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Interleukin‑17 (IL‑17), an inflammatory cytokine primarily secreted by T helper 17 cells, serves a crucial role in numerous inflammatory diseases and malignancies via its receptor, IL‑17R. In addition to stimulating inflammatory responses, IL‑17 exhibits dual functions in tumors, exerting both pro‑ and antitumor effects. Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and accounts for >90% of pancreatic cancer cases. PDAC is characterized by a prominent stromal microenvironment with significant heterogeneity, which contributes to treatment resistance. IL‑17/IL‑17R signaling has a notable effect on tumorigenesis, the tumor microenvironment and treatment efficacy in various cancer types, including PDAC. However, the specific mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer remain uncertain. This review presents a brief overview of the current knowledge and recent advances in the role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer. Furthermore, the potential of IL‑17‑targeted therapeutic strategies for PDAC treatment is also discussed.

The diagnosis of solid pseudopapillary neoplasm of the pancreas (SPN) can be challenging due to potential confusion with other pancreatic neoplasms, particularly pancreatic neuroendocrine tumors (NETs), using current pathological diagnostic markers. We conducted a comprehensive analysis of bulk RNA sequencing data from SPNs, NETs, and normal pancreas, followed by experimental validation. This analysis revealed an increased accumulation of peroxisomes in SPNs. Moreover, we observed significant upregulation of the peroxisome marker ABCD1 in both primary and metastatic SPN samples compared with normal pancreas and NETs. To further investigate the potential utility of ABCD1 as a diagnostic marker for SPN via immunohistochemistry staining, we conducted verification in a large-scale patient cohort with pancreatic tumors, including 127 SPN (111 primary, 16 metastatic samples), 108 NET (98 nonfunctional pancreatic neuroendocrine tumor, NF-NET, and 10 functional pancreatic neuroendocrine tumor, F-NET), 9 acinar cell carcinoma (ACC), 3 pancreatoblastoma (PB), 54 pancreatic ductal adenocarcinoma (PDAC), 20 pancreatic serous cystadenoma (SCA), 19 pancreatic mucinous cystadenoma (MCA), 12 pancreatic ductal intraepithelial neoplasia (PanIN) and 5 intraductal papillary mucinous neoplasm (IPMN) samples. Our results indicate that ABCD1 holds promise as an easily applicable diagnostic marker with exceptional efficacy (AUC=0.999, sensitivity=99.10%, specificity=100%) for differentiating SPN from NET and other pancreatic neoplasms through immunohistochemical staining., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct., Methods and Analysis: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ 2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests., Ethics and Dissemination: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal., Trial Registration Number: NCT05523778., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pancreatic cancer is one of the deadliest cancer, with a 5-year overall survival rate of 11%. Unfortunately, most patients are diagnosed with advanced stage by the time they present with symptoms. In the past decade, microbiome studies have explored the association of pancreatic cancer with the human oral and gut microbiomes. However, the gut microbial antibiotic resistance genes profiling of pancreatic cancer patients was never reported compared to that of the healthy cohort., Results: In this study, we addressed the gut microbial antibiotic resistance genes profile using the metagenomic data from two online public pancreatic cancer cohorts. We found a high degree of data concordance between the two cohorts, which can therefore be used for cross-sectional comparisons. Meanwhile, we used two strategies to predict antibiotic resistance genes and compared the advantages and disadvantages of these two approaches. We also constructed microbe-antibiotic resistance gene networks and found that most of the hub nodes in the networks were antibiotic resistance genes., Conclusions: In summary, we describe the panorama of antibiotic resistance genes in the gut microbes of patients with pancreatic cancer. We hope that our study will provide new perspectives on treatment options for the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Li, Yang, Cao, Xu, He and Wu.)

Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, low-grade malignant pancreatic tumor with a highly favorable prognosis. Most SPN patients are young and middle-aged women. The main controversial topic for SPN is local resection (LR) versus radical resection (RR). Theoretically, LR could lead to better gastrointestinal function (GIF) and less mental stress. However, no data is available to support this hypothesis., Methods: All SPN patients undergoing surgical treatment in Peking Union Medical College Hospital from 2001 to 2021 were included in the study. A cross-sectional online multiquestionnaire survey containing 110 questions was sent to them (Clinicaltrial.org, NCT05604716). This online multiquestionnaire survey focused on GIF and mental stress and consisted of eight questionnaires. Multiple linear regression analysis was conducted to identify independent factors impacting GIF and mental stress., Results: A total of 183 cases provided valid results. Among them, 46 patients (25.1%) underwent LR, and 137 (74.9%) underwent RR. Ninety-four cases (51.4%) underwent minimally invasive surgery (MIS), while 89 (48.6%) underwent open surgery. The average GSRS score of the patients was 1.9±0.7, indicating that most suffered from mild gastrointestinal dysfunction. The scores of PHQ-9 and GAD-7 in 16 patients (8.7%) and 27 (14.8%) patients, respectively, were beyond 10.0, which indicated clinical depression and anxiety. Additionally, 19 (10.4%) patients reported poor ability to work, and 31(16.9%) patients had significant body image concerns. Compared to other clinicopathological characteristics, LR (LR vs. RR: PHQ-9 score, P =0.018; WAI average score, P =0.010; EORTC QLQ-C30, nine subdomains, P <0.05; GSRS average score, P =0.006) and MIS (MIS vs. open surgery: EORTC QLQ-C30, three subdomains, P <0.05; GSRS average score, P =0.006) were the most significant factors predicting improved GIF and reduced mental stress., Conclusions: This study systematically presents postoperative GIF and mental stress of SPN patients using validated multiquestionnaires for the first time. It provides solid evidence that LR and MIS can improve GIF and reduce mental stress after surgery for SPN patients, which could be helpful for the surgeons to make more personalized surgical plans for their patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To present comprehensive information on the clinicopathological, molecular, survival characteristics, and quality of life (QOL) after surgery for solid pseudopapillary neoplasm (SPN) of the pancreas in a large cohort after long-term follow-up., Background: SPN is a rare tumor with an uncertain malignant potential, and solid information on long-term prognosis and QOL remains limited., Methods: All hospitalized patients with SPNs who underwent surgery between 2001 and 2021 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinicopathological characteristics of the patients were retrieved. A cross-sectional telephone questionnaire was administered to inquire about the QOL. Molecular analyses were performed using whole-exome sequencing., Results: Exactly 454 patients with SPN were enrolled, of whom 18.5% were males and 81.5% were females. The mean patient age was 31 ± 12 years. In total, 61.3% of the patients had no symptoms. The size of the tumors was 5.38 ± 3.70 cm; 83.4% were solid cystic tumors, and 40.1% had calcifications. The proportions of local resection, distal pancreatectomy with or without splenectomy, and pancreaticoduodenectomy with or without pylorus preservation were 29.7%, 28.9% or 22.9%, and 11% or 6.8%, respectively. Over the years, there has been a significant shift from open to minimally invasive surgery. Among all surgical procedures, pylorus-preserving pancreaticoduodenectomy (PPPD) had the highest incidence of grade 2 to 4 complications (up to 32.3%), compared with 6.7% in distal pancreatectomy ( P < 0.001). Regarding histopathology, tissue invasion, perineural invasion, cancerous microvascular emboli, lymph node metastasis, and distant metastasis were present in 16.5%, 2.2%, 0.7%, 2.0%, and 3.1% of patients, respectively. Sixty patients were lost to follow-up. Sixteen of the 390 patients who underwent resection (4.1%) experienced local recurrence or distant metastasis after surgery. In total, 361 patients responded to the telephone survey. Nearly 80% of patients claimed their QOL was not significantly affected after surgery; however, the remaining 20% complained of lower QOL during 3 to 6 years of follow-up after surgery. No clinicopathological factor could reliably predict clinical recurrence or metastasis after resection. A total of 28 driver genes were detected with mutations in at least 2 tumor samples and the top 3 frequently mutated genes were CTNNB1 , ATRNL1 , and MUC16 ., Conclusions: This study presented the largest cohort of patients with SPN after surgery from a single center and reported the QOL of these patients. SPN is associated with extremely favorable long-term survival, even in patients with metastasis, and most patients have a good QOL after surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Anatomical and molecular staging strategies are needed for the personalized treatment of localized pancreatic ductal adenocarcinoma (PDAC). This study evaluated the performance of [ 68  Ga]Ga-FAPI-04 and [ 18 F]F-FDG PET/CT on the disease staging and prognostic value of patients with localized PDAC on contrast-enhanced (CE)-CT images., Methods: Patients with suspected localized PDAC on CE-CT were recruited for static [ 68  Ga]Ga-FAPI-04 and 18 [F]F-FDG and PET/CT, and select patients underwent simultaneous 60-min dynamic 68  Ga-FAPI-04 PET/CT. The diagnostic and staging performances of the static PET/CT results were evaluated by delineating regions of interest in the primary tumor, whole pancreas, and distal pancreas in both types of scans and then evaluating correlations between the PET/CT findings and clinicopathological characteristics. Furthermore, Kaplan-Meier and hazard ratio (log-rank) methods were used to evaluate the prognostic value of the combined dynamic [ 68  Ga]Ga-FAPI-04 and static [ 18 F]F-FDG PET/CT method., Results: We included 49 patients with histologically confirmed PDAC adenocarcinomas; 32 underwent 60-min dynamic [ 68  Ga]Ga-FAPI-04 PET/CT imaging simultaneously. The static [ 68  Ga]Ga-FAPI-04 method had significantly higher accuracy and uptake values than the static [ 18 F]F-FDG method for primary PDAC lesions, metastatic lymph nodes, and distal metastases. Furthermore, 18.4% and 10.2% of the patients' stages changed after using the [ 68  Ga]Ga-FAPI-04 and [ 18 F]F-FDG PET/CT methodologies, respectively, compared to the CE-CT-designated stage. The Ki values obtained from dynamic [ 68  Ga]Ga-FAPI-04 PET/CT did not differ between PDAC and distal obstructive pancreatitis lesions. Pathologically enlarged tumor size, poor differentiation, and perineural invasion were associated with increased [ 68  Ga]Ga-FAPI-04 uptake but not with [ 18 F]F-FDG uptake. The preoperative prognostic performance of [ 68  Ga]Ga-FAPI-04 was better than that of [ 18 F]F-FDG. Interestingly, combined [ 68  Ga]Ga-FAPI-04 and [ 18 F]F-FDG uptake results in the whole pancreas could further stratify patients based on their postoperative prognosis., Conclusion: 6 [ 68  Ga]Ga-FAPI-04 PET/CT was more sensitive and accurate than [ 18 F]F-FDG PET/CT for tumor, node, and metastasis staging of PDAC identified on CE-CT. Additionally, [ 68  Ga]Ga-FAPI-04 uptake was significantly associated with pathologically aggressive tumor features. Combined [ 68  Ga]Ga-FAPI-04 and [ 18 F]F-FDG PET/CT findings improved the prognostic value, potentially providing a non-invasive guide for clinical management. Finally, increased fibroblast activity in PDAC-induced obstructive pancreatitis may be associated with poor patient survival rates., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Our aim was to assess the prognostic value of [ 68  Ga]Ga-FAPI-04 positron emission tomography (PET) uptake in PDAC and to evaluate the correlation between in vivo lesional radioactivity with pathological characteristics of pancreatic ductal adenocarcinoma (PDAC)., Methods: We retrospectively analyzed treatment-naïve PDAC patients who underwent preoperative [ 68  Ga]Ga-FAPI-04 PET/CT followed by pancreatectomy. The tracer uptake was determined as maximum tumor standardized uptake value (SUV max ), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) as well total pancreatic uptake (TSUV max ), total FAPI-avid pancreatic volume (FPV), and total pancreatic FAP expression (TPF). Spearman's correlation analysis was performed to evaluate the association between [ 68  Ga]Ga-FAPI-04 PET/CT imaging and ex vivo immunohistological FAP expression and pathological characteristics of surgical specimens (differentiation, size, vascularity, perineural invasion, and lymph node metastases). Kaplan-Meier and hazard ratio (HR, log-rank) methods were used to evaluate the prognostic value of [ 68  Ga]Ga-FAPI-04 PET/CT and clinicopathological factors., Results: Thirty-seven surgical PDAC patients were included. The ex vivo expression of FAP was significantly associated with the tumor SUV max and TLF. FAP expression was more abundant in poorly differentiated PDAC than in well- to moderately differentiated neoplasms. Tumor SUV max or TLF and pancreatic TSUV max or TPF were significantly correlated with tumor size, differentiation, and perineural invasion, respectively. SUV max had a significant independent prognostic value for recurrence-free survival (HR = 2.46, P < 0.05), while [ 68  Ga]Ga-FAPI-04 TPF predicted overall survival (HR = 12.82, P < 0.05)., Conclusion: The in vivo [ 68  Ga]Ga-FAPI-04 uptake in localized PDAC showed a significant correlation with ex vivo FAP expression and aggressive pathological characteristics. [ 68  Ga]Ga-FAPI-04 PET/CT also presented a potential for postoperative prognostication of PDAC. Elevated fibroblast activity induced by obstructive pancreatitis might be associated with the patient's survival., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: An end-of-fast insulin level ≥ 3 µIU/ml, C-peptide level ≥ 0.6 ng/ml, and proinsulin level ≥ 5 pmol/l with end-of-fast glucose level ≤ 3.0 mmol/l have been established as the criteria for endogenous hyperinsulinemic hypoglycemia. However, all these criteria have been proposed based on patients in Western populations. This study aimed to determine the optimal criteria using a large series of Chinese patients., Methods: This retrospective study comprised 144 patients with surgically proven insulinoma and 40 controls who underwent a 72-h fasting test at the Peking Union Medical College Hospital(PUMCH) from 2000 to 2020. Receiver operating characteristic curves were used for analysis., Results: In this series of patients, the optimal diagnostic criteria for endogenous hyperinsulinemic hypoglycemia were insulin  ≥ 5.5 μIU/ml, C-peptide ≥ 0.7 ng/ml, and proinsulin ≥ 12 pmol/l with end-of-fast glucose ≤ 2.8 mmol/l; the sensitivity and specificity were 99% and 100% for insulin, 100% and 100% for C-peptide, and 93% and 100% for proinsulin, respectively. The diagnostic efficacy of the criteria based on Western populations was then tested. The sensitivity and specificity of end-of-fast insulin ≥ 3 μIU/ml, C-peptide ≥ 0.6 ng/ml, and proinsulin ≥ 5 pmol/l with end-of-fast glucose ≤ 3.0 mmol/l were 100% and 83%, 100% and 80%, and 97% and 78%, respectively., Conclusions: New and optimized diagnostic criteria for endogenous hyperinsulinemic hypoglycemia in Chinese populations have been proposed, and these criteria yield satisfactory accuracy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Liu, Lyu, Zhao, Qi, Ping, Xu, Li, Xu, Zhang, Wu and Li.)

