Oral (pre-recorded)
Pancreas 		  
OP03 Pancreas: Tumours 
Selection of Presentations from Abstract Submissions
OP03-01 Incidence and Prognosis of Pathologic Complete Response Following Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma
Jordan Cloyd, United States

J. Cloyd1, C. Shen2, M. Dillhoff2, A. Manilchuk2, T. Pawlik2, A. Tsung2
1Surgery, The Ohio State University, United States, 2The Ohio State University, United States

Introduction: Neoadjuvant therapy (NT) is increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC). While a pathologic complete response (pCR) to NT has been shown to be an important prognostic factor in single-institution studies, the incidence, characteristics, and outcomes of pCR have not been investigated in a population-based cohort.
Methods: Patients with localized PDAC and known cT and pT stage who received NT prior to pancreatectomy were identified using the National Cancer Database from 2004-2016. The clinical, demographic, socioeconomic, and hospital-related characteristics as well as long-term outcomes of patients who did and did not experience pCR were compared.
Results: Among 7,902 patients who underwent NT prior to pancreatectomy, 244 (3.1%) experienced a pCR while 7,658 (96.9%) did not. Patients who experienced a pCR were younger (62.6 vs 63.9 years, p< 0.05), had a longer duration of NT (200.5 vs 141.9 days, p< 0.001), and were more likely to have advanced cT stage
(T4: 26.2% vs 14.6%, p< 0.001), cN0 stage (72.4% vs 66.4%, p< 0.05) and to have received preoperative radiation
(67.6% vs 47.3%, p< 0.001). Median overall survival (OS) was longer among patients who experienced pCR compared to those who did not (76.6 vs 26.0 months, p< 0.001) (Figure). On multivariate cox regression, a pCR was the strongest predictor of improved OS (HR 0.43, 95% CI 0.32-0.58).
Conclusions: A pCR following NT for PDAC occurs infrequently but is associated with significantly improved OS. Better predictors of response to NT and more effective preoperative regimens should be aggressively sought.
[Overall Survival of Pathologic Complete Response]
OP03-04 The Tumor Burden and Immune Dynamic Changes in Pancreatic Cancer Liver Metastasis
Hanlin Yin, China

H. Yin, N. Pu, W. Wu
Zhongshan Hospital, Fudan University, China

Background: The prognosis of the patient with pancreatic cancer liver metastasis is very poor. Investigating the dynamic changes of pancreatic cancer (PC) liver metastasis may contribute to alleviate PC liver metastasis progression.
Methods: Murine pancreatic cancer cell line Panc02 was transfected with GFP protein as tumor marker. 3×106 Panc02GPF+/mouse were injected into spleen to establish PC liver metastasis animal model. In 1 hour and Day1, 5, 10, 20, 35 after the operation, four mice were sacrificed and their liver were embedded into paraffin. Immunohistochemistry were uesd to evaluate the tumor burden and infiltrating CD8+T cell.
Results: In 1 hour after operation, the tumor cells evenly distributed in liver. The tumor burden of liver metastasis slightly increased in Day5-10 and the distribution of the metastasis became clumped. In Day20, no metastasis was found in some mice but some had large patchy metastasis in their liver. In Day35, some had “normal” liver and some had nodular metastasis in the liver. No obvious characteristic distribution of CD8+T cell was found in 1hour and Day1 group. In Day5 CD8+T cells distributed in the edge of the metastasis. In Day10, CD8+T cells reached the peak and infiltrated in the center of metastasis. In Day20 and Day35 groups, those who had nodular liver metastasis obviously had lower CD8+T cell infiltration.
Conclusions: Single pancreatic cancer cell successfully developing into nodular liver metastasis is the result of cancer cell and host interaction. Intervening the tumor microenvironment in early stage of metastasis may help reduce PC liver metastasis.
OP03-05 Clinical Impact of ATRX, TSC2, and PTEN Expression on Prognosis in Patients with Grade 1 and 2 Pancreatic Neuroendocrine Tumor
Keiichi Okano, Japan

K. Okano1, J. Uemura1, M. Oshima1, H. Suto1, Y. Ando1, H. Matsukawa1, K. Kadota2, Y. Suzuki1
1Gastroenterological Surgery, Kagawa University, Japan, 2Pathology, Kagawa University, Japan

Objective: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs).
Background: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that five genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear.
Methods: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings.
Results: Kaplan-Meier analysis indicated that loss of TSC2 (n=58) or PTEN (n=37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n=41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n=31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, p=0.003) in G2 PNETs.
Conclusions: Given the widespread availability of immunohistochemistry, loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs.
OP03-06 Geographic Variation in Attitudes Regarding Locally Advanced Pancreatic Cancer Management
Alex B. Blair, United States

