph node sampling for the vast majority of patients, either through open or laparoscopic techniques. Those with insulinomas, however, may be candidates for enucleation. Cytoreductive surgery is also recommended for patients with locoregional recurrences or hepatic metastases. Regional adjuvants such as radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and others are often employed in an attempt to palliate symptoms and prolong survival. Unfortunately, cytotoxic chemotherapy has been largely ineffective in treating patients with PanNETs. The somatostatin analogue octreotide, however, has been effective in palliating symptoms and slowing the progression of disease. Other promising systemic agents, including sunitinib and everolimus, have targeted critical PanNET signaling pathways. In summary, surgery remains the principal therapeutic strategy for patients with PanNETs, but continued research may identify more robust systemic therapies for those with advanced disease.

10 Review Pancreatic surgery for the radiologist, 2011: an illustrated review of classic and newer surgical techniques for pancreatic tumor resection. 2011

Wolfgang, Christopher L / Corl, Frank / Johnson, Pamela T / Edil, Barish H / Horton, Karen M / Schulick, Richard D / Fishman, Elliot K. ·Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. ·AJR Am J Roentgenol · Pubmed #22109288.

ABSTRACT: OBJECTIVE: Pancreatic surgery has evolved considerably since the earliest described pancreatectomies were performed in the late 1800s. Emerging surgical techniques for pancreatic cancer have modified what was traditionally deemed unresectable disease. This review summarizes the main type of pancreatic resections used for tumor removal on the basis of location and biologic behavior. CONCLUSION: CT interpretation should incorporate an understanding of current surgical techniques to provide surgeons with the information necessary for patient selection and preoperative planning.

11 Review Immuno- and gene-therapeutic strategies targeted against cancer (mainly focusing on pancreatic cancer). 2010

Yoshimura, Kiyoshi / Olino, Kelly / Edil, Barish H / Schulick, Richard D / Oka, Masaaki. ·Department of Surgery II, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. ·Surg Today · Pubmed #20425541.

ABSTRACT: Current treatment modalities of surgical resection and chemotherapy against cancers have improved survival. However, mortality from tumor recurrence remains high. Immunotherapy and gene therapy are potential additions to the treatment arsenal in the care of cancer patients. These novel therapeutic approaches need further investigation in in vitro and in vivo models as they are developed for potential use in humans. Here we reviewed immunotherapies and gene therapies that included clinical trials against cancers (mainly focusing on pancreatic cancer) suggesting the strong possibility of using these novel approaches.

12 Clinical Trial Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer. 2013

Herman, Joseph M / Fan, Katherine Y / Wild, Aaron T / Hacker-Prietz, Amy / Wood, Laura D / Blackford, Amanda L / Ellsworth, Susannah / Zheng, Lei / Le, Dung T / De Jesus-Acosta, Ana / Hidalgo, Manuel / Donehower, Ross C / Schulick, Richard D / Edil, Barish H / Choti, Michael A / Hruban, Ralph H / Pawlik, Timothy M / Cameron, John L / Laheru, Daniel A / Wolfgang, Christopher L. ·Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA. jherma15@jhmi.edu ·Int J Radiat Oncol Biol Phys · Pubmed #23773391.

ABSTRACT: PURPOSE: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. METHODS AND MATERIALS: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). RESULTS: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. CONCLUSION: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

13 Article Quality of Life Following Major Laparoscopic or Open Pancreatic Resection. 2019

Torphy, Robert J / Chapman, Brandon C / Friedman, Chloe / Nguyen, Christina / Bartsch, Christan G / Meguid, Cheryl / Ahrendt, Steven A / McCarter, Martin D / Del Chiaro, Marco / Schulick, Richard D / Edil, Barish H / Gleisner, Ana. ·Department of Surgery, University of Colorado, Aurora, CO, USA. · Department of Surgery, University of Oklahoma, Oklahoma City, OK, USA. · Department of Surgery, University of Colorado, Aurora, CO, USA. ana.gleisner@ucdenver.edu. ·Ann Surg Oncol · Pubmed #31228131.