Objective: To investigate the clinical characteristics of patients with multiple endocrine neoplasia type 1 (MEN1)-related insulinoma and their relationship with specific biochemical changes and to summarize the features of treatment options for the Chinese population with this disease and the impact on long-term prognosis., Methods: "MEN1" and "insulinoma" were used when searching the Peking Union Medical College Hospital (PUMCH) medical record retrieval system to obtain clinical information about patients. We identified patients diagnosed with MEN1-associated insulinoma based on endocrinological, radiological, and pathological examinations, and subsequently analyzed their clinical data., Results: A total of 55 patients with MEN1-associated insulinoma were included, including 29 (52.7%) men and 26 (47.3%) women. The parathyroid gland was the most commonly affected (78.2%), followed by the pituitary gland (69.1%) and adrenal gland (16.4%). Insulinoma was the first manifestation of MEN1 in at least 23.6% (13/55) of patients. Nineteen (34.5%) patients presented with initial symptoms of hypoglycemia before the age of 22 years. Among the 24 Patients with high serum calcium (Ca) had significantly lower serum insulin levels than those with normal serum Ca levels (p < 0.001) during hypoglycemic episodes. However, serum C-peptide level at 0.5 h and serum insulin level at 1 h was higher in patients with hypercalcemia than in patients with normal serum Ca levels in the oral glucose tolerance test (OGTT), although the differences were not statistically significant. Multifocal pancreatic neuroendocrine tumors (pNETs) were present in 38 (69.1%) patients; most of them (55.6%, 20/36) underwent multiple enucleations, and 45% (9/20) had a postoperative recurrence. Five patients (10%) who underwent distal pancreatectomy developed pancreatic insufficiency after an average of seven years. patients who underwent genetic testing, 23 (95.8%) were positive for MEN1 mutation, with mutations most commonly found in exons 2 (21.7%) and 3 (13%)., Conclusions: In our study, the rates of postoperative recurrence and long-term complications in patients with MEN1 with multifocal pNETs were significantly different from those in other international centers and might be related to the choice of surgical method. In addition, elevated serum Ca levels in patients with primary hyperparathyroidism may affect insulin secretion., (© 2022. The Author(s).)

Objectives: The pancreatic neuroendocrine tumors (PanNETs) are a group of clinically heterogeneous neoplasms. Although previous studies illustrated the somatic mutation pattern for PanNETs, the germline mutation pattern is still unclear. Here, we comprehensively screened the underlying germline mutations in a cohort of multiple endocrine neoplasia type 1 (MEN1)-related and sporadic PanNETs to reveal the characteristics of germline mutation in PanNET patients., Methods: Patients diagnosed with PanNETs by biopsy or surgical pathology were enrolled in this study. Peripheral blood samples were used for genomic DNA purification and subsequent sequencing. The following sequencing techniques were used and compared for validation: (1) targeted gene capture with a customized panel; (2) whole exome sequencing data from previous study., Results: A total of 184 PanNET patients were enrolled, including 20 MEN1-related and 164 sporadic cases. In this study, MEN1 mutation rate in MEN1-related PanNETs was 60% (12/20), of which 50% were novel mutation sites. For sporadic PanNETs, the overall germline mutation rate was very low. Besides the rare MEN1 mutation, previously unreported germline variant in DAXX was found in one non-functional PanNET., Conclusions: This study revealed distinctive germline mutation rates between MEN1-related and sporadic PanNETs. The novel MEN1 mutations contribute to revealing the spectrum of MEN1 mutations in PanNETs. The newly discovered germline variant of DAXX in sporadic PanNET implies a tendency of convergence between germline and somatic mutation genes.

