Benign Pancreatic Disease Research Articles

Study on the diagnostic value of VEGF, CA19-9 and CEA in pancreatic cancer and the risk factors of vascular invasion

Background: Pancreatic cancer is a malignant tumor of the gastrointestinal tract. Due to its insidious onset, most patients with newly diagnosed pancreatic cancer have missed the opportunity for radical surgery, which offers patients the best chance of survival. The 5-year survival rate of patients with pancreatic cancer can be improved with early diagnosis, and serum tumor makers are an inexpensive and convenient diagnostic tool that is widely used in the diagnosis of malignancies. Objective: To determine the diagnostic value of vascular endothelial growth factor (VEGF), carbohydrate antigen 19-9 (CA 19-9), and carcinoembryonic antigen (CEA) in patients with pancreatic cancer and the risk factors of vascular invasion. Methods: An experimental group comprising 52 patients with pancreatic cancer admitted to our department from July 2021 to July 2022 and a control group comprising 21 patients with benign pancreatic diseases during the same period were included in our study. Their serum VEGF, CA 19-9, and CEA levels were detected and compared between the two groups, and the correlation between the three markers in the invaded vessel and non-invaded vessel groups was investigated. The diagnostic value of a single tumor marker and in combination for pancreatic cancer was analyzed, and the three tumor marker levels of the experimental group in different pathological characteristics were detected and compared. Results: The experimental group had higher serum VEGF, CA 19-9, and CEA levels than the control group (P < 0.05). Through a receiver operating characteristic (ROC) curve analysis, the combined detection had the highest value for the diagnosis of pancreatic cancer, in which the area under the curve (AUC) was 0.9158 (95% CI: 0.8415–0.9900), while the sensitivity and specificity were 76.19% and 98.08%, respectively. Serum VEGF and CA 19-9 levels were higher in stage III–IV pancreatic cancer patients and those with tumor metastasis compared with stage I–II patients and those without metastasis (P < 0.05), respectively. Binary logistic regression analysis was performed to determine the risk factors of vascular invasion in pancreatic cancer, and the results showed that only serum VEGF was a risk factor (P < 0.05), OR (95% CI): 1.001–1.006. Conclusion: Patients with pancreatic cancer have significantly higher serum VEGF, CA 19-9, and CEA levels, and the combined detection of tumor markers is of high clinical value in its diagnosis. In addition, serum VEGF is an independent risk factor of vascular invasion in pancreatic cancer, which can predict vascular invasion to a certain extent.

Multianalyte Serum Biomarker Panel for Early Detection of Pancreatic Adenocarcinoma.

We determined whether a large, multianalyte panel of circulating biomarkers can improve detection of early-stage pancreatic ductal adenocarcinoma (PDAC). We defined a biologically relevant subspace of blood analytes on the basis of previous identification in premalignant lesions or early-stage PDAC and evaluated each in pilot studies. The 31 analytes that met minimum diagnostic accuracy were measured in serum of 837 subjects (461 healthy, 194 benign pancreatic disease, and 182 early-stage PDAC). We used machine learning to develop classification algorithms using the relationship between subjects on the basis of their changes across the predictors. Model performance was subsequently evaluated in an independent validation data set from 186 additional subjects. A classification model was trained on 669 subjects (358 healthy, 159 benign, and 152 early-stage PDAC). Model evaluation on a hold-out test set of 168 subjects (103 healthy, 35 benign, and 30 early-stage PDAC) yielded an area under the receiver operating characteristic curve (AUC) of 0.920 for classification of PDAC from non-PDAC (benign and healthy controls) and an AUC of 0.944 for PDAC versus healthy controls. The algorithm was then validated in 146 subsequent cases presenting with pancreatic disease (73 benign pancreatic disease and 73 early- and late-stage PDAC cases) and 40 healthy control subjects. The validation set yielded an AUC of 0.919 for classification of PDAC from non-PDAC and an AUC of 0.925 for PDAC versus healthy controls. Individually weak serum biomarkers can be combined into a strong classification algorithm to develop a blood test to identify patients who may benefit from further testing.

Circulating Tumor DNA Is an Accurate Diagnostic Tool and Strong Prognostic Marker in Pancreatic Cancer.

