Pancreas

The 49th Annual Meeting of the American Pancreatic Association in Collaboration With the International Association of Pancreatology No abstract available

Next-Generation Sequencing in Pancreatic Cancer Pancreatic ductal adenocarcinoma (PDAC) is lethal, and the majority of patients present with locally advanced or metastatic disease that is not amenable to cure. Thus, with surgical resection being the only curative modality, it is critical that disease is identified at an earlier stage to allow the appropriate therapy to be applied. Unfortunately, a specific biomarker for early diagnosis has not yet been identified; hence, no screening process exists. Recently, high-throughput screening and next-generation sequencing (NGS) have led to the identification of novel biomarkers for many disease processes, and work has commenced in PDAC. Genomic data generated by NGS not only have the potential to assist clinicians in early diagnosis and screening, especially in high-risk populations, but also may eventually allow the development of personalized treatment programs with targeted therapies, given the large number of gene mutations seen in PDAC. This review introduces the basic concepts of NGS and provides a comprehensive review of the current understanding of genetics in PDAC as related to discoveries made using NGS.

KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound–Fine-Needle Aspiration in Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis To evaluate the diagnostic accuracy of KRAS mutation in pancreatic cystic fluid and compare it with carcinoembryonic antigen and cytology, we identified studies with cyst fluid obtained by endoscopic ultrasound prior to surgery. We classified cysts as malignant, premalignant, and benign. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic curve analysis were conducted. We analyzed 16 studies, with 3429 patients, including 731 referred for surgery. Carcinoembryonic antigen was better for clinically significant cysts (premalignant and malignant) with sensitivity = 0.58 (95% confidence interval [CI], 0.53–0.65), specificity = 0.9 (95% CI, 0.76–0.97), and area under the curve (AUC) = 0.69. Cytology performed better in malignant cysts, with sensitivity = 0.37 (95% CI, 0.27–0.48), specificity = 0.96 (95% CI, 0.93–0.98), and AUC = 0.78. Isolated, KRAS mutation failed the diagnosis of malignant and significant cysts, with sensitivities = 0.43 (95% CI, 0.34–0.43) and 0.46 (95% CI, 0.42–0.51), specificities = 0.62 (95% CI, 0.56–0.68) and 0.97 (95% CI, 0.92–0.99), and AUCs = 0.56 and 0.53, respectively. Carcinoembryonic antigen and cytology are more accurate than KRAS. Additional studies are lacking to recommend KRAS as a single diagnostic test.

Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer At the 2018 PancreasFest meeting, experts participating in basic research met to discuss the plethora of available animal models for studying exocrine pancreatic disease. In particular, the discussion focused on the challenges currently facing the field and potential solutions. That meeting culminated in this review, which describes the advantages and limitations of both common and infrequently used models of exocrine pancreatic disease, namely, pancreatitis and exocrine pancreatic cancer. The objective is to provide a comprehensive description of the available models but also to provide investigators with guidance in the application of these models to investigate both environmental and genetic contributions to exocrine pancreatic disease. The content covers both nongenic and genetically engineered models across multiple species (large and small). Recommendations for choosing the appropriate model as well as how to conduct and present results are provided.

Frequency of Appropriate Use of Pancreatic Enzyme Replacement Therapy and Symptomatic Response in Pancreatic Cancer Patients Objectives Pancreatic cancer (PC) and its treatments can result in pancreatic exocrine insufficiency that requires pancreatic enzyme replacement therapy (PERT). Appropriate PERT usage is during meals and snacks. The aim was to determine the frequency of appropriate use of PERT and its impact on symptom alleviation in PC through a patient-reported outcomes online platform. Methods Users in the Pancreatic Cancer Action Network's Patient Registry were prompted to answer a standalone questionnaire about their experience with PERT. Results Two hundred sixty-two users completed the PERT questionnaire (January 2016–January 2018). Patients who reported taking PERT with meals had higher alleviation of symptoms compared with those taking PERT prior to or after meals. Specifically, "feeling of indigestion," "light-colored or orange stools," and "visible food particles in stool" were significantly decreased. Patients taking PERT with meals reported weight gain and less weight loss. Conclusions Of the 89% of PC patients prescribed PERT, 65% were prescribed PERT appropriately with all meals and snacks. Overall compliance with PERT administration guidelines was low (50% [105/208]). Improvement in symptoms significantly correlated with appropriate use of PERT. Increase in PC patient and provider education about appropriate PERT usage and administration is warranted.

