Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

The bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells

Metachronous Intraductal Papillary Neoplasm of the Bile Duct and Intraductal Papillary Mucinous Neoplasm of the Pancreas in a Patient Diagnosed With Mucinous Adenocarcinoma.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare biliary tumor, which shares some radiologic and histologic similarities with pancreatic intraductal papillary mucinous neoplasm (IPMN). IPNB is a recognized precursor lesion of invasive adenocarcinoma. We present a case of metachronous IPNB and IPMN lesions in a patient with mucinous adenocarcinoma of the pancreas who presented with jaundice and abdominal pain. The patient was treated with surgery and adjuvant chemotherapy

Development and Congenital Anomalies of the Pancreas

Understanding how the pancreas develops is essential to understand the pathogenesis of congenital pancreatic anomalies. Recent studies have shown the advantages of investigating the development of frogs, mice, and chickens for understanding early embryonic development of the pancreas and congenital anomalies, such as choledochal cysts, anomalous pancreaticobiliary junction, annular pancreas, and pancreas divisum. These anomalies arise from failure of complete rotation and fusion during embryogenesis. There are many theories in the etiology of congenital anomalies of the pancreas. We review pancreas development in humans and other vertebrates. In addition, we attempt to clarify how developmental failure is related to congenital pancreatic anomalies

Lymphangiogenesis and angiogenesis during human fetal pancreas development

Background: The complex endocrine and exocrine functionality of the human pancreas depends on an efficient fluid transport through the blood and the lymphatic vascular systems. The lymphatic vasculature has key roles in the physiology of the pancreas and in regulating the immune response, both important for developing successful transplantation and cell-replacement therapies to treat diabetes. However, little is known about how the lymphatic and blood systems develop in humans. Here, we investigated the establishment of these two vascular systems in human pancreas organogenesis in order to understand neovascularization in the context of emerging regenerative therapies. Methods: We examined angiogenesis and lymphangiogenesis during human pancreas development between 9 and 22 weeks of gestation (W9-W22) by immunohistochemistry. Results: As early as W9, the peri-pancreatic mesenchyme was populated by CD31-expressing blood vessels as well as LYVE1- and PDPN-expressing lymphatic vessels. The appearance of smooth muscle cell-coated blood vessels in the intra-pancreatic mesenchyme occurred only several weeks later and from W14.5 onwards the islets of Langerhans also became heavily irrigated by blood vessels. In contrast to blood vessels, LYVE1- and PDPN-expressing lymphatic vessels were restricted to the peri-pancreatic mesenchyme until later in development (W14.5-W17), and some of these invading lymphatic vessels contained smooth muscle cells at W17. Interestingly, between W11-W22, most large caliber lymphatic vessels were lined with a characteristic, discontinuous, collagen type IV-rich basement membrane. Whilst lymphatic vessels did not directly intrude the islets of Langerhans, three-dimensional reconstruction revealed that they were present in the vicinity of islets of Langerhans between W17-W22. Conclusion: Our data suggest that the blood and lymphatic machinery in the human pancreas is in place to support endocrine function from W17-W22 onwards. Our study provides the first systematic assessment of the progression of lymphangiogenesis during human pancreatic development

A surgical model of short bowel syndrome induces a long-lasting increase in pancreatic beta-cell mass

Several surgical techniques are used nowadays as a severe treatment for obesity and diabetes mellitus type 2. These techniques are aggressive due to drastic changes in the nutrient flow and non-reversible modifications on the digestive tube. In this paper we present the effects of a massive intestinal resection on the pancreas. Results have shown that short bowel technique is less aggressive to normal anatomy and physiology of the intestinal tract than Gastric bypass or biliopancreatic diversion (e.g.). In this paper we reproduce a model of short bowel syndrome (SIC), with similar surgical conditions and clinical complications as seen in human cases. This work was conducted on normal Wistar rats, with no other concurrent factors, in order to determine the effects on normal pancreas islets. We measured pancreatic implications by histomorphometric studies, which included beta-cell mass by immunocytochemistry, and apoptosis/proliferation test with TUNEL technique and Ki-67. Briefly, we reported on an increased relative area of the islets of the pancreas, as well as an increase in the average size of islets in the SIC versus the control group. Furthermore we stated that this increase in size of the pancreatic islets is due to the mechanisms of proliferation of beta cells in animals undergoing SIC. These goals could reveal a direct influence of surgical modification of the digestive tract over the pancreatic beta cell homeostasis. In this sense, there are many potential stimulators of intestinal adaptation, including peptide hormones and growth components which are associated or involved as effectors of the endocrine pancreas

