The aims of this study were to identify the morphological diversities and anatomical variations of pancreatic ductal system and to define the relationships between pancreatic ductal systems, pancreaticobiliary diseases, and procedure-related complications, including post-ERCP pancreatitis. This study included 582 patients in whom both pancreatic duct (PD) and common bile duct were clearly visible by ERCP. PD systems were categorized into four types according to the relationship between common bile duct and PD. In types A and B, Wirsung duct formed the main PD. In type C, Wirsung duct did not form the main PD. If PD system did not fall into any of these three types, it was categorized as type D. The distribution of types among pancreatic ducts examined was as follows: type A: 491 cases (84.4%), type B: 56 cases (9.6%), type C: 20 cases (3.4%), and type D: 15 cases (2.6%). The anomalous anatomic variations of PD systems were divided into migration, fusion, and duplication anomalies. PD anomalies were noted in 51 patients, of which 19 (3.3%) were fusion anomalies (12 complete pancreas divisum, 7 incomplete pancreas divisum), and 32 (5.5%) were duplication anomalies (5 number variations, 27 form variations). No significant relationships between various PD morphologies and pancreaticobiliary diseases were found. However, post- ERCP hyperamylasemia was more frequently found in types C (41.7%), D (50%) and A (19.8%) than in type B (9.4%). In summary, whether Wirsung duct forms the main PD and the presence or absence of the opening of the Santorini duct are both important factors in determining the development of pancreatitis and hyperamylasemia after ERCP.
Sex Factors ; Pancreatitis/diagnosis/pathology ; Pancreatic Ducts/*anatomy & histology/*pathology ; Pancreatic Diseases/diagnosis ; Middle Aged ; Male ; Humans ; Female ; Common Bile Duct/anatomy & histology/pathology ; Cholangiopancreatography, Endoscopic Retrograde/*methods ; Bile Ducts/*anatomy & histology/metabolism/pathology

Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHR is upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition of GHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming ability and reduced invasiveness. Flow cytometric and western blot analyses revealed the induction of apoptosis in GHR silenced cells. GHR silencing affected phosphatidylinositol 3 kinase/AKT, mitogen extracellular signal-regulated kinase/extracellular signal-regulated kinase, Janus kinase/signal transducers and activators of transcription and mammalian target of rapamycin signaling, as well as, epithelial to mesenchymal transition. Interestingly, silencing GHR also suppressed the expression of insulin receptor-beta and cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals its importance in pancreatic cancer pathogenesis.
Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Metastasis/genetics/pathology ; Pancreatic Ducts/metabolism/*pathology ; Pancreatic Neoplasms/*genetics/*pathology ; *RNA Interference ; RNA, Small Interfering/administration & dosage/genetics ; Receptors, Somatotropin/*genetics ; Transfection

OBJECTIVETo study the clinicopathologic features and diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

METHODSNineteen cases of IPMN encountered during the period from 1999 to 2007 were studied by light microscopy and immunohistochemistry.

RESULTSIPMN occurred more often in males (68%). It affected patients in older age group (mean age = 59) and was located mainly in the head of pancreas (60%). The mean tumor size was 4.2 cm (range = 1 to 8 cm). The clinical presentation was epigastric pain (53%), weight loss (32%), diabetes (21%), pancreatitis (21%) and jaundice (10%). Pancreatectomy was performed in 18 cases. The remaining patient received bypass surgery only. Features of in-situ or invasive malignancy were present in 15 of the 19 cases (78%). Histologically, the tumor consisted of papillary proliferations protruding into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic parenchyma was noted in 12 cases and chronic pancreatitis was present in 16 cases. Follow-up data (4 to 48 months) were available in 13 patients. Apart from 1 patient who died of other disease, all were still alive. Immunohistochemical study showed that p53 was positive in 6 cases, p16 in 5 cases and fascin in 8 cases. The expression of c-erbB-2 was all negative. Ki-67 index ranged from 1% to 80% (mean = 38%).

CONCLUSIONSMalignant changes are not uncommon in IPMN. The prognosis after surgical resection however is better than that of conventional pancreatic adenocarcinoma. The overexpression of p53, p16 and fascin may be related to tumor progression. The possibility of malignant transformation needs to be considered if the Ki-67 index is over 15%. Early recognition by radiologic examination (including ERCP) and pancreatic cytology would be helpful in early diagnosis. Surgical resection represents the mainstay of treatment and long-term post-operative follow up is needed.

Adaptor Proteins, Signal Transducing ; analysis ; Adenocarcinoma, Mucinous ; diagnosis ; metabolism ; Adult ; Aged ; Carcinoma, Pancreatic Ductal ; diagnosis ; metabolism ; pathology ; Carcinoma, Papillary ; pathology ; Cell Cycle Proteins ; analysis ; Cholangiopancreatography, Endoscopic Retrograde ; Female ; Humans ; Immunohistochemistry ; trends ; Ki-67 Antigen ; analysis ; Male ; Middle Aged ; Pancreas ; metabolism ; pathology ; Pancreatectomy ; Pancreatic Ducts ; metabolism ; pathology ; Pancreatic Neoplasms ; diagnosis ; metabolism ; pathology ; Prognosis ; Receptor, ErbB-2 ; analysis ; Treatment Outcome

OBJECTIVETo explore the significance of mitochondrial D-loop alterations in hyperplastic pancreatic ductal cells in vicinity of pancreatic cancer coexisting with chronic pancreatitis.