Heme Oxygenase-1 Polymorphism Is Associated With the Development of Necrotic Acute Pancreatitis Via Vascular Cell Adhesion Molecule-1 and the E-Selectin Expression Regulation Pathway Objectives Severe acute pancreatitis can lead to systemic complications. Here, we explore the mechanisms based on our previous study associated with the deregulation of heme oxygenase-1 (HO-1) and development of severe acute pancreatitis. Methods Acute pancreatitis patients (n = 135) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed with an ABI 3130 genetic analyzer and GeneMapper software. A short allele was defined ≤27 dinucleotide (GT) repeats, whereas a long allele was defined >27 GT. Levels of 12 different cytokines in blood serum were measured by enzyme-linked immunosorbent assay. All samples in this study were consistently stored in −80°C. Results Patients with the long long genotype expressed E-selectin and vascular cell adhesion molecule-1 at statistically significantly higher levels in serum compared with short short genotype or short long genotypes. Vascular cell adhesion molecule-1 and E-selectin serum levels significantly correlate with the total allele length of the HO-1 promoter region. Conclusion Polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute necrotizing pancreatitis due to deregulation of the immune response.

Per Oral Pancreatoscopy Identification of Main-duct Intraductal Papillary Mucinous Neoplasms and Concomitant Pancreatic Duct Stones: Not Mutually Exclusive Objectives Per oral pancreatoscopy (POP) assists in the evaluation and treatment of select benign and neoplastic pancreatic disorders including main-duct intraductal papillary mucinous neoplasm (MD-IPMN). Although pancreatic duct stones are classically thought of as pathognomonic for chronic pancreatitis, its co-occurrence with MD-IPMN as identified via POP may help identify an alternative etiology for presumed idiopathic chronic pancreatitis. Methods This was a multicenter retrospective case series of patients found to have pancreatic duct stones with concomitant MD-IPMN by POP. Results Thirteen patients with presumed idiopathic chronic calcific pancreatitis were found on POP to have both pancreatic duct stones and MD-IPMN. All patients had a dilated pancreatic duct, and most (92.3%) were symptomatic. Conclusions Per-oral pancreatoscopy may identify MD-IPMN as an etiology for patients with presumed idiopathic chronic calcific pancreatitis and associated dilated pancreatic duct. Larger prospective studies are needed to validate these findings.

Ki-67 Index of 5% is Better Than 2% in Stratifying G1 and G2 of the World Health Organization Grading System in Pancreatic Neuroendocrine Tumors Objective The World Health Organization (WHO) grading system for the stratification of G1 and G2 pancreatic neuroendocrine tumors (pNETs) using an optimal Ki-67 index cutoff is still controversial. The present study aimed at finding one optimal Ki-67 cutoff value that distinguishes G1 and G2 tumors by analyzing the prognosis of patients with pNET in our center. Methods Data from 84 patients with pNET undergoing surgical resection in The First Affiliated Hospital of Sun Yat-sen University between March 2003 and October 2015 were retrospectively analyzed. Results The 5-year overall survival rate was 74.2%. Univariate analysis revealed that functional secretion, WHO grade, and TNM stage were significantly associated with long-term survival (all P < 0.05). Multivariate analysis demonstrated that WHO grade (P = 0.023) and TNM stage (P = 0.040) were independent prognostic factors. The receiver operating characteristic curve showed that the Ki-67 index of 5% had the best predictive ability (76.7%) for 5-year survival with a hazard ratio of 44.7. The hazard ratio was only 8.14 when the Ki-67 index cutoff was 2%. Conclusions TNM stage and WHO grade were independent prognostic factors of pNETs. A Ki-67 index of 5% is better than 2% in stratifying G1 and G2 pNET tumors.

Pancreatobiliary Versus Head and Neck Manifestations in Immunoglobulin G4–related Disease: Distinct Subsets of the Same Disease? Objectives We compared the clinical profiles and organ manifestations of the commonly encountered immunoglobulin G4–related diseases (IgG4-RDs) on either side of the diaphragm: head and neck (HN) versus pancreatobiliary (PB) in IgG4-RD. Methods From the Mayo Clinic, Rochester, database, we identified 53 HN and 88 PB IgG4-RD based on the first affected organ manifestation. Results Compared with HN IgG4-RD, subjects with PB IgG4-RD were likely to be older (median, 64.8 vs 50.2 years; P < 0.0001), male (83% vs 60.4%; P = 0.003), and with a shorter duration of follow-up (24.4 vs 48.7 months; P < 0.0001). In HN versus PB-IgG4-RD orbital, lacrimal gland, submandibular, parotid gland, asthma, and sinusitis manifestations were more common (77% vs 4.5%, 21% vs 0%, 32% vs 8%, 13% vs 0%, 36% vs 9%, and 51% vs 6.8%; P < 0.0001, respectively), whereas lung manifestations were similar (13.2% vs 5.6%; P = 0.12). In contrast, in PB versus HN IgG4-RD, pancreas and biliary were more frequent (98.8% vs 15%, 56.8% vs 3.7%; P < 0.0001), whereas renal lesions were similar (12.5% vs 7.5%; P = 0.36). Conclusion Pancreatobiliary and HN IgG4-RD have distinct clinical profiles. Proximity matters in other organ involvement in IgG4-RD, and organs involved tend to cluster close to each.