A.B. Blair1, B. Reames2, R. Krell3, A. Ejaz4, M. Falconi5, C. Wolfgang6, M. Weiss7, C. Are8, J. He6
1Surgery, Johns Hopkins Hospital, United States, 2Surgery, University of Nebraska Medical Center, United States, 3Brooke Army Medical Center, United States, 4Ohio State University, Wexner Medical Center, United States, 5IRCCS San Raffaele Hospital, Italy, 6Johns Hopkins University School of Medicine, United States, 7Northwell Health, United States, 8University of Nebraska Medical Center, United States

Introduction: Studies suggest attitudes regarding management of locally advanced pancreas cancer (LAPC) vary widely. We sought to examine the influence of geographic practice location on attitudes regarding LAPC management.
Methods: An electronic survey was distributed by email to an international cohort of pancreas surgeons. Data collected included practice characteristics, preferences for management, and 6 vignettes (with videos of post-neoadjuvant imaging) to assess attitudes regarding eligibility for exploration. Descriptive and comparative statistics were used to examine differences in attitudes across geographic locations.
Results: A total of 153 eligible responses were received from 4 continents: North and South America (NSA, N=94, 61.4%), Europe (EUR, N=25, 16.3%), and Asia (N=34, 22.2%). Neoadjuvant chemotherapy is always recommended by a majority of participants in NSA (81.9%) and EUR (68.0%), but a minority in Asia (47.1%, P=0.001). The preferred duration of neoadjuvant chemotherapy also varies: participants from Asia commonly prefer 2 months (61.8%), while NSA participants prefer 4 months (52.1%), and responses from EUR were mixed(P=0.006). Participants from Asia are less likely to consider isolated liver (Asia: 67.6% vs. NSA: 90.4% vs. EUR: 72.0%;
P< 0.005) or lung (Asia: 61.8% vs. NSA: 88.3% vs. EUR:72.0%; P< 0.005) metastases contraindications to exploration, and consequently had a greater propensity to consider exploration in a vignette of oligometastatic disease (56.7%, vs. NSA: 25.6% and EUR: 43.5%,P=0.007).
Conclusions: In an international survey of pancreas surgeons, attitudes regarding LAPC management varied widely across geographic locations of practice. This variation highlights the need for evidence-based guidelines regarding the optimal management of LAPC.
OP03-07 Discovery Proteomic Analysis of Pancreatic Tumor Tissue to Identify Biomarkers for the Prediction of Response to Neoadjuvant Chemotherapy
Sumit Sahni, Australia

S. Sahni1, C. Nahm1, C. Krisp2, M. Molloy1, S. Maloney1, M. Itchins1, A. Gill1, J. Samra1, A. Mittal1
1The University of Sydney, Australia, 2University Medical Center Hamburg, Germany

Introduction: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders.
Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was preformed to characterize affected canonical pathways in good- and poor-NAC responders.
Results: A total of 3156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2ratio >2, p< 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2 and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signalling and macrophage activation, indicating a heightened immune response in these patients.
Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.
OP03-09 Comparative Bioinformatical Analysis of Pancreatic Head Cancer and Pancreatic Body/Tail Cancer
Lingdi Yin, China

L. Yin1, L. Xiao2, Y. Gao1, G. Wang1, H. Gao1, Y. Peng1, Y. Miao1, K. Jiang1, Z. Lu1
1Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, China, 2First School of Clinical Medicine, Nanjing Medical University, China

Introduction: The clinical differences between pancreatic head cancer and pancreatic body/tail cancer have been noticed for a long time. This study is to explore the biological disparities between these two from a bioinformatical perspective.
Methods: RNA-seq, mutation and clinical data were downloaded and collected from The Cancer Genome Atlas (TCGA), FireHose and CBioPortal. The patients were divided into 146 cases of pancreatic head cancer and 28 cases of pancreatic body/tail cancer. Then survival analysis was performed. DEGs were screened by R package Deseq2. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) were then carried out by DAVID and String. R package maftools and GenVisR were applied to analyze frequently-mutated genes and mutant-allele tumor heterogeneity (MATH) of PDAC.
Results: Survival of patients with pancreatic body/tail cancer was better than those with pancreatic head cancer (median survival, 24.05 vs 19.45 months, p= 0.048). And 496 significant DEGs were identified including 253 down-regulated genes and 243 up-regulated genes. And there were 13 Go terms (4 biological processes, 6 cellular components and 3 molecular functions) and 3 KEGG pathways (Pancreatic secretion, Fat digestion and absorption, Protein digestion and absorption) (FDR< 0.05). MATH scores of pancreatic body/tail cancer were higher than pancreatic head cancer, while chi-square test of top 10 frequently-mutated genes showed little difference between them.
Conclusion: There were prognostic and genetic differences between pancreatic head cancer and pancreatic body/tail cancer. PDAC originated from different location may have different biological natures and should be considered with different management.
OP03-10 Efficient Targeted Therapy for Pancreatic Cancer Using Nanosystem and Focusing on the Suppression of Pancreatic Stellate Cell Activation
Sokichi Matsumoto, Japan

