Obese men have more advanced and more aggressive prostate cancer at time of surgery than non-obese men after adjusting for screening PSA level and age: results from two independent nested case-control studies.

BACKGROUND: It remains unclear whether the hemodilution effect of body mass index (BMI) on PSA levels translates to inappropriate prostate cancer (PCa) screening in obese men. To address this, we conducted two nested case-control studies within prospective cohorts of men undergoing radical prostatectomy for newly diagnosed PCa. METHODS: We identified 1817 men with BMI 30 kg m(-2) (cases) and 1244 men with BMI <25 kg m(-2) (controls) who underwent surgery to treat PCa at Mayo Clinic in Rochester between 2000 and 2009. Cases and controls were frequency matched on age and PSA level. In a similar manner, we identified 206 cases and 133 controls treated at Mayo Clinic in Florida between 2006 and 2011. We employed logistic regression models to evaluate the association of pathologic features of aggressiveness with obesity status. RESULTS: After adjusting for age and PSA level, we noted that obese men in the Rochester population are more likely to present with Gleason grade 8-10 tumors (OR= 1.50; 95% CI 1.14-1.96; P=0.003) and pT3, pT4, pTxN+ stage disease (OR=1.30; 95% CI 1.05-1.62). We noted a similar association seminal vesicle involvement (OR= 1.41; 95% CI 1.03-1.92; P=0.03). Results from the smaller Florida population supported these same associations but did not achieve conventional statistical significance. CONCLUSIONS: Obese men present with more aggressive PCa tumors compared with non-obese men of similar age and PSA screening values. If confirmed, this would support the need to explore PSA-based screening in obese men to possibly account for a hemodilution effect.

Dual-energy CT for the evaluation of urinary calculi: image interpretation, pitfalls and stone mimics.

Urolithiasis is a common disease with a reported prevalence between 4% and 20% in developed countries. Determination of urinary calculi composition is a key factor in preoperative evaluation, treatment, and stone recurrence prevention. Prior to the introduction of dual-energy computed tomography (DECT), available methods for determining urinary stone composition were only available after stone extraction, and thereby unable to aid in optimized stone management prior to intervention. DECT utilizes the attenuation difference produced by two different x-ray energy spectra to quantify urinary calculi composition as uric acid or non-uric acid (with likely further classification in the future) while still providing the information attained with a conventional CT. Knowledge of DECT imaging pitfalls and stone mimics is important, as the added benefit of dual-energy analysis is the determination of stone composition, which in turn affects all aspects of stone management. This review briefly describes DECT principles, scanner types and acquisition protocols for the evaluation of urinary calculi as they relate to imaging pitfalls (inconsistent characterization of small stones, small dual-energy field of view, and mischaracterization from surrounding material) and stone mimics (drainage devices) that may adversely impact clinical decisions. We utilize our clinical experience from scanning over 1200 patients with this new imaging technique to present clinically relevant examples of imaging pitfalls and possible mechanisms for resolution.

'Born in Michigan? You're in the biobank': engaging population biobank participants through Facebook advertisements.

BACKGROUND/AIMS: Despite a broad call for biobanks to use social media, data is lacking regarding the capacity of social media tools, especially advertising, to engage large populations on this topic. METHODS: We used Facebook advertising to engage Michigan residents about the BioTrust for Health. We conducted a low-budget (

High predictability of a sustained virological response (87%) in chronic hepatitis C virus genotype 1 infection treatment by combined IL28B genotype analysis and γ-glutamyltransferase/alanine aminotransferase ratio: a retrospective single-center study.

BACKGROUND: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-α and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. METHODS: Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. RESULTS: The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low γ-glutamyltransferase (γ-GT) serum activities, a low pretreatment γ-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1-16.7, p < 0.001), low pretreatment γ-GT/ALT ratio (OR = 2.5, CI: 1.7-3.3, p < 0.001), age (OR = 0.96, CI: 0.94-0.98, p = 0.001) and RVR (OR = 4.18, CI: 2.85-8.65, p < 0.001) to be significantly related to treatment outcome. Patients with the IL28B rs12979860 CC genotype and a low pretreatment γ-GT/ALT ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10-71.1, p < 0.0001). CONCLUSION: The pretreatment γ-GT/ALT ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-α-based combination therapy in a nontriaged ordinary setting.