Deep Learning to Classify Intraductal Papillary Mucinous Neoplasms Using Magnetic Resonance Imaging Objective This study aimed to evaluate a deep learning protocol to identify neoplasia in intraductal papillary mucinous neoplasia (IPMN) in comparison to current radiographic criteria. Methods A computer-aided framework was designed using convolutional neural networks to classify IPMN. The protocol was applied to magnetic resonance images of the pancreas. Features of IPMN were classified according to American Gastroenterology Association guidelines, Fukuoka guidelines, and the new deep learning protocol. Sensitivity and specificity were calculated using surgically resected cystic lesions or healthy controls. Results Of 139 cases, 58 (42%) were male; mean (standard deviation) age was 65.3 (11.9) years. Twenty-two percent had normal pancreas; 34%, low-grade dysplasia; 14%, high-grade dysplasia; and 29%, adenocarcinoma. The deep learning protocol sensitivity and specificity to detect dysplasia were 92% and 52%, respectively. Sensitivity and specificity to identify high-grade dysplasia or cancer were 75% and 78%, respectively. Diagnostic performance was similar to radiologic criteria. Areas under the receiver operating curves (95% confidence interval) were 0.76 (0.70–0.84) for American Gastroenterology Association, 0.77 (0.70–0.85) for Fukuoka, and 0.78 (0.71–0.85) for the deep learning protocol (P = 0.90). Conclusions The deep learning protocol showed accuracy comparable to current radiographic criteria. Computer-aided frameworks could be implemented as aids for radiologists to identify high-risk IPMN. Review Surgical and Oncological Outcomes of Laparoscopic Versus Open Pancreaticoduodenectomy in Patients With Pancreatic Duct Adenocarcinoma Yin, Zi; Jian, Zhixiang; Hou, Baohua; More Pancreas. 48(7):861-867, August 2019. Abstract Favorites  PDF  Get Content & Permissions It is not clear which of the 2 principal treatments for patients with pancreatic duct adenocarcinoma (PDAC), laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD), has greater safety and efficacy. We performed the present meta-analysis to assess the efficacy of both treatments for PDAC patients undergoing LPD. Multiple electronic databases were systematically searched to identify studies (up to October 2018) comparing LPD with OPD for PDAC. Short- and long-term oncological outcomes were evaluated. Six studies were qualified for inclusion criteria in this meta-analysis with a total of 9144 PDAC participants. Regarding safety, there were fewer overall postoperative complications associated with LPD ( P = 0.005), but the results were similar in terms of pancreatic fistula and mortality. Laparoscopic pancreaticoduodenectomy was associated with a better trend of performance both in R0 resection (relative risk, 1.03; 95% confidence interval [CI], 1.00–1.07; P = 0.07) and preserved lymph nodes (median, 2.14; 95% CI, −0.21 to 4.49; P = 0.07). Long-term overall survival was comparable between LPD and OPD (hazard ratio, 1.03; 95% CI, 0.95–1.13; P = 0.49). In conclusion, LPD was found to be a suitable alternative to OPD in selected PDAC patients with respect to both surgical and oncological outcomes. BUY Table of Contents Outline | Back to Top  Collapse Box Original Articles New-Onset Diabetes Mellitus After Chronic Pancreatitis DiagnosisA Systematic Review and Meta-analysis Zhu, Xiangyun; Liu, Dechen; Wei, Qiong; More Pancreas. 48(7):868-875, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives The aim of this study was to assess the occurrence of new-onset diabetes mellitus (DM) after chronic pancreatitis (CP) diagnosis via systematic review and meta-analysis. Methods A systematic review of literature and meta-analysis of relevant reports were performed. The primary outcome measures studied were newly diagnosed DM and DM treated with insulin. For the binary outcomes, pooled prevalence and 95% confidence interval (CI) were calculated. Methods Fifteen studies involving 8970 patients were eligible. The incidence of new-onset DM after CP diagnosis was 30% (95% CI, 27%–33%). Among all patients, 17% (95% CI, 13%–22%) developed insulin-dependent new-onset DM. The prevalence of newly diagnosed DM after CP diagnosis increased from 15% within 36 months to 33% after 60 months. The proportion of alcoholic CP, sex, age, and body mass index had minimal effect on the studied outcomes. Conclusions This systematic review identified a clinically relevant risk of new-onset DM after CP diagnosis. Therefore, patients should be informed of the risk of DM and monitored. BUY Impact of Changes in the American Joint Committee on Cancer Staging Manual, Eighth Edition, for Pancreatic Ductal Adenocarcinoma Kassardjian, Ari; Stanzione, Nicholas; Donahue, Timothy R.; More Pancreas. 