ABSTRACT: PURPOSE: This study was designed to compare quality of life (QoL) among patients who underwent open versus laparoscopic pancreatic resection, including distal pancreatectomy and pancreaticoduodenectomy, and to identify clinical characteristics that are associated with changes in QoL. METHODS: Quality of life (QoL) was assessed in patients undergoing pancreatic resection with the Functional Assessment of Cancer Therapy-Hepatobiliary questionnaire preoperatively and 2 weeks, 1, 3, and 6 months postoperatively. Multilevel regression modeling was used to determine the variability in each QoL domain within the first 2 weeks (postoperative period) and thereafter (recovery period). RESULTS: Among 159 patients, 60.4% underwent open and 39.6% underwent laparoscopic surgery. Physical, functional, hepatobiliary, and total QoL scores decreased in the postoperative period but returned to baseline levels by 6 months postoperatively. Emotional QoL improved from baseline by 2 weeks after surgery (p < 0.001) and social QoL improved from baseline by 3 months after surgery (p < 0.001). Emotional QoL was the only domain where significant differences were observed in QoL in the postoperative and recovery periods between patients who underwent open and laparoscopic pancreatic resection. Controlling for surgical approach, patients who experienced a grade III or IV complication experienced greater declines in physical, functional, hepatobiliary, and total QoL in the postoperative period. The negative impact of complications on QoL resolved by 6 months postoperatively. CONCLUSIONS: The impact of pancreatic resection on QoL was comparable between patients who underwent laparoscopic versus open pancreatic resection. Complications were strongly associated with changes in postoperative QoL, suggesting that performing a safe operation is the best approach for optimizing patient reported QoL.

14 Article Cystic pancreatic neuroendocrine tumors: A distinctive subgroup with indolent biological behavior? A systematic review and meta-analysis. 2019

Zhu, Jian-Kang / Wu, Dong / Xu, Jian-Wei / Huang, Xin / Jiang, Yuan-Yuan / Edil, Barish H / Li, Min / Hu, San-Yuan / Zhan, Han-Xiang. ·Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, China. · Department of Pulmonary and Critical Care Medicine, Qilu Hospital Shandong University, Jinan, 250012, China. · Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, China. Electronic address: zhanhanxiang@126.com. ·Pancreatology · Pubmed #31160191.

ABSTRACT: BACKGROUND/OBJECTIVES: The clinicopathological features and biological behaviors of cystic pancreatic neuroendocrine tumors (pNETs) are unclear and controversial. Here we performed a systematic review and meta-analysis to investigate the unique characteristics of cystic pNETs, to determine whether they represent a distinct clinical entity. METHODS: We selected comparative studies published since January 2000 that explore the differences between clinicopathological features of cystic and solid pNETs. Demographic information, pathological characteristics, and survival information were analyzed. RESULT: The 12 selected studies comprised 355 and 1530 patients diagnosed with cystic and solid pNETs, respectively. Compared with solid pNETs, cystic pNETs were less likely to be functional (odds ratio, OR = 0.31, 95% confidence interval (CI) 0.19-0.50, p < 0.00001), more likely to affect males (OR = 1.56, 95% CI 1.22-2.00, p = 0.0005), and significantly associated with multiple endocrine neoplasia type 1 (OR = 2.71). Cystic pNETs were more likely to present with G1 and G2 rather than G3 (OR = 1.66). Cystic pNETs were associated with less frequent distant organs and lymph node metastasis, microvascular invasion, perineural invasion, and a low Ki-67 index and mitotic count. There were no significant differences between 5- and 10-year overall survival. However, the 5-year disease-free survival (DFS) and 10-year DFS rate of patients with cystic pNETs was significantly higher compared with those with solid pNETs (94.6% vs 83.5%, OR = 3.00; 92.7% vs 63.6%, OR = 5.92, respectively). CONCLUSIONS: Cystic pNETs represent a distinct subgroup of pNETs that present with an indolent biological behavior, and patients experience better DFS. Observation and surveillance should be considered in some selected cases.

15 Article ZIP4 Promotes Muscle Wasting and Cachexia in Mice With Orthotopic Pancreatic Tumors by Stimulating RAB27B-Regulated Release of Extracellular Vesicles From Cancer Cells. 2019