Introduction: Radical antegrade modular pancreatosplenectomy (RAMPS) was proposed a decade ago with the aim to achieve higher R0 tangential margin and radical N1 lymph node resection for left-sided pancreatic adenocarcinoma (PDAC), which has been widely accepted worldwide at present. Laparoscopic RAMPS (Lap-RAMPS) has been attempted for PDAC during last several years, however, no outcomes evaluation by comparison between laparoscopic vs open RAMPS has been reported yet., Materials and Methods: From August, 2012 to March, 2018, patients undergoing open or lap-RAMPS for the diagnosis of left-sided PDAC were reviewed from a prospective database. Patients excluded if they were related with combined organs or vessels resection, systematic metastasis as well as conversion from open RAMPS to lap RAMPS. The surgical and oncologic outcomes were compared., Results: A total of 48 PDAC patients were enrolled (25 underwent lap-RAMPS and 23 underwent open-RAMPS). There were no significant differences in demographic or perioperative morbidity. In the lap-RAMPS group, R0 transection margin and retroperitoneal margin were both achieved in 23 of 25 patients (92%). In the open RAMPS group, R0 transection margin was achieved in 21 of 23 patients (91.3%), R0 retroperitoneal margin was 22 of 23 patients (95.65%). There were no differences in pathological examinations. The number of lymph node (LN) retrieved between lap-RAMPS and open- RAMPS group was not significant difference (15.84 vs 18.22; P = 0.268). Median disease-free survival (DFS) was analogous in two groups (18.11 m vs 20.00 m, P = 0.999). Median overall survival (OS) was 24.53 m in lap-RAMPS group and 28.73 m in the open-RAMPS group (P = 0.633)., Conclusions: Lap-RAMPS is technically feasible, and has comparable long-term oncological outcome with open-RMAPS.

Interleukin (IL)-17 is a prominent cytokine that promotes pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) and is associated with the oncogenic pathways in tumor progression. However, the mechanism and therapeutic value of the IL-17 axis remain unclear. In this study, we verified the activation of the IL-17 and Notch pathways in PanIN/PDAC via complementary approaches and validated their pro-tumor effects on tumor progression. Additionally, we found a positive correlation between IL-17 and Notch; the IL-17 axis can upregulate Notch activity via the canonical NF-κB pathway in vitro, thus synergistically promoting PanIN/PDAC. Furthermore, we observed that the co-inhibition of IL-17 and the Notch pathway can enhance the therapeutic effect by restricting tumor growth in vivo. Our study highlights the synergistic effect of the IL-17 axis and Notch pathway in promoting PanIN/PDAC and further suggests that IL-17-Notch co-inhibition is a novel therapeutic strategy with superior potential in treating PDAC., (Copyright © 2021. Published by Elsevier B.V.)

The incidence of pancreatic neuroendocrine neoplasms (PanNENs) has gradually increased. PanNENs comprise two subtypes with different clinical manifestations and molecular mechanisms: functional PanNENs and nonfunctional PanNENs. Excessive hormones and tumor progression severely affect the quality of life of patients or are even life threatening. However, the molecular mechanisms of hormone secretion and tumor progression in PanNENs have not yet been fully elucidated. At present, advancements in sequencing technologies have led to the exploration of new biological markers and an advanced understanding of molecular mechanisms in PanNENs. Multiomics sequencing could reveal differences and similarities in molecular features in different fields. However, sequencing studies of PanNENs are booming and should be summarized to integrate the current findings. In this review, we summarize the current status of multiomics sequencing in PanNENs to further guide its application. We explore mainly advancements in the genome, transcriptome, and DNA methylation fields. In addition, the cell origin of PanNENs, which has been a hot issue in sequencing research, is described in multiple fields., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Pancreatic inflammation accelerates mutant Kras-driven tumorigenesis in mice, suggesting high selectivity in the cells that oncogenic Kras transforms, although the mechanisms dictating this specificity are poorly understood. Here we show that pancreatic inflammation is coupled to the emergence of a transient progenitor cell population that is readily transformed in the presence of mutant KrasG12D. These progenitors harbor a proto-oncogenic transcriptional program driven by a transient enhancer network. KrasG12D mutations lock this enhancer network in place, providing a sustained Kras-dependent oncogenic program that drives tumors throughout progression. Enhancer co-option occurs through functional interactions between the Kras-activated transcription factors Junb and Fosl1 and pancreatic lineage transcription factors, potentially accounting for inter-tissue specificity of oncogene transformation. The pancreatic ductal adenocarcinoma cell of origin thus provides an oncogenic transcriptional program that fuels tumor progression beyond initiation, accounting for the intra-tissue selectivity of Kras transformation., (© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)