48(7):876-882, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objective Consistent and reliable tumor staging is a critical factor in determining treatment strategy, selection of patients for adjuvant therapy, and for therapeutic clinical trials. The aim of this study was to evaluate the number and extent of pancreatic ductal adenocarcinoma (PDAC) cases that would have a different pT, pN, and overall stages based on the new eighth edition American Joint Committee on Cancer staging system when compared with the seventh edition. Methods Patients diagnosed with PDAC who underwent pancreaticoduodenectomy, total pancreatectomy, or distal pancreatectomy from 2007 to 2017 were retrospectively reviewed. A total of 340 cases were included. Results According to the seventh edition, the vast majority of tumors in our cohort were staged as pT3 tumors (88.2%). Restaging these cases with the new size-based pT system resulted in a more equal distribution among the 3 pT categories, with higher percentage of pT2 cases (55%). Conclusions The newly adopted pT stage protocol for PDAC is clinically relevant, ensures a more equal distribution among different stages, and allows for a significant prognostic stratification. In contrast, the new pN classification (pN1 and pN2) based on the number of positive lymph nodes failed to show survival differences and remains controversial. BUY The Surveillance Patterns of Incidentally Detected Pancreatic Cysts Vary Widely and Infrequently Adhere to Guidelines Schenck, Robert J.; Miller, Frank H.; Keswani, Rajesh N. Pancreas. 48(7):883-887, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives We aimed to determine incidental pancreatic cyst ("cyst") surveillance patterns, predictors of receiving surveillance, and guideline adherence. Methods We performed a retrospective cohort study of all patients receiving longitudinal care at a single tertiary care center with a newly diagnosed incidental pancreatic cyst over a 2-year period (2010–2011). All follow-up care was abstracted over a 5-year period. Results Of 3241 eligible imaging studies reviewed, 100 patients with newly diagnosed incidental cysts eligible for surveillance were identified. A majority (53%) received no follow-up. We identified 4 predictors of cyst surveillance: radiology report conclusion mentioning the cyst (odds ratio [OR], 14.9; 95% confidence interval [CI], 1.9–119) and recommending follow-up (OR, 5.5; 95% CI, 2.1–13.9), pancreas main duct dilation (OR, 10.7; 95% CI, 1.3–89), and absence of multiple cysts (OR, 2.5; 95% CI, 1.1–10.0). Of the 47 patients who received surveillance, 66% met minimum surveillance imaging intervals of at least one guideline. Conversely, 21% of patients met the criteria for overutilization in at least one guideline. Conclusions Although guidelines recommend that surgically fit patients with incidental cysts undergo surveillance, most patients receive no follow-up. When follow-up occurs, surveillance patterns vary widely and infrequently conform to guidelines. Interventions to reduce care variation require study. BUY Acute Recurrent and Chronic Pancreatitis as Initial Manifestations of Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator–Related Disorders Baldwin, Christina; Zerofsky, Melissa; Sathe, Meghana; More Pancreas. 48(7):888-893, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives Recurrent pancreatitis is considered a rare manifestation of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction; this case series highlights that pancreatitis can be a presenting symptoms of cystic fibrosis (CF) or a CFTR-related disorder (CFTR-RD). Methods Retrospective review of patients younger than 30 years diagnosed as having acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) and subsequently diagnosed as having CF or CFTR-RD. Results Among 18 patients, median time from diagnosis of ARP/CP to diagnosis of CF was 0.4 years (range, 0–33 years). Eight were classified as having CF by elevated sweat chloride testing (SCT). Five had intermediate SCT (30–59 mmol/L) with 2 pathogenic mutations. Five had CFTR-RD with intermediate SCT and 0 to 1 pathogenic mutations. Eight patients (44%) had exocrine pancreatic insufficiency, and pancreatic fluid collections were more common in this group. Based on the CFTR mutation, 6 patients were eligible for CFTR potentiator therapy, although none received it during the study period. Nine of the 18 had ≥1 other likely CF manifestations, including sinusitis (33%), nasal polyps (11%), pneumonia (22%), and gallbladder disease (22%). Conclusions Cystic fibrosis or CFTR-RD can present as ARP/CP. Complete diagnostic testing for CFTR-RD in patients with ARP/CP will broaden treatment options and help to identify comorbid illness. BUY Endogenous Gastrin Collaborates With Mutant KRAS in Pancreatic Carcinogenesis Nadella, Sandeep; Burks, Julian; Huber, Matthew; More Pancreas. 