Update on contemporary management of clinically localized renal cell carcinoma.

Renal cell carcinoma (RCC) continues to increase in incidence with the largest increase manifesting in small, organ-confined tumors. This review outlines the epidemiology and current data pertaining to the management of clinically-localized RCC. In this manuscript, the current data outlining the benefit of nephron sparing to the overall survival of the patient is described. The data pertaining to minimally invasive nephron sparing is also explained in detail. From laparoscopic and robotic partial nephrectomy to watchful waiting and percutaneous ablation, the urologist is continually assaulted with new data for the management of clinically-localized RCC. The data can be confusing, and much of it is conflicting. The addition of new scoring systems or nomograms may aid in predicting which therapy would be most beneficial in certain patient groups. New scoring systems may also predict the difficulty of surgical resection and predict surgical complications. The limitations of the data pertaining to the management of clinically-localized RCC are also outlined.

Efficacy of high-dose intra-dermal hepatitis B virus vaccine in previous vaccination non-responders with chronic liver disease.

BACKGROUND: Hepatitis B virus (HBV) vaccination is essential in chronic liver disease (CLD), because it can help prevent acute-on-chronic disease, which has potentially fatal complications. Unfortunately, this group has a significant proportion of HBV vaccination non-responders. A variety of intra-muscular (IM) vaccination methods have been used in an attempt to remedy this poor-response, but with limited success. AIMS: Herein is reported the safety and efficacy of high-dose intra-dermal (ID) HBV vaccination in CLD individuals who had failed previous IM standard and boost-dosing regimens. METHODS: Forty-eight CLD individuals, known HBcAb negative, who had failed both a three-dose schedule of 40 µg IM vaccination, and boost dosing of either 40 or 80 µg IM, were identified, of which 42 completed the vaccination course. Each received a 40 µg ID total dose (20 µg per arm) during their clinic visits until a response was documented or a maximum of three doses had been administered. HBsAb titer ≥ 10 mIU/ml was regarded as an immunologic response; the intention was to achieve an optimum response of ≥ 100 mIU/ml. RESULTS: Twenty-nine of forty-two (69%) individuals had an immunologic response, with 15 (51%) of the responders having the optimum response. No changes in serologic data occurred. No serious dermatologic reactions were observed. No differences between those who responded and those who did not were observed with regard to the presence of cirrhosis, diabetes mellitus, or chronic kidney disease. CONCLUSIONS: High-dose ID HBV vaccination of previous CLD non-responders to the standard IM regimen with boost dosing is both safe and efficacious, and should be considered for all such groups.

Reduced memory B cells in patients with hyper IgE syndrome.

Dominant-negative mutations in STAT-3 have recently been found in the majority of patients with sporadic or autosomal-dominant hyper IgE syndrome (HIES). Since STAT-3 plays a role in B cell development and differentiation, we analyzed memory B cells in 20 patients with HIES, 17 of which had STAT-3 mutations. All but four patients had reduced non-switched and/or class-switched memory B cells. No reduction in these B cell populations was found in 16 atopic dermatitis patients with IgE levels above 1000 KU/L. There was no correlation between the reduction of memory B cells and the ability to produce specific antibodies. Moreover, there was no correlation between the percentage of memory B cells and the infection history. Analysis of memory B cells can be useful in distinguishing patients with suspected HIES from patients with atopic disease, but probably fails to identify patients who are at high risk of infection.

Robotic assisted laparoscopic pyeloplasty.

