Dutasteride, a 5 alpha reductase inhibitor, could be associated with the exacerbation of inflammation in patients with benign prostatic hyperplasia.

BACKGROUND: α-1 blockers and dutasteride are widely used as agents to treat benign prostatic hyperplasia (BPH); the impact of these drugs on prostatic inflammation is still unclear. Herein, we investigated the impact of α-1 blockers and dutasteride treatment of BPH in terms of the degree of prostatic inflammation. MATERIALS AND METHODS: Tissue specimens were obtained from 143 BPH patients who were administered α-1 blockers up until their operation. Thirty-three of the patients had also been treated with dutasteride before the procedure. The degree of prostatic inflammation was quantified histologically by the ratio of high endothelial venule (HEV)-like vessels. We divided this retrospective cohort into α-1 blocker monotherapy and combination therapy (α-1 blockers + dutasteride) groups and evaluated clinical parameters of the two groups in relation to the degree of chronic prostatic inflammation. At the same time, we assessed factors exacerbating chronic prostatic inflammation. RESULTS: Comparison of the monotherapy and combination therapy groups showed no significant differences in the parameters of the urodynamic study or degree of chronic prostatic inflammation, whereas the IPSS total score, voiding subscore, nocturia, intermittency, weak stream, and straining were significantly lower in the combination than the monotherapy group. The duration of α-1 blockers administration was not correlated with the ratio of HEV-like vessels, while that of dutasteride was strongly correlated (correlation coefficient = 0.595; p < 0.001). Multiple regression analysis demonstrated that the duration of dutasteride administration was a key factor exacerbating the degree of chronic prostatic inflammation. CONCLUSIONS: The present study showed that despite their ameliorating effect on prostatic hyperplasia, dutasteride contributed significantly to chronic prostatic inflammation.

Preferential expression of sialyl 6'-sulfo N-acetyllactosamine-capped O-glycans on high endothelial venules in human peripheral lymph nodes.

Lymphocyte "homing", the physiologic trafficking of lymphocytes from the circulation to secondary lymphoid organs, is regulated by sequential adhesive interactions between lymphocytes and endothelial cells that constitute high endothelial venules (HEVs). Initial lymphocyte "rolling" is mediated by relatively weak, transient adhesive interactions between L-selectin expressed on lymphocytes and sulfated mucin-type O-glycans expressed on HEVs. Keratan sulfate galactose (Gal)-6-O-sulfotransferase (KSGal6ST) catalyzes 6-O-sulfation of Gal in keratan sulfate glycosaminoglycan chains but also transfers sulfate to Gal in much shorter glycan chains, such as sialylated N-acetyllactosamine (LacNAc)-capped O-glycans. In mice, KSGal6ST is reportedly expressed in HEVs and functions in synthesizing 6-sulfo Gal-containing O-glycans on HEVs. However, in humans, the presence of 6-sulfo Gal-containing O-glycans on HEVs is not reported. Employing the newly developed monoclonal antibody 297-11A, which recognizes non-sialylated terminal 6'-sulfo LacNAc, we demonstrate that sialyl 6'-sulfo (and/or 6,6'-disulfo) LacNAc-capped O-glycans are preferentially displayed on HEVs in human peripheral lymph nodes (PLNs) and to a lesser extent in mesenteric LNs (MLNs) but not in Peyer's patches (PPs). We also found that the scaffold protein mucosal addressin cell adhesion molecule 1 (MAdCAM-1), which is expressed on HEVs in PPs and MLNs but not PLNs, was modified by 297-11A-positive sulfated glycans less efficiently than was CD34. Moreover, 297-11A-positive sulfated glycans were also displayed on HEV-like vessels induced in tumor-infiltrating lymphocyte (TIL) aggregates formed in various cancers. These findings collectively indicate that 297-11A-positive sulfated glycans potentially play a role in physiologic lymphocyte homing as well as in lymphocyte recruitment under pathologic conditions.

Serum C-reactive protein level is not associated with prostatic inflammation but with overactive detrusor in patients with benign prostatic hyperplasia.

AIM: Chronic prostatic inflammation is a critical factor that exacerbates lower urinary tract symptoms (LUTS). The serum C-reactive protein (CRP) level is one of the most common markers with which to assess the degree of inflammation, and it has been reported to be related to the severity of LUTS. However, it is not clear whether the CRP level is linked to the magnitude of prostatic inflammation. We evaluated the relationship between the serum CRP level and the magnitude of prostatic inflammation and assessed the influence of CRP on the severity of LUTS. METHODS: We evaluated the tissue specimens of 121 benign prostatic hyperplasia (BPH) patients who underwent surgery for BPH and preoperative measurement of the serum CRP level. We quantified the magnitude of prostatic inflammation histologically by determining the number of high endothelial venule (HEV)-like vessels and assessed the relationship between the serum CRP level and the HEV-like vessels. We divided the patients into two groups based on the median serum CRP level and compared the clinical parameters of the two groups. RESULTS: The serum CRP level was correlated with the overactive bladder symptom score, whereas it was not correlated with the number of HEV-like vessels. In filling cystometry and pressure-flow study, the proportion of patients with detrusor overactivity in the higher-CRP group was higher than that in the lower-CRP group. CONCLUSIONS: Our present study showed that the serum CRP level was significantly associated with storage dysfunction; in contrast, it was not a surrogate marker of prostatic inflammation.

Prostatic stromal inflammation is associated with bladder outlet obstruction in patients with benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urologic disease in older men. Prostatic inflammation research has focused on the magnitude of inflammation; its location has received little attention. We investigated whether the anatomic location of prostatic inflammation is related to the severity of lower urinary tract symptoms (LUTS), measured subjectively and objectively. METHODS: We retrospectively analyzed hematoxylin+eosin-stained tissue specimens from 179 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). Chronic prostatic inflammation was assessed by the grade (lymphocyte density), extent (lymphocyte distribution), and location of inflammation. Each inflammation-finding type was evaluated in relation to these clinical parameters: age, prostate volume, prostate-specific antigen (PSA) value, body mass index (BMI), the frequency of acute urinary retention (AUR) episodes, the international prostatic symptom score (IPSS), and urodynamic study results. RESULTS: The magnitude and extent of inflammation were not associated with any clinical parameters. We classified the BPH patients into stromal (n = 72) versus non-stromal (n = 105) groups based on their inflammation's dominant location. The stromal group's prostatic volume was significantly larger than the non-stromal group's (63.8 vs 53.8 mL; P = 0.032). AUR episodes were more significantly frequent in the stromal group (36.1% vs 11.4%; P = 0.006). Between-group differences in storage parameters (ie, maximum cystometric capacity) in the urodynamic study were not significantly different. Voiding parameters differed significantly between the stromal and non-stromal groups: maximum detrusor pressure (maxPdet) (116.8 vs 94.5 cmH2 O, P = 0.014), Pdet at the maximum flow rate (Qmax) (95.8 vs 75.4 cmH2 O, P = 0.014), and the bladder outlet obstruction index (BOOI) (78.5 vs 56.3, P = 0.014). The stromal group's Qmax was significantly lower than the non-stromal group's (7.3 vs 9.8 mL/s, P = 0.004). CONCLUSIONS: The location of inflammation in the prostate might be an important factor affecting the severity of LUTS, especially voiding dysfunction.