48(7):894-903, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objective The KRAS gene is the most frequently mutated gene in pancreatic cancer, and no successful anti-Ras therapy has been developed. Gastrin has been shown to stimulate pancreatic cancer in an autocrine fashion. We hypothesized that reactivation of the peptide gastrin collaborates with KRAS during pancreatic carcinogenesis. Methods LSL-Kras G12D/+ ; P48-Cre (KC) mutant KRAS transgenic mice were crossed with gastrin-KO (GKO) mice to develop GKO/KC mice. Pancreata were examined for 8 months for stage of pancreatic intraepithelial neoplasia lesions, inflammation, fibrosis, gastrin peptide, and microRNA expression. Pancreatic intraepithelial neoplasias from mice were collected by laser capture microdissection and subjected to reverse-phase protein microarray, for gastrin and protein kinases associated with signal transduction. Gastrin mRNA was measured by RNAseq in human pancreatic cancer tissues and compared to that in normal pancreas. Results In the absence of gastrin, PanIN progression, inflammation, and fibrosis were significantly decreased and signal transduction was reversed to the canonical pathway with decreased KRAS. Gastrin re-expression in the PanINs was mediated by miR-27a. Gastrin mRNA expression was significantly increased in human pancreatic cancer samples compared to normal human pancreas controls. Conclusions This study supports the mitogenic role of gastrin in activation of KRAS during pancreatic carcinogenesis. BUY SDC The Importance of a Conjoint Analysis of Tumor-Associated Macrophages and Immune Checkpoints in Pancreatic Cancer Xu, Jun-Ying; Wang, Wang-Sheng; Zhou, Jing; More Pancreas. 48(7):904-912, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives Tumor-associated macrophages are dominant players in establishing the inmmunosuppressive microenvironment in pancreatic ductal adenocarcinoma (PDAC). Immune checkpoint inhibitor monotherapy has achieved limited clinical effectiveness. To date, the interaction of macrophages and checkpoint regulators and their correlation with clinicopathologic characteristics in PDAC have been largely unavailable. Methods Macrophages and immune checkpoint expression were assessed by immunohistochemistry from 80 PDAC samples. Clinicopathologic features and the prognostic value of each marker were evaluated. In vitro changes in the expression of immune markers in cocultured macrophages and PDAC cells were detected by Western blot and immunosorbance assays. Results The macrophages marker CD163 and the checkpoint marker programmed death-ligand 1 (PD-L1) remained as the independent prognostic factors for overall survival (hazard ratio, 2.543; P = 0.017 and hazard ratio, 2.389; P = 0.021). Furthermore, integrated analysis of CD163 and PD-L1 served as more optimal indicators of survival ( P = 0.000). In vitro coculture of macrophages and PDAC cells significantly increased the expression of CD163 and PD-L1, compared with monocultured counterpart ( P < 0.05). Conclusions Combined analysis of CD163 and PD-L1 was enhanced indicators of survival in PDAC patients. The interaction of macrophages and immune checkpoints implied the value of the combination therapy. BUY Induction Therapy in Localized Pancreatic Cancer Shaib, Walid L.; Sayegh, Layal; Zhang, Chao; More Pancreas. 