scholarly journals Loss of Jag1 cooperates with oncogenic Kras to induce pancreatic cystic neoplasms

2020 ◽  
Vol 4 (2) ◽  
pp. e201900503
Author(s):  
Wen-Cheng Chung ◽  
Lavanya Challagundla ◽  
Yunyun Zhou ◽  
Min Li ◽  
Azeddine Atfi ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Early Stage ◽  
Rapid Development ◽  
Ductal Adenocarcinoma ◽  
Cystic Neoplasm ◽  
Cystic Lesions ◽  
Poor Overall Survival ◽  
Cystic Neoplasms ◽  
Serous Cystic Neoplasm ◽  
Acinar To Ductal Metaplasia

Notch signaling exerts both oncogenic and tumor-suppressive functions in the pancreas. In this study, deletion of Jag1 in conjunction with oncogenic KrasG12D expression in the mouse pancreas induced rapid development of acinar-to-ductal metaplasia and early stage pancreatic intraepithelial neoplasm; however, culminating in cystic neoplasms rather than ductal adenocarcinoma. Most cystic lesions in these mice were reminiscent of serous cystic neoplasm, and the rest resembled intraductal papillary mucinous neoplasm. Jag1 expression was lost or decreased in cystic lesions but retained in adenocarcinoma in these mice, so was the expression of Sox9. In pancreatic cancer patients, JAG1 expression is higher in cancerous tissue, and high JAG1 is associated with poor overall survival. Expression of SOX9 is correlated with JAG1, and high SOX9 is also associated with poor survival. Mechanistically, Jag1 regulates expression of Lkb1, a tumor suppressor involved in the development of pancreatic cystic neoplasm. Collectively, Jag1 can act as a tumor suppressor in the pancreas by delaying precursor lesions, whereas loss of Jag1 promoted a phenotypic switch from malignant carcinoma to benign cystic lesions.

Mucinous Cystic Neoplasms of the Pancreas: How Much Preoperative Evaluation is Needed?

2010 ◽  
Vol 76 (8) ◽  
pp. 812-817 ◽  
Author(s):  
Tom P. Theruvath ◽  
Katherine A. Morgan ◽  
David B. Adams
Keyword(s):  
Operative Treatment ◽  
Endoscopic Ultrasound ◽  
Preoperative Evaluation ◽  
Mucinous Cystic Neoplasm ◽  
Cystic Neoplasm ◽  
Cystic Lesions ◽  
Mri Imaging ◽  
Diagnostic Dilemma ◽  
Cystic Neoplasms ◽  
Preoperative Workup

Cystic lesions of the pancreas are identified with increasing frequency by modern imaging. The mucinous cystic neoplasm (MCN) is treated with resection for its malignant potential. How much preoperative evaluation is needed before undertaking operation is frequently a diagnostic dilemma. A retrospective review of 32 patients who underwent resection of a MCN between 1994 and 2007 was performed to define the preoperative evaluation and operative treatment of MCN patients. Thirty-two patients (30 women; mean age 49) had histology-proven MCN. Twenty-seven patients had symptomatic cysts (84%). Five had a history of gallstones and/or acute pancreatitis. All patients were worked up with CT and/or MRI. Endoscopic ultrasound was performed in 14 (44%) and endoscopic retrograde cholangiopancreatography in six (18%). Cytology was obtained in 13 (40%). Pathology revealed 22 benign MCNs (68%), five malignant MCNs (16%), and five MCNs with borderline pathology. Preoperative workup including CT or MRI imaging and cytology suggested MCN as the lesion in 15 patients (46%). CT features by itself predicted MCN in three patients (9%). Cytology revealed another six patients (19%) with possible MCN. In this series, preoperative workup did not identify three of five patients with MCN malignancy. A preoperative diagnosis cannot be made in most patients with MCN. Operative treatment can be based on clinical presentation and CT imaging because endoscopic ultrasound and fine needle aspiration for evaluation may be misleading. Middle-aged women with cystic lesions in the tail of the pancreas without prior gallstone or pancreatitis history most typically fit the profile of the MCN patient.

scholarly journals European evidence-based guidelines on pancreatic cystic neoplasms

Gut ◽  
2018 ◽  
Vol 67 (5) ◽  
pp. 789-804 ◽  
Author(s):  
Keyword(s):  
Mucinous Cystic Neoplasm ◽  
Cystic Neoplasm ◽  
Evidence Based ◽  
Indications For Surgery ◽  
Cystic Neoplasms ◽  
Serous Cystic Neoplasm ◽  
Pancreatic Cystic Neoplasms ◽  
Grade Methodology ◽  
Evidence Based Guidelines

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring <40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter ≥40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule >5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

scholarly journals A Serous Cystic Neoplasm of the Pancreas with Synchronous Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 25 (2) ◽  
pp. 118-122
Author(s):  
Hyun Jin Park ◽  
Jun Seong Hwang ◽  
Sung Woo Ko ◽  
Hoonsub So ◽  
Jae Woo Kwon ◽  
...  
Keyword(s):  
Literature Review ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Mucinous Cystic Neoplasm ◽  
Malignant Potential ◽  
Ductal Adenocarcinoma ◽  
Cystic Neoplasm ◽  
Solitary Lesion ◽  
Mucinous Neoplasm ◽  
Serous Cystic Neoplasm ◽  
Cystic Pancreatic Lesions

