Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding

Purpose

To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens.

Methods

Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007–2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013–2016, n = 129). The impact of 3D TRUS-guidance with pre-embedding on Gleason score (GS) concordance between biopsy and RP was evaluated using the κ-coefficient. Predictors of biopsy GS 6 upgrading were assessed using logistic regression models.

Results

Gleason concordance was comparable between the two cohorts with a κ = 0.44 for the 3D cohort, compared to κ = 0.42 for the 2D cohort. 3D TRUS-guidance with pre-embedding, did not significantly affect the risk of biopsy GS 6 upgrading in univariate and multivariate analysis.

Conclusions

3D TRUS-guidance with biopsy core pre-embedding did not improve Gleason concordance. Improved detection techniques are needed for recognition of low-grade disease upgrading.

     

Main lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in HIV-1 subtypes C and B

Journal of NeuroVirology - HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared with HIV-1B. The impact of HIV-1C Tat on the chemotaxis of the main lymphocyte...     

Effect of beta adrenergic blockade on renin response to renal nerve stimulation.

The ability of d,l-propranolol to block renin secretion in response to various extrarenal stimuli, such as hemorrhage and hypoglycemia, has been interpreted to indicate the presence of an intrarenal beta receptor regulating renin release. However, two problems complicate this interpretation: (a) the stimuli have effects outside the kidney, and (b) d,l-propranolol has a local anesthetic, as well as a beta adrenergic blocking, action. In the present study, the effects of a purely intrarenal stimulus, in the form of renal nerve stimulation (RNS), on renin secretion was examined. The effects of d,l-propranolol (anesthetic and beta-blocking activity), l-propranolol (beta-blocking activity only), and d-propranolol (local anesthetic activity only) on the renin response to RNS were examined. In a control group of animals, two sequential RNS increased mean renin secretion from 401 to 1,255 U/min (P less than 0.25) and from 220 to 2,179 U/min (P less than 0.01). In a second group the first RNS increased renin secretion from 201 to 1,181 U/min (P less than 0.01), but after d,l-propranolol was given RNS did not significantly alter renin secretion (33 to 55 U/min). In a third group the initial RNS increased renin secretion from 378 to 1,802 U/min (P less than 0.025), but after l-propranolol was given RNS had no significant effect on renin secretion (84 to 51 U/min). A fourth group of dogs showed a rise in renin secretion from 205 to 880 U/min (P less than 0.001) in response to the first RNS, while the second RNS, given after an infusion of d-propranolol, caused a rise in renin secretion from 80 to 482 (P less than 0.005). The nature of the electrical stimulus was consistent in all groups and caused no detectable changes in renal or systemic hemodynamics or in urinary electrolyte excretion. The results, therefore, indicate that renin secretion can be stimulated through intrarenal beta receptors independent of changes in systemic or renal hemodynamics or in tubular sodium reabsorption. Hence the effect of beta stimulation on renin secretion would appear to result from a direct action on the renin-secreting cells of the juxtaglomerular apparatus.     

Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels.     

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.     

Uric acid handling in autosomal dominant polycystic kidney disease with normal filtration rates

PURPOSE: Patients with autosomal dominant polycystic kidney disease (ADPKD) are alleged to have more frequent or more pronounced alterations of uric acid homeostasis than are seen in most other types of chronic renal diseases. We performed this study to examine the hypothesis that individuals with ADPKD have abnormal uric acid homeostasis that is manifest before the development of renal insufficiency. PATIENTS AND METHODS: We studied 301 subjects, 163 with ADPKD and 138 relatives without ADPKD (NADPKD), by ultrasonography. The subjects were interviewed and examined. Venous blood and two 24-hour urine collections were obtained for uric acid and creatinine determinations. RESULTS: Presence of hyperuricemia, serum uric acid levels, uric acid clearance, and fractional excretion of uric acid did not differ between ADPKD and NADPKD subjects with normal renal function (creatinine clearance greater than 80 mL/minute/1.73 m2). Clearance of uric acid decreased and fractional excretion increased in subjects with decreased renal function in both groups. Female gender enhanced renal excretion of uric acid in both groups and hypertension depressed it except in men with ADPKD, who had higher fractional excretions of uric acid than did hypertensive NADPKD men. CONCLUSIONS: Uric acid homeostasis is preserved in individuals with ADPKD with normal renal function when compared to unaffected family members. Hyperuricemia and decreased renal excretion of uric acid develop as renal function worsens in ADPKD, similar to that in control subjects. The expected depressing effect of hypertension on renal handling of uric acid was not seen in men with ADPKD, speculatively due to an effect of atrial natriuretic factor.     