48(7):913-919, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives Pancreatic cancer (PDAC) with localized stage includes resectable (RPC), borderline resectable (BRPC), or locally advanced unresectable (LAPC). Standard of care for RPC is adjuvant chemotherapy. There are no prospective randomized trials for best treatment of BRPC and LAPC. We evaluate the impact of induction chemotherapy on localized PDAC. Methods Charts of PDAC patients treated at Emory University between 2009 and 2016 were reviewed. The primary end point was overall survival (OS). Results A total of 409 localized PDACs were identified. Resectability was prospectively determined at a multidisciplinary tumor conference. Median age was 67 years (range, 30–92 years), 49% were male, 66% were white, 171 had RPC, 131 had BRPC, and 107 had LAPC. Median OSs for RPC, BRPC, and LAPC were 19.5, 16.1, and 12.7 months, respectively. Type of chemotherapy and age were predictors of OS. Induction chemotherapy was used in 106 with BRPC (81%) and 74 with RPC (56.5%); patients with BRPC who received combination chemotherapy and resection had a median OS of 31.5 compared with 19.5 months in patients with RPC ( P = 0.0049). Patients with LAPC had a median OS of 12.7 months. Conclusions In patients with BRPC who undergo resection after induction treatment, the OS was significantly better than in patients with RPC. Neoadjuvant treatment should be considered for all localized PDACs. BUY Comparisons of Outcomes of Real-World Patients With Advanced Pancreatic Cancer Treated With FOLFIRINOX Versus Gemcitabine and Nab-PaclitaxelA Population-Based Cohort Study Papneja, Neha; Zaidi, Adnan; Chalchal, Haji; More Pancreas. 48(7):920-926, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives The aim of this study was to compare the efficacy and safety of FOLFIRINOX (5-FU/leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) in patients with advanced pancreatic cancer. Methods Patients with newly diagnosed advanced pancreatic cancer in Saskatchewan, Canada, from 2011 to 2016, who received FOLFIRINOX or GnP were assessed. A Cox proportional multivariate analysis was performed to evaluate prognostic variables. Results One hundred nineteen eligible patients with median age of 61 years and male/female ratio of 70:49 were identified. Seventy-seven percent had metastatic disease. Of 119 patients, 86 (72%) received FOLFIRINOX and 33 (28%) were treated with GnP. Median progression-free survival of the FOLFIRINOX group was 6.0 months [95% confidence interval (CI), 4.5–7.5] versus 4.0 months (95% CI, 2.9–5.1) with GnP ( P = 0.39). The median overall survival of the FOLFIRINOX group was 9.0 months (95% CI, 7–11) compared with 9.0 months (95% CI, 4.2–13.8) with GnP ( P = 0.88). On multivariate analysis, albumin [hazard ratio (HR), 0.63; 95% CI, 0.41–0.97], male sex (HR, 0.65; 95% CI, 0.43–0.97), and second-line therapy (HR, 0.50; 95% CI, 0.28–0.86) were correlated with survival. Conclusions Our results showed that real-world patients with advanced pancreatic cancer treated with FOLFIIRNOX or GnP had comparable survival with different safety profile. BUY Alternate Week Gemcitabine and CapecitabineAn Effective Treatment for Patients With Pancreatic Adenocarcinoma Johns, Claire; Diaz, Celso L.; Hwang, Jimmy; More Pancreas. 48(7):927-930, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objective Determine whether a regimen of fixed dose rate gemcitabine plus capecitabine is effective and tolerable for advanced pancreatic adenocarcinoma. Methods We performed a retrospective analysis of 62 patients with locally advanced or metastatic pancreatic adenocarcinoma treated at the University of California San Francisco between 2008 and 2016. Treatment was an alternate week schedule of fixed dose rate 1000 mg/m 2 gemcitabine and capecitabine 1000 mg/m 3 (58 patients), 1200 mg/m 3 (12 patients), or 650 mg/m 3 (1 patient) for intended 12 cycles. We evaluated overall survival (OS), progression-free survival (PFS), radiologic response, and adverse events necessitating treatment modification. Results For metastatic patients, median OS was 10.3 months (95% confidence interval [CI], 6.7–12.1 months), and PFS was 5.6 months (95% CI, 2.6–7.7 months). In locally advanced patients, OS was 12.0 months (95% CI, 4.9–17.1 months), and PFS was 5.4 months (95% CI, 2.5–9.4 months). Radiologic response for metastatic disease (42 patients) was 19% objective response, 45% stable disease, and 36% progressive disease. Treatment required modification for 22 patients due to adverse events, most frequently hand-foot syndrome (18 patients). Conclusions Alternate week schedule of fixed dose rate gemcitabine and capecitabine was active and tolerable for advanced pancreatic adenocarcinoma. Overall survival and PFS were comparable to first-line treatments. Importantly, adverse effects appear less severe than first-line treatments. BUY Differences in Pancreatic Cancer Incidence Rates and Temporal Trends Across Asian Subpopulations in California (1988–2015) Liu, Lihua; Zhang, Juanjuan; Deapen, Dennis; More Pancreas. 