Introduction: Several previous studies have reported the incidence of new-onset diabetes mellitus (NODM) after pancreatectomy. Nevertheless, the results were inconsistent. The true rate of NODM after distal pancreatectomy (DP) is still unknown., Research Design and Methods: The aim of this study was to investigate the incidence of and the risk factors for NODM after DP. This study enrolled patients who underwent DP between January 2004 and February 2016 at Peking Union Medical College Hospital. Patients with preoperative diabetes mellitus or diagnosed with pancreatic cancer were excluded. The primary outcome was NODM., Results: A total of 485 patients were enrolled. The median (IQR) of follow-up duration was 30.95 (9.26-180.30) months. The accumulative incidence of NODM was 8.9% at postoperative 6 months, 14.0% at postoperative year one, 22.3% at year three, 27.1% at year five, and 35.5% at year ten. Multivariate analysis showed that the risk of postoperative NODM was positively correlated with age (HR 1.029 (1.013-1.045), p<0.001), preoperative body mass index (BMI) (HR 1.042 (1.003-1.083), p=0.001), operative blood loss (HR 1.0003 (1.0002-1.0010), p<0.001), and length of resected pancreas (HR 1.079 (1.013-1.148), p = 0.017). Moreover, concomitant splenectomy (HR 2.001 (1.202-3.331), p=0.008) was associated with significantly higher risk of postoperative NODM., Conclusion: NODM incidence increased with postoperative time progression. Age, BMI, surgical blood loss, length of resected pancreas and splenectomy were independent risk factors for NODM after DP., Trial Registration Number: NCT03030209., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The interactions between tumor immune microenvironment (TIME) and pancreatic cancer cells can affect chemotherapeutic efficacy; however, the mechanisms still remain largely unknown. Thirty items in TIME were comprehensively screened by using tissue microarray from pancreatic cancer patients. Their expressions, interconnections and predictive roles for survival were analyzed. Twenty-one of 30 items could stratify the survival of the patients; however, multivariate analysis found that only 5 independent risk factors could predict worse survival (M2-polarized tumor-associated macrophages (TAMs), IgG4 positive cells, TGF-β1, GM-CSF and lymphangiogenesis). They had a much higher expression levels in tumoral tissue, compared to peritumoral tissue. The Spearman analysis showed that M2-polarized TAM, TGF-β1 and GM-CSF were positively correlated with pancreatic cancer stem cells (PCSC), angiogenesis and lymphangiogenesis. Both human and murine pancreatic cancer cells could induce M2-polarized TAM, which showed substantial roles to decease chemotherapeutic effects. After treated by gemcitabine, both human and murine pancreatic cancer cell lines expressed higher level of immune check points, PCSC markers and varieties of immunosuppressive factors; however, TGF-β1 and GM-CSF had the highest increase. Based on the above results, TGF-β1 and GM-CSF were proposed to be the optimal potential targets to improve chemotherapeutic effects. In immunocompetent murine models, we demonstrated that combined blockade of TGF-β1 and GM-CSF improved the chemotherapeutic effects by inhibition of M2-polarized TAM and induction of CD8 positive T cells. This study presents a novel promising combined strategy to improve the chemotherapeutic effects for pancreatic cancer.

Objective: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients' and clinicians' safety and safeguard health care capacity., Summary Background Data: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer., Methods: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement., Results: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2-5] to 1 (IQR 0-2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement., Conclusions: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.

Objective: Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs., Design: The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed., Results: PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period., Conclusion: These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Long-standing hypoglycemia can cause cognitive impairment, and whether recurrent severe hypoglycemia impacts cognitive function in patients with insulinoma has not been studied. This study focused on exploring the cognitive function in patients with insulinoma., Methods: A prospective study was conducted to assess cognitive function in patients with insulinoma by administering the Montreal Cognitive Assessment (MoCA) questionnaire between January 2016 and July 2017, and patients with cognitive impairment were followed up to undergo the MoCA test 1 year after surgery. The MoCA scores after surgery were compared with the scores before surgery, and the associations between cognitive impairment and relevant factors were further evaluated by multiple linear regression analysis., Results: Eighteen out of thirty-four patients (53%) with insulinoma were screened positive for cognitive impairment as defined by a MoCA score <26. Performance in certain cognitive domains, including visuospatial and executive functions, delayed memory, attention, language, and abstraction, was significantly worse in patients with cognitive impairment. Multivariate analysis indicated that MoCA scores correlated significantly with tumor grade and years of education. Eight patients with cognitive impairment were lost to follow-up. The remaining ten patients with cognitive impairment showed improvements 1 year postoperatively, and seven patients recovered to normal cognitive function., Conclusions: Cognitive impairment was found in patients with insulinoma and was reversible in some patients 1 year after surgery. More studies are needed to explore the underlying mechanisms of the existence and reversibility of cognitive impairment in patients with insulinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) are rare neuroendocrine tumors that often present as watery diarrhea, hypokalemia, and achlorhydria or hypochlorhydria. In this study, we present our institutional experience of diagnosis and treatment of VIPomas, along with a review of the Chinese literature since 1980. Patient #1, diagnosed in 1984 and with intact clinical records, shows the natural history of this disease. Patient #2, diagnosed in 2015, shows the results of evaluation by nuclear medicine techniques and the outcomes of standardized treatment. Comprehensive review of 41 cases allows evaluation of clinical characteristics, treatments and outcomes of pancreatic VIPoma patients. All patients presented with watery diarrhea. The average stool volume reached 3247 mL per day. Average serum VIP level was 839.3 ng/L. Twelve of the 41 cases were reported to have metastases at diagnosis. Somatostatin receptor scintigraphy and 18 FDG PET-CT are efficient methods for detection of VIPoma. Surgical excision can promptly alleviate hormonal symptoms., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Efficient computational recognition and segmentation of target organ from medical images are foundational in diagnosis and treatment, especially about pancreas cancer. In practice, the diversity in appearance of pancreas and organs in abdomen, makes detailed texture information of objects important in segmentation algorithm. According to our observations, however, the structures of previous networks, such as the Richer Feature Convolutional Network (RCF), are too coarse to segment the object (pancreas) accurately, especially the edge., Method: In this paper, we extend the RCF, proposed to the field of edge detection, for the challenging pancreas segmentation, and put forward a novel pancreas segmentation network. By employing multi-layer up-sampling structure replacing the simple up-sampling operation in all stages, the proposed network fully considers the multi-scale detailed contexture information of object (pancreas) to perform per-pixel segmentation. Additionally, using the CT scans, we supply and train our network, thus get an effective pipeline., Result: Working with our pipeline with multi-layer up-sampling model, we achieve better performance than RCF in the task of single object (pancreas) segmentation. Besides, combining with multi scale input, we achieve the 76.36% DSC (Dice Similarity Coefficient) value in testing data., Conclusion: The results of our experiments show that our advanced model works better than previous networks in our dataset. On the other words, it has better ability in catching detailed contexture information. Therefore, our new single object segmentation model has practical meaning in computational automatic diagnosis.

