The V2 receptor antagonist tolvaptan counteracts proliferation and invasivity in human cancer cells.

PURPOSE: Hyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V2) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours [i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS)]. METHODS AND RESULTS: First, we showed that these cell lines express the V2 receptor. Tolvaptan significantly reduced cell proliferation with an IC50 in the micromolar range. Accordingly, reduced levels of cAMP, of the catalytic α subunit of PKA, and a reduced pAKT/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA/ROCK1-2 pathway, which has a pivotal role in regulating cell movement. CONCLUSIONS: Overall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V2 receptor might be considered a possible target in anti-cancer strategies in the future.

Can fifth nerve mapping guide rhizotomy for recurrent trigeminal neuralgia? Case report.

INTRODUCTION: Microvascular decompression (MVD) is usually considered the first-line treatment for trigeminal neuralgia (TN) when medical treatments fail. Recurrence is rare and best treatment option is controversial. MVD was proposed as a feasible and effective technique for recurrent TN by many authors. Nevertheless, in a substantial number of cases, not any impingement or deterioration are found intraoperatively and partial selective rhizotomy is then advised. The rhizotomy site is mostly guided by anatomical landmarks, but variations due to scarring and adhesions are common pitfalls in these second surgeries. Intraoperative monitoring is infrequently used during MVD for trigeminal neuralgia. We describe the use of nerve mapping in a case of recurrence, revealing an unexpected rootlet distribution and thus safely guiding partial rhizotomy. CLINICAL PRESENTATION: A 53-year-old woman had suffered from bilateral trigeminal neuralgia for 10 years. Symptoms began on the right side. MVD resolved her symptoms but, after a few months, she developed left TN which persisted after left MVD, radiofrequency and radiosurgery. She was referred to our center for a second MVD on the left side. Intraoperative inspection detected no relevant findings, and nerve mapping followed by partial selective rhizotomy was performed. Complete pain relief was achieved. There were no complications. CONCLUSION: Rhizotomy is seldom employed for refractory trigeminal neuralgia. The effects of previous treatments can jeopardize anatomical landmarks. Nerve mapping seems a promising tool to improve results.

Pain-related middle-latency somatosensory evoked potentials in the prognosis of post anoxic coma: a preliminary report.

BACKGROUND: Regarding hypoxic-ischemic encephalopathy, while the bilateral absence of N20/P25 somatosensory evoked potentials (SEPs) is considered to be the best indicator of adverse outcomes, the presence of middle latency evoked potentials (MLCEPs) is associated with a favourable neurological prognosis. The main aim of the present study was to investigate whether painful electrical stimulation might be considered a provocative test in producing MLCEPs and predictor of patient's outcomes after cardiac arrest. METHODS: Retrospective pilot study. SEPs with and without pain-related electrical stimulation in both median nerves were recorded in 17 patients with post anoxic coma after cardiac arrest. Glasgow Coma Scale, electroencephalograms, heart rate and blood pressure changes were also recorded at the same time. Three months after cardiac arrest the same measures with inclusion of Glasgow Outcome Scale Extended were also performed only in the remaining patients with severe neurological outcome. No one intervention was made. RESULTS: Patients who showed MLCEPs had a good outcome, while patients without N20/P25 SEPs but with increases in blood pressure remained in a vegetative state. Patients who did not show N20/P25 SEPs and increase in blood pressure died within one week. Only one patient who showed N20/P25 SEPs was minimally conscious. CONCLUSION: These preliminary data suggest that MLCEPs elicited by painful electrical stimulation seem to be a sensitive method to predict the neurological outcome of patients in the acute phase of coma. Blood pressure response might be a prognostic physiological measure of survival in the vegetative state in patients without N20/P25 SEPs.

The role of asymmetry and the nature of microembolization in cognitive decline after heart valve surgery: a pilot study.

Our objective was to determine the role of asymmetry and the nature of microembolization on postoperative cognitive decline in patients who had undergone heart valve surgery. Continuous transcranial Doppler ultrasound was intraoperatively used for both middle cerebral arteries in 13 right-handed heart valve surgery patients to detect microembolization. The Trail Making Test A and B, Memory with 10/30 s interference, the Digit Span Test and Phonemic Fluency were performed preoperatively, at discharge and three months after surgery. Our data suggest that early and late postoperative psychomotor and executive functions may be sensitive to microemboli in the left, but not in the right middle cerebral artery. Moreover, solid and gaseous microemboli are both similarly associated with early postoperative cognitive decline while, surprisingly, late postoperative cognitive decline is more likely to be associated with gaseous than solid microemboli.