The significance of angiogenesis in malignant pheochromocytomas

The purpose of this study was to investigate tumor angiogenesis in a series of benign and malignant pheochromocytomas and to determine whether there is a correlation between angiogenesis and the presence of distant metastases. In this study, the CD31 monoclonal antibody was selected to measure intratumoral microvessel density. Nineteen patients with malignant pheochromocytomas and nineteen patients with benign pheochromocytomas who underwent operation were studied. In order to quantify intratumoral microvessel density, the total number of pixels of CD31-positive reactivity was assessed and expressed as a percentage of the total tissue area in the analyzed field. Analysis of variance revealed a statistically significant correlation between malignancy and intratumoral microvessel density (p=0.0009). Although there was a considerable variability in the intratumoral microvessel density from tumor to tumor within both the benign and the malignant group, a percentage of more than 28.5% anti-CD31 stained area was found only in malignant tumors. In conclusion, this study shows that the mean intratumoral microvessel density in malignant pheochromocytomas is increased approximately two-fold as compared with benign tumors. However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvesel density higher than this threshold of 28.5%.     

Tackling the scaling-up problem of digital health applications

Journal of Public Health - The purpose of this editorial is to provide guidance for the readers concerning the broad realm of approaches towards successful implementation of digital health...     

Revision of gastrointestinal mesenchymal tumours with CD117.

BACKGROUND: Tyrosinekinase inhibitors improve the treatment of gastrointestinal stromal tumours (GISTs) and their diagnosis has been facilitated by recently developed immunohistochemical markers. It is hypothesised that in the past, the true incidence of GISTs has been underestimated. AIMS: To study the clinicopathological features of previously resected mesenchymal tumours of the gastrointestinal tract and determine the accuracy of previous diagnostic results. PATIENTS AND METHODS: Patients with mesenchymal tumours of the gastrointestinal tract operated on between 1987 and 2002 were identified using medical and pathologic files. Immunohistochemical staining for CD117, CD34, desmin and S100 was performed, and diagnosis reviewed. RESULTS: Thirty-six mesenchymal tumours were reanalysed. Before revision, diagnosis of GIST was correctly made in only six cases. Supportive use of immunohistochemical markers for accurate diagnosis of the remaining 30 previously undefined mesenchymal tumours yielded 17 additional GISTs. Therefore, 23 of 36 (63%) gastrointestinal mesenchymal tumours were shown to be GISTs. CONCLUSIONS: The true incidence of GISTs has been underestimated. There is merit in reviewing the clinical diagnoses of all mesenchymal tumours of the gastrointestinal tract with modern immunohistochemical markers. This may enhance clinical decision making.     

Disagreement between splenic switch-off and myocardial T1-mapping after caffeine intake

Caffeine is an adenosine receptor antagonist and a possible cause of inadequate stress perfusion. Splenic switch-off (SSO) and splenic rest-stress T1-mapping have been proposed as indicators of stress adequacy during perfusion cardiac magnetic resonance (CMR). We compared myocardial rest-stress T1-mapping with SSO and splenic rest-stress T1-mapping in patients with and without recent coffee intake. We analyzed 344 consecutive patients suspected of myocardial ischemia with adenosine perfusion CMR. All 146 normal CMR studies with a normal T1-rest of the myocardium, used as standard of reference, were included and divided in two groups. 22 patients accidentally ingested coffee <?4 h before CMR, compared to control group of 124 patients without self-reported coffee intake. Two independent readers graded SSO visually. T1-reactivity (ΔT1) was defined as percentual difference in T1-rest and T1-stress. Follow-up data were extracted from electronic patients records. In patients with recent coffee intake SSO was identified in 96%, which showed no significant difference with SSO in controls (94%, p?=?0.835), however event rates were significantly different (13.6 and 0.8%, respectively (p?<?0.001), median FU 17 months). Myocardial ΔT1 in the coffee group (??5.2%) was significantly lower compared to control (+?4.0%, p?<?0.001), in contrast to the splenic ΔT1 (??3.7 and ??4.0%, p?=?0.789). The splenic T1-mapping results failed to predict false negative results. SSO and splenic rest-stress T1-mapping are not reliable indicators of stress adequacy in patients with recent coffee intake. Therefore, the dark spleen sign does not indicate adequate myocardial stress in patients with recent caffeine intake. Myocardial rest-stress T1-mapping is an excellent indicator of stress adequacy during adenosine perfusion CMR.     

Imaging the myocardial ischemic cascade

Non-invasive imaging plays a growing role in the diagnosis and management of ischemic heart disease from its earliest manifestations of endothelial dysfunction to myocardial infarction along the myocardial ischemic cascade. Experts representing the North American Society for Cardiovascular Imaging and the European Society of Cardiac Radiology have worked together to organize the role of non-invasive imaging along the framework of the ischemic cascade. The current status of non-invasive imaging for ischemic heart disease is reviewed along with the role of imaging for guiding surgical planning. The issue of cost effectiveness is also considered. Preclinical disease is primarily assessed through the coronary artery calcium score and used for risk assessment. Once the patient becomes symptomatic, other imaging tests including echocardiography, CCTA, SPECT, PET and CMR may be useful. CCTA appears to be a cost-effective gatekeeper. Post infarction CMR and PET are the preferred modalities. Imaging is increasingly used for surgical planning of patients who may require coronary artery bypass.     

Local gentamicin reduces perineal wound infection after radiotherapy and abdominoperineal resection

Background  

Perineal wound complications are frequently observed after abdominoperineal resection (APR) for rectal cancer, especially in preoperatively irradiated patients. This is the first study to investigate whether local application of gentamicin-impregnated collagen fleece reduces deep perineal wound infection after APR for rectal cancer following short-term radiotherapy.     

Variation in hospital mortality after pancreatoduodenectomy is related to failure to rescue rather than major complications: a nationwide audit

Background

In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated.

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.