Multiparametric MRI with in-bore targeted biopsy in the diagnostic pathway of prostate cancer: Data from a single institution experience.

BACKGROUND: Accuracy of multiparametric MRI (mpMRI) for the detection of significant prostate cancer (CaP) varies in the literature as only few studies use radical prostatectomy specimens as their gold standard. On another hand, MRI-targeted prostate biopsy is emerging as an alternative to the traditional randomized biopsy, with a higher detection rate of high-grade cancers. However, data on MRI guided in bore biopsy is lacking. MATERIAL AND METHODS: We reviewed every patient that had his mpMRI, MRI guided in bore biopsy and radical prostatectomy performed in our hospital between November 2015 and December 2020. The diagnostic performances of both mpMRI and MRI targeted biopsy in sampling PIRADS index lesions were studied, using radical prostatectomy specimens as the gold standard. Sensitivity, specificity, positive predictive value and negative predictive value of mpMRI for detecting T3 stage, extra-capsular extension, seminal vesicles involvement and lymph node disease were also evaluated. RESULTS: Sixty-two met our inclusion criteria. For PIRADS≥3 lesions, sensitivity and positive predictive value for detecting clinically significant CaP were of 83.5% and 94.7%. A total of 32.2% prostate cancers on targeted biopsy were upgraded on final pathology, with an upgrading to ISUP≥2 in 3.2% and to ISUP≥3 in 14.5%. A total of 20.9% of cancers were downgraded but without any downgrading to ISUP 1. When final pathology is taken as a gold standard, sensitivity of mpMRI was 31.8% for T3 staging prediction, 30.0% for extra-capsular extension, 28.7% for seminal vesicles involvement and 66.7% for lymph node disease prediction. Specificity was 89.3%, 93.1%, 95.3%, and 92.7%, respectively. CONCLUSION: mpMRI has an acceptable accuracy for the prediction of significant CaP and index lesion detection but is unreliable for CaP staging. Comparison between pathology and biopsy results revealed that the in-bore biopsy technique has an upgrading and downgrading rate comparable in the literature to fusion biopsy, but higher than the combined biopsy approach.

Adenovirus Infection as a Cause of Fever of Unknown Origin and Allograft Dysfunction in a Kidney Transplant Recipient.

With the recent introduction of more potent modern immunosuppressive regimens in solid-organ transplant, new types of viral infections such as adenovirus are emerging as a potential cause for graft dysfunction and loss. We report a case of 41-year-old male patient with end-stage renal disease from recurrent kidney stones who underwent kidney transplant from a deceased 12-year-old female donor. He developed adenoviral infection with acute cystitis, microscopic hematuria, and necrotizing interstitial nephritis associated with graft dysfunction within the first month of the postoperative period. Diagnosis was made by graft biopsy that showed more than 60% necrosis with tubulointerstitial hemorrhage, thrombotic microangiopathy, and histologic features suggestive of viral infection with negative Cytomegalovirus and polyomavirus stains in the graft and elevated adenovirus PCR in the blood. Simultaneously, the patient had very low absolute total lymphocyte count of 70 cells/µL during which he received supratherapeutic tacrolimus at whole blood trough levels and mycophenolate mofetil. This prompted the tapering of immunosuppression and the discontinuation of all antimicrobial drugs. Within a 2-week period, the immune reconstitution was sufficient for the clearance of the infection and the subsequent gradual recovery of graft function.

Bortezomib as a Novel Approach to Early Recurrent Membranous Glomerulonephritis After Kidney Transplant Refractory to Combined Conventional Rituximab Therapy.

We report a case of early recurrent membranous glomerulonephritis after kidney transplant from a deceased donor. The patient received induction therapy and was discharged with a serum creatinine level of 0.78 mg/dL on triple maintenance immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and prednisone. At 7 months after transplant, a graft biopsy for new-onset isolated proteinuria (2.7 g/day) revealed stage 2 recurrent membranous glomerulonephritis. In the face of persistent proteinuria despite combined conservative rituximab therapy over several months and the total eradication of CD20-positive cells, bortezomib was introduced. This resulted in a substantial decline in proteinuria within 2 months and its subsequent disappearance several months later. This was paralleled by a considerable drop in plasma CD34-positive and CD138-positive cell counts. These preliminary observations indicate that recurrent posttransplant membranous glomerulonephritis is associated in part with a B-cell- mediated immunologic process that may involve both CD20-positive and plasma cells. Rituximab-resistant or partially responsive recurrent posttransplant membranous glomerulonephritis may benefit from a proteasome inhibitor-based therapy.

