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Pancreatic Neoplasms: HELP
Articles by V. Raman Muthusamy
Based on 15 articles published since 2008
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Between 2008 and 2019, V. R. Muthusamy wrote the following 15 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline The role of endoscopy in the diagnosis and treatment of cystic pancreatic neoplasms. 2016

Anonymous6580868 / Muthusamy, V Raman / Chandrasekhara, Vinay / Acosta, Ruben D / Bruining, David H / Chathadi, Krishnavel V / Eloubeidi, Mohamad A / Faulx, Ashley L / Fonkalsrud, Lisa / Gurudu, Suryakanth R / Khashab, Mouen A / Kothari, Shivangi / Lightdale, Jenifer R / Pasha, Shabana F / Saltzman, John R / Shaukat, Aasma / Wang, Amy / Yang, Julie / Cash, Brooks D / DeWitt, John M. · ·Gastrointest Endosc · Pubmed #27206409.

ABSTRACT: -- No abstract --

2 Editorial Radiofrequency ablation for intraductal extension of ampullary neoplasms: Are we ready to feel the burn? 2017

Watson, Rabindra R / Muthusamy, V Raman. ·Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. ·Gastrointest Endosc · Pubmed #28610856.

ABSTRACT: -- No abstract --

3 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.

4 Article Per-Pass Performance Characteristics of Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Malignant Solid Pancreatic Masses in a Large Multicenter Cohort. 2018

Ge, Phillip S / Wani, Sachin / Watson, Rabindra R / Sedarat, Alireza / Kim, Stephen / Marshall, Carrie / Wilson, Robert H / Makker, Jitin / Mohamadnejad, Mehdi / Komanduri, Srinadh / Muthusamy, V Raman. · ·Pancreas · Pubmed #29401169.

ABSTRACT: OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely performed for the evaluation of pancreatic masses. We evaluated the performance characteristics of EUS-FNA in obtaining a diagnosis of pancreatic malignancy. METHODS: We performed a multicenter study of patients who underwent EUS-FNA for a solid pancreatic mass. Endoscopic ultrasound-guided FNA was standardized using a 25-gauge needle, slow-pull stylet technique for specimen acquisition, and on-site cytopathology. For the primary analysis, only malignant cytology was regarded as positive. A secondary analysis was performed in which malignant and/or suspicious cytology was regarded as positive. RESULTS: A total of 138 patients underwent EUS-FNA. In the primary analysis, the sensitivity of EUS-FNA for malignancy was 56.7% on first pass, 73.3% on second pass, 83.3% on third pass, 89.2% on fourth pass, and 90.8% on fifth pass, with no increase beyond the fifth pass. In the secondary analysis, the sensitivity was 75.0% on first pass, 89.2% on second pass, 93.3% on third pass, and 95.8% on fourth pass, with no increase beyond the fourth pass. No significant relationship was seen between lesion size and diagnostic yield. CONCLUSIONS: Using a 25-gauge needle, the maximal diagnostic yield of EUS-FNA for a solid pancreatic mass is reached after 4 needle passes.

5 Article A Comprehensive Assessment of Accurate Lymph Node Staging and Preoperative Detection in Resected Pancreatic Cancer. 2018

Masuda, Toshiro / Dann, Amanda M / Elliott, Irmina A / Baba, Hideo / Kim, Stephen / Sedarat, Alireza / Muthusamy, V Raman / Girgis, Mark D / Joe Hines, O / Reber, Howard A / Donahue, Timothy R. ·Department of Surgery, David Geffen School of Medicine, 10833 Le Conte Ave, CHS Room 72-215, PO Box 956904, Los Angeles, CA, 90095, USA. · Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjyo, Chuo-ku, Kumamoto, 860-0811, Japan. · Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, USA. · Department of Surgery, David Geffen School of Medicine, 10833 Le Conte Ave, CHS Room 72-215, PO Box 956904, Los Angeles, CA, 90095, USA. tdonahue@mednet.ucla.edu. · Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, Los Angeles, CA, USA. tdonahue@mednet.ucla.edu. ·J Gastrointest Surg · Pubmed #29043580.