Comparison of the natriuretic response to atriopeptin III and loop diuretic in the isolated perfused rat kidney

1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 microgram) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods. 2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (UNa V, 5.6 +/- 1.1 and 4.6 +/- 0.6 vs control 1.8 +/- 0.3 mumol min-1 g-1, mean +/- SEM, P less than 0.01 and P less than 0.05, respectively), fractional sodium excretion (FENa, 4.8 +/- 1.1 and 6.7 +/- 0.8 vs control 2.0 +/- 0.2%, P less than 0.05 and P less than 0.001, respectively) and potassium excretion (UKV, 3.2 +/- 0.3 and 3.0 +/- 0.3 vs control 1.5 +/- 0.3 mumol min-1 g-1, both P less than 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 +/- 55 vs 590 +/- 24 microliter min-1 g-1, P less than 0.01) and urine flow rate (V 97.5 +/- 8.0 vs 44.1 +/- 5.2 microliter min-1 g-1, P less than 0.001). Calculated distal delivery of sodium (CNa +/- CH2O, 76.6 +/- 6.8 vs 30.7 +/- 3.8 microliter min-1 g-1, P less than 0.005) as well as fractional distal delivery of sodium [(CNa +/- CH2O)/CIn, 9.4 +/- 0.9 vs 5.1 +/- 0.6%, P less than 0.01] were increased by AP-III, but not frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorenal Syndrome: Pathophysiology and Treatment

The coexistence of an acute coronary syndrome (ACS) and non-cardiac surgery (NCS) in an individual patient can be summarized in two challenging clinical scenarios for the treating physician: 1) Post-operative patients who develop ACS and 2) Patients with ACS who subsequently require NCS. Both settings are characterized by a struggle on the part of treating physicians attempting to optimize antithrombotic therapies for ACS while minimizing post-surgical bleeding risk. In this review we address specific clinical issues related to patients with coexistent NCS and ACS, discussing possible management strategies balancing ischemic and bleeding risk in these complex patient scenarios.     

Mechanism of Effect of Thoracic Inferior Vena Cava Constriction on Renal Water Excretion

Persistent secretion of vasopressin and/ or diminished distal fluid delivery have been proposed to explain the impaired water excretion associated with low-output cardiac failure. In the present investigation cardiac output (CO) was diminished in anesthetized dogs undergoing a water diuresis by constriction of the thoracic inferior vena cava (TIVC). In intact animals (group I) acute TIVC constriction decreased CO from 3.5 to 2.2 liters/min (P < 0.005) as urinary osmolality (U(osm)) increased from 103 to 543 mosmols/ kg (P < 0.001) and free water clearance (C(H2o)) decreased from 2.1 to -0.6 ml/min (P < 0.001). This antidiuretic effect was disassociated from changes in renal arterial and venous pressures, glomerular filtration rate, solute excretion, and renal innervation. To examine the role of vasopressin in this antidiuresis, studies (group II) were performed in acutely hypophysectomized, steroid-replaced animals. In these animals TIVC constriction decreased CO to a similar degree from 3.4 to 2.1 liters/min (P < 0.001). However, the effects on U(osm) (87-104 mosmols/kg) and C(H2o) (2.1-1.6 ml/min) were significantly less than in intact dogs. In another group of hypophysectomized animals, (group III) renal arterial and venous pressures were not controlled, and the effect of TIVC constriction on U(osm) was not significant (65-79 mosmols/kg) although C(H2o) decreased from 3.3 to 1.9 ml/min (P < 0.001). In both the group II and III studies, there were linear correlations between the changes in C(H2o) and the urine flow. Studies were also performed in baroreceptor-denervated animals with intact hypothalamo-neurohypophyseal tracts, and acute TIVC constriction altered neither U(osm) nor C(H2o) when renal arterial pressure was controlled. These results therefore indicate that the effect of TIVC constriction on U(osm) is primarily vasopressin mediated while the effect on C(H2o) is mediated both by vasopressin release and diminished distal fluid delivery. A decrease in renal arterial pressure, or some consequence thereof, seems to be an important determinant of the latter effect.