S. Matsumoto, K. Nakata, N. Ikenaga, S. Date, W. Guan, A. Sagara, K. Ohuchida, T. Ohtsuka, M. Nakamura
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Japan

Introduction: Pancreatic cancer is characterized by remarkable desmoplasia which causes poor drug delivery and resistance to anticancer therapy. Pancreatic stellate cells (PSCs) play a key role in construction of such tumor environment and enhance the malignancy of pancreatic cancer cells. We have previously reported PSC activation was suppressed by inhibiting autophagy of PSC using a lysosomal inhibitor, chloroquine (CQ). However, CQ requires high dosage to be effective in vivo. In this study, we developed nanoparticle-based drug delivery system (DDS) and evaluated its availability in the tumor-bearing mouse model.
Methods: Poly lactic-co-glycolic acid (PLGA) was used as a DDS carrier. The PLGA nanoparticles were loaded with ICG (Nano-ICG) or CQ (Nano-CQ). The accumulation of Nano-ICG in pancreatic tumor was evaluated by in vivoimaging system (IVIS). The effects of CQ, Nano-CQ, or the combination of these agents and gemcitabine (GEM) on the activation of PSC and tumor growth were investigated in the orthotopic xenograft mouse model.
Results: Nano-ICG showed pancreatic tumor-specific accumulation and persisted for more than one week after administration. No obvious accumulation was observed in other major organs including liver, kidney, and normal pancreatic tissue. The fraction of activated PSC was significantly decreased in Nano-CQ group compared to the control group. The combination of Nano-CQ and GEM showed the best ability to restrain tumor progression among all the groups.
Conclusion: Our PLGA-based nanosystem was considered to be a promising DDS for the treatment of pancreatic cancer and nano-CQ could enhance the efficacy of anticancer drugs.
OP03-11 Lymph Node Ratio as Predictor of Survival in Patients with Resected Pancreatic Ductal Adenocarcinoma
Gaëtan-Romain Joliat, Switzerland

G.-R. Joliat1,2, I. Labgaa1, J. Sulzer3, D. Vrochides3, A. Zerbi4,5, G. Nappo4, J. Perinel6, M. Adham6, S. van Roessel7, M. Besselink7, J.S.D. Mieog8, J. Groen8, N. Demartines1, M. Schäfer1
1Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland, 2Graduate School for Health Sciences, University of Bern, Bern, Switzerland, 3Division of Hepatobiliary and Pancreatic Surgery, Carolinas Medical Center, Charlotte, United States, 4Humanitas Cancer Center - IRCCS, Milan, Italy, 5Department of Biomedical Sciences, Humanitas University, Milan, Italy, 6Department of Digestive Surgery, Edouard Herriot Hospital, Lyon, France, 7Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, 8Department of Surgery, Leiden University Medical Center, Leiden, Netherlands

Introduction: Lymph node ratio (LNR) was proven to be predictive of survival in several gastrointestinal cancers. Its predictive role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. This study aimed to assess if LNR predicted overall survival (OS) after pancreatoduodenectomy for PDAC.
Method: Data were collected from six international tertiary centers. Patients with PDAC who underwent upfront pancreatoduodenectomy were included (2000-2018). LNR (positive lymph nodes/harvested lymph nodes) was calculated for all patients based on pathology reports. Prognostic OS factors were assessed using multivariable Cox regression.
Results: In total, 1513 patients were included. Ninety-day mortality rate was 5.9% (89/1513). Lymph node invasion (pN+) was present in 1175 patients (77%). Median number of harvested lymph nodes and positive lymph nodes were 18 (IQR 12-24) and 3 (IQR 2-6). Median LNR was 0.148 (IQR 0.042-0.333) in the entire cohort and 0.214 (IQR 0.107-0.372) in pN+ patients. Best LNR threshold to predict OS in pN+ patients was 0.043 (C-index 0.562). A total of 368 and 1101 patients had LNR< 0.043 and LNR≥0.043 (44 missing data). Patients with LNR≥0.043 had worse median OS (23 vs. 50 months, p< 0.001). On multivariable analysis, LNR was an independent OS predictor (HR 4.7, 95% CI 1.1-19.2, p=0.033). In the pN+ group, patients with LNR≥0.043 also had worse median OS (23 vs. 44 months, p=0.037). In N1 and N2 subgroups, LNR was also an independent OS predictor.
Conclusions: In this international, multicenter cohort study, LNR was a strong independent prognostic factor of OS in patients with PDAC who underwent pancreatoduodenectomy.
OP03-12 Use of Deep Learning to Predict Tumor Response to Neoadjuvant Therapy in Pancreatic Adenocarcinoma: Pure and Hybrid Modelling
Michael Watson, United States