ABSTRACT: BACKGROUND: The current (seventh edition) American Joint Commission on Cancer (AJCC) Staging System for pancreatic ductal adenocarcinoma (PDAC) dichotomizes pathologic lymph node (LN) involvement into absence (pN0) or presence (pN1) of disease. The recently announced eighth edition also includes stratification on the number of positive nodes. Furthermore, LNs detected on preoperative imaging (CT, MRI, or endoscopic ultrasound-EUS) are considered to be pathologically involved in other gastrointestinal cancers. However, this is less well defined for PDAC. Therefore, the three aims of this study were to determine (1) whether the new AJCC staging system led to more accurate staging, (2) the number of nodes needed to be examined to detect pathologic involvement, and (3) if pN disease could be reliably detected on preoperative imaging in PDAC. METHODS: A retrospective review of all patients undergoing pancreatectomy at a single US academic center from January 1990 to September 2015. Pathology reports of resected specimens were reviewed to determine the total number of LNs examined and those positive for metastasis. CT, MRI, and/or EUS reports were used to determine the presence or absence of preoperatively detectable LN enlargement. RESULTS: Of the 490 surgical resections for PDAC, pN1 disease was detected in 59.4% (n = 291) and was positively correlated with the number of LNs pathologically examined (P < 0.001). Patients with pN1 disease had a shorter overall survival (OS) than those without nodal involvement (25.1 vs. 44.0 months; P < 0.001); however, OS was not different when stratifying by the number of nodes as on the eighth AJCC system. Pathologic examination of > 20 LNs in treatment naïve patients was optimal to detect pN1 disease and predict longer OS for those without nodal involvement (median survival > 41.1 months, P = 0.03 when compared to < 15 or 15-19 LNs examined). LNs were detected by CT, MRI, or EUS in 30.7% (103/335) of patients. The positive predictive value (PPV) of preoperative LN detection for pathologic involvement was 77.3% for treatment naïve patients and 84.2% for those without biliary obstruction. CONCLUSIONS: Although the LN scoring in the seventh PDAC AJCC Staging System was sufficient to predict OS of our patients, more LNs than previously considered (20 vs. 15) were optimal to detect pathologic involvement. Preoperative LN detection was an accurate predictor of pN1 disease for treatment naïve patients without biliary obstruction.

6 Article Digital PCR Improves Mutation Analysis in Pancreas Fine Needle Aspiration Biopsy Specimens. 2017

Sho, Shonan / Court, Colin M / Kim, Stephen / Braxton, David R / Hou, Shuang / Muthusamy, V Raman / Watson, Rabindra R / Sedarat, Alireza / Tseng, Hsian-Rong / Tomlinson, James S. ·Department of Surgery, University of California Los Angeles, Los Angeles, California, United States of America. · Department of Surgery, Greater Los Angeles Veteran's Affairs Administration, Los Angeles, California, United States of America. · Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, United States of America. · UCLA Center for Pancreatic Diseases, University of California Los Angeles, Los Angeles, California, United States of America. · Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, United States of America. · Department of Pathology, University of California Los Angeles, Los Angeles, California, United States of America. ·PLoS One · Pubmed #28125707.

ABSTRACT: Applications of precision oncology strategies rely on accurate tumor genotyping from clinically available specimens. Fine needle aspirations (FNA) are frequently obtained in cancer management and often represent the only source of tumor tissues for patients with metastatic or locally advanced diseases. However, FNAs obtained from pancreas ductal adenocarcinoma (PDAC) are often limited in cellularity and/or tumor cell purity, precluding accurate tumor genotyping in many cases. Digital PCR (dPCR) is a technology with exceptional sensitivity and low DNA template requirement, characteristics that are necessary for analyzing PDAC FNA samples. In the current study, we sought to evaluate dPCR as a mutation analysis tool for pancreas FNA specimens. To this end, we analyzed alterations in the KRAS gene in pancreas FNAs using dPCR. The sensitivity of dPCR mutation analysis was first determined using serial dilution cell spiking studies. Single-cell laser-microdissection (LMD) was then utilized to identify the minimal number of tumor cells needed for mutation detection. Lastly, dPCR mutation analysis was performed on 44 pancreas FNAs (34 formalin-fixed paraffin-embedded (FFPE) and 10 fresh (non-fixed)), including samples highly limited in cellularity (100 cells) and tumor cell purity (1%). We found dPCR to detect mutations with allele frequencies as low as 0.17%. Additionally, a single tumor cell could be detected within an abundance of normal cells. Using clinical FNA samples, dPCR mutation analysis was successful in all preoperative FNA biopsies tested, and its accuracy was confirmed via comparison with resected tumor specimens. Moreover, dPCR revealed additional KRAS mutations representing minor subclones within a tumor that were not detected by the current clinical gold standard method of Sanger sequencing. In conclusion, dPCR performs sensitive and accurate mutation analysis in pancreas FNAs, detecting not only the dominant mutation subtype, but also the additional rare mutation subtypes representing tumor heterogeneity.