Yang, Jingxuan / Zhang, Zicheng / Zhang, Yuqing / Ni, Xiaoling / Zhang, Guohua / Cui, Xiaobo / Liu, Mingyang / Xu, Can / Zhang, Qiang / Zhu, Huiyun / Yan, Jie / Zhu, Vivian F / Luo, Yusheng / Hagan, John P / Li, Zhaoshen / Fang, Jing / Jatoi, Aminah / Fernandez-Zapico, Martin E / Zheng, Lei / Edil, Barish H / Bronze, Michael S / Houchen, Courtney W / Li, Yi-Ping / Li, Min. ·Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; The Vivian L. Smith Department of Neurosurgery, the University of Texas Health Science Center at Houston, Houston, Texas. · Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas. · Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · The Vivian L. Smith Department of Neurosurgery, the University of Texas Health Science Center at Houston, Houston, Texas; Department of General Surgery, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. · The Vivian L. Smith Department of Neurosurgery, the University of Texas Health Science Center at Houston, Houston, Texas; Department of Gastroenterology, Changhai Hospital, Shanghai, China. · The Vivian L. Smith Department of Neurosurgery, the University of Texas Health Science Center at Houston, Houston, Texas. · Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Gastroenterology, Changhai Hospital, Shanghai, China. · Department of Gastroenterology, Changhai Hospital, Shanghai, China. · The Key Lab of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao, China. · Department of Oncology, Mayo Clinic, Rochester, Minnesota. · Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, Minnesota. · The Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas. Electronic address: Yi-Ping.Li@uth.tmc.edu. · Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; The Vivian L. Smith Department of Neurosurgery, the University of Texas Health Science Center at Houston, Houston, Texas; Department of Integrative Biology and Pharmacology, the University of Texas Health Science Center at Houston, Houston, Texas. Electronic address: Min-Li@ouhsc.edu. ·Gastroenterology · Pubmed #30342032.

ABSTRACT: BACKGROUND & AIMS: Cachexia, which includes muscle wasting, is a frequent complication of pancreatic cancer. There are no therapies that reduce cachexia and increase patient survival, so it is important to learn more about its mechanisms. The zinc transporter ZIP4 promotes growth and metastasis of pancreatic tumors. We investigated its effects on muscle catabolism via extracellular vesicle (EV)-mediated stimulation of mitogen-activated protein kinase 14 (p38 MAPK). METHODS: We studied nude mice with orthotopic tumors grown from human pancreatic cancer cell lines (AsPC-1 and BxPC-3); tumors were removed 8 days after cell injection and analyzed by histology. Mouse survival was analyzed by Kaplan-Meier curves. ZIP4 was knocked down in AsPC-1 and BxPC-3 cells with small hairpin RNAs; cells with empty vectors were used as controls. Muscle tissues were collected from mice and analyzed by histology and immunohistochemistry. Conditioned media from cell lines and 3-dimensional spheroid/organoid cultures of cancer cells were applied to C2C12 myotubes. The myotubes and the media were analyzed by immunoblots, enzyme-linked immunosorbent assays, and immunofluorescence microscopy. EVs were isolated from conditioned media and analyzed by immunoblots. RESULTS: Mice with orthotopic tumors grown from pancreatic cancer cells with knockdown of ZIP4 survived longer and lost less body weight and muscle mass than mice with control tumors. Conditioned media from cancer cells activated p38 MAPK, induced expression of F-box protein 32 and UBR2 in C2C12 myotubes, and also led to loss of myofibrillar protein myosin heavy chain and myotube thinning. Knockdown of ZIP4 in cancer cells reduced these effects. ZIP4 knockdown also reduced pancreatic cancer cell release of heat shock protein (HSP) 70 and HSP90, which are associated with EVs, by decreasing CREB-regulated expression of RAB27B. CONCLUSIONS: ZIP4 promotes growth of orthotopic pancreatic tumors in mice and loss of muscle mass by activating CREB-regulated expression of RAB27B, required for release of EVs from pancreatic cancer cells. These EVs activate p38 MAPK and induce expression of F-box protein 32 and UBR2 in myotubes, leading to loss of myofibrillar myosin heavy chain and myotube thinning. Strategies to disrupt these pathways might be developed to reduce pancreatic cancer progression and accompanying cachexia.

16 Article Perioperative and Survival Outcomes Following Neoadjuvant FOLFIRINOX versus Gemcitabine Abraxane in Patients with Pancreatic Adenocarcinoma. 2018

Chapman, Brandon C / Gleisner, Ana / Rigg, Devin / Messersmith, Wells / Paniccia, Alessandro / Meguid, Cheryl / Gajdos, Csaba / McCarter, Martin D / Schulick, Richard D / Edil, Barish H. ·Department of Surgery, University of Colorado School of Medicine, Aurora, CO. · Division of Surgical Oncology, University of Colorado School of Medicine, Aurora, CO. · Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO. · Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104. ·JOP · Pubmed #29950957.