M. Watson, M. Baimas-George, K. Murphy, R. Pickens, D. Iannitti, J. Martinie, E. Baker, D. Vrochides, L. Ocuin
Division of HPB Surgery, Carolinas Medical Center, United States

Introduction: Neoadjuvant chemotherapy (NAC) is a growing treatment of pancreatic adenocarcinoma (PDAC) however, determining response to NAC is difficult from preoperative imaging. Our hypothesis is that a deep learning model can be used to predict tumor response to neoadjuvant therapy.
Method: Patients with PDAC that received NAC before pancreaticoduodenectomy between November 2009 and February 2019 were identified. Computed tomography (CT) images of the entire pancreas with 5mm width were obtained. Patients were grouped by CAP-TRG grade (0-2 good response vs 3 poor response). Images were used to train a convolutional neural network (CNN) deep learning model (LeNet-type). Image augmentation was used to increase the number of images available for model creation and validation.
Results: 81 patients were identified, 35 patients with good response (333 images) and 46 patients with poor response (443 images). A "training set" of 80% of patient images (n=65) was used to create the deep learning model. The model had good internal validity (100%) with loss function < 0.02. The "testing set" of 20% of patient images (n=16) was analyzed with the trained model. The AOC was 0.7383 (p< 0.0001) with Brier statistic of 0.2347. The same procedure was used to analyze patients with >10% reduction in CA19-9 after NAC (n=51). This improved the model with AOC of 0.7846 (p< 0.0001) and Brier statistic of 0.1735.
Conclusion: Deep learning can be used to predict response to NAC for patients with PDAC from imaging or CA19-9 response. Further model improvements are needed before widespread clinical application.
OP03-13 Conditional Survival During Follow-up after Resection for Pancreatic Cancer: A Population-based Study and Prediction Model
Anouk Latenstein, Netherlands

A. Latenstein, S. van Roessel, L. van der Geest, J. Wilmink, M. Besselink, Dutch Pancreatic Study Group
Amsterdam UMC, Location AMC, Netherlands

Background: Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed.
Methods: This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005-2016). Conditional survival was calculated as the median and the probability of surviving up to 8 years in patients who already survived 0-5 years after resection using the Kaplan-Meier method. A prediction model was constructed.
Results: Overall, 3,082 patients were included with a median age of 67 years. Median overall survival was 18 months (95%CI 17-18 months) with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability to survive the next year) increased from 55% to 74% to 86% at 1, 3, and 5 years after surgery, respectively. The median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability to achieve 5-year survival at 1 year after surgery varied from 1-58% depending on patient- and tumor characteristics.
Conclusions: This population-based study showed that one-year conditional survival was 55% one year after resection and 74% three years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers.
OP03-14 Prognostic Value of TP53, CDKN2A/P16 and SMAD4/DPC4 in Resected Locally Advanced Pancreatic Cancer
Niccolò Napoli, Italy

N. Napoli, E.F. Kauffmann, C. Cacace, F. Menonna, S. Iacopi, V.G. Perrone, A. Tudisco, F. Vistoli, U. Boggi
Division of General and Transplant Surgery, University of Pisa, Italy

Introduction: Prognostic factors are needed in patients with locally advanced pancreatic cancer (LAPC). We herein evaluate the prognostic impact of TP53, CDKN2A/p16 and SMAD4/DPC4 in patients who received a pancreatectomy with arterial resection (P-Ar) for LAPC.
Methods: Gene status was immunohistochemically assessed in patients operated between 2000 and 2017, based on tissue availability. Differences in disease specific survival (DSS) and disease free survival (DFS) between patients with positive and negative status were calculated by using Kaplan-Meier curves and Log-rank test. Relationship between preoperative features and genes expression was evaluated by using logistic regression.
Results: Among 99 P-Ars, 38 patients were eligible for this study. The superior mesenteric artery was resected in 16 (42.1%) patients and the celiac axis/hepatic artery in 26 (68.4%) patients. Median DSS and DFS were of 25.3 (14.2-74) and 12.8 (10.3-22) months, respectively. Abnormal immunolabeling of TP53 was present in 21 (55.2%) LPACs. Loss of p16 and SMAD4 was identified in 23 (60.5%) and 22 (57.9%) LPACs, respectively. DSS and DFS were longer in patients with positive SMAD4, positive p53 and loss of p16 (table 1). Association of loss of SMAD4 with abnormal labelling of p53 and p16 expression resulted in shorter DSS (13.3 vs. 26.7 months, p=0.03) and DFS (10.3 vs 15 months, p=0.01). Preoperative level of Ca 15.3 correlated with SMAD4/DPC4 (p=0.01) and worst prognosis (p=0.24).
Conclusion: Positive SMAD4 and p53 and negative p16 predicted survival in a cohort of 38 patients with LAPC following P-Ar. More patients are required to validate our results.
[Table 1 - Median disease specific survival and progression free survival in patients with LA- PDAC b]
OP03-17 Pancreatic Cancer Risk Prediction Model Using a Multi-biomarker Panel
Yoo Jin Choi, Korea, Republic of