The objectives of the study are to investigate the sensitivity and specificity of circulating tumor DNA (ctDNA) for the diagnosis of pancreatic cancer and to assess the utility of ctDNA as a prognostic marker in this disease. Cell-free DNA was extracted from plasma of patients who underwent endoscopic ultrasound fine-needle aspiration or surgical resections for pancreatic cancer. The cell-free DNA was then analyzed using droplet digital polymerase chain reaction for KRAS G12/13 mutations. Eighty-one patients with pancreatic cancer and 30 patients with benign pancreatic disease were analyzed. ctDNA KRAS G12/13 mutations were detected in 63% of all patients with pancreatic cancer and in 76% of those patients who also had KRAS G12/13 mutations detected in the pancreatic primary. Specificity and tissue concordance were both 100%. Circulating tumor DNA corresponded with tumor size and stage, and high ctDNA was associated with significantly worse prognosis on both univariate and multivariate testing. Our study shows that ctDNA is an accurate diagnostic tool and strong prognostic marker in patients with pancreatic cancer. The continued investigation of ctDNA will enable its implementation in clinical practice to optimize the care and survival outcomes of patients with pancreatic cancer.

The Adverse Effect of Analgesics and Coeliac Plexus Block for the Relief of Pain in Carcinoma of Pancreas – A Prospective Observational Study

Introduction: Pancreatic cancer is a formidable health problem with increasing incidence. Worldwide, over 200000 people die annually of pancreatic cancer Because of high fatality rates; pancreatic cancer incidence rates are almost equal to mortality rates. Pancreatic cancer is diagnosed late in the natural history of the disease, given the few early indicators of illness, and the lack of screening tests for this disease. Neurolytic celiac plexus block (NCPB) is commonly used to treat pain of upper abdominal cancer that fails to respond to narcotic analgesics. CPB refers to the temporary inhibition of the celiac plexus often achieved with a corticosteroid injection in patients with benign pancreatic diseases like chronic pancreatitis. Aim of the study: The aim of this study was to determine and compare the adverse effect of analgesics and coeliac plexus block in relieving pain in carcinoma of pancreas. Methods: This study was a randomized comparative study and was conducted in the Department of Anesthesia, Analgesia and Intensive Care Medicine of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh during the period from July, 2008 to June, 2009. A total number of 60 patients were enrolled in this study. All patients were divided into two groups- Group A (treated with NCPB) & Group B (treated with conventional analgesic drugs). Result: In total 60 patients from both the groups completed the study. In our study we found the majority (58%) of our patients were aged between 41-60 years old followed by 30% were aged above 60 years old. The least prevalence 5% &7% was found among <= 20 and 21-40 years old respectively. In this study we found majority of our patients were male (63%) compared to female (37%).The mean age in the group A and group B patients were 48.73 ± 14.26 years and 51.47 ± 12.35 years respectively. In our study we found after 15th day of treatment severe vomiting was 13% in group B on the other hand vomiting was absent in. 13% in group ........

Pancreatic duct stents.

Pancreatic duct stenting using endoscopy or surgery is widely used for the management of benign and malignant pancreatic diseases. Endoscopic pancreatic stents are mainly used to relieve pain caused by chronic pancreatitis and pancreas divisum, and to treat pancreatic duct disruption and stenotic pancreaticointestinal anastomosis after surgery. They are also used to prevent postendoscopic retrograde cholangiopancreatography pancreatitis and postoperative pancreatic fistula, treat pancreatic cancer, and locate radiolucent stones. Recent advances in endoscopic techniques, such as endoscopic ultrasonography and balloon enteroscopy, and newly designed stents have broadened the indications for pancreatic duct stenting. In this review we outlined the types, insertion procedures, efficacy, and complications of endoscopic pancreatic duct stent placement, and summarized the applications of pancreatic duct stents in surgery.

Racial and Ethnic Disparities in Opioid Prescriptions in Benign and Malignant Pancreatic Disease in the United States.