ABSTRACT: Context: Neoadjuvant chemotherapy is increasingly used in borderline resectable and locally advanced pancreatic cancer to facilitate surgical resection. Objective: To compare progression free survival and overall survival in patients receiving neoadjuvant FOLFIRINOX with those receiving gemcitabine/abraxane. Design: Retrospective cohort study. Setting: University of Colorado Hospital from 2012-2016. Participants: Patients with pancreatic adenocarcinoma. Interventions: Neoadjuvant FOLFIRINOX or gemcitabine/abraxane. Outcome Measures: Perioperative outcomes, progression free survival, and overall survival were compared between groups. A multivariate Cox proportional hazard model was applied to evaluate survival outcomes. Results: We identified 120 patients: 83 (69.2%) FOLFIRINOX and 37 (30.8%) gemcitabine/abraxane. The FOLIFRINOX group was younger and had a lower ECOG performance status (p<0.05). Patients in the FOLFIRINOX group were more likely to undergo surgical resection compared to gemcitabine/abraxane (66.3% Conclusion: Neoadjuvant FOLFIRINOX may improve progression free survival by increasing the proportion of patients undergoing surgical resection. Improved understanding of the role for selection bias and longer follow up are needed to better define the impact of neoadjuvant FOLFIRINOX on overall survival.

17 Article Utility of Viscoelastic Assays Beyond Coagulation: Can Preoperative Thrombelastography Indices Predict Tumor Histology, Nodal Disease, and Resectability in Patients Undergoing Pancreatectomy? 2018

Moore, Hunter B / Paniccia, Alessandro / Lawson, Peter J / Torphy, Robert J / Nydam, Trevor L / Moore, Ernest E / McCarter, Martin D / Schulick, Richard D / Edil, Barish H. ·Department of Surgery, University of Colorado School of Medicine, Denver, CO. Electronic address: hunter.moore@ucdenver.edu. · Department of Surgery, University of Colorado School of Medicine, Denver, CO. ·J Am Coll Surg · Pubmed #29605725.

ABSTRACT: BACKGROUND: Hypercoagulability and malignancy have been linked since the 1860s. However, the impact of different neoplasms on multiple components of the coagulation system remains poorly understood. Thrombelastography (TEG) enables measurement of coagulation incorporating clotting through fibrinolysis. We hypothesize that specific TEG indices that are associated with hypercoagulability can be appreciated in patients with adenocarcinoma undergoing pancreatic resection. STUDY DESIGN: Blood samples were obtained from patients undergoing pancreatic resection before surgical incision and assayed with TEG. The 4 indices of coagulation measured by TEG included in the analysis were R time, angle, maximum amplitude, and lysis at 30 minutes. Patient tumor type, nodal disease, and mass resectability were contrasted with TEG indices. RESULTS: One hundred patients were enrolled over 18 months. The majority (63%) of patients had adenocarcinoma. Patients with adenocarcinoma had increased angle compared with other lesions (49 degrees [interquartile range {IQR} 37 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.011). When excluding patients that underwent neoadjuvant therapy, patients with adenocarcinoma had shorter R times (13 minutes [IQR 9 to 16 minutes] vs 14 minutes [IQR 12 to 18 minutes]; p = 0.051), steeper angles (49 degrees [IQR 40 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.010), and higher maximum amplitude (67 mm [IQR 61 to 69 mm] vs 62 mm [IQR 57 to 67 mm]; p = 0.017). Nodal disease was associated with a significantly increased angle (49 degrees [IQR 42 to 59 degrees] vs 40 degrees [IQR 32 to 50 degrees]; p = 0.002) and maximum amplitude (64 mm [IQR 61 to 69 mm] vs 62 mm [IQR 56 to 67 mm]; p = 0.017). Patients who underwent successful mass resection had longer R times (14 minutes [IQR 11 to 17 minutes] vs 10 minutes [IQR 9 to 15]; p = 0.033) and shorter angles (44 degrees [IQR 35 to 55 degrees] vs 58 degrees [IQR 45 to 66 degrees]; p = 0.025). CONCLUSIONS: Patients with adenocarcinoma undergoing pancreatic resection have multiple TEG abnormalities consistent with hypercoagulability. These TEG outputs are associated with tumor type, nodal disease, and probability of a successful resection. The use of preoperative TEG has the potential to aid surgeon and patient discussions on anticipated disease burden and prognosis before resection.

