The association of benign prostatic hyperplasia with lower urinary tract stones in adult men: A retrospective multicenter study

Objective:To examine the relationship between benign prostatic hyperplasia(BPH)and the presence of lower urinary tract stones.Methods:We retrospectively reviewed the records of men with lower urinary tract stones who presented to three clinical centers in Korea over a 4-year period.We divided the patients into two groups based on the location of urinary stones:Group 1(bladder calculi)and Group 2(urethral calculi).We compared the characteristics of both groups and performed univariate and multivariate analyses with a logistic regression model to investigate the relationship between BPH and lower urinary tract stones.Results:Of 221 patients,194(87.8%)had bladder calculi and 27(12.2%)had urethral calculi.The mean age of Group 1 was higher than that of Group 2(68.96
12.11 years vs.55.74
14.20 years,p<0.001).The mean prostate volume of Group 1 was higher than that of Group 2(44.47
27.14 mL vs.24.70
6.41 mL,respectively,p<0.001).Multivariate logistic regression showed that age(OR Z 1.075,95%CI:1.023e1.129)and prostate volume(OR Z 1.069,95%CI:1.017e1.123)were independently associated with increased risk for bladder calculi.Upper urinary tract stones and/or hydronephrosis conferred a 3-fold risk for urethral calculi(OR Z 3.468,95%CI:1.093e10.999).Conclusion:Age and prostate volume are independent risk factors for bladder calculi.In addition,men with upper urinary tract disease are at greater risk for urethral calculi,which may migrate from the upper urinary tract rather than from the bladder.

Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B

AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B.

S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis

Bone destruction induced by breast cancer metastasis causes severe complications,including death,in breast cancer patients.Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis.Tumor-derived factors play fundamental roles in this form of communication.To identify soluble factors released from cancer cells in bone metastasis,we established a highly bone-metastatic subline of MDA-MB-231 breast cancer cells.This subline(mtMDA)showed a markedly elevated ability to secrete S100A4 protein,which directly stimulated osteoclast formation via surface receptor RAGE.Recombinant S100A4 stimulated osteoclastogenesis in vitro and bone loss in vivo.Conditioned medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate osteoclasts.Furthermore,the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown cells.In addition,administration of an anti-S100A4 monoclonal antibody(mAb)that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in mice.Taken together,our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis.

A case of hypereosinophilic syndrome presenting with intractable gastric ulcers

We report a rare case of hypereosinophilic syndrome(HES)presenting with intractable gastric ulcers.A 71-year-old man was admitted with epigastric pain.Initial endoscopic findings revealed multiple,active gastric ulcers in the gastric antrum.He underwent Helicobacter pylori(H pylori)eradication therapy followed by proton pump inhibitor(PPI)therapy.However,follow-up endoscopy at 4,6,10 and 14 mo revealed persistent multiple gastric ulcers without significant improvement.The proportion of his eosinophil count increased to 43%(total count:7903/mm 3).Abdominal-pelvic and chest computed tomography scans showed multiple small nodules in the liver and both lungs.The endoscopic biopsy specimen taken from the gastric antrum revealed prominent eosinophilic infiltration,and the liver biopsy specimen also showed eosinophilic infiltration in the portal tract and sinusoid.A bone marrow biopsy disclosed eosinophilic hyperplasia as well as increased cellularity of 70%.The patient was finally diagnosed with HES involving the stomach,liver,lung,and bone marrow.When gastric ulcers do not improve despite H pylori eradication and prolonged PPI therapy,infiltrative gastric disorders such as HES should be considered.

Blockade of PD-L1/PD-1 signaling promotes osteo-/odontogenic differentiation through Ras activation

The programmed cell death ligand 1(PD-L1)and its receptor programmed cell death 1(PD-1)deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases.However,the role of PD-1 signaling and its blockade effect on human dental pulp stem cells(h DPSCs)differentiation into the osteo-/odontogenic lineage remain unknown.We show here that PD-L1 expression,but not PD-1,is downregulated during osteo-/odontogenic differentiation of h DPSCs.Importantly,PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of h DPSCs.Mechanistically,depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity,which plays a pivotal role during h DPSCs osteo-/odontogenic differentiation.Treatment with nivolumab(a human anti-PD-1 monoclonal antibody),which targets PD-1 to prevent PD-L1 binding,successfully enhanced osteo-/odontogenic differentiation of h DPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT.Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation,and h DPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation.These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in h DPSCs-mediated dental pulp regeneration.