Racial-ethnic disparities in pain management are common but not known among pancreatic disease patients. We sought to evaluate racial-ethnic disparities in opioid prescriptions for pancreatitis and pancreatic cancer patients. Data from the National Ambulatory Medical Care Survey were used to examine racial-ethnic and sex differences in opioid prescriptions for ambulatory visits by adult pancreatic disease patients. We identified 207 pancreatitis and 196 pancreatic cancer patient visits, representing 9.8 million visits, but weights were repealed for analysis. No sex differences in opioid prescriptions were found among pancreatitis (P = 0.78) or pancreatic cancer patient visits (P = 0.57). Opioids were prescribed at 58% of Black, 37% of White, and 19% of Hispanic pancreatitis patient visits (P = 0.05). Opioid prescriptions were less common in Hispanic versus non-Hispanic pancreatitis patients (odds ratio, 0.35; 95% confidence interval, 0.14-0.91; P = 0.03). We found no racial-ethnic differences in opioid prescriptions among pancreatic cancer patient visits. Racial-ethnic disparities in opioid prescriptions were observed in pancreatitis, but not pancreatic cancer patient visits, suggesting possible racial-ethnic bias in opioid prescription practices for patients with benign pancreatic disease. However, there is a lower threshold for opioid provision in the treatment of malignant, terminal disease.

Usefulness of Adding Maspin Staining to p53 Staining for EUS-FNA Specimens of Pancreatic Ductal Adenocarcinoma.

Background: Endoscopic ultrasound-guided puncture aspiration biopsy (EUS-FNA) of pancreatic ductal adenocarcinoma (PDAC) is highly diagnostic, but it is difficult to distinguish from benign disease. Our objective was to determine the usefulness of maspin staining, in addition to conventional p53 staining, in the diagnosis of PDAC by EUS-FNA. Methods: Of the patients who underwent EUS-FNA and were diagnosed with PDAC, we retrospectively identified 90 cases in which both maspin and p53 staining were performed. In addition, we identified 28 cases of benign pancreatic disease diagnosed using EUS-FNA and these were selected as a control group. For analysis of EUS-FNA specimens, Cohen’s Kappa (κ) coefficient and the prevalence and bias adjusted Kappa statistic (PABAK) were applied to assess the significance of sensitivity and specificity, comparing p53, maspin, p53+maspin. Results: The sensitivity and specificity of p53 staining were 48.9% and 100%. The κ coefficient was 0.31 (95%CI 0.18–0.44) (p < 0.01) and the PABAK coefficient was 0.22 (95%CI 0.03–0.40). The results for maspin staining were 88.9% and 92.9%. The κ coefficient was 0.72 (95%CI 0.54–0.90) (p < 0.01) and the PABAK coefficient was 0.78 (95%CI 0.64–0.88). The results for the combination of maspin and p53 staining were 94.4% and 92.2%. The κ coefficient was 0.82 (95%CI 0.64–1.00) (p < 0.01) and the PABAK coefficient was 0.86 (95%CI 0.74–0.94). Conclusion: Adding maspin staining to p53 staining showed high sensitivity and specificity. Our results demonstrated the usefulness of their combined use that might contribute to the improvement of tissue diagnostic performance of PDAC by EUS-FNA.

CA19-9 in Combination with Methylated HOXA1 and SST Is Useful to Diagnose Stage I Pancreatic Cancer

Introduction: We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. Methods: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. Results: For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. Conclusion: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.

S92 Racial and Ethnic Disparities in Opioid Prescriptions in Benign and Malignant Pancreatic Disease in the United States, 2006-2015