18 Article Perioperative outcomes and survival following neoadjuvant stereotactic body radiation therapy (SBRT) versus intensity-modulated radiation therapy (IMRT) in pancreatic adenocarcinoma. 2018

Chapman, Brandon C / Gleisner, Ana / Rigg, Devin / Meguid, Cheryl / Goodman, Karyn / Brauer, Brian / Gajdos, Csaba / Schulick, Richard D / Edil, Barish H / McCarter, Martin D. ·Department of Surgery, University of Colorado School of Medicine, Aurora, CO. · University of Colorado School of Medicine, Aurora, CO. · Division of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO. · Division of Gasteroenterology, University of Colorado School of Medicine, Aurora, CO. ·J Surg Oncol · Pubmed #29448308.

ABSTRACT: BACKGROUND AND OBJECTIVES: To compare outcomes in patients receiving neoadjuvant stereotactic body radiation therapy (SBRT) with those receiving intensity-modulated radiation therapy (IMRT) for pancreatic adenocarcinoma. METHODS: We analyzed patients receiving neoadjuvant SBRT for borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) (2012-2016). Differences in baseline characteristics, perioperative outcomes, progression-free survival (PFS), and overall survival (OS) were compared. RESULTS: Seventy-five (82.4%) patients received SBRT and 16 (17.6%) received IMRT. There were no differences in surgical resection rates in the SBRT (n = 38, 50.7%) and IMRT (n = 11, 68.8%) groups (P = 0.188). Among resected patients, there was no difference in postoperative outcomes or pathologic outcomes including lymph node status, margin status, lymphovascular and perineural invasion, or pathologic response to neoadjuvant treatment (P > 0.05). Among all patients, median PFS and OS were 9.9 and 23.5 months in the SBRT group, respectively, and 15.3 and 21.8 months in the IMRT group, respectively (P > 0.05). Similarly, there was no difference in PFS or OS between groups when stratified by BRPC, LAPC, and surgically resected patients (P > 0.05). CONCLUSIONS: In the neoadjuvant setting, SBRT and IMRT appear to have similar rates of resection, perioperative outcomes, and survival outcomes, but additional studies with increased sample size and longer follow up are needed.

19 Article Comparison of laparoscopic to open pancreaticoduodenectomy in elderly patients with pancreatic adenocarcinoma. 2018

Chapman, Brandon C / Gajdos, Csaba / Hosokawa, Patrick / Henderson, William / Paniccia, Alessandro / Overbey, Douglas M / Gleisner, Ana / Schulick, Richard D / McCarter, Martin D / Edil, Barish H. ·Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. · Adult and Child Center for Health Outcomes Research and Delivery Science (ACCORDS), Aurora, CO, USA. · Division of Surgical Oncology, University of Colorado School of Medicine, 1665 Aurora Court Room 3337, MS-F-703, Aurora, CO, 80045, USA. barish.edil@ucdenver.edu. ·Surg Endosc · Pubmed #29067580.

ABSTRACT: INTRODUCTION: The purpose of the study is to compare perioperative and survival outcomes in elderly patients undergoing laparoscopic pancreaticoduodenectomy (LPD) to those undergoing open pancreaticoduodenectomy (OPD). METHODS: Patients aged ≥ 75 years with pancreatic adenocarcinoma undergoing LPD or OPD were identified from the NCDB (2010-2013). Baseline characteristics and perioperative outcomes were compared using a χ RESULTS: We identified 1768 patients aged ≥ 75 years who underwent LPD (n = 248, 14.0%) or OPD (n = 1520, 86.0%). The majority of patients in the LPD group had their surgery at facilities performing less than 5 LPDs per year (n = 165, 66.5%). 90-day mortality was significantly lower in the LPD compared to the OPD (7.2 vs. 12.2%, p = 0.049). The laparoscopic conversion rate was 30% (n = 74) and was associated with higher readmission rates (13.5 vs. 8.1%), 30-day mortality (8.0 vs. 3.8%), and 90-day mortality (10.4 vs. 6.0%), but these did not reach statistical significance. Median OS was significantly longer in the LPD group (19.8 vs. 15.6 months, p = 0.022). After adjusting for patient and tumor-related characteristics, there was a trend towards improved survival in the LPD group (HR 0.85, 95% CI 0.69-1.03). CONCLUSION: The vast majority of the NCDB participating facilities perform less than 5 LPD cases per year, which was associated with an increased risk of perioperative mortality. Overall 90-day mortality was significantly lower in the LPD group and there was a trend towards improved OS in the LPD group compared to the OPD group after adjusting for patient and tumor-related characteristics. Studies with increased sample size and longer follow-up are needed before definitive conclusions can be made.