COMPARISON OF ULTRASOUND WITH ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY AND SURGERY IN THE DETECTION OF SITE AND CAUSE BILE DUCTS DILATATION

background and Objectives: Ultrasound (US) is the initial imaging test used in the evaluation of patients with biliary tract disease. Our retrospective study was designed to evaluate the capacity of ultrasound to determine the cause and site of bile ducts dilatation, and to compare the accuracy of ultrasound with endoscopic retrograde cholangiopancreatography (ERCP), a well-accepted procedure and surgery as practiced on 53 patients. Patients and Methods: 40 patients with ultrasonographic, endoscopic retrograde cholangiopancreatography and surgery reports were entered into the study. sonographic reports of each patient were compared with endoscopic retrograde cholangiopancreatography and surgery findings. Results: The most common cause of dilatation was stones followed by bile ducts tumors. Tumors were located in intrapancreatic common bile duct in 81.8%. The sensitivity of ultrasound was 100% in diagnosis of stones and 83.3% in tumors respectively. Comparison of the ultrasound and endoscopic retrograde cholangiopancreatography and surgery findings revealed a correct sonographic diagnosis in 92.5% of cases. Conclusion: Our study showed that ultrasound had a high accuracy and sensitivity of 92.5% and 94.4%, respectively in the diagnosis of bile ducts dilatation

Development of the sphincteric apparatus of the extrahepatic bile ducts in the prenatal period of human ontogenesis

In this study, authors found the sources of anlages, and the peculiarities in development and formation of topography of structural components of sphincteric apparatus of the extrahepatic bile ducts (EBD). We found that beginning from the sixth month of the development, EBD are traced in the form of a well-defined tubular structure. The extrahepatic and intrahepatic bile ducts are well contoured, but in the end of the embryonal period, a tendency to mutual fuse has been noticed. Formation of the intraorgan blood vessels of the common bile duct is detected at the end of the seventh week of the intrauterine development in fetuses starting with 18.0-19.0 mm of parietococcygeal length (PCL). The peculiarities of spatial structure of the arterial anastomoses around the coiled part of the cystic duct proved the existence of the locking device (sphincter) between the neck of gallbladder and cystic duct and play an important role in functioning of vascular (arterial) component of it. The peculiarities of topography and spatial structure differences in arterial and venous plexuses in the sphincter segments of the biliary system were observed clearly in the end of the fetus period of development and in newborns. This may indicate an important role of these vessels in the function of sphincters, which provides biliodynamics

Partial pancreatic resection along the embryological fusion plane — no longer a fantasy

Background: The embryological connection between the dorsal and ventral pancreatic regions divides the pancreas into two segments. This anatomical dependence allows segmental pancreatic resection through the embryological fusion plane (EFP). The advantages of limited pancreatic resection are the preservation of the natural continuity and function of the gastrointestinal tract and the avoidance of the metabolic and endocrine consequences of total resectionof the pancreas and the duodenum. Materials and methods: Two patients are described who underwent anatomical segmentectomy of the pancreatic head along the EFP for the treatment of pancreatic cystic tumour and main duct intraductal papillary-mucinous neoplasm. The authors suggested diagnostic and intraoperative management leading to qualification for pancreatic resection along the EFP. Results: Pancreas and duodenum sparing surgery is an opportunity for patients in terms of the post-operative quality of life. Indications for this kind of surgery are limited and case selection is very difficult. The procedure for embryological bud resection is highly complicated includes a high rate of possible complications. On the other hand high volume centres may offer this procedure at an acceptable rate of complications in selected cases. Conclusions: Accurate diagnosis with a vascular anatomy and biliary and pancreatic duct configuration give grounds to analyse pancreas-sparing surgery. The operation plan requires careful three-dimensional planning and an experienced team. Bipolar electrocautery, micro-surgical tools and intraoperative cholangiography and pancreatography are helpful

Adult human biliary tree stem cells differentiate to β-pancreatic islet cells by treatment with a recombinant human Pdx1 peptide

Generation of β-pancreatic cells represents a major goal in research. The aim of this study was to explore a protein-based strategy to induce differentiation of human biliary tree stem cells (hBTSCs) towards β-pancreatic cells. A plasmid containing the sequence of the human pancreatic and duodenal homeobox 1 (PDX1) has been expressed in E. coli. Epithelial-Cell-Adhesion-Molecule positive hBTSCs or mature human hepatocyte cell line, HepG2, were grown in medium to which Pdx1 peptide was added. Differentiation toward pancreatic islet cells were evaluated by the expression of the β-cell transcription factors, Pdx1 and musculoapo-neurotic fibrosarcoma oncogene homolog A, and of the pancreatic hormones, insulin, glucagon, and somatostatin, investigated by real time polymerase chain reaction, western blot, light microscopy and immunofluorescence. C-peptide secretion in response to high glucose was also measured. Results indicated how purified Pdx1 protein corresponding to the primary structure of the human Pdx1 by mass spectroscopy was efficiently produced in bacteria, and transduced into hBTSCs. Pdx1 exposure triggered the expression of both intermediate and mature stage β-cell differentiation markers only in hBTSCs but not in HepG2 cell line. Furthermore, hBTSCs exposed to Pdx1 showed up-regulation of insulin, glucagon and somatostatin genes and formation of 3-dimensional islet-like structures intensely positive for insulin and glucagon. Finally, Pdx1-induced islet-like structures exhibited glucose-regulated C-peptide secretion. In conclusion, the human Pdx1 is highly effective in triggering hBTSC differentiation toward functional β-pancreatic cells