Citations

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA‐containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in‐person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

Object Resection of cancer and the involved artery in the neck has been applied with some success, but the indications for such an aggressive approach at the skull base are less well defined. The authors therefore evaluated the outcomes of advanced skull base malignancies in patients who were treated with bypass and resection of the internal carotid artery (ICA). Methods The authors retrospectively reviewed the charts of all patients with advanced head and neck cancers who underwent ICA sacrifice with revascularization in which an extracranial-intracranial bypass was used between 1995 and 2010 at the Barrow Neurological Institute. Results Eighteen patients (11 male and 7 female patients; mean age 46 years, range 7–69 years) were identified. There were 4 sarcomas and 14 carcinomas that involved the ICA at the skull base. All patients underwent ICA sacrifice with revascularization. One patient died of a stroke after revascularization. A second patient died of the effects of a fistula between the oral and cranial cavities (surgery-related mortality rate 11.1%). Eight months after the operation, 1 patient developed occlusion of the bypass and died. Complications associated with the bypass surgery included 1 case of subdural hematoma (SDH) with blindness, 1 case of status epilepticus, and 1 case of asymptomatic bypass occlusion (bypass-related morbidity 16.7%). Complications associated with tumor resection included 3 cases of CSF leakage requiring repair and shunting, 1 case of hydrocephalus requiring shunting, 1 case of SDH, and 1 case of contralateral ICA injury requiring a bypass (tumor resection morbidity rate 33.3%). In 1 patient treated with adjuvant therapy before surgery, the authors identified only a radiation effect and no tumor on resection. In a second patient the bypass was occluded, and her tumor was not resected. The other 16 patients underwent gross-total resection of their tumor. Excluding the surgery-related deaths, the mean and median lengths of survival in this series were 13.2 and 8.3 months, respectively (range 1.5–48 months). Including the surgery-related deaths, the mean and median lengths of survival were 11.8 and 8 months, respectively (range 17 days–48 months). At last follow-up all patients had died of cancer or cancer-related causes. Conclusions Despite maximal surgical intervention, including ICA sacrifice at the skull base with revascularization, patient survival was dismal, and the complication rate was significant. The authors no longer advocate such an aggressive approach in this patient population. On rare occasions, however, such an approach may be considered for low-grade malignancies.