Introduction: Racial and ethnic disparities in pain management are well established, but not for patients with pancreatic disease. We sought to evaluate racial-ethnic disparities in opioid prescriptions for patients with acute and chronic pancreatitis and pancreatic cancer. Methods: Data from the National Ambulatory Medical Care Survey (NAMCS) were used to examine opioid prescriptions recorded during ambulatory visits by adult pancreatic disease patients between 2006 and 2015. Diagnoses were determined by ICD-9 codes 557.0 and 577.1 for acute and chronic pancreatitis and 157 for pancreatic cancer. Visits by patients with other painful conditions associated with opioid use were excluded. Bivariate analysis was used to detect differences in opioid prescriptions by patient race, ethnicity, and sex. Data weights for national-level estimates were not applied in accordance with NAMCS guidelines requiring a relative standard error of 30% or less. Results: We identified 421 outpatient visits by adults with pancreatic disease. Eighteen patients with comorbid painful conditions (lumbago, myalgia, generalized pain, ankylosing spondylitis, osteoarthritis, multiple sclerosis, and mononeuritis) were excluded. A total of 207 pancreatitis and 196 pancreatic cancer patient visits were identified, representing 9.8 million visits, but weights were repealed for analysis. No sex differences in opioid prescriptions were found among pancreatitis (p=0.78) or pancreatic cancer patient visits (p=0.57). Opioids were prescribed at 58% of non-Hispanic Black, 37% non-Hispanic White, and 19% Hispanic pancreatitis (P=0.05) patient visits (Table). Opioid prescriptions were less common in visits by Hispanic compared to non-Hispanic pancreatitis patients (OR 0.35, 95% CI 0.14-0.91, p=0.03) and there was a trend toward higher rates in non-Hispanic Black versus non-Hispanic White patient visits. No racial-ethnic differences in opioid prescriptions were seen among pancreatic cancer patient visits. Conclusion: While racial-ethnic disparities in opioid prescriptions were observed in pancreatitis patient visits, none were seen in pancreatic cancer patient visits. These findings suggest racial and ethnic bias in opioid prescription practices for patients with painful but benign pancreatic disease, but there may be a lower threshold for opioid provision in the treatment of malignant and terminal pancreatic disease. Table 1. - Demographic characteristics and likelihood of opioid use among visits by adult pancreatitis and pancreatic cancer patients in NAMCS, 2006-2015 No opioid Opioid Prescription OR (95% CI) p-value Pancreatitis N=132 (64%) N=75 (36%) Race/Ethnicity, % A) Non-Hispanic 106 (61) 69 (39) Reference Reference Hispanic 26 (81) 6 (19) 0.35 (0.14-0.91) .03 B) White non-Hispanic 87 (63) 52 (37) Reference Reference Black non-Hispanic 10 (42) 14 (58) 2.34 (0.97-5.65) .06 Hispanic 26 (81) 6 (19) 0.39 (0.15-1.00) .05 Other non-Hispanic 9 (75) 3 (25) 0.56 (0.42-0.84) .40 Sex, % Female 59 (65) 32 (35) Reference Reference Male 73 (63) 43 (37) 1.09 (0.61-1.92) .78 Pancreatic Cancer N=126 (64%) N=70 (36%) Race/Ethnicity, % White non-Hispanic 97(64) 54(36) Reference Reference Black non-Hispanic 17(65) 9(35) 0.95 (0.40-2.28) .91 Hispanic 8(62) 5(38) 1.12 (0.35-3.60) .85 Other non-Hispanic 4(67) 2(33) 0.90 (0.16-5.06) .90 Sex, % Female 63(62) 38(38) Reference Reference Male 63(66) 32(34) 0.84 (0.47-1.51) .57

Pancreaticoduodenectomy for benign and premalignant pancreatic and ampullary disease: is robotic surgery the better approach?

The robotic platform is increasingly being utilized in pancreatic surgery, yet its overall merits and putative advantages remain to be adjudicated. We hypothesize that the benefits of minimally invasive pancreatic surgery are maximized in pancreatic benign and premalignant disease, in the setting of friable pancreatic tissue and small pancreatic duct. Retrospective analysis of our prospectively maintained pancreatic database of all consecutive patients who underwent pancreaticoduodenectomy (PD) for benign or premalignant conditions between 2010 and 2020. Peri-operative outcomes and long-term complications were compared between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). One hundred and eighty eight (n = 188) patients met our inclusion criteria, of which 68 were OPD and 120 RPD. Malignant histologies were excluded. There were only minor differences in baseline characteristics between the two groups. Post-operative merits of the RPD included lower clinically relevant post-operative pancreatic fistula 10 (8.3%) vs 24 (35.3%), p < 0.001, fewer surgical site infections; 9 (7.5%) vs 11 (16.2%), p = 0.024, shorter operative time, greater lymph node yield; 29 (IQR 21, 38) vs 21 (IQR 13, 34), p = 0.001, and lower 90days mortality; 1 (0.8%) vs 4 (5.9%), p = 0.039. Rates of long-term complications were similar, exception made for a higher occurrence of small bowel obstruction (SBO) 2 (1.7%) vs 4 (5.9%), p = 0.031 and need for surgical intervention for SBO 0 (0.0%) vs 2 (2.9%), p = 0.019 in the OPD group. Our study suggests that RPD benefits include lower 90-day mortality, shorter LOS, and lower rates of selected complications compared to open pancreaticoduodenectomy.

