TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system

Criteria for the staging and grading of neuroendocrine tumors (NETs) of midgut and hindgut origin were established at the second Consensus Conference in Frascati (Rome) organized by the European Neuroendocrine Tumor Society (ENETS). The proposed tumor-node-metastasis (TNM) classifications are based on the recently published ENETS Guidelines for the Diagnosis and Treatment of gastroenteropancreatic NETs and follow our previous proposal for foregut tumors. The new TNM classifications for NETs of the ileum, appendix, colon, and rectum, and the grading system were designed, discussed, and consensually approved by all conference participants. These proposals need to be validated and are meant to help clinicians in the stratification, treatment and follow-up of patients.

Neuro-imaging of cerebral ischemic stroke

Major progress has recently been made in the neuro-imaging of stroke as a result of improvements in imaging hardware and software. Imaging may be based on either magnetic resonance imaging (MRI) or computed tomography (CT) techniques. Imaging should provide information on the entire vascular cervical and intracranial network, from the aortic arch to the circle of Willis. Equally, it should also give information on the viability of brain tissue and brain hemodynamics. CT has the advantage in the detection of acute hemorrhage whereas MRI offers more accurate pathophysiological information in the follow-up of patients.

A Drosophila XPD model links cell cycle coordination with neuro-development and suggests links to cancer

XPD functions in transcription, DNA repair and in cell cycle control. Mutations in human XPD (also known as ERCC2) mainly cause three clinical phenotypes: xeroderma pigmentosum (XP), Cockayne syndrome (XP/CS) and trichothiodystrophy (TTD), and only XP patients have a high predisposition to developing cancer. Hence, we developed a fly model to obtain novel insights into the defects caused by individual hypomorphic alleles identified in human XP-D patients. This model revealed that the mutations that displayed the greatest in vivo UV sensitivity in Drosophila did not correlate with those that led to tumor formation in humans. Immunoprecipitations followed by targeted quantitative MS/MS analysis showed how different xpd mutations affected the formation or stability of different transcription factor IIH (TFIIH) subcomplexes. The XP mutants most clearly linked to high cancer risk, Xpd R683W and R601L, showed a reduced interaction with the core TFIIH and also an abnormal interaction with the Cdk-activating kinase (CAK) complex. Interestingly, these two XP alleles additionally displayed high levels of chromatin loss and free centrosomes during the rapid nuclear division phase of the Drosophila embryo. Finally, the xpd mutations showing defects in the coordination of cell cycle timing during the Drosophila embryonic divisions correlated with those human mutations that cause the neurodevelopmental abnormalities and developmental growth defects observed in XP/CS and TTD patients.

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.