20 Article Laparoscopic Spleen-Preserving Total Pancreatectomy for a Main-Duct Intraductal Papillary Mucinous Neoplasm. 2017

Chapman, Brandon C / Paniccia, Alessandro / Ryan, Carrie / Schulick, Richard D / Edil, Barish H. ·Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. · University of South Florida Morsani College of Medicine, Tampa, FL, USA. · Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. barish.edil@ucdenver.edu. ·Ann Surg Oncol · Pubmed #27590330.

ABSTRACT: INTRODUCTION: Main-duct intraductal papillary mucinous neoplasms of the pancreas (M-IPMN) are potentially malignant cystic neoplasms that can degenerate into invasive malignancy in 43 % of cases.1 Although laparoscopic pancreaticoduodenectomy and distal pancreatectomy have been previously described for the management of pancreatic neoplasms, laparoscopic total pancreatectomy is rarely described. We present a video demonstrating a laparoscopic spleen-preserving total pancreatectomy in a patient with M-IPMN. CASE PRESENTATION: A healthy 66-year-old male was diagnosed with recurrent pancreatitis. A computed tomography of the abdomen demonstrated a diffusely dilated pancreatic duct (10 mm) and a 5 mm mural nodule in the neck of the pancreas. Endoscopic retrograde cholangiopancreatography demonstrated a 'fish mouth' appearance at the major papilla, with a villous mass (15 mm) in the pancreatic head. Biopsy was consistent with M-IPMN, and tumor markers were normal. RESULTS: A spleen-preserving laparoscopic total pancreatectomy was performed over a period of 270 min, with 150 cc of blood loss without complications. The patient was admitted to the intensive care unit for continuous insulin infusion. On postoperative day (POD) 1, his nasogastric tube was discontinued, transitioned to subcutaneous insulin injections, and transferred to the floor. He tolerated a diabetic diet on POD 4. His surgical drain had minimal output with no evidence of a bile leak, and was discontinued on POD 5. The patient's hospital course was uncomplicated and he was discharged home on POD 7. Pathology demonstrated IPMN with moderate dysplasia. CONCLUSION: Laparoscopic total pancreatectomy can be safely performed in patients with M-IPMN. This video presentation describes the technique we used for this procedure.

21 Article Evolving Trends Towards Minimally Invasive Surgery for Solid-Pseudopapillary Neoplasms. 2016

Stewart, Camille L / Meguid, Cheryl / Chapman, Brandon / Schulick, Richard / Edil, Barish H. ·Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. Camille.Stewart@ucdenver.edu. · University of Colorado Hospital, Aurora, CO, USA. · Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA. ·Ann Surg Oncol · Pubmed #27510845.

ABSTRACT: BACKGROUND: Solid-pseudopapillary neoplasms are rare pancreatic neoplasms with low malignant potential that predominantly arise in young women. We sought to characterize this population and the evolving trend at our institution towards laparoscopic management. METHODS: We identified all patients at our institution that were surgically treated for solid-pseudopapillary neoplasm from 2008-2015. Demographic and clinical information were queried from the medical record, and descriptive statistics were performed. Student's t test and chi-square analysis were used for comparison where appropriate. RESULTS: We identified 11 women and 1 man (average age 26 years; range 14-48 years) who were surgically treated for solid-pseudopapillary neoplasms; 5 with distal pancreatectomy (4 open, 1 laparoscopic), 6 with pancreaticoduodenectomy (3 open, 3 laparoscopic), and 1 open enucleation. From 2008 to 2013, seven of eight (87 %) procedures were performed open. Since 2014, three of four (75 %) procedures have successfully been completed laparoscopically (see video clips). Length of stay was similar for patients who had open versus laparoscopic procedures (8 vs. 9 days, p = 0.61). Two-thirds of patients (5/8) who had open procedures experienced postoperative complications compared with half (2/4) of patients who had laparoscopic procedures (p = 0.28). There have been no recurrences. CONCLUSIONS: Minimally invasive surgical management of solid-pseudopapillary neoplasms is becoming more popular, can be performed safely, and appears to have comparable outcomes to an open approach. Quality of life is an important metric for this relatively young population and may be improved with a laparoscopic approach, which warrants further investigation.