Clinical outcomes of organ-preserving pancreatectomy for benign or low-grade malignant pancreatic tumors: A multicenter nationwide survey in Japan.

Whether organ-preserving pancreatic surgery has an advantage in postoperative short- and long-term outcomes or not is still unknown because only small case series studies have been available to date. In this multicenter retrospective study, we aimed to elucidate the clinical advantage and disadvantage of organ-preserving pancreatectomy among patients with low-grade malignant pancreatic tumors and benign pancreatic diseases. We included patients diagnosed with benign or low-malignant pancreatic tumor who underwent pancreaticoduodenectomy (PD) in 621 cases, duodenum-preserving pancreatic head resection (DPPHR) in 31 cases, middle pancreatectomy (MP) in 148 cases, distal pancreatectomy (DP) in 814 cases, and spleen-preserving distal pancreatectomy (SPDP) in 259 cases between January 1, 2013, and December 31, 2017. Preoperative backgrounds, surgical outcomes and pre- and postoperative (3, 6, 12, 24, and 36months) nutritional status were compared between these procedures. In terms of short-term outcomes, the incidence of pancreatic fistula in patients who underwent MP was significantly higher than in patients with standard pancreatectomy. As for the long-term pancreatic functions in the cases of head or body lesion, both exocrine and endocrine functions after MP were significantly favorable compared with the PD group from 3 to 36months after surgery. In pancreatic body or tail lesion, significant advantage of endocrine function, but not exocrine function, was found in the MP group compared to standard DP at all time points. MP may contribute to the improvement of postoperative quality of life for patients with pancreatic body low-malignant tumors, rather than PD or DP; however, reducing the incidence of short-term complications such as pancreatic fistula is a future challenge.

Evaluation of Ultrasound-Based Point Shear Wave Elastography for Differential Diagnosis of Pancreatic Diseases.

Introduction: A variety of imaging techniques exists for the diagnosis of pancreatic disorders. None of the broadly applied diagnostic methods utilizes elasticity as an indicator of tissue damage. A well-known fact is that both chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDA) are associated with the development of prominent fibrosis (increased tissue stiffness). Purpose: To prospectively assess the accuracy of point shear wave elastography (pSWE) in differentiating between benign and malignant pancreatic diseases, establish a cut-off value for the diagnosis of PDA, and evaluate the influence of certain variables on the obtained results. Materials and methods: The present study included 78 patients who were admitted at the Department of Gastroenterology at the university hospital “Kaspela” between December 2017 and August 2021 for diagnosis and/or treatment of pancreatic disorders. Based on the clinical criteria, diagnostic imaging, and histological findings, patients were divided into the CP and PDA group. The ultrasound based pSWE technique was applied and shear wave velocity (SWV) was measured. The depth of region of interest (ROI) and successful measurement rate were also recorded. Results: The mean ± SD SWV values established through pSWE were 1.75 ± 0.34 m/s and 2.93 ± 0.91 m/s for the CP and PDA, respectively. With a cut-off value of 2.09 m/s, we calculated the sensitivity (Se), specificity (Sp), and accuracy for differentiating between CP and PDA of 89.47%, 91.20%, and 88.60%, respectively. Of the examined variables, BMI and depth of ROI in the CP group and sex in the PDA group showed a statistically significant influence on the obtained results. Conclusions: pSWE may be utilized as a differential diagnostic modality in patients with suspected CP or PDA.

