Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2

We recently identified the transcription factor (TF) islet 1 gene product (ISL1) as a marker for well-differentiated pancreatic neuroendocrine tumors (P-NETs). In order to better understand the expression of the four TFs, ISL1, pancreatico-duodenal homeobox 1 gene product (PDX1), neurogenin 3 gene product (NGN3), and CDX-2 homeobox gene product (CDX2), that mainly govern the development and differentiation of the pancreas and duodenum, we studied their expression in hormonally defined P-NETs and duodenal (D-) NETs. Thirty-six P-NETs and 14 D-NETs were immunostained with antibodies against the four pancreatic hormones, gastrin, serotonin, calcitonin, ISL1, PDX1, NGN3, and CDX2. The TF expression pattern of each case was correlated with the tumor's hormonal profile. Insulin-positive NETs expressed only ISL1 (10/10) and PDX1 (9/10). Glucagon-positive tumors expressed ISL1 (7/7) and were almost negative for the other TFs. Gastrin-positive NETs, whether of duodenal or pancreatic origin, frequently expressed PDX1 (17/18), ISL1 (14/18), and NGN3 (14/18). CDX2 was mainly found in the gastrin-positive P-NETs (5/8) and rarely in the D-NETs (1/10). Somatostatin-positive NETs, whether duodenal or pancreatic in origin, expressed ISL1 (9/9), PDX1 (3/9), and NGN3 (3/9). The remaining tumors showed labeling for ISL1 in addition to NGN3. There was no association between a particular TF pattern and NET features such as grade, size, location, presence of metastases, and functional activity. We conclude from our data that there is a correlation between TF expression patterns and certain hormonally defined P-NET and D-NET types, suggesting that most of the tumor types originate from embryologically determined precursor cells. The observed TF signatures do not allow us to distinguish P-NETs from D-NETs.

Serotonin-producing enterochromaffin cell tumors of the pancreas: clinicopathologic study of 15 cases and comparison with intestinal enterochromaffin cell tumors

Serotonin-producing tumors of the pancreas are rare endocrine neoplasms composed of enterochromaffin (EC) cells that have been mainly described in the literature as case reports. This study analyzes the clinicopathologic features of a series of pancreatic EC cell neoplasms and their similarities to and differences from intestinal EC cell tumors.

Clinical aspects, diagnostic challenges and management of patients with neuroendocrine tumors (NETs)

Neuroendocrine tumor (NET) entities are rare malignancies. Higher awareness and improved diagnostic methods have led to an increasing incidence of these diseases, and most oncologists deal with such patients in their daily practice. The symposium on NETs that was held in Merano (Italy) in October 2009 was organized by the German-speaking European School of Oncology (dESO) and gathered specialists from different disciplines of transalpine countries to bring together experiences and observations regarding these tumors. The goal of the meeting and of this review was to illustrate both well- and poorly differentiated NETs and to encourage interdisciplinary approaches.

Endovascular Therapy of 623 Patients With Anterior Circulation Stroke

Endovascular therapy of acute ischemic stroke has been shown to be beneficial for selected patients. The purpose of this study is to determine predictors of outcome in a large cohort of patients treated with intra-arterial thrombolysis, mechanical revascularization techniques, or both.

68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

By targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUV(max)) and sst mRNA.

Adverse Effect of Early Epileptic Seizures in Patients Receiving Endovascular Therapy for Acute Stroke

The aim of this study was to analyze epileptic seizures and their impact on outcome in patients with stroke treated with endovascular therapy.

Determination of hemispheric dominance with mental rotation using functional transcranial Doppler sonography and FMRI

the aim of this study was to investigate specific activation patterns and potential gender differences during mental rotation and to investigate whether functional magnetic resonance imaging (fMRI) and functional transcranial Doppler sonography (fTCD) lateralize hemispheric dominance concordantly.

Clearance of p-cresol sulfate and β-2-microglobulin from dialysate by commercially available sorbent technology

Dialysate regeneration by sorbents is an alternative to conventional single-pass dialysis. Little is known about the capacity of sorbents to clear dialysate of “middle molecules” and protein-bound uremic toxins. We studied p-cresol sulfate (PCS) and β-2-microglobulin (β2M) removal from dialysate by a sorbent: 1. PCS (40 mg PCS dissolved in 4 L of fresh dialysate) was recirculated through a sorbent cartridge (SORB Technology, Inc.) for analysis of PCS removal. 2. Spent peritoneal dialysate was recirculated on the “blood” side of a high-flux dialyzer. On the “dialysate” side of the membrane, bicarbonate dialysate was recirculated through a sorbent cartridge. β2M was measured in both streams. Two results are of particular importance for the use of regenerated fluid in chronic dialysis: 1. PCS was virtually completely removed from the dialysate. On average, PCS concentration was reduced to 1.4% of the starting concentration after 60 minutes. PCS extraction across the sorbent was nearly complete at any time. 2. β2M was on average reduced to 14.3% of the starting concentration after 60 minutes. Postsorbent concentrations were consistently below the validated range of the test method. We conclude that PCS and β2M are efficiently removed from the dialysate by commercially available sorbent technology. Spent peritoneal dialysis fluid can be cleared of β2M when circulated against sorbent-regenerated dialysate using a high-flux membrane.

Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: The CoRisk Study

RATIONALE: Copeptin independently predicts functional outcome and mortality at 90 days and one-year after ischemic stroke. In patients with transient ischemic attack, elevated copeptin values indicate an increased risk of further cerebrovascular events. AIMS: The Copeptin Risk Stratification (CoRisk) study aims to validate the predictive value of copeptin in patients with ischemic stroke and transient ischemic attack. In patients with ischemic stroke, the CoRisk study aims to further explore the effect of treatment (i.e. thrombolysis) on the predictive value of copeptin. DESIGN: Prospective observational multicenter study analyzing three groups of patients, i.e. patients with ischemic stroke treated with and without thrombolysis and patients with transient ischemic attack. OUTCOMES: Primary end-point: In patients with ischemic stroke, the primary end-point includes disability (modified Rankin scale from 3 to 5) and mortality (modified Rankin scale 6) at three-months after stroke. In patients with transient ischemic attack, the primary end-point is a recurrent ischemic cerebrovascular event (i.e. ischemic stroke or recurrent transient ischemic attack). Secondary end-point: In patients with ischemic stroke, the secondary end-points include in-house complications (i.e. symptomatic intracerebral hemorrhage, malignant edema, aspiration pneumonia or seizures during hospitalization, and in-house mortality).

An ice-core based history of Siberian forest fires since AD 1250

Forest fires play a key role in the global carbon cycle and thus, can affect regional and global climate. Although fires in extended areas of Russian boreal forests have a considerable influence on atmospheric greenhouse gas and soot concentrations, estimates of their impact on climate are hampered by a lack of data on the history of forest fires. Especially regions with strong continental climate are of high importance due to an intensified development of wildfires. In this study we reconstruct the fire history of Southern Siberia during the past 750 years using ice-core based nitrate, potassium, and charcoal concentration records from Belukha glacier in the continental Siberian Altai. A period of exceptionally high forest-fire activity was observed between AD 1600 and 1680, following an extremely dry period AD 1540-1600. Ice-core pollen data suggest distinct forest diebacks and the expansion of steppe in response to dry climatic conditions. Coherence with a paleoenvironmental record from the 200 km distant Siberian lake Teletskoye shows that the vegetational shift AD 1540-1680, the increase in fire activity AD 1600-1680, and the subsequent recovery of forests AD 1700 were of regional significance. Dead biomass accumulation in response to drought and high temperatures around AD 1600 probably triggered maximum forest-fire activity AD 1600-1680. The extreme dry period in the 16th century was also observed at other sites in Central Asia and is possibly associated with a persistent positive mode of the Pacific Decadal Oscillation (PDO). No significant increase in biomass burning occurred in the Altai region during the last 300 years, despite strongly increasing temperatures and human activities. Our results imply that precipitation changes controlled fire-regime and vegetation shifts in the Altai region during the past 750 years. We conclude that high sensitivity of ecosystems to occasional decadal-scale drought events may trigger unprecedented environmental reorganizations under global-warming conditions.

A multi-proxy approach for revealing recent climatic changes in the Russian Altai

For the first time we present a multi-proxy data set for the Russian Altai, consisting of Siberian larch tree-ring width (TRW), latewood density (MXD), δ13C and δ18O in cellulose chronologies obtained for the period 1779–2007 and cell wall thickness (CWT) for 1900–2008. All of these parameters agree well between each other in the high-frequency variability, while the low-frequency climate information shows systematic differences. The correlation analysis with temperature and precipitation data from the closest weather station and gridded data revealed that annual TRW, MXD, CWT, and δ13C data contain a strong summer temperature signal, while δ18O in cellulose represents a mixed summer and winter temperature and precipitation signal. The temperature and precipitation reconstructions from the Belukha ice core and Teletskoe lake sediments were used to investigate the correspondence of different independent proxies. Low frequency patterns in TRW and δ13C chronologies are consistent with temperature reconstructions from nearby Belukha ice core and Teletskoe lake sediments showing a pronounced warming trend in the last century. Their combination could be used for the regional temperature reconstruction. The long-term δ18O trend agrees with the precipitation reconstruction from the Teletskoe lake sediment indicating more humid conditions during the twentieth century. Therefore, these two proxies could be combined for the precipitation reconstruction.