Y.J. Choi1, W. Yoon2, Y. Han1, H. Kim1, W. Kwon1, A. Lee3, J.-Y. Jang1, T. Park4
1Department of Surgery, Seoul National University Hospital, Korea, Republic of, 2Research Institutes of Basic Science/Seoul National University, Korea, Republic of, 3Seoul National University Hospital, Korea, Republic of, 4Department of Statistics, Seoul National University, Korea, Republic of

The pancreatic ductal adenocarcinoma (PDAC) has dismal survival rate due to late detection. Thus, many researches have been tried to discover diagnostic biomarkers for early detection of PDAC. Previously, we developed the triple marker panel, including leucine-rich alpha-2 glycoprotein (LRG1), transthyretic (TTR), and CA 19-9, with sensitivity of 82.5%; specificity of 92.1%1. Now, in this study, using this panel, we were to discover a risk prediction model for pancreatic cancer for early diagnosis with the enzyme-linked immunosorbent assay (ELISA).
There were 744 samples assessed with ELISA, including PDACs (n=396) and normal samples (n=348). We proposed a risk prediction model with machine-learning method, logistic regression (LR), and compared it with support vector machine (SVM) and random forest (RF). To commercialize this model, we searched two optimal thresholds to distinguish three risk groups (high, intermediate, and low) that reliably satisfy four measurements, negative predictive value (NPV), positive predictive value (PPV), sensitivity (SEN), and specificity (SPE), simultaneously greater than 0.95%.
The Pearson correlation between the triple marker panel examined with ELISA and the individual marker panel examined with ELISA1 was 0.884. The risk prediction model distinguished pancreatic cancer from normal individuals with AUC 0.935. The thresholds in between low, intermediate and high groups were 0.11 and 0.77, that satisfied NPV 95.15%, PPV 97.55%, SEN 97.55%, and SPE 95.15%.
We first validated reproducibility of the performance of the triple marker panel in this study. And our risk prediction model for pancreatic cancer achieved high accuracy prediction, which can be easily used in the clinic.
OP03-18 Molecular Profiling Practices in Pancreatic Adenocarcinoma: Academic versus Community Providers
Christine Chung, United States

C. Chung1, R. Galvin2, E. Achenbach3, S. Sen3
1General Surgery, Swedish Medical Center, United States, 2General Surgery, HCA Swedish Medical Center, United States, 3Sarah Cannon Research Institute at HealthONE, United States

Introduction: Molecular profiling is currently being explored as a tool for selecting patients in targeted therapy clinical trials and to determine prognosis for patients with pancreatic adenocarcinoma (PDAC). Noninvasive molecular profiling strategies are critical given the invasiveness of obtaining tissue biopsies. We examined the practice patterns of academic versus community providers in relation to molecular profiling practices and PDAC.
Methods: We evaluated eighty-two patients referred to a tertiary clinic center to analyze patterns of molecular profiling in patients with metastatic PDAC prior to referral.
Results: A total of 42/82 (51%) were men, median age being 66 years (range 40-85). 62% (51/82) of patients were referred from the community, 25% (21/82) academic, and 7% (6/82) self-referred. 48% received profiling prior to referral, 30/51 (58%) community and 10/21 (47%) academic. FoundationOne was the most commonly ordered test with 21/82 (25%), and Guardant the second most common with 8/82, (9%). Six patients (7%) received both Guardant and Foundation one testing, and 3/82 (3%) received Caris MiProfile. One received a Mocha assay and one the Ascend/Clarient Fish. Another was self-referred, the test ordered by the primary care physician.
Conclusion: This study analyzes practice patterns of PDAC and the use of molecular profiling in Denver, Colorado. Both academic and community providers were found to order profiling about half of the time, with FoundationOne being the most common. Further research is needed to determine which factors affect ordering and impact on trial enrollment and survival.
OP03-19 Controversial Oncologic Benefit of Adjuvant Therapy for Ampullary Cancer: A Propensity Score Matched Analysis
Hyeyeon Kim, Korea, Republic of

H. Kim, W. Lee, K.B. Song, J.H. Lee, D.W. Hwang, S.C. Kim
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Korea, Republic of