Identification of potential biomarkers for digestive system cancers from serum-derived extracellular vesicle RNA

BackgroundPoor prognosis of digestive system cancers is mainly owing to lack of accurate and timely diagnosis. The exploration of novel tumor biomarkers from extracellular vesicle (EV) might be helpful to clinical diagnosis for digestive system cancers. MethodsSeveral public databases were first used for a preliminary screening of candidate genes. The RNA levels of these candidate genes were then detected in cancer cell lines and the patients serum-derived EVs by PCR Array or digital PCR, respectively. ResultsWe found that 4 EV-RNAs, ANLN, ITGA6, KRT18, and MMP9, had a lower level in gastrointestinal cancer patients than in benign gastrointestinal diseases patients and healthy controls, while 3 EV-RNAs, ANLN, ITGA6, and KRT18, had a lower level in pancreatic cancer patients than in benign pancreatic diseases patients or healthy individuals. And EV-RNA of MMP9 had a relatively higher level in advanced pancreatic cancer patients than in early-stage patients. Moreover, ROC analysis demonstrated that the determination of the above EV-RNAs could increase the ability of traditional tumor biomarkers to distinguish benign and malignant diseases. ConclusionsThe serum-derived EV-RNAs of ANLN, ITGA6, KRT18, and MMP9 could be served as novel, non-invasive biomarkers for digestive system cancers.

Liquid biopsy, using a novel DNA methylation signature, distinguishes pancreatic adenocarcinoma from benign pancreatic disease

We tested the ability of a novel DNA methylation biomarker set to distinguish metastatic pancreatic cancer cases from benign pancreatic cyst patients and to monitor tumor dynamics using quantitative DNA methylation analysis of cell-free DNA (cfDNA) from blood samples. The biomarkers were able to distinguish malignant cases from benign disease with high sensitivity and specificity (AUC = 0.999). Furthermore, the biomarkers detected a consistent decline in tumor-derived cfDNA in samples from patients undergoing chemotherapy. The study indicates that our liquid biopsy assay could be useful for management of pancreatic cancer patients.

Validation of IL-7R as an Immunological Biomarker for Human Pancreatic Ductal Adenocarcinoma.

Simple SummaryDespite being the fourth-leading cause of cancer-related deaths worldwide, pancreatic ductal adenocarcinoma (PDAC) lacks early diagnostic methods. We performed mRNA sequencing on peripheral blood mononuclear cells isolated from PDAC patients and identified IL-7R as a potential early diagnostic biomarker for PDAC. Furthermore, we found that IL-7R had improved diagnostic performance when combined with CA19-9. Our previous study’s results with 23 individuals were validated in a cohort of 522 patients. Our findings suggested that IL-7R in combination with CA19-9 could have important clinical implications that contribute to an earlier PDAC diagnosis and improved patient survival.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer for which no early diagnostic method is available. The immune surveillance hypothesis suggests that the immune system plays crucial roles in tumor development and progression. We validated a PDAC-specific biomarker derived from peripheral blood mononuclear cells (PBMCs) to facilitate early PDAC diagnosis. mRNA levels of interleukin-7R (IL-7R), reportedly a potential immunological marker for PDAC, were measured in PBMCs isolated prospectively from healthy controls (n = 100) and patients with PDAC (n = 135), pancreatic cysts (n = 82), chronic pancreatitis (n = 42), acute pancreatitis (n = 47), and other malignancies (n = 116). The IL-7R level was significantly higher in patients with PDAC than in healthy controls, patients with benign pancreatic disease, and patients with other malignancies. As diagnostic parameters, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IL-7R were 58.5%, 92%, 90.8%, 62.2%, and 72.8%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.766. IL-7R levels did not differ between resectable and unresectable PDAC cases. The combined measurement of IL-7R and carbohydrate antigen 19-9 (CA19-9) significantly improved the diagnostic parameters and AUROC compared with the use of IL-7R or CA19-9 alone. IL-7R is significantly upregulated in PBMCs in patients with PDAC, and it may be a novel diagnostic marker for PDAC. The combined use of IL-7R and CA19-9 enhanced the diagnostic performance.

Large scale proteomics of circulating extracellular vesicles to reveal novel biomarkers for pancreatic cancer.