22 Article Predictors for Surgical Referral in Patients With Pancreatic Cystic Lesions Undergoing Endoscopic Ultrasound: Results From a Large Multicenter Cohort Study. 2016

Ge, Phillip S / Gaddam, Srinivas / Keach, Joseph W / Mullady, Daniel / Fukami, Norio / Edmundowicz, Steven A / Azar, Riad R / Shah, Raj J / Murad, Faris M / Kushnir, Vladimir M / Ghassemi, Kourosh F / Sedarat, Alireza / Watson, Rabindra R / Amateau, Stuart K / Brauer, Brian C / Yen, Roy D / Hosford, Lindsay / Hollander, Thomas / Donahue, Timothy R / Schulick, Richard D / Edil, Barish H / McCarter, Martin D / Gajdos, Csaba / Attwell, Augustin R / Muthusamy, V Raman / Early, Dayna S / Wani, Sachin. ·From the *Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, †Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, MO; ‡Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO; §Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA; ∥Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora; and ¶Division of Gastroenterology, Veterans Affairs Medical Center, Denver, CO. ·Pancreas · Pubmed #26262589.

ABSTRACT: OBJECTIVE: Endoscopic ultrasound (EUS) plays an integral role in the evaluation of pancreatic cysts lesions (PCLs). The aim of the study was to determine predictors of surgical referral in patients with PCLs undergoing EUS. METHODS: We performed a multicenter retrospective study of patients undergoing EUS for evaluation of PCLs. Demographics, EUS characteristics, and fine-needle aspiration results were recorded. Patients were categorized into surgery or surveillance groups on the basis of post-EUS recommendations. Univariate and multivariate analyses were performed to identify predictors of surgical referral. RESULTS: 1804 patients were included. 1301 patients were recommended to undergo surveillance and 503 patients were referred for surgical evaluation, of which 360 patients underwent surgery. Multivariate analysis revealed the following 5 independent predictors of surgical referral: symptoms of weight loss on presentation (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.44-5.03), EUS findings of associated solid mass (OR, 7.34; 95% CI, 3.81-14.16), main duct communication (OR, 4.13; 95% CI, 1.71-9.98), multilocular macrocystic morphology (OR, 2.79; 95% CI, 1.78-4.38), and fine-needle aspiration findings of mucin on cytology (OR, 3.06; 95% CI, 1.94-4.82). CONCLUSIONS: This study identifies factors associated with surgical referral in patients with PCLs undergoing EUS. Future studies should focus on creation of risk stratification models to determine the need for surgery or enrollment in surveillance programs.

23 Article Longer Course of Induction Chemotherapy Followed by Chemoradiation Favors Better Survival Outcomes for Patients With Locally Advanced Pancreatic Cancer. 2016

Faisal, Farzana / Tsai, Hua-Ling / Blackford, Amanda / Olino, Kelly / Xia, Chang / De Jesus-Acosta, Ana / Le, Dung T / Cosgrove, David / Azad, Nilofer / Rasheed, Zeshaan / Diaz, Luis A / Donehower, Ross / Laheru, Daniel / Hruban, Ralph H / Fishman, Elliot K / Edil, Barish H / Schulick, Richard / Wolfgang, Christopher / Herman, Joseph / Zheng, Lei. ·*Departments of Oncology, Surgery, and Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD †Department of Surgery, University of Colorado School of Medicine, Denver, CO. ·Am J Clin Oncol · Pubmed #24351782.