Background: Although surgical treatment is the main stay for ampullary cancer(AC), the role of adjuvant chemotherapy for better prognosis is not confirmed yet.
Methods: AC patients who underwent pancreaticoduodenectomy were included between 2011 and 2019. Survival and recurrence were compared between observation(OB) and adjuvant chemotherapy(CTx) group after propensity score matching(PSM) using perioperative variables.
Results: Of 476 patients, OB group showed larger tumor size(2.1 vs 1.8cm, p=0.002), higher T stage(1,2 vs 3,4; 55.8 vs 19.0%,p< 0.001), N stage(0 vs 1; 58.3 vs 18.4%,p< 0.001) using AJCC 7th, poor differentiation(17.5 vs 6.8%,p< 0.001), lymphovascular invasion (LVI) (83.5 vs 30.1%,p< 0.001), perineural invasion(PNI) (44.3 vs 13.4%,p< 0.001), and high carbohydrate antigen 19-9 >37 IU/L (42.2 vs 26.7%,p=0.006) compared with OB group before PSM. Median follow up period was 33.4months. The 5-year overall survival(OS) (68.8 vs 60.3%,p=0.005) and recurrence free survival(RFS) rate(71.5 vs 42.2%,p< 0.001) showed poor prognosis in CTx group compared OB group before PSM. Higher N stage(Hazard ratio[HR] 3.592, 95% confidence interval(CI) 1.822-7.082,p< 0.001), tumor size 9HR 1.294, 95% CI 1.044-1.605,p=0.019), LVI(HR 2.126, 95% CI 1.180-3.830,p=0.019) PNI (HR 1.935, 95% CI 1.206-3.103,p=0.006), were prognostic factors for OS. After PSM, perioperative outcomes were comparable. In oncologic outcomes, the 5-year OS(65.7 vs 62.6%, p=0.659) and RFS(48.7 vs 56.1%, p=0.741) rate was not different between OB and CTx groups even after stratified tumor stage.
Conclusion: The patients with adjuvant chemotherapy showed comparable oncologic outcome compared the patients without adjuvant therapy. Large study will give us confirmative results of role of adjuvant therapy for ampullary cancer.
OP03-20 Relation between Quality of Life and Survival in Patients with Pancreatic and Periampullary Cancer: A Multicenter Cohort Analysis
Tara Mackay, Netherlands

T. Mackay1, A.E.J. Latenstein1, L.G. van der Geest2, M.G. Besselink1, H.W.M. van Laarhoven1, Dutch Pancreatic Cancer Group (DPCG)
1Amsterdam UMC, AMC, Netherlands, 2Netherlands Comprehensive Cancer Organisation (IKNL), Netherlands

Background: A relation between quality of life (QoL) and survival has been demonstrated for several types of cancer, yet is unclear for patients with pancreatic/periampullary cancer.
Methods: Analysis of QoL data from a prospective multicenter patient reported outcome registry in patients with pancreatic/periampullary carcinoma registered in the nationwide Netherlands Cancer Registry (2015-2018). Baseline and delta QoL (i.e. baseline - three months) was assessed with the Happiness, EORTC QLQ-C30 and QLQ-PAN26 questionnaires. The relation between QoL and survival was assessed with Cox regression models and additional prognostic value of separate items with Nagelkerke's R2 .
Results: For the baseline and delta analyses, 233 and 148 patients were available. The majority had pancreatic adenocarcinoma (n=194, 83.3%), stage III disease (n=77, 33.0%), with a median overall survival of 13.6 months. Multivariate analysis using baseline scores, indicated several scales to be of prognostic value for the total cohort (i.e. happiness today, role functioning, diarrhea, pancreatic pain, body image, all P < 0.05) and for patients without resection (i.e. satisfaction with life, physical/cognitive functioning, summary score, fatigue, pain, constipation, diarrhea, body image, all P < 0.05). Except for diarrhea, all QoL items accounted for >5% of the additional explained variance. Multivariate analysis using delta QoL revealed that only constipation was of prognostic value for the total cohort.
Conclusion: In a multicenter cohort of patients with pancreatic/periampullary carcinoma, QoL scores predicted survival, regardless of patient, tumor and treatment characteristics. QoL scores may thus be used for shared decision making regarding disease management and choice of treatment.
OP03-22 Prognostic Values of SUVmax Value of PET/CT and CA19-9 as Biologic Markers in Patients with Pancreatic Ductal Adenocarcinoma
Dokyoon Moon, Korea, Republic of

D. Moon, H. Kim, Y. Byun, Y. Han, Y.J. Choi, J.S. Kang, W. Kwon, J.-Y. Jang
Department of Surgery, Seoul National University Hospital, Korea, Republic of