523 Background: Robust biomarkers are urgently needed to assist in diagnosing pancreatic cancer. Earlier cancer diagnosis could increase survival rates by an estimated 5-fold and more reliable and real-time assessment of treatment effects in patients with cancer could improve quality of life and reduce healthcare costs. Isolation of circulating extracellular vesicles (cEVs) as ‘liquid biopsies’ offers an advantageous approach to diagnose and monitor disease status. Methods: We conducted a comprehensive proteomics study of cEVs from plasma samples to identify EV proteins that may be used as biomarkers for the diagnosis and prognosis of pancreatic cancer. Patients with pancreatic ductal adenocarcinoma (PDAC) of various tumor stages, chronic pancreatitis, intraductal papillary mucinous neoplasm (IPMN), and age-matched controls were enrolled. EVs were isolated directly from plasma samples using the affinity-based EVTrap method then subject to quantitation by liquid chromatography-tandem mass spectrometry. Results: A total of 124 patients (93 with PDAC, 12 with chronic pancreatitis, 8 with IPMN and 11 controls) were included in the discovery cohort. The isolation of EVs with EVtrap allowed the identification on average of 912 EV proteins per 100µL of sample. Principal component analysis of the cEV proteome showed clear separation between PDAC and benign pancreatic diseases. Individuals with IPMN were more closely related to controls, whereas chronic pancreatitis cases were more related to PDAC. At the functional level, we noted that cytokeratin, protein folding chaperons, and actin dynamics regulators were among protein clusters more highly altered in the cEV of patients with PDAC. We further identified new cEV markers associated with metastatic disease, such as PSMB4, RUVBL2, and ANKAR, as well as other EV proteins with strong correlation to prognosis, such as CRP, RALB, and CD55. Finally, we validated a 7-protein PDACEV signature in a validation cohort of 36 separate patients (24 with PDAC, 6 with chronic pancreatitis and 6 with IPMN) which yielded an 89% prediction accuracy for the diagnosis of PDAC. Conclusions: This study provides a valuable resource to the scientific community with a comprehensive catalog of novel proteins on circulating EVs that may assist in the development of novel biomarkers and improve the outcomes of patients with pancreatic cancer.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer.

The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer. Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls. The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse. Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

Yield of testing for micronutrient deficiencies associated with pancreatic exocrine insufficiency in a clinical setting: An observational study

BACKGROUNDPancreatic exocrine insufficiency (PEI) can be difficult to diagnose and causes maldigestion symptoms and malabsorption. There has been a number of studies that have identified PEI associated micronutrient deficiencies (PEI-MD), however there is variation in both the frequency and type of PEI-MD reported, with the majority of studies including patients with PEI due to chronic pancreatitis (CP) or CP without PEI. There is a paucity of information regarding the prevalence of PEI-MD in patients with PEI without CP and the yield of testing for PEI-MD in a clinical setting in patients with suspected benign pancreatic diseases.AIMTo prospectively assess the yield and type of PEI–MD in patients with and without PEI secondary to benign pancreatic disease. METHODSPatients investigated for maldigestion symptoms with Faecal Elastase-1 (FEL-1) and suspected or proven benign pancreatic disease were prospectively identified. At the time of FEL-1 testing, serum samples were taken for micronutrients identified by previous studies as PEI-MD: prealbumin, retinol binding protein, copper, zinc, selenium, magnesium and later in the study lipid adjusted vitamin E. FEL-1 was recorded, with a result < 200 µg/g considered diagnostic of PEI. Patients underwent computed tomography (CT) imaging when there was a clinical suspicion of CP, a new diagnosis of PEI recurrent, pancreatic type pain (epigastric abdominal pain radiating to back with or without previous acute pancreatitis attacks) or weight loss.RESULTSAfter exclusions, 112 patients were recruited that underwent testing for FEL-1 and PEI-MD. PEI was identified in 41/112 (36.6%) patients and a pancreatic CT was performed in 82 patients. Overall a PEI-MD was identified in 21/112 (18.8%) patients. The yield of PEI-MD was 17/41 (41.5%) if PEI was present which was significantly higher than those without 4/71 (5.6%) (P = 0.0001). The yield of PEI–MD was significantly higher when PEI and CP were seen together 13/22 (59.1%) compared to CP without PEI and PEI without CP (P < 0.03). Individual micronutrient assessment showed a more frequent occurrence of prealbumin 8/41 (19.5%), selenium 6/41 (14.6%) and magnesium 5/41 (12.2%) deficiency when PEI was present (< 0.02). The accuracy of using the significant micronutrients identified in our cohort as a predictor of PEI showed a positive predictive value of 80%-85.7% [95% confidence interval (CI): 38%-100%] and a low sensitivity of 9.8%-19.5% [95% CI: 3.3%-34.9%].CONCLUSIONTesting for PEI-MD in patients with suspected pancreatic disease has a high yield, specifically when PEI and CP are found together. PEI-MD testing should include selenium, magnesium and prealbumin.