Purpose: To evaluate the diagnostic performance of biphasic contrast-enhanced CT (CECT), volume perfusion CT (VPCT) and 3 Tesla MRI with diffusion-weighted imaging (DWI), in patients with clinically suspected insulinomas., Materials and Methods: This prospective study was approved by the institutional review board. Sixty-four patients with clinically suspected insulinomas underwent biphasic CECT, VPCT, and 3T MR with DWI. Two radiologists independently determined the presence/absence of tumor using a 5-scale confidence level. Conspicuity of the lesion and clarity of tumor-to-pancreatic duct distance were graded. Receiver operating characteristic analysis was performed to compare diagnostic performance., Results: Forty-seven patients were tumor positive, with 51 tumors. The differences between the areas under the curve values for tumor detection were as follows: 0.715 (CECT), 0.903 (VPCT), 0.832 (MRI without DWI) and 0.955 (MRI with DWI) for reader 1, and 0.738 (CECT), 0.895 (VPCT), 0.841 (MRI without DWI), and 0.956 (MRI with DWI) for reader 2. MRI with DWI and VPCT were significantly more accurate than CECT for insulinoma detection (P = 0.01 and 0.02 for reader 1, and P = 0.01 and 0.03 for reader 2). Lesion conspicuity was better on MRI compared with VPCT (P = 0.01), and both were better than CECT (both P < 0.01). Tumor-to-pancreatic duct distance was better appreciated on MRI, compared with CECT and VPCT (both P < 0.01). The weighted k values indicate good to excellent agreement between observers for determining tumor presence/absence (k = 0.64-0.84)., Conclusion: The 3T MRI with DWI and VPCT are significantly more accurate than CECT for insulinoma detection. MRI demonstrates higher tumor conspicuity and is superior in depicting the tumor-to-duct distance., Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1648-1655., (© 2017 International Society for Magnetic Resonance in Medicine.)

The aim of this article was to investigate and emphasize the clinical benefits of organ-preserving surgeries by comparing the pancreatic head resection with segmental duodenectomy (PHRSD), pylorus-preserving pancreatoduodenectomy (PPPD), and classic pancreatoduodenectomy (PD).A retrospective analysis of PHRSD (20 patients), PPPD (42 patients), and PD (92 patients) with benign lesions, low-grade malignancies, or early-stage carcinomas at the pancreatic head was performed since 2008. The intraoperative and postoperative courses and a long-term statuses were compared.The overall average age of the patients in 3 groups was 48.82 years old (range 12-76). The mean operative time and the blood loss were significantly less in the PHRSD and PPPD groups than that in the PD group (P < .05), but there were no differences between the PHRSD and PPPD groups. The possibilities of postoperative complications were equivalent in all 3 groups. During an average follow-up time of 61.1 months, there were no recurrence or distant metastasis happened. Patients in the PHRSD and PPPD groups had a better long-term nutritional status because they had less body weight loss (P < .01), and suffered less from long-term diarrhea (P < .001) than that in the PD group. However, the results in the PPPD group seemed to be better than that in the PHRSD group.PHRSD and PPPD are ideal procedures of organ-preserving pancreatectomy to fulfill the curative goals of benign lesions, low-grade malignancies, or early-stage carcinomas at the pancreatic head. It was proved to be operative safe and could bring patients with a better nutritional status and quality of life after surgery. However, PHRSD was more difficult with no better long-term benefits than PPPD, which asked a comprehensive consideration when made the surgical choice., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Weight loss induced by the complete resection of insulinoma is controversial in overweight patients. The study sought to explore postoperative weight loss and metabolic changes in overweight insulinoma patients., Methods: A retrospective study was conducted to review the follow-up data of insulinoma patients with a BMI ≥25kg/m 2 who underwent complete lesion resection between May 2010 and May 2015. Body mass index (BMI), weight loss (WL) and percentage weight loss (%WL) were main outcomes., Results: Fifty-one patients were included with a median follow-up of 28 months. The BMI at 3 months, 1 year, 2 years and 3 years postoperatively were significantly lower than the preoperative BMI values (p < .01). The WL% was 12.9% at 3 months postoperatively without significant changes throughout the 3-year follow-up. WL and the %WL were significantly higher in the high BMI group (BMI≥ 27.5 kg/m 2 ). Multivariate analysis indicated that higher initial BMI was associated with increased weight loss (p = .001). 63.8% of patients with hypertension recovered and improved sleep quality was evident in all patients with obstructive sleep apnea syndrome within 1 year postoperatively., Conclusions: Weight significantly decreased postoperatively in overweight insulinoma patients, which was more evident in patients with higher BMI and metabolic comorbidities were largely improved.

Objective: The purpose of this study is to investigate the role of whole-pancreas perfusion in detecting insulinomas with the use of MDCT., Materials and Methods: From January 2011 to December 2011, a total of 70 consecutive patients (33 men and 37 women; mean age, 46 years; range, 17-73 years) who underwent biphasic contrast-enhanced CT and whole-pancreas CT perfusion for suspected insulinomas were identified retrospectively. Patients were monitored for at least 3 years. Two radiologists who were blinded to the clinical and surgical data independently evaluated the images, first assessing only the biphasic contrast-enhanced CT images to detect tumor and assess diagnostic confidence on a 5-point scale. Next, perfusion parametric maps were evaluated and pancreatic perfusion parameters measured, and the presence of tumor was reidentified using a combination of the biphasic CT and perfusion image sets. A ROC curve was generated to compare the diagnostic accuracy of the two image sets., Results: The mean blood flow (BF) values of both the insulinomas and the insulinoma-harboring regions were statistically significantly higher (p < 0.01, for both) than the BF value of tumor-free pancreatic parenchyma. For the detection of insulinoma, biphasic CT had a sensitivity of 88.1%, a specificity of 85.7%, a positive predictive value of 91.1%, and a negative predictive value of 81.4%, whereas combined biphasic CT and perfusion had a sensitivity of 94.6%, a specificity of 94.7%, a positive predictive value of 96.7%, and a negative predictive value of 91.5%. The mean area under the ROC curve increased from 0.939 with biphasic CT to 0.999 with the addition of perfusion. Nine of 46 tumors (19.6%) for which findings were negative (n = 2) or indeterminate (n = 7) on biphasic CT were correctly diagnosed with the addition of perfusion., Conclusion: The addition of pancreatic perfusion to biphasic contrast-enhanced CT may improve the detection of insulinomas.