Among various prognostic factors of pancreatic cancer, most of clinical information before surgery is obtained by imaging modality. However tumor biologic characteristics also should be considered to decide treatment plan. Purpose of this study is to evaluate clinical usefulness of preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography and carbohydrate antigen as biologic markers for prognosis of resectable pancreatic ductal adenocarcinoma.
189 patients with pancreatic adenocarcinoma underwent preoperative FDG-PET testing were studied. SUVmax was calculated for each primary lesion. Patients who underwent neoadjuvant chemotherapy, R2 resection, and sequential resection were excluded. Analysis about correlation between SUVmax and clinicopathologic parameters was performed. C-tree statistical method was drawn to estimated cutoff values of SUVmax and CA19-9 for survival rate. Multivariate analysis was conducted to identify prognostic factors for overall survival.
Median duration of overall survival was 26 months, five-year survival rate was 22.4%. C-tree analysis revealed the optimal cutoff values for SUVmax was 5.5 and that of CA19-9 was 150 about survival rate. When subjects were divided into three groups according to combination of SUVmax and CA19-9 values from C-tree (high group, SUVmax >5.5 and CA19-9>150, intermediate group and low group, SUVmax≤5.5 and CA19-9≤150), there was a significant 5YSR difference (5.6%, 24.3% and 36.5%, p < 0.001) The multivariate analysis revealed low BMI and high SUVmax and venous invasion were prognostic factor in overall survival.
As biologic markers, SUVmax and CA19-9 are prognostic factors in pancreatic cancer patients. Especially, patients with high SUVmax and CA19-9 ​​are not indication to upfront sugery.
OP03-23 Current Status and Long-term Outcome of Neoadjuvant Chemoradiotherapy for Resectable Pancreatic Cancer
Kenji Nakagawa, Japan

K. Nakagawa, T. Akahori, K. Nakamura, T. Takagi, N. Ikeda, M. Sho
Department of Surgery, Nara Medical University, Japan

Introduction: The progress of multidisciplinary treatment made significant improvement in survival of pancreatic cancer. However, the efficacy of neoadjuvant treatment for resectable pancreatic cancer remains to be established. We evaluated the impact of neoadjuvant chemoradiothrapy (NACRT) on perioperative and long-term outcome in resectable pancreatic cancer.
Method: This retrospective study enrolled 295 patients of resectable pancreatic ductal adenocarcinoma at Nara medical university hospital between 2006 and 2018. One hundred fifty-six patients who preoperatively received full-dose gemcitabine (1000mg/m2) with concurrent radiation of 54 Gy were analyzed. One hundred thirty-nine patients who proposed upfront surgery were served as control.
Results: Among 156 patients treated with NACRT, 14 (8.9%) couldn't undergo pancreatectomy after NACRT because of distant metastasis in 7, tumor progression in 4 and bad condition in 3. While among 139 patients who proposed upfront surgery, 7 (5.0%) couldn't undergo pancreatectomy at laparotomy because of distant metastasis. In overall survival of patients with resected and unresected tumor, patients treated with NACRT had better prognosis than those without (50.2 vs. 32.6M, P=0.017). Also only for resected tumors, the rate of Grade B/C pancreatic fistula, abdominal abscess and ≥ Clavien-Dindo Ⅲa complication were lower in NACRT than control (P=0.071, P=0.085, P=0.075). Furthermore, lymph node metastasis (17.6 vs. 51.5％, P< 0.001), and R0 resection rate (91.6 vs. 79.6％, P< 0.001) were favorable in NACRT group. Moreover, completion of adjuvant chemotherapy was also higher in NACRT (74.7 vs. 56.1％, P=0.001).
Conclusions: NACRT had a variety of favorable impact in surgical and prognostic outcomes for resectable pancreatic cancer.
OP03-24 CDK5 Activation Drives Pancreatic Neuroendocrine Tumorigenesis and is a Therapeutic Target
Sushanth Reddy, United States

A. Carter1, J. Bibb1, R. Telange1, W. Howse1, J. Schrader2, C. Tan3, B. Robinson4, S. Reddy1
1Surgery, University of Alabama at Birmingham, United States, 2General, Visceral, and Thoracic Surgery, University Medical Center Hamburg, Germany, 3Psychiatry, University of Texas Southwestern Medical Center, United States, 4Cancer Genetics, Kolling Institute of Medical Research, Australia

Introduction: Pancreatic neuroendocrine tumors(PNET) are frequently seen with significant morbidity/mortality. Most PNET are non-functional, yet existing animal models are functional. Therefore, they do not accurately recapitulate human disease. We hypothesize that Cdk5 activity (previously shown to be important in other neuroendocrine diseases) plays a role in PNET pathogenesis and maybe a therapeutic target.
Methods: Cdk5 expression was quantified in human PNET(hPNET) tissues. hPNET cell lines were treated with Cdk5 inhibitors. Bi-transgenic mice were created with inducible Cdk5 activity under control of the tet-operon. Growing/arrested tumors were studied for phosphorylation sites that were upregulated in growing tumors. Short interfering peptides (SIPs) were generated to these targets to identify potential downstream signaling pathways.
Results: All hPNET samples tested had increased Cdk5 expression(Figure A). A Cdk4/5 inhibitor(IndolamineA) affected growth of hPNET cells in a dose-dependent manner without effecting fibroblasts(Figure B). Cdk4 inhibition(IndolamineB) did not effect these cells. All transgenic mice developed PNET with most nonfunctional. Phosphoproteomic analysis identified 50 potential Cdk5 targets upregulated in growing tumors. SIPs to 15 sites inhibited growth of BON cells but not fibroblasts(Figure D, top). Six of these sites included known proteins implicated in human tumorigenesis (but unknown in hPNET). Phosphorylation of each was reduced in BON cells with Cdk5 inhibition, implicating each in PNET formation and growth.
Conclusion: Aberrant Cdk5 activity is seen in all hPNET and is a potential therapeutic target. We have created the first transgenic model of PNET that behaves like human disease and have identified molecular pathways that are being activated in PNET.
[A:Cdk5 in hPNET;B:Cdk5 inhibition of PNET;C:Blood sugars of mouse PNETs;D:phosphoproteomics]
OP03-25 Morphological Pattern and Gene Expression Analysis of Pancreatic Neuroendocrine Neoplasms
Keiichi Akahoshi, Japan