Robotic versus Open Pancreatoduodenectomy for Pancreatic and Periampullary Tumors (PORTAL): a study protocol for a multicenter phase III non-inferiority randomized controlled trial

BackgroundPancreatoduodenectomy is a complex and challenging procedure that requires meticulous tissue dissection and proficient suturing skills. Minimally invasive surgery with the utilization of robotic platforms has demonstrated advantages in perioperative patient outcomes in retrospective studies. The development of robotic pancreatoduodenectomy (RPD) in specific has progressed significantly, since first reported in 2003, and high-volume centers in pancreatic surgery are reporting large patient series with improved pain management and reduced length of stay. However, prospective studies to assess objectively the feasibility and safety of RPD compared to open pancreatoduodenectomy (OPD) are currently lacking.Methods/designThe PORTAL trial is a multicenter randomized controlled, patient-blinded, parallel-group, phase III non-inferiority trial performed in seven high-volume centers for pancreatic and robotic surgery in China (> 20 RPD and > 100 OPD annually in each participating center). The trial is designed to enroll and randomly assign 244 patients with an indication for elective pancreatoduodenectomy for malignant periampullary and pancreatic lesions, as well as premalignant and symptomatic benign periampullary and pancreatic disease. The primary outcome is time to functional recovery postoperatively, measured in days. Secondary outcomes include postoperative morbidity and mortality, as well as perioperative costs. A sub-cohort of 128 patients with pancreatic adenocarcinoma (PDAC) will also be compared to assess the percentage of patients who undergo postoperative adjuvant chemotherapy within 8 weeks, in each arm. Secondary outcomes in this cohort will include patterns of disease recurrence, recurrence-free survival, and overall survival.DiscussionThe PORTAL trial is designed to assess the feasibility and safety of RPD compared to OPD, in terms of functional recovery as described previously. Additionally, this trial will explore whether RPD allows increased access to postoperative adjuvant chemotherapy, in a sub-cohort of patients with PDAC.Trial registrationClinicalTrials.govNCT04400357. Registered on May 22, 2020

SP3.1.2 The influence of frailty on outcomes for older adults admitted to hospital with benign biliary and pancreatic disease

Abstract Aims To study the prevalence and complications of biliary disease with increasing age. We describe the prevalence of frailty in older patients hospitalised with benign biliary and pancreatic disease and establish its association with mortality and duration of hospital stay. Methods Prospective observational cohort study of patients aged 75 years and over admitted with acute biliary disease between 17/09/2014 and 20/03/2017. Clinical Frailty Scale (CFS) score was recorded on admission. Results 200 patients with a median age of 82 (75-99), 60% females, 154 (77%) were independent for personal and 99 (49.5%) for instrumental activities of daily living. Acute cholecystitis was the most common diagnosis (43%), acute cholangitis (36%) and acute pancreatitis (21%). 99 patients were non-frail (NF = CFS 1-4) and 101 were frail (F= CFS ≥5). 104 patients received medical treatment only. Surgery was more common in non-frail (F 2% vs. NF 11%), percutaneous drainage more frequently carried out in frail patients (15% vs. NF 5%) and endoscopic cholangiopancreatography (ERCP) was similar in both groups (F 32%vs. NF 31%). Frailty was associated with worse clinical outcomes. F vs. NF: functional deconditioning (34% vs. 11%), increased care level (19% vs 3%), length of stay (12 vs. 7 days), 90-day (8% vs. 3%) and 1 year-mortality (48% vs. 24%). Conclusions : Higher frailty scoring is associated with increased mortality in acute biliary disease. Individuals living with frailty were less likely to undergo surgical treatment, spent longer in hospital and were less likely to remain alive at 12 months after hospital discharge.