Introduction: The aim of this study was to report a new case of mixed serous neuroendocrine neoplasm (MSNN) and review the literature concerning this type of lesion, which was added to the World Health Organization classification of pancreatic tumors in 2010., Results: A 73-year-old woman presented with a pancreatic mass. The lesion was an intriguing combination of serous cystic neoplasm (SCN) and pancreatic neuroendocrine tumor (PanNET), in which the PanNET component grew into the wall of the serous oligocystic adenoma. We searched different databases for studies that had investigated MSNN. A total of 15 patients (age, 28-78), including the patient in the present study, were evaluated. We discuss these cases in detail especially regarding morphology and pathology; our case was the only one involving a collision type combination., Conclusion: Although MSNN is recognized as a variant of SCN, it is quite different from SCN or PanNET. A new morphological analysis of MSNN may help in elucidating its histogenesis and prognosis.

Introduction: Pancreatic panniculitis is a very rare complication of pancreatic cancer, most often accompanying rare acinar cell carcinoma. We herein report a case of pancreatic panniculitis that was associated with pancreatic mucinous adenocarcinoma., Patient Information: A 57-year-old male was referred to our hospital for weight loss. A physical examination revealed subcutaneous nodules on his lower extremities. The blood test showed abnormal increases in amylase, lipase, and carbohydrate antigen 19-9 levels. A computed tomography scan detected a hypodense 2 × 1.5 cm solid mass with an unclear margin in the head of the pancreas. The biopsy of subcutaneous nodules on the lower extremities was conducted and revealed lobular panniculitis. Pancreatic cancer and pancreatic panniculitis were strongly suspected. After the administration of octreotide acetate and the Whipple procedure, the serous amylase and lipase levels returned to normal, and the pancreatic panniculitis had almost resolved by 4 weeks later., Conclusion: Pancreatic panniculitis is a rare complication of pancreatic cancer. However, in the presence of a pancreatic mass, as in this case, clinicians should be aware that panniculitis may be the sentinel of pancreatic carcinoma.

Unlabelled: Preoperative localization of insulinoma is a clinical dilemma. We aimed to investigate whether glucagon-like peptide-1 receptor (GLP-1R) PET/CT with (68)Ga-NOTA-MAL-cys(40)-exendin-4 ((68)Ga-NOTA-exendin-4) is efficient in detecting insulinoma., Methods: In our prospective cohort study, patients with endogenous hyperinsulinemic hypoglycemia were enrolled. CT, MRI, endoscopic ultrasound, and (99m)Tc-hydrazinonicotinamide-TOC SPECT/CT were done according to standard protocols. GLP-1R PET/CT was performed 30-60 min after the injection of (68)Ga-NOTA-exendin-4. The gold standard for diagnosis was the histopathologic results after surgery., Results: Of 52 recruited patients, 43 patients with histopathologically proven insulinomas were included for the imaging studies. Nine patients did not undergo surgical intervention. (68)Ga-NOTA-exendin-4 PET/CT correctly detected insulinomas in 42 of 43 patients with high tumor uptake (mean SUVavg ± SD, 10.2 ± 4.9; mean SUVmax ± SD, 23.6 ± 11.7), resulting in sensitivity of 97.7%. In contrast, (99m)Tc-hydrazinonicotinamide-TOC SPECT/CT showed a low sensitivity of 19.5% (8/41) in this group of patients; however, it successfully localized the tumor that was false-negative with GLP-1R PET/CT. The sensitivities of CT, MR, and endoscopic ultrasonography were 74.4% (32/43), 56.0% (14/25), and 84.0% (21/25), respectively., Conclusion: (68)Ga-NOTA-exendin-4 PET/CT is a highly sensitive imaging technique for the localization of insulinoma., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Caerulein-induced acute pancreatitis accelerates the progression of pancreatic intraepithelial neoplasia (PanIN) lesions in a pancreas-specific KrasG12D mouse model. The purpose of this study was to explore whether serum microRNAs (miRNAs) can serve as sensitive biomarkers to detect occult PanIN in the setting of acute pancreatitis. Serum miRNA profiles were quantified by an array-based method and normalized by both Variance Stabilization Normalization (VSN) and invariant methods. Individual miRNAs were validated by TaqMan real-time PCR with synthetic spike-in C. elegans miRNAs as external controls. Serum miRNA profiles distinguished KrasG12D mice with pancreatitis from wild-type mice without pancreatitis, but failed to differentiate KrasG12D mice with pancreatitis from wild-type mice with pancreatitis. Most individual miRNAs that increased in KrasG12D mice with pancreatitis were not significantly different between KrasG12D mice without pancreatitis and wild-type mice without pancreatitis. Mechanistically, Gene Set Enrichment Analysis (GSEA) of the mRNA array data and immunohistochemical assays showed that caerulein-induced acute pancreatitis involved acinar cell loss and immune cell infiltration, which might contribute to serum miRNA profile changes. This study highlighted the challenges in using sensitive serum miRNA biomarker screening for the early detection of pancreatic malignancies during acute pancreatitis., Competing Interests: All authors declares no conflicts of interest.