ABSTRACT: OBJECTIVES: At diagnosis, 30% of patients with pancreatic cancer are unresectable stage 3 locally advanced. The standard treatment for locally advanced pancreatic cancer (LAPC) is not defined. The current study was conducted to assess the roles of chemotherapy and chemoradiation for LAPC treatment. MATERIALS AND METHODS: Between June 2006 and March 2011, 100 patients with LAPC were treated at the Johns Hopkins Hospital. Retrospective analysis was performed to compare cumulative incidence of progression (CIP) and overall survival (OS) among different subgroups. RESULTS: For the 100 patients, the median OS was 15.8 months and the median CIP was 8.4 months. The combination of chemotherapy and chemoradiation before disease progression was significantly associated with improved CIP (P=0.001) and improved OS when compared with chemoradiation alone (median OS: 16.4 vs. 11.1 mo, P=0.03). Among patients receiving combination treatment, patients who received chemotherapy first followed by chemoradiation had a trend toward lower CIP (P=0.09) and improved OS (median OS: 18.1 vs. 11.0 mo, P=0.09). Patients who received >2 cycles of chemotherapy before chemoradiation had a significantly decreased CIP (P=0.008) and a trend toward better OS (median OS: 19.4 vs. 15.7 mo, P=0.10). On multivariate analysis, receiving >2 cycles of chemotherapy before chemoradiation was associated with improved CIP. CONCLUSIONS: Although combination chemotherapy and chemoradiation is favored in the treatment of LAPC, longer induction chemotherapy may play a more important role in sensitization of tumors to subsequent chemoradiation. Our results support treating patients with induction chemotherapy for at least 3 cycles followed by consolidative chemoradiation. These results merit further validation by a prospective study.

24 Article Pancreatic Neuroendocrine Tumors: an Update. 2015

Paniccia, Alessandro / Edil, Barish H / Schulick, Richard D. ·Division of GI, Tumor and Endocrine Surgery, Department of Surgery, University of Colorado at Denver, Aurora, CO USA. · Division of GI, Tumor and Endocrine Surgery, Department of Surgery, University of Colorado at Denver, Aurora, CO USA ; Department of Surgery, University of Colorado Anschutz Medical Campus, 12631 E. 17th Avenue, C-305, Aurora, CO 80045 USA. ·Indian J Surg · Pubmed #26722203.

ABSTRACT: Pancreatic neuroendocrine tumors (pNETs) are rare and comprise only 1-2 % of all pancreatic neoplastic disease. Although the majority of these tumors are sporadic (90 %), pNETs can arise in the setting of several different hereditary genetic syndromes, most commonly multiple endocrine neoplasia type 1 (MEN1). The presentation of pNETs varies widely, with over 60 % having malignant distant disease at the time of initial diagnosis involving the liver or other distant sites. Functioning pNETs represent approximately 10 % of all pNETs, secrete a variety of peptide hormones, and are responsible for several clinical syndromes caused by profound hormonal derangement. Surgery remains the cornerstone of therapy and the only curative approach. It should be pursued for localized disease and for metastatic lesions amenable to resection. Multimodality therapies, including liver-directed therapies and medical therapy, are gaining increasing favor in the treatment of advanced pNETs. Their utility is multifold and spans from ameliorating symptoms of hormonal excess (functional pNETs) to controlling the local and systemic disease burden (non-functional pNETs). The recent introduction of target molecular therapy has promising results especially for the treatment of progressive well-differentiated G1/G2 tumor. In this review, we summarize the current knowledge and give an update on recent advancements made in the therapeutic strategies for pNETs.

25 Article Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study. 2015

Gaddam, Srinivas / Ge, Phillip S / Keach, Joseph W / Mullady, Daniel / Fukami, Norio / Edmundowicz, Steven A / Azar, Riad R / Shah, Raj J / Murad, Faris M / Kushnir, Vladimir M / Watson, Rabindra R / Ghassemi, Kourosh F / Sedarat, Alireza / Komanduri, Srinadh / Jaiyeola, Diana-Marie / Brauer, Brian C / Yen, Roy D / Amateau, Stuart K / Hosford, Lindsay / Hollander, Thomas / Donahue, Timothy R / Schulick, Richard D / Edil, Barish H / McCarter, Martin / Gajdos, Csaba / Attwell, Augustin / Muthusamy, V Raman / Early, Dayna S / Wani, Sachin. ·Division of Gastroenterology and Hepatology, Washington University School of Medicine, St. Louis, Missouri, USA. · Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. · Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Centennial, Colorado, USA. · Division of Gastroenterology, Feinberg School of Medicine Northwestern University, Chicago, Illinois, USA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. · Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Centennial, Colorado, USA; Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, Denver, Colorado, USA. ·Gastrointest Endosc · Pubmed #26077458.

ABSTRACT: BACKGROUND AND AIMS: The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS: Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS: A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS: Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

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