Serous cystic neoplasm (SCN) represents 10–16% of cystic pancreatic lesions, first classified by Compagno and Oertel at 1978. In contrast to mucinous cystic neoplasm or intraductal papillary mucinous neoplasm of pancreas which have malignant potential, SCN is thought to be exclusively benign as solitary lesion in nearly all cases. There has been rare reported association between the SCN and pancreatic ductal adenocarcinoma, and few cases were documented their coexistence. In this report, we present the case of SCN of the pancreas with literature review in which synchronous pancreatic ductal adenocarcinoma and pancreatic intraepithelial neoplasm coexist together.

scholarly journals Nonmucinous Cystic Lesions of the Pancreas

2021 ◽  
Author(s):  
Irene Esposito ◽  
Lena Haeberle
Keyword(s):  
Accurate Diagnosis ◽  
University Hospital ◽  
Ductal Adenocarcinoma ◽  
Molecular Profile ◽  
Cystic Lesions ◽  
Heinrich Heine ◽  
Clinical Context ◽  
Diagnostic Challenge ◽  
Cystic Neoplasms ◽  
Diagnosis And Classification

Context.— Pancreatic cystic lesions are increasingly diagnosed. Among other criteria, they are often distinguished in mucinous versus nonmucinous cysts. Mucinous pancreatic cystic lesions have received increasing attention, especially those known as precursors of pancreatic ductal adenocarcinoma. However, the group of nonmucinous cystic lesions of the pancreas includes numerous entities that may pose a diagnostic challenge. Their accurate diagnosis and classification are crucial for adequate patient management. Objective.— To review the spectrum of nonmucinous cystic lesions of the pancreas, taking into consideration their epidemiology and typical clinical context, their characteristic gross morphology and histomorphology, as well as their immunohistochemical and molecular profile. Data Sources.— Literature was searched and reviewed with MEDLINE via PubMed. Macroscopic and microscopic images were obtained from the archives of the Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Germany. Conclusions.— Nonmucinous cysts of the pancreas comprise numerous, mostly rare entities displaying different biological behaviors. The most frequent are serous cystic neoplasms, solid-pseudopapillary neoplasms, cystic neuroendocrine tumors, and pancreatitis-associated pseudocysts. Accurate diagnosis can be achieved if characteristic clinical context, histomorphology, and immunoprofile are taken into account.

A nomogram for predicting pancreatic mucinous cystic neoplasm and serous cystic neoplasm

2021 ◽  
Author(s):  
Chengwei Shao ◽  
Xiaochen Feng ◽  
Jieyu Yu ◽  
Yinghao Meng ◽  
Fang Liu ◽  
...  
Keyword(s):  
Mucinous Cystic Neoplasm ◽  
Cystic Neoplasm ◽  
Serous Cystic Neoplasm

scholarly journals Deep Learning-Based Differentiation between Mucinous Cystic Neoplasm and Serous Cystic Neoplasm in the Pancreas Using Endoscopic Ultrasonography

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1052
Author(s):  
Leang Sim Nguon ◽  
Kangwon Seo ◽  
Jung-Hyun Lim ◽  
Tae-Jun Song ◽  
Sung-Hyun Cho ◽  
...  
Keyword(s):  
Decision Making ◽  
Deep Learning ◽  
Network Model ◽  
Endoscopic Ultrasonography ◽  
Data Augmentation ◽  
Clinical Information ◽  
Training Data ◽  
Fine Tuning ◽  
Cystic Neoplasm ◽  
Cystic Neoplasms

Mucinous cystic neoplasms (MCN) and serous cystic neoplasms (SCN) account for a large portion of solitary pancreatic cystic neoplasms (PCN). In this study we implemented a convolutional neural network (CNN) model using ResNet50 to differentiate between MCN and SCN. The training data were collected retrospectively from 59 MCN and 49 SCN patients from two different hospitals. Data augmentation was used to enhance the size and quality of training datasets. Fine-tuning training approaches were utilized by adopting the pre-trained model from transfer learning while training selected layers. Testing of the network was conducted by varying the endoscopic ultrasonography (EUS) image sizes and positions to evaluate the network performance for differentiation. The proposed network model achieved up to 82.75% accuracy and a 0.88 (95% CI: 0.817–0.930) area under curve (AUC) score. The performance of the implemented deep learning networks in decision-making using only EUS images is comparable to that of traditional manual decision-making using EUS images along with supporting clinical information. Gradient-weighted class activation mapping (Grad-CAM) confirmed that the network model learned the features from the cyst region accurately. This study proves the feasibility of diagnosing MCN and SCN using a deep learning network model. Further improvement using more datasets is needed.

scholarly journals Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Noncoding Rna ◽  
Pancreatic Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

scholarly journals Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Serum Samples ◽  
Tissue Samples ◽  
Non Invasive ◽  
Specific Symptoms ◽  
Generation Sequencing

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

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