Dismembered pyeloplasty is the gold standard treatment for adult ureteropelvic junction obstruction with published success rates consistently over 90%. The morbidity of the open flank incision required for dismembered pyeloplasty led to experimentation with other less invasive modalities such as endopyelotomy and laparoscopic techniques. Modern laparoscopic pyeloplasty series demonstrate success rates equivalent to those of their open counterparts with improved postoperative convalescence. The requirement of complex intracorporeal reconstruction has limited widespread application of laparoscopic pyeloplasty. The daVinci surgical robotic platform offers features that improve intracorporeal reconstruction and suturing thereby flattening the learning curve of laparoscopic pyeloplasty for residents, fellows, and novice laparoscopists. Multiple variations in robotic technique exist but short term outcomes and convalescence appear equivalent to open and laparoscopic pyeloplasty. Complications related to robotic assisted laparoscopic pyeloplasty are minimal and usually self-limiting. The indications for robotic pyeloplasty have expanded to include difficult cases such as those who have failed previous therapy for ureteropelvic junction obstruction including failed endopyelotomy or previous pyeloplasty. The appeal of robotic technology is tempered somewhat by its high cost compared to standard laparoscopic techniques but it is hoped that overall costs will decrease with time.

Efficacy of repeated high-dose hepatitis B vaccine (80 microg) in patients with chronic liver disease.

Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.

Inclusion cyst and graft contraction in Tutoplast human cadeveric pericardium following Peyronie's grafting: a previously unreported complication.

Tutoplast human cadaveric pericardium has been utilized safely and successfully in numerous series of tunica albuginea grafting for Peyronie's curvature without reported rejection, cyst formation, or foreign body reaction. We describe a previously unreported complication of inclusion cyst formation and graft contraction in a 40-year-old white male following Tutoplast human cadaveric pericardial graft surgical correction of Peyronie's curvature. The complication was successfully treated with surgical graft excision and replacement with autologous temporalis fascia.

Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?

Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects.

Lymphoproliferative disorders in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is associated with the development of lymphoproliferative disorders (LPDs). The aim of this investigation was to determine the prevalence and characterization of monoclonal gammopathy and benign and malignant LPDs in individuals with chronic hepatitis C. A total of 233 subjects diagnosed with chronic hepatitis C (male/female ratio: 131/102, median age; 49 years) were studied. Serum and urine were examined for the presence of a monoclonal gammopathy. A bone marrow aspirate and biopsy was obtained in individuals with a monoclonal gammopathy. Thirty-two patients (13.7%, 32 of 233) had a monoclonal gammopathy; 75% of them were benign and were not associated with malignant disorders (24 of 32) while 25% were associated with malignant LPDs or a plasma cell disorder (eight of 32). Two additional subjects without monoclonal gammopathy were diagnosed as having a malignant LPDs. The prevalence of malignant LPDs/plasma cell disorder in individuals with HCV-induced chronic liver disease was 4.3%. No difference was found in terms of disease duration, HCV genotype, viral load, alanine aminotransferase level or histopathologic score between the subjects with or without a monoclonal gammopathy. The presence of mixed cryoglobulinaemia was strongly associated with the presence of an underlying malignant disorder. Hence a monoclonal gammopathy is found in 14% of patients with chronic hepatitis C and is associated with malignant B-cell LPD in more than a quarter of such patients. The prevalence of LPDs in individuals with HCV-induced chronic liver disease is greater than that of the normal healthy population.