Mammalian Target of Rapamycin Inhibitors and Nephrotoxicity: Fact or Fiction.

Mammalian target of rapamycin inhibitors, such as rapamycin and more recently everolimus, have substituted calcineurin inhibitors in many minimization strategies. Despite their acclaimed renal safety profile, several lines of evidence are emerging on their potential nephrotoxic effect. Predisposing conditions for nephrotoxicity involve a complex interplay between several environmental and genetic factors in the donor-recipient pair. Renal injury may be enhanced by pharmacodynamic interactions when combined with other drugs such as calcineurin inhibitors or nutrients that are predominantly related to an increase in local tissue exposure. These toxic interactions may occur within adequate doses and therapeutic blood levels. This explains the occurrence of nephrotoxicity in some but not all cases. Here, we postulated that activity of a low permeability glycoprotein efflux pump related to low protein expression and/or inhibition enhanced immunosuppressive drug entry in different cells. A rise in intracellular drug concentration increases bioactivity, leading to greater immunosuppression and more immune-related, nonrenal adverse events in the recipient and increased nephrotoxicity in the kidney graft. Under specific isolated or combined environmental and/or genetic conditions in both the recipient and donor affecting the glycoprotein efflux pump and/or the mammalian target of rapamycin pathway, these renal injuries may be aggravated by heightened drug tissue concentrations despite adherence to therapeutic drug and blood levels. Mammalian target of rapamycin inhibitors may induce predominantly a dose-dependent renal epithelial cell injury affecting either the glomerular or the renal tubular epithelial cells, leading to cell death and apoptosis. Epithelial mesenchymal transition mediated interstitial fibrosis and tubular atrophy observed with these drugs may be the result of a cumulative toxic renal tubular injury induced by the direct insult of the drug itself and/or podocytopathy-associated proteinuria. The resulting glomerular tubular damage will ultimately lead to graft failure and loss, if exposure persists.

Cyclosporine lymphocyte maximum level: a new alternative for cyclosporine monitoring in kidney transplantation.

OBJECTIVES: To determine the relationship between clinical outcome, lymphocyte count (LC), and cyclosporine (CsA) lymphocyte maximum level (LT(m)L) in kidney transplant recipients. MATERIALS AND METHODS: CsA LT(m)L was determined in patients with biopsy-proven graft dysfunction and in patients with normal graft function. Clinical outcome was compared according to CsA LT(m)L, dosage, blood trough (C(0)) and maximum (C(max)) levels, hematocrit level, and LC. RESULTS: Rejecting patients had significantly lower LT(m)L than did those with normal graft function (27 -/+ 11 pg/Lc vs 71 -/+ 79 pg/Lc; P < 0.01) and similar LTmL to those with nephrotoxicity (27 -/+ 8 pg/Lc). Patients with normal graft function exhibited significantly lower LC (0.001292 -/+ 696 x 10(9)/L) and serum creatinine levels (88.4 -/+ 35 micromol/L) when compared with rejecting patients (0.001717 -/+ 364 x 10(9)/L, 132.6 -/+ 8.8 micromol/L) and those with nephrotoxicity (0.001884 -/+ 582 x 10(9)/L, 123.7 -/+ 8.8 micromol/L) (P < 0.03, P < 0.001). No significant difference was observed among the 3 groups with regard to CsA dosage, C(0), C(max), mycophenolate mofetil (MMF) dosage, and mycophenolic acid (MPA) plasma levels. CsA LT(m)L closely correlated in an exponential (R(2) = 0.98) and linear (R(2) = 0.35) fashion with LC and hematocrit level, respectively. Conversely, CsA C(max) failed to correlate with C(0) and these 2 latter parameters. Weak correlations were observed between CsA C(max) and its corresponding LT(m)L. CONCLUSIONS: CsA LT(m)L appears to correlate better than CsA C(max) with rejection-free outcome and LC. An increase in hematocrit appears to have an adverse effect on CsA lymphocyte binding. CsA LT(m)L may offer a new alternative for CsA monitoring in kidney transplantation.