review of literature on clinical pancreatology - The Pancreapedia

25-111 pg/mL). Mean Hemoglobin A1C levels are 8.3 + 3.3 percent (normal 3.8-6.4 %). Thisinitial operation may provide tumor control and prevent metastases but recurrent PENs aremultifocal and progressive. Completion pancreatectomy and duodenectomy is arduous butoutcomes are acceptable. Considering the radical nature <strong>of</strong> this treatment, individualconsideration should be given to MEN-1 patients amenable to initial alternative pancreaticresections that preserve pancreatic mass and allow future pancreas-preserving reoperations[668].Multiple endocrine neoplasia type 1 (MEN1) is an autosomal syndrome caused by mutationsin the MEN1 tumor suppressor gene. Whereas the protein product <strong>of</strong> MEN1, menin, isubiquitously expressed, somatic loss <strong>of</strong> the remaining wild-type MEN1 allele results in tumorsprimarily in parathyroid, pituitary, and endocrine pancreas. To understand the endocrinespecificity <strong>of</strong> the MEN1 syndrome, it was evaluated biallelic loss <strong>of</strong> Men1 by inactivatingMen1 in pancreatic progenitor cells using the Cre-lox system. Men1 deletion in progenitorcells that differentiate into exocrine and endocrine pancreas did not affect normal pancreasmorphogenesis and development. However, mice having homozygous inactivation <strong>of</strong> theMen1 in pancreas developed endocrine tumors with no exocrine tumor manifestation,recapitulating phenotypes seen in the MEN1 patients. In the absence <strong>of</strong> menin, theendocrine pancreas showed increase in cell proliferation, vascularity, and abnormal vascularstructures; such changes were lacking in exocrine pancreas. Further analysis revealed thatthese endocrine manifestations were associated with up-regulation in vascular endothelialgrowth factor expression in both human and mouse MEN1 pancreatic endocrine tumors.Together, these data suggest the presence <strong>of</strong> cell-specific factors for menin and a permissiveendocrine environment for MEN1 tumorigenesis in endocrine pancreas. Based on thisanalysis, it was proposed that menin's ability to maintain cellular and microenvironmentintegrity might explain the endocrine-restrictive nature <strong>of</strong> the MEN1 syndrome [669].To investigate if transcription factors involved in pancreatic differentiation and regenerationare present in pancreatic endocrine tumors and if they are differentially expressed in normalpancreas compared with multiple endocrine neoplasia type 1 (MEN1) nontumorous pancreasthe expression <strong>of</strong> neurogenin 3 (NEUROG3), neurogenic differentiation 1 (NEUROD1), POUclass 3 homeobox 4 (POU3F4), pancreatic duodenal homeobox factor 1 (PDX1), ribosomalprotein L10 (RPL10), delta-like 1 homolog (DLK1), and menin was analyzed byimmunohistochemistry in normal pancreas and pancreatic endocrine tumors from 6 patientswith MEN1 and 16 patients with sporadic tumors, as well as pancreatic specimens fromMen1 heterozygous and wild type mice. Quantitative polymerase chain reaction wasperformed in a subset <strong>of</strong> human tumors. Tumors and MEN1 nontumorous endocrine cellsshowed a prominent cytoplasmatic NEUROG3 and NEUROD1 expression. These factorswere significantly more expressed in the cytoplasm <strong>of</strong> Men1 heterozygous mouse islet cellscompared with wild type islets; the latter showed an exclusively nuclear reactivity. Thedegree <strong>of</strong> Pou3f4, Rpl10, and Dlk1 immunoreactivities differed significantly between islets <strong>of</strong>heterozygous and wild type mice. The expressions <strong>of</strong> RPL10 and NEUROD1 were prominentin the MEN1 human and heterozygous mouse exocrine pancreas. Insulinomas hadsignificantly higher PDX1 and DLK1 messenger RNA levels compared with other tumor types[670].DiagnosticsThe aim <strong>of</strong> one study was to characterize the ultrasonographic features <strong>of</strong> neuroendocrinetumors (NET) and their metastases with contrast-enhanced ultrasonography (CEUS) and tocompare this to clinical data. During a period <strong>of</strong> 5 years, 82 patients with 83 histologicallyproven NET were prospectively examined using conventional US and pulse inversion USwith a second generation contrast agent (SonoVue, Contrast Pulse Sequencing) focusing on