SEREX identification of new tumour-associated antigens in cutaneous T-cell lymphoma.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative disorder of mainly CD4+ T cells, with primary manifestation in the skin. OBJECTIVES: To detect new CTCL-associated antigens for immunological therapies and to define their specificity in terms of RNA expression and seroreactivity. METHODS: A newly constructed CTCL cDNA phage library was screened and cross-reactivities against the detected clones were tested using 15 mycosis fungoides and six Sézary syndrome sera. The mRNA expression of the identified genes was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using 22 tumour tissues, nine cell lines and up to 29 different types of normal tissue. RESULTS: We identified nine different tumour antigens (HD-CL-01 to HD-CL-09) of which seven clones had high homology to genes with known functions. Several of these genes had previously been associated with cancer, namely inositol 1,4,5-triphosphate 5-phosphatase, vimentin, aldose reductase and elongation factor-1alpha. Variations in the deduced protein sequences were observed in three cases, mostly due to variations in protein length. The individual clones were recognized by up to 56% of patients' sera, while control sera were negative except in one case. Using RT-PCR, we found a frequent expression of these new tumour antigens in tumour specimens (26-100%). In contrast to humoral specificity, specific mRNA was also detected in selected normal tissues (29-89%). CONCLUSIONS: SEREX (serological identification of antigens by recombinant expression cloning) identified multiple tumour-associated antigens in CTCL. The serological specificity and the high percentage of reactive sera of CTCL patients against several clones suggest these genes as potential targets for diagnostic and prognostic purposes.

Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies.

Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV-related mortality was observed in either group. In the lamivudine-treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine-related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy-induced HBV reactivation.

Evidence for expression of a single distinct form of mammalian cysteine dioxygenase.

Cysteine dioxygenase (CDO) plays a critical role in the regulation of cellular cysteine concentration. Because multiple forms of CDO ( approximately 23 kDa, approximately 25 kDa, and approximately 68 kDa) have been claimed based upon separation and detection using SDS-PAGE/western blotting (with antibodies demonstrated to immunoprecipitate CDO), we further investigated the possibility of more than one CDO isoform. Using either rabbit antibody raised against purified rat liver CDO or against purified recombinant his(6)-tagged CDO (r-his(6)-CDO) and using 15% (wt/vol) polyacrylamide for the SDS-PAGE, we consistently detected the approximately 25 kDa band, but never detected a approximately 68 kDa band, in rat liver, kidney, lung and brain. Nondenatured gel electrophoresis of r-his(6)-CDO yielded a molecular mass estimate of 25.7 kDa and no evidence of dimerization. Mass spectrometry of r-his(6)-CDO yielded two peaks with molecular masses of 24.1 kDa and 24.3 kDa. Anion-exchange FPLC of r-his(6)-CDO also gave two peaks, with the first containing CDO that was 7.5-times as active as the more anionic form that eluted second. When the two peaks recovered from FPLC were run on SDS/PAGE, the first (more active) CDO fraction yielded two bands (perhaps as an artifact of SDS/PAGE), whereas the second (less active) CDO fraction yielded only the approximately 23 kDa band. We conclude that the physiologically active form of CDO is the approximately 25 kDa (i.e., 23.5 kDa based on mass spectrometry) monomer and that this active form is probably derived by post-translational modification of the 23 kDa gene product.

Utility of magnetic resonance imaging in evaluating inflatable penile prosthesis malfunction and complaints.

The introduction of oral pharmacotherapy dramatically changed practice patterns in erectile dysfunction. The direct effect was to decrease the numbers of patients seeking penile implants; an indirect effect has been the changing ratio of new, to re-do operations. Patients seeking replacement inflatable penile prosthesis (IPP) surgery pose challenges both in diagnosis and management; in very select cases preoperative MRI can be useful in the evaluation of the patient's complaint and in planning operative management. Imaging can supplement the physical exam; in certain cases imaging will reveal: crural herniation, corporal distortion, corporal fibrosis, and hardware migration. Inflatable penile prosthesis has a high rate of satisfaction for patients (89%) and partners (70%). The principal reasons for dissatisfaction are penile shortening, pain and frustration with reoperation. If pain is not due to infection, it may be secondary to malpositioning, improper sizing, cylinder cross-overs, or herniation. After one or more reoperations, penile distortion may occur secondary to tunica albugenia thinning or fibrosis. A series of cases will be presented to highlight the utility of MRI for IPP problems, define normal appearance and abnormal appearance of penile hardware. Careful collaboration between the Urologist and Radiologist in the review and final dictation of these cases is warranted to properly document problems and to plan device replacement/penile reconstruction.