METHODSMalignant lesions and foci of pancreatic ductal intraepithelial neoplasia of the pancreas and paired normal gastric mucosal epithelial cells from the same patients, respectively, were assessed by polymerase chain reaction. Somatic point mutations and sequence variants of D-loop were searched by direct sequencing of the mitochondrial genome. D-loops were sequenced by BLAST to identify their mutations.

RESULTSEleven of 12 pancreatic cancers displayed at least one D-loop variants and one tumor presented heteroplasmy. There was an apparent increase in incidence of D-loop mutational rate from PanIN1 (33.3%) to PanIN3 (75%, P < 0.01).

CONCLUSIONMitochondrial D-loop alterations in the pancreas occur in the earliest premalignant lesions and exhibite an increasing occurence that parallels histological severity. These alterations may serve as a valuable marker to follow the histopathological progression of the lesions. Large number of further studies are required to clarify clinical implications of the mitochondrial DNA alterations.

Adenoma ; complications ; genetics ; Adult ; Aged ; Base Sequence ; DNA, Mitochondrial ; genetics ; Epithelial Cells ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pancreatic Ducts ; metabolism ; pathology ; Pancreatic Neoplasms ; complications ; genetics ; Pancreatitis, Chronic ; complications ; genetics ; Precancerous Conditions ; complications ; genetics ; Sequence Analysis, DNA

BACKGROUND: Cell competition is an important feature in pancreatic cancer (PC) progression, but the underlying mechanism remains elusive. This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression. METHODS: PC cells and pancreatic stellate cells (PSCs) were treated with exosomes isolated from pancreatic ductal epithelial cells. Cell proliferation was assessed by CCK8 assays. Cell migration and invasion were assessed by Transwell assays. PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017. Tissue miR-485-3p and p21-activated kinase-1 (PAK1) expression was examined by real-time polymerase chain reaction (RT-PCR), and the relationship of the two was analyzed using Pearman's product-moment correlation. The clinical significance of miR-485-3p was analyzed using the Chi-square test, Wilcoxon rank-sum test, and Fisher exact probability, respectively. The binding of miR-485-3p to PAK1 5'-untranslated region (5'-UTR) was examined by luciferase assay. PC cells were xenografted into nude mice as a PC metastasis model. RESULTS: Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs. MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs, in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells. And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells, to inhibit PC cell migration and invasion. Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues (P < 0.05) and was negatively associated with lymphovascular invasion (P = 0.044). As a direct target of miR-485-3p, PAK1 was found to exert an inhibitory effect on PC cells, and there was a significantly negative correlation between the expression levels of miR-485-3p and PAK1 (r = -0.6525, P < 0.0001) in PC tissues. Moreover, miR-485-3p could suppress PC metastasis in vivo by targeting p21-activated kinase-1. CONCLUSIONS Exosomal miR-485-3p delivered by normal pancreatic ductal epithelial cells into PC cells inhibits PC metastasis by directly targeting PAK1. The restoration of miR-485-3p by exosomes or some other vehicle might be a novel approach for PC treatment.
Animals ; Mice ; MicroRNAs/metabolism* ; Mice, Nude ; p21-Activated Kinases/metabolism* ; Cell Line, Tumor ; Pancreatic Neoplasms/genetics* ; Epithelial Cells/metabolism* ; Pancreatic Ducts/pathology* ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

Animals ; Biliary Tract ; abnormalities ; diagnostic imaging ; Cats ; Cholangiography ; Disease Models, Animal ; Female ; Liver ; metabolism ; pathology ; Liver Diseases ; diagnostic imaging ; etiology ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Liver ; diagnostic imaging ; pathology ; Pancreatic Ducts ; abnormalities ; diagnostic imaging

OBJECTIVETo explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.

METHODSHuman embryonic pancreatic tissue at 7-14 weeks of gestation was collected. Diabetes mellitus rat model was induced with 65 mg/kg of streptozotocin. Insulin, glucagon, somatostatin, nestin, and cytokeratin 19 (CK19) of pancreatic tissues were observed by immunohistochemistry.

RESULTSAt 9 weeks of gestation, pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin, and CK19 before migration. Islet cells gradually congregated along with the increase of aging, and at 14 weeks of gestation histological examination showed islet formation. At 12 weeks of gestation, nestin-positive cells could be seen in the pancreatic mesenchyme. During early embryogenesis, islet cells of pancreatic ducts co-expressed insulin, glucagon, and somatostatin. During pancreatic regeneration after damage, nestin expression of islet cells increased.

CONCLUSIONIn the early stage of embryogenesis, islet cells of primary pancreatic ducts can be differentiated to multipotential endocrine cells before migration. During tissue regeneration, pancreatic stem cells may differentiate and proliferate to form pancreatic islet.

Animals ; Cell Differentiation ; Diabetes Mellitus, Experimental ; chemically induced ; metabolism ; pathology ; Embryonic Development ; physiology ; Epithelial Cells ; cytology ; physiology ; Humans ; Insulin-Secreting Cells ; cytology ; physiology ; Islets of Langerhans ; cytology ; physiology ; Male ; Pancreas ; cytology ; embryology ; physiology ; Pancreatic Ducts ; cytology ; embryology ; physiology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; physiology ; Stem Cells ; cytology ; metabolism ; physiology