DW-MRI predictive factors for radiation-induced vaginal stenosis in patients with cervical cancer.

AIM: To find diffusion-weighted (DW) magnetic resonance imaging (MRI) parameters predictive for radiation-induced vaginal stenosis (VS) in locally advanced cervical cancer (LACC) treated with neoadjuvant chemoradiation therapy (CRT). MATERIALS AND METHODS: Retrospective analysis of 43 patients with LACC who underwent 1.5 T DW-MRI before (baseline), after 2 weeks (early), and at the end of CRT (final). At MRI, vaginal length, thickness, width, and cervical tumour volume (TV) were measured. Vaginal signal intensity at DW-MRI was analysed at final MRI. CRT-induced VS was graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Correlations between DW-MRI and clinical data were made using Wilcoxon's test, Mann-Whitney test, Fisher's exact test, or chi-squared test as appropriate. Receiver operating characteristic (ROC) curves were generated for variables to evaluate diagnostic ability to predict CRT-induced VS using a logistic regression model. RESULTS: Asymptomatic vaginal toxicity (CTCAE Grade 1) was observed in 14 patients and symptomatic CRT-induced VS (CTCAE Grade ≥2) was detected in 29 patients. Baseline TV was higher in Grade 1 than in Grade ≥2 (p=0.013). Median vaginal length, thickness, and width decreased between baseline and final MRI in all patients (p<0.0001) without significant variances between CTCAE grades. Significant differences were observed in DW-MRI patterns (p<0.0001). In Grade ≥2, DWI showed signal loss of vaginal mucosa in 17 patients (63%) and diffuse restricted diffusion of vaginal wall in eight patients (30%). AUC was 0.938 (coefficient=4.72; p<0.001) for DWI and 0.712 (coefficient=-2.623×10 -5; p=0.004) for TV. CONCLUSIONS: This is the first study using DW-MRI for predicting CRT-induced VS. DWI is useful tool in patients with LACC after CRT for early prevention and management strategies for VS.

Endothelin-A blockade attenuates systemic and renal hemodynamic effects of L-NAME in humans.

Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either N(G)-nitro-L-arginine methyl ester (L-NAME) 3.0 mg. kg(-1). min(-1) or endothelin-A receptor (ET-A) blocker BQ-123 (BQ) 0.125 nmol. kg(-1). min(-1) or both. Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistances (RVR), and sodium excretion rate (UNaV) were measured at baseline (b) and from 0 to 45 minutes (period 1) and 45 to 90 minutes (period 2) of infusion. BQ alone had no effect. GFR declined by 4.9% (P<0.001 versus b) in period 1, to 9.9% (P<0. 001) in period 2 with L-NAME, and by 3.3% (P<0.01) to 6.6% (P<0.001) with L-NAME plus BQ (P=NS between L-NAME and L-NAME plus BQ). UNaV fell equally with L-NAME or L-NAME plus BQ. MAP rose significantly in period 2 with L-NAME (6.9%; P<0.001) but not with coinfused BQ (2. 1%; P=NA versus b, P=0.005 versus L-NAME alone). RBF declined by 12. 2% (P<0.001) to 18.3% (P<0.001) with L-NAME and by 4.6% (P<0.005) to 8.2% (P<0.001) with L-NAME plus BQ. These changes were smaller with L-NAME plus BQ (P<0.05 in period 1 and P<0.02 in period 2). Blunted changes were also seen for RVR (P<0.005 in period 1 and P<0.001 in period 2 between L-NAME alone and L-NAME plus BQ). These findings show that systemic and renal vasoconstriction due to L-NAME are attenuated by BQ, which suggests that an interaction between endogenous nitric oxide production and ET-A activity participates in the maintenance of baseline systemic and renal vascular tone in humans.

A new diagnostic test for primary aldosteronism.

Isotonic-isooncotic central volume expansion by head-out water immersion was induced in six aldosterone-producing adenoma subjects and in six patients with idiopathic hyperaldosteronism. Plasma renin activity and plasma aldosterone levels did not significantly change during water immersion while serum cortisol was significantly suppressed (P less than .001) and the aldosterone-cortisol ratio increased (P less than .02) in aldosterone-producing adenoma patients. Water immersion also revealed the failure of plasma aldosterone levels to decrease below 10 ng/dL in these subjects, thus confirming previous results obtained during isotonic saline infusion. Otherwise, plasma renin activity and plasma aldosterone were significantly reduced (P less than .05 and P less than .01 respectively) by water immersion and plasma aldosterone invariably fell below 10 ng/dL in patients with idiopathic aldosteronism. In view of the diagnostic reliability of such a suppression test we conclude that water immersion is suitable for discriminating between the two forms of primary aldosteronism. We therefore suggest its use for assessing renin-aldosterone responsiveness in primary aldosteronism.

Sodium homeostasis and hormonal responses during dopaminergic blockade in normal humans.

Six normal subjects were submitted to 2 h water immersion (WI) with and without pharmacological dopaminergic (DA) blockade with metoclopramide (MCP). Urinary sodium excretion showed a marked increase during WI alone while it was blunted during WI plus DA blockade. Plasma aldosterone was significantly suppressed by WI alone but remained unchanged during WI plus MCP. Plasma atrial natriuretic factor showed similar augmentation during WI alone and during WI plus MCP. The reduced sodium and 6-keto-PGF1 alpha excretion, observed during WI plus MCP administration, suggests that dopamine might induce prostacyclin synthesis in the kidney during WI.