Objective: To evaluate the effect and safety of enucleation of insulinoma under the Da Vinci robotic surgical system combination with intraoperative ultrasonography(IOUS) for the localization., Methods: The clinical materials of 50 insulinoma cases which underwent IOUS and assisted by the robotic surgical system from September 2012 to September 2014 in Peking Union Medical College Hospital were reviewed retrospectively. The patients were followed up by outpatient review and telephone until October 2014. The diagnostic accuracy rate, operation time, blood loss, complications and cure rate were analyzed by t-test., Results: The locations of tumors were 13 in the head, 21 in the body and 13 in the tail of pancreas, 2 were multiple insulinoma, 1 was ectopic to mesenterium.The average operation time was 142 minutes; the average blood loss was 165 ml.Three(6.0%) patients were transformed to open.One patient experienced postoperative bleeding about 300 ml on the 7(th) day after operation and no infection and perioperative death.Thirty-five cases were of class A and 14 of class B according to the clinical grading of postoperative pancreatic fistula.The blood glucose 60 minutes after tumor dissection was significantly elevated than that before operation ((6.2±1.8)mmol/L vs.(3.7±1.2)mmol/L)(t=-6.89, P<0.01). The cure rate was 100% as all the patients' symptoms were disappeared during follow-up time., Conclusions: Combination IOUS is a highly sensitive method for the localization of insulinoma, which is helpful in localizing tumors precisely in insulinoma cases assisted by robotic surgical system and shortening operation time.It is safe and effective for insulinoma enucleation.

Catechol-O-methyltransferase (COMT) is an important molecule in different types of cancers. Its biological effect and therapeutic significance, however, rarely been investigated fully in pancreatic cancer. Immunohistologically, high COMT expression was significantly correlated with the longer overall survival of patients (P < 0.05), indicating its protective nature. The effects of COMT on cell growth, apoptosis, and invasion were evaluated using overexpression and silencing methods. In detail, we carried out experiments using one stably transduced and two transiently transfected pancreatic cancer cell lines in vitro, and one stably transduced cell line in vivo mice xenograft models. In vitro experiments showed that COMT inhibited cell proliferation, enhanced gemcitabine-induced apoptosis, and inhibited cell invasion in stably transduced and transiently transfected cell lines by regulating the PI3K/Akt pathway, p53, and E-cadherin. The COMT overexpressed and silenced cell lines showed significantly inhibited and enhanced growth capacities in in vivo xenograft models, respectively. In conclusion, COMT suppressed pancreatic cancer and its high expression predicted longer survival time. The interaction of COMT with the PI3K/Akt pathway makes it a potential target for therapy., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Competing Interests: None.

Solid serous cystadenoma (SCA) of the pancreas is a rare type of pancreatic solid tumors. Postoperative pathological evaluation is of particular importance for distinguishing solid SCA of the pancreas from other pancreatic solid tumors. Here we present 2 cases of solid SCA of the pancreas, both preoperatively diagnosed with pancreatic neuroendocrine tumors. One case had positive OctreoScan test. Surgical resections were done for both cases. Postoperative immunohistochemistry assays were conducted with marker panels for SCA and 2 types of pancreatic solid tumors, which were neuroendocrine tumor (pNET) and solid pseudopapillary tumor (SPT). Two cases showed typical staining patterns for SCA markers. Notably, both cases showed positivity for 4 SPT markers (vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin). Emphasis should be paid to those 4 new markers for future pathological diagnosis of solid SCA of the pancreas.

Background: The therapeutic effect of lymph node dissection for pancreas invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. The study investigated whether cancer-specific survival (CSS) and overall survival (OS) rates among invasive IPMN patients improve when more lymph nodes are harvested during surgery., Study Design: The study cohort was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The lymph node count was categorized into quartiles. The relationship between lymph node count and survival was analyzed using Kaplan-Meier curves and a Cox proportional-hazards model. The stage migration was assessed by Chi-square tests. Propensity score matching (PSM) was used to minimize confounding variables between groups., Results: In total, 1,080 patients with resected invasive IPMNs from 1992 to 2011 were included. Univariate and multivariate Cox models indicated that an increased lymph node count independently improves survival. The Kaplan-Meier and log-rank tests identified 16 nodes as an optimal cut-off value that yielded a significant survival benefit for all invasive IPMN patients. The stage migration effect existed in this cohort. After PSM, the 5-year CSS increased from 36% to 47%, and the median survival rate increased from 30 months to 40 months by increasing the lymph node count to over 16, alone. The 5-year OS rate also provided additional support for this result., Conclusion: Increased lymph node counts were associated with improved survival in invasive IPMN patients. One cut-off value of lymph node count was 16 for this improvement.

Introduction: Insulinoma and annular pancreas are both rare disorders. In this report, we describe a patient who had insulinoma in association with an annular pancreas., Results and Conclusion: Because the computed tomography scan revealed no relationship between the tumor and the major pancreatic duct, we performed a laparoscopic insulinoma enucleation. As for the asymptomatic annular pancreas, no bypass procedure was performed. The patient recovered well.

Catechol-O-methyl transferase (COMT) is an enzyme involved in estrogen metabolism. Proteomic and immunoproteomic screens suggested COMT might be an immunogenic membrane antigen in human pancreatic cancer. The aim of this study was to investigate the dynamic expression of COMT in pancreatic ductal adenocarcinoma (PDAC) and noncancerous pancreatic tissue, and to determine the relationship between COMT expression and clinicopathologic parameters. COMT expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blot in five pancreatic cell lines and five pairs of PDAC and noncancerous pancreatic tissue. Immunohistochemistry was used to evaluate COMT expression in tissue microarrays and 20 cases of paraffin-embedded clinical specimens. The results indicated that COMT expression was detected in AsPC-1, BxPC-3, MIA PaCa-2, Capan-1 and SW1990 pancreatic cell lines, and in five pairs of PDAC and noncancerous pancreatic tissue, at the mRNA and protein levels. Immunohistochemistry analysis revealed that COMT expression was significantly higher in PDAC than in nonmalignant pancreatic tissue. High expression of COMT significantly correlated to early T stages. Therefore, we conclude that COMT might serve as a potential biomarker for applied clinical pathology in PDAC.