48(7):931-933, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objective Ethnic disparities in pancreatic cancer (PanCan) incidence exist, but little is known about incidence trends in heterogeneous Asian Americans. We examined PanCan incidence and temporal patterns among detailed ethnic populations, including Asian American subgroups. Methods A total of 71,099 invasive exocrine PanCan cases were identified using the California Cancer Registry between 1988 and 2015. Cases were grouped into mutually exclusive groups of non-Hispanic (NH) white, NH black, Hispanic, NH Asian/Pacific Islander (API), and NH American Indian/Alaska Native (AIAN). Asians were further identified by specific ethnicity. Results The age-adjusted incidence rates (AAIRs, per 100,000) of PanCan varied significantly across racial/ethnic groups, ranging from the highest of 10.4 in NH blacks to 7.6 in NH whites, 7.1 in Hispanics, 6.2 in NH APIs, and to the lowest of 5.2 in NH AIAN. Despite the relatively low rate in the NH APIs, the rates across Asian subgroups varied significantly, with rates similar to NH whites in Japanese (8.1) and Koreans (7.5) to the low rate in South Asians (4.4). Conclusions Significant heterogeneity of PanCan incidence in disaggregated Asian Americans is a novel finding. These results fill a gap regarding PanCan burden in Asian Americans and underscore the importance of disaggregating ethnic populations in cancer research. BUY SDC Diagnostic and Management Challenges in Vasoactive Intestinal Peptide Secreting TumorsA Series of 15 Patients Angelousi, Anna; Koffas, Apostolos; Grozinsky-Glasberg, Simona; More Pancreas. 48(7):934-942, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives Vasoactive intestinal peptide–secreting tumors (VIPomas) are rare functioning neuroendocrine tumors often characterized by a difficult-to-control secretory syndrome and high potential to develop metastases. We hereby present the characteristics of 15 cases of VIPomas and provide a recent literature review. Methods This was a retrospective data analysis of 15 patients with VIPoma from 3 different centers and literature research through PubMed database during the last 10 years. Results Fifteen patients with VIPomas (9 with hepatic metastases at diagnosis) with watery diarrhea and raised VIP levels were studied. Ten patients (67%) had grade 2 tumors, 6 of 15 had localized disease and underwent potentially curative surgery, whereas the remaining 9 received multiple systemic therapies; 3 patients died during follow-up. The median overall survival was 71 months (range, 41–154 months). Patients who were treated with curative surgery (n = 7) had longer median overall survival compared with patients who were treated with other therapeutic modalities (44 vs 33 months). Conclusions The management of VIPomas is challenging requiring the application of multiple treatment modalities. Patients who underwent surgical treatment with curative intent appear to have higher survival rate. Central registration and larger prospective studies are required to evaluate the effect of currently employed therapies in these patients. BUY Significance of Lymph Node Metastasis in Resectable Well-differentiated Pancreatic Neuroendocrine Tumor Harimoto, Norifumi; Hoshino, Kouki; Muranushi, Ryo; More Pancreas. 48(7):943-947, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives Understanding the effect of lymph node metastasis (LNM) on prognosis in pancreatic neuroendocrine neoplasm is helpful for surgery and follow-up. In this study, we investigated the significance of LNM in well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification. Methods We retrospectively collected data for 95 consecutive patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at 6 institutions. The clinicopathological factors were compared in patients with and without LNM, and prognostic factors were analyzed. Results Lymph node metastasis was significantly associated with malignant potential of PanNET, such as larger tumor size, higher Ki-67 index, higher tumor grade, and higher incidence of lymphatic, vessel, and neural invasion. Lymph node metastasis was also associated with disease-free but not overall survival. Multivariate analysis identified NET grade 2 (G2) and G3 as independent risk factors for recurrence after curative resection. Conclusions World Health Organization 2017 classification was the most independent prognostic factor in patients with resectable well-differentiated PanNETs. Patients with G2 and higher-grade tumors require lymph node dissection to improve prognosis. BUY Correlation of DOTATOC Uptake and Pathologic Grade in Neuroendocrine Tumors Chan, Hilary; Moseley, Christian; Zhang, Li; More Pancreas. 