7 Article Increasing Number of Passes Beyond 4 Does Not Increase Sensitivity of Detection of Pancreatic Malignancy by Endoscopic Ultrasound-Guided Fine-Needle Aspiration. 2017

Mohamadnejad, Mehdi / Mullady, Daniel / Early, Dayna S / Collins, Brian / Marshall, Carrie / Sams, Sharon / Yen, Roy / Rizeq, Mona / Romanas, Maria / Nawaz, Samia / Ulusarac, Ozlem / Hollander, Thomas / Wilson, Robert H / Simon, Violette C / Kushnir, Vladimir / Amateau, Stuart K / Brauer, Brian C / Gaddam, Srinivas / Azar, Riad R / Komanduri, Srinadh / Shah, Raj / Das, Ananya / Edmundowicz, Steven / Muthusamy, V Raman / Rastogi, Amit / Wani, Sachin. ·University of California, Los Angeles, Los Angeles, California; Liver and Pancreatobiliary Disease Research Center, Digestive Disease Research Institute, Tehran University of Medical Science, Tehran, Iran. · Washington University School of Medicine, St. Louis, Missouri. · University of Colorado Anschutz Medical Campus, Aurora, Colorado. · Kansas City VA Medical Center and University of Kansas, Kansas City, Missouri. · Feinberg School of Medicine, Northwestern University, Chicago, Illinois. · Arizona Center for Digestive Health, Gilbert, Arizona. · University of California, Los Angeles, Los Angeles, California. · University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address: sachinwani10@yahoo.com. ·Clin Gastroenterol Hepatol · Pubmed #28025154.

ABSTRACT: BACKGROUND & AIMS: It is not clear exactly how many passes are required to determine whether pancreatic masses are malignant using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We aimed to define the per-pass diagnostic yield of EUS-FNA for establishing the malignancy of a pancreatic mass, and identify factors associated with detection of malignancies. METHODS: In a prospective study, 239 patients with solid pancreatic masses were randomly assigned to groups that underwent EUS-FNA, with the number of passes determined by an on-site cytopathology evaluation or set at 7 passes, at 3 tertiary referral centers. A final diagnosis of pancreatic malignancy was made based on findings from cytology, surgery, or a follow-up evaluation at least 1 year after EUS-FNA. The cumulative sensitivity of detection of malignancy by EUS-FNA was calculated after each pass; in the primary analysis, lesions categorized as malignant or suspicious were considered as positive findings. RESULTS: Pancreatic malignancies were found in 202 patients (84.5% of the study population). EUS-FNA detected malignancies with 96% sensitivity (95% confidence interval [CI], 92%-98%); 4 passes of EUS-FNA detected malignancies with 92% sensitivity (95% CI, 87%-95%). Tumor size greater than 2 cm was the only variable associated with positive results from cytology analysis (odds ratio, 7.8; 95% CI, 1.9-31.6). In masses larger than 2 cm, 4 passes of EUS-FNA detected malignancies with 93% sensitivity (95% CI, 89%-96%) and in masses ≤2 cm, 6 passes was associated with 82% sensitivity (95% CI, 61%-93%). Sensitivity of detection did not increase with increasing number of passes. CONCLUSIONS: In a prospective study, we found 4 passes of EUS-FNA to be sufficient to detect malignant pancreatic masses; increasing the number of passes did not increase the sensitivity of detection. Tumor size greater than 2 cm was associated with malignancy, and a greater number of passes may be required to evaluate masses 2 cm or less. ClinicalTrials.gov number, NCT01386931.

8 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.

9 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.

10 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.

11 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.

12 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.

13 Article Plastic biliary stent patency in patients with locally advanced pancreatic adenocarcinoma receiving downstaging chemotherapy. 2015

Ge, Phillip S / Hamerski, Christopher M / Watson, Rabindra R / Komanduri, Srinadh / Cinnor, Birtukan B / Bidari, Kiran / Klapman, Jason B / Lin, Cui L / Shah, Janak N / Wani, Sachin / Donahue, Timothy R / Muthusamy, V Raman. ·Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. · Interventional Endoscopy Services, California Pacific Medical Center, San Francisco, California, USA. · Division of Gastroenterology, Northwestern Memorial Hospital, Chicago, Illinois, USA. · Department of Internal Medicine, Oregon Health and Science University, Portland, Oregon, USA. · Gastrointestinal Tumor Program, Section of Endoscopic Oncology, Moffitt Cancer Center, University of South Florida, Tampa, Florida, USA. · Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. ·Gastrointest Endosc · Pubmed #25442083.