K. Akahoshi, A. Kudo, S. Watanabe, K. Inoue, H. Ono, K. Ogawa, S. Tanaka, M. Tanabe
Department of HBP Surgery, Tokyo Medical and Dental University, Japan

Background: Pancreatic neuroendocrine neoplasms (PNEN), a rare occurrence, have been increasing. A method for evaluating the malignant potential of PNEN is needed. Thus, we investigated the predictive ability of morphological pattern using multi-detector computed tomography (MDCT), and relationship between morphological pattern and gene expression pattern of PNEN.
Methods: Between 2010 and 2018, 64 patients underwent surgical resection for PNEN. The primary tumors were classified based on MDCT into two types: simple nodular (SN) and multi-nodular (MN). Characteristics of SN and MN were compared and survival analysis was performed. Then, genome-wide gene expression analysis of 10 patients were performed to compare the gene expression differences of SN and MN.
Results: Of all 64 patients, 43 were SN and 21 were MN. Compared to SN, MN showed bigger tumor size (median 39mm) and higher Ki 67 index (median 3%). Recurrence-free survival (RFS) was significantly poorer in MN compared with SN (p < 0.001) The 5-year RFS of SN and MN was 95% and 56%, respectively. Of 10 cases who were performed gene expression analysis (DNA microarray), 5 were SN and 5 were MN. Gene expression profiling revealed that 22 probes were significantly upregulated in MN. And, gene set enrichment analysis (GSEA) showed that the genes grouped to extra cellular matrix receptor interaction were significantly upregulated in MN.
Conclusions: Morphological pattern of PNEN using MDCT was related to prognosis of PNEN. MN showed significantly poorer RFS compared with SN. And, there were difference of gene expression pattern between SN and MN.
OP03-21 Preventing Delayed Gastric Emptying after Whipple´S Procedure - Isolated Roux Loop Reconstruction with Pancreatico-Gastrostomy
Prakash Om, India

V. Bansal1, P. Om1, A. Krishna1, M. Jain1, A. Baksi1, S. Kumar1, P. Garg2, H. Bhattacharjee1, M. Misra3
1Department of Surgical Disciplines, AIIMS, India, 2Department of Gastroenterology, AIIMS, India, 3Department of Surgical Disciplines, Mahatma Gandhi University of Medical Sciences, India

Introduction: Although delayed gastric emptying (DGE) after Whipple's pancreaticoduodenectomy is not life threatening and can be treated conservatively, it results in discomfort and significant prolongation of the hospital stay and adds on to the hospital costs. To overcome this problem, we started using the isolated loop technique of reconstruction along with pancreaticogastrostomy and we present our series using this technique.
Methods: All consecutive patients undergoing Whipple's pancreaticoduodenectomy in a single surgical unit from January 2009 until December 2018 were included. In the absence of hepatic and peritoneal metastasis, resection (Whipple's procedure) with curative intent was done using isolated loop technique with pancreaticogastrostomy. Delayed gastric emptying was assessed clinically and on oral gastrograffin study. Bile reflux was also assessed on clinical parameters and evidence of beefy friable gastric mucosa on upper GI endoscopy and presence of reflux on hepatobiliary scintigraphy.
Results: A total of 101 patients were operated using this technique from January 2009 to December 2018. The mean operative time was 260.8 ± 50.3, and the mean operative blood loss was 1,068.0 ± 606.1 ml. Mean gastric emptying time 106.0 ± 6.1 min (89-258 min). 5 out of the 101 (4.9 %) patients had persistent vomiting in the post-operative period requiring reinsertion of NG tube. A HIDA scan done on POD7 for all patients did not show any evidence of bile reflux in any of the patients.
Conclusion: Pancreatogastrostomy with isolated loop in pancreaticoduodenal resection markedly reduces the post-operative incidence of alkaline reflux gastritis and DGE