48(7):948-952, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives 68 Gallium (Ga)–DOTATOC is a somatostatin analog used to detect neuroendocrine tumors (NETs). Ki-67 proliferation index (Ki-67 PI) has been established as a prognostic factor in NETs. We aimed to evaluate whether a correlation exists between Ki-67 PI and somatostatin receptor positron emission tomography (SSTR-PET) uptake. Methods We retrospectively reviewed 238 DOTATOC PET scans between 2014 and 2016. Patients were excluded if DOTATOC PET was performed more than 365 days from the date of biopsy. Maximum standardized uptake values (SUV max ) of SSTR-PET from biopsied lesions were measured and correlated with Ki-67 PI using the Pearson correlation coefficient. Results Among 110 lesions from 90 patients, DOTATOC PET had 92.7% sensitivity and 100% specificity (102 true positives, 8 false negatives) for detection of NETs. Among 63 lesions from 54 patients with Ki-67 PI available, there were 27 grade 1 lesions [median Ki-67 PI, 1.0%; interquartile range (IQR), 1.0–2.0], 30 grade 2 lesions (median, Ki-67 PI 7.5%; IQR, 5–10), and 6 grade 3 lesions (median Ki-67 PI, 30%; IQR, 26–34). There was a correlation between Ki-67 PI and SUV max ( r 2 = −0.3 , P = 0.018). Conclusions Our analysis demonstrates an inverse correlation between Ki-67 PI and SUV max in NETs. Somatostatin receptor–PET provides additional information that can help guide management of NETs. BUY Gastric Emptying and Distal Gastrectomy Independently Enhance Postprandial Glucagon-Like Peptide-1 Release After a Mixed Meal and Improve Glycemic Control in Subjects Having Undergone Pancreaticoduodenectomy Steiner, Emanuel; Breuer, Robert; Kazianka, Lukas; More Pancreas. 48(7):953-957, August 2019. Abstract Favorites  PDF  Get Content & Permissions Objectives New-onset diabetes frequently resolves after pancreaticoduodenectomy (PD). Glucagon-like peptide-1 (GLP-1) conceivably is involved as its release is enhanced by rapid gastric emptying and distal bowel exposure to nutrients. We aimed at studying factors associated with GLP-1 release after PD. Methods Fifteen PD subjects with distal gastrectomy (Whipple) and 15 with pylorus preservation were evaluated. A test meal containing 1 g paracetamol to measure gastric emptying was ingested. Blood for the measurement of paracetamol, glucose, insulin, and GLP-1 was drawn at baseline and 10, 20, 30, 60, 90, 120, 150, and 180 minutes thereafter. The Matsuda index of insulin sensitivity was calculated. Results In univariate analysis, gastric emptying correlated with GLP-1. Glucagon-like peptide-1 responses to the modes of operation did not differ. Multiple regression analysis confirmed gastric emptying and Whipple versus pylorus-preserving pancreaticoduodenectomy as independent predictors of GLP-1 release. The Matsuda index of insulin sensitivity correlated with GLP-1 concentrations and inversely with body mass index. Patients after Whipple procedure revealed lower glycated hemoglobin as compared with pylorus-preserving pancreaticoduodenectomy. Conclusions Following PD, the postprandial GLP-1 release seems to be enhanced by rapid gastric emptying and to improve insulin sensitivity. Partial gastrectomy versus pylorus preservation enhanced the release of GLP-1, conceivably because of greater distal bowel exposure to undigested nutrients. BUY Table of Contents Outline | Back to Top  Collapse Box Letters to the Editor The Relationship of Acute Pancreatitis and Pancreatic Cancer Li, Jia-su; Liu, Feng Pancreas. 48(7):e57, August 2019. Favorites  PDF  Get Content & Permissions BUY Reply to The Relationship of Acute Pancreatitis and Pancreatic Cancer Phillips, Anna Evans; Yadav, Dhiraj; Brand, Randall E.; More Pancreas. 48(7):e57-e58, August 2019. Favorites  PDF  Get Content & Permissions BUY Mathematical Model and Study Design Could Be Optimized in Spatial Distribution Analysis of Pancreatic Stones Xu, Zheng-Lei; Yao, Jun; Wang, Li-Sheng Pancreas. 48(7):e58, August 2019. Favorites  PDF  Get Content & Permissions BUY Reply to Comment on Zeng et al, Spatial Distribution of Pancreatic Stones in Chronic Pancreatitis Zeng, Xiang-Peng; Xie, Ting; Li, Zhao-Shen; More Pancreas. 48(7):e59, August 2019. Favorites  PDF  Get Content & Permissions BUY

Alexandros Sfakianakis
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