ABSTRACT: BACKGROUND: Plastic stents in patients with biliary obstruction caused by pancreatic adenocarcinoma are typically exchanged at 3-month intervals. Plastic stents may have reduced durability in patients receiving chemotherapy. OBJECTIVE: To determine the duration of plastic biliary stent patency in patients undergoing chemotherapy for pancreatic adenocarcinoma. DESIGN: Retrospective, multicenter cohort study. SETTING: Three tertiary academic referral centers. PATIENTS: A total of 173 patients receiving downstaging chemotherapy for locally advanced or borderline resectable pancreatic adenocarcinoma from 1996 to 2013. INTERVENTIONS: Placement of 10F or larger plastic biliary stents. MAIN OUTCOME MEASUREMENTS: Primary outcome was overall duration of stent patency. Secondary outcomes included the incidence of premature stent exchange (because of cholangitis or jaundice) and hospitalization rates. RESULTS: A total of 233 plastic stents were placed, and the overall median duration of stent patency was 53 days (interquartile range [IQR] 25-99 days). Eighty-seven stents were removed at the time of surgical resection, and 63 stents were exchanged routinely per protocol. The remaining 83 stent exchanges were performed for worsening liver function test results, jaundice, or cholangitis, representing a 35.6% rate of premature stent exchange. The median stent patency duration in the premature stent exchange group was 49 days (IQR 25-91 days) with a 44.6% hospitalization rate. The overall rate of cholangitis was 15.0% of stent exchanges, occurring a median of 56 days after stent placement (IQR 26-89 days). LIMITATIONS: Retrospective study. CONCLUSIONS: Plastic biliary stents placed during chemotherapy/chemoradiation for pancreatic adenocarcinoma have a shorter-than-expected patency duration, and a substantial number of patients will require premature stent exchange. Consideration should be given to shortening the interval for plastic biliary stent exchange.

14 Article Current recommendations for surveillance and surgery of intraductal papillary mucinous neoplasms may overlook some patients with cancer. 2015

Nguyen, Andrew H / Toste, Paul A / Farrell, James J / Clerkin, Barbara M / Williams, Jennifer / Muthusamy, V Raman / Watson, Rabindra R / Tomlinson, James S / Hines, O Joe / Reber, Howard A / Donahue, Timothy R. ·Department of Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, CHS 72-215, Los Angeles, CA, 90095, USA. ·J Gastrointest Surg · Pubmed #25373706.

ABSTRACT: BACKGROUND: The 2012 Sendai Criteria recommend that patients with 3 cm or larger branch duct intraductal papillary mucinous neoplasms (BD-IPMN) without any additional "worrisome features" or "high-risk stigmata" may undergo close observation. Furthermore, endoscopic ultrasound (EUS) is not recommended for BD-IPMN <2 cm. These changes have generated concern among physicians treating patients with pancreatic diseases. The purposes of this study were to (i) apply the new Sendai guidelines to our institution's surgically resected BD-IPMN and (ii) reevaluate cyst size cutoffs in identifying patients with lesions harboring high-grade dysplasia or invasive cancer. METHODS: We retrospectively reviewed 150 patients at a university medical center with preoperatively diagnosed and pathologically confirmed IPMNs. Sixty-six patients had BD-IPMN. Pathologic grade was dichotomized into low-grade (low or intermediate grade dysplasia) or high-grade/invasive (high-grade dysplasia or invasive cancers). Fisher's exact test, chi-square test, student's t test, linear regression, and receiver operating characteristic (ROC) analyses were performed. RESULTS: The median BD-IPMN size on imaging was 2.4 cm (interquartile range 1.5-3.0). Fifty-one (77 %) low-grade and 15 (23 %) high-grade/invasive BD-IPMN were identified. ROC analysis demonstrated that cyst size on preoperative imaging is a reasonable predictor of grade with an area under the curve of 0.691. Two-thirds of high-grade/invasive BD-IPMN were <3 cm (n = 10). Compared to a cutoff of 3, 2 cm was associated with higher sensitivity (73.3 vs. 33.3 %) and negative predictive value (83.3 vs. 80 %, NPV) for high-grade/invasive BD-IPMN. Mural nodules on endoscopic ultrasound (EUS) or atypical cells on endoscopic ultrasound-fine needle aspiration (EUS-FNA) were identified in all cysts <2 and only 50 % of those <3 cm. Forty percent of cysts >3 cm were removed based on size alone. DISCUSSION/CONCLUSIONS: Our results suggest that "larger" size on noninvasive imaging can indicate high-grade/invasive cysts, and EUS-FNA may help identify "smaller" cysts with high-grade/invasive pathology.

15 Minor Preoperative Treatment With FOLFIRINOX and Successful Resection for a Patient With Mixed Acinar-Endocrine Carcinoma of the Pancreas. 2017

Sugimoto, Motokazu / Hines, O Joe / Dawson, David W / Muthusamy, V Raman / Reber, Howard A / Donahue, Timothy R. ·Department of Surgery, UCLA Medical Center, Los Angeles, CA Department of Pathology and Laboratory Medicine, UCLA Medical Center, Los Angeles, CA Division of Digestive Diseases, UCLA Medical Center, Los Angeles, CA Department of Surgery, UCLA Medical Center, Los Angeles, CA, tdonahue@mednet.ucla.edu. ·Pancreas · Pubmed #28291165.

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